Opioid overdoses have become an alarming public health crisis; according to the WHO, there were 480,000 opioid-related deaths worldwide in 2019, with 150,000 of those deaths being opioid overdoses. Timely administration of opioid reversal agents is paramount to saving lives and mitigating the devastating effects of opioid overdose. While overdoses in victims of the opioid crisis is the primary concern of public health efforts, reversing opioids is also sometimes necessary in clinical settings. 

The opioid reversal agent Naloxone works by blocking opioid receptors in the brain¹. Because it has a stronger affinity to opioid receptors than opioids, it displaces opioids on those receptors, and rapidly reverses the associated life-threatening effects¹. Naloxone is available in the intranasal, intramuscular, and intravenous forms, with intranasal naloxone now being available over the counter¹. This legislative win for harm reduction activists allows for opioid-overdoses happening in the community to be reversed quickly even without a healthcare professional present.  

In clinical settings, one common indication for reversing opioids is respiratory depression. Patients may receive opioids for pain relief and anesthesia. While opioid administration in clinical settings is tightly controlled, patients in rare cases may experience stronger than expected effects leading to respiratory depression. In one meta-analysis of postoperative patients receiving morphine intravenously, intramuscularly and/or via PCA pump, the incidence of opioid-induced respiratory depression was as high as 18%¹.  

One rare complication with using naloxone for reversing opioids in clinical settings is that it has a shorter half-life than commonly used opioids, and thus once the naloxone is metabolized, the patient may have a recurrence of symptoms¹. One potential solution to this is a continuous naloxone drip³. This has been studied in postoperative patients who received morphine, sufentanil or fentanyl, and was found to be a safe bridge to extubation in those patients³. Another potential strategy is providing naloxone boluses on sliding scale dosing to meet respiratory criteria for extubation while ensuring adequate pain relief¹. While both strategies are safe and effective, they require close attention from skilled nursing staff, who may not always be available in post-anesthesia care units¹.  

Opioid oversedation is a related serious adverse effect to respiratory depression that can lead to death and severe brain damage². It’s highly preventable, especially with appropriate monitoring of opioid administration and symptomatic effects². However, as mentioned above, appropriate monitoring can be difficult due to staffing constraints, especially in larger volume settings². Thus, there have been some efforts to create prediction models for patients who might be at higher risk of oversedation².  

The PRODIGY trial developed a five-variable tool using monitoring data from capnography and pulse oximetry for patients receiving parenteral opioids². Another risk assessment tool using national cohort data from the United States has been validated for risk of oversedation and opioid-related respiratory depression for patients in the outpatient setting with prescription opioids². One paper published in the British Medical Journal attempted to create a prediction tool that could be used for all kinds of patients using all types of opioids². They used data from an acute care hospital in North Texas that spanned two years and collected data from all adult patients who received at least one opioid during their stay². They found that the strongest risk factor for oversedation was concurrent administrations of other sedative medications². Other risk factors include female sex, older age, a diagnosis of COPD, and evidence of liver insufficiency, renal insufficiency, sleep apnea or currently undergoing surgery². With these risk factors in mind, as well as data from the more focused trials, large healthcare facilities can identify higher risk patients to receive more intensive monitoring².  

Overall, opioid use in clinical settings is a careful balancing act. While they are essential tools for pain management, patients on them, and especially higher risk patients, should be monitored closely for signs of adverse events. Members of the surgical and anesthesia team must be trained in reversing opioids to ensure patient safety in clinical settings. 

References 

1. Dahan A, Aarts L, Smith TW. Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression. Anesthesiology 2010; 112:226–238 doi: https://doi.org/10.1097/ALN.0b013e3181c38c25 

2. Garrett J, Vanston A, Ogola G et al. Predicting opioid-induced oversedation in hospitalized patients: a multicentre observational study. BMJ Open 2021; 11:e051663. doi: 10.1136/bmjopen-2021-051663 

3. Shupak RC, Harp JR. Comparison between high-dose sufentanil-oxygen and high-dose fentanyl-oxygen for neuroanaesthesia. Br J Anaesth. 1985 Apr;57(4):375-81. doi: 10.1093/bja/57.4.375. PMID: 3157396.