Plethysmography for the assessment of opioid-induced respiratory depression

Using emka & SCIREQ plethysmography chambers and IOX software, the authors developed a rat model of acute and chronic fentanyl and heroin I.V. administration. Surgical catheter implantation and the use of Instech swivels, integrated with the plethysmography chambers, allowed for ventilatory parameters to be recorded, without removing subjects from the chambers for drug administration. The paper presents minute ventilation, tidal volume, inspiratory time, peak inspiratory flow, and apneic pause (expiratory time/relaxation time) – 1] data from a series of experiments that examine dose-responses, intermittent acute administration, and chronic administration, in both male and female subjects.

Respiratory depression is a well-known consequence of both heroin and fentanyl, which the dose-response experiments capture, demonstrating a more sustained effect with heroin over fentanyl (see figure 1).

No tolerance was observed with intermittent acute administration; however chronic administration of fentanyl produced a subsequently shortened respiratory depression to both heroin and fentanyl (a tolerance/ cross-tolerance effect), an effect which persisted in males only during withdrawal (see figure 2).

This study provides both an extremely well-constructed study design for the assessment opioid-induced respiratory depression and a compelling, in-depth analysis of plethysmography data. Models and experimental data, such as those presented in this paper will be critical to developing the tools required to address the on-going opioid epidemic.