DP44: DELAYED POSTOPERATIVE BRADYCARDIA AFTER FLUMAZENIL WEAR OFF: RECURRENCE OF MIDAZOLAM EFFECT
Tamara Stojilkovic, DO; Rojin Esmail, MD; Nicholas Nedeff, MD
HCA Florida Kendall Hospital
Introduction/Background: Flumazenil is a competitive benzodiazepine receptor antagonist commonly used to reverse the sedative effects of midazolam in the perioperative setting. Its elimination half-life (approximately 30–60 minutes) is shorter than that of midazolam (1.5–3 hours), creating the potential for recurrence of benzodiazepine effects after initial reversal. In elderly patients, altered pharmacokinetics and increased pharmacodynamic sensitivity may further prolong sedative effects, increasing the risk of delayed cardiorespiratory depression or autonomic instability.
Methods: We present the case of a 63-year-old female with a history of anxiety and depression who underwent elective left total hip arthroplasty for unilateral primary osteoarthritis. In the preoperative area, she received one dose of midazolam for anxiolysis and subsequently became agitated. She was treated with intravenous flumazenil, administered as an initial 0.2 mg dose followed by 0.1 mg increments to a total of 1 mg. The patient underwent a combined approach with a spinal and total intravenous anesthesia. The intraoperative course was uneventful, and she remained hemodynamically stable throughout the procedure.
Results: On arrival to the post-anesthesia care unit (PACU), the patient was initially stable. Approximately one hour later, she developed symptomatic bradycardia accompanied by hypotension and nausea. No surgical or anesthetic complications were identified to explain the event. She was treated with atropine 0.4 mg intravenously, resulting in rapid resolution of bradycardia and restoration of hemodynamic stability. She remained stable thereafter without recurrence of symptoms.
Discussion/Conclusion: The timing of this event suggests recurrence of midazolam’s sedative and autonomic effects as the antagonistic action of flumazenil diminished. Given flumazenil’s shorter half-life relative to midazolam, resedation and associated cardiovascular depression may occur after apparent initial recovery. Benzodiazepines can blunt sympathetic tone and enhance vagal predominance, which may manifest as bradycardia and hypotension, particularly in older adults with increased sensitivity to sedatives. Rather than representing a direct adverse effect of flumazenil, the delayed bradycardia in this case is more consistent with residual benzodiazepine activity following reversal. This case highlights the importance of continued postoperative monitoring after benzodiazepine reversal, especially in elderly patients. Clinicians should anticipate the possibility of recurrent sedation and associated hemodynamic changes, and be prepared to intervene promptly. Early recognition and treatment with anticholinergic therapy, such as atropine, can result in rapid clinical improvement and prevent further instability.