HAMISH GUTHRIE MILLER v. TAYSIDE HEALTH BOARD
| OUTER HOUSE, COURT OF SESSION |
| A1674/01 | OPINION OF LORD DRUMMOND YOUNG in the cause HAMISH GUTHRIE MILLER, as guardian of his daughter LAURA MAY MILLER Pursuer; against TAYSIDE HEALTH BOARD Defenders: ________________ |
Act: Scott, Q.C.; Dougall; Brodies, W.S. (for Burns Veal, Solicitors, Dundee)
Alt: Brodie, Q.C.; Cherry; Ranald F. Macdonald, Solicitor
21 October 2003
A. Introduction
[1]The pursuer has raised the present action as guardian of his daughter, Laura May Miller, who was born on 30 May 1986. Laura has since birth suffered from the condition known as ornithine transcarbamylase deficiency. On 24 September 1992 she became unwell, and on the morning of 25 September she was admitted to Ninewells Hospital, a hospital under the charge of the defenders. In Ninewells she received certain treatment, but ultimately she sustained serious brain damage. The pursuer contends that Laura's treatment in Ninewells was negligent, and that the brain damage was caused by the negligent treatment. A proof was allowed, but while it was proceeding the parties agreed that it should be restricted to two issues only: whether any persons for whom the defenders are responsible were in breach of a duty of reasonable care owed to Laura, and, if so, whether such breach of duty had caused damage to Laura. The quantification of loss, if the issue arose, was to be reserved for a further proof. The question of causation was sharply in dispute, and in order to determine causation it is necessary for me to reach a view on the precise duty or duties that were breached and the time at which such breach occurred. It is also important to consider whether, had the precise duty or duties in question not been breached, brain damage would have been prevented or reduced.
B. Ornithine transcarbamvlase deficiency
[2]Ornithine transcarbamylase deficiency (also known as ornithine carbomyltransferase deficiency; and hereinafter referred to as OTC deficiency) is a metabolic disorder that results from an inborn genetic error. The error occurs in the series of metabolic processes known as the urea cycle. The urea cycle involves a complex series of chemical reactions within the blood whereby nitrogen is converted into urea, and in due course excreted in the form of urine. So far as is material to an understanding of the present case, the urea cycle functions as follows. The body requires to ingest protein in order to replace and repair tissue. A consequence of the ingestion of protein is the production of nitrogen derived from the protein. That nitrogen rapidly combines with hydrogen to form ammonium ions. In persons who do not have errors in the urea cycle, the ammonium ions combine with other compounds to form urea. That process is dependent on the presence of certain enzymes, which are located principally in the liver and to a minor extent in the kidneys. One of those enzymes is ornithine transcarbamylase (OTC), and OTC deficiency occurs when that enzyme is not present in sufficient quantities to enable the reactions to work properly. The existence of OTC is linked to the X chromosome; consequently, because they have two X chromosomes, females with OTC deficiency usually produce some of the enzyme. That gives them on average a better chance of survival than males. That is particularly so in late onset cases, where the condition does not appear until some time after birth. Laura was such a late onset case. The condition is very rare.
[3]When OTC deficiency is present, the body is unable to convert the whole of the ammonia produced by the ingestion of protein into urea. (Strictly speaking the word "ammonia" refers to free-standing molecules of nitrogen and hydrogen, with the chemical formula NH3, while "ammonium" refers to the corresponding ion, NH4, which occurs as part of larger compounds. Most witnesses, however, referred simply to "ammonia" to cover both the free-standing compound and the ion, and I will follow that usage throughout the remainder of this opinion except where it is clear that only the ion is referred to). Consequently ammonia levels build up in the body. Initially, the ammonium ions combine with glutamic acid and glutamate to form a compound known as D-glutamine. In this way some of the ammonia is mopped up, and to that extent the presence of glutamic acid and glutamate provides a form of buffering against rising levels of ammonia. Nevertheless, this process does not mop up all of the excess ammonia, and when reserves of glutamic acid and glutamate have been exhausted ammonium levels will start to rise. One consequence of the buffering of ammonia in this way is that a rise in blood glutamine will typically be a precursor of a rise in the level of ammonia. Glutamic acid is an amino acid. There are approximately 20 such acids in the body. They are constituents of protein in the diet. They are active compounds, and are used in the metabolic activity of the body. Thus glutamic acid combines with ammonium to form glutamine. Because they are active compounds, the amounts present in the body vary continuously. Thus the measure of an amino acid at any particular time will reflect not only the body's protein intake but also its metabolic activity.
[4] Ammonia is neurotoxic; if it is allowed to build up in the brain to critical levels, it causes serious damage to the brain and can result in death. Thus the accumulation of ammonia in the blood and brain, a condition known as hyperammonaemia, is a very serious matter. Dr P.H. Robinson, a consultant in paediatric metabolic medicine at the Royal Hospital for Sick Children, Yorkhill, considered that in relation to permanent damage to the patient the level of 350 umol/l (micromols per litre) was "of ominous significance" (5 December 2001, 11.09); that referred to a risk rather than a certainty of permanent damage. The mechanism whereby such damage is caused was the subject of a debate among the expert witnesses who gave evidence, and I discuss it below at paragraphs [138] to [155]. It was a matter of agreement, however, that one of the results of hyperammonaemia was cerebral oedema, or swelling of the brain, which has grave consequences.
[5] Certain standard forms of treatment have been developed to deal with OTC deficiency. These were a matter of agreement among the experts who gave evidence. In the first place, the patient will invariably be placed on a low protein diet, as the fundamental problem is an inability to metabolise protein properly. In the second place, certain chemicals are regularly administered to those suffering from the disorder, to help them to mop up the excess nitrogen. The most basic of these is sodium benzoate, whose effects were described by Dr P.H. Robinson (30 November 2001, 2.59). This is a drug which is rapidly absorbed if given by mouth. It combines with glycine, one of the amino acids in the body, to produce hippuric acid, which is rapidly removed by the kidneys. Each molecule of sodium benzoate combines with and removes one molecule of glycine. Each molecule of glycine contains an atom of nitrogen, which is accordingly removed from the body. The body continues to produce glycine, using nitrogen from ammonia for that purpose. In this way a metabolic pathway is set up for the removal of nitrogen from the body. A metabolic pathway is in essence a chemical reaction that enables one substance within the body to be converted into another substance. The body needs various chemical substances to provide energy, growth and the maintenance of normal body tissues. The body tissues are continually broken down and remade, and complex interconversions of substances are required for that purpose. Those changes in body substances occur in the form of series of chemical reactions. Many such reactions exist, including the normal process for the removal of nitrogen using OTC, as described in paragraph [2] above. The use of sodium benzoate, in the manner described above, creates an additional pathway for the removal of nitrogen. As an alternative to sodium benzoate it is possible to use phenylacetate compounds, which combine with glutamine to produce phenyl acetyl glutamine, which is also extracted rapidly by the kidneys. Each glutamine molecule contains two nitrogen atoms, and those are removed by this process. The glutamine lost in this way is replaced by the body, using ammonia. Those suffering from OTC deficiency take sodium benzoate or a phenylacetate compound on a regular basis. In addition, they may take a number of other compounds which assist in the control of the deficiency; these include Citrulline, Arginine and Ketovite. Although these are mentioned below, it is unnecessary to discuss their precise effects in detail.
[6] A major problem for patients with OTC deficiency is intercurrent infection, which means an additional illness occurring along with the primary illness, OTC deficiency (Dr P.H. Robinson, 30 November 2001, 3.32; 4 December 2001, 2.07). In children these usually take the form of viral illnesses, involving colds, vomiting, diarrhoea and the like. During such illnesses, the normal breakdown of body tissues is accelerated. If the normal supply of carbohydrates or glucose for the production of energy is interrupted, as occurs with fever and infection, or if the patient is unable to eat and drink normally, the body tries to maintain energy by reducing its demand for glucose. It therefore begins to provide an alternative fuels for itself, by the breakdown of body tissues. That involves the creation of glucose (gluco-neogenesis). Initially fat is broken down, but then the body begins to break down muscle tissue, using amino acids. During the chemical reactions involved in the process the amino acids are broken down, and the first step in that process is the removal of the ammonia group from the acid, leaving a residual skeleton that enters into the pathway is for the creation of glucose. That means that free ammonia is produced, and that inevitably creates difficulties for those suffering from OTC deficiency because they cannot deal with that ammonia in the normal way. Hyperammonaemia can easily result. Consequently it is of the greatest importance that the risks of intercurrent infection should be recognised, and that a plan of management should be devised for such illnesses. With children, the parents will become involved. They are taught to recognise the symptoms that may attend such illnesses, and become experienced in recognising them. That includes the recognition of symptoms of hyperammonaemia.
[7]If an intercurrent infection develops, the standard initial treatment is to provide a glucose substitute; one example is a preparation known as Caloreen, a glucose polymer. Caloreen has a high proportion of glucose substitute to fluid by comparison with normal sources of glucose. The supply of extra glucose is an important aspect of therapy, because glucose is required to replace lost energy, to limit tissue breakdown and to reduce ammonia levels (Dr P.H. Robinson, 30 November 2001, 3.47). At the same time the metabolic medication referred to in paragraph [5] above is continued. If the condition persists, admission to hospital is required.
[8]The treatment that is required following admission to hospital is discussed in detail later in this opinion. Typically, it involves the administration of intravenous glucose at a relatively high rate, 10% or 25%, and if necessary insulin is given as well. The glucose is designed to replace energy and limit the breakdown of body tissue; in this way it promotes the reduction of ammonia levels. In addition, metabolic medication of the sort discussed in paragraph [5] above is administered, orally or intravenously; this is designed to eliminate ammonia. The most serious risk is cerebral oedema; consequently neurological observations are of great importance. The symptoms of hyperammonaemia in such cases (Dr P.H. Robinson, 4 December 2001, 3.57) begin typically with sleepiness, drowsiness and headaches. These are followed by confusion, perhaps irritability, and ataxia (unsteadiness). The irritability may progress to the stage of combativeness, and the patient may display a violent reaction if approached. Vomiting may feature at an early stage, but it may discontinue if the level of unconsciousness increases. Nevertheless, repeated intractable vomiting is a feature of hyperammonaemia. As matters progress, the patient shows an increasing loss of responsiveness to the world. Eye movements are lost, as is response to speech. Eventually the patient becomes unreactive to the world, and even to pain. At that point there is a serious risk to vital centres affecting matters such as heartbeat. The cranial nerves are liable to be impaired. In the final stages the patient lapses into a coma, perhaps accompanied by seizures. Then there is irregularity of breathing, the heart slows and ultimately the patient dies. There may be an initial period of rapid breathing, which is characteristic of raised blood ammonia.
C. Laura Miller's medical history prior to 25 September 1992
[9]Laura Miller's medical history prior to September 1992 was not the subject of significant dispute, but it is necessary to set it out in some detail, as it is relevant to the events of that month. Laura was born on 30 May 1986. On 5 July 1987, when she was 13 months old, she was admitted to Ninewells Hospital after her mother noticed that she had been unable to move her left arm. It was noted that her head was tending to fall to the left side, and that she was intermittently drowsy and irritable with dilated pupils. The ammonia level in her blood was raised at 350 umol/l (micromols per litre). A CT scan of her brain showed large bilateral areas of decreased density in both frontal lobes. Laura was subsequently transferred to the Royal Hospital for Sick Children in Edinburgh, where she was investigated further. She was treated in both hospitals by the intravenous administration of clear fluids, and made a complete recovery; the level of ammonia in her blood fell gradually from 232 umol/l to 136umol/l. At Ninewells she came under the care of Dr J.A. Young, a consultant paediatric neurologist, who remained responsible for her care thereafter. In August 1987 a liver biopsy was carried out, and was referred to the Institute of Child Health in London for analysis. In October 1987 Dr Young referred Laura to Dr A.P. Mowat, of King's College Hospital in London. In a letter to Dr Mowat dated 16 October 1987 Dr Young set out Laura's medical history, and raised the possible diagnosis of OTC deficiency, although he stated that had not been confirmed. In London Laura was transferred to the charge of Dr J. V. Leonard, a specialist in metabolic medicine at the Hospital for Sick Children at Great Ormond Street in London. It was decided that Laura should undergo a protein load test, and this was carried out in December in London. It confirmed the diagnosis of OTC deficiency. During the protein load test, which involved deliberately administering substantial quantities of protein, Laura became very drowsy. She was treated with intravenous dextrose and made a good response. She was subsequently discharged home. Thereafter she was given maintenance treatment. This involved a low protein diet, protein being limited to 1.5 g per kg of body weight per day, together with sodium benzoate, of which 1.25 g was administered twice daily. In addition, a Ketovite tablet was administered three times per day and 5 ml of Ketovite liquid was administered daily.
[10] The liver biopsy indicated that Laura's liver was normal, and that she did not suffer from liver disease. Dr Robinson, who has been involved in Laura's care since October 1994, indicated that she had not subsequently shown any signs of liver disease (30 November 2001, 3.10-3.15). I accordingly exclude liver disease as playing any part in her condition.
[11]On 17 December 1987 Dr Leonard wrote to Dr Young to formulate a three stage plan for the control of her OTC deficiency. He stated this as follows:
"Stage 1 is when the family noticed that Laura is slightly off-colour but are not really sure whether she is going to become ill or not. What we do is to suggest that they give a drink of 15% Caloreen and reassess progress in a few hours time. If it is clear that she was merely tired and is now improving, then no harm has been done, but if it is clear that she is developing an infection or is unwell, then she should start her emergency regime at the earliest possible time and then should proceed to stage 2. This stage is initiated for patients who clearly have mild infection but are not vomiting. They should have regular high carbohydrate drinks both during the day and the very importantly during the night. They should also continue with their sodium benzoate. If for any reason Laura does not tolerate this and either she starts to become encephalopathic or is vomiting, then it is clear she should proceed to hospital without delay for the ammonia to be measured and for a careful assessment of her general condition. In this way I think the family might well be able to cope with minor infections at home although obviously if they are at all worried they should still go to hospital".
In the same letter, Dr Leonard concluded
"I emphasize all this because if the ammonia can be controlled, then Laura's outlook is excellent. Failure to do so may result in disaster"
Dr Robinson was asked to comment on that statement (30 November 2001, 3.51). He replied that he agreed a very strongly with the statement. Provided that further episodes of encephalopathy (conditions involving disorder of the brain) were avoided, or were treated vigorously, he thought that Laura should have been able to grow and develop, and to maintain her existing abilities with no further loss of function. I accept that opinion. To the extent that the defenders' experts disagreed with it, I prefer the views of Dr Robinson for reasons that are set out in detail later in this opinion.
[12] At Ninewells Laura remained under the charge of Dr Young, who continued to consult Dr Leonard regularly. On 27 January 1988 Dr Young gave Laura's parents a letter (no 11/1 of process) for use in the event that she became unwell. He stated in his evidence that he intended that, if Laura's parents considered that she needed admission to hospital, the letter should be handed to the doctor dealing with her. This was in the following terms:
"Laura is thought to have ornithine transcarbamylase deficiency. Her maintenance treatment is a low protein diet, 1.5 g/kilo per day together with Sodium Benzoate 5 ml of the solution twice daily giving a total daily dose of 2.5 g Sodium Benzoate.
In the event of her developing irritability or other neurological symptoms she should be admitted, blood taken for ammonia level and urine for organic acid examination. The protein should be withdrawn and she should have glucose rich clear fluids at a rate that is a little below her standard intake and varied according to blood sugar monitoring. A more detailed protocol is available in her case notes".
On 3 April 1991 a handwritten note was added to the letter, in the following terms:
"Protein 1 g/kg
Na benzoate 5 ml tid [three times per day]
citrulline 1/2 scoop bd [twice daily]
ketovite liq 5 mls bd
" tab 1 tab bd
4 phenylbutyric acid 1 scoop bd
+ 1/4-1/2 scoop middaly
dialamine 1/2 scoop bd
metabolic mineral mix".
The note was in the handwriting of Dr W d'Arrigo, who was then Dr Young's registrar. A further letter (no 11/2 of process) was given to Laura's parents in February 1992, on this occasion by Dr P. Fowlie, who was Dr Young's registrar. This letter was as follows:
"Laura Miller suffers from OTC Deficiency. This is an inborn error of metabolism which requires strict dietary control. From time to time her behaviour may deteriorate which may represent poor control of her condition.
Under such circumstances Mrs Miller may bring Laura to hospital where she should have her ammonia and glutamine levels checked. Further information is available in her Ninewells Hospital notes".
[13] In January 1989 Dr Young referred Laura to a speech therapist, and it was found that by June she was making good progress in that connection. In June her ammonia level was measured, and was found to be 90 umol/l, a normal level. In October of the same year her ammonia was measured once again and found to be rather high, at 208 umol/l . This was unaccompanied by any clinical signs, and no treatment was given on this occasion; in his evidence Dr Young commented that it was important to treat the child, not the figure, and that Laura appeared healthy. It was not thought that Laura had symptomatic hyperammonaemia at this time. By now Laura was receiving 5 ml of sodium benzoate three times per day, giving 3.75 g per day. She was also administered 1 g of Citrulline twice daily, together with a mineral mix and Ketovite. In January 1990 she was recorded as having an ammonia level of 170 umol/l, but again showed no signs of clinical disturbance. On 11 January Dr Young wrote to Dr Mowat to ask for his advice. Dr Mowat replied that the first thing to do was to check with the laboratory that they had not changed the way that they were measuring the ammonia. On 21 March 1998 Dr Young's registrar noted that Laura's blood ammonia was 100 umol/l.
[14] Laura was again admitted to hospital on 24 April 1990. On this occasion she was brought by her parents because she had been irritable and having tantrums for two or three weeks previously and had vomited twice, once a week before her admission and once on the previous night. This occurred at about the time of the birth of Laura's younger sister, and the impression recorded by the doctor who examined her was that her irritability might be a response to this event. Nevertheless, her central nervous system was examined, and she was recorded as being alert. Her tone and reflexes were normal, and she had no focal signs. Her co-ordination appeared normal. She received a number of other tests, including blood ammonia. Her ammonia level was found to be 204 umol/l. She received fluids and oral metabolic therapy, including sodium benzoate, Citrulline, Ketovite and other substances. Her protein intake was restricted to 1 g per kg per day. She had seemed hyperactive on admission, but she settled during the night. The following day Laura was recorded as being well. Blood ammonia was found to be 130 umol/l. By 26 April 1990 Laura's blood ammonia level had returned to normal. The tantrums and vomiting had ceased. She was returned home, with her condition to be followed up in May. She continued with a diet restricted to 1 g of protein per kg per day. On this occasion, therefore, treatment by administering fluids, restricting protein intake and providing metabolic therapy was successful. Following this episode Laura's glutamine level increased sharply, to 2538 umol/l on 16 May. On the same date, however, her blood ammonia level had come down to 85 umol/l. Dr Young reported these developments to Dr Leonard, who stated that Laura's ammonia level should be kept as low as possible. To that end, he recommended that, instead of sodium benzoate, she should be given phenylbutiric acid, which is more efficient in removing free nitrogen from the blood. Dr Young implemented the recommendation in June, and by September Laura's ammonia level had come down to 50 umol/l. In that month Dr Young recorded that there seemed to have been a marked improvement in Laura since the phenylbutyrate had been added to her maintenance medication. Dr Young reported this to Dr Leonard, who recommended that Laura's medication should make use of Arginine rather than Citrulline, the latter being cheaper. Dr Young implemented that recommendation, and on 17 November Laura was started on Arginine instead of Citrulline.
[15] On 22 December 1990 Laura was again admitted to Ninewells Hospital for a protein restricted diet. Her ammonia level on 18 December had been found to be 205 umol/l. It was recorded that she had been more restless since she started on Arginine, and had had a disturbed sleep pattern. In the preceding month she had contracted a number of colds. On examination, she was found to be afebrile (free from fever), but was mildly dehydrated and had enlarged tonsils and bilateral cervical (neck) glands. Her ammonia level was noted as high. She was put on a protein restricted diet, under which her intake of protein was limited to 0.75 g per kg per day. Her condition was discussed with Dr Young, who returned her to Citrulline in place of Arginine, increased her dose of phenylbutyric acid, and restricted her intake of protein to 0.5 g per kg per day. On 23 December Laura's blood ammonia was measured once again, and had fallen to 32 umol/l. Laura was discharged, but her medication reverted to Citrulline in place of Arginine. In a letter dated 31 December 1990 to Dr Gilmour, Laura's general practitioner, Dr Young stated that the improvement in her condition after her admission to hospital had been associated with but was not unequivocally due to her returning to Citrulline from Arginine.
[16] On 17 January 1991 Laura was once again admitted to Ninewells Hospital. She had been hyperactive and would not settle, and was suffering from lower abdominal pain. She was still eating and drinking well. On examination, she was recorded as "well looking". Her tonsils were red. Her blood ammonia was measured at 89 umol/l. Her condition was discussed with Dr Young on 18 January, and it was decided to send her home on a pass. On 19 January, at approximately 2:30 pm, she returned to Ninewells. She had vomited on the journey home from hospital, and had not tolerated any foodstuffs or oral fluids. She had vomited four or five times in total. By the time of her readmission she was drowsy, and appeared disorientated. She had earlier complained of a sore head and a vague abdominal pain. On examination she appeared distressed and disorientated. She was recorded as irritable. Her central nervous system was examined, and she was found to be drowsy and irritable, with a high-pitched cry. Her eyes were rolling backwards, and she pushed her head back. In evidence, Dr Young described her as showing evidence of cerebral dysfunction. Dr Robinson (4 December 2001, 11.44) considered that on this occasion Laura displayed signs of encephalopathy (brain disorder). Her ammonia level was 165 umol/l. By that time she was noted as being distressed and screaming. Dextrose was administered intravenously in a 10% solution from 3.05 pm on 19 January, dextrose at 5 % having been administered from 2.45 pm. Dextrose was administered in a 10% solution at 70 ml/kg over 24 hours. By 20 January Laura's ammonia level had dropped to 103 umol/l, and by 21 January it was 31umol/l. This had been the first occasion since Laura's first admission to Ninewells when she had shown signs of cerebral dysfunction.
[17] Between May and August 1991 Dr Young continued to take advice from Dr Leonard about the administration of sodium benzoate and phenylbutyric acid. On 3 May Dr Leonard agreed with Dr Young that Laura had not tolerated the change from Citrulline to Arginine. He further stated that, while Laura's plasma ammonia concentration was satisfactory, her plasma glutamine and alanine were rather high, with the result that Laura's intake of sodium benzoate and phenylbutyric acid might have to be increased. On 6 August he repeated the advice, and stated that up to 5 g of either sodium benzoate or phenylbutyric acid could be given daily. He further suggested that Laura's Citrulline intake might be increased to 1.5 or even 2 g per day. On 20 August Dr Young reported to Dr Leonard that Laura's ammonia level was generally a little over 100 umol/l, and that she continued to enjoy good general health. For glutamine level, however, was high, at 1056 umol/l. Dr Leonard replied on 2 September 1991. He stated that, if Laura were relatively well with a plasma ammonia of 100, he would not worry too much. Nevertheless, it was frequently found that if better control could be achieved the family considered that it made a notable difference, with the child being less irritable and making better progress at school. Ideally her glutamine concentration should be kept below 800 or 900 umol/l. In late October 1991 Laura's ammonium profile was measured once again, and levels between 63 and 83 were recorded. Her glutamine was also better, at 890 and 870 umol/l. On 14 November Dr Young wrote to Dr Gllmour to report these figures. He concluded
"I think that all this means that Laura is under satisfactory biochemical control and that much of the difficulty in school is of a behavioural nature".
On 15 April 1992 Laura's blood ammonia was recorded at 74 umol/l.
[18] On 9 July 1992, at approximately 4.45 pm, Laura was once again admitted to Ninewells. She had been ill for one day, and had been vomiting and drowsy; she had also been mouth breathing. She was seen by a senior house officer, Dr Smith. Dr Young was on holiday at this time. In the clinical note made on her admission, it was recorded that she was vomiting but not drinking. Since the previous day she had had a snuffly nose. On the day of her admission she had not kept anything down. That included medicine. She felt quite hot and was slightly drowsier than usual. On examination, it was recorded that Laura was not too unwell looking, but had slightly droopy eyes and a slightly elevated temperature. She was recorded as having a cervical lymphederopathy, which indicated that she had considerably enlarged glands in the neck. The tonsils were recorded as enlarged and inflamed. The impression recorded was that Laura had tonsillitis. At 5.10 pm Laura was given oral fluids, and at 6 pm she was given an intravenous infusion of 10 % dextrose. Various tests were ordered, including ammonia and testing of the urine for organic acids. Her ammonia level was measured at 141 umol/l. On 10 July 1992 it was recorded that Laura had been unsettled all night. She was seen that day by Dr Karen Naismith, who was then a registrar at Ninewells, who described her as miserable and hoarse. A repeat test for ammonia was ordered, which disclosed a level of 121 umol/l. On 11 July 1992 it was recorded that Laura's temperature was settling, and that she was tolerating some oral fluids but was not managing drugs. Dr Kate McKay, another registrar, saw Laura and noted no neurological signs. She formulated a plan, which involved encouraging oral fluids and stopping intravenous fluids to see what could be managed orally. At 2 pm it was recorded that Laura was managing oral fluids. On 12 July it was recorded that Laura was now better. She was of intravenous fluids and was taking oral fluids. A rash from which she had been suffering had disappeared. She was allowed home on 13 July. Dr McKay prepared a discharge summary for Dr Gilmour (no 10/6 of process, pp.144-145). In this she stated
"The impression was of a six year old girl with known metabolic defect with an intercurrent illness, probably tonsillitis. ... She was initially tried on oral fluids but did not tolerate these and therefore an I.V. was established with 10% Dextrose. ... Her temperature settled within 24 hours, her I.V. was continued for 48 hours and then tissued and she was encouraged on oral fluids. She started Penicillin on 12.07.92 and continued to manage oral fluids.... By 13.07.92 she was well enough to be eating and drinking and was not vomiting. She managed all her medication and therefore she was allowed home to continue her Penicillin for a further five days and to re-start her normal medication".
[19] Two further aspects of Laura's developmental history should be mentioned; these relate respectively to Laura's intellectual functioning and to her education and employment prospects. First, in relation to Laura's intellectual functioning, Dr Young referred in his evidence to the fact that Laura had experienced a problem with higher intellectual processes, in particular communication. Thus early in 1991 she had refused to speak to new staff members at the nursery that she attended. This was noted by Dr Wendy D'Arrigo, Dr Young's then registrar, on 3 April 1991. On 28 June 1991 Dr D'Arrigo referred Laura to the ENT Department at Ninewells for investigation. She stated as follows:
"[Laura] has markedly delayed expressive language although her receptive language seems to be reasonably good. It is thought more likely that for a problem is one of social interaction since her mutism seems to be very situationally dependent".
In relation to this letter, Dr Young stated that very often children reach a stage of development where they elect not to speak, a condition known as elective mutism; usually, however, such children grow out of the condition. He expected that to happen in Laura's case. The mutism appeared to be largely confined to adults with whom Laura was not familiar. Laura received speech therapy to deal with the difficulty. Dr Young stated that Laura's elective mutism was quite different from the aphasia (inability to speak) and lack of understanding that she has displayed since September 1992. Secondly, although Laura had difficulties with language, as described above, she attended a normal school. She did, however, receive learning support. Dr Robinson (5 December 2001, 11.30) described Laura's intellectual function prior to September 1992 as involving a mild degree of mental retardation. She had some difficulties with motor planning skills, and a degree of difficulty with speech; the speech difficulty, however, was specific to certain situations, and she spoke if she wanted to. The full assessment for establishing the record of Laura's educational needs had not been completed by September 1992, but she was able to attend a mainstream school, with extra help. She had mild learning difficulties (on a mild-moderate-severe scale). Her IQ would have been at least 70. She could well have grown out of the speech difficulty. She would have been able to obtain employment in a semi-skilled or unskilled occupation, in which verbal and written fluency was not required. She could have carried out light manual work, but not work involving communication skills or dealing with the public. It is therefore likely that a wide range of occupations would have been open to her.
D. Events of 25 September 1992
(i) Circumstances leading to Laura's admission to Ninewells Hospital
[20] The evidence on this matter came from Laura's parents, Hamish Miller and Mrs Moira Miller. I found both Mr and Mrs Miller to be reliable witnesses, and accept their account of events prior to Laura's admission. That applies in particular to the details of the signs and symptoms that Laura was displaying prior to the night of 24/25 September. In this connection, I have had regard not only to Mr and Mrs Miller's demeanour in giving evidence but also to the evidence of a number of the medical witnesses, notably Dr P.H. Robinson and Dr J.H. Walter; these witnesses stated that the parents of children with inborn errors of metabolism are given detailed instructions about looking for signs of rising ammonia levels, and normally develop considerable skill in observing their children's behaviour, and in detecting signs that may indicate raised ammonia levels. Dr Young stated that Mr and Mrs Miller had been given such instruction (21 November 2001, 11.27, 11.39).
[21] The evidence of Mr and Mrs Miller was as follows. In September it was planned that Laura should attend school full-time. Some days prior to 25 September she had developed a red throat, and Mrs Miller took her to their general practitioner, who prescribed antibiotics. Laura completed the course of antibiotics on 24 September. She continued to attend school during this period. She appeared to suffer from a slight snuffle, and she coughed from time to time. She also seemed tired in the evenings, but Mrs Miller thought that that was merely a reaction to attending school. Mrs Miller stated that during this period Laura was quite bright and did not seem ill, unlike the previous occasion, in July, when she had been taken to hospital. In cross-examination both Mr and Mrs Miller were asked whether Laura had been off her food during the period when she was receiving antibiotics, and both replied that they had no recollection of that. Mrs Miller added that Laura tended to stay off high-protein foods, and to stick to potatoes and vegetables and drinks. When asked if Laura had lost weight, she stated that she had not weighed Laura, but that she had formed no impression that she had lost weight. Mr Miller stated that he had no recollection of Laura's losing weight during the period prior to her admission to hospital. I am satisfied, on the basis of Mr and Miller's evidence, that if Laura had been off her food during the period prior to her admission to hospital, that would have been noticed by her parents.
[22]On 24 September Laura had tea at about 5 pm, which was the usual time. Her parents did not notice anything abnormal at that stage. Mrs Miller went out to a keep fit class at about 8 pm and returned home at about 10 pm. When she was out, Laura vomited at about 8.15 pm. Mr Miller stated that she was not very sick, and he was not very concerned at the time. Thereafter Laura did her homework and watched television. Then she had supper, which consisted of a drink and possibly some toast, and certain of her medication, which she took orally. Thereafter she went to bed, at about 9 pm. When Mrs Miller returned home, she was asleep. Nothing appeared wrong at that time; she had kept her medication and drink down. In the early hours of the following morning Laura awoke, complaining of a sore tummy. At this point she retched, but did not actually vomit. She asked for a drink, which she took; after that she appeared to settle. Some time later, however, Laura got up, and Mrs Miller thought that something was wrong. Laura appeared irritable and restless; she seemed tired but something was preventing her from sleeping. Mr Miller stated that she lay down on her parents' bed, but she was restless, falling asleep and then wakening again. This went on for about an hour. Eventually Mrs Miller telephoned the family's general practitioner, who said to take Laura to Ninewells Hospital. After arranging a babysitter for their younger child, Mr and Mrs Miller drove with Laura to Ninewells, leaving the house at some point after 6 am.
(ii) Arrival at Ninewells
[23] The Millers reached Ninewells at some point between 7 and 7.30 am; the record made on Laura's arrival contained a computer-generated time of 7.32. Mr Mark Ballany, the nurse who was responsible for Laura's initial admission in the Accident and Emergency Department stated that the reception process must have started earlier, as a written form would be produced first. In the event, I do not think that the precise time of arrival is of great significance, beyond the fact that it was before 7.30 am.
[24] The first doctor who saw Laura after her admission was Dr Rachel Cummine, a senior house officer in the paediatric wards. Dr Cummine saw Laura shortly after 7.30, and made a clinical note (found at no 10/6 of process, pp.191-192). She took a history from Mrs Miller. Laura's complaint was noted as "vomiting, irritable, lethargic". It was recorded that she suffered from known OTC deficiency. The note continued:
"Started on antibiotics 10 days ago for tonsillitis (amoxil). Course finished yesterday. Has been tired & snuffly for 2/52 [2 weeks]. Coughing. Irritable/hyperactive. Tired in the evenings.
Mum concerned that counts now rising.
Seemed better with antibiotics.
Last night not hungry
-vomited dinner
-continued retching several hours
-very tired
-c/o abdo pain [complaint of abdominal pain]
-wanted to defaecate but unable to move bowels
-more & more irritable".
There followed information about Laura's previous admission in July 1992, and her past medical history. Her metabolic therapy was recorded as follows:
"Drugs
sodium benzoate 5 ml tid [three times per day]
phenylbutyric acid 2 1/4 g/day
dialamine 1/2 scoops bd [twice daily]
L Citrulline 1g/day
Ketovite 5ml bd
metabolic mineral mixture 8 g/day
Ketovite tab 1 tid"
The note concluded with a statement that Laura attended a normal school with special needs provision.
[25] The terms of Dr Cummine's note were put to Mr and Mrs Miller. They accepted much of the note, but Mrs Miller in particular had a number of qualifications. First, Laura had not suffered from vomiting, irritability and lethargy at the same time. Secondly, while Laura had had a snuffle, it did not amount to much. Thirdly, her tiredness was in the evenings, and Mrs Miller attributed that to Laura's reaction to school. Fourthly, so far as hyperactivity was concerned, Laura was always "full of beans". There was no indication that she had been any different during the period immediately prior to 25 September. Fifthly, irritability had only started that morning, although it had increased in the course of the morning. Sixthly, it was not accurate that Laura had not been hungry the previous night. Seventhly, Mrs Miller stated that it was not accurate to refer to continued retching over several hours; Laura had only retched once during the night so far as she could recall. Mr Miller differed on this point, as he considered that Laura had retched a number of times. In relation to these differences, I accept the evidence of Mrs Miller, in particular, that Laura had not appeared very ill prior to 24 September. She merely appeared to be suffering from fairly mild tonsillitis, with a minor snuffle. I further accept that any tiredness during that period could be attributed to the fact that she was attending school full-time. I also accept the evidence of both Mr and Mrs Miller that there was a sudden deterioration in Laura's condition during the evening of 24 September and early morning of 25 September. The irritability referred to in the clinical note only appeared during that night, and there had been no sign of loss of appetite prior to the vomiting episode during the evening of 24 September. I do not think that it is of great significance whether Laura retched once or more than once during the night; in either event, the combination of vomiting and retching was significant in the manner discussed below.
[26] When they arrived at Ninewells, Mr and Mrs Miller had the two letters, nos 11/1 and 11/2 of process, that had been given to them by Dr Young and Dr Fowlie. They handed these letters to Dr Cummine, and she read them. That was accepted by Dr Cummine in her evidence. I am also satisfied, on the evidence of Mrs Miller, in particular, that she expressed serious concern about Laura's condition to Dr Cummine. Dr Cummine in her evidence stated that she did not think that Mrs Miller was particularly concerned, but in her clinical note she recorded that Mrs Miller was concerned that Laura's counts were now rising. On this matter I prefer the evidence of Mrs Miller. In her evidence Dr Cummine relied largely on the clinical notes that she had prepared. She stated that she had taken a long history, as she did not feel that matters were urgent. She did, however, make one comment that I regard as of great significance. She stated that when Mrs Miller told her that Laura attended a normal school with special needs provision she was surprised. Until then she had thought that Laura's state that morning was how she normally was: lying down, taking no active part and throwing her arms around restlessly. At that point, it is clear that Dr Cummine fully understood that Laura's condition was serious. She stated in evidence that she realised then that she would have to speak to someone senior, and she decided to move Laura to one of the paediatric wards. She knew that Dr Greene, one of the paediatric consultants, was due to start a ward round shortly before 9 am, and she thought that he would examine Laura. Dr Cummine did not conduct a full examination of Laura's central nervous system. Laura was drowsy, was not talking and was waving her arms around. On the basis of that behaviour, Dr Cummine thought that she had a neurological problem, and she did not think that a full examination would add anything that would assist in her management of Laura's case. Her intention was, of course, that someone more senior should take over at an early stage.
(iii) Dr Greene's ward round
[27] When his ward round started, Dr Greene took over the management of Laura's case. Dr Cummine could not recall what she said to Dr Greene at this point, but she stated that she usually read through the history that she had taken. She accepted that that history did not contain a note of any neurological abnormality. She stated, however, that as soon as Dr Greene saw Laura it the would have been obvious that she was suffering neurological impairment. She was not taking part in the conversation, and was randomly moving her arms. That was an abnormal state. Dr Cummine was not certain whether she had told Dr Greene that Laura was at a normal school. On the basis of her evidence, however, which I accept on this point, I reach two important conclusions. In the first place, it was obvious that Laura was drowsy, not responding to speech, not talking and waving her arms about. That should have been noticed by Dr Greene, as these are important signs that Laura was neurologically unwell. In the second place, I consider it likely that Dr Greene was made aware that Laura attended a normal school. Although Dr Cummine could not recall telling him this, she stated that she read out what she had put in the clerking (the clinical note that she had prepared previously). That contained a statement that Laura attended a normal school. If Dr Greene was aware that Laura attended a normal school, it made the seriousness of her condition all the more obvious.
[28] The ward round was attended by Dr Greene, Dr Cummine, Dr Karen Naismith, a registrar in paediatrics, Dr Maalouf, another senior house officer, and a nurse. Laura's clinical notes were not available. Evidence was led from Mr Brian McGowan, the Clinical Records Manager of Tayside University Hospitals, and the person ultimately in charge of medical records at Ninewells. He stated that, if a request for Laura's records had been made at the time of the ward round, the records could have been made available within five minutes. I accept that evidence. Dr Naismith gave evidence that she thought that she had said at the ward round that the medical notes were needed.
[29] During the ward round Dr Greene examined Laura. A note of his examination was made by Dr Cummine (found in no 10/6 of process at page 193). She stated that its terms would have been those used by Dr Greene. The note, so far as material, is as follows:
"Examined by Dr Greene on ward round (0850 hrs).
O/E restless & confused
irritable
no focus of pain....
no rash. Looks dry
...
Plan IV fluids at 130% of requirements
4% dextrose + 0.18% Na Cl -100ml
Check ammonia,U &E [urea and electrolytes], glutamine".
Witnesses were generally agreed that the statement "Looks dry" indicates that Dr Greene observed a degree of dehydration. The plan for Laura's treatment involved setting up an intravenous drip providing her with dextrose at a strength of 4% in a saline solution, at a rate of 130% of normal requirements. Blood samples had to be taken to check for ammonia, urea and electrolytes, and glutamine. Dr Cummine stated that the plan originated with Dr Greene, and Dr Naismith agreed with that.
[30] Dr Greene accepted that he was given a letter at Laura's bedside. He thought that it was no 11/1 of process, although he could not remember whether it included the manuscript addition. He could not specifically remember receiving Dr Fowlie's letter, no 11/2 of process, but stated that he could well have seen it. Dr Naismith recalled that Dr Cummine had a letter in her possession, which she presented to Dr Greene. Dr Cummine spoke to receiving the two letters from Mr and Mrs Miller, and it is obviously likely that she would have made them available at the ward round. I accordingly conclude that at least Dr Young's letter no 11/1 of process was available to Dr Greene at the ward round. The medical staff who took part in the ward round were aware in any event that Laura had been under Dr Young's care in the past; it seems likely that that information had come from Mr and Mrs Miller, and the point was not in dispute. It was a matter of agreement among all of the witnesses who were present at the ward round, and also Dr Young, that Dr Greene formulated his plan for Laura's treatment without making any attempt to speak directly to Dr Young. In her evidence in chief, Dr Naismith stated that in the circumstances of Laura's case, where there was a possibility of neurological compromise, it would be usual practice for the doctor primarily responsible for a patient to be contacted. The note of the ward round does not contain any indication that Dr Greene carried out any investigation of Laura's central nervous system. Dr Naismith thought that if such an examination had been carried out it would have been recorded. She could not, however, recall that any such examination had been carried out. That view was to some extent supported by the evidence of Dr Cummine, who stated that she had noted what Dr Greene had said. I formed the impression that Dr Cummine performed her clerking function diligently, and that, if a full central nervous system examination had been carried out, she would have noted it. In these circumstances I draw the inference that no such examination was carried out by Dr Greene in the course of the ward round.
(iv) Events after the ward round
[31] Dr Cummine gave evidence that she was given responsibility for setting up the intravenous drip and taking the necessary blood samples. She had never taken blood for an glutamine test before, however, and she did not think that she had taken blood for an ammonia test. She expressed concern about this to the ward round, but no one else knew how to take the samples. She was accordingly sent to telephone the laboratory to find out how to do it. So far as the intravenous drip was concerned, her intention was to take the blood sample and immediately thereafter put the drip up. She had not been told to leave the blood tests and merely put the drip up. Consequently she did not put up the drip. She telephoned the laboratory, but they did not know how to take the samples and said that they would telephone back. Dr Cummine accordingly rejoined the ward round, and stated that she was waiting for the laboratory to tell her how to take the samples. Eventually Dr Cummine was told by the laboratory how to take the samples. Immediately thereafter, however, she was told that something was wrong with the ammonia machine, and that she would be told when to send the samples, after the machine was working. Consequently she waited. By then it was about 10.30 am. Dr Cummine agreed that, in the note of the ward round, there was no record of any urgency. Nor did Dr Greene tell her to put up the drip immediately. Nor did he say anything about getting in touch with Dr Young. Dr Cummine was asked whether Dr Greene instructed neurological observations to be carried out. She said that she did not recall, but she would expect to have noted that if she had heard him say it. She agreed that Dr Greene did not instruct maintenance of Laura's metabolic treatment; had that been discussed, she would have written it down. Dr Cummine further stated that no junior doctor was specifically delegated by Dr Greene with the responsibility of looking after Laura after the ward round. I accept that part of her evidence.
[31] Eventually, at about 10.30 according to her evidence, Dr Cummine put up the drip instructed by Dr Greene. Mr Miller thought that the drip was not put up until about 11.00. The relevant fluid administration chart (no 10/5 of process, page 660) indicates that the drip started at 11.00. The same form indicates, however, that the amount of fluid given by 12.00 was 111 ml, which suggests that the administration of fluid started before 11.00, as the rate of administration was between 70 and 80 ml per hour. The entry on that chart at 11.00 was made by Nurse Gwyneth Stuart, who gave evidence but was unable to explain the discrepancy; she was inclined to think that administration must have started at about 11.00. The corresponding prescription form (no 10/5 of process, page 659) indicates that the drip started at 10.30. For reasons that I will explain later, I do not think that this conflict is of great importance, as the drip should have been started immediately after the ward round. The likelihood is, I think, that the drip was set up closer to 10.30 than 11.00, with the prescription form being completed first, and bearing a slightly earlier time.
[33] The fluid administered by the drip was dextrose at 4%, but administered at a rate of 130% of normal requirements. Dr Young's letter no 11/1 of process stated that, if Laura developed irritability or other neurological symptoms, she should be given "glucose rich clear fluids" at a rate a little below her standard intake. Dr Young stated in his evidence that the 4 % dextrose solution administered on Dr Greene's instructions did not constitute the administration of "glucose rich clear fluids". 4% glucose was a standard intravenous fluid to prevent dehydration, but it did not actively correct anything. He stated that any competent paediatrician would know that that was the way to treat a slightly dehydrated child with an infection, but the purpose of a strong glucose solution was not just maintain a balance but to stop the break-up of protein, to enable Laura to deal with the nitrogen and ammonia that were liable to damage her brain. Strong glucose was required in the circumstances to encourage an anabolic state, and thereby mop up the nitrogen. Dr J.O. Beattie, who was a consultant in paediatric medicine at Yorkhill Hospital, and whose evidence is discussed in detail at paragraphs [69] - [78] below, stated that the standard response to cases such as Laura's on the morning of 25 September was to administer a moderately concentrated glucose solution. In general, a moderately concentrated solution meant 10% dextrose; that was the standard solution in such cases. He expressed the view that any paediatrician of ordinary competence should know that. I accept Dr Beattie's evidence on this matter. Dr P.H. Robinson also gave evidence on this matter, from the point of view of a consultant in metabolic medicine. He stated that in the circumstances a concentration of 4% glucose was insufficiently high to meet the patient's needs, and could not be considered "glucose rich". In all the circumstances, I consider that Dr Greene should have realised, on the basis of both Dr Young's letter no 11/1 of process and the knowledge that is reasonably to be expected of a paediatrician of ordinary competence, that a glucose rich solution was required, and that no less than 10% dextrose was appropriate.
[34] Neurological observations were in fact started at 10.00 (no 10/5 of process, page 622). As I have mentioned in paragraph [31], Dr Cummine gave evidence that, if during the ward round Dr Greene had instructed neurological observations, she would have noted it. Her note of the ward round contains no such statement. Dr Maalouf, the other senior house officer who had been present at the ward round, stated that it would be normal to note any instructions to carry out neurological observations. Dr Naismith's evidence was to similar effect. No evidence was led as to how neurological observations actually came to be started in Laura's case. I accordingly draw the inference that the neurological observations that were started at 10.00 were not carried out on Dr Greene's instructions, but were probably carried out by a member of the nursing staff on her own initiative. In the entry made at 10.00 in the neurological observation chart, Laura's state of consciousness was described as "confused". In the column for remarks was the entry "Eyes reacting to light, moving all limbs. No response to language". On that basis, Laura should possibly have been described not as "confused" but as "drowsy", the next step down in the state of consciousness section of the chart. It is difficult to be certain of the meaning of the entry in question in the observation chart in the absence of evidence from the person who made the observations. The general picture, however, is that Laura was suffering considerable neurological disturbance, but that disturbance was well short of a coma.
[35] The next neurological observation was made at 11.00; this was recorded on a different observation chart (no 10/5 of process, page 621). Once again, no evidence was available as to why this chart was begun, or who filled it in. It appeared, however, that it had been filled in by someone who was not entirely familiar with it. Thus, in the section dealing with best verbal response, both "confused" and "none" were ticked. The difference between the two entries would, however, be of significance on the Glasgow Coma Scale, the standard method of measuring consciousness in such circumstances. In addition, the movements were shown as being of normal strength, but against "best motor response" the entry ticked was "none". Further entries were made on this chart at 12.00, 1.00 and 1.40. These indicated a significant increase in both blood pressure and heart rate between 11.00 and 1.40.
(v) Developments after 11 am
[36] In Laura's clinical notes, the next entry after the report of the ward round was made at 11.30, by Dr Maalouf. It was as follows:
"Very agitated
biting lips
Discussed with Dr McKay in Armistead [Clinic]
10% Dext.
Maintenance fluids
>encephalopathic picture
Ammonia level important
But lab cannot guarantee it can be done today".
Dr Kate McKay was in September 1992 a registrar working for Dr Young in the field of paediatric neurology. She is now a consultant paediatrician at the Royal Hospital for Sick Children, Yorkhill. Dr Maalouf had no recollection of the events that led to his making that note. He recalled that the note was made at 11.30, after he had discussed the situation with Dr McKay and taken her instructions. That would mean that he had observed Laura's condition at about 11.00, although he accepted that that was merely a guess on his part. Dr Maalouf accepted that, on the basis of his note, there had been a deterioration in Laura's condition between 8.50 and 11.00. He stated that, in the circumstances, he would have notified Dr Greene, but would also seek help from the expert in Laura's condition, Dr Young. He would presume that Dr Greene would tell him to consult the expert. He accepted, however, that according to the medical records there was no indication that Dr Greene was informed of the deterioration in Laura's condition. In the event, he had sought help from Dr Young's registrar, Dr McKay; he did not think that he was competent to deal with Laura without such assistance. He reported Laura's condition as he had observed it, and Dr McKay informed him that she was displaying an encephalopathic picture; that was the significance of the arrow beside those words.
[37] Dr McKay's recollection of the telephone call from Dr Maalouf was not clear, and she stated that she could not remember the details of the conversation. Dr Maalouf had told her that Laura had been admitted, and he must have given an indication that she was quite sick, and asked for advice on her management. Dr McKay asked whether the ammonia level was known, and Dr Maalouf replied that it was impossible to get it because the machine was broken. Dr McKay said to get the machine fixed quickly, and that she would speak to Dr Young and get back to Dr Maalouf. She thought it likely that Dr Maalouf would have asked about the administration of fluids, and that she would have advised him to give 10% dextrose. In her examination in chief, Dr McKay stated that it was her impression that there was a degree of urgency in Dr Maalouf's call, and that Laura was sicker than she had been on her last admission to Ninewells. In cross-examination, however, Dr McKay went back on that evidence to some extent. She stated that she did not think that Dr Maalouf's telephone call had suggested an emergency; all that was involved was a level of sickness that required help in management. For that reason she concluded that, when she spoke to Dr Young, she did not give the impression that there was a medical emergency. I deal with Dr McKay's conversation with Dr Young below, at paragraphs [63] - [67]. At the conclusion of Dr McKay's evidence, I asked her whether any sense of urgency had been communicated in her conversation with Dr Maalouf. She replied that she did not get an impression of urgency. What was involved was one level down from an emergency. Laura was seriously unwell, but the conversation was at the level of an exchange of information. In response to further questioning by counsel, Dr McKay stated that the exchange of information was not at a level where Dr Maalouf required immediate and urgent help with Laura's management. I should mention two further points arising out of Dr McKay's account of her conversation with Dr Maalouf. She stated that her conversation with Dr Maalouf had been too short for her to know what was going on. She agreed that, if she had been told that Laura's blood pressure was rising, that she was unresponsive to speech, that her arms were waving, that she was very agitated and that she was biting her lips, she would have recognised the likelihood of brain damage and brain swelling. Moreover, she would have conveyed such a description to Dr Young when she spoke to him. She did not, however, recollect that information of that nature was given to her by Dr Maalouf. In particular, she could not say that Dr Maalouf had informed her of a deteriorating encephalopathic picture.
[38] Dr McKay's evidence about the telephone call was not particularly satisfactory. Much of her evidence was supposition as to what must have happened, where she could not recall the actual details of the conversation. She was not even sure whether she had had one or two telephone conversations with Dr Maalouf. The significance of this is that, if two conversations were involved, she would in all probability have spoken to Dr Young about Laura's condition and conveyed his advice. In fact Dr Maalouf only spoke to one telephone call, and it was not suggested to him that there was a second call. Nor was there any suggestion in the note that he made of the conversation that advice had been obtained from Dr Young. Likewise, Dr McKay changed her position on whether Dr Maalouf had conveyed a sense of urgency. No doubt Dr McKay's lack of detailed recollection was caused by the passage of time since the events in question, and she cannot be criticised for that. Nevertheless, I thought that substantial parts of her recollection were unreliable, and were based largely on supposition. Consequently the conclusions that I am prepared to reach on the basis of her evidence are limited.
[39] On the basis of the evidence of Dr Maalouf and Dr McKay it is difficult to reach detailed conclusions about their conversation at 11.30. I think it probable, however, that Dr Maalouf did not give full details of Laura's condition. In particular, I consider it unlikely that he conveyed a true impression of the seriousness of the encephalopathic picture. I consider it highly unlikely that he conveyed any real sense of urgency. I reach that view for two reasons. In the first place, although Dr McKay changed her position, I formed the impression that her considered view was that no sense of urgency was communicated. In the second place, on the basis of Dr Maalouf's own evidence I did not form the impression that he had appreciated the urgency of the situation; he admitted that he was dealing with matters beyond his competence. I also conclude that the diagnosis of an encephalopathic picture was only made after Dr Maalouf spoke to Dr McKay; it seems clear from Dr Maalouf's note that she was the person who first used the expression.
(vi) Developments after 1.30 pm
[40] After the note of the telephone conversation at 11.30, the next entry in Laura's clinical notes contains results from the analysis of a blood sample. There is no evidence that there was any clinical response to Dr Maalouf's observations of Laura's condition, as recorded in the note made at 11.30. The fluid prescription and balance chart (no 10/5 of process, page 660) does not even indicate that 10% dextrose was administered before 3 pm. The next doctor to become involved was Dr Karen Naismith. She had had to leave the ward round at an early stage, in order to attend a meeting. At approximately 1.30 pm, a nurse spoke to her in the coffee room to asked her to go to see Laura. She was anxious about Laura's condition, and in particular her blood pressure. Dr Naismith stated that it was unusual to be contacted by a nurse in this way.
[41] Dr Naismith had been involved in Laura's treatment in the past. She knew that Laura suffered from OTC deficiency, and knew that she needed metabolites and protein restriction; she also knew that her ammonia levels could become elevated if she were unwell. She was aware that ammonia is toxic to the nervous system. She had no experience, however, of OTC deficiency in an acute state. Dr Naismith went to see Laura, and noted her observations at 1.30 pm. She recorded as follows:
"BP [elevated] 156/132
O/E Very agitated, body withdrawal response to painful stimuli/speech
Pupils dilated, poor reaction equal size
Tone [elevated]...
...
Clonus R & L
...
Ammonia machine is out of order-unlikely to obtain any result today
Imp[ression] Encephalopathy with signs of [raised]ICP [intracranial pressure] and coning.
Glasgow Coma Scale 4".
Clonus is an abnormal neurological sign; it is detected by applying sudden force to the food and ankle, in a backward direction; if that produces a rhythmic beating of the food, that is an abnormal sign. Dr Naismith explained that she was particularly concerned about the signs of coning that she had observed. Coning occurs when the brain is swollen and, because of the pressure, is pushed through the hole at the base of the skull, the furamen magnum. That causes compression of the brain stem and the spinal cord. Dr Naismith was also concerned about the figure of 4 on the Glasgow Coma Scale; that indicated severe neurological compromise. She then attempted to contact Dr Young and Dr Greene. She paged Dr Greene, and was told that he was in the library. In evidence, she expressed some surprise that he was there. When she saw him, she told him that she was very concerned about Laura and that he needed to go to see her. She understood that thereafter he had done so. She further stated that Dr Greene had given her no indication that anyone had contacted him about Laura's condition since 9 am. Dr Naismith further expressed the view, in very clear terms, that if a junior doctor in circumstances such as obtained that morning encountered an abnormal result or a difficulty in the treatment plan, he or she should immediately seek the advice of a senior doctor, either a registrar or, if no registrar were available, the relevant consultant (14 November 2001, 10.11, 10.26).
[42]Dr Naismith ordered that Laura should be given Mannitol, a drug that is thought to shrink the brain (see below, paragraph [85]), and arranged for her admission to the intensive care unit for hyperventilation.
[43] After she had seen Laura, Dr Naismith also tried to contact Dr Young at the Armistead Clinic, where he was conducting a clinic that morning. She was told that he was already on his way to Ninewells. She saw Dr Young when he arrived on the ward. He was very worried about Laura's condition. A treatment plan was provided by Dr Young. As recorded by Dr Naismith in Laura's medical notes, it was as follows:
"Drugs-maintain hydration
max tolerable non-protein intake 25% dextrose & insulin
Na benzoate 500 mg/kg/day > 10 g
Neanycin & lactulose
L Arginine 400 mg/kg/day >
L Carnitine 100 mg/kg/day
L Citrulline 400 mg/kg/day
IV insulin/3g glucose".
This corresponded to a note in Dr Young's handwriting (no 10/5 of process, page 612). Dr Naismith recalled that Dr Young had that note with him, but she did not know when it was written.
(vii) Dr Greene's account of events on 25 September
[44] In 1992 Dr Stephen Greene was a consultant paediatrician at Ninewells Hospital. He had undergone training in paediatrics at hospitals in London, Swindon and Oxford, including Great Ormond Street Hospital. He had been a consultant in Dundee since 1987. His area of special interest was paediatric endocrinology; that involved treatment of hormone disorders, notably diabetes. It is clear, however, that he was an experienced paediatric consultant.
[45] As I have already mentioned, Dr Greene accepted that Dr Young's letter no 11/1 of process was available to him at the ward round. He accepted that that letter made clear that Laura had OTC deficiency, and that she might develop irritability or other neurological symptoms, or that her behaviour might deteriorate. He further accepted that the letter indicated that blood tests should be carried out, that more detailed information was available in the hospital notes, and that Laura was under the care of Dr Young. Dr Greene was aware in general terms of the consequences of failure to treat a patient with a metabolic disorder. His knowledge of metabolic disorders was limited apart from diabetes, which was usually classified as a hormonal disorder, although it has metabolic consequences. He had very little experience of OTC deficiency; he knew the description of the disorder and the basic treatment, but he realised that further knowledge would be required to treat a patient properly. He knew in particular that an acute metabolic crisis could lead to brain damage if it were treated inadequately, and that a child could develop a condition leading to brain damage relatively quickly. He was aware that, if the ability of the body to metabolise nitrogen was compromised, there would be a rise in ammonia levels, and he realised that a rise in ammonia could be very serious. He realised that such a situation could develop rapidly, particularly with OTC deficiency. In relation to Laura's own circumstances, Dr Greene accepted that during the ward round he had heard Laura's medical history as recorded by Dr Cummine in the medical notes. He could not recall whether Dr Cummine had mentioned that Mrs Miller was concerned about Laura's counts rising, but he accepted that it would be extraordinary if she had not mentioned that fact. In the circumstances I conclude that Dr Greene was aware that Mrs Miller was concerned about rising ammonia levels.
[46] In his evidence (15 November 2001, 11.49 am) Dr Greene stated that on the morning of 25 September he prepared a treatment plan without Laura's medical records; steps were being taken to obtain these. He was asked about the appropriateness of administering intravenous dextrose at 4%, as he directed, rather than 10%. He replied that that was perfectly appropriate; "We decided against 10% in our discussion about the case". He thought that 10% would also have been appropriate, but did not think that it would have prevented Laura's metabolizing protein. He added that he thought it impossible to say what the appropriate rate would have been. He agreed that administration of 10% glucose in a catabolic state would have given greater reserves of sugar, depending on the rate of infusion. He thought, however, that the high solute load was potentially worrying because of the possibility that Laura was hyperglycaemic. I may say that this concern did not appear to be shared by any of the other consultants who gave evidence in the case, and I discount it; all of the other consultants accepted that 10% glucose was a standard procedure in treating possible hyperammonaemia. Dr Greene further stated that his interpretation of events was that an infusion of 10% glucose was discussed and rejected. When asked why, he fell back on the fact of discussion as justification. I am bound to say that I am not impressed by this reason, if it can be described as such; on the ward round, he was the consultant, with ultimate responsibility for Laura's care; it was for him to decide on the appropriate rate of infusion, and to do so for sound medical reasons. Falling back on some notion of consensus is simply not acceptable.
[47] Dr Greene accepted that his treatment plan was formulated without reference to Dr Young. In his evidence (15 November 2001, 12.57), he said that he considered that Laura was not merely dehydrated but was possibly suffering from hyperammonaemia at that time when the plan was formulated. He reached this conclusion on the basis of her medical history of OTC deficiency, together with the fact that she was showing physical signs of hyperammonaemia. He further stated that he reached the view that Laura might be suffering from hyperammonaemia on the basis of the clinical picture alone, irrespective of any blood test results, but added that he had no experience of the level of hyperammonaemia. He accepted that at the time he was aware that hyperammonaemia could have serious and immediate consequences.
[48] Dr Greene was subsequently asked whether he made the junior doctors on the ward round aware that Laura was possibly suffering from hyperammonaemia (16 November 2001, 11.13). He replied that he thought they made him aware as much as he made them aware. Dr Naismith, in particular, knew about Laura's condition. The matter was in any event clear from the letters that were available. He suspected that he expressed very little to the junior doctors about the stage that Laura's condition had reached because of his lack of knowledge of her condition. He thought, however, that it was obvious to anticipate hyperammonaemia. He considered that Laura was already displaying clinical symptoms of hyperammonaemia, and he and the junior doctors expressed that view to one another. I am bound to say that, in view of the evidence of Dr Cummine and Dr Maalouf, I do not think that the junior doctors were genuinely aware of the serious risk of hyperammonaemia at the time of the ward round. I likewise consider that Dr Greene certainly did not communicate that risk to them, nor the fact that the risk meant that immediate treatment was required. That explains the total lack of urgency with which Dr Cummine approached the tasks that she was set during the ward round.
[49] In an important passage of evidence starting at 1.55 pm on 15 November 2001, Dr Greene was questioned about the appropriateness of his treatment of Laura during the morning of 25 September. In this and the following paragraph I have attempted to provide a fairly full summary of this passage, with my comments on certain of Dr Greene's answers. Dr Greene was first asked whether from the clinical picture alone and without blood tests he was aware that Laura might have hyperammonaemia. He agreed. He was then asked whether that was an emergency, and he again agreed. Counsel then suggested that a paediatrician of ordinary competence would carry out an immediate examination of the central nervous system. Dr Greene replied that he felt that he had done an appropriate examination as recorded. The irritability and restlessness fitted the description of an acute hyperammonaemic state. There was a neurological examination in that sense. When asked about the record of the examination, he replied that it was stated that Laura was irritable, confused, restless and had no focus of pain; that was compatible with hyperammonaemia. (At this point I should add that, in an earlier passage in his evidence (15 November 2001, 11.14) Dr Greene had stated that a full neurological examination would have added nothing; the picture that he could observe told him that Laura had severe and worrying neurological symptoms). Dr Greene was then asked whether, in view of the fact that there was an obvious emergency, a consultant of ordinary competence should have instructed regular neurological observations. He replied that he thought so, among other observations. In the present case, he did not recollect such a discussion. When pressed about the position of an ordinarily competent paediatrician, he replied that an instruction for regular neurological observations would have been appropriate. Dr Greene further accepted that a consultant paediatrician of ordinary competence would order blood tests as a matter of urgency, but said that he had done so. He also appeared to accept that such a paediatrician should have got in touch with Dr Young; he stated that that is what "we" were trying to do. When asked how, he replied "The team discussed it; I don't know who was delegated and how it was delegated, but there was such a decision to get in touch with Dr Young". It was then suggested that, as he was the consultant who had devised the treatment plan, it was appropriate for him to get in touch with Dr Young personally. Dr Greene did not accept this; he stated that often team members would get in touch with the consultant who had previously had care of a patient.
[50] Dr Greene then expressed the view that his plan was appropriate on the information that he was given. He did not think it necessary to contact Dr Young before devising the plan, because the plan would not be detrimental to Laura; Dr Young's function would be to see whether further therapy was required. Dr Greene accepted that Laura's case involved an actual emergency, and was asked whether a rapid answer would be expected if a junior doctor were asked to contact Dr Young. He replied in the affirmative, but said that he had moved away from the scene. Counsel put to him that there was no record of contact with Dr Young that morning. He agreed, but stated that there were "competent people around". When asked who they were, he replied that Dr Naismith was such a person. The difficulty with that answer, of course, was that Dr Naismith had left the ward round to attend a meeting, and was therefore not available to take part in Laura's management. Dr Greene had no recollection of that circumstance. When asked who else competent was around, he replied Dr Maalouf, Dr Cummine and the nursing staff. In relation to that answer, I do not think it can possibly be said that relatively inexperienced junior doctors, at senior house officer level, and the nursing staff can be expected to take charge of a patient such as Laura, suffering from a rare disorder and in a condition that obviously presented grave risks. Obviously such persons can be expected to perform specific tasks, but it seems clear to me that they must do so under the close control of an appropriate consultant. Dr Greene accepted that Laura presented an emergency; she was suffering from a metabolic disorder of which he knew little, and was at risk of hyperammonaemia and possible cerebral damage. When asked whether, in such a case, it was appropriate that the consultant should take a direct interest, he replied that he thought that he had done so. He formulated a plan, which involved first putting up a drip. It was then suggested that he could not know whether his plan was appropriate until he obtained advice from Dr Young. He appeared to agree with that, but stated that he had been guided by information already given. In view of the unusual nature of Laura's underlying disorder, OTC deficiency, and the very obvious seriousness of her condition at 8.50 am on 29 September, I am bound to say that I do not understand how a paediatrician such as Dr Greene could possibly have concluded that his treatment of Laura was appropriate without first consulting Dr Young, who was the expert on Laura's treatment at Ninewells. In this context, a further answer given by Dr Greene is perhaps of significance. He was asked (15 November 2001, 10.39) whether it was appropriate to contact the consultant normally responsible for a patient's care at an early stage after that patient's admission. He replied "If it was a child with a serious illness or a specific medical problem which you felt you were inexperienced to deal with". In my opinion that comment is directly applicable to Laura's case. I am further of opinion that it was not appropriate to its leave responsibility for contacting Dr Young on a vague and uncertain basis. Even if it was not necessary for Dr Greene to contact Dr Young personally, I consider that a specific member of the medical staff should have been expressly allocated the task of making contact with Dr Young and obtaining his instructions. There was no evidence that Dr Greene gave any such instruction.
[51] In a subsequent passage of Dr Greene's evidence (16 November 2001, 11.18), counsel referred to the clinical notes and suggested that there was no note of any suspicion of hyperammonaemia. Dr Greene agreed that the word was not used. He further agreed that, if hyperammonaemia were suspected, the risk was that the patient had already begun to decompensate in respect of their metabolic disorder, with the result that the body was no longer able to cope with its inability to metabolise nitrogen, and ammonia levels had begun to rise. He accepted that he did not know how to treat hyperammonaemia arising out of OTC deficiency. He considered that his initial treatment was appropriate for hyperammonaemia; it was the only one that he could come up with given his experience. When asked whether it was appropriate to speak directly to somebody who knew, he replied that "we" were trying to do that. He agreed that there was no note to that effect, but he did not agree that he should have done that personally. He was then asked whether the only reasonable and safe alternative to going to the library to find out about treatment was to contact Dr Young, and he replied in the affirmative. Counsel then suggested that it was in an emergency, and he replied "For which we started an emergency plan". He was then asked whether the response was appropriate for an emergency. He replied that in retrospect he did not think that it was, but it was "the plan agreed by the team at the time". Counsel then suggested that those on the ward round had no knowledge of the treatment of hyperammonaemia, and he replied that that was possible, but that Dr Naismith had a special interest in paediatric neurology. I have already commented on the fact that Dr Naismith required to attend a meeting. In any event, it was clear from her evidence that her knowledge of the treatment of metabolic disorders was very limited indeed. Dr Greene then went on, in the passage of evidence that I have been summarising, to say that it was obvious from the team's actions that they did not know more. When asked whether he appreciated the need to treat Laura urgently, he replied in the affirmative.
[52] In cross-examination (20 November 2001, 3.36), Dr Greene was asked whether he accepted that it was his duty to interpret the information that he had in front of him at 8.50 and come to a conclusion that Laura was already displaying clinical signs of encephalopathy. He replied in the affirmative. He was then asked what his assessment was. He replied that this was a child with known OTC deficiency who had signs and symptoms suggestive of hyperammonaemia. He was asked whether he accepted that what he had noted on examination suggested encephalopathy. He replied in the affirmative. He was then asked whether that meant some sort of adverse effect on the brain, and he replied in the affirmative.
[53] Dr Greene instructed Dr Cummine to take blood samples for ammonia and glutamine and have them tested by the laboratory. In evidence, (15 November 2001, 2.10) he stated that he would have expected to have the results back in half an hour. The ammonia machine was, of course, broken, and it was impossible to obtain the relevant results. According to the clinical notes, however, Dr Greene is not recorded as having done anything about this situation. Nor did any witness suggest that he took any action. He claimed (15 November 2001, 2.20) that he would have been surprised if the intravenous infusion had only started at 10.30 or 11, because it was supposed to start as soon as possible. He agreed that a consultant paediatrician of ordinary competence should have ensured that it started as soon as possible. He accepted that that did not happen, but was unable to say whose fault it was. He further accepted that, if he had supervised matters personally, he would have been aware of the difficulties.
[54] Dr Greene (15 November 2001, 2.43) thought that Dr Maalouf had contacted him at about 11.30, but could not remember what he had said. On the basis of the clinical notes, Dr Greene accepted that there had been a deterioration in Laura's condition at about 11.30. The fact that she was agitated was a definite change, causing concern. Dr Greene stated that at that point he decided that he required further information regarding hyperammonaemia. He did not go to see Laura; because he had no experience of the condition, he had to find out about it, and he had received no feedback from Dr Young. He had therefore gone to the library. In relation to this part of Dr Greene's evidence, I may say that I find it extraordinary that he did not go to see Laura, in view of the obvious deterioration in her condition. I also think it extraordinary that he did not at this stage take personal responsibility for contacting Dr Young. Dr Greene stated (15 November 2001, 2.49) that he had experience of a condition known as diabetic ketoacidosis, and had a particular interest in diabetes. That condition can lead to rapid neurological deterioration, with the onset of cerebral oedema. In such cases, he accepted, rapid intervention may be necessary. That arose because of the risk of damage from brain swelling. Dr Greene agreed that the entry for 11.00 on the neurological observation chart (no 10/5 of process, page 621) showed a developing encelopathic picture. That obviously involved similar risks. I observe that, in spite of that, no further action was taken until after 1.00.
[55] At about 11.00 Dr Greene went to the library to carry out research. He stated (15 November 2001, 3.46) that he was in some way called back to the ward, and as he entered the ward he met Dr Young. At this point Dr Greene was carrying information that he had obtained in the library. He understood that it was a protocol for the treatment of hyperammonaemia derived from the leading work on metabolic disease, "The Metabolic Basis of Inherited Disease", New York, 1989; the excerpt came from a chapter on urea cycle enzymes by Brusilow and Horwich. He was referred to a document in Laura's medical notes (no 10/5 of process, page 474), and said that he thought he recognised that as the protocol in question. Thereafter Laura received the treatment described below.
(viii) Dr Young's involvement
[56] In 1992 Dr Young was the only paediatric neurologist at Ninewells Hospital. He had begun to specialise in that area in the mid 1980s. He had been involved with Laura's care since she was first admitted to Ninewells in July 1987. He had first raised the possibility that she was suffering from OTC deficiency, but he referred her to Great Ormond Street Hospital in London in order to obtain the advice of the metabolic specialists there. Thereafter he conducted correspondence with Dr J. Leonard, a specialist in paediatric metabolic medicine at Great Ormond Street, and regularly took advice from him in relation to Laura's treatment. I have already dealt with Dr Young's involvement in Laura's care prior to 25 September 1992. I should state at this point that I found Dr Young to be an extremely impressive witness. He was clearly very conscientious in the performance of his duties. That can be seen in the way that he corresponded at length with Dr Leonard about Laura. He obviously accepted that his primary speciality was neurology rather than metabolic medicine, although the two are related, especially when a metabolic disorder has neurological consequences, but he was determined to ensure that Laura should have the best possible care. It was clear that he took great care to carry out thorough research into OTC deficiency, both by reading medical literature and by corresponding with one of the United Kingdom's leading specialists in metabolic medicine at Great Ormond Street Hospital. In consequence, I am of opinion that he had arrived at a good working knowledge of OTC deficiency and its treatment.
[57] Dr Young was shown the clinical notes taken by Dr Cummine following Laura's admission on 25 September (21 November 2001, 2.19). He stated that Laura should have been given an infusion of 10% dextrose, as recommended in his letter no 11/1 of process; he was clear that a "glucose rich" solution must be of that strength or higher. He considered that 4% dextrose could not be described as glucose rich; 4% was not very strong, and in fact was the standard maintenance intravenous fluid designed to prevent dehydration. It did not correct anything. The point of strong glucose was to encourage an anabolic state, and thereby mop up nitrogen.
[58] At Ninewells in 1992, if a patient was admitted who was already under the care of a consultant, the normal practice was for that consultant to be informed (21 November 2001, 2.30). The consultant might be informed either by the consultant who saw the patient following admission or by junior staff. If the patient was unwell, the consultant should be told immediately. When Laura was admitted on 25 September, Dr Young would have expected to be told by Dr Cummine that she was there. In any event, he would have expected Dr Greene to telephone him. Dr Greene did not know how to treat Laura, and she was obviously ill. Dr Young developed this point in cross-examination. He stated (23 November 2001, at 12.28 and 12.53) that it had never crossed his mind that he would not be called if Laura were admitted to Ninewells. He was the only consultant in paediatric neurology at Ninewells, and consequently he was on call all the time. The letter no 11/1 of process dictated the first line of action while help was being obtained.
[59] On the morning of 29 September Dr Young had a clinic at the Armistead clinic, which was some distance from Ninewells Hospital (21 November 2001, 2.39). He would not have arrived there before 9 am. If he had been convinced that Laura was seriously ill and deteriorating he would have left the clinic at once. If her condition were not deteriorating, he would have given advice and asked to be telephoned back in half an hour. If he had been told what appeared in the clinical notes of Dr Greene's examination at 8.50 am (no 10/6 of process, page 193; summarised at paragraph [29] above), he would have instructed Dr Greene to give Laura stronger glucose and review the position in half an hour to consider her response. It would be necessary to see whether she was generally improving, and specifically to look at her level of consciousness. If, on the other hand, the consultant concerned had gone further than the notes and had indicated that Laura had severe worrying neurological symptoms and that her neurological condition gave rise to major concern, Dr Young would have left the clinic at or shortly after 9 am to see Laura. When he did, he would have carried out and recorded a full examination of her central nervous system, and would have instructed neurological observations every hour or half-hour, the latter if she were deteriorating rapidly. Dr Young was further of opinion that the intravenous infusion should have started as soon as possible, and the consultant should have ensured that that happened. Dr Young also explained the further treatment that he would have administered if he had been called to see Laura at 9 am. I deal with his evidence on that matter below, in the section of my opinion dealing with causation of loss.
[60] Dr Young than commented on the documentary evidence available as to Laura's condition at 11.30 (21 November 2001, 3.13). He considered that any competent clinician should have recognised that brain damage was occurring, and possibly brain swelling. Consequently a brain shrinking regime should have been initiated, to prevent secondary damage. That would have involved calling in an emergency team, including a brain surgeon and an anaesthetist.
[61] In the event, Dr Young stated that he was not told of Laura's condition when he was at Armistead. This involves a conflict of evidence between him and Dr McKay, which I deal with in the next part of this opinion. Dr Young explained that he completed his clinic at Armistead and had lunch there. He returned to Ninewells. When he arrived at the ward he found Laura in a very serious state indeed (21 November 2001, 3.24). He had gone to his room first, and found a note from Dr Naismith there. He distinctly remembered the shock and surprise that he experienced. He also remembered telling Mr and Mrs Miller that he had no knowledge that Laura had been admitted. He was sure that he would not have stayed at Armistead and had lunch if he had known about Laura. Moreover, if he had been given information at 11.30 that suggested an encelopathic picture, he would not have recommended glucose at that time, as it was too late. Instead he would have recommended the use of sodium benzoate and other metabolic drugs, and possibly a brain shrinking regime. He was therefore sure that he had not been told of Laura's admission.
[62] When Dr Young arrived on the ward, he found that Laura had been examined by Dr Naismith. When she saw Laura she had recognised an encephalopathic picture and had initiated a brain shrinking regime. Dr Young arrived as she had completed that. Dr Young then produced from his files the recipe for treatment, and added frusemide to it. He started the sodium benzoate and other intravenous drugs. He also arranged for Laura to have a CT scan and for a neurosurgical colleague to see her. Dr Young was referred to the list of drugs found in Laura's medical records at no 10/5 of process, page 612. This list corresponds to the prescription that was actually used after 1.30 (see paragraph [43] above). He identified the handwriting as his apart from the last four lines, which were in Dr Naismith's handwriting. He could not, however, recall when that document was written. He stated that he kept in his files extracts of current journals for treatment such as this. Often photocopies kept in medical notes were lost, and consequently he kept copies in his own room. The recipe might have come from a journal, and it was possible that it was written by him when he realised that there was a problem. He always kept the information that he felt he needed in the files in his office. The purpose of the drugs listed on that page was an acute treatment regime for the situation that they found themselves in. It is clear in my opinion that it was Dr Young's treatment that was used after 1.30; that is apparent from the correspondence between the recipe in his handwriting (no 10/5 of process, page 612) and the treatment that appears in Laura's clinical notes (no 10/6 of process, page 194). Dr Greene may have appeared with the protocol found at no 10/5 of process, page 474, but that does not appear to have been the treatment used.
(ix) Possible discussion between Dr Young and Dr McKay
[63] On the morning of 25 September Dr McKay was also at Armistead to conduct a clinic. She was there when she received the telephone call from Dr Maalouf referred to above. Dr McKay stated that, after she received the telephone call, she spoke to Dr Young about Laura. Dr Young had no recollection of such a conversation. Moreover, he was adamant that he had not heard about Laura's admission to Ninewells prior to 1.30 for the reasons stated in paragraph [61] above. In cross-examination, he repeated that he had no recollection of any such event (23 November 2001, 2.12-2.16). Dr McKay's account of such conversation was put to Dr Young in some detail. This included a statement that, when Dr McKay went to speak to him, he had brought something out of a drawer in his room at Armistead and had said to use intravenous dextrose, possibly at 10%. Dr Young replied that he did not keep any information regarding acute management at Armistead but in his office in Ninewells. Moreover, if he had prescribed intravenous dextrose on the basis of the picture found in Laura's clinical notes at 11 or 11.30 am, he would have been at fault; that treatment was only appropriate for drowsiness, and not for an encephalopathic picture. He did not think that he was at fault, however. During this part of his evidence, and indeed generally, I found Dr Young to be an extremely careful witness, and I made a note to that effect against this passage.
[64] Dr McKay gave evidence about her telephone conversation with Dr Maalouf (12 June 2002, 3.12). She described her recollection as "obviously a lot poorer than it was", and added that she did not remember the detail. She asked about the ammonia level, because that was important to management. Dr Maalouf told her that the machine was broken, and she said to get it fixed quickly. She told him that she would speak to Dr Young and get back to him. She thought it likely that she would ask Dr Maalouf about the administration of fluids, and would tell him to administer 10% dextrose; she knew about these matters as a result of having treated Laura previously. She stated that she then went to speak to Dr Young (12 June 2002, 3.36). She stated that she had a clear memory of that, and she remembered going to his room. Dr Young was sitting at his desk, and she told him about the telephone call. She stated that Laura had been admitted to hospital, and she thought that she was quite unwell; she did not, however, remember the details of what she said. Nor could she remember the detail of what Dr Young said. She thought that he had said something about a management protocol. He went into his desk and obtained a paper; she thought it was a protocol for the management of acute encephalopathy. She remembered seeing him reading from it, she thought to himself rather than aloud. She thought that she probably asked Dr Young if there were things that she had to record, or if a copy of the paper was available. She could not remember what he did with the paper. Dr McKay then stated that she went back to her own room and telephoned Dr Maalouf. She had no firm recollection that Dr Young said anything to her about drugs, but she thought that he did; managing Laura's condition involved unusual drugs in very specific amounts. Dr McKay also thought that the word encephalopathic was used by Dr Young to describe Laura's condition; it was not a word that she normally used, although she knew what it meant. Subsequently (13 June 2002, 11.06) Dr McKay stated that she had no clear memory of the specific details of what Dr Young told her to do. She was clear that she returned the telephone call after she had spoken to him, and she thought that she probably asked Ninewells to prepare the intravenous preparations and drugs that would be required, but she had no clear recollection of that. When questioned further, she thought that Dr Young must have told her the contents of the paper that he was reading from; alternatively he might have written down the drugs required, as Dr McKay was unfamiliar with these. She had no recollection, however, of taking away any piece of paper, but she would not have carried the information in her head. She said, in relation to the drugs, that she had no specific recollection, but that she was sure that Dr Young had said that these drugs were likely to be required when they got back to Ninewells.
[65] In cross-examination (13 June 2002, 4.30) Dr McKay stated that she possibly gave advice on management in the course of her first telephone conversation with Dr Maalouf. It was put to her that there was no note of Dr Maalouf's recording anything further in the note that he made at 11.30 (no 10/6 of process, page 193). She agreed, and claimed that she had always told the defenders' agents that she had spoken to Dr Maalouf in more than one telephone call. The following day (14 June 2002, 10.32) Dr McKay stated that she had been reflecting about the events on 25 September 1992 and re-reading her precognitions. She was now not clear that there was a second telephone call. She stated that she was very clear about the first telephone call and a conversation with Dr Young, but not the second. She also referred to the fact that, when she arrived at the ward, Dr Naismith was drawing the drugs up for administration to Laura. These must have come from the pharmacy, and that must have been on someone's instructions. Shortly thereafter (14 June 2002, 11.20) Dr McKay stated that she was not clear that Dr Young had had a piece of paper in his room at Armistead, or about the terms of discussion with him, or about writing the names of the drugs down.
[66] On the issue of a possible conversation at Armistead between Dr Young and Dr McKay, I prefer the evidence of Dr Young. I do so for a number of reasons. In the first place, it seemed to me that Dr Young gave his evidence in a careful manner. His recollection of other events on 25 September 1992 was clear, and it would be most surprising if he had completely forgotten about the telephone conversation at Armistead. In the second place, much of Dr McKay's evidence about the alleged conversation was expressly based on supposition rather than actual recollection. She regularly stated that she "thought" that something happened, or that something "must have" happened. I have attempted to convey some of the flavour of the evidence in the last two paragraphs, but this comment on her evidence is a general one. In the third place, Dr McKay changed her evidence to some degree on one very important matter, namely whether there was a second conversation with Dr Maalouf. Initially she was clear that such a conversation must have taken place; latterly, however, she was not sure. Dr Maalouf's note does not refer to more than one conversation, and indeed reads as a composite whole. That tends to suggest that there was only one such conversation. In the fourth place, Dr McKay supposed that Dr Naismith was drawing up Laura's drugs at Ninewells because she had previously been told by Dr McKay of what to do. Dr Naismith's evidence, however, was that she had devised the treatment plan used after 1.30, recorded at page 194 of 10/6 of process, in consultation with someone else, she thought Dr Greene or Dr Young (12 November 2001, 3.58). She agreed that that treatment plan was identical to the treatment plan found at page 612 of no 10/5 of process, which was in Dr Young's handwriting. She remained unclear on whose advice the treatment plan was prepared (14 November 2001, 10.38). There was no suggestion, however, that the information had come from Dr McKay, either directly or through Dr Maalouf. Dr Young's evidence, too, was that the prescription had originated with him (see paragraph [62] above). Dr McKay's evidence thus seems demonstrably wrong on this important point of detail. In the fifth place, Dr McKay was adamant that Dr Young had taken a piece of paper from his desk at Armistead containing, she supposed, the relevant treatment for a state of acute encephalopathy. Dr Young, on the other hand, stated that he could not have done so, because he kept information of that sort in his room at Ninewells. That seems inherently probable, as he would deal with acute medical conditions of that nature at Ninewells and not at Armistead. This is, I think, a telling point of detail, which strongly supports the account given by Dr Young. In the sixth place, if Dr Young had consulted a document at Armistead and produced a recipe for metabolic therapy, as Dr McKay seemed to suggest, it is likely that she would have told Dr Maalouf in the course of the second telephone conversation; Dr McKay stated in evidence that she would probably tell Dr Maalouf to get the drugs and preparations ready for further treatment. In that case, it is clearly likely that Dr Maalouf would have recorded what she said to him; the recipe would necessarily have been a complicated one that could not safely be memorised. In Dr Maalouf's note, however, there is no record of any metabolic therapy. Moreover, the treatment that is recommended there, 10% dextrose, is a matter that Dr McKay accepted was within her competence, as she had treated Laura on her last admission. The lack of any reference to metabolic therapy in the note is, I think, of considerable significance. In the seventh place, Dr Young impressed me as very clear and convincing in his evidence about the shock and surprise that he experienced when he returned to Ninewells and discovered Laura's condition. When all of the above matters are taken into consideration, I have little hesitation in preferring Dr Young's evidence. For this reason I find that the conversation spoken to by Dr McKay did not take place, and that on this point Dr McKay is mistaken.
[67] Even if that is wrong, and some sort of conversation about Laura took place between Dr Young and Dr McKay, I am satisfied that the full seriousness of Laura's condition was not conveyed to Dr Young. I reach this conclusion for three reasons. First, as explained in paragraph [37] above, I formed a distinct impression that in the conversation between Dr Maalouf and Dr McKay the true urgency of Laura's condition was not communicated. Against that background, I think it unlikely that Dr McKay would have communicated any real sense of urgency to Dr Young. Secondly, my impression of Dr Young's evidence as a whole is that, if he had understood that Laura was in a serious condition, he would have taken urgent action. It was clear that he had expended a great deal of time and effort in reaching an understanding of her condition and how to treat it, and I am satisfied that if he had been told that she was in a serious condition he would have taken immediate action. Thirdly, I formed a very distinct impression that he was greatly surprised by Laura's condition when he arrived at Ninewells. That would not have happened if the seriousness of her condition had been communicated to him.
E. Negligence
[68] The pursuer's averments of fault are obviously based on the proposition that it was the duty of the medical staff who treated Laura to provide her with the standard of care to be expected of ordinarily competent medical practitioners exercising reasonable skill and care. More specifically, the pursuer avers the following duties. First, it was the duty of the doctors responsible for Laura's care between the time of her admission and Dr Greene's ward round to make contact with Dr Young. Secondly, it was Dr Greene's duty to assess Laura carefully when he saw her at 8.50 am and to note the contents of the letters detailing the treatment to be administered to Laura when she presented with suspected hyperammonaemia. Thirdly, it was Dr Greene's duty to be aware that Laura was at risk of developing cerebral damage if her condition was untreated, and to note that Laura was already displaying clinical signs suggestive of encephalopathy at the time of the examination. Fourthly, it was Dr Greene's duty to prescribe immediate intravenous fluid therapy for Laura at the time when he examined her; such therapy would have consisted of a 10% dextrose solution with added saline. Fifthly, it was his duty to be aware that the severity of Laura's clinical signs was such as to indicate that her ammonia level was markedly elevated, even without waiting for confirmation of her blood ammonia level, particularly when it was apparent that there would be a considerable delay in obtaining such a level. In these circumstances, it was his duty to start Laura on sodium benzoate, sodium phenylacetate and amino acids at the time of his examination, and to check that those drugs were available for such administration. Sixthly, it was Dr Greene's duty to manage Laura himself or delegate her care to a senior doctor at the time of the ward round and ask that he be informed regularly of her progress throughout the morning. Seventhly, it was his duty to carry out a neurological examination and instruct that regular neurological observations be carried out, and further to review Laura at the end of the ward round. Eighthly, it was Dr Greene's duty to consult Laura's medical records and to inform Dr Young of her admission and clinical condition following his examination at 8.50 am. Ninthly, it was the duty of the doctor who examined Laura at or about 11.30 am (Dr Maalouf), upon realising that Laura were showing signs of encephalopathy, to institute immediate treatment to control her hyperammonaemia, and to institute immediate treatment for such encephalopathy. Tenthly, it was that doctor's duty to note that Laura's GCS had been no more than 6 at 11.00 am and to arrange for her admission to intensive care for management of her deteriorating cerebral state.
Evidence
[69] Evidence in support of those averments was led from Dr J.O. Beattie. Dr Beattie is a consultant paediatrician at the Royal Hospital for Sick Children, Yorkhill, and an Honorary Senior Lecturer in Child Health at Glasgow University. He has been a consultant paediatrician for 16 years. He practises as a general paediatrician involved in all aspects of acute and chronic paediatric medical care. He is currently Head of Service of Yorkhill's Acute Assessment Unit. Dr Beattie was in my opinion well qualified to express an opinion on the standard of care to be expected of a general paediatrician of ordinary competence exercising ordinary skill and care; that is, of course, the test that must be addressed. I found his evidence to be clear and convincing, and I accept it in its entirety. His views were fully supported by Dr P.H. Robinson (5 December 2001, 12.52). Dr Robinson was, however, a specialist in paediatric metabolic medicine, and in determining the standard of care that ought to have been demonstrated by a consultant paediatrician it is the evidence of a consultant paediatrician that is critical.
[70] Dr Beattie was asked (28 November 2001, 2.04) about the level of knowledge of inborn errors of metabolism that should be expected from paediatric consultants. He stated that all such paediatricians should have a broad general knowledge of such disorders, as it forms part of their undergraduate and postgraduate training. So far as OTC deficiency was concerned, paediatricians should know the consequences of failure to treat. They should know in particular that ammonia toxicity is a serious risk with the disorder; they should also know that high levels of ammonia threaten the patient's survival, and can affect organs including the brain. Checking brain ammonia is therefore part of the routine if there is evidence of brain dysfunction. A paediatrician should also know the general approach to treatment of such disorders, and that there is an urgent need for treatment involving particular drugs. A paediatrician should also know to remove protein from the diet, and to reduce the possibility of catabolism by giving a high energy source, orally or more usually intravenously. These were all matters which, in Dr Beattie's opinion, should be within the knowledge of any consultant paediatrician of ordinary competence. That level of knowledge would not apply, however, to a doctor at senior house officer level. In cross-examination Dr Beattie stated (29 November 2001, 12.20; 30 November 2001, 12.26) that he had been an examiner for the Royal College of Paediatricians for about ten years, and that the College examined on inborn errors of metabolism. In the same passage of his evidence, he stated that a competent paediatrician should know the general features of presentation of the five urea cycle disorders, including OTC deficiency, and the basic response to those disorders.
[71] Dr Beattie went on (28 November 2001, 2.14) to deal with intercurrent infections in patients with metabolic disorders. First, all illnesses in children usually produced lack of appetite and hence lack of energy intake. Consequently protein was broken down to provide energy, which produced a state of catabolism. Secondly, infection can slow down such minor enzyme activity as remains. The risk is accordingly that, as stores of energy run out, the body starts to break down protein as an alternative source of energy. The breakdown of protein produces high ammonia levels in the bloodstream. That in Dr Beattie's view was a risk of which a paediatrician of ordinary competence should be aware. Dr Beattie was then asked how a paediatrician should diagnose a child known to have OTC deficiency who presented at hospital with symptoms such as behavioural changes, irritability, vomiting and lethargy. He replied that the paediatrician had to assume that OTC deficiency had produced destabilisation until it was proved otherwise. So far as treatment was concerned, a rapid clinical response was required, in a variety of ways. Blood samples should be taken immediately, and a drip set up. That should be done without delay. If the paediatrician was unfamiliar with the disorder, he should contact the consultant who had knowledge of it. It might also be useful to examine the patient's records.
[72] The drip should be used to administer moderately concentrated glucose; that was the standard response (28 November 2001, 2.23). In general, 10% dextrose is standard in these situations. That should be known to any consultant paediatrician of ordinary competence. In this case the letter no 11/1 of process gave some guidance through the expression "glucose rich", but the standard response should be known independently of that. So far as blood tests were concerned, ammonia would be routinely checked, but not necessarily glutamine. In this case, however, the letter no 11/2 of process specified that blood glutamine should be tested. In cross-examination (29 November 2001, 2.01), Dr Beattie refused to accept that "glucose rich" simply meant that fluid should contain glucose; it meant that there should be more than the lowest amount of glucose, which is 4%; the next step up is 10%. Dr Beattie disagreed (29 November 2001, 2.14) with the suggestion that, in view of the terms of the letter no 11/1 of process, the paediatrician should have regard to high blood sugar levels in determining how much glucose to administer. He stated that paediatricians tend to ignore high blood sugar in non-diabetic children; high blood sugar is common in acute illness. Consequently he would expect 10% dextrose to be administered unless there were a clear reason not to do so.
[73] So far as other management was concerned, the case should be discussed with the child's consultant (28 November 2001, 2.26). That in Dr Beattie's opinion was fundamental with any rare disorder, if the treating consultant was not familiar with the disorder. Such discussion should take place when the drip is set up, and there should be no delay if the treating consultant is not sure how to manage the patient. In Dr Beattie's opinion no other course was safe. That, if I may respectfully say so, seems very obvious.
[74] Dr Beattie went on to deal with the position of a senior house officer in the situation faced by Dr Cummine following Laura's admission to Ninewells. He indicated that he was not certain that he would expect such a doctor to do more than Dr Cummine did. That was so even if the child's mother was concerned that counts were rising; he was not certain whether the senior house officer would have sufficient knowledge to react to that information. Dr Beattie was then referred to the clinical notes of Dr Greene's ward round found in no 10/6 of process at page 193 (28 November 2001, 2.38). He commented that what was missing was a neurological examination. He would expect the consultant to be aware of the risks of rising ammonia if a condition such as that described in the notes remained untreated. The purpose of the central nervous system examination would be to discover whether there were any unusual signs. That might include focal neurological signs, such as asymmetry of muscle tone. In addition, the examination would provide a baseline for future changes in the patient's condition. A similar point was made in cross-examination (29 November 2001, 3.06). At 9 am Laura was noted as being "dry", which indicated dehydration. The response that Dr Beattie would expect was the immediate setting up of a drip containing 10% dextrose. That is because dehydration promotes catabolism, and hence is itself a risk in a patient with OTC deficiency. Such a drip might have been instructed by the senior house officer who examined the child, as he or she would usually record dehydration, but it should certainly have been set up as soon as the child was seen on the consultant's ward round. Following the setting up of the drip, the general approach should be for someone to stay and manage the child, as she was in a highly threatening situation, involving a clinical emergency. In Dr Beattie's view the consultant should have recognised that.
[75] In relation to Dr Greene's treatment of Laura, Dr Beattie thought that the generous fluid volume in the drip (130% of normal requirements) was good, but he criticised the glucose concentration (4%) as the lowest available (28 November 2001, 2.47). He also thought that finding Laura's medical records was important, and that the case should have been discussed with Laura's normal consultant. In relation to the timing of the discussion with that consultant, Dr Beattie thought that if the ammonia figure was available immediately it might be useful to have the discussion thereafter. The maximum delay to obtain the figure, however, was 15 or 20 minutes. If the ammonia figure was not then available, he thought that the consultant was duty bound to overreact; he should assume the worst case, and call the patient's usual consultant immediately. In Laura's case, Dr Beattie stated that his general impression on studying the clinical notes was a lack of urgency. He thought that, as soon as it was known that there would be delay in obtaining the ammonia result, the drip should have gone in. While it was usual to take the blood sample before setting up the drip, that was a minor consideration compared with the threat to Laura. He thought that Dr Cummine was not aware of the urgency of the situation, and he assumed that she was not guided as to how to respond. It was acceptable to leave a senior house officer to take the blood sample and start the intravenous infusion, but it was essential to provide her with clear guidance that the case was urgent. Moreover, the consultant would be expected to review the case rapidly, coming back frequently over the next hour or so. Such rapid review by the consultant was necessary because of the biochemical urgency of the situation. The child was encephalopathic, and brain swelling had to be assumed. (The existence of encephalopathy at the time of the ward round was accepted by Dr Greene: see paragraph [52] above). That was so even at 9 am, and even if the child had not suffered from OTC deficiency; another possibility was meningitis, which had to be responded to in the same way. Dr Beattie also thought (28 November 2001, 3.15) that special nursing should have been instructed. A nurse should have provided direct care to Laura within a high dependency framework, monitoring her vital signs such as blood pressure and conducting neurological observations. Initially, monitoring of vital signs and neurological observations should have been carried out every 15 or 20 minutes, to get a feel for the dynamics of the situation, but the period might be extended if Laura's condition was not seen to change. If the nurse noted a change, she should inform the medical staff, as the purpose of such observations was to enable early intervention if Laura's condition deteriorated. Dr Beattie would have expected a consultant paediatrician of ordinary competence to have instructed such neurological observations.
[76] Observations had been made by 11 am. By this time, in Dr Beattie's opinion, Laura's neurological condition was extremely serious (28 November 2001, 3.25). In general, Laura should have been in the intensive care unit by this stage, with appropriate treatment to deal with brain swelling. Prior to that stage, Dr Beattie considered that Dr Greene ought to have taken a hands-on approach, either remaining at Laura's bedside or returning frequently. Junior doctors could set up the drip and take blood samples, but the matter had to be reviewed by an experienced clinician. There was a need to retain personal control. Even if the consultant had not seen OTC deficiency previously, he would have his broad experience to fall back on. Similar points were made in cross-examination (29 November 2001, 2.55).
[77]Dr Beattie stated that the consultant treating Laura at about 9 am should have got in touch with the consultant responsible for her overall management. In his opinion the treating consultant should not have left the job of contacting the general consultant to a junior doctor, although that depended on the degree of emergency involved (29 November 2001, 11.22). The present case, however, was very complicated, and would involve a highly technical discussion between two experienced paediatricians. Even if the matter were left to a senior house officer, the treating consultant would need to confirm that contact had been made and what the response was. If he simply asked the patient's usual consultant to come immediately to the ward, all he would require to know was that the consultant was coming, and any plan in the meantime. If he devised a treatment plan before speaking to the general consultant, the treating consultant should discuss it with his colleague to confirm that it was appropriate. In cross-examination (29 November 2001, 2.59) Dr Beattie commented on Dr Greene's instructions to contact Dr Young, and stated that he would expect a much more specific instruction than was apparently given. He should have identified a particular person to make the telephone call, and tell that person what to talk about and to report back. Because of the complexity of the case, and the complex treatment required, he would not have placed the matter in the hands of a junior doctor; if discussions were consultant to consultant, there was no room for error.
[78] If a child such as Laura did not have OTC deficiency but was suffering from confusion due to dehydration, that would be a clinical emergency and would need immediate treatment. Thus if a child is confused and dehydrated that is itself an emergency (29 November 2001, 11.36). In the presence of OTC deficiency, when the child was suffering from irritability and confusion, and was recognised to be dehydrated, there was a double emergency (29 November 2001, 11.42). The reaction then should have been immediate intravenous therapy, the choice of fluid depending upon overall status. In relation to the OTC deficiency, general supportive treatment would be needed, and specific treatment would be required for the disorder. To administer the latter, most paediatricians would want to confirm the treatment with the patient's regular consultant. In Laura's case, Dr Beattie was uncertain whether a paediatrician should have recognised the need for intravenous metabolites at 9 am; he would need to talk to the child's regular consultant to obtain guidance. Dr Beattie further considered (29 November 2001, 11.49) that a consultant paediatrician of ordinary competence should have recognised an encephalopathic picture at 9 am. Laura's confusion was most striking, as that is not normal in a child. A child may be restless and irritable as a result of many illnesses, but confusion is dramatic, and always needs to be dealt with. In that situation there was a need for the paediatrician to review the situation, and find out what Dr Young had to say. When asked how soon that should have been done, Dr Beattie replied that he found it hard to give a firm figure, but 15 minutes or so was his feeling.
[78] Dr Beattie was then referred to the entries at 11 and 11.30 in Laura's clinical notes and neurological observations sheet (29 November 2001, 11.53). He stated that these showed a deterioration in vital signs, including rises in blood pressure and pulse rate. Dr Beattie was asked to comment on the proposition that a junior doctor told Dr Greene what was happening and was advised that he, the junior doctor, should telephone Dr Young, Dr Greene went to the library to find out more about OTC deficiency. Dr Beattie replied that that was not what he would regard as appropriate in a consultant paediatrician of ordinary competence, and indeed not a normal human reaction. At least the paediatrician should go to see the child.
Conclusions
[80] Dr Beattie was subjected to searching cross-examination, but my view of his evidence was not significantly altered by it. In the light of his evidence, I conclude that the pursuer has established fault against the defenders. In the first place, I am of opinion that at 8.50 am it was Dr Greene's duty to make a careful assessment of Laura, to note the contents of the letters nos 11/1 and 11/2 of process, to be aware that Laura was at risk of developing cerebral damage if her condition was untreated, and to note that Laura was already displaying clinical signs suggestive of encephalopathy by that time. That was largely accepted by Dr Greene himself, and was clearly spoken to by Dr Beattie. It was not clear on the evidence whether Dr Greene actually concluded during the ward round that Laura was displaying an encephalopathic picture by 8.50; what is important, however, is that he ought to have done so, and ought to have based his treatment on that view. In the second place, I consider that the Dr Greene ought to have had sufficient knowledge of OTC deficiency to realise that ammonia levels could rapidly become elevated in the situation that Laura presented, and that high levels of ammonia can cause brain damage unless the very rapid treatment is provided. He should also have had knowledge in general terms of the treatment that was required to deal with the disorder, and in particular the urgent need to provide glucose to reduce Laura's catabolic state and the need to use metabolic therapy; the details of the metabolic therapy, however, and in particular the specific drugs and dosages that should be used were not matters that he ought to have known about. That leads on, however, to the next point, which is of critical importance.
[81] In the third place, I am of opinion that at or very soon after 8.50 Dr Greene should have made contact with Dr Young to obtain advice on Laura's treatment. I reach this conclusion for a number of reasons. First, Laura was known to suffer from OTC deficiency, a very rare disorder which required specialised treatment; Dr Young was the consultant who had been in charge of her in the past, and was obviously in the best position to advise on that treatment. Secondly, the treatment involved the use of metabolic therapy, which required that specialised drugs should be administered in very precise doses; only Dr Young could provide details of such treatment without the need for extensive research. Thirdly, in view of the conclusion that Laura was displaying an encephalopathic picture, there was a clear need for urgency in starting treatment. Dr Young was the only person who could provide detailed advice on Laura's treatment within a sufficiently urgent time scale. Dr Greene stated in evidence that he gave instructions to get in touch with Dr Young, although it is clear that those instructions were not carried out. In my opinion the duty to make contact with Dr Young is not fulfilled by vague and general instructions to junior doctors to get in touch. What was required was either action by Dr Greene personally or very specific instructions to a designated junior doctor to speak to Dr Young. In the latter event, Dr Greene should have followed up the instruction by asking, within 15 or 20 minutes, what Dr Young's response was. I regard the failure to make contact with Dr Young at or immediately after 8.50 as the most serious ground of fault, but in my view its effects were compounded by the four following grounds.
[82]In the fourth place, I consider that Dr Greene was at fault in not conducting a full central nervous system examination of Laura at 8.50, and in not instructing regular neurological observations thereafter. The significance of these matters was that they would provide basic information on Laura's condition on which Dr Young could assess her treatment, and would also indicate how Laura's condition was changing; that was also important in determining her treatment. This point was made by Dr Robinson (4 December 2001, 12.15). In the fifth place, I consider that Dr Greene was at fault in not ensuring that a drip containing intravenous glucose was set up immediately after his ward round. I consider that his instructions to Dr Cummine were inadequate; in particular, they did not convey the urgency of the situation. Dr Cummine should have been instructed to take the blood specimens and set up the drip immediately, and as soon as it became clear that the ammonia machine was not working the drip should have been set up. Dr Greene should have ensured that that happened. In the sixth place, I am of opinion that Dr Greene was at fault in prescribing intravenous glucose at 4%. I am satisfied that that was the standard maintenance dose, but what was required in the present case was a higher concentration. 10% would have been appropriate. I base that view both on Dr Beattie's evidence of general practice and on Dr Young's letter, no 11/1 of process. In relation to that letter, I am satisfied, on the basis of the evidence of Dr Beattie and Dr Young, and also Dr Robinson (5 December 2001, 12.54), that the expression "glucose rich" meant a concentration of at least 10%. In the seventh place, I am of opinion that Dr Greene ought to have retained personal control of Laura's management until Dr Young appeared. That would involve either remaining at her bedside or returning to see her at short intervals. If that had been done, the failure to set up the drip would have been obvious, and the treating consultant would have kept abreast of any changes that were noted in Laura's vital signs or neurological condition.
[83] I am satisfied on the evidence that Dr Greene failed in the third to seventh of the above duties. That involves a failure at approximately 8.50 or 9 am. On that basis is unnecessary to consider the position at 11 or 11.30, when Dr Maalouf noticed a significant deterioration in Laura's condition. Had I been required to do so, however, I would have come to the conclusion that similar failures in duty occurred at that stage. The one exception is that the drip had been set up, but the level of glucose being administered was still too low. In addition, I accept on the basis of Dr Beattie's evidence as summarised in paragraph [76] above that by this time a paediatrician of ordinary competence ought to have recognised the need to have Laura admitted to intensive care for treatment of her condition.
F. Causation
[84] The second issue in the present case is whether the breaches of duty described in the preceding paragraphs caused harm to Laura. That involves three questions. First, it is necessary to consider what actually happened to Laura. Secondly, it is necessary to consider what treatment would have been given to Laura if the above duties had been fulfilled. That involves what counsel described as a counterfactual situation; it must be assumed that the treatment that Laura received was not the treatment that she actually received but the treatment that she would have received had the steps set out above in paragraphs [80] - [82] been taken. This depends largely on the evidence of Dr Young, who would obviously have been the person primarily responsible for Laura's treatment. Thirdly, it is necessary to consider whether such treatment would have made a material difference to Laura's eventual condition. Three experts gave evidence on that issue, Dr P.H. Robinson for the pursuer and Drs J.H. Walter and R.C. McWilliam for the defenders, and it is necessary to discuss the evidence of those three witnesses in some detail. I deal with each of the three issues in turn.
(i) What happened to Laura?
[85] Dr Naismith went to see Laura at approximately 1.30 pm. She made the observations noted in paragraph [41] above, and immediately initiated a brain shrinking regime (spoken to by Dr Young; see paragraph [62] above). This consisted of the administration of Mannitol. Mannitol is a drug that is used on occasion to treat cerebral oedema and raised intracranial pressure (Dr P.H. Robinson, 4 December 2001, 1.56). It is thought to draw fluid out of the brain; it forms a hypertonic solution, or solution with a greater concentration than the body fluids, and consequently draws fluid into itself. Dr Naismith also arranged for Laura's admission to the intensive care unit for hyperventilation. After Dr Young appeared, further steps were taken, as recorded in paragraph [43] above. Laura was given 25% dextrose plus insulin. That was designed to supply a generous intake of glucose, to prevent the body from having to stop the normal production of glucose and use tissue breakdown as an alternative source of glucose (the process described in paragraph [5] above). Thus the dextrose is intended to reverse tissue breakdown (Dr P.H. Robinson, 4 December 2001, 2.11). Insulin is the hormone that allows glucose to be used by the muscles and the liver. It is administered along with generous glucose to prevent blood glucose levels from rising too high, producing the condition known as hyperglycaemia. Metabolic medicine was also administered intravenously, at 4 pm (no 10/7 of process, page 52; Dr Robinson, 4 December 2001, 2.56). At 3 pm Laura's ammonia level was found to be 717. She was transferred to the intensive care unit during the afternoon. On the way there she had a fit. In the intensive care unit she was hyperventilated and given dialysis to reduce her ammonia level. The administration of dextrose and insulin and sodium benzoate continued.
[86] Ultimately, however, Laura suffered very serious brain damage. It is not necessary at the present stage of the action to consider this matter in detail. The parties were agreed that the quantum of damages should be reserved for a further proof, and the details of Laura's condition since 25 September 1992 can more appropriately be dealt with in any opinion following such a proof. At present, it is sufficient to record that Laura is unable to speak, and lacks full understanding of what is happening about her. She needs extensive help to carry out the most ordinary functions. At present this is provided mostly by her parents, who are clearly devoted to her, but obviously that may not continue indefinitely, and in any event her parents will require respite. In relation to her life expectancy, it was agreed between the parties that the court should assume that Laura will survive to her 27th birthday, which falls on 13 May 2013; that is very much less than would have been the case if she had not suffered the brain damage.
(ii) What treatment would have been administered if the defenders' duty of care had been fulfilled?
Evidence
[87] As indicated in paragraphs [70], [80] and [81] above, I consider that Laura should have been given an intravenous infusion containing 10% glucose at an early stage. I consider that that should have been achieved by 9.30 at the latest.
[88] Dr Young gave evidence that he arrived at Armistead at about 9 am, and could not have been contacted before that when he was on his way (21 November 2001, 2.39). I do not think that that is relevant, because clearly Dr Greene had to examine Laura before he contacted Dr Young; realistically, therefore, Dr Young could not have been contacted before 9 am. Dr Young stated (22 November 2001, 10.59) that he would have instructed the intravenous administration of 10% dextrose and would have attempted to give Laura's oral metabolic therapy. He would initially have used her existing maintenance dose, on the basis that she was not yet encephalopathic. If Laura were unable to take her medication orally, and the reason for her failure appeared to be long-lasting, in the sense of lasting over one hour, he would have considered using a nasogastric tube. That would not have worked if she had been vomiting, and in that event he would have administered the drugs intravenously. As to the dosage of such drugs, he would have required to consult his references. The level would depend on the level of ammonia and his judgment of Laura's clinical state. If her ammonia level were serious, or she were encephalopathic, he would administer a daily dose over a few hours as a loading dose and then continue to administer the drugs at Laura's maintenance levels. If he had discovered that the ammonia equipment was not functioning, that would have made him much more careful in his clinical assessment. He would have to be convinced that things were deteriorating, but in that event he would have gone ahead with the treatment just described without knowing the ammonia level. In particular, he would have given a loading dose in the presence of overt encephalopathy.
[89] Dr Young was then referred to Laura's clinical notes for the morning of 25 September (no 10/6 of process, pp 191-193). On the basis of what was recorded in Dr Greene's examination, at the top of page 193, Dr Young considered that there was not yet overt encephalopathy. He would have been very worried, but he would have continued to watch Laura. Dr Young was thereafter referred to the neurological and other charts relating to Laura's condition at 10 am and 11 am (no 10/5 of process, pp 621-623). He stated (22 November 2001, 11.09) that clearly Laura's clinical state was deteriorating at 10 am. By 11, Laura was agitated and biting her lips; by then it was beyond doubt that she was encephalopathic. He would hope to have intervened before that. Nevertheless, he was not present and did not know whether the notes were complete or accurate. If encephalopathy did develop, he would have used 10% dextrose. If he felt that, despite that, he was losing, he would have increased that to perhaps 25 %, accompanied by insulin. The glucose metabolised by insulin promotes anabolism. In addition, sodium benzoate would have been administered initially, adding other chemicals as appropriate and available to bring down the ammonia. These would be essentially the chemicals listed in the prescription found in No 10/5 of process at page 612 (see paragraph [43] above); that was the prototype that Dr Young had available for guidance. Doses would be determined according to the guidance given in the literature. The standard dose of sodium benzoate is 250 mg per kg. Some authors say that up to 500 mg per kg is desirable. Sodium phenylbutyrate could also be used to bind the ammonia. On the list of chemicals found at page 612, sodium benzoate was specified at 500 mg per kg. The list also included Arginine, an essential amino acid, which promotes the body's handling of ammonia.
[90] In cross-examination (23 November 2001, 10.44), Dr Young was asked about the doses of metabolic drugs that he would have used, and their rates of administration. In relation to the sodium benzoate, Dr Young stated that the rate of his prescription was 500 mg per kg per day, but that would not have been administered over a day. Instead, an initiating regime would have been used, to be cut later to a maintenance regime. That did not appear in the prescription, but it was clear from his evidence that Dr Young had read the relevant literature and knew the general principles that lie behind initiating (also known as loading or priming) and maintenance regimes. He indicated that the daily dose would have been given over a period of six or twelve hours.
[91] In re-examination (27 November 2001, 2.56), Dr Young was referred to an article by Dr J.E. Wraith, of the Royal Manchester Children's Hospital (no 30 of process), at page 1412. In relation to that, Dr Young stated that the emphasis in the article was that an anabolic state should be promoted as soon as possible, and that the loading dose should be varied according to the patient's response. He felt that that was in accordance with general principles of medical treatment. This is the sort of statement on which he had based his views regarding the administration of dextrose and sodium benzoate.
[92]Thereafter (27 November 2001, 3.13), Dr Young was asked to describe the treatment that he would have used on the assumption that he had been advised at about 9 am that Laura was waving her arms about and was not responsive to speech, as observed by the senior house officer. He should also assume that Dr Greene had noted severe worrying neurological symptoms and appreciated a potential emergency with increased ammonia levels possible. Dr Young replied that that was, at least prospectively, an encephalopathic picture. He would have instructed the administration of strong glucose, at 10%; that was crucial. Thereafter he would have gone to see Laura to make his own assessment, leaving someone else to take his clinic. He would have arrived at Ninewells within half an hour, that is to say, by approximately 9.30 am. Before leaving Armistead he would have instructed the taking of blood samples for urea and electrolytes and also ammonia. Normally the results would be available within half an hour, or just after his arrival. Following his arrival at Ninewells, what he would have done would depend on what he found. If it were evident on examination that Laura was deteriorating, and there was a group of encephalopathic signs (relating to consciousness and limb and head movements), he would have moved on to a major vein intravenous line with 25% glucose, insulin and sodium benzoate. He would have used sodium benzoate when there were definite neurological signs of encephalopathy. If, on arrival at the ward at 9.30, he was given information from Laura's parents, and decided on examination that there was a deteriorating clinical picture, he would have administered sodium benzoate there and then; with the assistance of a pharmacist, administration could have started within a matter of minutes.
[93] Dr Young was further questioned in re-examination (28 November 2001, 11.05) about the circumstances in which he might have given sodium benzoate. He stated that his method of practice was to observe the patient and modify the treatment according to his observations. He was slightly hesitant because he was not certain of the conditions that he would have found. He would, however, start treatment at the first sign of deterioration with 10% dextrose, as it happened on Laura's previous admissions to hospital. In the absence of a desirable response, or if Laura continued to deteriorate, he would go on to the next stage. If Laura appeared drowsy, confused and irritable but otherwise reasonably well, he would continue with intravenous glucose. If, however, other signs appeared, such as lip biting, agitation, a high-pitched cry, or alterations in consciousness or muscle tone, these were signs of brain dysfunction, involving swelling and toxicity. In that event he would go on to the next stage. That would involve a combination of stronger glucose and insulin together with sodium benzoate. So far as the rate of administration of sodium benzoate was concerned, the information in Dr Young's handwritten note was 250 mg per kg going up to 500 mg per kg in severe cases. There is an upper limit to the rate at which it is possible to infuse sodium benzoate. He would, however, have infused at as rapid a rate as he could given Laura's state of hydration. Some specialists say that the appropriate loading dose is 250 mg over 12 hours; other regimes involve a more rapid rate. If Laura had developed an organic encephalopathy, he would certainly have given at least 250 mg per kg in as rapid an infusion as her circulation would have tolerated. If he had been very worried about the clinical situation, according to his observations, he would have gone up to 500 mg per kg; the literature advised that such a rate could be used in extreme circumstances. He would have used at least 250 mg per kg. Following certain calculations, Dr Young stated that that dose could be administered over six hours. I should record that counsel for the defenders objected to questioning relating to loading doses in re-examination (28 November 2001, 10.43). I was satisfied that the issue of loading doses had been raised in cross-examination, and that the questioning was accordingly permissible. I nevertheless intimated that I would permit the defenders to cross-examine Dr Young further if they thought it appropriate to do so. In the event, however, no such motion was made.
Conclusions
[94] Against the background of Dr Young's evidence, as narrated in the foregoing paragraphs, I have on a balance of probabilities reached the following conclusions about the treatment that Dr Young would have administered. I should say at the outset, however, that there is in the clinical notes a lack of detailed information about Laura's precise condition between 8.50 and 11.30. Dr Young obviously did not see her at that time, and those who did had relatively little recollection of the details of her condition other than by reference to the notes. The lack of detailed information undoubtedly created a difficulty for Dr Young in deciding what he would have done in the circumstances. In addition, the exercise that he performed was to state what he would have done in a situation that never in fact occurred. Dr Young's evidence, as narrated in paragraphs [83] - [93] above, appeared to alter to some extent as matters proceeded. I am of opinion, however, that such changes in his position can be explained by the two difficulties that I have just described. In any event, the differences between his position during examination in chief and that during re-examination did not appear to me to be fundamental; Dr Young was describing the same process, but rather more clearly. In the event, I consider that his evidence in re-examination, as narrated in paragraphs [92] - [93] above, indicates the procedure that he would probably have followed.
[95] I must make one further preliminary observation. Counsel for the defenders invited me to hold that Dr Young had no plan for Laura's management on the morning of 25 September, and that the treatment that Laura in fact received after 1.30 was the result of discussions between Dr Young and Dr Greene, and relied largely on Dr Greene's research in the library. I decline to make any such finding. In my opinion it is very clear that Dr Young did have a plan for Laura's management in the event of her admission to hospital in a hyperammonaemiac state. In his office at Ninewells, he kept published materials relevant to Laura's condition, and these contained protocols that dealt with just such an eventuality. I have already found that the metabolic treatment that was used at 1.30 was that contained in Laura's medical records, no 10/5 of process, at page 612. The main part of the document is in Dr Young's handwriting. In my opinion it is a document that either was contained in his files or was based on information that was contained in his files. Moreover, it was produced at short notice on 25 September. Counsel pointed out that the part of the document in Dr Young's handwriting does not indicate the rate of administration of the metabolic therapy that is specified there. It was clear from his evidence, however, that Dr Young was aware of the general principles that are used to determine the rate of administration of the metabolic drugs in question; he was cross-examined about the matter at some length, and this was followed up in re-examination. In the circumstances I think it clear that on 25 September 1992 Dr Young had the information necessary to prescribe metabolic drugs properly, and would have used that information in the course of the morning.
[96] Dr Young's evidence (27 November 2001, 3.13) was that, if he had been contacted at Armistead at about 9 am, he would immediately have instructed a drip containing 10% dextrose. I am satisfied that he would have communicated the urgency of the situation, and that the drip would have been in place by 9.30 at the latest. Dr Young would also have instructed the taking of blood samples for urea and electrolytes and ammonia, and that an attempt should be made to give Laura her metabolic medication orally. He would then have driven to Ninewells to see Laura. It was clear that Laura's condition at this stage was extremely serious; Dr Greene admitted as much in evidence. Because of that, I have no significant doubt that Dr Young would have gone immediately to Ninewells. When he arrived, he would have examined Laura immediately; that would have happened at approximately 9.45.
[97] The next issue is what he would have observed at that stage, and the conclusions that he would have reached on the basis of his examination. At 8.50 Laura is recorded as being restless, confused and irritable. Dr Greene stated in evidence that he considered that she was at risk of hyperammonaemia. She had signs and symptoms suggestive of hyperammonaemia, and he accepted that what he had noted on examination suggested encephalopathy (see paragraph [52] above). Dr Beattie also thought that Laura was encephalopathic by 8.50 (see paragraph [75] above), as did Dr Robinson (5 December 2001,1.00) and Dr Walter (18 June 2002, 4.25). Dr Young initially thought that Laura was not overtly encephalopathic by 8.50, even if, in addition to the matters recorded in the clinical note, she was not responding to speech and was waving her arms (22 November 2001, 11.05). In that event, however, he stated that he would be very worried and watching her condition. In re-examination, however, he accepted that on the hypothesis put to him there was a prospective encephalopathic picture by that time (see paragraph [92] above). By 11 or 11.30, when Dr Maalouf recorded that Laura was very agitated and biting her lips, Dr Young thought that overt encephalopathy existed beyond doubt. That view appears to be consistent with the evidence of the other witnesses. On Laura's condition between 8.50 and 11, the most detailed evidence came from Dr Robinson (4 December 2001, 12.33-12.45). I find his account of events during that period to be probable. Dr Robinson stated that the observation chart no 10/5 of process, page 622, disclosed that at 10 there was an absence of response to language. That suggested a significant depression of Laura's nervous system. If that were compared with the notes at 8.50 (no 10/6 of process, page 193), the earlier note recorded restlessness, confusion and irritability, but said nothing about response to language. If there had been no response to language, Dr Robinson would expect to see that recorded, as it was a matter that would have caused a great deal of concern to the paediatrician. The word "confused" at 8.50 showed an inappropriate response to language, but that was not as extreme as the lack of any response at all to language that is recorded at 10. By 11, the findings recorded in the observation chart indicated that Laura had a great degree of abnormality in the functioning of her nervous system.
[98] On the basis of the totality of the evidence mentioned in the last paragraph, I draw the inference that Dr Young would have concluded that Laura was displaying an encephalopathic picture when he examined her at about 9.45 am. I also take into account the fact that Laura's parents were extremely concerned about her condition. Dr Young made it clear that, in treating OTC deficiency, the information provided by parents can be of vital importance, and I am satisfied that he would have attached considerable importance to what they said. I also consider that, looked at objectively, Laura's condition was encephalopathic. Dr Young was clearly an experienced paediatric neurologist, and I think that, when he saw Laura, he would have reached the same conclusion about her condition as the other consultants who gave evidence. In addition, on the basis of Dr Robinson's evidence I consider that Laura's neurological condition deteriorated noticeably between 8.50 and 10 and between 10 and 11. Dr Young indicated that, even if he did not consider that there was an overt encephalopathy by the time he saw Laura, he would have continued to watch her closely, and I am satisfied that he would have noticed that deterioration at an early stage, and certainly by 10.
[99] Dr Young stated that, if when he saw Laura she was deteriorating and displaying neurological signs of encephalopathy, including those relating to consciousness, he would have moved on to the infusion of 25% glucose plus insulin by way of a major vein line, and would have introduced sodium benzoate (27 November 2001, 3.22 and 3.26). In my opinion by 9.45, and certainly by 10, Dr Young would have noticed a significant deterioration in Laura's condition, and also clear signs of encephalopathy. I accordingly conclude that he would at this stage have moved on to 25% glucose plus insulin and sodium benzoate. In this connection, I have had regard to Dr Young's evidence on 28 November 2001 at 11.07, where he indicated that if the child had appeared drowsy, confused and irritable but well, with no neurological signs, he would have continued with intravenous glucose, but if neurological signs indicating brain dysfunction had appeared, he would have moved on to the next stage, which included sodium benzoate. In my opinion it is quite clear that by 9.45 Laura did not appear at all well, and was displaying signs of brain dysfunction, and I accordingly consider it probable that Dr Young would have instructed moving on to the use of intravenous sodium benzoate at that time.
[100] The next issue is the manner in which Dr Young would have administered sodium benzoate. It is clear from his evidence that Dr Young was aware that the literature indicated that either 250 or 500 mg per kg could be used as a loading dose, although the latter figure was a maximum. Dr Young was also aware of the general principles underlying a loading dose. He was not able to say with certainty the precise period over which he would have administered the loading dose; either six or twelve hours would probably have been appropriate (23 November 2001, 10.54). If Laura had developed an encephalopathy, however, he stated (28 November 2001, 11.14) that he would certainly have given 250 mg per kg as rapidly as Laura's circulation would tolerate. If he had been very worried, that might have increased to 500 mg per kg. He thought (28 November 2001, 11.24) that the loading dose might have been administered over six hours in these circumstances. Dr Young indicated at a number of points during his evidence that his response would depend very much on his clinical judgment of Laura's condition. I have already concluded that Laura was encephalopathic by 8.50, and that there was a significant deterioration after that. In these circumstances, I consider that Dr Young would probably have started a loading dose of sodium benzoate at a rate of 250 mg per kg over six hours. If that did not arrest Laura's deterioration, I conclude that Dr Young would have increased the loading dose to 500 mg per kg. Exactly when that would have happened is not clear, as it would depend on Laura's reaction to the initial loading dose. If the initial loading dose had no effect, however, it would have been clear that there was a serious encephalopathy by approximately 11, the time when all of the consultants agreed that there was undoubted encephalopathy. Consequently I think that the higher rate of administration would have been instructed by that time at the latest. Dr Young indicated that administration of sodium benzoate can start within minutes of its been instructed. Consequently I consider that the loading dose would have started by 10.
(iii) Would such treatment have made a material difference to Laura's eventual condition?
[101] On this matter I accept the evidence of Dr Robinson. Contrary views were expressed by Dr Walter and Dr McWilliam, who gave evidence on behalf of the defenders. I discuss Dr Robinson's evidence in detail later in this opinion, at paragraphs [108] - [118] and [139] - [148]. That discussion proceeds in the context of the evidence of Dr Walter and Dr McWilliam, and I state my detailed reasons for preferring the evidence of Dr Robinson at paragraphs [131] - [137] and [149] - [150]. For the present, however, I proceed on Dr Robinson's opinion on the specific question whether the treatment proposed by Dr Young would have made a material difference to Laura's condition.
[102] Dr Robinson was asked to consider a number of hypothetical situations (5 December 2001, 2.08-2.28; 6 December 2001, 2.45 onwards). The first of these was that Dr Young was called at or shortly before 9 am, and instructed that intravenous dextrose should be started immediately at 10%. Dr Young then went to Ninewells to see Laura, and arrived at about 9.30. He examined Laura, and immediately re-established metabolic therapy at maintenance level, either orally or through a nasogastric tube. On that hypothesis, Dr Robinson was of opinion that the rate of rise of blood ammonia would be slowed as a result of the rehydration and glucose therapy. He was uncertain in relation to the metabolic drugs, however; the prescription was better than nothing, but would not be as good as intravenous administration. If, of course, Dr Young were present and found that oral metabolic therapy was working, then that would obviously be reasonable. In these circumstances, Dr Robinson was of opinion that the outcome would be less than ideal, but better than it in fact was. That outcome would, on the balance of probabilities, have been better than it would have been had intravenous therapy started at 11.30. The present deficit would have been ameliorated. It was difficult to predict what the degree of intellectual impairment would have been; there could have been some degree of impairment.
[103] In cross-examination (6 December 2001, 3.10, 3.24) Dr Robinson was asked about certain further situations. The most significant of these involved the administration of a day's dose of sodium benzoate over a period of six to eight hours, treatment having been started between 9.30 and 11 am. Dr Robinson expressed the view that that would have made a material difference. That was not merely a matter of judgment based on experience. Dr Robinson's practice was to measure blood ammonia before a loading dose was given and half an hour afterwards; in those circumstances he had invariably found a significant fall in blood ammonia.
[104] Dr Robinson was further asked in re-examination (7 December 2001, 3.12) to consider the position if Dr Young had been called at 9 am and had instructed that 10% dextrose should be administered immediately. Dr Young then travelled to Ninewells to examine Laura, arriving at 9.30, and instructed immediate metabolic therapy. Subsequently to that an overt encephalopathic picture developed, going beyond irritability and confusion. At that point Dr Young decided to increase the rate of dextrose to 25%, and gave insulin as well. He also gave a loading dose of 250 mg per kg of sodium benzoate, or possibly 500 mg per kg, depending on his clinical judgment, over six hours. The sodium benzoate might have started before 10. Dr Robinson stated that in the circumstances the outcome would have been very much better and close to the ideal. The ideal was to maximise aggressive therapy, possibly proceeding as far as haemodialysis. The ideal outcome was leaving hospital with no detriment. If Dr Young had followed the procedures described in the present hypothesis, Dr Robinson was of opinion that the outcome would have been close to that. That outcome was more probable than not. Dr Robinson explained that he based that view on his own experience of treating patients in similar circumstances. I should at that, although this evidence was given in re-examination, I considered that it arose properly out of cross-examination, where Dr Robinson was questioned closely about the hypotheses upon which he was proceeding.
[105] Dr Robinson was also asked about the possibility that metabolic therapy, including a loading dose of sodium benzoate, did not start until after 11.30. In that event, he considered that the outcome would have been less good than if treatment had started after 9 am, but it would still have been better than the final outcome. In the event, however, it is not necessary for me to consider this part of Dr Robinson's evidence in detail, because I have found that Dr Young would on the balance of probabilities have started significant metabolic therapy by about 10 am, or shortly thereafter.
[106] On the basis of my findings in paragraphs [96] - [100] above, I am of opinion that the hypothesis in paragraph [104] corresponds to what Dr Young would probably have done in the present case. I accordingly conclude that, had the defenders' duties of care been fulfilled, Laura would have left hospital without substantial impairment.
[107]If Laura had survived the episode on 25 September 1992 without substantial impairment, I consider that her future prospects would have been reasonably good. On this matter I accept the evidence of Dr Robinson (5 December 2001, 11.30). I have summarised this evidence at paragraphs [11] and [19] above. In essence, although Laura suffered from mild mental retardation, and had some difficulties with motor planning skills, she would have been able to lead a normal life, and would have been able to find employment in a semi-skilled or unskilled occupation. Dr Robinson stated (5 December 2001, 11.48) that most girls who are given continuing treatment for OTC deficiency maintain a stable IQ; support for that view was found in an article by Maestri, Brusilow, Clissold and Bassett, Long-term Treatment of Girls with Ornithine Transcarbamylase Deficiency, found in volume 335 of The New England Journal of Medicine at page 855 (no 17/6 of process). So far as life expectancy was concerned, Dr Robinson expressed the view (5 December 2001, 12.06) that, had the incident on 25 September 1992 not occurred, Laura's life expectancy would have been near normal, provided that there were no further severe episodes of hyperammonaemia, or such episodes were treated. If proper oral metabolic therapy were given, Dr Robinson further expressed the view that it would have been possible to avoid further hyperammonaemic episodes with irreversible effects. There was evidence (found in the article by Maestri and others, no 17/6 of process) that the frequency of hyperammonaemic episodes decreases with increasing age, and survival rates similarly improve with age. On the basis of this evidence, I conclude that, but for the episode on 25 September 1992, Laura would probably have enjoyed a near normal life expectancy, and her IQ would probably have been stable.
Dr Robinson's evidence
[108] Dr P.H. Robinson is a consultant paediatrician in metabolic medicine at the Royal Hospital for Sick Children, Yorkhill. He has occupied that position since June 1994. He provides a service for children with inborn errors of intermediary metabolism in Greater Glasgow and South West Scotland, and provides an informal consultation service for such children for much of Scotland. He has been involved directly in Laura's care from October 1994 onwards.
[109] Dr Robinson was taken through Laura's medical history, under reference to her medical records. During her initial presentations ammonia levels of 350 umol/l had been recorded, and at the time when the protein load test was administered ammonia had risen to 385 umol/l. When Laura was admitted to Ninewells in April 1990 an ammonia level of 204 umol/l had been recorded, and this had fallen to 130 umol/l by the following day with the administration of oral metabolic therapy. On her admission to Ninewells in December 1990, Laura's ammonia level had been recorded at 205 umol/l, which was relatively high, but no abnormality was noted with the central nervous system. There was evidence of catabolism, with a cold and swollen tonsils. Dr Robinson considered that the problem on this occasion had been caused not by the switch from Citrulline to Arginine but by the intercurrent infection (4 December 2001, 11.32). In January 1991 Laura was admitted to Ninewells, discharged home and then readmitted. When she was readmitted, Dr Robinson considered that she was displaying signs of encephalopathy (see paragraph [16] above). On this occasion intravenous dextrose at 10% had been provided within half an hour of admission, and Laura had made a complete recovery. Dr Robinson considered that the response on this occasion had been good (4 December 2001, 11.46). Laura's next admission to Ninewells was in July 1992. On this occasion the medical records disclosed that she had not been required to have her usual metabolic medication if she were not eating or drinking. Dr Robinson disagreed with this response; metabolic medication should be continued at all times to prevent any further rise in ammonia levels.
[110] Dr Robinson then dealt with Laura's admission to Ninewells on 25 September 1992 (4 December 2001, 12.08). He commented on the absence of any record of a detailed examination of the central nervous system. He explained that a doctor would normally be anxious to look for other signs of encephalopathy if the patient were restless, confused and irritable. It was important to establish the patient's clinical state accurately in order to discover whether any significant change occurred, for better or worse. Laura's blood analysis was recorded in the clinical notes underneath the entry made at 11.30 am (no 10/6 of process, page 193), but in fact it must have been obtained at 12.37 pm; that could be discovered from the printout (no 10/5 of process, page 318), which gave the time when the analysis was made. The analysis indicated a high white cell count and a high level of haemoglobin. The former could be the result of either infection or stress, and the latter indicated dehydration. Dr Robinson then commented on the observation charts found in no 10/5 of process at pp 622 and 621 (see paragraphs [34] and [35] above). In the entry for 10 am the most significant neurological finding was the absence of response to language, which indicated a significant depression of the nervous system. Nothing of that sort had been recorded in the medical notes relating to the ward round at 8.50; had there been no response to language, Dr Robinson would have expected that to be noted, because it would have caused a great deal of concern. The entries at 11 am indicated that Laura was already showing a grave degree of abnormality in the functioning of her nervous system. The entries between 11 and 1.40 disclosed significant increases in blood pressure and respiration rate. These were signs of rising intracranial pressure. This was confirmed by the entry made by the Dr Naismith at 1.30 (no 10/6 of process, page 194, set out at paragraph [41] above). Coning, in particular, was consistent with raised intracranial pressure, a condition that was capable of being diagnosed clinically without reference to scans or other similar devices. The signs of raised intracranial pressure, however, had been present by 12 noon (4 December 2001, 1.02).
[111] Thereafter, Dr Robinson considered Laura's treatment after 1.30 pm; so far as material, I have dealt with this part of his evidence in paragraph [85] above. Dr Robinson then explained (4 December 2001, 3.51) the manner in which in his opinion hyperammonaemia causes brain damage. I summarise this part of his evidence in paragraphs [139] and [140] below. He was then asked (5 December 2001, 10.48) when the effects of ammonia or raised intracranial pressure consequent upon hyperammonaemia become irreversible. He replied that it was difficult to be certain. His opinion, however, was that such effects became irreversible when the changes to the blood supply to the brain begin to affect the brain. The effects can rapidly become irreversible. Raised ammonia in the blood goes to the astrocytes; that causes glutamine production in the astrocytes, and they begin to swell when osmotic pressure in the cell causes fluid to enter. Before the blood supply to the brain is compromised by swelling, cerebral spinal fluid is expelled from the brain tissue. It is only at a subsequent stage that the blood supply to the brain is restricted by the swelling, and it is at that stage that the effects are potentially irreversible. Dr Robinson was then asked whether it was possible to state at what level of concentration of blood ammonia Laura was likely to show signs of sleepiness, confusion and irritability. He replied that he believed that a degree of tolerance to ammonia develops in such patients. On occasion blood ammonia at a level of 200 umol/l had no effect, but there were cases where blood ammonia was lower and symptoms were shown. A blood ammonia level of 350 umol/l or above was of extremely ominous significance, in terms of risk of damage. That would apply to Laura, but in her case there had been two previous occasions where she had made a good recovery from levels of 350 and 385 umol/l. The second of these was the protein load test. Dr Robinson further indicated that ammonia levels can rise very fast (5 December 2001, 12.40). The speed depends upon whether treatment in the form of glucose and metabolic therapy is administered; without such therapy, however, it could rise by 400 umol/l in 24 hours. This was supported by a paper and by Dr A.A.M. Morris and Professor J.V. Leonard , "Early recognition of metabolic decompensation", Archives of Disease in Childhood, 1997, 555-556 (no 17/11 of process).
[112] Dr Robinson then dealt with the response to Laura's condition on the morning of 25 September 1992 (5 December 2001, 12.52). It is not necessary to comment on this part of his evidence beyond stating that it fully corroborated the evidence of Dr Beattie. Thereafter, Dr Robinson was asked about the likely outcome given various hypotheses about what Dr Young would have done if he had been called. I have dealt with this evidence in paragraphs [102] - [105] above.
[113] In cross-examination, Dr Robinson was asked about Laura's likely condition on the evening of 24 September (6 December 2001, 11.10). He accepted that a process of catabolism is possible after minimal stress, and that Laura was quite ill when she was admitted to Ninewells at 7 or 7.30 am on 25 September. He further accepted that Laura's condition on that occasion was more serious than on earlier hospital admissions, apart from the first of these, and that on 25 September she was encephalopathic on admission to hospital. He thought that by that time Laura's blood ammonia might or might not have been elevated, but her brain glutamine was likely to have been high. Laura's condition was likely to have been precipitated by a viral infection, which might or might not have been the tonsillitis for which she had received treatment. He found it difficult to state exactly when the process of decompensation is likely to have begun; his inclination was that it was likely to have started close to 24 or 25 September, rather than at an earlier date. In this connection I consider that he was strongly supported by the evidence of Mr and Mrs Miller, who stated that there had been no sign that Laura was off her food; she was eating and drinking normally, and had been at school. That means that there was nothing to suggest encephalopathy until the evening of 24 September, and nothing to suggest that a process of decompensation had begun before that date.
[114] Dr Robinson was asked about Laura's apparent weight loss in the period prior to 25 September (6 December 2001, 11.22). Her weight that morning was found to be 19.3 kg, whereas when she was weighed on 9 September her weight was 21.45 kg. He accepted that that indicated dehydration, but he was unable to explain the degree of dehydration. He accepted that that appeared to point to a significant illness, but he replied that that could happen very rapidly; children can go to bed well and be unwell in the morning with severe dehydration.
[115] Dr Robinson was then asked to explain the mechanism whereby hyperammonaemia leads to brain damage (6 December 2001, 11.47). He explained that he expected clinical signs of encephalopathy at the early stage when blood ammonia rises. Such signs were not dependent on the stage when blood supply to the brain was impaired. It was not absolutely clear what caused the clinical manifestations that appeared at this relatively early stage. The astrocytes were believed to have the function of nourishing the other cells in the nervous system, and the effect of swelling of the astrocytes might affect the normal process of nourishment of those other cells. Consequently, even though Laura displayed symptoms of encephalopathy on admission, it did not follow that the blood supply to her brain had been impaired by that point. He thought that it was unlikely that the blood supply to her brain had been impaired by then, because at that stage Laura did not have all of the signs of critically elevated intracranial pressure that she developed later. When, by 11.30, she was noted to be very agitated and biting her lips, that pointed to an impairment of the blood supply. Part of the reason for this conclusion was the evidence on the clinical chart after 11.30 (no 10/5 of process, page 621). The blood pressure shown at 11 was just within acceptable normal limits for Laura's age, but the subsequent measurements were very high, and disclosed a clear trend of rising blood pressure. That showed a grave disturbance of the cerebral blood flow. Dr Robinson thought that that process could have been starting at 11, but was not fully developed until 1.40. The main factor producing that rising blood pressure was, he thought, cerebral oedema. The body contains certain compensating mechanisms that allow cerebral blood flow to be maintained relatively constantly. When the point is reached, however, when those mechanisms can no longer operate, raised intracranial pressure will manifest itself by a rise in blood pressure. Consequently the rising blood pressure was an ominous warning sign of dangerously elevated intracranial pressure. At 8.50, on the other hand, Laura's blood pressure had been normal; that indicated that there had probably been no impairment of blood flow to her brain at that time. When asked whether hyperammonaemia results in the appearance over several days of symptoms and signs attributable to the cerebral cortex, with seizures and the like only appearing thereafter, Dr Robinson stated that that may be so, but ammonia can have effects in hours rather than days (6 December 2001, 12.24).
[116] Thereafter, Dr Robinson was asked about the treatment of hyperammonaemia (6 December 2001, 12.37), and in particular the need to prevent a catabolic state. It was suggested that, in accordance with Dr Walter's views, it was appropriate to aim for a level of blood glucose between 9 and 11, in order to drive the body's own production of insulin. Dr Robinson agreed, but pointed out that single or even repeated measurements of blood glucose are just snapshots. What is involved is a continuing process, and what is important is the rate of supply of blood glucose to meet energy needs. The rate of supply was critical. In this connection, Dr Robinson drew the analogy of a bath being filled with water, with some of that water escaping; in such a case, the height of water in the bath does not indicate the rate at which it is being filled. Thus the actual level of blood glucose was of lesser importance. If an adequate supply of glucose for use by the body's tissues is ensured, the liver no longer has to produce it for that purpose. If insufficient glucose is supplied, on the other hand, the liver will continue to produce glucose, and that will cause more ammonia to be produced. It is consequently vital to stop catabolism, by administering glucose. The level of glucose in the blood is of secondary importance. That view was based on a particular scientific finding, namely the basal hepatic net production rate of glucose; that was a figure of 4-6 mg/kg/minute, and that amount is required to satisfy the body's energy requirements. It was also significant that the body's pool of available glucose is relatively small; that is why the supply of glucose is critical.
[117] Certain of the effects of glucose appear within minutes (6 December 2001, 1.58). That applies in particular to certain changes in body chemistry; for example, the high level of free fatty acids, which results from fat mobilisation, will begin to fall rapidly, and the level of insulin is likely to rise quite rapidly. Those changes occur as a result of the administration of a modest amount of glucose. Dr Robinson thought it highly likely that the administration of glucose would arrest the process of catabolism. Insulin is the major growth promoting hormone in the body, and the rise in insulin is a key factor in reversing catabolism. If glucose were to have effect, however, it had to be at a rate of at least 10%. The reason was the critical nature of the rate of supply of glucose. The administration of glucose at 10% or higher was sufficient to meet a child's needs, whereas if glucose were administered at 4% that would not be sufficient. The fact that the child's blood glucose level was relatively high, at 9.1, was irrelevant; the rate of flux was what mattered. Dr Robinson accepted that the process of arresting catabolism is gradual; nevertheless, the changes begin immediately. The administration of glucose prevents further tissue breakdown, and thus lowers the pool of ammonia in the brain. That allows glutamine and other amino acids to enter the muscle cells. It also allows a pool of new chemical substances to take up ammonia; an example is pyruvic acid, which is converted into alanine, thereby mopping up ammonia molecules. Likewise oxaloacetate is allowed to take up ammonia for conversion to aspartate. Gradually the pool of ammonia in the blood and other tissues falls. As a result glutamine is once again converted to glutamate, and the concentration of glutamine in the brain cells begins to fall. In addition, Dr Robinson stated that he would use intravenous metabolic medication at an early stage. They use of sodium benzoate and, if appropriate, sodium phenylacetate or sodium phenylbutyrate permitted the removal of the existing pool of ammonia in the blood. Sodium benzoate and sodium phenylbutyrate produce very rapid withdrawal of ammonia, if they are started in adequate dosages. Dr Robinson was then asked about certain specific dosages, according to Dr Young's recipe. Even at low dosages, sodium benzoate has an immediate effect on blood ammonia. Nevertheless, the effectiveness is related to the level of dosage and the period over which the dose is administered.
[118] As I have mentioned above (in the preceding paragraph and in paragraph [103]), Dr Robinson was questioned about a number of possible doses of sodium benzoate that might have been administered to Laura. He was then asked to comment on Dr Walter's view that, even if Laura had been given 10% sodium benzoate and Arginine by 9.30, it would not have prevented her illness from progressing. Dr Robinson replied that he understood that Dr Walter was saying that Laura's condition was irreversible and thus irretrievable by 9.30. He would say that that was not the case. The evidence for that was found in the blood pressure records (no 10/5 of process, pp 62 and 621). These showed a significant rise in blood pressure only after 11-11.30. Consequently cerebral oedema had not been established to maximal extent by then. Thus there was potential for reversing the cerebral oedema. In addition, the clinical observations differed between 9 and 11. By 11.30 there was a deterioration. Dr Robinson thought that there was potential for reversal in that period, if not beyond. By 11.30 Laura's condition was grave, but it was not hopeless even then. That was so even if the observation timed at 11.30 had been made at 11. The potential for reversing Laura's condition was not as great as it had been at 9, but it was still there, and the probability that reversal would be successful had not switched. Dr Robinson was subsequently asked to state the point when Laura's condition became irreversible (7 December 2001, 10.20). He stated that it was not possible to identify the point of irreversibility with certainty. The probability was, however, that it was at some time after 1.30 pm. That view was based on Dr Naismith's observations at that time, together with the sustained upward trend in blood pressure that occurred then.
Dr Walter's evidence
[119] Dr J.H. Walter is a consultant paediatrician with special interest in paediatric metabolic disease at the Royal Manchester Children's Hospital. He is one of three consultants at that hospital providing a regional and supraregional specialist service for children with inborn errors of metabolism.
[120] Dr Walter had examined Laura's medical records, and in particular the records relative to her presentation on 25 September 1992. He was taken through those in some detail (18 June 2002, 3.15), and asked for his opinion on Laura's condition that morning (18 June 2002, 3.33). He stated that, on the basis of the records of Laura's neurological condition found in the observation chart at no 10/5 of process, page 621, she was profoundly encephalopathic by 11 am, with a score of 3 on the Glasgow Coma Scale. Thereafter her blood pressure started to rise and her pupils were dilated. At about 9 am she was recorded as being restless, confused and irritable, and the picture from the clinical notes was not very complete; consequently it was hard to judge how encephalopathic she was at that stage. Dr Walter also referred to the weight that was recorded on the morning of 25 September. Laura's weight had previously been recorded on 9 September, and there was a significant drop by 25 September. Dr Walter stated that he thought it difficult to know how much weight had been lost with tonsillitis; certainly, if Laura had not been eating well she might have lost some weight as a result. Part of the loss might also be due to dehydration; the clinical observation was that she looked dry. By 1.30 pm Laura appeared very critically ill; at that stage she was only withdrawing to painful stimuli. That suggested very profound encephalopathy. There were also indications of raised intracranial pressure, notably the rising blood pressure after 11. In cross-examination (19 June 2002, 1.49) Dr Walter agreed that, if Laura had been at school and appeared well during the previous day, she was probably not encephalopathic prior to the evening of 24 September. He also agreed that, if there were no indication from Mrs Miller that Laura was in any way disturbed or not eating properly on 24 September, that would suggest that any encephalopathic involvement would be of a minor nature, although he could not explain the weight loss.
[121] On the basis of his examination of the clinical notes, including the nursing records, Dr Walter expressed the opinion that Laura's presentation on 25 September was unusual in that it progressed very quickly and became critical within a few hours. It was not possible to know for certain why that should happen on this occasion when it had not happened on previous admissions. It was possible to put forward a hypothesis that Laura had been unwell for two weeks or thereby in a chronic catabolic state. That would lead to the breakdown of body protein, with a consequent release of nitrogen. That would have saturated Laura's a buffering capacity. When she became more unwell, therefore, she had no capacity to cope with the increased nitrogen load. Consequently ammonia rose to a higher level than before. It was also possible that the glutamine in her astrocytes was relatively high before her admission on 25 September. From the history taken on 25 September there was some suggestion of cerebral symptoms before admission, because she appeared irritable, hyperactive and tired in the evenings. Dr Walter thought that she was perhaps not so well in the days, or even weeks, prior to her admission. He did not know whether stopping antibiotics had had a significant effect. Nevertheless, he thought that she was in a more fragile state before this admission than previously, which would explain why she became unwell so quickly. On previous occasions Laura had been admitted to hospital with irritability and confusion, but she had not progressed to such severe problems.
[122] Dr Walter was asked whether it was relevant that on earlier admissions Laura appeared to have been given 10% glucose not long after admission. He stated that in his judgment the change from 4% to 10% dextrose would not have made any difference to her illness. The administration of dextrose was a marginal treatment in the removal of nitrogen, or stopping the production of nitrogen. It was difficult, however, to judge what was happening on 24 September. If on 25 September Laura was restless, confused and irritable at 9 am and had a score of 3 on the Glasgow Coma Scale at 11 am, that was a very rapid progression. It was compatible with that view that, on the previous evening, Mrs Miller had not been concerned about Laura's condition before she went out. In Dr Walter's experience, children with OTC deficiency did not progress as rapidly as Laura did to severe encephalopathy; that is particularly true of the late onset form of the disorder, which is what Laura had. Laura had been encephalopathic by the time of her admission, in the sense that there was a disturbance of brain function. It was more difficult, however, to assess the severity of the encephalopathy.
[123] Dr Walter was asked whether in his opinion the outcome for Laura might have been different if her treatment had taken a different course (18 June 2002, 4.31). The first hypothesis put was that Laura was given an infusion of 10% dextrose from about 9 am, and that oral medication was given at about 9.30. If she were unable to take the medication orally it would be administered by nasogastric tube, and from perhaps 10 am intravenous sodium benzoate was administered at a rate corresponding to 500 mg per kg over six hours. Dr Walter replied that in his experience intravenous dextrose made no difference, and medication given orally or by nasogastric tube made no significant difference. He thought that intravenous sodium benzoate was unlikely to be set up before 10.30, and by that stage the process causing Laura's dysfunction was likely to have been irreversible. The factor that he had in mind was the time required to reduce blood ammonia with medication. This takes some hours, and there is an even greater lapse before it has an effect on levels in the brain. The only way in his opinion of reducing ammonia rapidly was dialysis. In Manchester, if a child had blood ammonia of 700, Dr Walter would proceed directly to dialysis. His experience was that intravenous medication was not effective when there had been massive accumulation of nitrogen. Dr Walter was asked to comment on the fact that, when the protein load test was administered in 1987, Laura's ammonia had risen to 385, but she recovered with the administration of dextrose only. Dr Walter replied that that was a very different situation, because she had been relatively well beforehand and her buffering capacity was not saturated; consequently, although ammonia went up there were mechanisms whereby it could be buffered. This observation clearly tied in with Dr Walter's view that Laura had been significantly unwell for some time prior to her admission on 25 September (see paragraph [121] above). Thereafter, Dr Walter was asked to consider the hypothesis put to Dr Robinson that is narrated in paragraph [102] above. Dr Walter's view was that he did not think that oral medication would have made any significant difference. It had not stopped Laura from becoming ill, and even with 10% dextrose he did not believe that it would have made a difference. Dr Walter was then asked to consider the hypothesis put to Dr Robinson that is narrated in paragraph [104] above. On this, he replied that he thought that it would have been highly unlikely to result in leaving Laura with no deficit. He thought that the process in her central nervous system could not be reversed that easily, and that intravenous therapy would not have materially altered the fact that she had an aggressive encephalopathy and was in the process of developing a cerebral oedema. Her ammonia level was unlikely to come down particularly rapidly. The production of glutamine in her brain would have continued, and the cerebral oedema and resulting damage would have continued. Once again, the underlying supposition appears to be that Laura had been significantly unwell for some time prior to her admission, and that the encephalopathy was well advanced by 9 am on 25 September.
[124] Dr Walter also commented on the decline in Laura's weight between 9 September and 25 September, from 21.25 kg to 19.3 kg (19 June 2002, 10.28). If she had been unwell and not eating, she would have lost weight from that, although dehydration might also have been a factor. In addition prior to admission Laura might have been in a catabolic state, breaking down fat and body protein. That would produce nitrogen, which would combine with hydrogen to form ammonia. In cross-examination (19 June 2002, 10.52), Dr Walter accepted that, if Laura had not been able to eat or drink properly, he would have expected her mother to notice.
[125] In cross-examination (19 June 2002, 12.24), Dr Walter accepted that, when a child suffering from OTC deficiency was admitted to hospital with suspected hyperammonaemia, he or she should be treated rapidly. Dr Walter thought, however, that that did not mean that treatment had to begin within minutes; in most cases there was a delay of some hours before treatment started. He thought that there was usually a window of opportunity to provide treatment without running into serious problems.
[126] As indicated in paragraphs [120], [121] and [122] above, an important part of Dr Walter's analysis of Laura's condition on 25 September was based on his interpretation of the clinical notes, including the nursing records found in no 10/5 of process at pages 621-623. It was essentially on the basis of those notes that he concluded that Laura's presentation on 25 September was unusual in that it developed very rapidly. Thus (18 June 2002, 3.33) he thought that by 11.00, if Laura's best verbal response was "none", as recorded in no 10/5 of process at page 621, her score on the Glasgow Coma Scale was 3, which was the lowest possible. In cross-examination (19 June 2002, 1.55) he was asked about the nursing records found on that page, and he agreed that there was a significant degree of ambiguity in the entries; in particular the best verbal response had ticks against both "confused" and "none". If Laura's state was properly described as confused, the score could have been as high as 8. Similarly, at 11.30 she was recorded as agitated and biting her lips, which would suggest that she was capable of movement; in that event the score would be higher than 3. Dr Walter further agreed (19 June 2002, 2.09) that on the basis of the medical notes, as against the nursing records, Laura's condition at 11.30 was nothing like as serious as at 1.40.
[127] In cross-examination (19 June 2002, 2.17) Dr Walter was questioned about his hypothesis that Laura had been unwell for two weeks or thereby prior to 25 September, in a state of chronic catabolism. He stated that he had no way of knowing whether that was correct or not, but it would explain why she had deteriorated so rapidly on that occasion. He accepted, however, that if Laura had been at school during that period and eating, drinking and sleeping normally, there would be no reason to suspect that she was in a chronic catabolic state, apart from the fact that she had an infection that was being treated with antibiotics. He further accepted that a child of Laura's age who was at school might be expected to be tired in the evenings. He thought that irritability and hyperactivity were more worrying, however, but he agreed that children of that age could be irritable and hyperactive without being catabolic. He agreed that vomiting would be an important sign of developing hyperammonaemia, although catabolism can exist without such signs. Encephalopathy, however, could not be confirmed until the evening of 24 September and ammonia and glutamine levels were not known until the afternoon of 25 September.
[128] Dr Walter was also asked in cross-examination about Laura's previous admissions to hospital (19 June 2002, 2.28). The most significant part of this evidence related to Laura's admission to Ninewells in January 1991. Dr Walter agreed that Laura was probably catabolic prior to that admission, and was exhibiting signs of encephalopathic disturbance; he agreed that the indications were of a more serious encephalopathy than at 8.50 on 25 September 1992. He further agreed that the symptoms that Laura displayed on that occasion were completely reversed, the treatment having been the administration of 10% dextrose. Dr Walter stated that he felt that there was something different on that occasion, and that Laura would have made a good recovery regardless of the administration of 10% dextrose. He agreed, however, that there might be features of Laura's condition which were not entirely typical; it is of the nature of OTC deficiency that it is very variable.
[129] So far as the admission on 25 September was concerned, Dr Walter was asked (19 June 2002, 2.46) whether he could say with confidence what the effect of administration of 10% glucose with insulin plus oral metabolites would have been. Dr Walter replied that in his experience he could not accept that the administration of dextrose at 10% rather than 4% alone would have prevented the illness from getting worse; it was not his experience that dextrose without more would prevent a hyperammonaemic state where there was severe stress on the relevant pathway. He was asked to distinguish his own practice from what might have happened had another form of treatment been used, and he agreed that he could not say definitely that the administration of 10% dextrose at 9 am would have had no effect, although his experience was that it was unlikely to have had a significant effect. He himself would never use 10% dextrose. When asked to consider the facts of Laura's case rather than his own practice (19 June 2002, 2.52), he again stated that he did not think that 10% dextrose would have any effect, although he could not say that for certain; he did not think that a small amount of glucose would reverse the stress. He again emphasised that in Laura's case there was a very severe stress on the relevant pathway. Dr Walter was then asked about Laura's admissions to hospital in 1987, at the time of her original diagnosis, and in January 1991, where the encephalopathic picture had been just as serious. Dr Walter replied that he thought that something was fundamentally different in September 1992; that view was based on what happened to Laura on 25 September. He accepted, however, that hyperammonaemia had been prevented by the administration of 10% dextrose in the past. He still thought, based on his experience with other patients, that that was not a reasonable form of treatment. Dr Walter was again asked to consider Laura's history rather than what he considered an ideal approach, and was asked whether it was logical to explain her improvement on previous occasions of raised ammonia and encephalopathy by the administration of 10% dextrose. He accepted that (19 June 2002, 2.57). He agreed that he could not say that the administration of 10% dextrose would have had no effect whatsoever, but he thought that it would not have been sufficient to prevent the progress of Laura's illness. He accepted, however, that such an approach had never been tried on 25 September, and he accepted that it was difficult to say in the light of Laura's history that it would have had no effect. In subsequent answers, Dr Walter made it clear that his opinion about Laura's admission on 25 September was based on the view that, when she was admitted, she already had a large accumulation of nitrogen and was experiencing a high level of catabolic stress (19 June 2002, 3.03 and 3.06).
[130] Dr Walter accepted (19 June 2002, 3.11) that Laura was not showing any signs of coma prior to her admission, and that generally speaking before the stage when coma is reached it is possible to treat hyperammonaemia successfully. He thought, however, that Laura's condition probably became irreversible at about 8 am (19 June 2002, 3.13). He based that view on the fact that Laura became unwell so rapidly, in a way that is not normal for children developing hyperammonaemic encephalopathy; frequently such children have been admitted first to a general hospital, and between six and eight hours elapse before they receive proper treatment in a specialist unit.
Assessment of Dr Walter's evidence
[131]It is clear that both Dr Robinson and Dr Walter are consultant physicians who have great knowledge and experience in the very specialised field of paediatric metabolic medicine. I have come to the conclusion, however, that the views of Dr Robinson are to be preferred to those of Dr Walter. I reach this conclusion for the following reasons.
[132] In the first place, Dr Walter's views were based on his theory that Laura had been in a state of catabolism for a significant period prior to 24 September 1992. The evidence of Laura's parents, however, was to the contrary. I have summarised this evidence at paragraphs [21], [22] and [25] above. Mrs Miller stated that, although Laura had been suffering from tonsillitis, she had seemed quite bright, and did not seem ill. That was unlike her admission to hospital in July 1992. Both parents were quite clear that nothing had seemed amiss until the evening of 24 September. Laura had been attending school daily and, although she seemed tired in the evenings, Mrs Miller attributed that to the fact that she was going to school; I accept that view. Laura had not been off her food. In these circumstances I conclude that there were no significant indications that Laura was in a catabolic state before the evening of 24 September. I formed a very clear opinion from the evidence of Mr and Mrs Miller that there was a sudden change in Laura at that time. I am further satisfied that they observed Laura carefully, and I think it very likely that they would have observed signs of catabolism if such signs had existed. In these circumstances I am of opinion that one of the major factual premises underlying Dr Walter's theory did not exist. By comparison, Dr Robinson pointed out that sudden deterioration can occur in patients suffering from OTC deficiency (paragraphs [114] and [115] above). Consequently he thought it likely that Laura's hyperammonaemia only began on or close to 24 September. That appears to accord much better with the evidence of Mr and Mrs Miller. Perhaps the strongest point in Dr Walter's favour is the apparent loss of weight suffered by Laura during the period from 9 September to 25 September (paragraph [114] above), taken together with the dehydration that Laura appeared to be suffering from on the morning of 25 September. Dr Robinson accepted that he was unable to explain the degree of dehydration, but pointed out that developments can take place very quickly in such patients (6 December 2001, 11.26). That may provide some explanation for the weight loss and dehydration. In any event, there was no evidence about how Laura was weighed on the two occasions in question. Counsel for the pursuer pointed out that if, for example, she had been wearing clothes on the first occasion but not on the second, that could account for some of the weight loss. While that suggestion was essentially speculative, the fact is that there was no evidence about how Laura lost weight, and in these circumstances I do not think it is possible to attach great significance to the apparent loss of weight. I find the evidence of Mr and Mrs Miller more reliable as an indicator of Laura's condition during the period preceding 24 September.
[133] In the second place, I formed the opinion that Dr Walter's theory about Laura's condition was to a substantial degree speculative, rather than based on the hard evidence about her physical state both before and after her admission to Ninewells. Indeed, to some extent Dr Walter accepted that he was proceeding without very much evidence. This appeared, for example, in the passage of his evidence summarised at paragraph [127] above, and also in a passage in his examination in chief where he dealt with the notes of the examination that took place during the ward round (18 June 2002, 3.35); in the latter case, Dr Walter stated that the notes did not contain a very complete neurological picture, and it was accordingly hard to judge how encephalopathic Laura had been at 9 am. As a matter of general impression, I thought that Dr Robinson's opinion was based more squarely on the evidence than Dr Walter's. Three particular examples illustrate this point clearly. First, in examination in chief Dr Walter expressed the view that Laura was profoundly encephalopathic at 11 am, with a score of 3 on the Glasgow Coma Scale (paragraph [120] above). That was based on the observation chart at no 10/5 of process, page 61. In cross-examination, however, Dr Walter accepted that there were problems with the entries for 11 am on that chart, and that on one view Laura's score on the Glasgow Coma Scale could have been as high as 8 (paragraph [126] above). The interpretation of that entry was clearly important for his overall theory, and I consider that the ambiguity in the entry undermined it substantially. Secondly, Dr Walter appears to have formed his opinion about Laura's condition without significant regard to the evidence of Mr and Mrs Miller (see paragraph [127] above). To the extent that he took account of information about Laura's condition prior to her admission to Ninewells, this appeared to be based on the clinical notes, in particular the note taken by Dr Cummine following Laura's admission (paragraphs [120] and [121] above). It was clear from the evidence of Mrs Miller, however, that that note was not entirely in accordance with her recollection; I have noted the discrepancies at paragraph [25] above, where I have indicated that I accept certain of Mrs Miller's criticisms of the clinical note. Thirdly, as explained in paragraph [130] above, Dr Walter accepted that Laura was not showing any signs of coma prior to her admission to Ninewells, a view that was clearly borne out by the evidence. He further agreed that in general it is possible to treat hyperammonaemia successfully before the point when coma is reached. If that is so, it tends to indicate that Laura's condition when she entered Ninewells was capable of successful treatment. Dr Walter seemed, however, to ignore this part of the recorded evidence about Laura's neurological condition when she was admitted to Ninewells, and the inferences that could reasonably be drawn from that part of the evidence. Once again, this illustrates the largely speculative nature of his views.
[134] Dr Walter further considered that Laura had shown a sudden and unexpected deterioration in the course of 25 September 1992. He explained this by means of his theory of prolonged catabolism prior to that date. On that basis, he expressed the view that the process of encephalopathy was irreversible by approximately 8 am (paragraph [130]). Dr Robinson, on the other hand, expressed the view that such rapid deterioration can occur in cases of OTC deficiency. He did not consider that Laura's condition had become irreversible until after 1.30 pm. He supported this view by reference to the evidence relating to Laura's blood pressure, found in no 10/6 of process at pages 622 and 621. While no witness spoke to how those records came to be made, they appear as part of the nursing records, and were not challenged; moreover the measurements made appear to have been of a routine nature. I accordingly consider that the measurements of blood pressure can be relied on. In these circumstances I find Dr Robinson's evidence on this matter to be powerful, based at it is on the hard factual evidence that is available about Laura's condition during the crucial period between 11 am and 1.30 pm. By contrast, Dr Walter's opinion appeared to be based on the view that Laura was profoundly encephalopathic by 11 am; I find that conclusion unsatisfactory for the reasons discussed in the preceding paragraph.
[135]In the third place, I formed a clear impression that Dr Walter's evidence was influenced to a significant degree by the current practice followed in the Royal Manchester Children's Hospital, where haemodialysis now appears to be used at a fairly early stage as a matter of course (19 June 2002, 10.45, and evidence summarised in paragraph [129] above). That may well represent best practice at the present day, but it is not the practice that Dr Young would have followed in September 1992. The critical question is whether the treatment that Dr Young would have used at that time would have made a significant difference to the outcome for Laura. Consequently what is required is an assessment of the latter treatment in its own right. Dr Robinson, by contrast, appeared in my view to address the critical issue more directly, with less regard to current practice, and to provide a direct assessment of the steps that Dr Young would have taken.
[136] In the fourth place, I found throughout Dr Robinson's evidence that he was willing to back up his opinion by detailed explanations of the underlying scientific theory, including references to literature where that was appropriate. At the same time he made reference to his own clinical experience, but usually against a general scientific background. Dr Walter's opinion, by contrast, appeared to be based much more exclusively on his own clinical experience. While clinical experience is clearly very important, and may be extremely valuable, I preferred the approach taken by Dr Robinson. I think that such an approach is particularly important in dealing with a condition such as OTC deficiency; OTC deficiency is very rare, and consequently the clinical experience of any individual specialist will inevitably be somewhat limited.
[137] In the fifth place, I consider that there is some support for Dr Robinson's approach in the history of Laura's previous admissions to hospital. Dr Walter considered that her condition on those occasions had been quite different from that on 25 September 1992. It is clear, however, that Laura had recovered fairly satisfactorily from ammonia levels in excess of 200 umol/l, and on one occasion as high as 350 umol/l. That, as Dr Robinson pointed out, tends to suggest that she could be treated successfully for the consequences of intercurrent illness. By itself this factor is perhaps not of great weight, but I consider that it lends some support to the other reasons for preferring Dr Robinson's evidence.
G. Causes of brain damage in hyperammonaemic episodes
[138] The defenders led evidence from Dr R.C. McWilliam, who is a consultant paediatric neurologist at the Royal Hospital for Sick Children, Yorkhill. Dr McWilliam expressed views on the causation of brain damage by hyperammonaemia which were sharply at variance with those of Dr Robinson. Dr Robinson's view, in short, was that the accumulation of ammonia in the brain caused the astrocytes (the cells in the brain that have the function of supporting the other cells) to swell, and that that swelling caused brain damage. Dr McWilliam, by contrast, considered that the accumulation of ammonia in the brain had a direct effect on cell energy production, and that that mechanism was a significant cause of brain damage, in addition to the indirect mechanism described by Dr Robinson. On the basis of those views, Dr McWilliam expressed the opinion that Laura was severely encephalopathic by the time of her admission to Ninewells on 25 September, and that her condition was irreversible by 8 am. On this matter, I prefer Dr Robinson's opinion, for reasons stated below. In addition, also for reasons stated below, I am of opinion that Dr McWilliam's approach to Laura's condition was not adequately stated on record by the defenders. An objection was taken to a critical part of his evidence in which he stated his theory of causation, and I will sustain that objection. In dealing with these matters, I will first summarise Dr Robinson's opinion on the causes of brain damage in hyperammonaemic episodes; secondly I will summarise Dr McWilliam's opinion; and thirdly I will state my reasons for preferring Dr Robinson's views and for sustaining the objection taken to one of the critical parts of Dr McWilliam's evidence. Finally, I will comment on Dr McWilliam's reliance on CT scans of Laura's brain in support of his opinion.
Dr Robinson's opinion
[139] Dr Robinson (4 December 2001, 1.58, 3.51) explained the mechanism whereby hyperammonaemia causes brain damage as follows. The presence of a high level of ammonia in the blood leads to a high level of ammonia in the fluids bathing the cells of the body, especially the brain. Of particular importance are the structural support cells of the brain, known as astrocytes. These have the function of supporting and nourishing the cells of the brain that carry out its operative functions. If ammonia diffuses from the tissue fluids into the astrocytes, it stimulates the production of glutamine within the astrocytes. That leads to the swelling of the astrocytes. The mechanism is not fully understood, particularly in relation to why the astrocytes are more vulnerable than other types of cell. It is possible that the ammonia may damage the lining surface of the cells, making them more permeable and spongy and thus allowing fluids to enter the cells and cause them to swell. When the astrocytes swell, they take up additional space, and the tissue fluids that nourish the other cells may be prevented from circulating in the normal way. Consequently some of the fluid circulating in the brain and in the cerebral spinal fluid pathways is squeezed out, into the spaces around the brain and around the blood vessels in the brain. As the pressure rises, the blood vessels into and out of the brain become compressed. That causes a reduction in the blood flow to the brain. Consequently important parts of the brain are deprived of blood, oxygen and nutrients. At a later stage in the process, parts of the brain are irreparably damaged by the loss of blood supply. The major effects of hyperammonaemia, and the point where cerebral oedema becomes irreversible, occur when the cerebral oedema prevents blood supply to parts of the brain. The swelling of the brain may produce coning, the stage where the brain pushes through the hole in the bottom of the skull. At that stage the functions of the brain stem become impaired. On this model, the symptoms of raised intracranial pressure may appear before irreparable brain damage has occurred. The pathology is progressive, and at a certain stage, as described above, its effects may become irreversible.
[140] In support of his opinion, Dr Robinson made reference to a number of published writings by leading researchers in the field of OTC deficiency (5 December 2001, 12.25; 7 December 2001, 2.02). Two of these writings are of particular significance for present purposes. These are a paper entitled Urea Cycle Disorders: Diagnosis, Pathophysiology, and Therapy, by Saul W Brusilow and Nancy E Maestri, found in Advances in Paediatrics, vol 43, at page 127 (no 17/10 of process) and a chapter entitled Urea Cycle Enzymes, by Saul W Brusilow and Arthur J Horwich, taken from The Metabolic Basis of Inherited Disease, edited by Scriver, Beaudet, Sly and Valle (McGraw Hill, New York, 1989) (no 17/8 of process). Professor Brusilow, who is a Professor of Paediatrics at Johns Hopkins University School of Medicine, in Baltimore, Maryland, was accepted by all of the medical witnesses to be one of the world's leading researchers in the field of OTC deficiency; indeed, my impression was that he was probably regarded as the leading expert in the field. In the article in Advances in Paediatrics, the authors write as follows (at 140-142):
"Pathophysiology of hyperammonaemic encephalopathy
Unlike any other chemical or neurochemical, ammonia is the only known substance that can reproduce all the clinical and pathological findings of hyperammonaemia; it was best shown in awake primates... Postmortem examination revealed cerebral oedema and herniation of the cerebellar tonsils. Of special significance were the light and electron microscopic changes -- swollen astrocytes with no demonstrable abnormality of neurons, axons, dendrites, oligodendroglia, and synapses [other brain and nerve cells and their connections]. These experimental gross and microscopic findings (cerebral oedema and swollen astrocytes) are regularly found in clinical hyperammonaemic states, e.g., hepatic encephalopathy, Reye syndrome, and urea cycle disorders.
...
That glutamine plays a role in hyperammonaemic encephalopathy is further suggested by studies in patients with urea cycle disorders; the plasma glutamine concentration increases before the onset of hyperammonaemia and hyperammonaemia is uncommon when plasma glutamine levels are normal or nearly so.
If hyperammonaemia induces cerebral oedema (and perhaps astrocyte dysfunction) as the primary cause of the signs and symptoms of encephalopathy, what are the roles of the energy deficits and neurochemicals about which much has been written? It appears reasonable to conclude that there is no major energy deficit because the synthesis of brain glutamine, an endergonic reaction requiring ATP as a substrate..., continues unimpaired. After pursuing this subject, Hindfelt [in a paper entitled 'Ammonia intoxication and brain energy metabolism', in Kleinberger and Deutsch (eds), New Aspects of Clinical Nutrition, Basle, Karger, 1983] concluded, 'From the present state of knowledge the early manifestations of ammonia toxicity can hardly be satisfactorily ascribed to energy failure as the energy stores are upheld.'
Although it is obvious that there are significant neurochemical changes in a hyperammonaemic patient (how else to account for the signs and symptoms?), rarely has the question been asked, 'Does hyperammonaemia independently affect neurochemicals or are the neurochemical changes simply a result of swollen astrocytes causing cerebral oedema and astrocyte dysfunction?' That neurochemicals by themselves are not responsible for cerebral oedema may be adduced by the absence of any experimental neurochemical model that mimics all the symptoms, signs, and pathology of hyperammonaemia. Furthermore, implication of the excitatory neurotransmitters in hyperammonaemia does not explain the absence of their characteristic dendritic pathology".
The authors of the paper then reach the following conclusion (at pp 142-143):
"Summary of the pathophysiology of hyperammonaemic encephalopathy
The mechanism causing cerebral oedema in hyperammonaemic states can be accounted for as follows. Ammonium activates the biosynthesis of glutamine via astrocytic glutamine synthetase; this results in an increase in whole-brain glutamine levels from 5 to 20 mmol/L. Assuming that all (or nearly all) the accumulated glutamine resides in astrocytes (which constitute 30% of the brain volume and which are the principal site of brain glutamine synthetase), intra-astrocyte osmolarity may increase by... an amount that would lead to large shifts of water into the cell and result in astrocyte swelling and cerebral oedema.... Astrocyte swelling provides an integrated explanation for the clinical, physiologic, neurochemical, and pathologic consequences found in acute hyperammonaemic encephalopathy, whether in patients with urea cycle disorders or patients with fulminant hepatic failure".
The same views are expressed in the chapter by Brusilow and Horwich in the textbook, The Metabolic Basis of Inherited Disease, which is perhaps the leading work on the subject; the relevant passage is found at pages 642-643. In my opinion these passages provide clear support for the mechanism put forward by Dr Robinson.
Dr McWilliam's opinion
[141] Dr McWilliam accepted that the mechanism described by Dr Robinson was one of the processes whereby hyperammonaemia caused brain damage. He considered, however, that two other mechanisms were also material (20 June 2002, 11.17, 12.03). First, glutamine is itself a neurotransmitter, that is to say, a substance which modifies the activity of neurones within the brain. Consequently glutamine by itself affects the function of the brain; if the level of glutamine is elevated, it can disrupt normal brain cell function. Secondly, glutamine and ammonia are general metabolic toxins. They are poisonous at high levels, and ammonia depresses cell metabolic processes. The result is interference with the production of energy in individual cells. All cells require energy, and take in oxygen and nutrients in order to produce such energy. If the production of energy falls below a certain level, the cell ceases to function normally, although it remains viable. If the production of energy falls to a lower level, the cell ceases to function at all, and the cell's viability is compromised. If there is a total or near total cessation of energy production for longer than a critical period, cell death will result. There is in addition an intermediate situation known as apoptosis, or programmed cell death. This is a normal part of cell behaviour, and eliminates cells that are not required by the body. If, however, energy production falls below the critical level, apoptosis will be induced prematurely, and it will be an irreversible process even if cell death is not immediate. The events leading to critical energy failure initiate the process, and over the next 24 to 48 hours cells die. In doing so, they swell. This is a similar mechanism to astrocyte swelling, in that fluid enters the cell because the cell wall is defective, energy being required to maintain it. Thus delayed cell death leads to the swelling of cells within the brain, and diffuse swelling of tissue within the brain. That leads to brain damage.
[142] Dr McWilliam stated (20 June 2002, 1.54) that he advanced the views stated in the last paragraph because the clinical presentation is different, in the early stages, in an encephalopathy due to hyperammonaemia. The outcome is also different; it is much worse in terms of intact survival in children who have a hyperammonaemic encephalopathy and raised intracranial pressure than in children who have an acute encephalopathy and raised intracranial pressure arising from other causes. That assumed identical severity and duration of raised intracranial pressure. I should record that this point was not put to Dr Robinson. In addition, hyperammonaemia was generally worse for neonates than older children. That was different from other conditions producing raised intracranial pressure in the newborn. One of the advantages of the neonate is that the skull is flexible and can expand, and thus it is difficult to generate very high intracranial pressure. Nevertheless, hyperammonaemia has a worse outcome than other instances of raised intracranial pressure. For that reason Dr McWilliam thought that an additional mechanism was operative. In advancing this theory, he stated that he was drawing on his own experience and published literature. No such literature was produced, however, and without it I have difficulty in concluding that his theory enjoys any significant degree of scientific support. The views of Professors Brusilow and Maestri in their paper on Urea Cycle Disorders (no 17/10 process) were put to Dr McWilliam (20 June 2002, 12.28), and he expressed disagreement with several aspects of their paper. The fact remains, however, that that paper is a work by leading researchers in the field, enjoying a worldwide reputation. No other research paper was placed before me to suggest a contrary view.
[143] Dr McWilliam then expressed an opinion, based on CT scans of Laura's brain taken on 25 September 1992 and subsequently, that there was no evidence of raised intracranial pressure on that date. I deal with the CT scans in paragraphs [150]-[153] below. Thereafter Dr McWilliam expressed his opinion about Laura's condition when she was examined at approximately 8.50 am on 25 September 1992 (20 June 2002, 3.50; 21 June 2002, 10.26). He stated that, if he had taken a correct picture from Dr Cummine's notes, Laura was severely encephalopathic by that time. If that was a hyperammonaemic encephalopathy, she was neurologically in a worrying state. When Laura's parents' opinion was taken into account, however, he found it difficult to get a clear clinical picture of the child. There was nothing to confirm that Laura's illness or symptoms the day before were due to hyperammonaemia. Nevertheless, Dr McWilliam had a concern that Laura was more ill than had been apparent to her parents, and had been ill for longer than had been apparent. That concern was based on the fact that she showed evidence of dehydration when examined by Dr Greene, a view that was confirmed by the electrolyte results, the haemoglobin level and the fact that her weight was about 10 % lower than it had been a few weeks earlier. Dr McWilliam accepted, however, that his view was difficult to equate with the evidence of Laura's parents that prior to the evening of 24 September she had seemed quite well, had gone to school, and had gone about her daily life (21 June 2002, 10.32). Dr McWilliam thought, however, that Laura's restlessness during the night, and probably her vomiting the previous evening, were symptoms of hyperammonaemic encephalopathy. Thus Laura had been displaying symptoms of encephalopathy for at least 11 hours by 8.50 am. She was probably catabolic by that time. During the morning of 25 September her condition became substantially worse. By 11 am she was in a profound coma, and by 1.40 pm she was seriously neurologically compromised.
[144] Dr McWilliam's explanation for the events of the morning of 25 September (21 June 2002, 11.15) was that the deterioration was due to secondary disturbance, resulting from hyperammonaemia, to the cellular metabolism, and especially to energy production. That supposed that glutamine was accumulating in the astrocytes at the same time, and that there was consequential swelling of the astrocytes and some degree of cerebral oedema. That explanation is in my opinion very important in the assessment of Dr McWilliam's evidence. It is clear that the explanation is based on his views about the manner in which brain damage occurs in hyperammonaemic episodes. The result of the explanation (21 June 2002, 10.36) was that at a very early stage after Laura's arrival in hospital, if not before, metabolic derangement was irreversible unless means were taken to remove ammonia. Consequently the treatment that Dr Young would have administered would not have made a material difference. The only effective means of removing the ammonia was haemodialysis.
[145] In cross-examination, Dr McWilliam accepted (21 June 2002, 12.04) that his primary speciality was paediatric neurology, and that he had no specialist training in the field of inborn errors of metabolism or urea cycle disorders. He stated that before he was instructed to consider the present case he had never been asked to consider the mechanisms by which brain damage was caused by hyperammonaemia in a child suffering from OTC deficiency. He had, however, made a search of the literature, and had come up with the hypothesis that glutamine toxicity and the direct toxicity of ammonia were causal mechanisms (21 June 2002, 12.14). He reiterated his views about the direct toxicity of glutamine (21 June 2002, 12.19); he stated that it was neurotoxic because it was a neurotransmitter and altered the neurotransmitter balance. He likewise reiterated his views about the direct toxicity of ammonia, whereby it caused cell death, but accepted that he was unable to say how much exposure was required to produce this result. Consequently his model was theoretical. Dr McWilliam subsequently accepted, however, (21 June 2002, 12.24) that it was glutamate rather than glutamine that was a neurotransmitter, and that he was not aware of any published work suggesting that glutamine was neurotoxic. In my opinion those concessions seriously undermined his views about the direct toxicity of glutamine in the brain. So far as the direct toxicity of ammonia was concerned, Dr McWilliam accepted that he could not give an indication of the length of time or degree of exposure that was required for accelerated apoptosis to occur (21 June 2002, 12.27). In Laura's case, he found it impossible to construct a mechanism whereby her state evolved other than by invoking something other than astrocyte swelling. The only hypothesis that presented itself to him was that of accelerated apoptosis. It was put to Dr McWilliam that his view was almost an article of faith: if the cause of Laura's condition was not raised intracranial pressure it must be something else; he accepted that that was a fair comment on his views. Dr McWilliam further accepted (21 June 2002, 12.44; 12.54) that he was not aware of any published experimental data which would confirm cell death following hyperammonaemia in the case of children suffering from late-onset OTC deficiency; that related at least to data of the same nature as that from the primate experiments referred to by Brusilow and Maestri in their paper on Urea Cycle Disorders (no 17/10 of process). He thought, however, that phenomena occurred in hyperammonaemic encephalopathy which were impossible to explain on Brusilow and Maestri's model alone; this applied in particular to why hyperammonaemic encephalopathy was different from brain swelling due to other causes. Dr McWilliam was not aware of any published data that could help on that matter. He considered, however, that his view was supported by published data relating to the outcome of brain swelling in newborn infants, although there was no specific published literature on the matter. When asked subsequently about the available literature (21 June 2002, 2.57), he stated that in an earlier textbook Professor Brusilow had suggested causal mechanisms other than astrocyte swelling, but he accepted that Professor Brusilow now proposed that mechanism as the sole explanation.
[146] I should add at this point that Dr Walter was also questioned to some extent about the present controversy (18 June 2002, 11.43; 19 June 2002, 11.20). In general, he found the views of Professors Brusilow and Maestri, as expressed in their paper on Urea Cycle Disorders (no 17/10 of process), to be convincing. He thought, however, that matters might not be quite as simple as the authors made out, in that he understood that some writers considered that other factors such as apoptosis might have some effect; he referred in particular to the views of a writer named Butterworth. No such papers were produced, however. Dr Walter also accepted that he was not particularly well qualified to deal with these matters.
Objection to line of evidence
[147] The possibility that glutamine was neurotoxic was put to Dr Robinson in cross-examination (5 December 2001, 3.17). At that point counsel for the pursuer objected to the line of evidence, on the ground that was no record for such a suggestion. I allowed the line of evidence to continue, reserving questions of competency and relevancy. Counsel for the pursuer maintained his objection in submission. The argument for the defender was that the process causing an encephalopathic condition had been explored with a number of witnesses prior to Dr Robinson, and they had explained that the problem arose from free nitrogen, which combined with other substances to form ammonia. Moreover, such witnesses had spoken about an increase in levels of glutamine, which contained a nitrogen ion.
[148]In my opinion the objection for the pursuer must be sustained. Both the parties' pleadings and the evidence led prior to Dr Robinson's cross-examination appeared to proceed on the basis that the causal mechanism whereby hyperammonaemia caused brain damage involved the effects of ammonia rather than glutamine. The notion of glutamine toxicity clearly involved different issues from toxicity brought about by ammonia. In my opinion notice should have been given in the pleadings that such a line was to be taken by the defenders. It is also notable that the defenders' productions do not contain any scientific literature that suggested that glutamine toxicity might be a causal factor. Consequently there was nothing to put the pursuer on notice that glutamine toxicity might be a significant issue in the case.
Reasons for preferring Dr Robinson's opinion
[149]My principal reason for preferring the approach taken by Dr Robinson is the fact that it appeared to be soundly based on received scientific opinion, particularly as expressed by Professors Brusilow and Maestri in their paper on Urea Cycle Disorders (no 17/10 of process). Dr McWilliam's views on the causation of brain damage were interesting, and might well promote valuable scientific debate. Nevertheless, when a court is faced with a conflict of expert scientific opinion, I consider that it must almost invariably follow the received opinion within the scientific community, if that can be discerned. No doubt on occasion that may result in a decision that ultimately proves to be wrong; all scientific opinions are necessarily provisional, based as they are on the existing state of knowledge, and from time to time they are subject to revision, sometimes of a radical nature. A judge is not an expert in any scientific discipline, however, and he is accordingly not well placed to choose between competing theories. Where it is reasonably clear that there is an opinion that enjoys fairly general support within the scientific community, the probability is that that is the opinion that best fits the existing state of knowledge. In the present case, it appeared to me on the basis of the whole of the evidence led before me that the views of Professors Brusilow and Maestri represented received scientific opinion among specialists in metabolic medicine, in particular in the field of inborn errors of metabolism. Moreover, no contrary literature was produced. While Dr McWilliam stated that at one time Professor Brusilow had expressed views different from those in his paper on Urea Cycle Disorders, the earlier writings were not produced, and it may in any event reasonably be assumed that Professor Brusilow eventually thought better of his earlier views. Apart from the weight of scientific and professional opinion in support of Professor Brusilow's present views, it appeared to me that those views were cogent and well argued. That applies in particular to the passage that I have quoted at some length in paragraph [140] above.
[150] Apart from the preponderance of scientific opinion, I am of opinion that the approach taken by Dr Robinson to the causation of brain damage is to be preferred for other reasons. Dr McWilliam accepted that inborn errors of metabolism, including OTC deficiency, were not his speciality. He accepted, moreover, that he had first produced the theory that he advanced as a response to the issues raised in the present case, and that the theory was based on a search of available literature. In my view an ad hoc theory of this sort, arrived at in a wholly academic manner, must be approached with some caution. That is especially so as the literature on which it was based was not produced; without detailed consideration of such literature, it was impossible to determine whether there was any real challenge to the views of Professor Brusilow and his colleagues. Exactly the same applies to the writings of Butterworth, referred to by Dr Walter. Furthermore, the original version of Dr McWilliam's theory assumed that glutamine was a neurotransmitter, but he ultimately accepted that that was not the case. He was, in addition, unable to be specific as to the duration and level of exposure to ammonia and glutamine that would cause brain damage. While no doubt absolute precision is impossible in these matters, Dr McWilliam's unwillingness to give figures was noticeable. Finally, Dr McWilliam appeared to concede in cross-examination that there were no published data that supported his theory. The views of Professor Brusilow, by contrast, were based on experimental data such as the report of the primate experiments referred to in the passage quoted in paragraph [140] above; these experiments were recorded in a paper by Voorhies and others, Acute hyperammonaemia in the young primate: Physiologic and neuropathologic correlates (Pediatr Res 17:971, 1983). The same research is referred to in the chapter by Brusilow and Horwich in the textbook The Metabolic Basis of Inherited Disease (no 17/8 of process). The absence of any published research in support of Dr McWilliam's theory, or at least the absence of any productions that evidence such research, is in my opinion a factor strongly in favour of the approach of Professor Brusilow.
CT scans
[151] In arriving at his opinion, Dr McWilliam placed significant reliance (20 June 2002, 2.03) on CT scans of Laura's brain taken in July 1987 and in the period immediately following the events of 25 September 1992 (no 10/8 of process). The first of the scans, taken on 5 July 1987, indicated that a number of significant changes had occurred in Laura's brain following the events surrounding the original discovery of her OTC deficiency. The first of the scans taken following the events of 25 September 1992 appeared to have been taken at some point before 4.50 pm on that day. In relation to the scan, Dr McWilliam stated that he did not see signs of cerebral oedema, but that did not necessarily mean that no changes had occurred in the amount of fluid in the brain that day. Dr McWilliam further stated that there was no sign of coning in the scan, because there was plenty of fluid-containing space around the foramen magnum, the hole in the base of the skull; that fluid would be expelled before coning occurred. There were also fluid-containing spaces within the skull. On that basis, Dr McWilliam thought that it was very unlikely that Laura's intracranial pressure was raised at the time when the scan was taken. He also considered that brain swelling could be excluded as a cause of raised intracranial pressure (20 June 2002, 2.57). Further scans were taken subsequently, on 29 September, 1 October and 27 October 1992. These showed extensive brain damage. In the scan taken on 29 September, the brain displayed diffuse swelling, although that was some days after the incident. In the last of these scans, the brain had shrunk generally, and showed widespread changes similar to those that had occurred in limited areas following the events in 1987.
[152] Evidence on the use of CT scans was also taken from Dr Beattie and Dr Robinson. Dr Beattie (29 November 2001, 3.48) was asked in cross-examination whether, if brain tissue is swollen by cerebral oedema, that should be apparent on a CT scan. He replied in the negative, stating that it can be apparent, but it is not exclusively so. He knew of cases where raised intracranial pressure existed but there was nothing on the CT scan. Dr Beattie was then asked (29 November 2001, 3.54) whether he was suggesting that Laura might have had raised intracranial pressure secondary to brain swelling caused by cerebral oedema which did not produce an effect on the CT scan. He stated that he had often seen that. He did not feel secure as to the details of why that should be so, and consequently was wary of giving an explanation. In such cases, however, he was satisfied that intracranial pressure was raised, because it was monitored in the intensive care unit. He agreed that it was an unexpected finding in a case of supposed raised intracranial pressure to find that there were no changes on the CT scan, but that was something that could happen.
[153] Dr Robinson was referred to the CT scan taken on the afternoon of 25 September 1992 (4 December 2001, 3.29). He was asked whether the absence of definite evidence of raised intracranial pressure on the scan was inconsistent with there having been signs of raised intracranial pressure between noon and 2 pm. He replied in the negative. The reason was that a CT scan was not a good way of assessing the presence or absence of cerebral oedema. A patient might have severe cerebral oedema with a normal CT scan. By contrast the reverse situation, signs of cerebral oedema on the scan but no oedema in fact present, was not possible. At best, a CT scan can show an abnormality from which it is possible to say that cerebral oedema is likely, but that is all. He thought that clinical evidence of raised intracranial pressure was much more important. Dr Robinson returned to this matter in cross-examination (6 December 2001, 3.44). He explained that, if the fluid-containing spaces within the skull were obliterated, that led to a strong inference that cerebral oedema was present. If they were not obliterated, however, that did not necessarily mean that cerebral oedema was not present. There were two reasons for this. First, the cerebral oedema might not be generalised, but might only affect parts of the brain. Secondly, Dr Robinson understood from conversations with radiologists that a CT scan was a relatively insensitive way of assessing cerebral oedema. Finally, in re-examination (7 December 2001, 3.01) Dr Robinson was asked whether there was anything unusual in the fact that brain swelling had appeared in the CT scan of 29 September, some days after the event. He replied that that was not unusual, and that to explain this result there was no need to resort to any theory of ammonia toxicity.
[154] On this matter I prefer the evidence of Dr Beattie and Dr Robinson. For reasons that I have already explained, I found their evidence and opinions to be generally convincing. Consequently I have no reason to doubt their opinion on the limited utility of CT scans. Dr McWilliam sought to use the evidence from the scans to exclude brain swelling as a cause of the raised intracranial pressure that Laura had suffered. He was not a radiologist, however, and accordingly the interpretation of such scans was not a matter on which he had direct expertise. I accordingly reject the inference that the CT scan taken on the afternoon of 25 September 1992 excluded the possibility that Laura's raised intracranial pressure was caused by brain swelling.
Conclusion on Dr McWilliam's evidence
[155] For the reasons stated above in paragraphs [148] and [149], I am of opinion that Dr McWilliam's fundamental theory, that brain damage in hyperammonaemic episodes is caused not merely by the swelling of the astrocytes but also by the direct toxic effects of glutamine and ammonia, is less probable than the theory put forward by Dr Robinson, based on the views of Professor Brusilow, that the sole causal mechanism is swelling of the astrocytes as a result of hyperammonaemia. As I have sought to explain in paragraph [144] above, it is clear that Dr McWilliam's views about Laura's condition on 25 September 1992 were based squarely on his theory about the causal mechanism involved in producing brain damage. If his theory is rejected, accordingly, his opinion on the events of 25 September must also be rejected. In addition, for the reasons stated in paragraphs [151] - [154], I consider that I cannot use the CT scan taken on 25 September as indicating that Laura did not suffer from raised intracranial pressure earlier that day. The evidence from that scan was a significant factor in Dr McWilliam's opinion. My rejection of that part of his evidence accordingly strengthens the opinion that the views of Dr Robinson on Laura's condition should be preferred.
H. Overall conclusions
[156] For the reasons stated above, I am of opinion that Dr Greene, for whose acts the defenders were responsible, was in breach of the duty of reasonable care that he owed to Laura, and that that breach of duty caused substantially the whole of the whole of the brain damage suffered by Laura on 25 September 1992. The critical findings are those on fault contained in paragraphs [80] - [83] and those on causation contained in paragraphs [94] - [100] and [101] - [107]. I will accordingly pronounce an interlocutor making findings to the foregoing effect. I will in consequence sustain the first plea-in-law for the pursuer, repel the first, second and third pleas-in-law for the defenders and allow a proof before answer restricted to the issue of the quantum of loss suffered by Laura Miller.