In the January 2015 ACEP Now article “True Cost of Stopping Overdoses,” Paul Kivela, MD, MBA, PhD, discussed several issues related to naloxone administration and sustainability of naloxone programs.¹ Many of his concerns are the focus of existing and emerging policies and research. His piece highlighted how important it is for emergency physicians to be familiar with the literature and practice regarding prehospital naloxone use.

Naloxone has been used for more than 40 years and distributed through community-based programs since 1996. Many emergency physicians have worked with first responders to expand naloxone access. Recognizing the lifesaving potential of increased naloxone access, ACEP approved two related resolutions in 2014: to train and equip first responders with naloxone and to expand pharmacy-based naloxone provision and education. This year, ACEP will develop a clinical policy on emergency physicians’ prescribing naloxone.² As we move forward in supporting expanded naloxone use, it is critically important for us to have a nuanced understanding of the existing literature.

Few Dangers With Prehospital Administration

Emergency medical services (EMS) providers are very experienced and familiar with naloxone administration and side effects. Research on EMS prehospital naloxone use has shown that serious complications, including violence and needle sticks, are rare.³ The most common side effect is precipitated opioid withdrawal, which is not life-threatening and is less likely with lower doses and intranasal administration.^4,5

We agree with Dr. Kivela’s recommendation of needleless naloxone delivery and intranasal naloxone, which are already being used in many areas. Until intranasal atomizers and intramuscular auto-injectors become widely available and affordable, however, EMS and other first responders should feel safe (when using appropriate universal precautions) using intramuscular formulations.

Medication Stability

We appreciate Dr. Kivela’s point that, like many other pharmaceuticals, naloxone should be stored at room temperature and shielded from light until use. Studies have demonstrated naloxone’s stability. In one study, naloxone hydrochloride was cycled daily for 28 days through extreme temperatures (2°F–129°F). Samples retained 90 percent of their original concentration, a small degradation similar to that of nitroglycerin.6 Recommended storage is no different from other medications commonly used in the prehospital setting, such as the EpiPen, which has similar temperature and humidity recommendations.^7,8 Quality-control checks of first responders’ equipment should include verifying expiration dates of naloxone, just as with any other transported medication.

Risks and Liabilities

After an overdose, most people are brought to the ED for evaluation and treatment. Refusal of treatment is a common concern faced by EMS providers and emergency physicians, and there is no clear consensus on how to manage these situations. The prehospital literature examining mortality among patients refusing transport after naloxone administration has shown no evidence of increased mortality and low incidence of ongoing respiratory depression.^9–11 In these studies, patients who needed further monitoring were immediately identifiable. Patients with overdoses of multiple substances, or long-acting opioid formulations, will certainly need continued hospital monitoring. For now, patients who refuse transport or opt to leave the ED must do so against medical advice.

Beyond the prehospital setting, there is substantial practice-based evidence supporting community opioid education and naloxone distribution (OEND) programs. Utilizing a similar approach as layperson CPR and automated external defibrillator training, more than 50 OEND programs in the United States provide training to community members in opioid overdose prevention, recognition, and response, combined with community-distributed naloxone.¹² OEND programs have been shown to decrease opioid overdose mortality in Massachusetts, New York City, Chicago, and North Carolina and have proven that laypeople, including intravenous drug users, can reliably administer naloxone.^13–18 Some EDs have started providing take-home naloxone rescue kits to patients identified as at risk for opioid overdose.^19,20

The risk of liability for incurred naloxone side effects pales in comparison to the risk of the loss of a life when naloxone is unavailable. Twenty-eight states and the District of Columbia have passed laws expanding naloxone access, and 20 states have passed Good Samaritan legislation, protecting individuals who administer naloxone or call 911 for an opioid overdose. Future iterations of Good Samaritan legislation provide opportunities to address concerns about liability related to first-responder naloxone administration.

The Clinton Foundation negotiated a lower price for Evzio, the naloxone auto-injector, which is currently cost-prohibitive for most municipalities and organizations at $600 per kit. It remains to be seen what the new “low” price will be.

Cost and Sustainability

Costs associated with naloxone training are generally modest, as it is easily incorporated into EMS training curricula. Training for laypeople and nonmedical first responders lasts 10 to 60 minutes, depending on local reporting protocols and education credit requirements.²¹ Fluctuating medication cost is a problem hospital administrators regularly address through negotiation. Rising costs are becoming more challenging not only for naloxone but also doxycycline, topical steroids, and other essential medications.^22–24 Despite current cost concerns, cost-modeling research has demonstrated that OENDs are, by all health care rubrics, extremely cost-effective.²⁵

New formulations of naloxone are being developed and manufactured, which should increase supply and competition, thereby driving down cost.^26,27 The Clinton Foundation negotiated a lower price for Evzio, the naloxone auto-injector, which is currently cost-prohibitive for most municipalities and organizations at $600 per kit.²⁸ It remains to be seen what the new “low” price will be.

Stigma and Understanding of Opioid Overdose Epidemiology

Finally, and most important, we caution against demonizing populations vulnerable to opioid overdose. Public health experts have recognized that opioid overdose is not only an urban phenomenon limited to illicit opioid use among young men. Opioid overdose is seen increasingly among women, older patients in nonurban environments, and patients using prescription opioids for chronic medical conditions.^29–32 Patients with severe liver disease, metastatic solid tumors, renal failure, bipolar disorder, depression, chronic obstructive pulmonary disease, posttraumatic stress disorder, and sleep apnea are also more likely to experience opioid-related overdose.^33,34 Describing overdose patients as “inherently violent” implies population assumptions and insinuates that these patients may be “undeserving” of overdose reversal. For people struggling with the chronic disease of addiction, only by surviving an overdose will they have the opportunity to seek treatment and recovery.

The ED is on the frontline of the overdose epidemic and offers tremendous opportunities for overdose rescue, opioid overdose prevention, and increased access and referral to addiction treatment. Cost, training, sustainability, access, and approach to potential ethical issues are basic challenges for all new and important public health measures, whether it is vaccination, use of child safety seats, or public-access defibrillation programs. Implementation obstacles do not determine the worth of programs with established benefits but demand thoughtful collaboration to find workable solutions.

We look forward to continuing to tackle issues of accessibility, cost, and liability to offer our patients the opportunities that come with survival.

Dr. Samuels is in the department of emergency medicine at the Alpert Medical School of Brown University in Providence, Rhode Island. Dr. Aks is in the department of emergency medicine at Cook County Health & Hospitals System and the Toxikon Consortium in Chicago. Dr. Bernstein is in the department of emergency medicine at Boston University School of Medicine’s Boston Medical Center and works at the Boston Medical Center Injury Prevention Center. Dr. Choo is in the department of emergency medicine at the Alpert Medical School of Brown University. Dr. Dwyer is in the department of emergency medicine at Brigham and Women’s Hospital in Boston. Dr. Green is in the department of emergency medicine at the Alpert Medical School of Brown University and works at the Boston Medical Center Injury Prevention Center. Dr. Hack is in the department of emergency medicine at the Alpert Medical School of Brown University. Dr. Juurlink is in the division of clinical pharmacology and toxicology at the University of Toronto. Dr. Mello is in the department of emergency medicine at the Alpert Medical School of Brown University. Dr. Ranney is in the department of emergency medicine at the Alpert Medical School of Brown University. Dr. Alexander Walley is in the clinical addiction research and education unit at Boston Medical Center. Dr. Whiteside is in the division of emergency medicine at the University of Washington in Seattle.

References

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