Anesthetic Pharmacology: Case Report
Sugammadex (ORG 25969) is a novel synthetic γ cyclodextrin that selectively encapsulates steroid-based nondepolarizing muscle relaxants (e.g., rocuronium). Recent studies (1–3) have demonstrated that sugammadex (>2 mg/kg IV) can rapidly reverse profound (“deep”) neuromuscular blockade after rocuronium when administered during general anesthesia. There have been no reports describing the use of sugammadex for emergency reversal of residual blockade in patients receiving a standard reversal drug combination of neostigmine and glycopyrrolate. Although sugammadex has been extensively investigated for reversing rocuronium, there are no published reports describing its use in reversing other steroid-based nondepolarizing muscle relaxants (e.g., vecuronium).
A 42-yr-old male (weighing 87 kg) with a history of hypertension and end-stage renal disease (his preoperative creatinine concentration was 15.6 mg/dL) was admitted to Parkland Memorial Hospital in Dallas for placement of a peritoneal dialysis catheter under general endotracheal anesthesia. The patient received midazolam (1 mg IV) for premedication. Anesthesia was induced with propofol (200 mg IV), fentanyl (150 mcg IV) and vecuronium (10 mg IV). After tracheal intubation, anesthesia was maintained with desflurane (4%– 4.5% end-tidal) in a 50:50 nitrous oxide (1 L/min) and oxygen (1 L/min) mixture. He also received cefazolin (2 g IV), ondansetron (4 mg IV), and normal saline.
At the end of the 1-h operation, a train-of-four stimulus elicited two small twitches. Neuromuscular blockade was reversed with neostigmine (5 mg IV) and glycopyrrolate (1 mg IV). Desflurane and nitrous oxide were discontinued and the oxygen flow rate was increased to 6 L/min. Five minutes after administering the reversal drugs, the patient was reported to have “four twitches” in response to the train-of-four stimulation. Although he resumed spontaneous ventilation in the operating room, his tidal volumes were small and he was transported to the postanesthesia care unit with the tracheal tube in place. Upon arrival in the postanesthesia care unit, the patient was awake and clearly agitated, and his respiratory efforts were labored. He was unable to sustain a hand grip (0/5), stick out his tongue, or lift his head off the gurney. Although his oxygen saturation was 100%, he became increasingly agitated and tachypneic (with a respiratory rate >40 breaths/min).
Under provisions of our local IRB at University of TX Southwestern Medical Center at Dallas for emergency use of an investigational drug on a one-time only basis, we administered sugammadex, 350 mg (approximately 4 mg/kg) by a rapid IV bolus injection. Within 60 s, the patient’s tidal volume markedly increased, and his respiratory rate declined to <20 breaths/min. Within 2 min, he was able to sustain a 5-s head lift and his grip strength improved to 5/5. The patient’s trachea was immediately extubated and on direct question, he reported no acute respiratory distress or residual muscle weakness.
The patient manifested no acute hemodynamic changes after the IV bolus administration of sugammadex. Although he subsequently developed mild shivering (which was treated with meperidine, 12.5 mg IV) and incisional discomfort (treated with fentanyl 25 μg IV), he recovered promptly. He was discharged home from the day-surgery unit after a 2-h observation period. On direct questioning in the day-surgery unit before discharge to home, he stated that he remembered being awake with the breathing tube in place and feeling extremely anxious, weak, and short of breath. He said that after removal of the breathing tube he felt no further respiratory distress or muscle weakness. A 24-h follow-up telephone call to the patient revealed that he experienced no side effects at home after discharge from the hospital.
Based on early clinical experience with this novel cyclodextrin compound (4), it is expected that sugammadex will produce complete reversal of rocuronium-induced neuromuscular blockade (1–3). There is also a rational scientific basis for supposing that sugammadex will reverse a vecuronium-induced neuromuscular blockade (5). This case report illustrates the potential utility of sugammadex in “rescuing” patients who fail to achieve adequate reversal of residual neuromuscular blockade produced by vecuronium with a combination of neostigmine and glycopyrrolate. Of course, a case report is not a substitute for proper clinical trials to establish the safety and efficacy of sugammadex reversal of steroid-based muscle relaxants other than rocuronium (e.g., vecuronium and pancuronium).
Editors Note: The Editorial Board of Anesthesia & Analgesia may request IRB documentation to validate compliance with IRB regulations and ethical treatment of patients and research subjects. This patient received an investigational drug without prior IRB approval and written informed consent. At our request, the authors provided the relevant documents filed with their IRB. These documents indicate full compliance with the requirements for one-time use of investigational products to treat potentially life-threatening emergencies as established by the University of TX Southwestern Medical Center at Dallas.
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3. Sacan O, White PF, Tufanogullari B, Klein K. Sugammadex reversal of rocuronium-induced neuromuscular blockade: a comparison with neostigmine glycopyrrolate and edrophonium-atropine. Anesth Analg 2007;104:569–74.
4. Gijsenbergh F, Ramael S, Houwing N, van Iersel T. First human exposure of Org 25969, a novel agent to reverse the action of rocuronium bromide. Anesthesiology 2005;103:695–703.
5. Suy K, Morias K, Hans P, Heeringa M, Demeyer I. Fast, effective and safe reversal of rocuronium and vecuronium-induced moderate neuromuscular block by the selective relaxant binding agent Org 25969. Anesthesiology 2005;103:A1119.