Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study

Mertes, PM; Petitpain, N; Tacquard, C; Delpuech, M; Baumann, C; Malinovsky, JM; Longrois, D; Gouel-Cheron, A; Le Quang, D; Demoly, P; Guéant, JL; Gillet, P; ALPHO Study Group

doi:10.1016/j.bja.2023.02.026

Perioperative medicine & outcomes

Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study

Br J AnaesthPublished 24 Mar 2023Case-control study

Main finding · NMBA-related anaphylaxis and pholcodine consumptionResultOdds ratio 4.2 95% CI 2.3–7.0

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Authors' conclusion

Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis.

Study context

Population: Patients undergoing anaesthesia with neuromuscular blocking agents (NMBAs) in France
Participants: 167 vs 334

Comparison: Cases vs Controls
Casesn = 167
Controlsn = 334reference
Outcome: Association between pholcodine exposure (self-administered questionnaire and pharmacy records) and NMBA-related anaphylaxis
Follow-up: Within a year before anaesthesia

Methodological detailsmulticentre, matched (two controls per case by age, sex, type of NMBA, geographic area, season)

Multicentre
Matched (two controls per case by age, sex, type of NMBA, geographic area, season)

Main finding

As reported in the abstract

NMBA-related anaphylaxis and pholcodine consumption

Odds ratio

4.2

95% CI 2.3–7.0

Pholcodine exposure within a year before anaesthesia: NMBA-related perioperative anaphylaxis cases vs controls with uneventful anaesthesia

OR 4.2 (95% CI 2.3–7.0)

Observational data: associations, not effects.

Further findings

NMBA-related anaphylaxis and occupational exposure to quaternary ammonium compounds

	← Lower odds ←→ Higher odds →	OR (95% CI)
Occupational exposure to quaternary ammonium compounds	0.050.21520	6.1 (2.7–13.6)
	0.050.21520Odds ratio (log scale)

Diagnostic value of pholcodine and quaternary ammonium specific IgE (sIgE) for NMBA-related reactions

NPV: 99.9%
PPV: <3%

Original publication

Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study. Br J Anaesth. Published 24 March 2023. doi:10.1016/j.bja.2023.02.026

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