Median effective dose of fospropofol disodium for suppression of the cough reflex during tracheostomy tube exchange in patients with disorders of consciousness receiving fixed-dose sufentanil.

OBJECTIVE

The aim of this study was to determine the median effective dose (ED50) and 95% effective dose (ED95) of fospropofol disodium required to suppress the cough response during tracheostomy tube exchange in patients with disorders of consciousness receiving a background dose of sufentanil 5 μg/kg.

METHODS

Twenty-nine patients with disorders of consciousness requiring general anesthesia for surgical procedures were enrolled. All had a pre-existing tracheostomy and were classified as ASA IV. General anesthesia was induced with intravenous sufentanil 5 μg/kg, followed by administration of fospropofol disodium using a sequential allocation design. A cough response graded as III or higher was defined as a positive response. The study was terminated after the occurrence of 10 effective crossover points. Probit regression analysis was used to estimate the ED50, ED95, and corresponding 95% confidence intervals. Mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) was recorded before anesthesia induction (T0), before tracheostomy tube exchange (T1), and immediately after tube exchange (T2). The incidences of hypotension and apnea were also recorded.

RESULTS

The ED50 and ED95 of fospropofol disodium for suppression of the cough response were 9.41 mg/kg (95% CI, 8.08-10.64 mg/kg) and 12.66 mg/kg (95% CI, 11.01-26.05 mg/kg), respectively. Repeated-measures analysis of variance demonstrated significant time-dependent effects on MAP and RR (both p < 0.001), whereas HR demonstrated no significant changes over time (p > 0.05). Compared with T0, MAP and RR were significantly reduced at T1 and T2 (both p < 0.01), with no statistically significant differences observed between T1 and T2 (both p > 0.05). The incidence rates of hypotension, apnea, and oxygen desaturation were higher in the 12 mg/kg group than in the 10 mg/kg group (66.67% vs. 15.38%, 50.00% vs. 7.69%, and 16.67% vs. 0%, respectively).

CONCLUSION

In the presence of sufentanil 5 μg/kg, the ED50 and ED95 of fospropofol disodium for suppressing the cough reflex during tracheostomy tube exchange in patients with disorders of consciousness were 9.41 mg/kg (95% CI, 8.08-10.64 mg/kg) and 12.66 mg/kg (95% CI, 11.01-26.05 mg/kg), respectively. The suppressive effect was dose-dependent; however, higher doses were associated with increased risks of hypotension and apnea, indicating the need for individualized dose titration.