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Created October 27, 2019, last updated almost 3 years ago.
Collection: 117, Score: 2095, Trend score: 0, Read count: 2765, Articles count: 9, Created: 2019-10-27 07:39:25 UTC. Updated: 2022-01-27 02:01:08 UTC.Notes
Australia and New Zealand both experience an unusually high incidence of perioperative anaphylaxis, particularly to neuromuscular blocking drugs. The opioid-based anti-tussive pholcodine has been implicated in increasing population hypersensitivity to muscle relaxants.
Although historically difficult to identify accurate denominator numbers for incidence calculations, more recent data shows that the anaphylaxis risk for rocuronium is particularly high in Australia & New Zealand and may in fact be roughly comparable to the local risk of suxamethonium anaphylaxis, at 1 in 2,000-3,000 exposures.
Rocuronium also has a higher risk of anaphylaxis than it’s aminosteroid-sibling vecuronium, and up to a ten-times greater risk than the benzylisoquinolinium atracurium (~1 in 22,500, depending on population). Cisatracurium demonstrates the lowest incidence of anaphylaxis (~1 in 50,000).
Additionally, as sugammadex appears as a new anaphylaxis cause the potential for a rocuronium-sugammadex combination having an even higher risk of anaphylaxis than suxamethonium needs to be considered.
Daniel Jolley
Collected Articles
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Neuromuscular blocking drugs (NMBDs) are the most common cause of intraoperative anaphylaxis in Western Australia. Differences in the rates of anaphylaxis between individual agents have been surmised in the past, but not proven, and are an important consideration if agents are otherwise equivalent. ⋯ Rocuronium has a higher rate of IgE-mediated anaphylaxis compared with vecuronium, a result that is statistically significant and clinically important. Cisatracurium had the lowest rate of cross-reactivity in patients who had previously suffered anaphylaxis to rocuronium or vecuronium.
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Comparative Study Observational Study
Anaphylaxis Is More Common with Rocuronium and Succinylcholine than with Atracurium.
This retrospective, observational cohort study over 6 years from Auckland, New Zealand identified a 10 fold higher incidence of anaphylaxis for rocuronium than for atracurium.
Also of note, the rate of anaphylaxis to rocuronium was similar to that for suxamethonium.
Anaphylaxis incidence for the three muscle relaxants were approximately:
- Atracurium – 1 in 22,500
- Rocuronium – 1 in 2,500
- Suxamethonium – 1 in 2,000
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Anaesth Intensive Care · Sep 2012
Anaphylaxis to muscle relaxants: an audit of ten years of allergy testing at the Royal Adelaide Hospital.
We audited patients with anaphylaxis to muscle relaxants during anaesthesia referred to the Department of Anaesthesia at the Royal Adelaide Hospital between the start of 2000 and the end of 2009. Of the 220 patients tested during this period, 43 had a positive intradermal test to the muscle relaxant given during their anaesthetic. The majority of these were to rocuronium and suxamethonium. Where rocuronium was the index agent, 65% of patients cross-reacted with another relaxant and 29% of patients with suxamethonium as their index agent demonstrated cross-reaction with another relaxant.
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Patients suspected of anaphylaxis during anaesthesia have been referred to the senior author's clinic since 1974 for investigation. Since release of rocuronium on to the worldwide market, concern has been expressed about its propensity to cause anaphylaxis. ⋯ The incidence of rocuronium allergy in New South Wales, Australia has risen in parallel with sales, while there has been an associated fall in reactions to other neuromuscular blocking drugs. Data from intradermal testing suggested that rocuronium is intermediate in its propensity to cause allergy in known relaxant reactors compared with low-risk agents (e.g. pancuronium, vecuronium) and higher-risk agents (e.g. alcuronium, succinylcholine).
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Asia Pacific allergy · Apr 2014
Pholcodine consumption and immunoglobulin E-sensitization in atopics from Australia, Korea, and Japan.
High pholcodine consumption in Australia is associated with higher prevalence of IgE antibodies to suxamethonium and probably a higher risk of anaphylaxis to NMBDs.
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This thorough review of the global epidemiology of perioperative hypersensitivity (POH), reflects our increasing awareness that anaphylaxis varies geographically.
Incidence
Reported incidence ranges from 1 in 18,600 to 1 in 353, although NAP6 (UK) and French studies independently estimate life-threatening anaphylaxis at 1 in 10,000.
Mortality
Anaphylaxis mortality was generally ~4% (UK, France, USA, Japan), although Western Australian data estimated a lower range of 0-1.4%.
Causal agents
Implicated agents commonly include neuromuscular blocking drugs (1st or 2nd commonest in most studies), although the higher incidence seen with specific NMBDs (eg. Sux and Roc) appears to occur in some regions but not others. Pholcodine has been implicated as causative in these regional differences.
Sugammadex has increasingly been implicated as a cause of POH, though notably also with regional variation. A dose-related effect has also been reported.
Antibiotics are an increasingly common cause of POH, in particular β-lactams. Nevertheless, ‘pan-β-lactam allergy’ is probably rare, and some examples like cefazolin, have limited cross-reactivity.
“Cefazolin does not share an R1 and R2 group with any other β-lactam...”
Latex POH is declining, while chlorhexidine is increasing (9% in NAP6, with significant regional variability), albeit often as a ‘hidden’ precipitant.
Surgical dyes (patent blue V, isosulfan blue, methylene blue) are also increasingly common causes of POH (4th most common in NAP6 (~1 in 7,000), 3rd in France).
Less common POH causes include povodine-iodine and colloids.
Hypnotics, local anaesthetic, aprotinin, protamine and NSAIDs are very uncommon-to-rare causes of POH. Opioids are sometimes implicated via the MRGPRX2 receptor, although true opioid IgE-mediated hypersensitivity is very rare.
Bottom-line
The wide geographic variations in anaphylaxis incidence and causation reveal a complex interplay of genetics and environment, along with our evolving understanding of the complexity of anaphylaxis.
Go deeper...
Read Florvaag & Johansson’s seminal article The Pholcodine Story for an intriguing story of geographic POH differences.
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The mortality from perioperative anaphylaxis has recently been quoted in a range between 3 and 9%. However, it was our impression in Western Australia that we had had no deaths from perioperative anaphylaxis for over a decade. As we have comprehensive processes in place to investigate both perioperative anaphylaxis and anaesthesia-related deaths, we undertook this study to determine our actual perioperative anaphylaxis mortality rate. ⋯ Our incidence of perioperative anaphylaxis was within expectations, but our mortality rate was lower than recently quoted figures. It is likely that the current true perioperative anaphylaxis mortality rate is within the range 0-1.4%.
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Adverse reactions (ARs) to drugs administered during general anesthesia may be very severe and life-threatening, with a mortality rate ranging from 3 to 9%. The adverse reactions to drugs may be IgE and non-IgE-mediated. ⋯ NMBA, anesthetics, antibiotics, latex devices) may cause severe systemic non-IgE-mediated reactions or fatal anaphylactic events even in the absence of any evident risk factor in the patient's anamnesis. For this reason, in order to minimize perioperative anaphylactic reactions, it is important to have rapid, specific, sensitive in vitro diagnostic tests able to confirm the clinical diagnosis of acute anaphylaxis.
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