Perioperative Anaphylaxis

Perioperative anaphylaxis is a severe hypersensitivity reaction during anaesthesia and surgery. It is rare but can cause cardiovascular collapse, and the cause must be investigated afterwards.

Pathophysiology. Most reactions are IgE-mediated, with some mediated by direct mast cell activation (MRGPRX2) or complement. Common triggers are neuromuscular blocking agents (rocuronium, suxamethonium), antibiotics (cefazolin and other beta lactams), chlorhexidine, sugammadex, patent blue dye and latex. Opioids, propofol and colloids are less frequent.

The incidence is roughly 1 in 10,000 anaesthetics, and the commonest first signs are hypotension, bronchospasm and tachycardia. Rash may be hidden by drapes.

Delay in giving adrenaline raises the risk of death.

• Hypotension or cardiovascular collapse, often the only sign
• Bronchospasm, high airway pressures, desaturation
• Tachycardia (bradycardia in some)
• Flushing, urticaria and facial swelling (may be missed)
• Loss of end tidal carbon dioxide or pulseless electrical activity
• Onset within minutes of an intravenous trigger, or up to an hour with latex or chlorhexidine

• Immediate recognition by timing of drugs and onset of signs.
• Serum tryptase: three samples: as soon as possible (within 1 hour), at 1 to 2 hours (peak), and at least 24 hours later or at baseline. A rise over 20% of baseline plus 2 microgram/L supports mast cell activation.
• Allergy testing 4 to 6 weeks later: skin prick and intradermal tests to all drugs given (neuromuscular blockers, antibiotics, chlorhexidine, sedatives, opioids, dyes), specific IgE (latex, chlorhexidine, suxamethonium), basophil activation test where available, and a supervised challenge with alternatives.
• Full drug and exposure record from the anaesthetic chart.

Differential diagnosis.

• Anaphylactoid reaction (non-IgE mast cell activation)
• Drug induced hypotension from anaesthetic agents
• Asthma and bronchospasm from airway instrumentation
• Tension pneumothorax, pulmonary embolism, hypovolaemia
• Cement or fat embolism, local anaesthetic toxicity
• Malignant hyperthermia

• Stop the suspected trigger, call for help, give 100% oxygen and secure the airway, and lie the patient flat with legs raised.
• Adrenaline: intravenous boluses of 50 microgram (0.5 mL of 1 in 10,000) in adults (children 1 microgram/kg), repeated every 1 to 2 minutes and titrated to response. Use 0.5 mg intramuscularly (children 0.01 mg/kg, maximum 0.5 mg) if there is no intravenous access. Start an infusion of 0.05 to 0.1 microgram/kg/minute for persisting hypotension.
• Fluids: rapid intravenous crystalloid, 20 mL/kg, repeated as needed. Avoid gelatin colloids.
• Refractory shock: noradrenaline, vasopressin, or glucagon 1 to 2 mg intravenously over 5 minutes for patients on beta blockers. Consider extracorporeal support in cardiac arrest.
• Bronchospasm: salbutamol 5 mg nebulised or 100 microgram boluses via the circuit, and increase volatile agent.
• Adjuncts: chlorphenamine and hydrocortisone do not treat shock and are given after resuscitation.
• After stabilising: postpone surgery if possible, keep the patient in high dependency for at least 6 hours, and take tryptase samples.
• Prevention: inform the patient and general practitioner of the culprit, record it in the notes and allergy register, and provide safe alternatives. Cefazolin allergy and other beta lactam labels are reviewed by testing.

Special groups.

• Patients with prior unexplained intraoperative reaction: delay elective surgery until allergy testing is done.
• Patients on beta blockers: adrenaline resistant reactions need glucagon.

Monitoring. Observe in high dependency for at least 6 hours after severe reactions. Review at 4 to 6 weeks for testing.

Referral and escalation. Refer to a drug allergy clinic for all suspected perioperative anaphylaxis. Emergency for any collapse, bronchospasm or unexplained hypotension during anaesthesia.