Low-Dose Propofol, Ketamine, and Their Combination for the Prevention of Post-Extubation Cough and Laryngospasm in Patients Undergoing Gynecologic Laparotomy: A Randomized Controlled Trial
Year: 2026
Type: preprint
Abstract: Background Coughing and laryngospasm during emergence from general anesthesia are common and may be particularly harmful after open abdominal surgery. Low-dose propofol and ketamine attenuate airway reflexes through different mechanisms, but their comparative and combined efficacy in a homogeneous surgical population remains incompletely defined. We compared low-dose propofol, ketamine, and their combination with control for preventing post-extubation cough and laryngospasm in women undergoing gynecologic oncologic laparotomy. Methods In this prospective, randomized, double-blind, placebo-controlled trial, 169 women (of 176 screened) undergoing elective gynecologic oncologic laparotomy were randomly assigned (1:1:1:1) to intravenous saline (control, n = 42), propofol 0.25 mg/kg (n = 41), ketamine 0.25 mg/kg (n = 43), or propofol–ketamine 0.25 mg/kg each (n = 43) immediately before extubation. The primary outcome was cough incidence within 2 minutes after extubation; the secondary outcome was laryngospasm. Intention-to-treat risk ratios (RRs) with 95% confidence intervals (CIs) were calculated versus control, with Holm-adjusted pairwise comparisons when the overall test was significant. Results Cough incidence differed significantly among groups (control, 69.0%; propofol, 43.9%; ketamine, 55.8%; propofol–ketamine, 25.6%; χ²=17.41, P < 0.001). After adjustment, only the combination remained significantly superior to control (RR, 0.37; 95% CI, 0.21–0.64; adjusted P < 0.001) and to ketamine alone (RR, 0.46; 95% CI, 0.26–0.81; adjusted P = 0.042); reductions with propofol (RR, 0.64) and ketamine (RR, 0.81) alone were no longer significant versus control after adjustment. Laryngospasm was infrequent and similar among groups (4.7–11.9%; P = 0.688), with no reintubations and similarly infrequent peri-extubation adverse events overall. Conclusions Low-dose propofol–ketamine administered immediately before extubation reduced post-extubation cough more effectively than control and than ketamine alone, without a significant effect on laryngospasm, in women undergoing gynecologic oncologic laparotomy. Adequately powered, multicenter trials with factorial designs are needed to define dose–response relationships, determine whether this effect is additive or synergistic, and establish its impact on patient-centered outcomes. Clinical trial registration: The trial was Retrospectively registered in the Iranian Registry of Clinical Trials (IRCT) under registration number IRCT20251215068344N1 on 18/07/2026.
Source: Research Square
Authors: Nasim Shamsa, Nazli Karami, Danial Hashemi
Institution: Urmia University of Medical Sciences
Language: English
Subfield: Anesthesiology and Pain Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225758612