Muscle relaxants


Family of agents widely used in general anesthesia to achieve muscle relaxation.
 
Suxamethonium, Vecuronium, Pancuronium, Atracurium, Mivacurium, Rocuronium, Cisatracurium
 
Incidence
One anaphylactic shock out of every 10000 general anesthesias.
 
10% of these reactions are fatal.
 
Muscle relaxants account for 60 to 70% of all allergic reactions occurring during general anesthesia.
 
Risk factors
Use of muscle relaxants with a "flexible chain".
 
Female gender (80% of cases).
 
No involvement of atopy.
 
Previous allergic reactions to muscle relaxants.
 
Clinical manifestations
General: collapse, tachycardia, arrhythmia, cardiac arrest.
 
Respiratory: bronchospasm.
 
Dermatological and mucosal: flush, diffuse erythema, diffuse urticaria, angioedema.
 
Digestive: diarrhea.
 
Haematological: disseminated intravascular coagulation.
 
Diagnostic methods
Intradermal skin tests or prick tests (using undiluted muscle relaxants). High diagnostic performance if conducted with proper concentrations, i.e. for intradermal skin testing:
 

£ 100 µg/ml for suxamethonium.

£ 200 µg/ml for pancuronium.

£ 100 µg/ml for rocuronium

£ 2 µg/ml for mivacurium

£ 400 µg/ml for vecuronium.

£ 10 µg/ml for atracurium.

£ 200 µg/ml for cisatracurium

Subjects remain positive for several years (up to 30 years).
 
Detection of anticurare and antisuxamethonium IgE antibodies by RAST methods.
 
Specific histamine release.
 
Mechanisms
Immediate IgE-mediated hypersensitivity: detection of IgE specific to muscle relaxants (quaternary ammonium ion determinants) accounting for cross reactions between different curarizing anesthetics and reactions upon first contact with a muscle relaxant (antihypertensors, antiseptics, antibiotics, cosmetics, and soaps with a quaternary ammonium ion structure).
 
Mediator release from target cells. Leukocytes from subjects with a history of anaphylactic accidentsbrought into contact with increasing concentrations of muscle relaxants in vitro, release histamine which can be measured (dose-dependent response). Histamine release from basophils involves IgE antibodies.
 
Role of quaternary ammonium ion determinants. The rigidity of the chain linking quaternary ammoniums plays a triggering role in allergic reactions. "Flexible" molecules with simple carbon chains (Suxamethonium) can stimulate sensitized cells more strongly than rigid molecules (Pancuronium).
 
Some reactions are not based on an IgE mechanism, but on a non-specific histamine release effect.
 
Management
Use safer muscle relaxants such as Pancuronium rather than Suxamethonium.
 
Systematic screening-tests in a general population are not advisable due to the poor positive predictive value of the tests.
 
Patients with a history of anaphylactic reactions:
 
Conduct preoperative skin-tests with all muscle relaxants.

(Frequent cross-reactivity between 2 or more muscle relaxants)
  • If skin-tests are positive, do not use the offending muscle relaxants.
     
  • If skin-tests are negative, the agents may be administered (good negative precitive value).

No preventive treatment can avoid anaphylactic reactions 

References

  1. Porri F, Lemiere C, Birnbaum J, Guilloux L, Lanteaume A, Didelot R, Charpin D, Vervloet D, "Prevalence of muscle relaxants sensitivity in a general population: implications for a preoperative screening", Clin. Exp. Allergy, 1998 ; in press
  2. Nicklas R.A, "Anaphylaxis during general anesthesia, the intraoperative period and postoperative period", J. Allergy. Clin. Immunol., 1998 ; 101: S512-6
  3. Laxenaire M.C et le groupe d’étude des réactions anaphylactoïdes peranesthesiques, " Substances responsables des chocs anaphylactiques peranesthesiques", Ann. Fr. Anesth., 1996 ; 15: 1211-8
  4. Porri F, Pradal M, Rud C, Charpin D, Alazia M, Gouin F, Vervloet D, "Is systematic preoperative screening for muscle relaxants and latex allergy advisable ?", Allergy, 1995 ; 50: 374-7
  5. Birnbaum J, Vervloet D, "Allergy to muscle relaxants", Clin. Rev. Allergy., 1991 ; 9 (3-4): 281-93
  6. Marone G, Stellato C, Mastronardi P, Mazzarella B, "Nonspecific histamine-releasing properties of general anesthetic drugs", Clin. Rev. Allergy, 1991 ; 9 (3-4): 269-80
  7. Leynadier F, Sansarricq M, Didier J.M, Dry J, "Prick-tests in the diagnosis of anaphylaxis to general anaesthetics", Br. J. Anaesth., 1987 ; 59: 683-9

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