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Lydia QN Liew,1 Lawrence SC Law,1 Edwin Seet,2 Fabio Di Piazza,3 Katherine E Liu,4 Ming Ann Sim,1 Vanessa TY Chua,1 Toby N Weingarten,5 Ashish K Khanna,6 Lian Kah Ti1,2 On behalf of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) Group Investigators1National University Hospital, Singapore, Singapore; 2National University of Singapore, Yong Loo Lin School of Medicine, Singapore; 3Medtronic Core Clinical Solutions, Study and Scientific Solutions, Rome, Italy; 4Patient Monitoring Clinical Research, Medtronic, Minneapolis, MN, USA; 5Departments of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; 6Wake Forest School of Medicine, Winston-Salem, North Carolina, US & Outcomes Research Consortium, Cleveland, OH, USACorrespondence: Lian Kah Ti, Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore, Tel +65 6779 5555, Email lian_kah_ti@nuhs.edu.sgPurpose: Postoperative monitoring of respiratory status on general care wards typically consists of intermittent checks of oxyhemoglobin saturation and respiratory rate, allowing substantial unmonitored time for severe opioid induced respiratory depression (RD) to develop unnoticed. Oxygen desaturation index (ODI) can be computed solely by continuous pulse oximetry monitoring. In this post-hoc analysis, we evaluate whether nocturnal ODI correlates with RD.Patients and Methods: The PRODIGY trial (NCT02811302) was a multinational study conducted where adult patients receiving parenteral opioids on the general care floor were continuously monitored by blinded pulse oximetry and capnography monitoring to detect episodes of RD. An RD episode was defined as: respiratory rate ≤ 5 breaths/min (bpm) for ≥ 3 minutes, oxygen saturation (SpO2) ≤ 85% for ≥ 3 minutes, end-tidal carbon dioxide (EtCO2) ≤ 15 or ≥ 60 mm Hg for ≥ 3 minutes, apnea episode lasting > 30 seconds, or any respiratory opioid-related adverse event. Data were used to calculate nocturnal (00:00 &boxh; 06:00) ODI4% based on desaturation episodes (4% decrease from mean oxyhemoglobin saturation in the past 120 seconds, lasting ≥ 10 seconds). Continuous monitoring began after a patient received parenteral opioids, allowing identification of potential RD and ODI4% episodes during opioid therapy. The average number of ODI4% episodes (≥ 1, ≥ 5, ≥ 10, ≥ 15 episodes/hour) were analyzed. Logistic regression and area under the receiver operating characteristic curve (AUC) were computed.Results: A final cohort of 1072 (out of 1335) patients had sufficient data, with 76% (N=817/1072) having ≥ 1 episode of ODI4%. Multivariable logistic regression showed that ODI4% was strongly associated with RD, with greater risk for higher ODI4% scores: ≥ 5 episodes/hour odds ratio 2.59 (95% CI 1.72– 3.89, p< 0.0001); ≥ 10 episodes/hour 3.39 (95% CI 1.80– 6.39, p=0.0002); ≥ 15 episodes/hour 4.71 (95% CI 1.93– 11.47, p=0.0006).There was no significant association between ODI4% and respiratory adverse events.Conclusion: Nocturnal ODI4% was highly correlated with RD among hospitalized patients receiving parenteral opioids. Patients with a high ODI4%, especially with ≥ 15 episodes/hour, are more likely to experience RD and should be evaluated for the need of closer monitoring after opioid administration.Keywords: opioids, oxygen desaturation index, respiratory depression, sleep apnea