Mixed Feelings About Naloxone: It Saves Lives, but at What Cost?

Michael T. Hilton, MD, MPH

Disclosures

December 07, 2018

EMS 'On the Scene'

"Did you hear the fire dispatch radio?"

"Another one?"

"Yeah. That's what? Three so far, 2 hours in. Not a good way to start the shift."

"[Beep...beep...beep...crackle] Medic 313 from North EMS Dispatch [crackle]."

"313 here, go ahead dispatch."

"Respond to 806 Main Street, report of an unresponsive male. Breathing status unknown. Fire department first responders have been dispatched."

"[Sighing] 313 acknowledges. Responding."

7 minutes later...

"What have we got?"

"OD. He was barely breathing when we got here. Bagged him up. Still bagging him. Used our new nasal naloxone. Still not responding."

"Ok. Keep bagging. We'll check his glucose and try some IV naloxone."

10 minutes later...

"Dude, what the...? Why you trying to ruin my high? [Shivering] Get me a blanket and get me some medicine, or I'm going to throw up all over you [starts retching]."

"We're trying to keep you alive. You weren't breathing."

"Yes, I was."

"Come with us so we can get you to the hospital. They can keep an eye one you. Make sure you keep breathing."

"I'm not going. I know my rights. I'll sign whatever I have to."

15 minutes later...

"Grab the refusal form, and get med control on the phone for me. Going to be a refusal."

"Should we leave him with the leave-behind IN naloxone kit? I can grab the pack and the instruction sheet."

"Is that a new policy? Leave him with naloxone? So he can feel free to shoot up again?"

The Opioid Epidemic

The opioid epidemic needs no introduction—the data speak for themselves. In New York, the death rate was 15.1 per 100,000 persons in 2016.[1] The rate in Pennsylvania was 18.5; in Ohio, it was 32.9; and in West Virginia, it was the highest, at 43.4.[2] Nationally, the average death rate was 13.3 per 100,000 persons in 2016. In New York, between 2012 and 2016, deaths due to synthetic opioids increased 10-fold. During the same years, deaths due to heroin doubled. Deaths due to prescription opioids doubled between 2009 and 2016.

Emergency department opioid-related visits increased 73% from 2010 to 2014. Naloxone administration by emergency medical services (EMS) more than doubled between 2013 and 2014.[1] Nationally, in 2016, there were over 42,000 deaths due to opioid overdose. More people died from opioid overdoses than in motor vehicle collisions.[3,4]

Naloxone Administration by EMTs and First Responders

Traditionally, in the out-of-hospital setting, suspected opioid overdoses have been managed through bag-valve-mask (BVM) assisted ventilation by emergency medical technicians (EMTs) and firefighter first responders.[5] If paramedics were available, they have had the ability to administer intramuscular (IM) or intravenous (IV) naloxone, an opioid antagonist.[6,7,8]

Naloxone can be administered through IV injections, IM injections, or IM autoinjectors, or intranasally (IN) through a generic nasal medication atomizer or a brand-name IN device.[8] IV naloxone has the most rapid onset of action, but is the most invasive route and requires the highest level of training for administration. IM injections require a moderate level of training, and IM autoinjectors require minimal training, because they are preloaded with a standard dose.

IN naloxone delivered through a nasal medication atomizer requires moderate training because, as with IV and IM injections, the medication must be drawn up from a vial in an accurate dose. However, the administration itself is much easier than with IM injections. There is also a brand-name IN naloxone device that eliminates the need to draw up medication, because it is preloaded with a standard dose and is very easy to administer.

Intranasal naloxone may be the safest administration method for providers because it is a needleless delivery method.[9] The least expensive form of naloxone is the generic IV/IM/IN atomizer naloxone, at about $35 per dose. The brand-name IN naloxone costs about $125 per two doses.[10] The autoinjector costs about $4500 per two doses (an increase from $575 in 2014).[11]

In response to the opioid overdose epidemic, EMS systems have expanded education, training, and protocols to allow basic EMTs,[12] fire department first responders,[13,14] and even law enforcement officers (LEOs)[15] to administer naloxone. EMTs, fire department first responders, and LEOs are more numerous than paramedics and can usually respond to a scene more rapidly. In some EMS systems, paramedics may not be available for every call.[16]

Some overdose victims would never have the chance to get treatment with naloxone in the field. Expanding naloxone access to nonparamedic providers increases the chances that more overdose victims receive this treatment and also ensures that they receive this treatment as rapidly as possible.[17,18,19]

Expanding naloxone administration to EMTs and fire department first responders is not without controversy. The expansion of naloxone administration to EMTs began in the mid-2010s.[12,20,21] Soon after EMTs had access to naloxone, fire departments began equipping and training firefighter first responders to use naloxone.[13,14] Although getting naloxone to overdose victims as rapidly as possible may seem to be beneficial, administering this medication can distract providers from delivering rapid and high-quality BVM artificial ventilation for patients with respiratory arrest.

Overdose or Cardiac Arrest? Start With Ventilation and Chest Compressions, not Naloxone

The initial and most important treatment for all patients with respiratory arrest, whether from overdose or not, is BVM artificial ventilation. Not all patients with respiratory arrest are overdose victims. If ventilation isn't started first, important time is wasted in administering naloxone.

Administering naloxone can also distract from providing high-quality chest compressions in the setting of cardiac arrest.[22] For patients in cardiac arrest, even if initially caused by hypoxemia from opioid overdose, the treatment is high-quality chest compressions, not naloxone.

According to the 2015 American Heart Association Guidelines for CPR and Emergency Cardiovascular Care, "Standard resuscitative measures should take priority over naloxone administration, with a focus on high-quality CPR (compressions plus ventilation)."[23] In the same guidelines, for respiratory arrest, the American Heart Association recommends that "for patients with known or suspected opioid overdose who have a definite pulse but no normal breathing or only gasping (ie, a respiratory arrest), in addition to providing standard BLS [basic life support] care, it is reasonable for appropriately trained BLS healthcare providers to administer IM or IN naloxone."

It is imperative that nonparamedics who administer naloxone do so with adequate training and education to ensure that practice adheres to these guidelines. Systems that allow nonparamedics to administer naloxone must have a continuous quality improvement program in place. Medical directors must ensure protocols are adequately written to address the importance of standard BLS care and high-quality chest compressions first and foremost.

The 2017 Pennsylvania statewide basic life support protocol for poisoning (protocol 831)[7] provides a good example of a naloxone protocol for nonparamedics:

Give Naloxone (if available) if decreased respiratory rate and suspected narcotic overdose

Goal = adequate respiration and oxygenation (not awakened patient)

a. Ventilation with BVM takes priority over naloxone administration.
SAFETY NOTE: If cyanotic, decreased respirations, or hypoxia (SpO2 < 95%), ventilate with BVM and oxygen to adequate color/SpO2 while preparing for administration of naloxone

b. In pulseless patients, naloxone is not indicated and CPR should be initiated immediately.

Law Enforcement Agencies Supplying Naloxone, but Not Without Opposition

In 2004, over 220 law enforcement agencies in 24 states carried naloxone.[24] Today, over 2400 law enforcement agencies carry naloxone.[15] Because LEOs are 10 times more numerous than EMTs and are typically dispatched to overdose calls, the time to naloxone administration can be made quicker by providing LEOs with naloxone.[24]

Some police department officials are opposed to carrying naloxone.[25,26] They cite public opinion concerning "people who overdose repeatedly" being encouraged to abuse opioids because of the better chances of being saved. They believe that naloxone administration diverts resources away from their primary mission of "crime fighting." The officials are also are concerned about the time and money needed for training, supply tracking, and storing the medication and cost of stocking the medication as barriers.

Yet other police officials report that the logistical barriers are easy to overcome and that the cost of the medication isn't usually an issue. In many cases, naloxone is provided by health departments or community organizations.[25,26] The Virginia state police received a $154,800 grant from the Virginia Department of Behavioral Health and Developmental Services.[27] In Pittsburgh, Pennsylvania, state police and fire stations received $5 million in funding for naloxone from the Pennsylvania Commission on Crime and Delinquency.[28]

Police officials are also concerned about the personal danger to their LEOs. Opioid users can behave violently after naloxone is used. If alone, a police officer may be placed in harm's way.[25,26]

Legal liability for LEOs and law enforcement agencies was also cited as a barrier to administering naloxone. However, this is unfounded. LEOs are at very low legal liability for using naloxone to treat an overdose victim. At the same time, LEOs are also not liable for failing to use naloxone, even if equipped with it. Some states have general or specific civil or administrative liability immunity for LEOs who use naloxone.[24]

In general, LEOs have a positive experience about receiving opioid overdose and naloxone administration training.[29,30] In New York State, the Harm Reduction Coalition provided "train-the-trainer" sessions for 55 LEOs. These sessions were well received, although a common concern regarded liability for using naloxone.[31]

The North Carolina Harm Reduction Coalition website provides FAQs, sample policies, and forms to help law enforcement agencies interested in carrying naloxone.[15] The American College of Emergency Physicians (ACEP), National Association of EMS Physicians (NAEMSP), and American College of Medical Toxicologists (ACMT) support naloxone administration by all levels of EMS providers, firefighters, and LEOs.[32]

'Take-Home' Naloxone Kits and Public Training Sessions

Most recently, access to naloxone has been expanded to the lay population in many states to broaden its availability in the community and allow the most rapid administration possible. Laypeople are also less likely to have the skills and equipment to provide artificial ventilation if they come across an overdose victim. Besides calling 911, naloxone may be the only way a layperson can save the life of an overdose victim.

There are also many ways that laypeople can get naloxone. Syringe exchange and opiate drop-in centers offer naloxone kits or prescriptions for naloxone.[33] They also provide education about causes, recognition, and prevention of overdoses and training in naloxone use.

In British Columbia, Canada, naloxone training and overdose education is available online. Once completed, using an electronic certification of training, naloxone can be obtained from hospitals or other approved sites.[34]

The Substance Abuse and Mental Health Services Administration, an agency within the US Department of Health and Human Services, offers free education and training at least once a month and provides information about where to obtain naloxone.[35] They also have a free online toolkit available to local governments and communities to develop policies and practices to help prevent opioid-related overdoses and deaths.

Twelve New York State Office of Alcoholism and Substance Abuse Services Addiction Treatment Centers offer free education, training, and naloxone kits.[36] New York State's Department of Health also has an online calendar of opioid overdose trainings located in communities throughout the state.[37]

Online training and education and referrals to naloxone suppliers are available at getnaloxonenow.org.[38] Information and resources for groups to run their own naloxone programs are available at naloxoneinfo.org.[39]

Pharmacy Distribution of Naloxone

A vial of naloxone, which can be used to block the potentially fatal effects of an opioid overdose, is shown on Friday, October 7, 2016, at an outpatient pharmacy at the University of Washington. Washington governor Jay Inslee announced an executive order to fight the rising abuse of opioids in Washington State that included measures to reduce the cost and increase the availability of naloxone for the treatment of overdoses. Photo courtesy of AP/Ted S. Warren

Pharmacies have been key to distributing naloxone to the lay public. In the past, naloxone distribution by a pharmacist required a prescription from a healthcare provider. In some states, naloxone is now available without a specific prescription from a physician. The legislative and regulatory means to allow this to occur differ state by state, but the end result is that naloxone is available "behind the counter" from pharmacies.

In Pennsylvania, the physician general has written a standing prescription order that serves as the prescription for any layperson in Pennsylvania to purchase naloxone from pharmacies that carry it.[40,41] In Maryland, the Deputy Secretary for Public Health Services has also issued a standing order.[42] In this order, naloxone can be distributed to those who have been trained and certified under the Maryland Overdose Response Program. The order also provides liability protection for pharmacists.

Naloxone is now available from CVS pharmacies without a prescription in 48 states,[43] and the CVS website provides educational information about naloxone.[44]

Whereas most states now permit naloxone through standing order prescription, five states allow pharmacists to distribute naloxone under their own authority without any prescription at all. In addition, civil and criminal legal protections for pharmacists and pharmacies have been implemented in over 35 states.[45] As of 2015, 43 states and the District of Columbia have passed specific laws to increase layperson access to naloxone.[46]

Laws providing for naloxone distribution with provisions for immunity have been shown to facilitate the distribution of naloxone.[47] ACEP, NAEMSP, and ACMT support over-the-counter pharmacist distribution of naloxone.[32] However, many pharmacies do not stock naloxone.[48] New York City maintains a list of pharmacies that participate in the naloxone standing order initiative.[49] An investigation by the New York Times found that of the 720 pharmacies listed, only one third actually stock naloxone and would dispense it without a prescription.[48]

Free online training directed to pharmacists interested in dispensing naloxone via non–patient-specific prescription is available through a course developed by the University at Buffalo and the New York State Department of Health.[50] This training is available to non-New York State pharmacists as well.

Naloxone Distribution Programs Raises Controversy Among Emergency Physicians

Because emergency department-based take-home naloxone programs are a new development, research on the outcomes of such programs is lacking. One pilot study showed no mortality benefit between patients who received a naloxone take-home kit in the emergency department after a heroin overdose.[51] However, the study is limited owing to its scale.

ACEP, NAEMSP, and ACMT support emergency physician naloxone prescriptions for at-risk patients, but do not provide an opinion on the take-home programs.[32] And some emergency physicians are conflicted about the effects of naloxone take-home programs, fearing that it increases opioid use and addiction.[52]

Another recent development are the EMS "leave-behind" programs, where naloxone is made available to at-risk opioid users. Through a statewide standing order, the Pennsylvania physician general has authorized EMS providers and EMS agencies to leave naloxone kits behind after responding to calls for opioid overdoses.[53]

Standing Order DOH-001-2018 states[53]:

This standing order authorizes Department-certified EMS providers or Department-licensed EMS Agencies who have responded to an individual experiencing an opioid-related overdose (At-Risk Person), and who are therefore in a position to assist that At-Risk Person, to leave behind naloxone with the At-Risk Person or with family members, friends, or other persons who are in a position to assist the At-Risk Person, along with instructions to follow the naloxone package insert directions and the guidance provided in Standing Order DOH-002-2017, available on the Department's website.

EMS leave-behind programs have been implemented in Pittsburgh [54] and New York City.[55] Maryland has a similar pilot program in place.[56]

PCPs Are Encouraged to Coprescribe Naloxone to At-Risk Patients

Laypeople can access naloxone through a primary care provider. Primary care providers may coprescribe naloxone when prescribing prescription opioids to at-risk patients. Coprescribing is considered acceptable among primary care physicians, and many use this practice for their patients on long-term opioids.[57] Barriers to this practice are mostly administrative, relating to time involved and pharmacy or payer logistics.

The American Medical Association Task Force to Reduce Opioid Abuse recommends coprescribing naloxone to patients and family members or close friends of patients when it is clinically appropriate.[58] Coprescribing naloxone does not increase the prescribers' risk for liability.[59]

Patients on long-term opioids for chronic noncancer pain generally are accepting of naloxone coprescribing, but they report receiving little education on opioid medication risks and have limited knowledge about naloxone. Providing this education and doing so in empowering, nonjudgmental language facilitates patient acceptance of naloxone prescribing.[60]

Naloxone Price Gouging and Copayment Assistance

One of the major barriers to layperson naloxone use is the cost of naloxone to consumers and possible price gouging by pharmaceutical companies.[61,62,63] To address this barrier, the New York State Department of Health AIDS Institute has implemented the Naloxone Co-payment Assistance Program (N-CAP), in which "copayments for naloxone in an amount up to $40 for each prescription dispensed will be billed to N-CAP, not to the individual getting naloxone."[64] Most other states have not provided similar assistance to consumers.

Another barrier is a concern that providing naloxone to laypeople might increase opioid use among at-risk individuals. Small studies have found no increased heroin use in those who have participated in overdose education and naloxone distribution programs.[65] In addition, laws that increase naloxone access to laypersons and laws that provide overdose-specific liability protection have been found to reduce opioid overdose mortality with no increase in nonmedical opioid use.[66] Further research definitely is needed in this area.

"You really want to leave him with the leave-behind kit?"

"In training, we learned that providing this isn't likely to make him use more or overdose again. Also, it has the chance to save his life before we get to him, or even before the fire department gets to him. Saving his life can give him another chance to get to treatment and turn his life around."

"All right. I'll grab the leave-behind kit. Can you provide him with training on how and when to use it? He also has some family here now. We can show them how to use the kit."

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