Anaphylaxis and Allergic Reactions

Perioperative anaphylaxis is a severe, rapidly developing hypersensitivity reaction triggered by an agent given around the time of surgery. Because patients are anaesthetised, draped, and unable to report early warning symptoms, the reaction often presents first as cardiovascular collapse, bronchospasm, or difficulty ventilating, making it one of the most challenging perioperative emergencies to recognise and one of the leading anaesthesia-related causes of harm.

Definition

Anaphylaxis is a severe, generalised or systemic hypersensitivity reaction of rapid onset that can be life-threatening; in the perioperative context it is an acute reaction to an agent administered around surgery, presenting most often as cardiovascular collapse, bronchospasm, and/or cutaneous changes in an anaesthetised patient.

Scope

This entry covers the mechanisms and triggers of perioperative hypersensitivity, the characteristic clinical features in the anaesthetised patient, how reactions are graded and investigated, and what large national audits have shown about their causes and outcomes. It treats anaphylaxis as a clinical entity and reference topic and does not provide drug doses or individualised management instructions.

Core questions

• Which agents most commonly trigger perioperative anaphylaxis?
• Why does perioperative anaphylaxis often present differently from anaphylaxis in awake patients?
• How are immediate (IgE-mediated) and non-immune reactions distinguished?
• How is a suspected reaction investigated after the event to identify the culprit agent?

Key concepts

• IgE-mediated (immune) hypersensitivity
• Non-IgE and direct mast-cell activation
• Neuromuscular blocking agents as triggers
• Antibiotics and chlorhexidine as triggers
• Mast cell tryptase as a marker
• Severity grading of reactions
• Skin testing and culprit identification

Mechanisms

Most severe perioperative reactions are immediate hypersensitivity events in which a previously sensitised patient's IgE antibodies, bound to mast cells and basophils, recognise an administered agent and trigger rapid release of histamine and other mediators; some reactions instead arise from direct, non-IgE mast-cell activation. The released mediators produce vasodilation and capillary leak (hypotension and collapse), bronchoconstriction, and mucosal and cutaneous changes. In the anaesthetised, draped patient the earliest subjective symptoms are masked, so the reaction is frequently detected through monitored signs such as sudden hypotension, raised airway pressures, or difficulty ventilating. National audit data identify antibiotics, neuromuscular blocking agents, and chlorhexidine among the commonest triggers (Harper et al., 2018; Cook et al., 2018).

Clinical relevance

Perioperative anaphylaxis is a model of how a systemic disease process must be inferred from monitored physiology rather than patient report, and it underpins practices such as post-event tryptase sampling and structured allergy referral to identify the responsible agent and prevent re-exposure. National audits have reshaped understanding of which agents matter most and how outcomes vary. This entry describes the entity and its investigation; it is not a source of emergency dosing or management protocols.

Epidemiology

Severe perioperative anaphylaxis is uncommon, occurring in a small number of cases per ten thousand to hundred thousand anaesthetics depending on definitions and surveillance. The 6th National Audit Project (NAP6) of the Royal College of Anaesthetists provided detailed population-level data on incidence, triggers, clinical features, and outcomes, including deaths, and highlighted antibiotics, neuromuscular blocking agents, and chlorhexidine as leading causes (Harper et al., 2018; Cook et al., 2018).

History

Recognition of anaesthetic anaphylaxis grew through the late twentieth century as monitoring improved and case series implicated specific drug classes, particularly neuromuscular blocking agents. Systematic national surveillance, exemplified by the French GERAP network and later the UK NAP6 project, transformed scattered case reports into robust epidemiology, clarifying trigger frequencies, the role of cross-sensitisation, and the importance of structured post-event investigation (Mertes et al., 2016; Cook et al., 2018).

Debates

Which agents are the dominant triggers, and how do they vary by region?

The relative contribution of neuromuscular blocking agents, antibiotics, and antiseptics such as chlorhexidine differs across countries and over time, reflecting prescribing patterns and surveillance methods rather than a single fixed ranking.

How should reactions be graded and reported?

Several severity grading schemes exist for perioperative hypersensitivity, and harmonising definitions affects how incidence and outcomes are compared between studies and audits.

Seminal works

• harper-2018
• cook-2018-nap6

Frequently asked questions

Why is perioperative anaphylaxis hard to recognise?

Because the patient is anaesthetised and cannot report early symptoms such as itching or throat tightness, the reaction often first appears as sudden hypotension, bronchospasm, or difficulty ventilating detected through monitoring.

What are the most common triggers of perioperative anaphylaxis?

National audit data point to antibiotics, neuromuscular blocking agents, and the antiseptic chlorhexidine as leading triggers, though the exact ranking varies by country and surveillance method.