SGEM#179: Chase the Dragon and Naloxone

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Date: May 19th, 2017

Reference: Willman et al. Do heroin overdose patients require observation after receiving naloxone? Clinical Toxicology 2017.

Guest Skeptic: Dr. Richard Hamilton (@RJHamiltonMD) is Chair of the Department of Emergency Medicine at Drexel University College of Medicine. He is also the host of EMToxCast and gave a talk at the Association of Academic Chairs of Emergency Medicine Annual Retreat called: Can Social Media Save Emergency Medicine?

Case: A 45-year-old male arrives via emergency medical services (EMS) complaining that he wants to be discharged. EMS states they found him unresponsive and with paraphernalia consistent with intravenous heroin use. His prehospital vital signs were oxygen saturation of 89% and respiratory rate of six breaths per minute prior to administration of oxygen and 1 mg of naloxone. After naloxone administration he is alert and oriented times three with a normal pulse oximetry and clear lung fields. It is 20 minutes after he received naloxone and he is asking to be discharged.

Background: Heroin use has been increasing in the USA since 2007 (1). Opioids depress the heart rate and breathing and overdoses can result in death. With the increase in heroin use there has also been an increase in the number of heroin deaths (2).

Naloxone is the specific treatment for heroin overdoses and is becoming widely available to first responders of all sorts (Police, Fire, First Aiders, lay people and EMS). It is an opioid antagonist that binds competitively to opioid receptors in the central nervous system and gastrointestinal tract. It can be administered in multiple ways (intranasal, subcutaneously, intramuscularly, intravenously, nebulization or endotracheal tube).

The American Heart Association (AHA) discussed opioid overdoses and the use of naloxone Part 10: Special Circumstances of Resuscitation in their 2015 Guidelines (3). There were two new recommendations.

One was about education and naloxone training and distribution. The second new recommendation was about opioid overdose treatment.

CanadiEM summarized the Top 5 changes to AHA 2015 Guidelines in a series of infographics (4). One infographic focused on Special Circumstances and said “trained providers should administer naloxone to respiratory arrest patients with suspected opioid overdose. Lay-people likely to see opioid overdoses may be trained to administer naloxone during targeted BLS training” (5).

Some heroin users may refuse further treatment or transport to the emergency department after receiving naloxone in the field and awaking. If transported to hospital, they may also refuse further treatment or observation in the emergency department.

Three Clinical Questions:

What are the medical risks to a heroin user treated with naloxone who refuses transport to the emergency department?
When a heroin user is treated in the emergency department with naloxone how long must they be observed before discharging?
How effective is naloxone administration in heroin users by first responders and bystanders and what are the risks associated with naloxone distribution programs?

Reference: Willman et al. Do heroin overdose patients require observation after receiving naloxone? Clinical Toxicology 2017.

Population: Patients suspected of heroin overdose
Intervention: Naloxone administration (by first responders or bystanders), transportation to hospital, observation and naloxone distribution programs
Comparison: N/A
Outcomes:
- Risks to heroin user treated with naloxone not transported to the emergency department
- Length of observation in the emergency department
- Effectiveness of naloxone administration in heroin users by first responders and bystanders and risks of naloxone distribution programs

Quality Checklist for Therapeutic Systematic Reviews:

 The clinical questions are sensible and answerable. Yes
The search for studies was detailed and exhaustive. No
The primary studies were of high methodological quality. Unsure
The assessment of studies were reproducible. Unsure
The outcomes were clinically relevant. Yes
There was low statistical heterogeneity for the primary outcomes. Unsure
The treatment effect was large enough and precise enough to be clinically significant. Unsure

Question #1: What are the medical risks to a heroin user treated with naloxone who refuses transport to the emergency department?

Authors’ Conclusion: “Patients revived with naloxone after heroin overdose may be safely released without transport if they have normal mentation and vital signs. In the absence of co-intoxicants and further opioid use there is very low risk of death from rebound opioid toxicity.”

Key Results: Seven studies were relevant to answering the first question. There are 5443 patients treated with naloxone and not transported to the emergency department. Only two of the studies exclusively looked at heroin (n=1,069) and there were no deaths.

* patients who went to hospital after naloxone who had recurrent opioid toxicity had it within 1 hr

Question #2: When a heroin user is treated in the emergency department with naloxone how long must they be observed before discharging?

Authors’ Conclusion: “For patients treated in the ED for opioid overdose, an observation period of one hour is sufficient if they ambulate as usual, have normal vital signs and a Glasgow Coma Scale of 15”.

Key Results: Five studies were considered relevant to answer the second question. Observation period recommendations appear to be anywhere from 4-6 hrs up to 24 hrs.

A retrospective chart review by Smith et al included 124 patients presenting to the emergency department following a heroin overdose. There were 46 patients discharged home, 42 patients left against medical advice, and 19 patients eloped from the emergency department. No patients were transported back to the emergency department or were found dead within six days. Most patients left the emergency department within two hours. The other studies showed similar results.

A clinical prediction rule was developed by Christenson et al to identify patients who could be safely discharged one hour after naloxone administration. The rule consisted of three variables:

Ability to Mobilize as Usual
Normal Vital Signs
Glasgow Coma Scale of 15

They had 573 patients included in the study. The rule had a sensitivity of 99% (95% CI; 96%-100%) and specificity of 40% (95% CI; 36-45%) for predicting adverse events within 24hrs. The rule requires validation before it can be recommended for use.

Question #3: How effective is naloxone administration in heroin users by first responders and bystanders and what are the risks associated with naloxone distribution programs?

Authors’ Conclusion: “Patients suffering opioid toxicity can be administered naloxone safely by first responders and trained lay people. Programs that train these individuals are likely safe and beneficial, however further research is necessary.”

Key Results: Fifteen studies were considered relevant to answer the third question.

EMS Personnel and Emergency Physicians are already using a common sense approach to the patient with heroin overdose who is revived with naloxone. This literature review appears to support that complications from opioid rebound toxicity are rare and that patients who have returned to normal (eg.as per Christenson study) may be discharged or released.

Limited Search: The search for relevant articles was not detailed and exhaustive. They only searched two data bases (PubMed and Google Scholar) and was limited to the English language. They also did not mention speaking to experts in the field or searching the grey literature.
Methodological Quality: We are unsure of the methodological quality of the included studies. They did not formally rate individual studies using an assessment tool to characterize the quality of the studies.
Level of Evidence: The included studies were mostly retrospective chart reviews and other observational studies. These are a low level of evidence on the evidence based medicine pyramid.
Precision of Results: Due to the level of evidence and missing data we are unsure of the precision of the results in this review.
Pre-Date Fentanyl Adulteration: Most of the studies included in the review predate heroin adulterated with fentanyl and other similar drugs. As Leon Gussow says “There’s no such thing as just plain heroin anymore”. What does this mean for this study? In general, heroin mixed with fentanyl requires larger doses of naloxone to reverse and patients will have, for example, difficult to treat respiratory depression. Therefore, this group will be clinically evident to most providers. Can we apply these findings to our new era of heroin laced fentanyl? Unsure, but as an educated guess, a well appearing patient revived with naloxone is still probably okay to discharge.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions. However, when we podcasted on this article at EMToxCast we were careful to point out one specific subtlety. Opioid overdoses may have respiratory depression and hypoxia when not stimulated, but when stimulated might meet all of the criteria from the Christenson study. It is important to not stimulate the patient when you are making your assessment as to whether they can be discharged. Then once you observe a lack of respiratory depression or desaturation, perform a careful pulmonary auscultation so as not to overlook rales from pulmonary edema and observe that they are able ambulate unassisted. This represents the type of heroin overdose patient revived with naloxone that may be discharged.

There was a letter to the Editors by Eggleston and Clemency expressing concern with a response from Willman et al.

SGEM Bottom Line: Delayed opioid toxicity is more likely overlooked opioid toxicity rather than rebound toxicity. There are patients that are safe to discharge, but perform a careful clinical exam and be certain to observe the patient’s respiratory pattern and mental status in a non-stimulated state. Of course, exercise caution in the ever changing world of heroin abuse and all its adulterants.

Case Resolution: When observed from the entrance to the room without stimulation, it was obvious that when not stimulated the patient’s respiratory rate would decrease and their oxygen saturation would dip to 90%. Rather than administering additional naloxone, you apply supplemental oxygen and allow the patient to sleep for another hour. At that time, you remove the oxygen and recheck the patient without overly stimulating him. He appears to be alert and oriented times three with clear lung fields and had no signs of respiratory depression; he can walk to the bathroom on his own and back without assistance. The patient is safe for discharge and receives a referral to addiction counselling and treatment.

Dr. Richard Hamilton

Clinical Application: The results of this study provides weak evidence applicable to EMS determining refusal of transport decisions after heroin overdoses, emergency department physicians assessing the same patients once brought into the emergency department, and naloxone distribution programs using bystanders or lay people

What do I tell my patient? You have just had a heroin overdose and you feel better because we gave you drug that blocks the effects (naloxone). If you feel like you are getting worse you should return immediately. Preferably go home or be with someone that can observe you for a period of time. If you would like to be referred to a detox program or perhaps even get a prescription for naloxone to take home we can start talking about that as well.

Keener Contest: Last weeks’ winner was Christopher White. He is training to be an Advanced Nurse Practitioner. Christopher knew that Maharishi Mahesh Yogi was the guru followed by the Beatles.

Listen to the SGEM podcast on iTunes to hear this weeks’ question. If you think you know the answer then send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Other FOAMed Resources:

EM Tox Cast: Heroin overdoses and naloxone reversal: ok for discharge or mandatory observation?
St. Emlyns: Opiate Overdose in the ED
EM Cases: Episode 74 Opioid Misuse in Emergency Medicine
EM Basic: Opioids Part 1 by Dr. Sheyna Gifford
EM Basic: Opioids Part 2 by Dr Sheyna Gifford
ALiEM: Treat and Release’ after Naloxone – What is the Risk of Death?
TPR: Treating “heroin” overdose: the past is no guide
TPR: Keys to the safe use of naloxone
AmboFOAM: Angling for Trouble? Catch and Release for Heroin Overdose.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

References:

NIH: What is the scope of heroin use in the United States?
CDC: Division of Vital Statistics, Mortality Data
AHA 2015 Guidelines Part 10: Special Circumstances of Resuscitation
CanadiEM: The ‘Top Five Changes’ Project: 2015 AHA guidelines on CPR + ECC update infographic series
CanadiEM: Top 5 Changes to Special Circumstances