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Naloxone`s Basic Benefit
Opioid overdoses are a growing cause of preventable death in many countries, including the United States. In March 2012 the United Nations declared narcotic overdoses a growing global health problem. Their rising rate is partially due to an increase in nonmedical use of prescription opioid painkillers.1 In New York there are two prescription painkiller addicts for every heroin addict.2 Prescription opioid medications can include hydrocodone, sold as Vicodin and Lortab, and oxycodone, sold as Percocet, as well as many others.3
According to the CDC, over the past 11 years the rate of death from overdose, including opioid narcotics, has increased. In 2010 about 43% (16,651) of overdose deaths were due to prescription opioid narcotics. To combat this, both the federal and state governments are implementing programs to improve treatment, education and prevention of opioid addiction.4
Why Are Opioids So Addictive?
The human body can naturally create its own endogenous opioid molecules. These molecules, which help stimulate pain relief, reward and sympathetic pathways, bind to opioid receptors. There are three main opioid receptor subtypes: µ (mu), δ (delta) and κ (kappa). Molecules from opioid narcotics bind to central nervous system (brain and spinal cord) opioid receptors and target the µ receptor. However, all of these receptors result in activation of neurological reward mechanisms, which can lead to addictive behavior.
Heroin is one of the most common forms of opioid narcotics. It is created from compounds found in opium poppies, namely plant alkaloids. After a person injects heroin into their bloodstream, they feel an immediate rush, often described as a sensation comparable to a sexual orgasm. After this quick reaction, they experience a feeling of generalized well-being for approximately an hour.5
All opioids can cause systemic relaxation and sleep. Indeed, morphine is named after Morpheus, the Greek god of dreams. Yet when a patient uses too much of an opioid and overdoses, there can be severe consequences. These include physiological depression and life-threatening respiratory arrest. The most common cause of premature death in the intravenous drug user population, including heroin users, is drug overdose. About 38%–68% of all drug users have overdosed at least once, and 3% of heroin overdoses result in death stemming from respiratory arrest. Since most of these fatalities do not occur immediately after injection, a quick response is key to preventing respiratory arrest, thereby reducing the likelihood of death.
Naloxone, sometimes known by the brand name Narcan, is a competitive opioid antagonist that works by displacing opioid molecules from their physiological receptor sites. It is used for reversing the opioid-induced respiratory arrest in overdose patients.6 Other side effects stemming from respiratory arrest due to opioids include neurological damage from hypoxia, rhabdomyolysis from lying in one position without moving, and pulmonary aspiration from vomiting. Across the country, opioid overdoses are treated by advanced prehospital providers who administer naloxone, and one of the safest methods for administration is through the intranasal route.2
Why Intranasal?
Overdoses pose risk not only to patients but to responding providers as well. Specifically, needlestick injuries are a major issue for healthcare workers in both emergency services and hospital settings. The CDC has estimated there could be as many as 460,000 needlesticks every year among hospital healthcare workers. In hospitals there is a direct correlation between hepatitis B infections and accidental exposures to hepatitis B. Moreover, there are multiple documented cases of healthcare worker infections with hepatitis C and HIV following needlestick injuries. Obviously, safety precautions must be taken to ensure the well-being of those working in healthcare.7 Opioid-addicted patients have a statistically greater probability of bloodborne viral infections, especially if they’re intravenous drug users. Thus, patients who are treated for opioid overdose may not only suffer from a devastating addictive disease but also from associated negative sequelae.
When naloxone is given intravenously or intramuscularly, there is a risk of a needlestick injury for the provider due to an agitated patient. Since there are many serious infectious diseases that can be obtained from needlestick injury, administering naloxone intranasally, using a needleless system, is safer.7
Intranasal naloxone works by diffusing across the nasal mucosa and entering the central nervous system through the circulatory system transportation. An atomizer is used to increase the amount of surface area onto which the medication is placed. The nose is an excellent site for naloxone administration due to its many blood plexuses. These increase the local circulatory system’s surface area in the nose, which allows for fast absorption of naloxone molecules into the body. If a patient has reduced nasal blood flow, there will be decreased absorption. An increase in nasal secretions or epistaxis will also reduce efficacy because naloxone has potential to be carried along with the excess fluid and flow out of the nose. The dosage of intranasal naloxone is a constant, usually 2 mg.8
Community Programs
To help opioid-using populations prone to overdose, many communities have started creating bystander naloxone-administration programs. Their goal is to provide quick, efficient administration of naloxone to those who overdose, while still training people to call 9-1-1.
In September 2006 Boston decided to combat its overwhelming numbers of opioid overdoses by allowing for bystanders trained by needle-exchange program staff to administer intranasal naloxone. These bystanders were members of the community deemed likely to witness an overdose. Although this training was quick—about 15 minutes—it was very effective.
In particular, during the 15 months studied, there were 385 people trained and 74 reported reversals. In 28% of these overdoses, emergency personnel were also involved (some bystanders did not report about emergency services interactions). As naloxone can have a shorter half-life than an opioid, it is occasionally necessary to administer a second dose; thus the bystanders were provided with two doses. Overall there were few complications with this program. Some participants did have negative interactions with responding emergency services, but there were no arrests of any administering bystander.9
Given this, it is important to recognize the potential difficulties that can occur within the intersection of the medical and legal systems. Many states have Good Samaritan laws that allow limited protection of bystanders who call emergency services to report overdoses.10 For example, in New York an opioid abuser can call in an overdose of another user without fear of being arrested, so long as the caller does not have an existing warrant and is not carrying more than a misdemeanor amount of any controlled substance. Other states with similar legislation include New Mexico, Washington, Connecticut, New York, Massachusetts, Rhode Island, California, Illinois, Colorado, Florida, North Carolina, Vermont, Delaware, Minnesota, Georgia and New Jersey.11,12 Hopefully Good Samaritan laws like these will help save lives because more overdoses will be reported. However, there is a need for increased dissemination of information pertaining to these laws among defense lawyers, police and drug abusers to help establish further compliance.
Naloxone and Public Safety
The actual physical process of administering intranasal naloxone to a patient suffering an opioid overdose is relatively simple. In 2011 the New York Department of Health authorized Basic Life Support (BLS) providers to administer naloxone as part of a pilot program. According to this program, first the provider should determine whether the patient is suffering from a suspected narcotic overdose and has respiratory depression. They should never give naloxone just to determine if a patient has actually used opioids. If there is an inadequate respiratory rate, artificial respirations should also be started based on local protocols. A patient with an inadequate respiratory rate will be breathing below 10 bpm, appear cyanotic and have an altered mental status. To determine if the patient is suffering from a narcotic overdose, at least one of the following criteria must be met: history of an overdose from bystanders; opioid/narcotic paraphernalia on scene; medical history consistent with opioid/narcotic use; or respiratory depression with accompanying pinpoint pupils.
If these criteria are met, a BLS provider can administer intranasal naloxone. The patient should then be transported to the closest medical facility while the provider maintains appropriate care. If the patient’s respiratory rate does not increase to 10 bpm after 10 minutes, they should get a second dose using the same procedure.
Additional exclusion criteria for use of intranasal naloxone may include cardiopulmonary arrest, nasal trauma, nasal obstruction and epistaxis. If naloxone is given during a cardiopulmonary arrest, it will not be effective until the person regains spontaneous circulation. Therefore, while intranasal naloxone can resolve opioid overdoses caused by heroin and opioid medications if the patient has a pulse, naloxone cannot pharmacologically revive a cardiac arrest patient.3
There are rare, but possible, physiological complications of naloxone administration after an opioid overdose. The most serious of these reported is noncardiogenic pulmonary edema. The mechanism behind this response has not been entirely elucidated but may be due to the rapidly induced sympathetic nervous system signals from the naloxone administration.13 The body’s sympathetic system induces the fight-or-flight response, leading to an increased heart rate, arterial vasoconstriction and elevated respiratory rates, along with many other physiological responses.2
One way to reduce the likelihood of pulmonary edema is to make sure the patient has a patent airway. Pulmonary edema is a serious and very uncommon side effect of naloxone.13 Withdrawal from opioids can also result in several negative physiological consequences, including confusion, headache, tremors, sweating, nausea, aggressiveness and tachycardias. These effects may also occur when a patient suffering from an opioid overdose is revived with naloxone, as naloxone will quickly displace opioid molecules from their physiological receptor sites.14 Therefore, since the opioid is no longer blocking pain pathways, signaling reward systems of the brain or stimulating peripheral sympathetic nerves, the patient may experience dysphoric symptoms.5
It is important to note that intranasal naloxone use is technically off-label, as naloxone is only approved by the FDA to be administered intravenously, intramuscularly or subcutaneously.15 However, a medical director may allow BLS providers to administer intranasal naloxone through a standing order.16
New York’s Program
New York’s intranasal naloxone pilot program for the emergency medical services community was developed for several reasons. This program specifically allows emergency medical technicians to administer intranasal naloxone. Since there are many more EMTs than paramedics, this has helped increase rates and hasten the administration of naloxone for overdose. It is especially useful in communities with a dearth of paramedics.
For example, in the rural upstate New York town of Hoags Corners, the local volunteer ambulance service, without a nearby paramedic, was able through this program to revive a patient suffering from an opioid overdose. Within minutes the patient went from being unresponsive without respirations to arguing with the volunteers. Many police officers are also certified as EMTs and are often the first on overdose scenes; thus they are an important component for improving the overdose reversal rate in New York as well.17 This pilot program was a success and has been incorporated directly into the state BLS protocols.18
In Suffolk County, local police officers carry intranasal naloxone and already have been able to revive multiple patients. Participating departments were chosen based on their annual rates of overdoses and hospital transportation times. In 2011, Suffolk County experienced 231 deaths due to controlled-substance overdoses, 75% of them owing to opioid painkillers. Overdose rates are increasing, and for that reason the local Suffolk Regional Emergency Medical Services Advisory Committee expanded its intranasal naloxone programs.19 The results are encouraging: In 2013, Suffolk County first responders treated 563 overdose patients, and 184 of them were given naloxone by Suffolk County police officers.20
Rochester is also expanding its naloxone administration program by training more than 400 firefighters and providing them with kits to revive patients. After this was implemented, within a two-week span, the department revived four people.21 Of additional interest is a recent effort by New York physicians to coordinate and provide training to the state police in naloxone use in emergency situations.22
Another state that has taken an innovative approach is New Mexico. In 2001, the state created a law to release from liability any physician or bystander who administers naloxone. As mentioned before, New Mexico also allows limited immunity for bystanders who report an overdose, and since 2004 various state police departments have received training to carry and administer intranasal naloxone.23
Finally, Massachusetts has notable history of aggressive treatment of opioid addiction. Boston EMS has long considered opioid overdose a basic life support call and has administered BLS naloxone since 2006. Several Boston-area cities have successfully expanded naloxone programs to their police departments as well. In fact, the Massachusetts model was reviewed at great depth prior to deciding to try the pilot project in New York, and its success prompted the decision to go forward.
Additionally, the Quincy police department recently made the news because it was the first department to train all its patrol officers in the use of naloxone and have each patrol unit equipped to treat opioid overdoses.24 Similarly, the New York’s Rensselaer County sheriff’s patrol requires each of its officers to be EMTs, and they have been equipped with naloxone since May 2012.17 It is encouraging that such law enforcement preparation for and treatment of opioid overdose is experiencing positive media coverage.
Survival and Recovery
Opioid addiction recovery is a long process. A survived overdose is frequently a chance for a user to enter rehabilitation. This will not work for everyone, but for as many as 10%–20%, the overdose that requires treatment may be the wakeup call to seek help. Most recovering addicts are not successful with only psychosocial interventions such as talk therapy and must also use pharmacological interventions like methadone, buprenorphine and naltrexone as supplements. Studies are currently being conducted to investigate recovery rates in various epidemiological groups, including adolescents, chronic pain patients and prisoners.7
By giving many of these overdose patients the potential for recovery, the administration of intranasal naloxone reaffirms the possibility of turning away from addiction toward a second chance at life.
Conclusion
Intranasal naloxone is an excellent method of safely administering an opioid antagonist to a person suffering a severe opioid overdose. It can restore spontaneous respirations and prevent cardiac arrests.1 Expanding the use of this drug to basic EMTs, as well as firefighters and police officers, allows the potential for earlier intervention prior to paramedic arrival and in many communities with only basic life support providers.23 The increased administration frequency will lead to improved survival and long-term recovery from opioid overdoses.2 Side effects from naloxone are exceedingly rare, and intranasal administration is a safe technique for the provider, since it does not involve needles.7
With so many examples of successful basic life support use of naloxone, there can be little doubt as to the necessity of training more first responders in its administration. Moreover, given the increasing rate of opioid overdoses in various communities—from the small town of Hoags Corners to the suburbs of Suffolk County to the city of Boston—it is not only a matter of necessity; it is one of urgency.
References
1. Walley AY. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ, 2013; 346: f174.
2. Kelly AM, Koutsogiannis Z. Intranasal naloxone for life-threatening opioid toxicity. Emerg Med J, 2002; 19: 375.
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9. Doe-Simkins M, Walley AY, Epstein A, Moyer P. Saved by the nose: bystander-administered intranasal naloxone hydrochloride for opioid overdose. Am J Public Health, 2009 May; 99(5): 788–91.
10. Drug Policy Alliance. 911 Good Samaritan: Explaining New York’s Fatal Overdose Prevention Law, www.drugpolicy.orghttps://s3.amazonaws.com/HMP/hmp_ln/imported/911_Good_Samaritan_Informational_Brief.pdf.
11. Drug Policy Alliance. 911 Good Samaritan Fatal Overdose Prevention Law, www.drugpolicy.org/911-good-samaritan-fatal-overdose-prevention-law.
12. The Network for Public Health Law. Legal Interventions to Reduce Overdose Mortality: Naloxone Access and Overdose Good Samaritan Laws, www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf.
13. Horng HC, Ho MT, Huang CH, Yeh CC, Cherng CH. Negative pressure pulmonary edema following naloxone administration in a patient with fentanyl-induced respiratory depression. Acta Anaesthesiol Taiwan, 2010 Sep; 48(3): 155–7.
14. Kerr D, Dietze P, Kelly AM. Intranasal naloxone for the treatment of suspected heroin overdose. Addiction, 2008 Mar; 103(3): 379–86.
15. Nelson R. Ethical and Regulatory Considerations in Drug Development for IN Naloxone, www.fda.gov/downloads/drugs/newsevents/ucm300877.pdf.
16. Walley AY. Overdose education and naloxone rescue kits in Massachusetts, https://redproject.org/wp-content/uploads/2014/01/Overdose-Education-and-Naloxone-Distribution-Massachusetts-Part-1.pdf.
17. Crowley CF. EMTs embrace overdose fix. Times Union, www.timesunion.com/local/article/EMTs-embrace-overdose-fix-4398670.php.
18. New York State Department of Health. Intranasal Naloxone (Narcan) for Basic Life Support EMS Agencies, www.health.ny.gov/professionals/ems/policy/13-10.htm.
19. Glowatz E. Suffolk initiative to combat overdoses shows early promise. Times Beacon Record, www.northshoreoflongisland.com/Articles-News-i-2012-08-02-93321.112114-sub-Suffolk-initiative-to-combat-overdoses-shows-early-promise.html.
20. Simon D. Heroin antidote Narcan made available statewide. Newsday, www.newsday.com/long-island/suffolk/heroin-antidote-narcan-made-available-statewide-1.7598007.
21. YNN Staff. RFD Uses New Drug to Revive Overdoses. Time Warner Cable News, https://rochester.twcnews.com/content/news/598343/rfd-uses-new-drug-to-revive-overdoses/.
22. New York State Division of Criminal Justice Services. New York State trains law enforcement officers to combat overdoses from heroin, other opioids; provides overdose reversal medication at no cost, www.criminaljustice.ny.gov/pio/press_releases/2014-06-26_pressrelease.html.
23. New Mexico Department of Public Safety. State police officers trained in use of Narcan, www.nmsp.dps.state.nm.us/newsReleases/NMSP/2004/NMSPnewsRelease_08.19.04.htm.
24. PoliceOne.com. Mass. police first to get overdose-reducing nasal spray, www.policeone.com/police-products/tactical/tactical-medical/articles/6340480-Mass-police-first-to-get-overdose-reversing-nasal-spray/.
Emma Furlano is currently attending Stony Brook University School of Medicine after graduating with a BS in biology from Rensselaer Polytechnic Institute. She has volunteered as an EMT in her community in addition to working several years in commercial EMS. Most recently she completed an internship at Suffolk Regional EMS Council in partnership with Albany Medical Center.
