Kerr v Minister for Health
[2007] WADC 61
•27 APRIL 2007
KERR -v- MINISTER FOR HEALTH [2007] WADC 61
| Link to Appeal : |
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| DISTRICT COURT OF WESTERN AUSTRALIA | Citation No: | [2007] WADC 61 | |
| Case No: | CIV:2205/2004 | 18-21 SEPTEMBER 2006 | |
| Coram: | GROVES DCJ | 27/04/07 | |
| PERTH | |||
| 37 | Judgment Part: | 1 of 1 | |
| Result: | Action dismissed | ||
| PDF Version |
| Parties: | MARIANNE KERR MINISTER FOR HEALTH |
Catchwords: | Tort Breach of duty Medical negligence Pain relief Post-operative prescription for Pethidine Norpethidine toxicity Risk of seizure Failure to warn of risks of complication Turns on own facts |
Legislation: | Nil |
Case References: | City of Stirling v Tremeer [2006] WASCA 73 Davies v Taylor [1974] AC 207 Nil |
JURISDICTION : DISTRICT COURT OF WESTERN AUSTRALIA
- IN CIVIL
- Plaintiff
AND
MINISTER FOR HEALTH
Defendant
Catchwords:
Tort - Breach of duty - Medical negligence - Pain relief - Post-operative prescription for Pethidine - Norpethidine toxicity - Risk of seizure - Failure to warn of risks of complication - Turns on own facts
Legislation:
Nil
Result:
Action dismissed
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Representation:
Counsel:
Plaintiff : Mr J R Johnson
Defendant : Mr D Clyne
Solicitors:
Plaintiff : Julian Johnson
Defendant : Dibbs Barker Gosling
Case(s) referred to in judgment(s):
City of Stirling v Tremeer [2006] WASCA 73
Davies v Taylor [1974] AC 207
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1 GROVES DCJ: The plaintiff sues the defendant as operator of the Osborne Park Hospital ("the hospital"). She alleges that by reason of the negligence and/or breach of duty of the defendant she suffered personal injury, loss and damage. The material facts are not substantially in dispute.
The facts
2 The plaintiff was born on 25 August 1969 and at the time of her admission to the hospital was 33 years of age. On 6 August 2003 she was admitted to the hospital for maxillary sinus surgery. At about 0800 hours she was taken to the operating theatre where Dr Sakarapani performed a submucosal resection, bilateral turbinate reduction and excision of a nasal polyp under general anaesthesia ("the surgery"). At the end of the surgery bilateral nasal packs were inserted.
3 Pre-operatively Dr Beahan an anaesthetist engaged by the defendant who had the management and supervision of the plaintiff's post-operative pain relief prescribed pethidine 100-150 mg intramuscularly second hourly as needed and Tramadol 100 mg orally fourth hourly as needed for pain.
4 The plaintiff was returned to the ward at approximately 1045 hours on 6 August 2003. Pethidine was given for post-operative pain as follows:
6 August 2003
1220 hours pethidine 100 mg
1600 hours pethidine 100 mg
1920 hours pethidine 100 mg
7 August 2003
0010 hours pethidine 100 mg
0335 hours pethidine 100 mg
0740 hours pethidine 100 mg
5 At about 0800 hours on 7 August 2003 the plaintiff was sat up in bed so that her nasal packs could be removed as ordered by her surgeon. At about 0805 hours a Nurse Durkalic employed by the defendant started to remove the nasal packing when the plaintiff began to fit and suffered a
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- seizure. At about 0810 hours three nurses were present and cardiopulmonary resuscitation ("CPR") chest compressions were commenced.
6 The plaintiff was noted by the nurse/s present:
(a) At about 0812 hours to be breathing.
(b) At about 0813 hours to have a pulse of approximately 30 beats per minute.
- At about 0814 hours an anaesthetist Mr Hennessy arrived and confirmed the plaintiff was breathing and in sinus rhythm.
7 At about 0930 hours the plaintiff was noted to be conscious with:
(a) a heart rate of 135 beats per minute;
(b) blood pressure reading of 117/76 mmHg;
(c) a temperature of 36.6ºC;
(d) a respiratory rate 16 breaths per minute.
- At some time after 0814 hours and prior to 1015 hours the plaintiff was given a chest x-ray which inter alia, noted:
"…there is no evidence of cardiac decompensation. The lungs are fully ventilated and clear."
The plaintiff's allegation
9 The plaintiff alleges that the dosage of pethidine prescribed by Dr Beahan and the dosage administered, being 600 mg in a 19 hour period:
"(a) exceeded the recommended safe dose of no more than 600 mg per 24 hour period and was consequently excessive;
(b) placed the plaintiff at a significantly increased risk of suffering a seizure due to norpethidine toxicity, associated with such pethidine's administration."
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10 The plaintiff alleges that the defendant, its servants or agents (including Dr Beahan) for whose breach and lack of care the defendant is vicariously liable was in breach of its duty of care owed to the plaintiff in:
"(a) prescribing doses of pethidine in excess of the recommended dosages;
(b) prescribing and administering pethidine in dosages which were known to cause or ought to have been known to cause the plaintiff to suffer:
(i) neurotoxicity;
(ii) seizures;
(iii) rapid onset respiratory depression;
(iv) proliferal circulatory collapse;
(v) bradycardia.
(c) failing to warn the plaintiff of the risks of complication."
11 The defendant denies those allegations. The defendant says:
(a) the dosage was not excessive;
(b) the probable cause of the seizure on all of the evidence was a vasovagal syncope ("VVS").
The plaintiff's evidence
12 On her admission to hospital the plaintiff gave a history of taking the prescription drug Zoloft 100 mg daily. That is confirmed in the Nursing History (Exhibit 1 p 52). She had been prescribed Zoloft for depression some months following the birth of a child in September 1996. The preoperative anaesthetic assessment (Exhibit 1 p 4) undertaken by Dr Beahan also notes that the plaintiff was medicating on Zoloft. She could not recall having discussed with anyone pre-operatively the type of pain medication she was to receive post-operatively. Dr Sakarapani outlined to her the procedure and she was aware that the nasal packs would be removed at some time post-operatively. The surgery was undertaken under a general anaesthetic.
13 Post-operatively she was aware that she was given injections intramuscularly for pain relief and also "…something orally." She was
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- not aware as to what the medication was. Having been forewarned that there would likely be pain associated with the removal of nasal packs she said that the thought of that procedure was not a cause for concern to her.
14 When she woke the following morning viz 7 August 2003–
"A nurse came in and she gave me an injection and she left again. A short while after that, I started to feel a bit strange. A little bit like I was drunk. Light headed.
How long after the injection?---5 to 10 minutes. I am not one hundred per cent sure.
Okay?---A short time after that, the nurse came back in. As I was talking to her, I felt that the words that I was trying to say to me sounded like they were coming from somebody else. They didn't sound right to me and then the nurse sat me up in bed at about a three quarter lay and I was just about to tell her that I was feeling a bit strange and I'd blacked out."
15 After having blacked out the next thing she remembered was waking up in a total sense of panic still in her bed at the hospital. She knew that something had happened but did not know what it was. Her recollection for the remainder of the day was vague save that she could recall briefly seeing her husband before being placed in an ambulance and taken to SCGH. She was discharged the following day and went home in some pain. The pain which she experienced was in the area of her thoracic spine. A few days later she saw her general practitioner Dr Dunstan who arranged an x-ray and a bone scan. She claimed to have suffered immense pain in that area through the rest of 2003 with gradual improvement over 2004 and 2005. She was initially restricted in undertaking household duties but gradually progressed to light household work. She can now do the majority of things which she needs to do although she continues to suffer pain and on occasions she is assisted by taking painkillers. She had a range of treatment over that period of time.
16 Prior to this surgery the plaintiff had undergone a number of surgical procedures of an elective or semi-elective nature. She had received pethidine on many occasions without any adverse consequence.
Evidence of nurse Edita Durkalic
17 Nurse Durkalic came on duty at 7.00 am on the morning following the surgery. She recalled greeting the plaintiff first thing in the morning,
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- bringing some towels and explaining to her the procedure for removal of the nasal packs and explaining that because it is an uncomfortable procedure she would be given some pethidine for pain relief. Nurse Durkalic administered an injection of 100 mg of pethidine which was recorded as having been done at 0740 hours. When she returned a little while later she again explained what was to be done and engaged in unrelated conversation to take the plaintiff's mind off the procedure. The back of the bed was raised up to about 75 degrees from the horizontal so that the plaintiff was partially sitting up. Nurse Durkalic said:
"[I] was just trying to take that sticky tape off because its elastoplast which is very hard sticky tape to keep those nasal packs in situ. So I was trying to take that sticky tape off while Ms Kerr just rolled her eyes and then she started fitting. That was happening within seconds."
"At 7.40 imi (intramuscular injection) of pethidine 100 mg plus 10 mg of Metoclopramide given as ordered before removing the nasal packs.
At 8.05 patient finished her breakfast, just half a toast and a few sips of coffee.
Patient sat up in bed and the nurse commenced removal of nasal packs. Bolus gauze removed. Just one part of the tape when the patient started fitting with her arms clenched across her chest. Alert bell rang three times, patient rolled on her right side, looking blue, unable to open her mouth. Stopped breathing. Unable to feel the pulse at that time. At 8.10 CPR commenced. CNS (clinical nurse specialist) and CN (clinical nurse) and RN (registered nurse), at 0812 patient pulse 30, at 0814 the anaesthetist arrived – airway inserted. At 0815 – patient turned on her right side, patient breathing spontaneously, but pulse 133/min. CXR (chest x-ray) attended. RMO checked the patient."
19 At the time of this incident Nurse Durkalic was not aware from any source that seizures had been reported in cases where patients had received relatively low doses of pethidine nor was she aware that there was any controversy in medical literature about pethidine being used post-operatively. In her almost three years experience at the hospital it was the usual practice for this type of surgery that pethidine or sometimes
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- morphine was prescribed for post-operative pain relief. An alternative analgesia fentanyl was not used intramuscularly but would, if used, be administered intravenously. She said that both pethidine and morphine was still used for post-operative pain. The higher the pain score which the patient upon enquiry gave the more likely pethidine or morphine would be used. With a lower pain level tramadol or panadol might be used. For this type of nasal surgery, submucosal resection which she understood to be one of the most uncomfortable surgeries and for the removal of the nasal packs also very painful, required a strong analgesia namely pethidine or morphine to be administered for pain relief. In administering pethidine prior to removing the nasal packs she was simply following the post-operative procedure as directed by the surgeon Dr Sakarapani. Although it was common where pethidine was ordered to be given post-operatively for there to be a limit placed on the amount of pethidine to be administered she could not recall whether that was the practice of this anaesthetist Dr Beahan. The purpose of giving the pethidine prior to removal of the nasal packs was for the relief of pain which the patient would experience during and following the uncomfortable procedure of the removal of the nasal packs.
Evidence of John Robert Raftos
20 Dr Raftos was called by the plaintiff. He describes himself as an accident and emergency physician. He has been a registered medical practitioner in New South Wales since 1976, a Fellow of the Australasian College for Emergency Medicines and a specialist in emergency medicine since 1983. He has been employed as Director of Emergency Medicine at the Sutherland Hospital, Caringbah since 1984 and as a senior specialist in emergency medicine at St Vincent's Hospital, Darlinghurst, NSW since 1997. He also lectures in medicine at the University of NSW. His extensive curriculum vitae (Exhibit 6) details his various appointments, memberships, grants, awards and publications. It is noted that he is not a specialist anaesthetist and nor has any research undertaken or publications written by him been in the field of anaesthesia.
21 In response to requests by the plaintiff's solicitor Dr Raftos prepared three reports dated 27 May 2004, 7 November 2005 and 12 May 2006 (contained in Exhibit 2). In the first of those reports after reciting the history based upon the letter of instruction and medical records provided to him he states (so far is relevant):
"There are two possible causes of the tonic/clonic seizure that Ms Kerr suffered on the morning of 7 August 2003. One is that
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- she fainted during the procedure to remove the pack from her nose and the resultant reduction in blood supply to her brain caused seizure activity. The second is that norpethidine, a metabolite of pethidine induced the seizure.
Vasovagal syncope (fainting) occurs when a stimulus causes the vagus nerve to fire excessively. This excessive vagal activity causes a sudden reduction in heart rate. The resultant reduction in blood flow to the brain causes transient unconsciousness. Very infrequently, if the patient faints in the sitting position, the reduction in brain blood flow may be more profound because of the additional contribution of gravity and may therefore cause hypoxic seizure activity. Pain, or the anticipation of pain, are common precipitants of vasovagal syncope.
The use of pethidine for analgesia has become in the past decade (sic) because it is the most addictive of the opiates and because one of its metabolites, norpethidine, causes cerebral excitation whose manifestations include seizures. Norpethidine has the potential to cause significant neurotoxicity. Pethidine is metabolised in the liver to norpethidine which has about half the analgesic potency of pethidine but two to three times the potency as a central nervous system excitatory agent. Pethidine has a half life of three to five hours compared to eight to twenty one hours for norpethidine. If pethidine is given in a second to fourth hourly intermittent dose regime (the frequency necessary for adequate pain relief), the active metabolite norpethidine accumulates because of its longer half life. This accumulated norpethidine may lead to potentially serious adverse effects including tremor, twitching, agitation, confusion and (rarely) fittings/seizures. It is commonly stated in the literature that a 600 mg per day limit should be set on pethidine in clinical practice in order to avoid serious neurological sequelae such as seizures.
Concern about the adverse effects of pethidine has caused a large number of hospitals in Australia to restrict its use to those patients who are intolerant to morphine and, even in those patients, many hospitals recommend the use of other, apparently safer opiates such as fentanyl rather than pethidine. 24 hour dosage should be restricted to an upper limit of 600 mg. The adverse effects of pethidine have been well documented and widely discussed in the literature to the extent that any doctor
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- who prescribes opiate analgesia should be aware of the risks involved in the use of pethidine compared to the apparently safer morphine and fentanyl.
. . .
The most likely course of events is that Ms Kerr suffered a vasovagal syncope because of pain, or the anticipation of pain, caused by the attempted removal of the nasal pack. Her heart rate dropped because of vagal overactivity and may have been imperceptible for a time. The reduction in blood flow to her brain was worsened by her sitting posture. She had a seizure because of a combination of norpethidine toxicity and reduced blood flow to the brain and recovered spontaneously without any specific treatment. Evidence of normal breathing may well have been absent for a short time during the faint and subsequent seizure.
The anaesthetist prescribed pethidine 100-150 mg second hourly as needed for Ms Kerr's post-operative pain. Despite its potential adverse effects pethidine is still considered to be a reasonable medication for post-operative pain and so the doctor was acting within the bounds of reasonable practice in prescribing pethidine. The dosage regimen, however, exceeded the upper limit of the reasonable range for pethidine. Were pethidine to be given at a dose of 100 mg every two hours, the 24 hour dose would be 1,200 mg which exceeds the recommended safe dose. As it was, Ms Kerr was given 600 mg of pethidine over some 19 hours. This dose exceeds the generally recommended upper limit for pethidine use of 600 mg over 24 hours and placed her at a significantly increased risk of suffering a seizure because of norpethidine toxicity. While the pethidine dosage may not have been the sole cause of her seizure, it is unlikely that she would have had a seizure in the circumstances if she had been treated with a safe dose of pethidine or with an opiate analgesic other than pethidine."
22 Later in his report he states:
"The excessive dose of pethidine was probably not the sole cause of Ms Kerr's seizure but it contributed substantially to the development of the seizure. She probably developed reduced cerebral blood flow due to vagal overactivity but this, on the
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- balance of probabilities, would not have caused seizure activity had she not had an elevated norpethidine level because of an excessive pethidine dosage regimen. Had she been prescribed an analgesic other than pethidine or had the dosage of pethidine been within the recommended safe level, she would not, on the balance of probabilities, have had a seizure."
23 In his following reports Dr Raftos cited medical journal writings (later referred to) in support of his opinion concerning the recommended safe daily dose of pethidine. He stated that:
"A reasonable summary of the recent literature concerning pethidine is that it may cause norpethidine associated toxicity at variable doses and at variable times and that the risk of norpethidine related neurotoxicity means that its use in more than single doses is not justified."
24 In his evidence-in-chief Dr Raftos said that for more than 20 years as an emergency physician a large part of his practice from day to day involved treatment of pain. For many years the standard opiate medication used was pethidine. In about 2001 however he stopped prescribing pethidine and gave as his reasons for that change in practice that in the late 1990's and early 2000's there had been discussions in medical circles concerning the adverse effects of pethidine, those being its potential for addiction, especially amongst health professionals, its interaction with other medications to cause hypertensive crisis and its potential to cause seizures with repeated dosing. That discussion was in the medical literature disseminated by the New South Wales Department of Health at that time and at clinical discussion at meetings and informally with his colleagues. He described the potential seriousness of seizures as including the potential for injury to body parts due to the muscle movements during seizure, the potential for regurgitation and aspiration of vomitus causing aspiration pneumonitis and respiratory distress and the potential, albeit a small risk, of death during a seizure. Neither literature nor current knowledge have been determinative as to an exact level in which seizures will or will not occur. He considered that a dose of 600 milligrams over 24 hours was "probably safe" and was not aware of any reported cases of seizure using such doses. He described that as being "a relevant arbitrary safe lower limit." In reference to the fact that the plaintiff was at the time taking the medication Zoloft for depression he stated that it was known that there is an interaction between the group of antidepressants known as SSRI of which Zoloft is one and pethidine. That interaction he said can cause the serotonin syndrome, but it is also
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- suggested that a combination of Zoloft and pethidine may lower the seizure threshold. To Dr Raftos' knowledge neither of the two alternatives to pethidine, namely morphine and fentanyl have been implicated in the causation of seizures. Asked to comment on the likelihood that this incident was simply a consequence of the syncope rather than a combination with pethidine he opined:
"Its possible that it was purely a syncope, but the dose of pethidine suggests to me that pethidine neurotoxicity was involved in the causation of the seizure. We know that pethidine neurotoxicity reduced the seizure threshold and so in a situation where there is going to be vagal stimulation, like removing a pack from a nose, certainly the influence of pethidine may well make the difference between whether the patient does have a seizure or not. … The vast majority of faints aren't associated with seizure activity. Less than … one in 10,000 faints or vasovagal syncopes may go on to involve seizure activity, so its uncommon."
26 In cross-examination Dr Raftos acknowledged that his practice did not generally involve post-operative anaesthesia or care or writing prescriptions of analgesia beyond one day and then no more than four doses each of 100 mg a day. Upon being referred to his first report he acknowledged that it was possible that the fact that the plaintiff could not breathe through her nose because of the nasal packs inserted that may have increased the possibility of hypoxic (meaning lack of oxygen) seizure activity.
27 In his report of 12 May 2006 Dr Raftos had stated:
"On this basis, it may be reasonable to prescribe pethidine second hourly but such a prescription must also have an accompanying limit concerning the number of doses or the total daily dose. For instance, 'pethidine 100 mg second hourly
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- x four doses only' or 'pethidine 100 mg second hourly, maximum 600 mg/day' would be safe and acceptable prescribing while 'pethidine 100-150 mg second hourly', without an upper dose limit, would not be safe or acceptable prescribing."
- In that context Dr Raftos conceded that the dosage of 600 mg in 19 hours fell within the second of the two examples which he gave as a safe and acceptable prescription. It was however his evidence that the recommendation is 600 mg over 24 hours but that the same dosage over a lesser period of time whilst conforming to the word of the recommendation did not conform to the science or the spirit of the recommendation as he understood it. He was not able to identify any authority or support in reference material for that statement.
The medical journal articles
28 Dr Raftos in his reports made reference to published articles in what he claimed were highly regarded and widely read journals. Those articles were (Exhibit 7):
(a) J L Plummer – "Is there still a place for pethidine in the management of post-operative pain?" - published in Current Anaesthesia and Critical Care (June 1995),
(b) J L Plummer, G K Gourley and D Cherry – "Norpethidin Toxicity" – published in Pain Reviews (2001),
(c) K S Latta, B Ginsberg and R L Barkin – "Meperidine: A Critical Review" – published in American Journal of Therapeutics (2002),
- J L Plummer, the author of the first article was attached to the Pain Management Unit, Department of Anaesthesia and Intensive Care, Flinders Medical Centre in South Australia. His first article published 1995 compared pethidine and morphine as effective analgesics for post-operative pain. He describes the history and pharmacology of pethidine and records that on average pethidine has a longer half life, ie effective duration of action, (3-8 hours vs 1-5 hours). He noted that "the non-opioid effects of pethidine may be involved in a number of adverse drug interactions."
29 Under the heading "Norpethidine Toxicity" he writes:
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- "Excitatory effects, such as … seizures, associated with prolonged used of pethidine were described as early as 1940. … In 1997 it was reported the norpethidine a metabolite of pethidine, accumulates when repeated doses of pethidine are given, especially in patients with renal failure."
- The estimated half life of norpethidine was 14-21 hours. He goes on to write:
"While many individual cases of norpethidine toxicity have been reported, the prevalence of symptoms in patients receiving pethidine for post-operative pain is unknown. It is possible that subtle effects are common."
Elsewhere he writes:
"Increasing awareness of the potential for norpethidine toxicity appears to be having a negative effect on pethidine's reputation at present."
After reviewing comparative studies, pethidine vs morphine, and evaluating that evidence his article concludes:
"Studies to date indicate a small overall advantage of morphine over pethidine in control of post-operative pain. Such small benefits observed in groups of patients do not necessarily indicate that each individual patient will benefit more from morphine than from pethidine. It is possible that future studies may demonstrate important differences between morphine and pethidine. However, based on currently available evidence, the clinician who prefers to prescribe pethidine for post-operative pain, in full awareness of its advantages and limitations, may continue to do so confident in the knowledge that it is a safe and effective analgesic."
"…repeated administration of pethidine leads to accumulation of norpethidine. High blood concentrations of norpethidine are associated with excitatory toxicity. Numerous cases of seizure have been reported in patients receiving pethidine over a period
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- of days or in some cases only hours. … When multiple doses of opioids are likely to be required, pethidine should be avoided. If it is used, patients should be informed of the risks and monitored closely for signs of toxicity."
- Results of clinical studies demonstrated that norpethidine accumulates with repeated pethidine administration. The authors of one study suggested that a cumulation of norpethidine contributes to the excitatory toxicity of pethidine. A variety of symptoms have been ascribed to norpethidine in the literature, but the full range has not been clearly defined. "The most characteristic appear to be unpleasant subjective feelings, behavioural changes, myoclonus and seizures." Under the heading of "Prevention of Norpethidine Toxicity" the authors write:
"It hardly needs be said that the most effective preventive measure is to not use pethidine when repeated doses may be required. With the availability of a number of effective alternatives, such as morphine, hydromorphone and fentanyl, this is generally a realistic option. … Certainly, pethidine should be avoided in patients with risk factors; impaired renal function, expected high or prolonged opioid requirement, or the use of enzyme-inducting drugs such as phenytoin and ritonavir. … Patients who do receive pethidine should be monitored for signs of central nervous system toxicity such as changes in mood and myoclonus. However, as noted above, seizures can occur without warning. Toxicity is generally associated with high doses of pethidine. An upper dose rate of 10 mg/kg per day has been suggested to provide a reasonable margin for safety. Using this upper dose limit, it was reported that no cases of norpethidine toxicity were seen in five years, except when the dose limit was ignored. Dose rates exceeding 600 mg/day are associated with a high risk of toxicity."
"The use of pethidine as a first line analgesic is clearly unjustified. Indeed, with the availability with a range of opioid and non-opioid analgesics, the need to resort to pethidine should rarely arise. When pethidine is to be used in more than a single dose, the risk of norpethidine toxicity is great enough that patients should be warned about it. The use of pethidine has been declining for some years. It would be appropriate for this decline to continue."
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32 In the third of the journal articles published 2002, Latta et al concluded:
"Certainly, meperidine '(the American terminology for pethidine)' is a medication whose time has passed in routine pain management and whose use must be questioned in all instances."
- In their abstract the authors state that meperidine use is complicated by unique side-effects including serotonergic crisis and normeperidine (norpethidine) toxicity. They say that poor efficacy, toxicity, and multiple drug interactions have resulted in a movement to replace meperidine with more efficacious and less toxic opioid analgesics. The article also discusses what is described as "serotonin syndrome".
"When meperidine is used in patients using 5-HT-selective reuptake inhibitors, ie antidepressant drugs there is the risk of increased 5-HT levels leading to possible serotonin syndrome."
In discussing the total amount of meperidine administered per day they state:
"It has often been stated in the literature that 1200 mg per day (100 mg every two hours parenterally) is a 'safe' level and a 600 mg per day limit in clinical practice is suggested."
In discussion they write that:
The spectre of (serotonin syndrome) and its connection with normeperidine toxicity must also be considered. Given the popularity of the 5-HT specific reuptake inhibitors and the possible interaction with meperidine, a clinician must be careful and have a thorough understanding of a patient's pharmacotherapy history."
They too expressed the opinion that alternatives such as morphine and fentanyl are more effective alternatives to meperidine.
Evidence of Peter Grattan Beahan
33 Dr Beahan has practised as a specialist anaesthetist since 1964. He attended on the plaintiff preoperatively and he noted on the anaesthetic record (Exhibit 1 p 4) a history that she was "In good health. No past serious illness. No medications. No known allergies. Chest clear. Cardio vascular system normal. Head and neck normal. Teeth normal."
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- He acknowledged that he had incorrectly noted "no medications" because under a separate heading of medications he did in fact note Zoloft.
34 For this type of operation it was not Dr Beahan's practice to discuss the type of medication to be prescribed post-operatively or the relative advantages and disadvantages of one medication over another. He would only do that if a patient asked questions about it. He agreed that he had no discussion with the plaintiff about any post-operative medication. On the medication chart (Exhibit 1 p 13) Dr Beahan prescribed for post-operative pain relief "pethidine 100 (100-150) mg intramuscularly 2 hourly as needed". It is noted that the prescription is "open ended" in that it did not prescribe either a maximum dosage or a maximum duration for use of pethidine. In his evidence however Dr Beahan said that he considered that pethidine would be used "for a period of roughly 48 hours". He also prescribed, so far as is relevant Tramadol an oral analgesia which could be used when the patient no longer needed to have (pethidine) intramuscular analgesia.
35 Dr Beahan has used pethidine in his practice since 1964. He was aware in 2003 that there were some moves suggesting that pethidine ought not to be used in certain circumstances. Nevertheless, he continues to still use pethidine. His reasons for continuing to still use pethidine are that first in his experience he has not had any problem with pethidine; secondly he sees advantages in its use and thirdly that there are disadvantages with the use of the main alternative which is morphine. It was his clinical impression that pethidine has slightly less side effects than morphine. He acknowledged that his clinical impression "…may or may not stand up to scrutiny, but on the other hand I have had really no problems with it in the past, other than those well known side effects which are well known to everyone and relatively easy to deal with." It was Dr Beahan's opinion that the dosage of 600 mg over 19 hours did not contribute to the plaintiff's seizure. His explanation in arriving at that conclusion was:
"Because the dose, if you look at it, the total dose of 600 mg, but the fit actually occurred only 20 minutes after the last dose, so that – the thing that causes a fit with prolonged use of pethidine is norpethidine metabolite. You can hardly expect there to be any significant build-up of norpethidine after the last dose because it was only 20 minutes before the fit, therefore you have to speculate that the build-up of norpethidine would have been from 500 mg of pethidine, which is less than is generally thought to be the minimum amount of pethidine you
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- need to have, which is I understand to be about 1000 mg. Secondly, it has just not been my experience – I mean, I've worked for 27 years at Royal Perth Hospital, which is a very busy place. I have seen and been in touch with very large numbers of patients, and I have never seen a patient of my own has had this condition and I have never had my attention drawn to anyone else who has had this condition either."
36 Dr Beahan was aware that norpethidine neuro-toxicity could occur in circumstances of prolonged use. Since being aware of that for some 15 years he had not used pethidine for long use or in patient controlled analgesia.
37 Dr Beahan did not consider prescribing fentanyl as an alternative to pethidine for the reason of its shorter effective life of ½-1 hour and because it would have to be used as a patient controlled analgesia.
38 By prescribing pethidine to be administered "as required" left its administration to the discretion of the nursing staff.
39 In cross-examination Dr Beahan was pressed as to his knowledge of the problem of norpethidine and warnings against the use of pethidine. He was aware that the problem of norpethidine had been around for perhaps more than 20 years. Approximately 15 years ago the focus then was on not using pethidine for the longer term so it was at that time that he stopped using it for patient controlled infusions. More recently he was aware that the Australian and New Zealand College of Anaesthetists had moved against the use of pethidine not for the reason of the norpethidine problem but for other reasons as well. He personally regarded the College's move as "…a bit of an over statement, somewhat of an over statement." He was able to produce from his pocket a document titled Acute Pain which he said was put out by the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. The publication was undated. He believed that he "…would have received that either within the last year or within the last 2 years." From that document he read the statement that: "The use of pethidine should be discouraged in favour of other opioids." The document was not tendered. Dr Beahan was reluctant to concede that he was aware from any literature prior to August 2003 expressing essentially that view. His response was "not in precisely those terms, no, more in relation to pethidine not being a suitable drug for long term use." Insofar as keeping up to date with literature in relation to his area of practice in anaesthetics he read journals, attended conferences and followed certain information through the
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- internet. He was aware of but not a reader of the publications referred to earlier in these reasons. He was however aware of an article which he read before August 2003, which suggested that it may be possible for norpethidine toxicity to occur with a dose less than 1000 mg. He could not recall where the article was published or the name of the article. Having read that article did not cause him to change his practise. When referred to the Plumber article published in 2001 where the opinion was expressed that there was a high risk of toxicity if a dose exceeding 600 mg per day was given it was Dr Beahan's response that he had not heard of that statement. Had he been aware of the statement he said "I would have had to look at that very critically because a single article is very difficult to make a judgment on." He would need some corroboration and a body of evidence and weigh it against his own experiences of using pethidine for 40 years and not having seen that problem. His experience was influential in terms of his continued practice.
40 Dr Beahan noted that the plaintiff was using the medication Zoloft. At that time however he was not "precisely aware" that Zoloft could reduce a patient's seizure threshold when receiving pethidine. Had he been aware he acknowledged that "it may have, possibly…" influenced his prescription of pethidine. It was not explained what he meant by "precisely aware of". That may suggest that he did have a little knowledge at least.
Evidence of Michael James Paech
41 Professor Paech is the Professor of Obstetric Anaesthesia at the University of Western Australia, the senior specialist anaesthetist at King Edward Hospital and a visiting specialist anaesthetist at Royal Perth Hospital. He gained his basic medical qualification in 1979 and holds a number of other qualifications, fellowships and memberships of numerous medical bodies which are detailed in his curriculum vitae (Exhibit 11). Professor Paech was called by the defendant.
42 The substance of Professor Paech's evidence was contained in three statements dated 15 July 2005, 21 February 2006 and 6 September 2006 (contained in Exhibit 3). In the first of those reports he states (so far as is relevant):
"It is extremely unlikely there is a link between the amount of pethidine given (and by implication the amount of its major metabolite, norpethidine, which is a less potent pain reliever but twice as potent as a convulsant) and the plaintiff's seizure. This metabolite accumulates in the blood because of very slow
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- elimination, and high levels of plasma pethidine and especially norpethidine, are associated with seizures (convulsions). The plaintiff, however, only received a total dose of 600 mg, which is well within the Product Information recommended dose range (up to 150 mg 3-4 hourly…for no longer than 24-36 hours ie a potential dose of 1200 mg in 24 hours). Almost all cases of seizure reported occur after several or many days of administration at this dose level, or in the presence of renal failure (which slows drug excretion). The blood tests performed after the seizure exclude significant renal impairment in the plaintiff.
It is never possible to be absolutely certain, because individuals vary in their propensity to have a seizure, but in this case the plaintiff had no medical reason for a lower "seizure threshold", and although the antidepressant drug sertraline (Zoloft) she was taking may confer a possible reduction in threshold, the combination of pethidine with sertraline is not contra-indicated. … My own research supports other studies, showing that when doses of pethidine of up to 500 mg per 12 hours are used by patients after surgery (dose requirements up to 1000 mg in 24 hours are common), the levels of plasma pethidine and norpethidine remain well below the lowest level associated with seizures.
It is also worth noting the intramuscular pethidine has a short duration of effect and, when used by anaesthetists it is routine for it to be prescribed at 2 hourly intervals rather than the outdated 3-4 hourly recommendation, to improve the quality of pain relief.
. . .
By far the most likely explanation for the seizure was that it followed a vaso-vagal collapse. This means a sudden profound fall in heart rate from reflex response involving over-activity of the vegas nerve, or even a transient cessation of cardiac electrical activity and output, leading to inadequate brain blood supply and hypoxia. It is an extreme "faint" – typical in a healthy and often younger patient who is sitting upright having, or about to have, something done they perceive as unpleasant or that is making them feel anxious (such as nasal packs being removed). This fits with the clinical situation, explains the
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- transient absence of a pulse and the rapid return of cardiac output, and the slow heart rate of 30 beats per minute noted shortly after resuscitation was commenced."
43 In further explanation of the last paragraph he opined that the seizure is brought about by the poor blood flow to the brain, a low level of oxygen supply to the surface of the brain and an hypoxic seizure. He did not consider that the actual onset of the seizure may have been influenced by the nasal packs. The subsequent response of the plaintiff may have been influenced by it because after a seizure the patient would normally start to breathe again and with the presence of the nasal packs, they being likely to obstruct their airway, there would be a reduced oxygen supply to the surface of the brain.
44 In his second statement 21 February 2006 Professor Paech responded to a number of matters raised by Dr Raftos. In particular he disagreed with Dr Raftos' assertion "…that the dose of 600 mg placed her at significant increased risk of suffering a seizure." His evidence was that:
"The reason for that is that is a dose that would have been frequently received by millions of patients in the past and we know that the seizures from pethidine are rare events. The vast majority occur in a situation of much, much higher doses over a prolonged period of time, so at that dose over a 1 day period, I would say it would be extremely unlikely that it would have resulted in a level of causing a fit."
45 In his final report dated 6 September 2006 Professor Paech in summary stated that it was his opinion:
"1. Ms Kerr was prescribed intramuscular pethidine in accordance with what had been normal practice for many years. Although over the past 5 years there has been an education campaign to discourage the use of pethidine as a first line analgesic and most anaesthetists no longer prescribe it as a first line treatment for post-operative pain, this change is still undergoing implementation; other doctors still use it extensively and many patients continue to receive this drug.
2. The regimen prescribed was not unacceptable based on the standard of care applicable at the time.
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- 3. The dose of 600 mg received was not unusually high judged on typical post-operative requirements and this dose falls within the extremely conservative dosing recommendations of the product information and regulatory recommendations.
4. The best estimate for risk of seizure, as a result of pethidine administration at this dose to a healthy patient, is that the risk is exceptionally rare.
5. Although it may be appropriate to do so in some circumstances, it is still not usual practice in 2006 to warn patients of a risk of seizure after more than one dose.
6. I maintain my opinion that the most likely cause of her seizure was 'vaso-vagal syncope' or 'faint'. As I have stated previously given the pethidine dose administered and the rarity of norpethidine induced seizure associated with the administration of such a dose, it is possible but unlikely that pethidine and norpethidine contributed substantially."
46 Professor Paech was pressed in cross-examination by reference to the published literature but was unwavering in his conclusions. Referred to one study which identified seizures occurring even with very low concentrations of norpethidine Professor Paech maintained:
"… Its possible that can happen and I've said in my statement that I believe that its possible that norpethidine may have contributed but I think its very unlikely to have and that wasn't substantial."
- Later he described the risk as "…exceptionally low and that's why it (pethidine) was still widely used and is still used." Later his cross-examination went as follows:
"You accept that the use of pethidine in this case involved a small but recognisable risk of seizures?---An exceptionally small, recognisable risk which would be considered to be clinically acceptable.
You have used that description a couple of times, what does clinically acceptable mean?---It means that on the basis of an individual case that quantifying, looking at all the potential risks of the drugs and the interventions and everything else that have
- been done, that something is viewed as acceptable or unacceptable. Obviously there is some degree of grey in there but that's the whole of medical practice is based on that fact.
Yes?---There are many risks with everything you do and we have to make judgments on what is clinically appropriate and what isn't appropriate.
So is it a matter of saying that the risk is sufficiently small, that it can be taken by the doctor?---Yes."
47 Professor Paech acknowledged that the use of Zoloft by the plaintiff may have conferred a possible reduction in her seizure threshold. Whilst that was something known in 2003 he did not agree that in prescribing pethidine the doctor should have taken account of the Zoloft when setting the dose. He described there being many drugs which do lower the seizure threshold but that Zoloft was not one which was contra-indicated in combination with pethidine. By "contra indicated" he said that the Product Information will normally state interactions in which a prescribing doctor needs to be cautious that there was not some interaction between two drugs that needed to be considered and where certain drugs should not be used. Zoloft was not contra-indicated in combination with pethidine. On the other hand he acknowledged that where a person has undergone an operation with consequent electrolyte changes in the body chemistry that such could lower seizure threshold. On another aspect he described the clinically observable signs of norpethidine toxicity as being agitation, jerkiness, jitteriness, twitching and seizures.
48 Having considered the literature before the Court Professor Paech maintained the opinion expressed by him that the most likely cause of the plaintiff's seizure was vasovagal syncope.
Brian Hennessy
49 Mr Hennessy was called by the defence. He has trained and practised in anaesthesia for some 15 years and has practised as a specialist anaesthetist since 2000. On the morning of the plaintiff's emergency he was anaesthetising in the operating suite when he was called to the ward to attend the plaintiff. When he arrived at the ward the plaintiff was supine on the bed and getting chest compressions by one nurse and was being ventilated by another nurse. Mr Hennessy moved to the head of the bed and took over the upper airway area and instructed the nurse to cease chest compressions. The plaintiff had a pulse of 30 beats per minute and she was spontaneously ventilating for herself. Oxygen was administered
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- and 2 minutes later the plaintiff was conscious again and had quite good cardiac parameters. He arranged for a chest x-ray, blood tests and monitoring of her condition. Once he had seen that all of these investigations were near normal he formed the opinion that the plaintiff had fainted and had a tonic clonic seizure – "tonic" meaning that when her seizure commenced she had increased muscle tone as indicated by clutching her arms across her chest which is a flexural tonic response and "clonic" meaning jerking as in an epileptic seizure where the patient is jerking backwards and forwards.
50 In his notes made immediately following resuscitation and prior to the plaintiff being sent for x-ray Mr Hennessy noted his assessment as "Likely bradycardiac arrest (vasovagal). Giving hypoxic seizure." (Exhibit 1 p 11).
51 In his capacity as a specialist anaesthetist the assertion that pethidine may have had some involvement in what had occurred was put to him. His opinion was that it was:
"…unlikely that the metabolite of pethidine, norpethidine, has caused Mrs Kerr to have a seizure… I think that Mrs Kerr received only 600 mg of pethidine which I think is an inadequate dose, or the amounts of norpethidine that's required before seizures to actually have built up in her system, and also the timing; it's likely to need about 36 hours for her to metabolise the pethidine to the norpethidine and for that norpethidine to accumulate in such an amount as to cause a seizure, so it's both the dose and the timing really that makes me think that would be an unlikely cause."
52 Asked whether there was anything in the fact that he noted the plaintiff was bradycardic he said:
"Yes. Pethidine was initially developed as an anticholinergic drug, not as an analgesic. One of its effects is to speed the heart up, not to slow it down. When she was initially noted to lose consciousness she was noticed to be bradycardic. This goes hand in hand with a neurological vagal phenomenon like a simple faint, so I think that the fact that she was bradycardic when she initially had the event I think is more consistent with having had a faint." (Bradycardic meaning a slow heart rate – converse to tachycardia meaning a fast heart rate).
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53 In cross-examination Mr Hennessy acknowledged that he was aware of the published literature referred to, that having been so in his capacity as an examiner in pharmacology with the College of Anaesthetists. He would not have surmised however that all anaesthetists in Australia and New Zealand would have been familiar with the articles within 12 to 18 months of their publication. Prior to mid 2003 he believed that there was minor discussion amongst the anaesthetics community about the advisability of pethidine's routine use in multiple doses. He disagreed with the statement in one of the published articles that the use of pethidine in routine pain management "…must be questioned in all instances". The conclusion in his opinion was over-stating the problem. His reason for that conclusion was that the incidence of seizure due to norpethidine toxicity is low in the dosage prescribed in this case. Rather, it was more common for norpethidine toxicity to occur in extended periods of administration and in particular situations where the patient developed renal impairment, for example after bowel surgery.
54 He did not consider that fentanyl was an alternative for use in the ward at the time because nursing staff were not permitted to administer it intramuscularly at that time. A good alternative however was morphine. In practice however it was a matter for the individual medical practitioner to choose their opioid based not only on its toxicity but its time to onset of effect and time to offset effects and its other cognitive effects. In this particular type of surgery where the amount of post-operative opioid that he would expect to be administered for the amount of pain the patient would have and the duration of it he considered that the pain relief medication outweighed the risk of norphethidine toxicity. He acknowledged that the antidepressant Zoloft had the potential to lower the seizure threshold. Similarly, body or electrolyte changes post-operation may have lowered the seizure threshold. Potentially those two factors may have increased the risk of seizure from pethidine. The patient reporting a feeling of drunkenness and a strange sensation when speaking, described as a sense of de-realisation, was in his opinion consistent with normal opioid administration rather than specifically norpethidine toxicity. His cross-examination continued:
"When you have commented that you don't believe the pethidine was the cause of the seizure are you talking about the primary cause or the reason in itself for the seizure?---Do I think that pethidine contributed to her having a seizure?
Yes?---From norpethidine toxicity, I think that's extremely unlikely.
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- What about the theory that has been put by Dr Raftos in this case that we have a combination of a seizure threshold which is reduced because of the Zoloft and other factors, we have the dose of pethidine that was administered, we then have the vaso-vagal syncope and part of the reason for the seizure occurring is the increased propensity to seizure resulting from the pethidine in her system, the norpethidine and the other factors. Would you agree that is a reasonable proposition?---Reasonable but I still think improbable.
And that's based upon your view that the likelihood of somebody suffering a seizure with 600 mg in 19 hours, very small. Is that fair?---I would say that's fair."
55 Mr Hennessy gave as a comparative example, evidence that fainting was not an unusual phenomenon for people sitting up and giving blood at the Red Cross. It can and does happen in simple circumstances without other factors being involved.
Causation – onus and burden of proof
56 There is no question but that the defendant, its servants and agents (including Dr Beahan) owed a duty of care to the plaintiff in their provision and management of her medical care at the hospital. However, a defendant is liable in negligence only if the damage suffered by the plaintiff was caused by the defendant's negligent act or omission. It is trite to say that the onus rests upon the plaintiff to prove her case. That is, the plaintiff carries the burden of satisfying the Court on the balance of probabilities that the seizure was caused as a consequence of the defendant's negligence as alleged.
57 When speaking of a degree of cogency which evidence must reach in order that it may discharge the legal burden in a civil case Denning J in Davies v Taylor [1974] AC 207 at 219 said:
"That degree is well settled. It must carry a reasonable degree of probability, but not so high as is required in a criminal case. If the evidence is such that the Tribunal can say: 'We think it more probable than not', the burden is discharged, but if the probabilities are equal it is not."
58 The negligent act or omission need not be the sole cause of the damage. This is reflected in the classic statement that causation will be established if the negligent act or omission caused or "materially
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- contributed to" the damage; see City of Stirling v Tremeer [2006] WASCA 73 per McClure JA at par 71.
59 Thus the question becomes can I be satisfied on the balance of probabilities that any negligent act on the part of the defendant caused or "materially contributed to" the injury suffered.
The issue for determination
60 The key issue for the Court's determination concerns the cause of the seizure experienced by the plaintiff at about 0805 am on 7 August 2003.
61 More particularly did the 600 mg of pethidine received by the plaintiff in the 19 hours prior to the seizure materially contribute to the seizure?
62 The answer to that question lies entirely on an assessment of the expert medical evidence.
The clinically observable signs of norpethidine toxicity
63 Plummer (2001) records that a variety of symptoms have been ascribed to norpethidine in the literature. The most characteristic appearing to be unpleasant subjective feelings, behavioural changes, myoclonus (spasm of muscles) and seizures. Dr Raftos described the potentially serious adverse effects as including tremor, twitching, agitation, confusion and (rarely) fittings/seizure. Dr Raftos said that "…you don't just get seizure, there are all sorts of other neurological changes that it causes too and … some of those are, altered consciousness, altered mental state and delirium. Professor Paech described the clinically observable signs of norpethidine toxicity as being agitation, jerkiness, jitteriness, muscle movements, twitching and seizures.
64 There was little evidence that the plaintiff exhibited any of those signs prior to the seizure. She did not describe unpleasant subjective feelings or exhibit any behavioural changes. There were no observed signs of agitation, jitteriness, twitching or tremor. Nurse Durkalic noted that the plaintiff "…started fitting with her arms clenched across her chest." Mr Hennessy formed the view that the plaintiff had a tonic clonic seizure. That it was "tonic" was indicated by the plaintiff clutching her arms across her chest being a flexural response. There was no evidence however that it was "clonic". That is there was no observation of "jerking as in an epileptic seizure where the patient is jerking backwards and forwards."
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65 On the evidence therefore I am not satisfied that prior to the seizure the plaintiff indicated any of the described clinically observable signs of norpethidine toxicity.
The plaintiff's symptoms
66 The plaintiff described that a short while after she was given an injection (being the 0740 hours pethidine 100 mg) she "…started to feel a bit strange. A little bit like I was drunk. Light headed." A short time later when talking to the nurse prior to being sat up in the bed she "…felt that the words that I was trying to say to me sounded like they were coming from somebody else."
67 Dr Raftos described the typical feeling before someone faints:
"…as feeling hot and flushed and sweaty and a bit light headed. The symptoms that Ms Kerr reported may have been along those lines, but they sound a little bit different."
- Mr Hennessy considered that the symptoms described by the plaintiff
"…would be consistent with normal opioid administration. The sense of de-realisation is something that's commonly reported by people who are administered opioids. Rather than specifically norpethidine toxicity I think that's quite common in just being administered opioids."
That is, the symptoms described were not of themselves an indicator of norpethidine toxicity.
68 In my opinion the symptoms described by the plaintiff particularly of feeling drunk and light headed are symptoms consistent with typical feelings which precede a faint or with normal opioid administration. I accept Mr Hennessy's evidence in that respect.
Bradycardia
69 Bradycardia is the slowing of the heart rate to less than 50 beats per minute. It is often found in healthy individuals but it is also seen in some patients with …vasovagal attacks. (See Oxford Concise Medical Dictionary).
70 Nurse Durkalic recorded in her report that after the plaintiff was sat up in bed she started fitting. The plaintiff stopped breathing. Shortly after CPR was commenced a pulse of 30 beats per minute was detected. Similarly Mr Hennessy on his arrival noted the plaintiff to have a pulse of
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- 30 beats per minute, she was spontaneous ventilating for herself and shortly after oxygen was administered the plaintiff was conscious again and had quite good cardiac parameters.
71 Dr Raftos in his first report of 27 May 2004 noted that "vasovagal syncope (fainting) occurs when a stimulus causes the vagus nerve to fire excessively. This excessive vagal activity causes a sudden reduction in heart rate. Similarly, Professor Paech in his first report in giving as the most likely explanation for the seizure a vasovagal collapse meaning "…a sudden profound fall in heart rate …". Mr Hennessy's assessment was that the likely cause of the seizure was a bradycardiac arrest giving hypoxic seizure. Having been bradycardic was consistent with having had a faint.
72 Mr Hennessy also stated that one of the effects of pethidine is to speed the heart up (tachycardia) not to slow it down. If a fast heart rate is a symptom of the use of pethidine then the event of bradycardia very much weighs against the cause of the seizure having been pethidine related.
Sitting the plaintiff up in bed
73 The medical specialists were consistent in their evidence that by raising the plaintiff to the sitting position would have caused a reduction in brain blood flow because of the additional contribution of gravity which could lead to hypoxic seizure activity.
74 That indicates that sitting the plaintiff up in bed as was done immediately prior to commencing removal of the nasal packs was almost certainly a factor contributing to her faint.
Removal of nasal packs
75 The plaintiff was aware that there would likely be pain associated with the removal of the nasal packs. She said that this was not a cause of concern to her. It would with respect be a brave person knowing that pain was imminent would not be a little troubled by the thought of it. Nurse Durkalic understood that submucosal resection was one of the most uncomfortable types of surgery and that a strong analgesia was required to overcome the pain. It was put to Mr Hennessy that his proposition that it was a vasovagal syncope was dependent upon acceptance that the plaintiff was apprehensive or afraid about the impending removal of nasal packs. His response was:
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- "The patient may not have really felt afraid of that beforehand. When you speak to people who are particularly afraid before a medical procedure I think they're much more likely to have those events, but I think it catches people out of the blue when they didn't realise that they were particularly afraid of what was about to happen to them, but nonetheless, they still had their faint."
76 Dr Raftos identified pain, or the anticipation of pain, as being common precipitants of vasovagal syncope. He acknowledged also that because the plaintiff was not able to breathe through her nose because of the nasal packs that circumstance may have contributed to the hypoxic seizure activity. Similarly Professor Paech indicated that the response of the plaintiff having had the faint may have been influenced by the presence of the nasal packs because they may have obstructed her airways.
77 Thus, there is here the potential contributing factor to the faint namely concern that pain would be experienced, albeit not acknowledged by the plaintiff, and then the blockage of the airways thereby reducing the level of oxygen supply to the surface of the brain leading to an hypoxic seizure.
Zoloft and electrolyte changes post-operation
78 The plaintiff's general practitioner Dr Dunstan has treated the plaintiff for anxiety and stress related mild depression. He prescribed "…a fairly low dose of an antidepressant, Zoloft" which he described as having been fairly effective. The plaintiff said that she had been prescribed Zoloft "…intermittently between 50 milligrams and 100 milligrams a day." She was taking that medication in August 2003.
79 Dr Raftos gave evidence that:
"Its known that there's an interaction between the group of antidepressants known as SSRI's of which Zoloft is one and pethidine. That interaction can cause the serotonin syndrome. Its also suggested that a combination of Zoloft and pethidine may lower the seizure threshold."
- Professor Paech and Mr Hennessy both acknowledge an awareness that Zoloft may lower the seizure threshold. Dr Beahan was not so aware. Latta (2002) averted to this as a side-effect and noted that "…a clinician
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- must be careful and have a thorough understanding of a patient's pharmacotherapy history."
80 Asked whether a doctor prescribing pethidine should have taken into account the potential effect of Zoloft on a seizure threshold Professor Paech said: "Not necessarily. We frequently prescribe drugs with interactions of that nature and it would depend on the clinical circumstances whether you choose to do so or not, recognising that the interaction exists, so I don't think that necessarily is the case." It meant however potentially taking a slightly greater risk. Furthermore, he said there were many drugs which do lower the seizure threshold but that Zoloft was not one which was contra-indicated in combination with pethidine. It was one of a category of drugs but not one specifically contra-indicated.
81 Professor Paech also indicated that after an operation there are changes in the body chemistry/electrolytes which can potentially increase or lower the seizure threshold as well. He described there being a number of interacting factors going on post-operatively and thus any one specific interaction did not necessarily preclude the combination of two drugs together. Similarly, Mr Hennessy acknowledged that body or electrolyte changes post-operation may lower the seizure threshold.
82 Potentially, those two factors may have increased the risk of seizure from pethidine. Whilst however that may be a factor which a prescribing physician should take into account that is not to say that it was inappropriate in the circumstances here not to prescribe pethidine. At best these two factors might be said to have increased the risk but I cannot conclude that that risk was something which should have absolutely been avoided.
Alternatives of morphine and fentanyl
83 It was universally accepted that morphine would have been an acceptable alternative to pethidine. Professor Paech could not see that there was any compelling advantage for using pethidine post-operatively with the plaintiff rather than fentanyl or morphine. Mr Hennessy indicated that fentanyl was not an alternative at the time because nursing staff were not permitted to administer it intramuscularly. Dr Beahan did not consider using fentanyl as an alternative because of its much shorter pain relieving action (1/2-1 hour) compared to that of pethidine (2-3 hours). Thus there would have to be much more frequent intramuscular injections. Professor Paech indicated that it was possibly familiarity that pethidine continued to be widely used despite the evidence
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- of its dangers. He also indicated a good safety record with pethidine such that choice morphine or pethidine would usually be determined by the prescribing physician's own familiarity and experience.
84 Dr Beahan, being aware of moves against the use of pethidine was asked in cross-examination why he continued to use it. His response was:
"I think there are three answers to that: one is that I have not had any problem with pethidine; secondly, that there are advantages with its use and, thirdly that there are disadvantages with the use of the main alternative, which is morphine. If you take the first one I've used pethidine for 40 years or more and have found it to be an extremely safe drug. There are – with all the opiates there are four side-effects or problems that you can have. They are respiratory depression, dysphoria, post-operative nausea and vomiting and pruritus. Pruritus is itching of the skin. Of those four respiratory depression is more or less the same no matter what you use, so if you take the other three, it has been my impression and possibly other people's impression overall that pethidine has slightly less of these problems than morphine. … It has been my belief that I have had less problem with side-effects although that's not a major thing its just more of a clinical impression. It may or may not stand up to scrutiny but on the other hand I have had really no problems with it in the past other than those well known side-effects which are well known to everyone and relatively easy to deal with. Lastly morphine itself has a metabolite that can cause neurotoxicity as well. Morphine has a disadvantage also in general use because it comes in three different strengths, whereas pethidine only comes in one strength; so if you're using it on a very wide scale I think there is a potential for a wrong dose being given which is greater than would be the case with pethidine."
85 The fact that an alternative morphine was available does not mean that the defendant was negligent insofar as the use of pethidine was concerned. Indeed, as indicated in Dr Raftos' first report conceded that Dr Beahan "…was acting within the bounds of reasonable practice in prescribing pethidine." Nor did Dr Raftos advocate against multiple doses provided however they did not exceed the upper limit of the reasonable range for pethidine.
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Failure to inform of risk
86 The plaintiff pleads that the defendant was in breach of its duty of care in that there was a failure to warn her of the risks of complication in the use of pethidine.
87 Plummer (2001) warned that when pethidine is to be used in more than a single dose the risk of norpethidine toxicity "…is great enough that patients should be warned about it." Professor Paech expressed the view that if there were a significant risk or a risk to which the patient may attribute significance then in those circumstances it may be appropriate to warn of such a risk. However, he did not consider the circumstances of this case to present a significant risk so as to warrant any such warning.
88 Some regard must be had also to the long experience of Dr Beahan in prescribing pethidine and the fact, as he stated, that in his experience he has had really no problems with pethidine in the past with this regimen. Conversely, he was aware that with larger doses or doses over a prolonged period that could lead to norpethidine toxicity. Whilst aware of such risks in other circumstances it was not the case here that he had any such concern which would have warranted any warning to the plaintiff.
89 Likewise, it was Professor Paech's opinion that although it may be appropriate to do so in some circumstances, it is still not usual practice in 2006 to warn patients of a risk of seizure after more than one dose.
90 In the circumstances but having regard to the whole of the evidence I am not able to conclude that the defendant was negligent in failing to give any warning to the plaintiff as to the risks of any complication which may have been consequent on the prescribed dosage.
Journal articles – level of knowledge of dangers of pethidine
91 It is common cause that knowledge of medical matters is disseminated in a number of ways to practitioners. It may be by way of learned publications, conferences and seminars, clinical discussion at meetings and informally with colleagues. A specialist in a particular field would be expected to keep abreast of research reports and developments in their field of expertise. It can also be accepted that by August 2003 concern was being indicated as to the use of pethidine because of certain adverse effects which had been identified. Furthermore there was an acceptable alternative to the use of pethidine.
92 Dr Raftos stopped prescribing pethidine in about 2001 for a variety of reasons including "…its potential to cause seizures with repeated
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- dosing." He said that the use of pethidine in New South Wales hospitals had almost ceased since 2002/3. At about the time of the publication of the journal articles Professor Paech stopped using pethidine in the post-operative setting. Mr Hennessy does not use pethidine but that is only for the reason that it is not an appropriate analgesic in his area of practice. Dr Beahan on the other hand who has practised in anaesthesia for some 40 years continues to prescribe pethidine post-operatively unless it is contra-indicated. He is very much reliant upon his experience despite his more recent awareness that the College has moved against the use of pethidine.
93 Professor Paech was not of the view that practitioners prescribing pethidine should have been aware of the debate raised in the journal articles. Debate had been developing in the period 2002/2003. It was his view that probably only academics and a small number of people would have been aware of those papers and that may well still be the case and "…that's probably the reason why its still being prescribed so frequently at the moment." Likewise Mr Hennessy was aware of the published literature at the time though he would have expected that such concern was widely known within 12-18 months after publication. I accept that the time of this event Dr Beahan should have been aware that concerns were being raised about the use of pethidine and its interaction with SSRI's.
The continued use of pethidine
94 As above stated it is well recognised that pethidine continues to be used in the control of post-operative pain. Whilst Professor Paech was willing to criticise the use of pethidine he was nevertheless adamant that whilst there had always been a very small risk of norpethidine toxicity in the context of the prescription and the dosage given to the plaintiff such has always been and still is considered to be clinically acceptable.
95 Professor Paech said that pethidine was still used intramuscularly in the setting of pain relief in labour widely throughout Australia and other countries and that he still prescribes it epidurally. He went on to say that:
"Certainly, anaesthetists have encouraged their colleagues and others who prescribe post-operative opioids to use drugs other than pethidine over the last few years … but if you look at any hospital around Australia now you will still find many patients who are prescribed pethidine post-operatively."
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96 Likewise, Dr Raftos did not take issue with the use of pethidine as such. Despite its potential adverse effects he said that it is still considered to be a reasonable medication for post-operative pain. It was his view that Dr Beahan was acting within the bounds of reasonable practise in prescribing pethidine.
Did 600 mg of pethidine in 19 hours exceed the recommended safe dose?
97 It was the opinion expressed by Dr Raftos in his first report that "the dosage regimen exceeded the upper limit of the reasonable range for pethidine." He opined that 24 hour dosage should be restricted to an upper limit of 600 mg. That level "…would be safe and acceptable prescribing…" However the dosage of 600 mg over 19 hours exceeded the generally recommended upper limit. Whilst accepting that the plaintiff had not received more than 600 mg in a day the point he was making was that having received that dose over a period less than 24 hours put her at greater risk of norpethidine toxicity leading to a seizure. One argument of course is that the plaintiff was not administered more than what was "safe and acceptable", ie 600 mg/day. Dr Raftos' response was that on his understanding it did not comply with the spirit of the recommendation.
98 That the prescription was "open ended" is neither here nor there. Even if the prescribed dosage (being open ended) was in excess of the recommended dosage that of itself was not the cause of the plaintiff suffering a seizure. That can only be considered in the context of what in fact happened, not what might have happened had the plaintiff been given more injections than in fact she was.
99 On the other hand it was Professor Paech's evidence that the total dose of 600 mg was well within the Product Information recommended dose range, viz up to 150 mg 3-4 hourly…for no longer than 24-36 hours, ie a potential dose of 1200 mg in 24 hours.
100 Latta et al (2002) refer to 1200 mg per day as being a "safe" level with a 600 mg per day limit in clinical practise suggested.
101 On the one hand the dosage of 600 mg did not exceed a safe recommended dosage of 600 mg/24 hours. On the other hand though she received that dosage in less than 24 hours.
102 Whichever interpretation might be favoured I think that in the end result regard needs to be had to the Product Information referred to by Professor Paech in his first report. He described the recommended dose
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- range (stated above) as being an "extremely conservative dosing recommendation…" Thus the dose of 600 mg received was within that recommendation. Furthermore he said that the dose of 600 mg received was not unusually high judged on typical post-operative requirements.
103 On balance therefore I conclude that a dosage of 600 mg of pethidine in 19 hours did not exceed the recommended safe dose.
Was the plaintiff's seizure "materially contributed to" by the pethidine?
104 Dr Raftos identified two possible causes of the plaintiff's seizure. One was a vasovagal syncope (fainting). The second was norpethidine toxicity consequent upon excessive dosage of pethidine. He does not conclude that it was just one or other of those causes. The vasovagal syncope alone would not have caused the seizure activity. That would be a very rare event. Therefore, he concludes that "…the excessive dose of pethidine…contributed substantially to the development of the seizure."
105 As I have indicated earlier Dr Raftos stands alone in concluding that the dosage of pethidine was excessive. His conclusion is premised on that basis and in view of my earlier finding that the dosage was not excessive I am not able to accept his conclusion.
106 Supporting that view is the fact that the weight of evidence being that of Professor Paech and Mr Hennessy is contrary to Dr Raftos' conclusion. They were both of opinion that the seizure was a consequence of a vasovagal syncope. Professor Paech did not totally dismiss the possibility that norpethidine may have contributed. He regarded the possibility however as being "very unlikely" and the risk of seizure as being "exceptionally low" and "exceptionally small, recognisable risk which would be considered to be clinically acceptable." Elsewhere he described the estimate for risk of seizure as a result of the pethidine administration as being "exceptionally rare" and in evidence as being "extremely unlikely". In cross-examination he said:
"I think there is a very low likelihood that it (norpethidine) contributed.
At all?---Yes."
107 At the same time he acknowledged that the occurrence of a vasovagal syncope leading to a seizure was a rare event. So too was a seizure consequent upon norpethidine toxicity. In assessing the probabilities of both rare events it was his experience that cases of
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- vasovagal were more common than those of norpethidine toxicity. His conclusion of a vasovagal syncope fitted with the clinical signs described.
108 To similar effect Mr Hennessy when asked in cross-examination whether he thought that pethidine contributed to the plaintiff's seizure said: "I think that's extremely unlikely." Even taking into account that the plaintiff was medicating on Zoloft which may have lowered her seizure threshold, a theory put by Dr Raftos, his response was that whilst the theory was reasonable he nevertheless regarded it as "…improbable."
Conclusion
109 As I have indicated earlier the clinical indicators, viz the plaintiff's symptoms, bradycardia and being sat up in the bed are consistent with a vasovagal collapse which led to a hypoxic seizure. It was "possible" albeit "unlikely" or "improbable" that norpethidine toxicity may have contributed to the seizure (and that cannot be ruled out completely). However, given the weight of evidence as I have described I am not able to be satisfied on the balance of probabilities that the seizure was in fact "materially contributed to" by the dosage of pethidine.
110 In the circumstances the plaintiff's claim must be dismissed.
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