Continuous Monitoring Detected Respiratory Depressive Episodes in Proximity to Adverse Respiratory Events During the PRODIGY Trial

Abstract

Purpose: The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial was a multicenter prospective trial conducted to develop a risk prediction score for opioid-induced respiratory depressive (OIRD) episodes. Several subjects in the PRODIGY trial developed critical respiratory depressive events, which were qualified as reportable adverse events (AEs). In this study, we determine whether those patients also had an episode of OIRD as detected by continuous capnography and pulse oximetry leading up to the critical clinical event.

Methods: Blinded capnography and pulse oximetry data from PRODIGY patients who had critical respiratory depressive AE were reviewed. The occurrence and timing of OIRD episodes were recorded in relationship to the AE.

Results: Of the 1335 subjects in PRODIGY, 7 patients had 8 reportable pulmonary AE and 187 OIRDs (150 apnea episodes, 14 bradypnea episodes, 23 hypoxic episodes) with median 12 (5-19.5) OIRDs per patient. Five patients were monitored before the AE, and multiple preceding OIRD episodes were detected. One patient had 2 AE, the first (hypoxemia) was recognized upon application of pulse oximetry. This patient subsequently had multiple OIRDs until the second AE occurred (somnolence requiring naloxone administration). Another patient's AE (hypotension and bradypnea) was recognized upon monitor application and subsequently had many OIRD episodes.

Conclusions: In the PRODIGY trial, patients who had a pulmonary AE had multiple preceding OIRDs detected by continuous capnography and pulse oximetry. When monitoring was initiated before the AE, numerous OIRDs, mostly apneic episodes preceded AE, suggesting continuous monitoring of both ventilation and oxygenation may allow for early detection and possible prediction of future clinical decompensation.

Trial registration: ClinicalTrials.gov NCT02811302.

Conflict of interest statement

T.N.W. has received consulting fees from Medtronic and Merck. A.K.K. has received consulting fees from Medtronic, Merck, and Edwards Lifesciences. The other authors disclose no conflict of interest.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1

Observed respiratory depressive episodes from continuous capnography and pulse oximetry in patient 2. The top panel is expired carbon dioxide and blue dashed lines represent apneic episode alarms. The bottom panel depicts oxyhemoglobin saturation in red and heart rate in green. Single arrows show apneic episodes before recording of the AE. Bidirectional arrow shows the apneic episode with corresponding hypoxemia at the time of the recorded AE.

FIGURE 2

Observed hypoxemia in patient 5 which triggered the reporting of an AE for hypoxemia. The top panel is expired carbon dioxide and the bottom panel depicts oxyhemoglobin saturation in red and heart rate in green. The red dashed line represents a hypoxemia episode alarm.