Anaphylaxis to Neuromuscular Blocking Drugs: Incidence and Cross-Reactivity in Western Australia

Among drugs causing rare intraoperative anaphylaxis, neuromuscular-blocking drugs (NMBDs) are the most common. Which one is the least likely to cause anaphylaxis is uncertain, and the likelihood of cross-reactivity to alternative NMBDs is not known for patients who have had previous anaphylactic reactions. This study was undertaken to estimate a rate of anaphylaxis to NMBDs by analyzing cases of NMBD anaphylaxis referred to a specialized diagnostic center in Western Australia. Patients underwent skin testing to the NMBD administered and all other possible triggering agents. Intradermal testing was done for the aminosteroid agents with a 1:1000 dilution of rocuronium, vecuronium, or pancuronium (10, 4, and 2 mg/mL, respectively. Atracurium was tested at a dilution of 1:10,000 (10 mg/mL) or cisatracurium at 1:1000 (2 mg/mL). Succinylcholine (50 mg/mL) was diluted to 1:1000. Avolume of 0.02 mL was injected in the volar forearm to yield a 4-mm intradermal bleb. If the wheal increased to 8 mm or greater at 20 minutes, the response was considered to be positive. Cross-reactivity testing was done for those with NMBD anaphylaxis. The severity of anaphylaxis was graded as follows: grade 1 had cutaneous signs only; grade 2 had the presence of measurable but not lifethreatening symptoms, including a decrease in arterial pressure by greater than 30% along with tachycardia and cutaneous signs, cough, or difficulty in mechanical ventilation; grade 3 had lifethreatening reactions, including cardiovascular collapse; and grade 4 had circulatory inefficacy or cardiac arrest. The number of patients exposed to NMBDs during the 10-year period was extrapolated from 5 years of NMBD ampoule sales data for Western Australia. A rate of NMBD anaphylaxis for each agent was calculated. During the study period, 80 patientswere diagnosedwith lifethreatening anaphylaxis to an NMBD; 56%, 21%, 11%, 9%, and 3% of the reactions were triggered by rocuronium, succinylcholine, vecuronium, atracurium, and mivacurium, respectively. No events were triggered by pancuronium or cisatracurium. Eleven patients (14%) had a grade 4 intraoperative anaphylaxis to an NMBD, and 10 of these individuals received external cardiac compressions. Grades 3 and 2 reactions occurred in 55 and 14 patients, respectively. The 3 most often implicated agents showed no difference in the severity of reactions. Surgery was halted in 60%, and the patient was admitted to an intensive care unit in 57% of cases. Rocuronium had the highest rate of anaphylaxis, 8.0 episodes/100,000 administrations during the 10-year period. The rate for vecuronium was 2.8/100,000 administrations. This difference was statistically significant when considered during the study period (P = 0.0013) or when limited to the 5 years that had sales data available (0.2 vs 3.1/100,000; P = 0.01). Atracurium had a rate of 4.01/100,000. Rocuronium, vecuronium, and atracurium caused 49%, 14%, and 11% of anaphylactic reactions during the 10-year period, respectively, but had 49%, 28%, and 15% share of the intermediate-duration market, respectively, during the 5-year period for which data are available. Patients with NMBD anaphylaxis most often had a cross-reaction with succinylcholine (30 of 63 patients tested). Eleven of 34 patients cross-reacted with rocuronium, 20 of 70 with vecuronium, and 16 of 76 patients with pancuronium. Benzylisoquinoliniums cross-reacted less often. Patients with rocuronium anaphylaxis were more apt to have positive skin tests for succinylcholine and vecuronium (44% and 40%, respectively); pancuronium and atracurium were cross-reactors at rates of 19% and 20%, respectively. Cisatracurium cross-reacted at a rate of only 5%. Anaphylaxis to NMBDs is a known major clinical problem. Although rocuronium causes immunoglobulin E (IgE)Ymediated anaphylaxis at a higher rate than vecuronium, this characteristic of rocuronium is often ignored. Clinicians should recognize that anaphylaxis to rocuronium is increased when they are evaluating a patient’s need for an intermediate-duration NMBD.