Beyond the Pharmacology: Observation after Opioid Reversal in the ED
By Carson Clay
Case
History
38 yo M with known PMH of PSUD who BIBEMS after a friends called EMS for a presumed overdose.
On the scene, nonresponsive, RR 7, SpO2 75%, pinpoint pupils, given 0.8mg IN naloxone in the field. Per EMS, patient stirred and was more responsive after naloxone and was put on nasal cannula in transit.
Physical Exam
BP 121/71 | Pulse 77 | Temp 37.2 °C (99 °F) (Oral) | Resp 12 | SpO2 96% on 2L NC
Alert and oriented, non-toxic appearing. Speaking in full sentences, intermittently dozing off. GCS 15. RRR, no murmur. Breath sounds clear and equal bilaterally, no crackles. Abdomen flat and nontender. No lower extremity edema or tenderness.
ED course
With the patient’s respiratory rate and O2 saturation improved on arrival, weaned off nasal cannula with SpO2 remaining above 95%.
NCHCT negative, CXR without signs of pulmonary edema
Now, 20 minutes after arrival and 30 minutes after naloxone administration, the patient remains alert and oriented but is agitated; yelling and asking to leave, threatening staff.
Clinical question: How long should patients be observed in the emergency department after naloxone administration to reasonably minimize adverse events?
Summary of evidence
This ethical and clinical question is clearly familiar to emergency physicians. A qualitative study that interviewed 59 EM physicians attending an annual ACEP conference, published in the Journal of EM, illuminated the issues:1
Providers were concerned about their ethical responsibility to the patient and legal ramifications of discharging the patient too soon. On the other hand, providers expressed concerns about violating patient autonomy and threatening staff safety by keeping patients under observation in the ED.
While the study was a convenience sample that likely has a bias towards academic-setting EM providers and thus does not fully represent the field, and the qualitative methodology limits statistical analyses, it outlines the problems many providers face in these situations and the underlying need for guidelines
One approach to a clinical solution came in 2000, when the St. Paul’s Early Discharge Rule was developed in 2000 in an urban hospital in Vancouver, British Columbia2
Their study was based on 573 patients who had received naloxone at any point before or during their presentation to the ED
One hour after naloxone administration, the patients were clinically evaluated by an emergency physician who documented their information and planned their disposition
The patients were then followed via patient-provided phone numbers, friend contacts, and for those unable to be reached, chart review of surrounding hospitals and coroner reports to capture adverse events
Based on the outcomes, the authors’ conclusion: patients can be safely discharged from the ED 1 hour after naloxone administration if they meet the following criteria:
Can mobilize as usual, have O2 saturation >92%, RR >10 and <20 bmp, Temp >35 and <37.5C, HR >50 and <100 bpm, GCS of 15
Strengths: two emergency physicians evaluated a subset of the patients to ensure inter-physician reliability, there was rigorous follow up over a short period to be reasonably sure of a lack of adverse events within 24 hours
Weaknesses:
The setting is in a city outside the US with unknown external generalizability (however, has since been validated in the US, called the HOUR study3)
Importantly, this study is now over 20 years old - there has since been a rise in potency of opioids including synthetic opioids with a longer half-life since then. Additionally, the study does not probe polysubstance 4intoxicationwhich is increasingly common5.
Likewise, the St. Paul’s Discharge Rule and the HOUR study were primarily focused on IN naloxoneresuscitation, which does not take into account the pharmacokinetics differences of the route of naloxoneadministration
Namely, as shown below, IN naloxone (especially at dosages >1mg) remains in the plasma longer than IM or IV naloxone:6
This is especially concerning given that fentanyl is more potent than heroin and requires higher doses of naloxone for resuscitation5 – which may require longer periods of observation based on the above diagram.
It also means that these discharge rules may not hold the same weight for IM, IV, or lower doses of IN naloxone.
A 2018 study addressed some of the weaknesses of the St. Paul’s Rule and HOUR study in the form of a retrospective chart review of 806 ED visits to an urban US academic center after receiving naloxone5
Findings: almost 4% of patients received a repeat dose of naloxone and 2% received oxygen over two hours after the original naloxone dose
Rates of interventions decreased significantly after 3 and 4 hours
Patients with polysubstance use in the study were significantly more likely to receive repeat naloxone
The authors concluded that a 3-hour observation period is sufficient, with extra attention to cases of presumed or known polysubstance use
Strengths: the study has a larger sample size, is more recent and therefore more applicable to current opioid types, and incorporates polysubstance use into the analysis
Weaknesses: the longer observation times can lead to more interventions that may have not occurred if the patient was not observed (e.g., giving oxygen for transient hypoxia commonly observed during sleep). Also, this study did not follow patients post-discharge and so could have missed later adverse events. Lastly, and importantly, the route of naloxone is not specified in this paper. The median of the dosages is specified and is about 2mg, which correlates most with the IN 2mg (red line on diagram above)
Recommendations
Based on the current trends in opioid use, including opioids with longer half-lives and increasing polysubstance use, a 3-hour observation following naloxone administration is appropriate
For patients who have received IN naloxone in doses >2mg, a 4-hour observation period (or otherwise increased scrutiny) is appropriate.
This balances the safety of the patient and their risk of adverse events, while also limiting the burden on already overcrowded EDs with boarding crises7and managing staff safety
St. Paul’s early discharge rule can be used during the 3-hour window as a helpful clinical measure supporting physician gestalt, ensuring the patient meets the criteria and is on their way to a safe discharge
Continued research is important to give updated recommendations as trends in opioid composition and use change over time and by region
References
1. Joseph JW, Marshall KD, Reich BE, Boyle KL, Hill KP, Weiner SG, et al. How Emergency Physicians Approach Refusal of Observation after Naloxone Resuscitation. Journal of Emergency Medicine [Internet]. 2020 Jan 1 [cited 2023 Aug 11];58(1):148–59. Available from: https://www.jem-journal.com/article/S0736-4679(19)30804-2/fulltext
2. Christenson J, Etherington J, Grafstein E, Innes G, Pennington S, Wanger K, et al. Early discharge of patients with presumed opioid overdose: development of a clinical prediction rule. Academic Emergency Medicine. 2000;7(10):1110–8.
3. Clemency BM, Eggleston W, Shaw EW, Cheung M, Pokoj NS, Manka MA, et al. Hospital Observation Upon Reversal (HOUR) With Naloxone: A Prospective Clinical Prediction Rule Validation Study. Academic Emergency Medicine [Internet]. 2019 [cited 2023 Aug 11];26(1):7–15. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/acem.13567
4. Tox & Hound. Tox and Hound - Great! Naloxone worked! Now what? [Internet]. The Tox and the Hound. 2019 [cited 2023 Sep 5]. Available from: https://toxandhound.com/toxhound/naloxone-now-what/
5. Heaton JD, Bhandari B, Faryar KA, Huecker MR. Retrospective Review of Need for Delayed Naloxone or Oxygen in Emergency Department Patients Receiving Naloxone for Heroin Reversal. The Journal of Emergency Medicine [Internet]. 2019 Jun 1 [cited 2023 Sep 5];56(6):642–51. Available from: https://www.sciencedirect.com/science/article/pii/S0736467919301210
6. McDonald R, Lorch U, Woodward J, Bosse B, Dooner H, Mundin G, et al. Pharmacokinetics of concentrated naloxone nasal spray for opioid overdose reversal: Phase I healthy volunteer study. Addiction. 2018 Mar;113(3):484–93.
7. Kelen GD, Wolfe R, D’Onofrio G, Mills AM, Diercks D, Stern SA, et al. Emergency Department Crowding: The Canary in the Health Care System. Catalyst non-issue content [Internet]. 2021 Sep 28 [cited 2023 May 8];2(5). Available from: https://catalyst.nejm.org/doi/full/10.1056/CAT.21.0217
Sample x-ray source: Normal chest x-ray. Radiopaedia.org [Internet]. [cited 2023 Aug 9]. Available from: https://radiopaedia.org/cases/normal-chest-x-ray
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