Prediction of Opioid-Induced Respiratory Depression on Inpatient Wards Using Continuous Capnography and Oximetry: An International Prospective, Observational Trial
Authors: Khanna Ashish K. , Bergese Sergio D. , Jungquist Carla R. , Morimatsu Hiroshi , Uezono Shoichi , Lee Simon , Ti Lian Kah , Urman Richard D. , McIntyre Robert , Tornero Carlos , Dahan Albert , Saager Leif , Weingarten Toby N. , Wittmann Maria , Auckley Dennis , Brazzi Luca , Le Guen Morgan , Soto Roy , Schramm Frank , Ayad Sabry , Kaw Roop , Di Stefano Paola , Sessler Daniel I. , Uribe Alberto , Moll Vanessa , Dempsey Susan J. , Buhre Wolfgang , Overdyk Frank J. ,   on behalf of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) Group Collaborators
Published: April 2020

BACKGROUND:
Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring.

METHODS:
PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and Asia. Vital signs were intermittently monitored per standard of care. A total of 1335 patients receiving parenteral opioids and continuously monitored on the general care floor were included in the analysis. A respiratory depression episode was defined as respiratory rate ≤5 breaths/min (bpm), oxygen saturation ≤85%, or end-tidal carbon dioxide ≤15 or ≥60 mm Hg for ≥3 minutes; apnea episode lasting >30 seconds; or any respiratory opioid-related adverse event. A risk prediction tool was derived using a multivariable logistic regression model of 46 a priori defined risk factors with stepwise selection and was internally validated by bootstrapping.

RESULTS:
One or more respiratory depression episodes were detected in 614 (46%) of 1335 general care floor patients (43% male; mean age, 58 ± 14 years) continuously monitored for a median of 24 hours (interquartile range [IQR], 17–26). A multivariable respiratory depression prediction model with area under the curve of 0.740 was developed using 5 independent variables: age ≥60 (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. The PRODIGY risk prediction tool showed significant separation between patients with and without respiratory depression (P < .001) and an odds ratio of 6.07 (95% confidence interval [CI], 4.44–8.30; P < .001) between the high- and low-risk groups. Compared to patients without respiratory depression episodes, mean hospital length of stay was 3 days longer in patients with ≥1 respiratory depression episode (10.5 ± 10.8 vs 7.7 ± 7.8 days; P < .0001) identified using continuous oximetry and capnography monitoring.

CONCLUSIONS:
A PRODIGY risk prediction model, derived from continuous oximetry and capnography, accurately predicts respiratory depression episodes in patients receiving opioids on the general care floor. Implementation of the PRODIGY score to determine the need for continuous monitoring may be a first step to reduce the incidence and consequences of respiratory compromise in patients receiving opioids on the general care floor.