British journal of anaesthesia · 2025
Effect of midazolam co-administered with oxycodone on ventilation: a randomised clinical trial in healthy volunteers.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Gershuny Victoria, Florian Jeffry, van der Schrier Rutger, Davis Michael C, Salcedo Pablo, Wang Celine, Burkhart Keith, Prentice Kristin, Shah Aanchal, Racz Rebecca, Patel Vikram, Matta Murali, Ismaiel Omnia, Boughner Rodney, Ford Kevin A, Rouse Rodney, Stone Marc, Sanabria Carlos, Dahan Albert, Strauss David G
Аннотация
BACKGROUND: Benzodiazepines can exacerbate opioid-induced respiratory depression by furthering the decrease in central respiratory drive and causing loss of upper airway patency potentially leading to airway obstruction. This study aimed to determine if co-administration of benzodiazepines and opioids significantly decreases hypercapnic ventilation compared with opioids alone.
METHODS: We conducted a randomised, double-blind, four-period crossover trial in 20 healthy participants to assess whether i.v. midazolam (0.0375 mg kg-1 in the first five participants; 0.075 mg kg-1 in 15 participants) plus oral oxycodone (10 mg), compared with oxycodone alone, decreases minute ventilation at an end-tidal carbon dioxide (Pco2) of 7.3 kPa using modified Read rebreathing methodology.
RESULTS: Midazolam administered with oxycodone, compared with oxycodone alone, did not significantly decrease minute ventilation at an end-tidal Pco2 of 7.3 kPa (23.5 vs 25.2 L min-1; mean difference -1.7 L min-1, one-sided 95% confidence interval -∞ to 1.6; P=0.21). However, midazolam plus oxycodone increased resting end-tidal Pco2 compared with oxycodone alone (5.8 vs 5.6 kPa; mean difference 0.2 kPa, 95% confidence interval 0.0-0.4). Nine of 15 (60%) participants fell asleep or snored on midazolam plus oxycodone, compared with 0 of 15 (0%) on oxycodone alone.
CONCLUSIONS: Midazolam co-administered with oxycodone did not decrease hypercapnic ventilation, compared with oxycodone alone, but did affect tidal volume, ventilatory frequency, and resting end-tidal Pco2. These findings support the hypothesis that benzodiazepines influence ventilation by inducing relaxation of the respiratory muscles and highlight the need for additional investigations to elucidate the potential for upper airway obstruction when benzodiazepines and opioids are co-administered.
CLINICAL TRIAL REGISTRATION: NCT04310579.
METHODS: We conducted a randomised, double-blind, four-period crossover trial in 20 healthy participants to assess whether i.v. midazolam (0.0375 mg kg-1 in the first five participants; 0.075 mg kg-1 in 15 participants) plus oral oxycodone (10 mg), compared with oxycodone alone, decreases minute ventilation at an end-tidal carbon dioxide (Pco2) of 7.3 kPa using modified Read rebreathing methodology.
RESULTS: Midazolam administered with oxycodone, compared with oxycodone alone, did not significantly decrease minute ventilation at an end-tidal Pco2 of 7.3 kPa (23.5 vs 25.2 L min-1; mean difference -1.7 L min-1, one-sided 95% confidence interval -∞ to 1.6; P=0.21). However, midazolam plus oxycodone increased resting end-tidal Pco2 compared with oxycodone alone (5.8 vs 5.6 kPa; mean difference 0.2 kPa, 95% confidence interval 0.0-0.4). Nine of 15 (60%) participants fell asleep or snored on midazolam plus oxycodone, compared with 0 of 15 (0%) on oxycodone alone.
CONCLUSIONS: Midazolam co-administered with oxycodone did not decrease hypercapnic ventilation, compared with oxycodone alone, but did affect tidal volume, ventilatory frequency, and resting end-tidal Pco2. These findings support the hypothesis that benzodiazepines influence ventilation by inducing relaxation of the respiratory muscles and highlight the need for additional investigations to elucidate the potential for upper airway obstruction when benzodiazepines and opioids are co-administered.
CLINICAL TRIAL REGISTRATION: NCT04310579.