The influence of midazolam and nitrous oxide on respiratory depression in laboratory rats

Midazolam in combination with nitrous oxide (N2O) is a commonly used sedative approach for pediatric dental patients. Respiratory morbidity and mortality have been reported with midazolam administration, particularly when used in combination with other drugs in the absence of supplemental oxygen. Thus, the purpose of this investigation was to determine the effect of midazolam alone and in combination with N2O on respiration in laboratory rats by measuring arterial blood gas levels. Sixty-four Sprague-Dawley rats, weighing 250-320 g, were assigned to one of eight groups (eight per group). Groups were allocated based upon the dosage of midazolam administered (0, 1.0, 2.0 or 4.0 mg/kg i.p.) and exposure to N2O/02 (50%/50%) or room air. Arterial blood was obtained from a femoral artery catheter and pH, O2, CO2 (mm Hg), and oxygen saturation (%) were determined. Samples were analyzed using a System 1306 pH/Blood Gas Analyzer. Baseline arterial blood gasses were obtained for each animal and at 15-min intervals following midazolam administration throughout the 45-min experiment. Following midazolam administration, animals were placed into a sealed chamber through which flowed either N2O or room air. Group comparisons demonstrated that: 1) arterial CO2 levels increased in midazolam-exposed animals breathing room air, but not in those exposed to N2O (P < 0.05), and 2) as expected, N2O/O2-exposed animals showed an increase in arterial O2 and a %saturation that was not observed in room air groups (P < 0.01). This investigation demonstrated that coadministration of N2O/O to midazolam-exposed animals did not result in hypercarbia, an early indicator of respiratory depression.