Diazepam


Leading benzodiazepine, widely used against seizures and as a muscle relaxant.
 
Incidence
Low in France but one injection out of 1000 when cremophor E.L. was used as the solvent (not in France).
 
The most common offending molecules are diazepam and flunitrazepam.
 

Clinical manifestations
General: anaphylactic shock, collapse.

Cutaneous: urticaria, angioedema, hives, flush, polymorphous erythema, purpura.

Respiratory: dyspnea, bronchospasm.

Renal: allergic interstitial nephropathy.
 

Diagnostic methods
Cutaneous testing

Usually negative

In one case prick-test positive with solvent

In one case patch-test positive

Positive reintroduction test (with caution) if necessary

Mechanisms
Unknown.
 
Major role of solvents (chromophor E.L., propylene glycol, sodium benzoate).
 
Other hypothesis
Immediate IgE-mediated hypersensitivity: Prausnitz-Kustner test positive in one case. The active metabolite common to all benzodiazepines is desmethyldiazepam, which appears to be an antigenic molecule and accounts for cross reactivity among different benzodiazepines.
 
Complement activation.
 
Non-specific histamine release.
 
Management
Manifestations are usually observed when cremophor E.L. is used as a solvent (not used in France).

References

  1. Daumal M, Gillon J.C, Guilbert J.M, Line B, Manoury B, Pila Y, "Syndrome de detresse respiratoire aigue après choc anaphylactique, (rôle du diazépam et de la succinylcholine"), Cahiers d’Anesthésiologie, 1984 ; 32 (4): 313-5.
  2. Huttel M.S, Schou Olesen A, Stoffersen E, "Complement-mediated reactions to diazepam with cremophor as solvent (Stesolid M.R.)". Br. J. Anaesth., 1980 ; 52: 77-9

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.