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Addressing Respiratory Compromise with the PRODIGY Study

It can be hard to predict which patients receiving opioids may be at risk for respiratory compromise or depression.1  The Prediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial provides clinicians with a risk prediction tool based on continuous, blinded oximetry and capnography data. It predicts the likelihood of respiratory depression in patients receiving opioids on the general care/medical-surgical floor.2

In this blog post, we’ll provide you with a summary of the results from the PRODIGY trial. You’ll learn:

  • Why respiratory compromise is often unrecognized and tends to be associated with poor outcomes
  • The methodology and results of the PRODIGY study
  • How respiratory depression impacts mean hospital length of stay and propensity-weighted healthcare costs


In low-acuity settings like the general care floor, patients receive less monitoring. Consequently, it may take clinicians longer to recognize deteriorating respiratory function compared to higher acuity environments.3 For example, a retrospective review of rapid response team calls found that 50 percent of respiratory distress events on the floor had a mean response delay of 12 hours.3 Likewise, a prospective blind study of more than 800 postoperative patients receiving continuous SpO2 monitoring found that standard-of-care spot check monitoring missed 90 percent of prolonged hypoxia events (SpO2 < 90 percent for greater than one hour).4

These unrecognized respiratory compromise events can lead to severe consequences. A recent registry study found that among 44,551 patients suffering acute respiratory compromise events, mortality is nearly 40 percent.5

The impact of respiratory compromise may be mitigated with continuous monitoring of respiratory function.  The implementation of continuous capnography monitoring in this setting is associated with a reduction in severe opioid-related adverse events and fewer ICU transfers.6,7




The PRODIGY trial methodology

PRODIGY is a prospective, multicenter, international cohort study that included 1,495 patients enrolled, with data from 1,335 patients analyzed, across16 centers in seven countries. All participating patients received opioids on the general care floor.2 Participants were continuously monitored for respiratory depression using ‘blinded’, non-alarming continuous capnography and oximetry monitoring on the general care floor.  Respiratory depression was defined by one or more of the following:

  • etCO2 ≤ 15 or ≥ 60 mmHg for ≥ 3 minutes
  • RR ≤ 5 breaths for ≥ 3 minutes
  • SpO2 ≤ 85% for ≥ 3 minutes
  • Apnea episode lasting > 30 seconds
  • Any respiratory Opioid-Related Adverse Event (rORADE)

Researchers then developed and validated a risk prediction tool that used significant predictors of respiratory depression derived from a multivariate model.

The PRODIGY trial results

  • Of 1,335 general care floor patients receiving opioids, 46 percent suffered one or more episode of respiratory depression
  • 1.3 percent of patients with respiratory depression progressed to more serious adverse events
  • Patients with one or more respiratory depression episodes had greater mean hospital length of stay and greater mean hospital costs (Figure 1)
  • Five risk factors were independently associated with respiratory depression in the multivariate risk:
  • Age ≥60 (in decades)
  • Sex (M)
  • Opioid naivety
  • Sleep disordered breathing
  • Chronic heart failure
  • The PRODIGY risk prediction tool (Table 1) identified 74 percent of patients with respiratory depression.
  • There was significant distinction in the incidence of RD in the low, intermediate, and high-risk PRODIGY risk prediction tool groups (Table 2).
  • Patients with ≥ 1 respiratory depression episode were more likely to experience an adverse event (AE) that required action.
  • Relative risk of 1.36 for AE requiring prolonged hospitalization
  • Relative risk of 2.46 for AE requiring rescue, including rapid response team activation

Related: Who should you monitor for opioid-induced respiratory depression? Read our blog for a summary of Dr. Ashish Khanna’s interview with the Society of Critical Care Medicine.

Figure 1. Mean hospital length of stay and propensity-weighted healthcare costs in patients with and without ≥1 respiratory depression episode2
Figure 1. Mean hospital length of stay and propensity-weighted healthcare costs in patients with and without ≥1 respiratory depression episode2


Table 1.  The PRODIGY Risk Prediction tool2


Table 2. Relationship between the PRODIGY risk prediction tool and percentage of patients with respiratory depression2

Detection and speedy intervention are key in reducing incidents of respiratory compromise.3,6,7 The PRODIGY risk prediction tool can help clinicians determine if the patient has low, moderate, or high risk of experiencing a respiratory depression episode and personalize monitoring to patient-specific need, which may improve safety in patients receiving opioids in low acuity environments.

Discover more at

Related: Access more information on the PRODIGY study.


1. Belcher AW, Khanna AK, Leung S, et al. Long-Acting Patient-Controlled Opioids Are Not Associated With More Postoperative Hypoxemia Than Short-Acting Patient-Controlled Opioids After Noncardiac Surgery: A Cohort Analysis. Anesth Analg. 2016;123(6):1471–1479. 
2. Khanna AK, Bergese S, Jungquist C, et al. Prediction of opioid-induced respiratory depression on inpatient wards using continuous capnography and oximetry: an international prospective, observational trial. Anesthesiology. 2020;TBD.
3. Quach JL, Downey AW, Haase M, Haase-Fielitz A, Jones D, Bellomo R. Characteristics and outcomes of patients receiving a medical emergency team review for respiratory distress or hypotension. J Crit Care. 2008;23(3):325–331. 
4. Sun Z, Sun Z, Sessler DI, Dalton JE, et al. Postoperative hypoxemia is common and persistent: a prospective blinded observational study. Anesth Analg. 2015;121(3):709–715.
5. Andersen LW, Berg KM, Chase M, Cocchi MN, Massaro J, Donnino MW. Acute respiratory compromise on inpatient wards in the United States: Incidence, outcomes, and factors associated with in-hospital mortality. Resuscitation. 2016;105:123–129.
6. Steele T, Eidem L, Bond J. Impact of Adoption of Smart Pump System With Continuous Capnography Monitoring on Opioid-Related Adverse Event Rates: Experience From a Tertiary Care Hospital [published online ahead of print, 2019 Mar 4]. J Patient Saf. 2019;10. 
7. Stites M, Surprise J, McNiel J, Northrop D, De Ruyter M. Continuous Capnography Reduces the Incidence of Opioid-Induced Respiratory Rescue by Hospital Rapid Resuscitation Team [published online ahead of print, 2017 Jul 20]. J Patient Saf. 2017;10.

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About the Author

Scott Stoneburner is a Principle Medical Affairs Specialist who focuses on disseminating evidence-based information for Medtronic’s Respiratory and Monitoring Solutions franchise.

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