Identifying Patients At Risk of Opioid-Induced Respiratory Depression: Interview with Dr. Ashish K Khanna

Identifying Patients At Risk of Opioid-Induced Respiratory Depression: Interview with Dr. Ashish K Khanna

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By Michael Wong, JD (Founder/Executive Director, Physician-Patient Alliance for Health & Safety)

Opioid-induced respiratory depression can lead to serious adverse events and even death, in hospitalized patients. In its Sentinel Event Alert #49, titled “Safe use of opioids in hospitals”, the Joint Commission stated, “While opioid use is generally safe for most patients, opioid analgesics may be associated with adverse effects, the most serious effect being respiratory depression, which is generally preceded by sedation.” The alert was retired as of February 2019 and is now addressed in the commission’s pain management standards for hospitals. 

About half of in-hospital cardiorespiratory events occur on the general care floor. Often these events are fatal. Lars W. Andersen, MD (Department of Medicine, Regional Hospital Holstebro, Aarhus University & Department of Emergency Medicine, Beth Israel Deaconess Medical Center) and his colleagues concluded that acute respiratory events are common in inpatient wards in the US and are associated with a mortality rate of almost 40%.

Consequently, identifying the patients who are at risk of opioid-induced respiratory depression will be immensely helpful in preventing these dreaded events. With this goal in mind, Ashish K. Khanna, MD, FCCP, FCCM, FASA (Associate Professor and Vice-Chair of Research; Director, Perioperative Outcomes and Informatics Collaborative; Department of Anesthesiology, Section on Critical Care Medicine, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist) and his colleagues conducted the PRODIGY (PRediction of Opioid-induced Respiratory Depression In Patients Monitored by capnoGraphY) trial. I interviewed Dr. Khanna about the trial.

Image source: https://www.wakehealth.edu/Providers/K/Kumar-Khanna

Tell me about the PRODIGY trial and why it is so important in improving patient safety?

The PRODIGY trial investigated the early detection of patient deterioration using continuous, electronic cardiorespiratory monitoring – pulse oximetry and capnography – with an enrollment target of 1,650 patients at 16 centers in North America, Europe, and Asia. A total of 1,335 patients receiving parenteral opioids on the general care floor were included in the analysis. These patients were continuously monitored with pulse oximetry, which measures a patient’s oxygen saturation level, and with capnography, which measures the amount of (or end-tidal concentration of) the carbon dioxide released at the end of the patient’s expiration. From those measurements, my team and our collaborators in the trial group were able to develop a risk prediction tool for Opioid-Induced Respiratory Depression (OIRD).

What does the PRODIGY risk assessment tool tell us about which patients are most at-risk for opioid-induced respiratory depression?

The PRODIGY risk assessment tool uses five independent variables: age over 60 years of age (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. All of these variables are easily available in the EMR or can be gathered from a thorough history taking and clinical assessment. Importantly, the tool is easy to use, available and can be configured at the bedside by all levels of providers (not just physicians ), and would also be very easily deployable as an actionable alert in the EMR. 

Let’s talk about age and opioid-induced respiratory depression. I’m over 60 years of age. Am I more at risk than a 50-year-old man of suffering from opioid-induced respiratory depression? Or, put another way, am I less at risk of suffering from opioid-induced respiratory depression than an 80-year-old man?

The PRODIGY trial found that advancing age (measured in decades) is a predictor of opioid-induced respiratory depression. This is consistent with other respiratory depression risk prediction models. 

Patients who are more than 60 years old are at a greater risk for opioid-induced respiratory depression. This risk increases significantly in a patient who is in his 80s versus a patient who is in his 60s. For example, with no other PRODIGY risk factors, only having an age > 80 puts a patient at a PRODIGY score of 16 which is the highest risk of OIRD and about 6 times as much as a patient less than 60, and twice as much as a patient between 60-70 with a similar profile. Age-related changes in respiratory physiology and altered opioid pharmacokinetics are most likely contributing to this increased risk.

We assigned point scores for each of the five characteristics ─ age, sex, opioid naivety, sleep-disordered breathing, and chronic heart failure:

Of course, the PRODIGY risk assessment tool is only a guide. It is not an absolute predictor. For example, while a patient’s age over 60 is a good predictor, there have been many instances where teenagers have suffered and even died from opioid-induced respiratory depression.

So, does the PRODIGY risk assessment tool work in “real” life? What has the experience of a hospital using the PRODIGY risk assessment tool?

In January 2019, two hospitals in the Lehigh Valley Health Network started using PRODIGY-guided bedside monitoring of all postoperative patients on the general care floor prescribed parenteral opioids. These patients were monitored with continuous pulse oximetry until at least 9 a.m. on postoperative day 1. Continuous capnography was added in those with sleep-disordered breathing, morbid obesity, neuraxial opioid administration, supplemental oxygen administration, or at the anesthesiologist’s discretion.

The researchers were led by Thomas M. McLoughlin Jr., MD, the chair of anesthesiology at Lehigh Valley Health Network. I am pleased to report that they have not observed a single opioid-induced respiratory depression-related mortality or code blue event in a monitored patient since implementing the PRODIGY risk assessment tool. Other as yet unpublished data and information coming through from academic and non-academic medical centers has been very encouraging and all trends point to the value of improving continuous monitoring for our patients with an increasing emphasis on wireless wearables that are less obtrusive to general post operative rehabilitation. 

What are the biggest impediments to hospitals and healthcare facilities using the PRODIGY risk assessment tool?

Capital costs, in particular the purchase of pulse oximetry and capnography equipment, are factors. In our analysis of the cost-benefit of using continuous pulse oximetry and capnography monitoring of general care floor patients, we found that continuous pulse oximetry and capnography monitoring of high-risk patients is projected to reduce annual hospital costs by $535,531 and cumulative patient length of stay by 103 days. A mere 1.5% reduction in respiratory depression would achieve a break-even point and justify the investment. The probability of cost-saving is ≥ 80% if respiratory depression is decreased by ≥ 17%. 

Expansion of continuous monitoring to high- and intermediate-risk patients, or to all patients, is projected to reach a break-even point when respiratory depression is reduced by 2.5% and 3.5%, respectively, with a ≥ 80% probability of cost savings when respiratory depression decreases by ≥ 27% and ≥ 31%, respectively.

Additionally, learning new processes and changing old habits must be considered. Business experts have identified a number of obstacles to the adoption of new technologies, and healthcare professionals are certainly not immune to such challenges. These obstacles include resistance to change. In other words, doing something new or different can indeed be difficult.

In a recent survey of 5744 anaesthesiologists I did with Frederic Michard, MD, PhD, and his colleagues, we found that “Continuous monitoring of vital signs with wireless sensors is wanted by most anaesthesiologists from university hospitals in Western Europe and in the USA. They believe it may improve patient safety and outcome, but may also be challenging to implement because of cost and connectivity issues.”

What can medical societies and patient safety advocates do to encourage the use of the PRODIGY risk assessment tool?

Medical societies and patient safety advocates like the Physician-Patient Alliance for Health & Safety should encourage adoption and facilitate a better understanding of the use of the PRODIGY risk assessment tool. 

Get to know how the PRODIGY risk assessment tool, become familiar with it and find out how to implement it ─ these are steps healthcare professionals should take to improve patient safety. Dr. Frank Overdyk, who was a co-investigator for the PRODIGY trial, and I will be putting together a continuing medical education course on the patient safety implications and using the PRODIGY risk assessment tool. I would encourage my fellow doctors, nurses, and respiratory therapists to take this course.