0467 Effect of Hypoxia on Ventilatory Responsiveness in Opioid-Related Sleep Disordered Breathing

Abstract Introduction Ventilatory control mechanisms mediating opioid-associated sleep disordered breathing (SDB) are unclear, with reduced hypoxic ventilatory response (HVR) observed acutely with opioids, but increased HVR with chronic methadone use. Increased chemoresponsiveness may contribute to breathing instability during sleep. Aim: Determine the effects of chronic oral prescription opioids on HVR in individuals with opioid-associated SDB. Hypothesis: Compared to controls without opioid use, individuals with chronic prescription opioids-associated SDB will have increased HVR during wakefulness. Methods We studied 5 males on prescription opioids with SDB (age: 55±15 years, BMI: 33±7 kg/m2, apnea hypopnea index (AHI): 30±24/hr; CAI 3±6/hr, morphine equivalent dose: 31±12 mg , serum opiate levels: 23±22 ng/ml), and 5 control males with SDB, not on opioids, (age: 48±11 years, BMI: 28±2 kg/m2, AHI 37±15/hr, CAI 0.2±0.5/hr; urine drug screen negative for opioids). Opioid-SDB and controls underwent multiple trials with exposure to 2-minute episodes of isocapnic hypoxia (Hypoxia PetO2: 5-7%), each trial interspersed with room air, during wakefulness. Isocapnia was maintained by bleeding in CO2. Number of hypoxia (Hx) trials: opioid-SDB: 8.2±1.3; controls 7.0±0.7. All ventilatory parameters were analyzed breath by breath. For each trial, the ventilatory parameters during hypoxic exposure were compared with the room air baseline period immediately preceding the exposure. HVR was calculated as the change in minute ventilation during nadir hypoxia compared to control breaths for a corresponding change in PetO2. Results Minute ventilation (VI) during hypoxia trial was 99.1±28.5% of baseline Vi in opioid-SDB vs. 105±16% baseline Vi in control participants. The coefficient of variation of Vi was 29% in opioid-SDB vs. 15% in control-SDB (p=0.05). Opioid-SDB: PetCO2 37±4 mmHg at baseline and 37±3 mmHg during Hx trials; Control: PetCO2 37±4 mmHg at baseline and 41±3 during Hx trials. Opioid-SDB: PetO2 100±6 mmHg at baseline and 33±6 mmHg during Hx trials; Control: PetO2 101±5 mmHg at baseline and 46±7 during Hx trials. HVR: 0.6±2.4 L/min/mmHg vs. 1.4±4.2 L/min/mmHg in opioid-SDB vs. controls. Conclusion HVR tended to be reduced in opioid-SDB vs. controls during wakefulness. There was variability in minute ventilation in opioid users. Additional studies in a larger sample are required to delineate hypoxic ventilatory responsiveness in opioid-SDB. Support (if any) VHA CSR&D:1I01CX001938-02A0