Histamine release during treatment with rocuronium (Esmeron) and suxamethonium

Fråga: What is known regarding histamine release during treatment with rocuronium (Esmeron) and suxamethonium (Celocurin)?

Sammanfattning: The evidence to support recommendations regarding treatment with muscle relaxants in patients with mastocytosis is very sparse. If neuromuscular blocking drugs are used the choice of drug should be guided by previous reactions that the patient may have had. Benzylisoquinolines, such as atracurium and mivacurium should be avoided in patients with mastocytosis since they are more potent in causing histamine release. No support has been found in the literature for specific recommendations regarding the choice of one drug rather than any other. Premedication with an antihistamine and/or a corticosteroid can be considered and it is important to minimize factors during surgery that might trigger histamine release.

Svar: In clinical studies, increased histamine levels have been observed when rocuronium was given rapidly (1). A direct mediated histamine release with flush, bronchospasm and chock has been reported during use of suxamethonium (2). Neuromuscular blocking drugs are the cause of up to 70% of anaphylactic reactions during anesthesia. Anaphylactic reactions have been described both for muscle relaxants that cause a chemically mediated reaction and for those that do not. E.g. rocuronium does not cause a chemically mediated reaction but has caused reactions in several cases. In skin tests 80% cross reactivity has been seen between different muscle relaxants (3). Most neuromuscular blocking drugs are known to cause a non specific histamine release from mast cells. Benzylisoquinolines such as atracurium and mivacurium are more potent in causing histamine release than aminosteroid muscle relaxants such as rocuronium (4,5). Benzylisoquinolines should consequentially be avoided in patients with mastocytosis (5). All cases (n=491) of anaphylactic or anaphylactoid reactions during anesthesia that were referred to 40 allergo-anesthesia centra between January 1 and December 312002 were reported in a study. The most common cause of anaphylaxis was neuoromuscular blocking drugs (55%). Rocuronium and suxamethonium were the most common drugs in the reports (6).

Patients with mastocytosis have an increased risk of anaphylaxis and a prevalence between 22 and 49% has been reported for adults. According to a recently published review, the literature on perioperative drug safety in patients with mastocytosis is very sparse and it is thus not possible to give general recommendations regarding what drugs are tolerated and not by these patients. Extra attention is recommended to avoid potential physical triggers such as sudden changes in temperature, infusion of cold solutions, substantial tissue damage, friction and other mechanical factors. To avoid degranulation of mast cells due to anxiety, anxiolytic premedication with e.g. benzodiazepines can be considered (5,7). Premedication with antihistamines or corticosteroids to avoid systemic reactions can be considered, but there is no evidence in support of this (5,7).

Histamine releasing drugs given to patients with mastocytosis should be administered as slowly as possible (5). Induction drugs are generally regarded to be well tolerated (7). Inhaled flurane anestheteics have not been associated with anaphylaxis (7,8). The choice of method of anesthesia should be based on an assessment of the patients medical history and drugs that previously caused a reaction should be avoided (8). If neuromuscular blocking drugs are used a skin test can sometimes help in guiding the choice of drug (7). Skin tests are however difficult to interpret in patients with mastocytosis. Opioids such as morphine and codeine have been associated with mast cell activation in patients with mastocytosis and should be avoided, fentanyl and related drugs such as remifentanil, sufentanil and alfentanil does not seem related to a large risk of reactions (7).