Comparing Benzodiazepines-morphine-induced Respiratory Depression by Analyzing Respiratory Pattern in Rats

Background and Aim: Opioid and benzodiazepine family drugs are concurrently used in various patients. Considering the respiratory depressant effects of both classes, in this study, we investigated the effect of coadministration of morphine and several widely used benzodiazepines in the clinic on the rate of respiratory depression in rats. Methods & Materials: Seventy adult male Wistar rats were randomly divided into 10 groups; morphine, midazolam, diazepam, lorazepam, alprazolam, morphine-midazolam, morphine-diazepam, morphine-lorazepam, and morphine-alprazolam. Respiration signal was recorded using whole-body plethysmography 15 minutes after the intraperitoneal injection of the drugs. The respiratory pattern was examined using several parameters; the mean value of inter-breath interval and the respiratory rate, as well as the coefficient of variation and sample entropy analysis of inter-breath interval. Ethical Considerations: This study was approved by the Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1397.327). Results: Analyzing respiratory data revealed that injecting the anxiolytic dose of alprazolam, and the combination of morphine-alprazolam and morphine-midazolam, altered the respiratory pattern. Such changes were associated with a decrease in the number of breaths and an increase in the inter-breath interval in the explored test animals, compared with the controls. The obtained data also indicated that morphine-midazolam injection increased the variability of the breathing pattern; such an alternation was associated with increased irregularity and decreased coefficient of variation of the inter-breath interval. Conclusion: The present research results suggested that the short-term injection of morphine-midazolam changes the respiratory pattern more severely than morphine combined with other benzodiazepines.