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Three Part Question

In [adults presenting to the emergency department with an acute porphyric attack requiring rapid sequence induction] is [Propofol better than Etomidate ] at [safely inducing anaesthesia].

Clinical Scenario

A 24 year old female with acute intermittent porphyria presents to the emergency department with abdominal pain, paresis and difficulty breathing after a night of heavy drinking. You fear progression to respiratory paralysis so decide to perform rapid sequence induction. You wonder whether Etomidate or Propofol will be the most effective induction agent and whether these may exacerbate the acute porphyric attack.

Search Strategy

Medline 1966-06/06 using the Ovid interface and Embase 1980-06/06 using the Ovid interface
Medline: [exp etomidate/ or amidate.mp. or exp propofol/ or diprivan.mp.] AND [exp porphyrias/ or porphyria.mp. or AIP.mp.] LIMIT to humans and english
Embase: [exp etomidate/ or amidate.mp. or exp propofol/ or diprivan.mp.] AND [exp porphyria/ or porphyria.mp. or porphyrias.mp. or AIP.mp.]LIMIT to humans and english

Search Outcome

Medline:29 results of which 19 were relevant
Embase:51 results of which 1 was new and relevant
Cinahl-0 relevant results
Cochrane-0 relevant results

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Meissner, P.N. et al 1991 South Africa	13 patients with variegate porphyria requring general anaesthesia for elective surgery. Patients excluded were those with severe underlying disease, an allergy to propofol, previous adverse experience with general anaesthesia, those undergoing operations on bladder or bowel and those who were pregnant. All were given a mean induction dose of IV propofol of 2.45 mg/kg. (Atracurium, suxamethonium, fentanyl, alfentil, halothene and morphine were also given)	Case series (level 3)	Number of patients with symptoms suggestive of an acute attack after administration of propofol	No patients suffered symptoms suggestive of an acute attack of porphyria	Small study group.
			Urinary ALA, PBG measured on day before operation-day 0, day 1, day 3 and day 5	No significant increase in concentrations of ALA and PBJ following administration of propofol(p>0.1). These did not exceed the limits established for VP patients in remission.
Dover S.B., Plenderleith L, MR Moore, KEL Mc Coll 1994 UK	25 patients with acute porphyria undergoing 38 surgical operations under general anaesthetic.20 operations were performed in patients with AIP, 4 had variegate porphyria and one hereditary coproporphyria. 19 patients were known to have porphyria and 8 were not at the time of surgery. 5 patients (who had been previusly diagnosed) had ALA and PBJ measured perioperatively for variable durations between days -2 to 7, Propofol was used in 15 of the patients known to have porphyria	Combined retrospective and prospective case study (level 3)	Symptoms suggestive of an acute attack	None of the patients known to have porphyria at the time of surgery had symptoms of an acute attack but of the patients with undiagnosed porphyria 7 had crisis, 2 resulting in death.	It was stated that 15 patients had been given propofol but did not say which patients. The data was incomplete-only 5 patients had urinary PBG and ALA measured perioperatively and for variable amounts of time. The basic data was not adequately described-no exact figures were given-only a roughly drawn diagram and terms such as 'a transient rise (in PBG)' and '(PBG) nearly doubled' used when describing the perioperative changes in PBG and ALA. No statistical analysis was performed. Numbers do not add up. It says that the study was conducted in 25 patients but later says that 19 patients had diagnosed porphyria and 8 had undiagnosed porphyria at the time of the operation.
			Urinary ALA excretion	2 patients of the 5 with their ALA monitored showed incresed ALA excretion-one more than 4 times the upper limit of normal and one within normal limits.
			Urinary PBG excretion	3 of the 5 patients with their PBG monitered had a 'transient rise' in ABG.

Comment(s)

There were no papers comparing the efficacy and safety of etomidate and propofol. There were two case series in which patients were anaesthetized with propofol. In both case series (13 patients and 15 patients), no patients suffered an acute attack and there was no significant rise in the urinary heme precursors. There was one case study in which a patient was anaesthetized with etomidate;there was no acute attack or rise in porphrin precursors. Drug databases listing safe and unsafe drugs in porphyria are of use in the treatment of acute porphyrias. Propofol has been classified as 'safe' and etomidate as 'unsafe' (or not listed) by The Norwegian Porphyria Centre,University of Cape Town Porphyria Service,The Welsh Medicines Information centre and the European Porphyria Initiative .

Clinical Bottom Line

Propofol should be used with caution for the induction of anasethesia in acute porphyria with monitoring of the urinary porphyrin precursor PBG. Although the search revealed no evidence to say etomidate is unsafe it has been classified by expert bodies as unsafe therefore should not be used.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. Meissner P.N., G.G Harrison and R. J. Hift. Propofol as an IV anaesthetic induction agent in variegate porphyria. British Journal of Anaesthesia. 1991; 66(1):60-5.
2. Dover S.B., Plenderleith L, MR Moore et al. Safety of general anaesthesia and surgery in acute hepatic porphyria. Gut. 1994; 35:1112-1115.