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by Mike McEvoy

Why intranasal naloxone is a safe antidote for anyone to administer

It shouldn’t be a turf battle; EMTs, police, firefighters, friends and family members can all use this life-saving tool

By Mike McEvoy

Opioid abuse is a major international health problem that is worsening each year, causing increased 911 call volume for opioid induced respiratory depression, altered levels of consciousness and deaths.

The opioid heroin spiked in use in the United States from 373,000 yearly users in 2007 to 669,000 users in 2012 according to SAMSHA (Substance Abuse and Mental Health Services Administration).

Not surprisingly, fatal heroin overdoses also increased by 45 percent between 2006 and 2010, according to the U.S. Drug Enforcement Administration. Drug overdoses have surpassed motor vehicles crashes as a cause of death in the U.S. for the past several years.

In March, U.S. Attorney General Eric Holder deemed rise in heroin overdoses a public health crisis, and vowed to increase law enforcement actions.

He urged law enforcement agencies and first responders to carry naloxone, an opioid reversal agent [1]. This caused a surge and in some cases, local competition between law enforcement, fire and EMS to carry and use intranasal (IN) naloxone.

Heroin is on the rise

Opioids are natural or synthetic substances with morphine-like activity. They depress the central nervous system, provide analgesia (pain control) and can cause feelings of euphoria. Both prescription and nonprescription opioids are involved in recreational misuse, abuse, addiction, dependence, and overdoses.

Prescription opioids include: morphine, fentanyl, codeine, buprenorphine, hydrocodone, hydromorphone, tramadol, meperidine, methadone, oxycodone, oxymorphone, loperamide, and others. Heroin is a derivative of morphine and garners considerable media attention. 

“Designer” opioids are created in makeshift laboratories and change frequently in attempts to evade legislation and law enforcement. Examples include 3-methylfentanyl (aerosolized during the Moscow theater hostage situation in 2002) and α-fentanyl (also known as China White). 

Factors fueling the rise in heroin use include increased supply, decreased cost, and greater purity[2]. Latin American drug cartels have vastly increased their heroin production, significantly increasing supply throughout the United States despite efforts to curtail shipments.

A bag of street heroin in Chicago sells today for $20 and is 7 to 10 percent pure. Ten years ago, the same heroin (if a potential buyer could even find it) would have cost up to $150 and been only 2 to 3 percent pure.

Today’s purity means the drug can be snorted rather than injected, as was necessary with less pure heroin. Needleless administration and cheaper cost have made heroin more accessible and cheaper than prescription opioids such as oxycodone (Percocett, Oxycontin) and hydrocodone (Vicodin), which are increasingly difficult to obtain on the black market. Greater numbers of prescription opioid users are turning to heroin, which is also leading to a great number of overdoses.

How to recognize a heroin overdose

Most overdoses fall into the following categories:

  • Recreational use.
  • Attempt to hide drugs from law enforcement by stuffing them into a body orifice.
  • Deliberate attempt to cause self-harm.
  • Accidental overdose — a child chews on a discarded fentanyl patch or ingests an adult’s prescription opioid, or a post surgical patient takes excessive amounts of a prescribed opioid.
  • Swallowing large packages of opioids to transport them across borders (body packing).

In some of the previous instances, a high index of suspicion is necessary. Physical exam findings in opioid overdose classically include pinpoint pupils (miosis), respiratory and CNS depression, and often flushing, hypotension and decreased bowel sounds.

Miosis typically lasts about six hours but may not be present if the patient co-ingests a stimulant or if respiratory depression was prolonged and profound enough that a hypoxic brain injury occurred. Other, less common findings associated with opioid overdose include non-cardiogenic pulmonary edema, bradycardia, and rhabdomyolysis.

Death from opioid overdose is rare and uncommonly immediate. Surveys of heroin users indicate that upwards of 38 percent have overdosed at least once. Fortunately, mortality associated with heroin overdoses is very low, in the range of 3 to 6 percent.

The common cause of death is hypoxia resulting from respiratory depression, with about 15 percent of deaths occurring immediately after drug use. This offers a typical window of 40 to 50 minutes during which interventions are likely to be successful [3]. We continue to have a very minimal understanding of the actual pathophysiology associated with death from opioid overdose.

Who’s qualified to administer naloxone?

Naloxone is a synthetic derivative of oxymorphone that competes to bind with opioid receptors and is the antagonist of choice for opioid overdoses. While originally given intravenously (IV) or intramuscularly (IM), naloxone is increasingly being administered intranasally.

First reported in 1984 as effective for opioid reversal in rats, IN naloxone has been studied repeatedly in humans since 1992 [4]. When administered IV, naloxone is effective within three to five minutes (mean 3.7 minutes) and typically has a short duration of action, lasting for 30 minutes to an hour. Given IM or IN, naloxone’s effects are usually evident within three to seven minutes (mean 4.2 minutes) and the duration of action longer, lasting up to 90 minutes IN and up to 2 hours IM [3]. 

Actual pharmacokinetic studies comparing IM to IN naloxone in human volunteers show peak concentrations of IN naloxone occur in six to nine minutes and IM peaks in 12 minutes [5].

Early studies of alternative routes for administration of naloxone met some stumbling blocks. There was considerable uncertainty about IN dosing of naloxone, coupled with the only strength available being 0.4 milligrams per mL, yielding a concentration significantly greater than the maximum 1 mL volume recommended for intranasal medications [4].

One prehospital study used nebulized naloxone with good success, but only in patients with spontaneous respirations (not requiring bag-valve-mask assistance)[6]. Subsequent studies using IN naloxone manufactured or compounded at 1 or 2 milligram per mL found that a total dose of 2 milligrams, administering 1 milligram into each nostril (nare) with an atomizing device designed for intranasal drug administration (MAD™ Nasal, Wolfe Tory Medical, Inc.) had the best effect. Most protocols currently in effect utilize this dosing strategy, with naloxone concentrations that limit the total volume to 1 mL or less per nostril [7].

Between 1996 and 2010, community prevention programs reported training 53,032 people in naloxone administration, with 10,171 overdose reversals [8]. The vast majority of these were citizens, either family members or friends of known opioid drug users. The success of these programs speaks for itself and suggests that, like AEDs and epinephrine auto-injectors, anyone can be trained to administer naloxone in the prehospital environment.

Published studies on EMS use of intranasal naloxone cite numerous advantages over other routes of administration. Chief among these are scene safety issues.

Eighty percent of intravenous drug users (IVDU) in major metropolitan areas are HIV or hepatitis C positive [7]. Given the ongoing incidence of needle stick injuries to prehospital providers, IN administration of naloxone seems an intuitive provider safety advantage.

Although often cited as a disadvantage, IN administration has been repeatedly shown to be more rapid than IV dosing. Multiple studies comparing median time from arrival to clinical response demonstrate an eight minute time for IN and 10 minute time for IV when factoring in the equipment set-up and IV placement delays [7]. 

Despite the less invasive nature of IN naloxone, another advantage is an equal efficacy when compared to IV administration. Numerous studies of IN naloxone have demonstrated an overall response rate of 83 percent, matching that seen with IV naloxone [7].   

Intranasal administration is best for basic care

IN administration of naloxone is a hot topic, but not a new concept in prehospital medicine. Optimal outcomes can be achieved if we make it our mission to equip as many friends and family members of IV drug users, law enforcement officers, firefighters, EMS providers and other first responders with the only antidote needed to save a life: intranasal naloxone. 

This should not be a turf battle; patients are dying before we can arrive to treat them. It’s time to put a harmless life-saving tool into the hands of everyone and anyone who might be there or get there before we show up on scene. That would be caring for our community.

While poorly documented with any large studies, IN naloxone clearly results in a slower, more gradual distribution resulting in a much more gradual emergence from opioid effects and considerably less prehospital violence and aggression. A small number of studies have highlighted this additional scene safety advantage [7] and a search of paramedic and EMS blogs  yields dozens of anecdotal reports confirming gradual awakening is the norm with IN naloxone. 

Every time I read an editorial or blog post from a physician or paramedic touting the grievous risk of violent awakenings associated with “inexperienced” rescuers administering IN naloxone, I immediately recognize an author who has no experience in actual use of IN naloxone. 

In my experience and the studies I have participated in, not once have I seen an abrupt or untoward awakening following IN naloxone administration. I have, however, witnessed (and caused) innumerable unpleasant awakenings with IV naloxone.

A Seattle study of IN naloxone administered by BLS providers cited a 15 percent rate of “naloxone associated violence” which was probably exaggerated as the authors included agitation and vomiting as violent behavior when, in fact, these were probably withdrawal symptoms [9].

Also consider the odd locations where opioid overdoses often occur. In the absence of ALS, and the inability of BLS or law enforcement responders to administer an opioid antidote, it is quite likely that overdose victims would need to be carried significant distances to a waiting ambulance or ALS unit.

Such patient movements, especially over difficult terrain, have tremendous potential to result in back or other musculoskeletal injuries to the care providers. Patient compromise is also possible should the rescuers not be able to support respirations throughout patient movement. With the availability of IN naloxone, many overdose patients recover their ability to ambulate from the scene, thus limiting potential injury to responders.

Disadvantages of naloxone include the initiation of withdrawal symptoms (regardless of how it’s administered). Unlike other agents, opioid withdrawal signs and symptoms, which include tremors, sweating, agitation, nausea, vomiting, and anxiety are non-life threatening and resolve relatively quickly (30 to 60 minutes) due to the short half-life of naloxone [7]. 

Shortages of naloxone have occurred and the recent surge in use may result in additional shortages. Originally sold by Endo Pharmaceuticals under their brand name, Narcan, the surge in community naloxone programs unfortunately coincided with Endo’s discontinuation of their naloxone products in July 2013 after 41 years of sales. The resulting shortage has since been alleviated by the two remaining manufacturers, Amphastar and Hospira. 

On the fast track for approval, expected by March 2015, is a naloxone nasal spray from AntiOp. Naloxone is not currently approved by the U.S. Food and Drug Administration for intranasal use hence, manufacturers cannot sell naloxone prepackaged for IN use.

EMS services can order naloxone IN kits, but such use is considered “off label” by the FDA. The end result increases the price of IN naloxone kits used by civilians, law enforcement and first responders to the $50 range whereas the naloxone itself retails for only $20 per dose.

We have a problem and a solution. Opioid overdoses are increasing worldwide. While heroin is a common culprit today, even in rural areas,, patients may overdose on any variety of both prescription and non-prescription opioids. Recognizing the circumstances and classic signs and symptoms of opioid overdose can save a life.


1. U.S. Department of Justice, Public Affairs.  News Release: Attorney General Holder, Calling Rise in Heroin Overdoses ‘Urgent Public Health Crisis,’ Vows Mix of Enforcement, Treatment.  March 10, 2014.  On-line, available at:

2. Gray E. Heroin gains popularity as cheap doses flood the U.S.  Time. 2014 (Feb 4);183.  On-line, available at:

3. Kerr D, Dietze P, Kelly A.  Intranasal naloxone for the treatment of suspected heroin overdose.  Addiction.  2008; 103:379-386.

4. Ashton H, Hassan Z.  Intranasal naloxone in suspected opioid overdose.  Emerg Med J. 2006;23:221-223.

5. Dowling J, Isbister GK, Kirkpatrick CM, Naidoo D, Graudins A.  Population pharmacokinetics of intravenous, intramuscular, and intranasal naloxone in human volunteers.  Ther Drug Monit. 2008;30:490-496.

6. Weber JM, Tataris KL, Hoffman JD, Aks, SE, Mycyk MB.  Can nebulized naloxone be used safely and effectively by emergency medical services for suspected opioid overdose?  Prehosp Emerg Care.  2012;16:289-292.
7. Wermeling DP. A response to the opioid overdose epidemic: naloxone nasal spray.  Drug Deliv Transl Res.  2013;3:63-74.
8. Centers for Disease Control and Prevention. Community-Based Opioid Overdose Prevention Programs Providing Naloxone — United States, 2010.  MMWR. 2012;61:101-105.  On-line, available at:
9. Belz D, Lieb J, Rea T, Eisenberg MS. Naloxone use in tiered-response emergency medical services system.  Prehosp Emerg Care.  2006;10:468-471.


About the author

Mike McEvoy, PhD, NRP, RN, CCRN is the EMS Coordinator for Saratoga County, New York and a paramedic supervisor with Clifton Park & Halfmoon Ambulance. He is a nurse clinician in cardiothoracic surgical intensive care at Albany Medical Center where he also Chairs the Resuscitation Committee and teaches critical care medicine. He is a lead author of the “Critical Care Transport” textbook and Informed® Emergency & Critical Care guides published by Jones & Bartlett Learning. Mike is a frequent contributor to and a popular speaker at EMS, Fire, and medical conferences worldwide.Contact Mike at
The comments below are member-generated and do not necessarily reflect the opinions of or its staff. If you cannot see comments, try disabling privacy and ad blocking plugins in your browser. All comments must comply with our Member Commenting Policy.
The Jennifer Act The Jennifer Act Monday, June 02, 2014 9:46:56 AM I am researching on Naloxone kits for Indiana. I have contacted ISP. They told me their first responders do not carry Naloxone kits. If you know how we can get these kits in Indiana, please let me know. Thank you. Sharon Blair (Advocate for Indiana & Florida)
Helen Tolbert Helen Tolbert Friday, June 06, 2014 4:19:35 PM Dr. Ariba God will continue to bless you more abundantly, for the good works you are doing in peoples life, I will keep on writng and posting testimonies about you on the Internet, I’m Helen Tolbert, I was a HIV patient, I saw a blog on how Dr. Ariba cured someone, I contacted him and also got my healing, kindly email him now on Or email me on
Karen Carrera Karen Carrera Friday, June 13, 2014 9:33:38 PM I never believed that I would ever be cured of HIV on till now. Am From USA i saw some testimonies on the internet on how Dr. Ariba cured a girl of HIV/AIDS. but because i was desperate i tried and contacted him on and luckilly he prepared the cure for me and sent me a parcel and after two days of drinking the content of the percel as instructed, i was healed totally. if you need his help, you can contact him on Or and get cured. Kind regards,
Clarice Whiteside Clarice Whiteside Wednesday, July 23, 2014 9:26:24 AM You shouldn't post this bull shit.
Katie Mennow Noetzel Katie Mennow Noetzel Wednesday, July 23, 2014 11:58:10 AM I think that due to the sue happy country we have, this just sets people up for liability. "I didn't know this would wear off before the heroin" and they die anyway. It is all about choices.
Dwayne Womack Dwayne Womack Wednesday, July 23, 2014 12:12:18 PM What a disappointing article. It obviously set out with an agenda and then tried (unsuccessfully in my opinion) to bend everything to fit that agenda. And to choose to use a drug based on the fact that it will allow you to walk patients to the ambulance instead of carry them...Except in extreme cases (remote/wilderness) the immoral and unethical nature of this suggestion makes me want to spit. There's no turf war for most of us, but it appears that there is for the author. He's either too ignorant to see the actual issues, or is purposely misrepresenting the issues...either case make this article kind of a joke.
Christopher Bare Christopher Bare Wednesday, July 23, 2014 1:40:58 PM I don't know man. It's far better than the typical "Narcan enables bad behaviour" and Darwan Award arguments against making naloxone more widely available. Having providers just look outside of their limited and often jaded box is a step in the proper direction.
Nick Marx Nick Marx Wednesday, July 23, 2014 2:03:09 PM If cops want ems back take it all back.
Wendy Alice Whittaker Heath Wendy Alice Whittaker Heath Wednesday, July 23, 2014 4:03:38 PM Actually, that was an EXCELLENT article that was well written. With citations. And awareness of drug shortage and the fact that IN administration of naloxone is currently OFF LABEL for chrissake. I'm not saying hand IN naloxone to every bystander... but I am saying give it to the FD and the BLS units, with ALS chase. That makes the most sense. Reverse the respiratory depression enough to prevent the patient from dying, get the ALS unit there, get them to definitive treatment. Dunno about giving it to PD... but BLS and Fire? Certainly.
Michael N. Ruff Michael N. Ruff Wednesday, July 23, 2014 5:56:48 PM Karen, post your snake charmer medicine elsewhere.
Benjamin Harris Benjamin Harris Wednesday, July 23, 2014 10:31:39 PM I only have 10 years of experience in prehospital care, with a background in chemistry, biology, pharmacology, and pathophysiology. Therefore I will let Timmy the 120 hour EMT-B wonder kid answer for me, as his opinion will be given equal weight to my own anyway. Take it away, Timmy.
Christopher Grace Christopher Grace Thursday, July 24, 2014 4:28:59 AM My issue with giving BLS the naloxone kits has nothing to do with the medication it self. The medication is pretty benign. My issue is with incompetence, and lack of accountability. While I agree that ALS can screw up, they are not perfect, there is a least a system in place to review and reprimanded them when needed. BLS, in NJ anyways, have next to no over site and in turn if they do something to harm a pt no backlash. In fact I've had BLS providers say let them try and sue us they can't because I'm just a volunteer, or for the paid providers just kinda shrug like it would not happen. Again while the drug it self is no biggy, my issue is it being giving to say a diabetic and then just sitting there and watching the pt become hypoxic and die. Some may say that would never happen, and I'm just paranoid, but when I watch providers all but kill pt's and several occasions, and still are on ambulance it worries me. Instead of giving them more responsibility, we need to make sure they can handle and perform the responsibility we give them now.
Adam 'Gonzo' Gonzalez Adam 'Gonzo' Gonzalez Thursday, July 24, 2014 6:44:25 AM The issue with that isn't the part where you say 'giving it to say a diabetic,' but rather the part where you say 'watching the pt become hypoxic and die.' Anyone who does that, who watches a patient become hypoxic and die, does not have an issue with using narcan properly. Their issue is with the 'B' in 'ABCs,' and they shouldn't have an EMT cert to start with.
Christopher Grace Christopher Grace Thursday, July 24, 2014 7:00:50 AM And the is my point Adam. There is no clinical oversight on the BLS side. What recourse is there when BLS screws up? Paid or volly You have seen it just as much as I have. I would have no problem with naloxone if we there was better clinical oversight and the norm would become providers who can hand the ABC of EMS.
Scott Crittenden Scott Crittenden Thursday, July 24, 2014 8:01:05 PM Everyone seems to forget that the providers they want to give IN Naloxone to should already have the capability to keep an OD patient alive with a BVM. People die from hypoxia, not a Naloxone deficiency. Like Mr. Grace I too fear many providers will skip over ABC and go straight to N.
Reg Allen Reg Allen Friday, July 25, 2014 11:33:56 AM Not sure how I feel about this just yet. I'm wondering if just putting BVM's in patrol cars (already in Fire Trucks) would be a better and cost effective option. BVM's dont expire. Never the less, the one fix fits all is probally not the answer. If a system truely has extended paramedic response times, narcan may be warranted. If paramedics are typically arriving with, or a minute or two behind the BLSFR, then it seems like a well trained EMT with a BVM may be a better answer. It'll be interesting to see what really happens as Narcan gets distributed to and used by BLS providers. At this point our opinions dont matter, the Jeanie is out of the bottle.
Helen Tolbert Helen Tolbert Saturday, July 26, 2014 12:02:25 AM Dr. Ariba God will continue to bless you more abundantly, for the good works you are doing in peoples life, I will keep on writing and posting testimonies about you on the Internet, I’m Helen Tolbert, I was a HIV patient, I saw a blog on how Dr. Ariba cured someone, I contacted him and also got my healing, kindly email him now on Or
Helen Tolbert Helen Tolbert Sunday, July 27, 2014 3:09:30 AM Dr. Ariba God will continue to bless you more abundantly, for the good works you are doing in peoples life, I will keep on writing and posting testimonies about you on the Internet, I’m Helen Tolbert, I was a HIV patient, I saw a blog on how Dr. Ariba cured someone, I contacted him and also got my healing, kindly email him now on Or
Jeffrey Brown Jeffrey Brown Wednesday, August 06, 2014 6:24:43 AM One thing I think the Author missed is that most IV drug users have very poor veins. (from long years of shooting up). I've seen Paramedics search for 5-10 mins looking for a vein, and missing IV's, the IN route allows ready access and fast and safe administration on Narcan. I'm wondering if an increase in dosage is needed, one concern I have is the fact that IN route relies on the Patients respiratory to deliver the Narcan, we may need to assist respirations to ensure proper distribution of the drug. All in all I felt this was a good article, and am forwarding it to my services clinical director for his attention.
Mike von Neupert Mike von Neupert Wednesday, August 06, 2014 5:31:01 PM Wendy Alice Whittaker Heath By "Fire", I'm guessing (read: hoping) you mean medically trained firefighters and not members with their only medical credentials being a CPR card and a pair of gloves.

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