Rocuronium allergy: Case report and review of the literature

Authors: Spanou E^1a*, Stamatakis E^2b, Pavlidis M^3b, Valsamidis D^2b

¹ MD, MSc, Anesthesiology
² MD, MSc, PhD, Anesthesiology
³ MD, Anesthesiology

^a Department of Anesthesiology and Pain Medicine, 401 General Military Hospital, Athens, Greece
 ^b Department of Anesthesiology and Pain Medicine, Alexandra General Hospital, Athens, Greece

Correspondence: Kifisias Avenue 118b, Ambelokipoi, Athens, 11526
Tel: 00306975737967, email:

 

ABSTRACT

Perioperative anaphylaxis is a rare but potentially life-threatening event requiring rapid recognition and immediate intervention. Neuromuscular blocking agents (NMBAs) remain among the most common culprits, with rocuronium being a frequent trigger. This report presents a case of severe anaphylaxis during anesthesia induction, followed by a second uneventful anesthetic exposure after modification of the anesthetic approach.

 

 INTRODUCTION

Perioperative anaphylaxis represents a rare but potentially life-threatening complication during anesthesia, requiring immediate recognition and intervention.

We present the case of a young woman who developed severe anaphylactic shock during induction of anesthesia for elective laparoscopic ovarian cystectomy.

 

CASE REPORT

First admission

A 28-year-old (body weight: 69kg, height: 176cm, BMI 22.3), otherwise healthy female patient (ASA 1), with no prior history of surgery, was scheduled for elective laparoscopic ovarian cystectomy. According to her medical history, she mentioned neither health problems nor allergies; she was a non-smoker and was not on any medication.

On arrival at the theatre, two 20G peripheral intravenous lines were established, and basic monitoring was initiated (ECG, NIBP, SPO₂, ETCO₂). Her pre-induction vitals were normal, with systolic blood pressure 98 mmHg, diastolic blood pressure 56 mmHg, heart rate 66 bpm, and oxygen saturation 99%. Midazolam 1 mg, metoclopramide 10 mg, cimetidine 200 mg, and ampicillin/sulbactam 3g infusions were administered in the pre-induction phase.

After preoxygenation of 2 minutes, induction of anesthesia was performed with propofol 2.3mg/kg, fentanyl 1.4μg/kg and rocuronium 0.65mg/kg to facilitate endotracheal intubation. This was achieved with a size 7.0 cuffed endotracheal tube on the first attempt, with direct laryngoscopy (Cormack-Lehane score IIA) without complications. Capnography was detected, and mechanical ventilation was initiated in PCV-VG mode with a tidal volume of 450 mL, a respiratory rate of 12 bpm, and a PEEP of 5 cmH₂O.  Shortly after induction, the patient developed severe hypotension [57/32 mmHg (systolic/diastolic blood pressure)], generalized erythematous rash, angioedema, tachycardia (139 bpm), and bronchospasm. Oxygen saturation remained above 98% throughout. However, capnography demonstrated a sudden reduction in end-tidal CO₂ (22 mmHg) accompanied by elevated airway pressures (Paw 38 cmH2O).

A diagnosis of anaphylactic shock was strongly suspected. Immediate treatment included 80 μg adrenaline (1,1 μg/kg) given IV in four boluses, oxygenation with FiO₂ 100%, administration of 12 puffs of salbutamol via the endotracheal tube, followed by intravenous dexamethasone 8 mg, hydrocortisone 250 mg, magnesium sulfate 2.5 g, and dimetindene 4 mg. The patient showed gradual improvement (20 min-40 min after induction) with resolution of cutaneous manifestations, relief of bronchospasm, hemodynamic stabilization, and return of heart rate to baseline.

Anesthesia was maintained with Sevoflurane/Air/O₂ at a MAC of 1.0 and a reduced FiO₂ to 40%. Once stabilized, the decision was made to abort the surgical procedure since multiple agents had been co-administered at induction, making it impossible to identify the causative drug. The patient’s neuromuscular blockade was slowly reversed with 2 mg/kg sugammadex, achieving a train-of-four ratio of 4/4, and she was extubated uneventfully. Postoperatively, she remained hemodynamically and respiratory stable (heart rate 68-72 bpm, mean blood pressure 75-90 mmHg, oxygen saturation 98%) in the recovery unit, where she received nebulized salbutamol 2.5mg, ipratropium 0.5 mg, and budesonide 0.25mg. She remained in the recovery unit for 90 minutes, and then she was transferred to a step-down unit for further monitoring.

Blood samples for serum tryptase were collected at 1 hour and again at 10 hours post-event.

The results confirmed an anaphylactic reaction (Table 1).

 

 

 

Readmission

Following outpatient allergology evaluation, skin prick tests were negative; however, rocuronium or the administered antibiotic was suspected as the most probable triggers. The allergologist recommended avoidance of these drugs in the future and suggested a modified anesthetic plan involving slow and sequential administration of alternative agents under vigilant monitoring.

The patient was rescheduled 30 days after the incident for laparoscopic ovarian cystectomy. On the ward, two peripheral intravenous lines were secured.

One hour before arrival at the theatre, prophylactic intravenous dexamethasone 8mg, hydrocortisone 250mg, and dimetindene 4mg were administered.

On arrival at the theatre, basic monitoring was applied , two peripheral intravenous lines were established, one 20G and one 18G, and midazolam 1mg, metoclopramide 10 mg, cimetidine 200 mg, and cefoxitin 2 g were administered. After preoxygenation for 2 minutes, anesthesia was induced with propofol 2.3 mg/kg, fentanyl 1.4 μg/kg, and cisatracurium 0.17 mg/kg to facilitate endotracheal intubation. No allergic manifestations were observed, and the patient was successfully intubated with a size 7.0 cuffed endotracheal tube (Cormack-Lehne score IIA).

She remained hemodynamically stable, with easy and effective ventilation in PCV-VG mode, Tidal volume 450ml, respiratory rate 12 bpm, and PEEP 5 cmH2O. Anesthesia was maintained with air/sevoflurane at a MAC 1.0 with FiO2 45%. Intraoperatively, she received fentanyl 200 μg, ondansetron 4 mg, acetaminophen 1 g, dexketoprofen 50 mg, and tramadol 100 mg for postoperative analgesia. The surgery lasted 120 minutes. Reversal of neuromuscular blockade was performed with neostigmine 2.5mg and atropine 1mg, achieving a train-of-four ratio of 4/4.

Extubation was uneventful. Postoperative care was uncomplicated, and the patient was discharged in good health.

 

DISCUSSION

Neuromuscular blocking agents (NMBAs) are among the most frequent triggers of immediate perioperative hypersensitivity reactions, most often presenting as IgE-mediated anaphylaxis with bronchospasm, tachycardia, hypotension, and rash. Anaphylactoid reactions, however, mimic these symptoms but arise from nonspecific complement activation, complicating differential diagnosis. Anaphylaxis requires prior sensitization, sometimes to structurally similar compounds, whereas anaphylactoid reactions do not require previous exposure. Because perioperative patients often receive multiple drugs, pinpointing the causative agent based on symptoms alone is unreliable, necessitating allergological evaluation with skin testing, specific IgE, basophil activation test (BAT), and, where appropriate, drug provocation^1,2,3. Skin prick and intradermal tests, although first-line, have limited sensitivity depending on the drug. NMBA challenge tests must be conducted in a monitored setting due to risks of residual blockade and respiratory compromise. Drug provocation remains the gold standard for diagnosis^1,2,3.

Cross-reactivity among NMBAs is frequent—up to 60–70%—especially among aminosteroidal agents (rocuronium, pancuronium, vecuronium), while benzylisoquinolines (atracurium, cisatracurium) are notably potent histamine releasers^4,5,6. Concordance between skin testing and BAT is low (≈15%), highlighting the need for further research and standardization⁷.

The ultimate aim is a robust algorithm for safe anesthetic management. Perioperative anaphylaxis is a life-threatening emergency; clinical manifestations range from mild hypotension to severe, even fatal cardiovascular and respiratory compromise, requiring rapid intervention with epinephrine and corticosteroids.

Over 90% of perioperative allergic reactions are caused by NMBAs, latex, or antibiotics^7,8 . The high incidence of NMBA cross-reactivity —driven by shared quaternary ammonium structures—necessitates systematic evaluation for safe anesthetic planning when hypersensitivity is identified.

Recent research has shown that rocuronium-induced anaphylactic shock may occur via MRGPRX2 (Mas-related G protein-coupled receptor-X2) – mediated mast cell activation, even in patients with low IgE levels⁹.

Although cross-reactivity among NMBAs is generally common, reactions between rocuronium and cisatracurium appear rare: Sadleir et al.¹⁰ reported a 5% cross-reactivity rate, Li et al.⁷ found 3%, while a French study reported a higher 29%, suggesting regional variability¹¹. Accurate diagnostic testing is thus critical, as patients allergic to both agents have limited anesthesia options.

The incidence of allergic reactions varies across NMBAs: 8.0 per 100,000 for rocuronium, 2.8 for vecuronium, and 4.0 for atracurium. Among patients allergic to rocuronium, cross-reactivity rates are 44% with succinylcholine, 40% with vecuronium, 19% with pancuronium, 20% with atracurium, and only 5% with cisatracurium^10,12. These data reinforce the need for careful selection of alternative NMBAs and, when necessary, consideration of non-NMBA anesthetic techniques. Case reports have documented anaphylactic shock after cisatracurium administration, highlighting the clinical relevance of these risks¹³.

While anaphylactoid reactions to cisatracurium are uncommon, severe bronchospasm and anaphylactic shock have been reported, indicating a significant perioperative risk¹⁴. Succinylcholine, often used for rapid sequence induction, can also trigger life-threatening anaphylaxis. In a series of 21 severe cases, cardiovascular collapse occurred immediately after administration, with six experiencing cardiac arrest and three fatalities¹⁵. The National Clinical Guideline Center (2014) recommends that when a perioperative allergic reaction occurs, the procedure should be terminated and the patient referred to an allergist for investigation of the causative drug¹⁶ . This approach improves patient safety, reduces system costs, and alleviates patient anxiety by clarifying safe alternatives. Notably, allergic reactions during anesthesia remain under-referred.

In our case, we consulted with an allergologist and, despite a negative skin test, adjusted the anesthetic plan based on positive tryptase and known limitations of skin testing. We premedicated with dexamethasone, hydrocortisone, and dimetindene, changed the antibiotic to a previously tolerated cephalosporin, and used cisatracurium instead of rocuronium, as literature supports a low cross-reactivity between these agents.

Anaphylaxis to sugammadex is rare (<0.02%), and cross-reactivity with NMBAs has not been confirmed. Even in countries with high sugammadex use, such as Japan, the incidence of allergic reactions is not increased¹⁷. While some reports suggest that sugammadex may reverse rocuronium-induced anaphylaxis by encapsulating the drug, this remains controversial; once the anaphylactic cascade is triggered, reversal of neuromuscular blockade may not halt progression, especially in severe cases requiring epinephrine^12,17 .This case underscores the importance of clinical vigilance, rapid recognition of allergic symptoms and prompts intervention.Detailed documentation and serum sampling for allergological evaluation are crucial for guiding future anesthetic management. Careful monitoring, early treatment, and appropriate diagnostic follow-up are essential to optimize patient safety.

Conclusion

Perioperative anaphylaxis represents a critical anesthetic emergency that demands prompt recognition, aggressive management, and thorough postoperative evaluation. This case illustrates the challenges in identifying the causative agent when multiple drugs are administered concurrently and highlights the value of serum tryptase measurements in confirming the diagnosis. Despite the limitations of skin testing, careful interpretation of clinical findings along with available diagnostic tools can guide safe future anesthetic strategies. The significant differences in cross-reactivity patterns among neuromuscular blocking agents underscore the importance of choosing an alternative NMBA with a lower risk profile, such as cisatracurium in patients suspected of rocuronium hypersensitivity. Ultimately, individualized perioperative planning, interdisciplinary collaboration, and pre-emptive measures are essential to ensure patient safety and to prevent recurrent anaphylactic episodes.

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Addittional materials: No

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Acknowledgements: Not applicable

Authors’ contributions: SpE: primary case management, manuscript preparation, final draft, lead author, SE, PM, VD: literature review, critical review.All authors read and approved the final manuscript.

Availability of supporting data: The datasets analyzed during the current article are available from the corresponding author on reasonable request.

Funding: Not applicable.

Ethical approval and consent to participate: Ethics committee approval required. Patient’s consent was obtained

Competing interests: The authors declare that they have no competing interests.

Received: June 2026, Accepted: September 2026, Published: September 2026

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Citation: Spanou E, Stamatakis E, Pavlidis M, Valsamidis D: Rocuronium allergy: Case report and review of the literature. Greek e j Perioper Med. 2026;25(b): 40-47.

 

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