Article Notes
- Ultra-low dose intrathecal (≤50 mcg) or epidural (≤1 mg) morphine in low-risk women does not require extra respiratory monitoring.
- Low dose intrathecal (50-150 mcg) or epidural (1-3 mg) morphine in low-risk women should have respiratory rate and sedation monitored every 2h for the first 12h.
- Women with significant comorbities, sedation risk factors or if receiving higher morphine doses should be monitored as per ASA/ASRA guidelines.
- Low-dose intrathecal (50-150 mcg) or epidural (1-3 mg) morphine provides the best balance between analgesia and minimising side effects.
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.
Daniel Jolley
“Cyclodextrin is frequently used in foods and cosmetics because it can change the physical properties of various compounds by their encapsulation within the cyclic structure. The average person is thought to ingest about 4 g of gamma-cyclodextrin per day from food. ... even people who have never received sugammadex may be sensitised by food and cosmetics.” (Mertes 2019)
Daniel Jolley
This consensus statement from the Society for Obstetric Anesthesia and Perinatology (SOAP) provides post-operative monitoring guidelines for women receiving neuraxial morphine for cesarean section analgesia.
The context
Neuraxial morphine is a widely used and effective technique for managing post-cesarean pain in the first 24 hours. However because of morphine’s low-lipid solubility, the risk of delayed repsiratory depression has required frequent respiratory monitoring in this first 24 hour period.
The SOAP task force aimed to balance opioid safety needs while avoiding excessive respiratory monitoring in new mothers. Existing ASA/ASRA guidelines were considered by many obstetric anesthesiologists to be too rigorous when applied to the healthy post-natal population, both because of their lower risk of respiratory depression and even greater need to minimize sleep interruptions.
“The SOAP Task Force members strongly agree that neuraxial morphine should be the preferred method for postcesarean delivery analgesia in healthy women.”
The recommendations
Explore more...
The paper’s full-text goes into more detail covering the evidence for the safety and efficacy of neuraxial morphine, the incidence of respiratory depression, respiratory monitoring techniques and duration, optimal dosing and analgesic regimes.
Daniel Jolley