Opioid abuse is a major public health epidemic in the United States and Canada as the number of deaths related to opioid toxicity continues to rise. In 2013, there were 16,325 prescription opioidrelated deaths in the U.S., quadruple the number of deaths that occurred in 1999,1 and an additional 8,257 deaths from heroin.2,3 A similar situation exists in Canada.4
There have been multiple efforts to combat this crisis, including calls to improve opioid prescription practices, access to addiction treatment, and enhanced treatment tools and protocols for first responders.
With the implementation of public naloxone (Narcan) distribution programs,5 and administration of naloxone by police departments and first response programs,6 naloxone is becoming widely available to treat patients with suspected opioid toxicity in the out-of-hospital setting.
In cities across North America, laypeople are being equipped with naloxone kits and overdose resuscitation training, while many paramedic and EMS agencies still restrict naloxone administration.
This has led to debate regarding the role of naloxone in the out-of-hospital setting. Who should be administering it? When and how should it be administered?
EMS providers are often called to respond to situations involving opioid-related emergencies. These calls may involve a variety of patient conditions including chronic pain management for musculoskeletal pain or cancer-related pain, illicit drug use and intentional overdose.
In general, the term “opioid-associated resuscitative emergency” is preferable to “opioid overdose” because the patient’s critical condition is seldom due to opioids alone. “Opioid-associated resuscitative emergency” refers to any clinical condition that’s known or thought to be associated with opioids where the patient is obtunded without obvious signs of life.
Isolated opioid toxicity is associated with central nervous system and respiratory depression that can quickly progress to respiratory and cardiac arrest. However, most critical and life-threatening drug-related emergencies involve multidrug toxidromes, co-ingestion or other complicating comorbidities.7-10
In many situations EMS providers encounter in the field, the patient’s clinical presentation may not be the result of opioid toxicity alone. EMS providers must be ready to manage undifferentiated resuscitative emergencies involving opioids, and therefore must be prepared to manage opioid toxicity in the presence of other comorbidities and co-ingestions.
In addition to standard resuscitation procedures, the goal of naloxone administration by first responders and EMS providers should be to improve breathing and restore airway reflexes in the obtunded patient, not to restore full level of consciousness.
MECHANICS OF NALOXONE
Naloxone is an opioid antagonist that competitively binds to opioid receptors, reversing the effects of opioids in the central nervous system and gastrointestinal tract.
For reversing overdose, naloxone can be administered using a variety of different methods: IV,11,12 intramuscularly (IM),12,13 subcutaneously (SC),14 intranasally, 13,15 by nebulization (NB),16,17or via endotracheal tube (ETT).18
The optimal route of administration depends on a number of factors including availability, provider skill and level of training, and the clinical circumstances.
The ideal dosage of naloxone isn’t known and is dependent upon the route of administration. An initial dose of 0.4 mg IV or IM is reasonable to avoid severe opioid withdrawal, with repeated doses up to 2 mg to achieve the desired effect. Intranasal naloxone should start with a dose of 2 mg.19
Naloxone has a good safety profile with a low incidence of serious side effects, even when administered to patients who are ultimately determined not to have opioidtoxicity.20
Adverse reactions from naloxone administration are generally a result of reversing dependency and precipitating withdrawal states, leading to sympathetic excess.21 Adverse reactions are rarely life-threatening and can include: unmasked pain, sweating, nausea and vomiting, pulmonary edema, hypertension, tachycardia, agitation and irritability.21
Though precipitating severe withdrawal is a common concern among prehospital healthcare providers, it’s a very rare occurrence when small doses of naloxone are given to obtunded patients—patients with resuscitative emergencies don’t immediately go from deeply obtunded to severe withdrawal.
2015 AHA GUIDELINES UPDATE
The 2015 American Heart Association (AHA) Guidelines Update examined evidence around the use of naloxone by first aid providers, BLS providers and ALS providers for severe opioid toxicity and cardiac arrest.19
Several recommendations were made based on available evidence pertaining to the administration of naloxone in the prehospital setting. The guidelines were designed to provide a safe and effective approach to opioid-associated resuscitative emergencies, recognizing that most cases involve multiple pathophysiological processes and comorbidities.
The 2015 AHA Guidelines Update place an emphasis on incorporating lay rescuers in the chain of survival, not only for cardiac arrest patients but for all patients with suspected opioid toxicity. As with patients in cardiac arrest, bystanders have an important role in recognizing and responding opioidrelated emergencies.
Community-based education programs targeting high-risk populations are an important component of prehospital response systems. These education programs may include naloxone distribution as a component. Most fatal opioid-related emergencies are witnessed, and patients with severe opioid toxicity won’t be able to administer their own treatment. Therefore, it’s reasonable to train bystanders and anyone likely to witness an overdose on what to do in case of an opioid-related emergency.5,22 These programs generally train participants to recognize overdose, activate EMS, deliver basic first aid and to stay with the patient until help arrives.
These programs generally train participants to recognize overdose, activate EMS, deliver basic first aid and to stay with the patient until help arrives.
EMS personnel should be familiar with these programs, and prepared to assume care from trained bystanders who may have administered naloxone prior to EMS arrival. EMS personnel also need to be aware of these programs so they can provide reassurance and support to bystanders who may have saved a life by following their first aid training.
Studies have shown that community-based education programs and naloxone distribution programs are safe and effective and it’s recommended that education in opioid response and naloxone administration is available for at-risk populations.5
Bystanders trained in these programs often administer naloxone successfully and there’s good evidence to show that the availability of naloxone in the community isn’t associated with increased opioid misuse or higher-risk drug behaviors. In fact, it’s often associated with an increased awareness of these behaviors and recognition of opioid-related emergencies among high-risk populations.5
The appropriate treatment for opioidrelated emergencies in the out-of-hospital setting is dependent upon the level of training of the provider (e.g., first aid, BLS, ALS), as well as confirmation that the patient is in cardiac arrest.
The chaotic, high-stress and uncontrolled environment of prehospital medicine can make it extremely difficult to differentiate patients who are severely obtunded with decreased respiratory effort, from those patients who are in cardiac arrest.
Although naloxone has no clear role in the treatment of patients who are in confirmed cardiac arrest, rapid naloxone administration can be lifesaving for patients who still have a pulse but are severely obtunded with decreased respiratory effort. Furthermore, naloxone administration isn’t associated with any known harms in cardiac arrest patients.
For first aid and BLS non-healthcare providers who don’t perform pulse checks, differentiating between patients who are severely obtunded with respiratory depression and those patients who are in cardiac arrest is impossible. In this situation, where the provider is unable to differentiate cardiac arrest, providers should follow standard BLS care according to the 2015 AHA Guidelines Update, including immediate activation of EMS, initiation of CPR and application of an automated external defibrillator (AED).5
Once standard resuscitation measures are in place, it’s reasonable for providers to administer naloxone to these patients without interrupting ongoing resuscitation processes. (See Figure 1.)
Although there’s no clear benefit of naloxone for a patient who is in cardiac arrest, in this situation the potential benefit of administration of naloxone to a patient who isn’t in cardiac arrest outweighs any theoretical risk of naloxone administration to a patient in cardiac arrest.
For BLS and ALS healthcare providers responding for patients of suspected opioidrelated emergencies in the out-of-hospital setting, as with non-healthcare providers, it’s important that standard resuscitation measures take precedence over naloxone administration. The focus of EMS providers should be on assisting respirations with a bag-valve mask and initiating high-quality chest compressions and rapid defibrillation where indicated.
Both basic and advanced EMS providers should be trained and capable of administering naloxone. As healthcare providers perform pulse checks it may be possible to differentiate between obtunded patients and those in cardiac arrest. Patients with a confirmed opioidassociated cardiac arrest should be managed according to standard cardiac arrest guidelines.23,24
There are no studies to guide recommendations on the administration of naloxone during cardiac arrest, and no data to show if naloxone improves patient outcomes (i.e., return of spontaneous circulation or survival to discharge)19 compared to standard resuscitation care.25 Many opioidrelated ardiac arrests aren’t the result of isolated opioid toxicity but involve co-ingestion of multiple agents, and medical or mental health comorbidities that won’t respond to naloxone administration.
Out-of-hospital clinicians should be aware that pulse checks are of limited reliability in deeply sedated patients, even when performed by healthcare providers, so confirming cardiac arrest can be very challenging in this patient population.26
In patients with an opioid-associated resuscitative emergency, naloxone should be administered by properly trained providers if there’s a definitive perfusing cardiac rhythm (i.e., pulse determined in less than 10 seconds) or uncertainty about whether the patient is in cardiac arrest. Bag-valve mask ventilations should be continued after naloxone administration until spontaneous respirations return, and standard ACLS measures may be required if spontaneous respirations don’t occur.
Access to more advanced care shouldn’t be delayed for naloxone administration. Furthermore, patients who respond to naloxone administration should receive follow-up care from advanced healthcare providers, unless further care is competently refused by the patient.
Patients who initially respond to treatment may develop recurrent episodes of decreased respiratory effort, sedation and central nervous system depression and should be monitored for an appropriate period of time by advanced healthcare providers.21
New Hampshire residents whose family members or friends are at risk of an opioid overdose can obtain free naloxone kits provided by state health officials. AP Photo/Jim Cole
As 9-1-1-calls for opioid-associated emergencies continue to increase, EMS providers of all levels must be properly trained to respond to these life-threatening emergencies, including the administration of naloxone.
The goal of prehospital naloxone administration should be to restore adequate respiratory status and airway reflexes, not to restore full level of consciousness. EMS providers must be aware that many critical situations they encounter may not be the result of isolated opioid toxicity, and must therefore be prepared to respond to emergencies involving multiple comorbidities and co-intoxications.
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