A case series of life-threatening succinylcholine-induced anaphylaxis.

Editor,

Since 1952, succinylcholine has been widely used worldwide as the first choice of muscle relaxant to facilitate tracheal intubation in rapid sequence induction of anaesthesia. Despite its unique properties (i.e. short onset and offset and intense blockade), succinylcholine may induce some severe adverse reactions, such as anaphylactic reactions.[1,2] Diagnosing anaphylactic reactions remains challenging.[3] Although guidelines are available, the evidence base for the assessment and subsequent management of patients with anaphylaxis is weak due to the absence of randomised, controlled studies of therapeutic interventions performed during an anaphylactic reaction.[4-6]

We report here the prevalence of clinical symptoms, the appropriateness of rescue therapy and the diagnosis difficulty of succinylcholine-induced anaphylaxis, based on the analysis of 21 case reports of life-threatening (Ring and Messmer grades III and IV) reactions. These cases were reported between October 2011 and January 2015 at two French university hospitals (Lariboisière-Saint-Louis University Hospital and Brest University Hospital). The role of succinylcholine was confirmed by two senior allergologists with much experience in diagnosing perianaesthetic anaphylactic reactions. Ethical approval for this study was provided by the Ethical Committee of Société de Reanimation de Langue Française, (No. CE SRLF 14-1).

This case series documents the acuteness, suddenness and severity of cardiovascular events in succinylcholine-related anaphylaxis and demonstrates the difficulty of diagnosing anaphylaxis, which led to frequent sub-optimal and/or inappropriate management at the time of anaesthetic induction. Patients had a median age of 64 years (range 27 to 81), 57% were women, 48% had a history of hypertension with 14% being treated with beta-blocker and 24% were obese. A total of 67% of cases occurred during scheduled surgery and 33% during emergent surgery. Indications for succinylcholine were in accordance with the French recommendations. Overall, clinical signs appeared immediately after IV succinylcholine administration and were graded as severe, with 21/21 cardiovascular collapse and 6/21 cardiac arrest. The systolic and diastolic arterial blood pressures rapidly decreased in all patients after the administration of succinylcholine, associated with an increased heart rate (Fig. 1). In six cases, cardiac arrest appeared less than 5 min after succinylcholine administration and was preceded by cardiovascular collapse in all cases. For these six cases of cardiac arrest, one patient died in the operating room; one patient died in the ICU 2 days after the anaphylactic reaction from a refractory shock; one patient had a refractory cardiac arrest with extracorporeal membrane oxygenation assistance and died 12 days later in the ICU; and three of them survived with an ICU stay of 8, 12 and 30 days, respectively. All patients who did not suffer cardiac arrest survived. Although cardiovascular events were present in all patients, clinical diagnosis remains difficult as cutaneous and respiratory symptoms were lacking in half of the patients (cutaneous signs in 10/21 cases and bronchospasm in 11/21 cases) and as collapse is relatively frequent during anaesthesia. The difficulty of diagnosing perianaesthetic anaphylaxis probably led to suboptimal and/or delayed use of epinephrine, the recommended first-line therapy drug.[4] Indeed, management of these severe anaphylactic reactions was heterogeneous, particularly for catecholamine administration. Only 6/21 cases received epinephrine as the first-line therapy, 12/21 received it as the second-line therapy and 3/21 did not receive epinephrine. These results are in accordance with a previous report.[7] These results demonstrated that the rescue therapy was suboptimal and/or delayed in at least 70% of the reported patients. In only 55% of cases was the administered epinephrine dose in accordance with the French recommendations (i.e. 1 mg for cardiac arrest and 100 to 200 μg for hypotension). A total of 73% of cases with bronchospasm received inhaled salbutamol, and 18% of these patients received additional intravenous salbutamol.

Fig. 1

Individual data of heart rate, oxygen saturation, SBP, DBP for the 21 cases before induction (T1), at the time of anaphylactic shock (T2) and after resuscitation (T3). DBP, diastolic blood pressure; HR, heart rate; SBP, systolic blood pressure.

It also emphasises the difficulty in determining the causality of succinylcholine in such adverse reactions. Patient history, clinical symptoms, histamine and tryptase measurements, IgE-specific assays and skin tests are the gold standard for diagnosing anaphylactic reactions. The diagnosis of anaphylaxis during anaesthesia should include different confirmatory tests rather than a single test and patients presenting an anaphylactic reaction during anaesthesia should be fully investigated. Results of biological (i.e. plasma histamine, plasma tryptase and specific plasma IgE) and skin tests are presented in Table 1. Skin tests (intradermal tests, succinylcholine 10 mg ml−1), which remain the gold standard to prove drug-induced anaphylaxis, were performed in 14/21 cases and were systematically positive for succinylcholine. They were not performed in 4/21 cases because of death and in 3/21 cases because of loss of follow-up. Finally, only 9/21 cases were fully investigated with biological tests (i.e. plasma histamine and/or tryptase and specific plasma IgE) followed by skin tests. The three patients who died after cardiac arrest related to succinylcholine anaphylaxis had been fully investigated for biological tests (i.e. plasma histamine, plasma tryptase and specific plasma IgE) and had concordant positive results. The difficulty in obtaining the completeness of confirmatory tests and particularly skin tests explains the difficulty for allergologists to draw definite conclusions. Indeed, when a single test is negative, it is not possible to determine whether it is a false-negative test or whether the patient is tolerant to the tested agent. None of the available diagnostic tests demonstrates absolute accuracy.[3] However, physicians need definite conclusions to be able to adapt their practice to each patient.

Table 1

Biological and skin tests

	Test performed	Positive result	Quantitative result
Plasma histamine (nmol l−1)	19/21 (90%)	15/19 (79%)	100 (67 to 1479)
Plasma tryptase (μg l−1)	19/21 (90%)	17/19 (89%)	95 (48 to 188)
Plasma IgE succinylcholine (kU l−1)	17/21 (81%)	16/17 (94%)	0.8 (0.3 to 4.9)
Skin test succinylcholine	14/21 (67%)	14/14 (100%)

Values are expressed as n (%). Quantitative results are expressed as median (25–75 percentile). Histamine was considered positive if more than 15 nmol l−1, tryptase if more than 15 μg l−1 and IgE if more than 0.1 kU l−1.

Close collaboration between the allergologist and the anaesthesiologist is a key issue when investigating anaphylactic reactions.

In conclusion, when using succinylcholine to induce general anaesthesia, our study strongly suggests that, in cases of collapse resistance to ephedrine and phenylephrine, epinephrine should be quickly used. Final diagnosis remains difficult, and biological and skin tests should be fully performed.