Organ failure type in fatal and near-fatal anaphylaxis: a systematic review

McKenzie B, Marshall SD, Sanci L, Poonian J, Nair R, J Selman C, Douglass JA. BMJ Open. 2026 Mar 9;16(3):e108996. doi: 10.1136/bmjopen-2025-108996.

Abstract

Objectives Anaphylaxis is a sudden onset multiorgan allergic reaction that infrequently but regularly causes fatalities which may be preventable with appropriate organ support. There is limited data about the type of organ failure leading to death or near-fatal episodes resulting in permanent neurological disability. To assist clinicians facing anaphylaxis in diverse clinical settings, we aimed to quantify the frequency of organ failure type contributing to death or neurological disability from anaphylaxis according to allergen trigger.

Design Systematic review of published peer-reviewed literature.

Data sources Three databases were searched to January 2025: MEDLINE from 1946, Embase from 1947 and Web of Science from 1900.

Eligibility criteria Studies were eligible if they contained data about the type of clinical deterioration during anaphylaxis resulting in death or permanent neurological disability. No language restriction was implemented. Exclusion criteria were: hydatid anaphylaxis; five or more stings from an insect; death from acute atheromatous myocardial infarction and where anaphylaxis was only a differential diagnosis.

Data extraction and synthesis We extracted information using pre-specified criteria to determine the primary organ failure involved: either upper airway obstruction, lower respiratory obstruction (bronchospasm) or cardiovascular failure. Baseline demographics including age and asthma status were collected along with the allergen trigger, time course and treatment. We reported frequencies according to allergen trigger for case reports and a narrative analysis of case series weighted by risk of bias assessment.

Results 277 case studies and 14 case series were identified reporting 896 deaths and 28 disabilities. There were no other study types. Separate case series and case report analyses produced similar findings despite varying quality of published clinical data. Respiratory failure was the most common primary organ failure in case reports (73.4%), whereas primary cardiovascular failure was reported in 26.6% of case reports. Primary organ failure type differed in frequency by allergen trigger and was primarily caused by: respiratory failure when food was the allergen trigger (95%); respiratory failure in 65% of cases of drug allergen triggers; cardiovascular failure in 65% venom allergen triggers.

Conclusion In this review, respiratory failure (primarily bronchospasm) is the most common primary physiological event leading to decompensation in fatal anaphylaxis, particularly for food and drug allergen deaths. Emphasising the significance of respiratory involvement, particularly from bronchospasm, in both patient and clinician facing anaphylaxis treatment guidelines may help further reduce the risk of fatalities. Prospective anaphylaxis management registries or whole population data are needed to better capture primary organ failure present in fatal anaphylaxis to validate this finding.

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