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Three Part Question

In [adults presenting to the emergency department with an acute porphyric attack]are [IV morphine and pethidine] safe and effective [at controlling pain].

Clinical Scenario

A 44 year old South African female with variegate porphyria presents to the ED with severe abdominal pain. You wonder whether IV pethidine or morphine would be safe and effective at relieving the pain.

Search Strategy

Medline 1966 to 06/06 via the Ovid interface
Embase 1980-06/06 via the Ovid Interface
Cinahl 1982-06/06 via the Ovid Interface
The Cochrane Library Issue 2 2006
Medline: [exp pethidine/ or pethidine .mp. or exp meperidine/ or meperidine.mp. or exp morphine/ or morphine.mp. or exp analgesics, opioid/ or exp narcotic/ or opiate.mp.] AND [exp porphyrias/ or porphyria.mp or porphyrias.mp. or AIP.mp.]LIMIT humans and english language
Embase:[exp pethidine/ or pethidine .mp. or exp meperidine/ or meperidine.mp. or exp morphine/ or morphine.mp. or exp analgesics, opioid/ or exp narcotics.mp. or opiate.mp.] AND [exp porphyria/ or porphyria.mp. or porphyrias.mp. or AIP .mp.] LIMIT humans and english language
Cinahl:exp pethidine/ or pethidine .mp. or exp meperidine/ or meperidine.mp. or exp morphine/ or morphine.mp. or exp analgesics, opioid/ or exp narcotics/or opiate.mp.] AND [exp porphyria/ or porphyria.mp. or porphyrias.mp. or AIP .mp.] LIMIT humans and english language
Cochrane:porphyria

Search Outcome

Medline: 17 results. 1 relevant
Embase:129 results. 1 new relevant
1 additional paper was found in the results of the search of the BETs 'Heme treatment in acute porphyria'.
Cinahl:4 result 0 relevant
Cochrane:; 32 results; 0 relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Dover SB, Moore M, Fitzsimmons, Graham A, McColl KE. 1993 USA	8 patients with acute intermittent porphyria with 34 acute attacks. All were treated with opiate analgesia. The effects of tin protoporphyrin and heme arginate individually and combined were compared with placebo.	Randomised controlled trial (level 3)	Exacebation of acute attack after opiate analgesia	No exacerbations occured	Small study group
Herrick AL, McColl MR, Cook A, Goldberg A. 1989 UK	12 patients with acute intermittent porphyria. 21 attacks, All received diamorphine or pethidine in the range 0- 20650 mg.	Randomised controlled trial comparing haem arginate and placebo (level 3)	Exacerbation of acute attack	No exacerbations occurred
Mustajoki P, Nordmann Y. 1993 Finland	22 patients with acute porphyria. 51 attacks. Opiate analgesia given in 43 attacks.	Randomised controlled trial comparing haem arginate, tin protoporpyrin and placebo (level 3)	Exacerbation of acute attack	No exacerbations occurred

Comment(s)

Severe unremitting abdominal pain occurs in 85-95% of cases of acute porphyric attacks therefore analgesia is important in the treatment of the acute attack. As many drugs can exacerbate the attack it is important to know which drugs are safe and care should be taken when administering any drug, due to the unpredicable response of an individual to a particular drug. The safe use of opiate analgesia was described on 106 occasions in the papers found. Drug databases listing safe and unsafe drugs are useful in the treatment of acute porphyria. The information they provide is based on published case reports, previously published drug lists, theoretical considerations and clinical experience. Morphine and Pethidine been classified as safe in drug lists produced by the European Porphyria Initiative, The Welsh Medicines Information Centre and Dr Mike Badminton (a porphyria specialist) of the University hospital of Wales, University of Cape Town Porphyria Service and The Norwegian Porphyria Centre (NAPOS).

Clinical Bottom Line

Morphine and pethidine are safe to use in acute porphyria.

References

1. Dover SB, Moore M, Fitzsimmons E, Graham A, McColl KE. Tin Protoporphyrin prolongs the biochemical remission produced by heme arginate in acute hepatic porphyria Gastroenterology 1993;105:500-506.
2. Herrick AL, McColl MR, Cook A, Goldberg A. Controlled trial of haem arginate in acute hepatic porphyria. Lancet. 1989:1(8650)1295-1297.
3. Mustajoki P, Nordmann Y. Early administration of heme arginate for acute porphyric attacks. Archives of internal medicine. 1993;153:2004-2007.
4. University of Cape Town Porphyria Service. Drug Safety: Alphabetical Listing [Online]. 2006 [Accessed 19th July 2006].
5. The norweigan porphyria centre. NAPOS. The Drug Database for Acute Porphyria [Online]. 2006 [Accessed 19th July 2006].
6. European Porphyria Initative. Drugs and Porphyria [Online]. 2006. [Accessed 19th July 2006].