Overdoses and Naloxone

I have been treating heroin overdoses for over 25 years. I remember my first few in the projects of Atlantic City. At that time, people would overdose in their homes and someone would call 911 and then usually run away. We would find a patient cyanotic with agonal breathing. BLS would ventilate, ALS would give naloxone (the generic name for Narcan) and we would transport to the hospital. People rarely died for the heroin of the time.

In general it was a condition of the poor and usually minorities. (Different ethnic groups and regions had their own drugs of choice, for example reference the use of methamphetamine by Caucasians in the northwestern part of the US.). So, no one talked about it. It wasn’t in the media. It was not an overly large percentage of our calls in EMS.

Fast forward to about 5-8 years ago. The heroin was becoming ‘stronger’ and ‘more pure.’ Users (I am going to use this term instead of addicts) were looking for a better high. Note none of them wanted to go unconscious – that’s not a high. Just like if you drink to much and miss most of the party. But they wanted to shoot for the edge.

So, what is happening physiologically here? In order to understand it well, we need to discuss the subjects of dependency, tolerance and addiction.

Humans have addictive personalities. Whether it is football, gambling, social media, we want it and in some cases we want it know.

Let’s say you need you coffee in the morning. Whatever your routine is, whether it is making it at home or going to your local Starbucks, you feel you need it to function. We see memes about “Don’t talk to me until I have my coffee.” This is dependency. If you don’t get it you will be miserable.

Now coffee does not have the next concept but many other substances do. Perhaps you like drinking alcohol. You can still function, have a job, etc., but every Friday and Saturday you enjoy your beer, whiskey, white claw or red wine. You may like the relaxation you feel, a slight buzz. Over time, one you find that you need to have a little more than you used to have to achieve the same feeling. Your body adapts to the amount and needs more. This is tolerance, and is common with many substances, even narcotics used for chronic pain management.

Lastly, lets go back to coffee. You arrive at your local Starbucks and find it closed. There is no other coffee to be had for 10 miles. You look threw the window and inside you see….coffee! You think for a minute, look around and find a rock. You throw it threw the window and you go get your coffee. This is a behavior, this is addiction.

Now there are some that will say well you still made a choice, that being addicted is a choice. I believe the first few times someone uses in their life it is a choice. But over time, the brain is re-wired to where this is no longer a choice – the desire and cravings are so strong, that virtually no one can just stop cold turkey.

Here is where medicine is failing. We need to address two things – the desire and cravings for the drug, and the brain changes that force the behavior, the addiction.

We actually have tools to address the cravings. Initially it was only methadone, an opioid invented by the Germans during World War 2. We have found tat methadone does satisfy most of the cravings but does not cause the ‘high’ that is felt with other drugs. It is controversial. Some addiction treatment groups feel we are just replacing one addiction for another, and that might be the case. But until we can figure out part two above, managing the addiction and behavior, it is the best we have. It is part of MAT – Medication Assisted Treatment.

Another controversy about methadone is that it is very limited in who can give it out so they are centralized in methadone clinics, and of course no one wants them in their neighborhood. In order to prevent someone from stockpiling and taking a bunch of methadone to possibly cause a high, those using it as part of their treatment plan come every day and get it in liquid form.

In order to address this obstacle, recently additional options have become available that could be prescribed in a medical office setting. One is buprenorphine (“bupe”), which was approved by the FDA in 2002. It’s brand name is Subutex. The problem with bupe is that it was possible for the pills to be crushed and several to be injected causing a high.

So shortly thereafter, another drug was formulated – Suboxone. This was a combination of buprenorphine and naloxone, in either pill or strip formats. Naloxone was virtually no bio-availability when given orally, but if the patient in treatment tries to crush up the Suboxone pills and inject it, the naloxone is present and mitigates the euphoria. These are starting to be prescribed from emergency departments if overdose victims come in and are willing to try to get help.

These are stop gaps. One EMS physician I know said this is our dialysis. Other than transplant, we can’t treat kidney failure. So dialysis keeps them alive until we can. Same with MAT – not ideal but it has been found to decrease crime – fewer users steal to get heroin.

At the same time that the heroin was getting stronger, the users were becoming more diverse. We would start hearing whisperings of young adults dying in surburbia. A group of parents, mostly moms, recognized two things. Their children were dying alone, when they knew most of the time they were not using alone. They would go unconscious and then their friends or fellow users would run away and sometimes their child died. Second, they started to hear about the reversal drug naloxone.

Naloxone had just started to be carried by law enforcement in other states, notably Quincy, MA, which had a large overdose and drug use problem. This was controversial. Many police felt it was not their job and I do not disagree with this concept. I believe we do our law enforcement a large injustice sending them to medical calls with minimal or no training. However, we also recognize that the two most important changes that has resulted in a huge survival rate in cardiac arrest are bystander CPR and LEO AED use. There are public relations aspects. And, if the LEO (law enforcement officer) is there anyway, they really need to do something. I remember going to a call where an overdose victim was not breathing and 4 officers were just standing around. I this day of video clips and cameras everywhere, that is no longer acceptable.

So what is naloxone? We have had it for decades. It is a competitive antagonist of opioids for the narcotic receptor. It blocks the receptor so the effects of the opioid are reversed. It lasts from 30-90 minutes and formerly was given only by ALS or the hospital.

Initially we would give 2mg IV. However we found that we were putting these patients into immediate withdrawal – they would wake up vomiting, sweating and combative. So we reduced that to 0.4mg IV, it was better but not perfect.

Soon it was found that it could be given IN – intranasally as well. Initially this was done by attaching a mucosal atomizer device to the standard luer lock of the injectable naloxone, giving 2mg IN to the patient. More recently a 4mg version has come out that is simpler with no assembly.

Now some advanced providers feel this 4mg is too much. But if you look at the actual data below, 4mg IN achieves the SAME blood levels of 0.4mg of IV naloxone, just a few minutes later with a more gentle rise. This is why we see less withdrawal symptoms in the IN version.

Link to image:

https://www.researchgate.net/figure/Mean-plasma-naloxone-concentrations-observed-values-dosing-to-120-minutes-left-and_fig1_321108378

My opinion is once the patient receives 2 doses of 4mg naloxone by any source, the patient should not receive any more and just ventilate to the hospital. Perhaps is a poly-pharmacy overdose, or it is something else in its entirety. Remember it should only be given in a suspected opioid overdose with decreased ventilation and level of consciousness. An unconscious patient with a RR of 30 and a normal pulse is NOT experiencing an opioid overdose.

The next controversy I often hear is we should not have a goal of waking the patient up completely but rather just get them breathing. I do not disagree. That is why I want to see a single dose given and up to 5 min of ventilation assistance. I know LEOs often are giving multiple doses especially if they do not carry BVMs. We are doing our best to educate them. But I do not support giving minute doses of narcan every 5 minutes to get them breathing but not waking them up – that is just going to take too long. If they start breathing and are just somnolent, then start transport and give no additional. This is rare however. And, note that in the hospital we kinda need a real diagnosis. I can’t leave someone unconscious for hours ‘hoping’ it is just opioids and then find out later they have something else going on. I need the bed too.

Among the most absurd things I have heard is that we should just intubate them all until it wears off. Do you know how dangerous intubation and ventilator use is? And just how many ICU beds do we have? Not an option.

Perhaps you have heard that large amounts of naloxone can cause pulmonary edema. This is not accurate.

This article by an EMS Physician goes more in depth:

http://www.naemsp-blog.com/emsmed/2018/9/13/not-your-typical-wake-up-a-review-of-opioid-related-noncardiogenic-pulmonary-edema

Essentially we are not sure what causes pulmonary edema in an apneic overdose but it is largely multi-factorial. The first case was described by Dr. Osler in 1880, long before naloxone existed. There may be an association, not a causation – perhaps larger overdoses cause it which in turn need larger doses of naloxone. Regardless, this is something to evaluate post naloxone use with lung sounds, pulse ox and questioning the patient. If crackles, dyspnea or low pulse ox are noted, then initiate CPAP and transport. CPAP has been found to work very well in these patients.

OK, so we give one dose of naloxone and ventilate, and the patient wakes up. What then? Ideally, just say lets go the hospital so they can keep an eye on you for a bit. Some hospitals also have various resources to assist if the patient is amenable. ALS can be canceled if they are awake and alert and vitals are relatively normal.

What if they don’t want to go and are adamant? Well, they are no longer considered intoxicated because naloxone is blocking all receptors. The concern of them going unconscious again and dying is actually unfounded – medical research has looked at thousands of cases and there have been no deaths post naloxone in the next 2 hours except 3 in Copenhagen, Denmark. They must have some good stuff there!

Should we force them to go to the hospital? There is really no need. If they show up at my ER and absolutely want no help, they are promptly discharged. Unless they are suicidal (and overdosing does not mean they are suicidal), I have no cause to hold him. Many people find this incredulous, but it is the reality. I have waiting rooms full of people that need to and want to be seen.

That brings us to the next controversy. Some police departments and prosecutor’s offices are saying these patients must be transported even though they are awake and alert and want no help. The treatment of overdose patients is a medical function, not a law enforcement one, unless the patient is in custody. If they are and the LEO will accompany us in the ambulance, then fine. But since it is a medical function, then physicians are the subject matter experts, not prosecutors. We set the standards and protocol. Prosecutor’s directives do not apply to EMS, but rather to LEOs. They are the tool to comply with these directives, either by transporting themselves, or accompanying in the ambulance.

This is an issue that EMS administration and LEO administration needs to work out in advance. One of my concerns is we are putting angry and unpredictable patients in the back of ambulances with no LEO present and this is dangerous. In reality, one block down the road if the patient demands to be let out, we have to pull them over and let them out. For a good example, find the LEO bodycam video of the firefighter that was shot and killed by a post-naloxone patient after the police were going to force him to go to the hospital.

One additional note, none of this counts for a large oral intake of opioid pills. These should be assumed to be a suicide attempt until proven otherwise, should be placed in custody and transported to the hospital.

Lastly, be cautious what you post in the media and social media. You are entitled to your opinion, but go back to the station and vent to each other privately. Your comments reflect on your organization.

Stay safe.

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