Combined use of etomidate and propofol reduce the duration of apnea vs propofol along in patients undergoing hysteroscopy: a randomised double-blind trial

Technical Summary: Combined Use of Etomidate and Propofol in Hysteroscopy

Problem Statement
Outpatient hysteroscopy procedures frequently utilize deep intravenous sedation, with propofol being the standard agent. However, high-dose propofol administration is associated with significant risks, including vasodilation, hypotension, and respiratory compromise, specifically respiratory suppression and apnea. While etomidate offers minimal cardiovascular and respiratory depression, its standalone use carries risks of muscle tremors, rigidity, and postoperative nausea. The authors posit that a combination of etomidate and propofol may mitigate the respiratory depression associated with propofol monotherapy while maintaining adequate sedation depth, thereby improving patient safety during hysteroscopy.

Methodology
The study was a prospective, randomized, double-blind, parallel-group trial conducted at Renji Hospital, Shanghai, between September 2022 and December 2023.

• Participants: 365 women (aged 18–65) scheduled for elective hysteroscopy under intravenous sedation. Exclusion criteria included upper airway abnormalities, severe cardiac/hepatic/renal disease, preoperative respiratory insufficiency, high aspiration risk, and allergies to study drugs.
• Intervention: Patients were randomized (1:1) into two groups:
  • Combination Group (n=182): Received 10 mg (5 mL) of 0.2% etomidate combined with 100 mg (10 mL) of 1% propofol.
  • Control Group (n=183): Received 150 mg (15 mL) of 1% propofol.
  • Both groups received a total volume of 15 mL and were pre-medicated with sufentanil (0.15 µg/kg).
• Protocol: Anesthesia was induced with a 0.2 mL/kg bolus of the trial drug over 10 seconds, with additional dosing (0.1 mL/kg) permitted for signs of insufficient anesthesia. Respiratory status was monitored using microstream capnography to quantify apnea episodes and end-tidal CO2. Hemodynamics and oxygenation (SpO2) were continuously monitored.
• Outcomes:
  • Co-primary outcomes: Non-inferiority of sedation efficacy (defined by a Modified Observer's Assessment of Alertness and Sedation [MOAA/S] score of 0–2) and superiority in reducing apnea duration.
  • Secondary outcomes: Incidence of hypoxemia, need for manual ventilation, hemodynamic stability, and adverse events (e.g., myoclonus, PONV).
• Statistical Analysis: The study was powered to detect non-inferiority in sedation efficacy with a 7% margin and superiority in apnea duration. Analysis was performed on an intention-to-treat basis.

Key Results

• Sedation Efficacy: The combination regimen demonstrated non-inferiority to propofol alone. All patients in both groups achieved adequate sedation (MOAA/S 0–2), with the 95% confidence interval for the difference falling well within the non-inferiority margin.
• Apnea Duration: The combination group exhibited a significantly shorter duration of apnea compared to the propofol-only group (73 seconds vs. 116 seconds; mean difference -43 s; P < 0.001).
• Respiratory Safety:
  • The incidence of apnea was lower in the combination group (78%) compared to the propofol group (91%).
  • Severe hypoxemia (SpO2 ≤ 90%) occurred significantly less frequently in the combination group (14%) versus the propofol group (34%; P < 0.001).
  • The need for manual mask ventilation was significantly reduced in the combination group (17%) compared to the propofol group (37%; P < 0.0001).
• Hemodynamics: Hemodynamic responses (blood pressure and heart rate) were similar between groups, though the combination group required fewer vasopressors (1 patient vs. 6 patients).
• Adverse Events: Intraoperative hypotension rates were comparable. Transient myoclonus occurred in 4 patients (2%) in the combination group but was mild and self-limiting. No serious adverse events were observed.

Significance and Claims
The authors conclude that the combination of etomidate and propofol provides sedative efficacy comparable to propofol monotherapy for hysteroscopy while significantly shortening the duration of apnea induced by intravenous sedatives. The study claims that this regimen offers a superior safety profile regarding respiratory depression, evidenced by a 20% absolute reduction in severe hypoxia and a roughly 42-second reduction in apnea duration. The authors suggest that by allowing for a lower total propofol dose, the addition of etomidate effectively reduces the risk of respiratory compromise without compromising the depth of anesthesia required for the procedure.

Limitations Noted by Authors
The paper acknowledges several limitations: the single-center nature of the study limits generalizability; the lack of electroencephalographic monitoring (e.g., BIS) meant sedation depth was inferred via clinical scales rather than objective measures; and formal recovery time data were not recorded, though all patients completed a standard 60-minute PACU observation.