Is there cross-allergenicity between succinylcholine and rocuronium?

Comment by InpharmD Researcher

Cross-allergenicity has been reported between succinylcholine and rocuronium, but the true incidence is unknown. In cases of documented NMBA allergy, skin testing can be used to assess for safe agents to use.

Background

A 2019 study aimed to use basophil activation testing (via intradermal testing) to assess for cross-allergenicity of NMBAs in 61 patients from an anesthesia allergy clinic. Patients were given minute quantities of rocuronium, vecuronium, pancuronium, succinylcholine, cisatracurium via intradermal skin and assessed for allergic symptoms (i.e., wheal grew larger or increased by 3 mm) or presence of IgE antibodies. Most patients presented with rocuronium allergy at baseline (79%), and 9 (15%) had a baseline succinylcholine allergy. Of the 61 total patients, 51 had positive skin testing to the culprit NMBA and 53 had positive IgE values. Of the 51 patients with positive skin testing to the culprit NMBA, 20 (39%) showed no cross-reactivity on skin testing, while 31 (61%) showed cross-reactivity to at least one other NMBA. Of these 31 patients, 12 (39%) had sensitization to one or more aminosteroids (rocuronium, vecuronium, pancuronium), 15 (48%) had sensitization to aminosteroids and succinylcholine, and 4 (13%) had sensitization to aminosteroids, succinylcholine, and cisatracurium. When assessed for cross-reactivity, 13 of 48 (27%) of patients allergic to rocuronium at baseline were also allergic to succinylcholine. Of the 9 patients with a baseline succinylcholine allergy, 3 (33%) also reported cross-reactivity to rocuronium. [1]

Over a 10 year period from 2002 to 2011, a study in Australia evaluated the prevalence of cross-reactivity in patients with previous neuromuscular blocking agent (NMBA) anaphylaxis. Of 63 patients diagnosed with NMBA anaphylaxis, 30 (48%) cross-reacted with succinylcholine. Additionally, 11 of 34 (32%) patients cross-reacted with rocuronium. Patients with rocuronium prophylaxis were most likely to cross-react to succinylcholine (44%), while patients with succinylcholine anaphylaxis were less likely to cross-react with rocuronium (24%). Of the agents that cross-reacted with rocuronium, succinylcholine had the highest rate of cross-reactivity; similarly, of the agents that cross-reacted with succinylcholine allergy, rocuronium was the highest observed. [2]

A case study described an occurrence of an anaphylactic reaction to rocuronium in a 31-year-old male patient confirmed as having multiple cross-reactivities to various neuromuscular blocking agents (NMBAs) via an allergic skin test after discharge. The patient, who had no history of allergies or previous surgery, was scheduled for a lobectomy of the right lower lung. Preoperative tests and vitals while in the operating room all initially showed as normal and stable. The patient was put under general anesthesia using propofol infusion, after which rocuronium 60 mg was administered and endotracheal intubation was performed. Following intubation, the patient began to experience moderate hypotension, with blood pressure 85/40 mmHg and heart rate 75 beats/min. After intravenous ephedrine 10 mg and lactated Ringer’s, the patient’s blood pressure did not improve. Propofol was halted and midazolam 3 mg and rocuronium 20 mg were administered, after which the patient began to experience severe hypotension, with a blood pressure of 50/30 mmHg, along with a skin rash, urticaria, and edema on his face, neck, arms, and legs. The patient was given intravenous epinephrine 0.1 mg and a continuous infusion of dopamine, dobutamine, and phenylephrine. After a few minutes, vitals stabilized, with blood pressure 90/45 mmHg, heart rate 105 beats/min, and SpO2 100%. The patient was also administered intravenous hydrocortisone 100 mg and chlorpheniramine 4 mg. Following time in the intensive care unit, the patient eventually stabilized without inotropics and vasopressors and was discharged three days after the event. Three and four months after discharge, allergic skin tests revealed positive results for remifentanil, rocuronium, vecuronium, atracurium, and succinylcholine. [3]

A retrospective observational review done in New Zealand between 2006 and 2012 investigated the occurrence of anaphylaxis triggered by neuromuscular blocking agents (NMBAs). After evaluating a total of more than 400,000 anesthetic records, 21 patients (average age 59 years, 81% female) were included with documented anaphylaxis to NMBAs out of 92,858 new patient exposures to NMBAs. The incidence of anaphylaxis was 1 in 22,451 for new patient exposures to atracurium, 1 in 2,080 for succinylcholine, and 1 in 2,499 for rocuronium (p<0.001). The authors concluded that the rate of anaphylaxis with succinylcholine and rocuronium is about 10x higher than atracurium. Skin tests revealed that one patient with a reaction to succinylcholine showed cross-sensitivity to rocuronium despite not having been administered rocuronium. Three rocuronium patients were found to have cross-sensitivity to other NMBAs which they were not administered. Cross-sensitization was discovered in a total of 9 of 21 cases (43%). [4]

A 17-year-old male with no prior history of reaction to anesthesia use developed hypotension, skin flushing, and angioedema 19 minutes after induction with sevoflurane, propofol, lidocaine, rocuronium, and fentanyl prior to a partial left ethmoidectomy. The procedure was canceled and he improved after phenylephrine, epinephrine, diphenhydramine, and hydrocortisone. Four weeks later, he underwent skin prick testing to the agents used plus other NMBAs (succinylcholine, vecuronium, and cisatracurium). Results of his skin prick testing only showed positive for rocuronium; all other NMBAs tested did not produce an allergic reaction. The authors suggest allergy to one NMBA may not require avoidance of the whole class and that skin testing or sensitization should be assessed prior to his future surgical procedures. [5]

References:

[1] Li J, Best OG, Rose MA, et al. Assessing cross-reactivity to neuromuscular blocking agents by skin and basophil activation tests in patients with neuromuscular blocking agent anaphylaxis. Br J Anaesth. 2019;123(1):e144-e150. doi:10.1016/j.bja.2019.03.001
[2] Sadleir PH, Clarke RC, Bunning DL, Platt PR. Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011. Br J Anaesth. 2013;110(6):981-987. doi:10.1093/bja/aes506
[3] Oh YJ, Lee HJ. Multiple cross-reactivity to several types of neuromuscular blocking agents in a patient with rocuronium anaphylaxis. Korean J Anesthesiol. 2013;65(5):473-474. doi:10.4097/kjae.2013.65.5.473
[4] Reddy JI, Cooke PJ, van Schalkwyk JM, Hannam JA, Fitzharris P, Mitchell SJ. Anaphylaxis is more common with rocuronium and succinylcholine than with atracurium. Anesthesiology. 2015;122(1):39-45. doi:10.1097/ALN.0000000000000512
[5] Haehn D, Carrillo-Martin I, Restrepo D, Incontri-Abraham D, Gonzalez-Estrada A. M057 anaphylaxis to rocuronium and evidenced lack of cross reactivity with other neuromuscular blocking agents. Annals of Allergy, Asthma & Immunology. 2019;123(5):S79. doi:10.1016/j.anai.2019.08.126

Relevant Prescribing Information

Rocuronium
In addition, inform your patient that severe anaphylactic reactions to neuromuscular blocking agents, including rocuronium bromide, have been reported. Since allergic cross-reactivity has been reported in this class, request information from your patients about previous anaphylactic reactions to other neuromuscular blocking agents. In clinical practice, there have been reports of severe allergic reactions (anaphylactic and anaphylactoid reactions and shock) with rocuronium bromide, including some that have been life-threatening and fatal. [6]

Succinylcholine
Since allergic cross-reactivity has been reported in this class, request information from your patients about previous anaphylactic reactions to other neuromuscular blocking agents. In addition, inform your patients that severe anaphylactic reactions to neuromuscular blocking agents, including succinylcholine have been reported.
There have been post-marketing reports of severe allergic reactions (anaphylactic and anaphylactoid reactions) associated with use of neuromuscular blocking agents, including succinylcholine. These reactions, in some cases, have been life threatening and fatal. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency. [7]

References:

[6] Rocuronium bromide [prescribing information]. Deerfield, IL: Baxter Healthcare Corporation; 2019.
[7] Succinylcholine [prescribing information]. Durham, NC: Accord Healthcare, Inc.; 2021.