Patient Care

Beyond Naloxone: Providing Comprehensive Prehospital Care to Overdose Patients in the Midst of a Public Health Crisis

Issue 1 and Volume 43.

Providing comprehensive prehospital care to overdose patients

Medic 3 arrives on scene to find a 36-year-old male patient supine on the living room floor. The patient is in respiratory arrest and fire department first responders are providing rescue breaths with a bag-valve mask (BVM). The patient has a bounding carotid pulse. A nasopharyngeal airway is placed in the patient’s left nares and the patient is ventilated easily with adequate bilateral lung sounds.

The floor is bare wood and the patient is only wearing light undergarments. The ambient temperature in the room is approximately 55 degrees F. The patient’s roommate states that he last saw the patient approximately six hours ago. The crew notes that the patient’s pupils are pinpoint and there is drug paraphernalia surrounding the patient. There is no evidence of trauma.

Assessment of the patient’s vital signs reveals a heart rate of 123 beats per minute, blood pressure of 122/86 mmHg, and an oxygen saturation of 98% with assisted ventilation (his room air oxygen saturation was 66%). His initial end tidal CO2 is 70 mmHg and his blood glucose is 269 mg/dL. The patient’s skin is pale, dry and cold to the touch. After establishing IV access and starting a normal saline bolus, the crew administers 0.4 mg of IV naloxone (Narcan).

After five minutes, his spontaneous respiratory effort improves and he becomes agitated and combative. The patient’s movement isn’t purposeful and he isn’t able to speak. The patient is placed on high flow oxygen via non-rebreather mask. Reassessment of vital signs reveals a heart rate of 140 beats per minute, a blood pressure pf 134/83 mmHg, a SpO2 of 99%, a respiratory effort of 30 breaths per minute, and an EtCO2 of 34 mmHg. The patient now has a Glasgow coma score of 8.

One of the first responders suggests an additional dose of naloxone because the patient is still obtunded. Though the patient continues to exhibit decreased mentation, he’s breathing adequately, so there’s no indication to give additional naloxone. The crew captures an ECG which is unremarkable and prepares the patient for transport to the hospital.

While en route to the receiving facility, the patient becomes increasingly combative and the crew is forced to sedate him with midazolam (Versed). After two 2.5 mg of IV midazolam, the patient is appropriately sedated. The patient doesn’t experience any respiratory depression and the rest of the transport is uneventful.

Upon arrival at the ED, the patient is transferred to staff, and the crew starts to get their gear back together for the next call. The patient’s urine drug screen is found to be positive for opioids as well as cocaine, and his core body temperature is 84 degrees F. Active rewarming is initiated in the ED and the patient is admitted to the ICU. A CT scan of the patient’s brain reveals evidence of anoxic brain injury and his prognosis is unclear.

Presumably, the patient overdosed on heroin, experienced respiratory depression with a prolonged period of hypoxia, as well as significant hypothermia after being immobile on the cold floor for approximately five hours.

The fact that untrained people are advised to give naloxone without any other interventions doesn’t mean that EMS providers should do the same. AP Photo/Michelle R. Smith

The fact that untrained people are advised to give naloxone without any other interventions doesn’t mean that EMS providers should do the same. AP Photo/Michelle R. Smith

A Public Health Crisis

Opioid addictions and overdose have become a public health crisis of epidemic proportions. For every 100,000 people in the United States, 200 are addicted to heroin.1 According to the Centers for Disease Control (CDC), since 1999 the number of overdose deaths involving opioids has quadrupled; 91 Americans die every day from opioid overdoses.2

These trends are driven by an increasing number of addicts as well as a market that’s being flooded with powerful synthetic opioids and opioid analogs like fentanyl and carfentanyl. There are increasing numbers of new heroin users every year, and 3 out of 4 of them abused prescription opioids prior to using heroin.2 The increased availability, lower price and increased purity of heroin in the U.S. are also contributing factors to the increasing epidemic.

EMS agencies need to be proactive and aggressive when responding to the increasing number of calls for opioid overdoses. Naloxone, which reverses the respiratory depression associated with opioid ingestion, is the ubiquitous treatment for these overdoses. Today, a multitude of civilians and non-medically trained responders like police officers are administering naloxone to victims.

EMS providers must be prepared to provide comprehensive care to this patient population, which includes securing the airway and providing adequate ventilation, prompt nalaxone administration as well as considering other possible causes attributing to the patient’s condition.

Pathophysiology

The term opioid refers to natural and synthetic substances that act at one of the three main opioid receptor systems: mu, kappa and delta. Opiates are a subclass of opioids consisting of alkaloid compounds that occur naturally in the opium poppy. Opium, which is extracted from the opium poppy, contains morphine and codeine. It’s most commonly self-administered by smoking, but can also be eaten.

Heroin is manufactured from opium through a chemical refinement processes where a majority of the organic matter left from the poppy plant is removed. The overwhelming majority of heroin found in the U.S. is produced in Afghanistan and then smuggled into the country across the southern border by drug cartels.3

Fentanyl is a synthetic opioid that’s commonly used for acute pain management in the hospital and prehospital environment. Only a small amount of pharmaceutical fentanyl is diverted to the black market each year. Most of the fentanyl, as well as other opioid analogs like carfentanyl, are produced in illicit labs in Asia and smuggled into the country.4

Opioids act by activating specific transmembrane receptors (mu, kappa or delta) that couple with G proteins. This coupling initiates the intracellular communication process that ultimately leads to signal transduction. Opioid receptors are located in the central and peripheral nervous systems. The effects of their activation will depend on the location of the receptors, the type of G proteins present in the activated neural tissues, and the frequency and duration of activation. Mu receptor activation in the central nervous system (CNS) results in responses such as respiratory depression, euphoria, analgesia and miosis. Stimulation of peripheral mu receptors, like those in the smooth muscles of the bronchi and intestines, will result in cough suppression and constipation, respectively.

When it comes to pharmacokinetics, heroin has a half-life of about 30 minutes, and a duration of action approaching four to five hours due to its active metabolites, which include morphine.5 Heroin is metabolized to 6- monoacetylmorphine (6-MAM), a metabolite specific for heroin and can be detected in the urine by standard urine drug screen for one to three days after the last use, and occasionally longer in chronic users.6

Like all opioids, heroin binds to receptors that are part of the endogenous opioid systems. Certain opioids can also act on several other CNS neurotransmitter systems such as dopamine, gamma-amino-butyric acid (GABA) and glutamate. Opioid dependence is likely attributed to the activation of the brain’s reward centers stimulated by dopamine release. Heroin is more lipid-soluble than other opioids, allowing it to rapidly cross the blood-brain barrier and reach high brain levels within seconds.7

Acute opioid toxicity can present classically as depressed mental state, decreased respiratory rate or even apnea, decreased tidal volume, decreased bowel sounds and miotic (constricted) pupils.

A common pitfall is to associate miosis with opioid overdose. The presence of co- ingestants, such as sympathomimetics (amphetamine and cocaine) or anticholinergics, can make pupils appear normal or even dilated. Users of meperidine (Demerol) often present with normal pupils.8

The best predictor of opioid toxicity is a respiratory rate < 12 per minute. EMS providers should measure the respiratory rate and pay close attention to chest wall excursion. Subtle changes in respiratory effort are often not identified in the busy and sometimes distracting prehospital environment.

Initial Assessment & Interventions

The fact that untrained people are advised to give naloxone without any other interventions doesn’t mean that EMS providers should do the same. When EMS providers make contact with a patient experiencing respiratory depression or arrest after an opioid overdose, the initial priority must be ventilation and oxygenation. Hypoxia is fatal, but fortunately, trained medical professionals can easily correct this with BLS airway adjuncts and BVM ventilation with 100% oxygen.

Once the patient’s airway has been managed and they’ve been ventilated appropriately, then it’s time to administer naloxone. The current research shows that larger doses of naloxone increase the incidence of adverse effects and acute withdrawal syndrome like vomiting, agitation and pulmonary edema.9

Some protocols currently recommend giving 0.4 mg naloxone IV.9 If IV access isn’t available, then providers can administer 2 mg naloxone intramuscular (IM) or intranasal (IN). Repeat doses can be given as needed.

There are some providers who believe that the synthetic opioids like fentanyl require significantly higher doses of naloxone to achieve reversal. This is anecdotal and hasn’t been validated by research. In fact, there’s little to no published guidance available. EMS providers must always follow their local protocols and contact online medical direction as needed.

Furthermore, it should be noted that the goal of naloxone administration is the resolution of apnea or hypoventilation, as opposed to the return of normal mentation. If providers administer 4 mg of naloxone via any route and the patient doesn’t begin to breathe spontaneously, then providers must consider other possible causes.

What Else Could it Be?

EMS providers should keep in mind a broad differential of diagnoses when evaluating patients who remain confused or comatose despite naloxone administration. Anchoring on the diagnosis of opioid overdose without considering other life-threatening emergencies can result in poor patient outcome once they arrive in the ED.

The differential diagnoses of opioid toxicity includes toxic and nontoxic conditions. There are many drugs that produce coma; the most frequently encountered toxic agents that patients co-ingest with opioids are ethanol, sedative-hypnotics (e.g., benzodiazepines) and clonidine (a commonly-prescribed medication used for the treatment of hypertension and/or withdrawal symptoms). Clonidine can produce miosis and obtundation, though bradycardia and hypotension are more prominent. Ethanol intoxication produces little to no miosis and no change in bowel sounds. Benzodiazepines result in much less respiratory depression than opioids, especially when taken orally.

Sympathomimetic agents like cocaine are also commonly co-ingested with opioids, and their effects can become more prominent when naloxone is used to reverse respiratory depression. Patients become combative, agitated, tachycardic, diaphoretic and hypertensive. Though it’s frequently impossible for EMS providers to determine the exact substances to which the patient was exposed, a careful history from family members and bystanders can later help ED providers determine the correct course of management.

There are many medications that can cause cardiac disturbances and fatal arrhythmias. An ECG should be obtained when evaluating the comatose patient who doesn’t respond to the initial doses of naloxone, or for whom there’s a high index of suspicion for polypharmacy overdose.

Loperamide is associated with disturbances in cardiac conduction ranging from QRS widening to QT prolongation, ventricular tachycardia (polymorphic and monomorphic) and idioventricular rhythm.10

Many patients with drug addiction are on methadone, which can increase QT interval and potentially cause Torsades de Pointes. This phenomenon more commonly occurs in patients taking high daily doses of the drug.11,12 Patients who use illicit drugs chronically, or who have suffered a prolonged period of anoxia due to overdose, may also exhibit evidence of cardiac injury or ischemia that’s readily apparent on ECG.

Any medical condition that produces coma may be mistaken for, or occur in conjunction with, opioid overdose. EMS providers should evaluate for and consider medical conditions in which delay of diagnosis will delay definitive care. These conditions include a hemorrhagic or embolic stroke, electrolyte abnormalities like hyperkalemia, and sepsis.

Hypothermia may arise from a persistently unresponsive state in a cool environment. In addition, patients who have been lying immobile in an opioid-induced stupor may be subject to rhabdomyolysis, myoglobinuric renal failure and compartment syndrome.

After securing the airway and providing adequate oxygenation and ventilation, EMS providers should expose the patient and look for underlying traumatic injuries, bleeding, firmness and/or swelling of muscle groups that could indicate compartment syndrome. Patients then should be covered with warm blankets and IV fluid therapy should be initiated to correct any underlying electrolyte or metabolic disturbances.

We must look for solutions to prevent overdose and offer further treatments—specifically in a population that’s already had an overdose event. Photo by Matthew Strauss

We must look for solutions to prevent overdose and offer further treatments—specifically in a population that’s already had an overdose event. Photo by Matthew Strauss

What Can We Do?

In the U.S., drug overdose deaths nearly tripled to 47,055 between 1999 and 2014, with 60.9% involving an opioid. A study of nationally representative data on U.S. ED visits found that the population-based rate of ED visits for opioid overdose nearly quadrupled between 1993 and 2010.13

EMS providers on the frontlines of the opioid overdose epidemic have a unique opportunity for public education and death prevention. Given the profoundly increased risk of death antecedent to one overdose event, EMS providers can identify at-risk individuals and provide them with the necessary resources and educational material on how to obtain naloxone along with available drug rehabilitation programs in the areas they live in.

Recognition of these high-risk individuals may also lead to additional focus on discharge planning processes for patients who have been treated and released by EMS providers after an overdose event. In some systems, there are likely opportunities to track ambulance contacts and even send follow-up teams for every patient that receives naloxone. EMS and ED providers may even establish this as an opportunity for opioid or naloxone education.

Although prehospital cardiac arrest care is a poor parallel for opioid overdose, the need for rigorous review and prudent solutions is similar. We must look for solutions to prevent overdose and offer further treatments— specifically in a population that’s already had an overdose event.

There’s a great deal of chatter from a variety of media outlets discussing which overdose patients deserve care and which ones don’t. EMS providers must ignore this. When a patient presents to you, they must be treated appropriately, regardless of whether it’s their first overdose or their 100th. Every time patient contact is made, there’s an opportunity to impact a life and precipitate change. We must not let our prejudices determine who we attempt to help and who we give up on.

Conclusion

Today, heroin kills more people in the U.S. than guns.14 In October, the U.S. Department of health and Human Services declared the opioid crisis a public health emergency to help mitigate the situation.15

Though the wheels of bureaucracy are slow to turn, EMS providers across the country are on the frontlines doing battle. As a profession, we must move beyond just administering naloxone. We must provide comprehensive care where an understanding of the disease process and common associated comorbidities leads to thoughtful, patient-centric clinical decision making.

Finally, it must always be remembered that the true victims of this disease are those unfortunate individuals who suffer from addiction.

References

1. Mohammad A. Treating heroin addiction with suboxone. (Mar. 17, 2017.) The Huffington Post. Retrieved Nov. 20, 2017, from www.huffingtonpost.com/entry/treating- heroin-addiction-with-suboxone_us_58c097a4e4b070e55af9eb62.

2. Centers for Disease Control and Prevention. (Aug. 30, 2017.) Understanding the epidemic: Drug overdose deaths in the United States continue to increase in 2015. CDC.gov. Retrieved Nov. 20, 2017, from www.cdc.gov/drugoverdose/epidemic/index.html.

3. Woody C. (March 3, 2016.) Here’s where America’s heroin comes from. Business Insider. Retrieved Nov. 20, 2017, from www.businessinsider.com/heroin-in-the-us-from-mexico-and-afghanistan-2016-3.

4. Cass A. (Feb. 7, 2017.) Where does fentanyl come from? China is primary source in U.S., and much is ending up in Ohio. The News-Herald. Retrieved Nov. 20, 2017, from www.news-herald.com/general-news/20170207/where-does-fentanyl-come-from-china-is-primary-source-in-us-and-much-is-ending-up-in-ohio.

5. Reisine T, Pasternak G. Opioid analgesics and antagonists. In Hardman JG, Gilman A, Limbird LE (Eds.), Pharmacological basis of therapeutics, 9th Edition. McGraw-Hill: New York, p. 521, 1996.

6. Way WL, Way EL. Opioid analgesics and antagonists. In Katzung BG (Ed.), Basic and clinical pharmacology. Appleton & Lange: Norwalk, Conn., p. 368, 1989.

7. Sporer KA. Acute heroin overdose. Ann Intern Med. 1999;130(7):584–590.

8. Ghoneim MM, Dhanaraj J, Choi WW. Comparison of four opioid analgesics as supplements to nitrous oxide anesthesia. Anesth Analg. 1984:63(4);405–412.

9. Pennsylvania Department of Health Bureau of Emergency Medical Services. (June 10, 2017.) Pennsylvania statewide advanced life support protocols. Pennsylvania Department of Health. Retrieved Nov. 20, 2017, from www.health.pa.gov/My%20Health/ Emergency%20Medical%20Services/EMS%20Statewide%20Protocol/Documents/ FINAL%202017%20ALS%20PROTOCOL.pdf.

10. Marraffa JM, Holland MG, Sullivan RW, et al. Cardiac conduction disturbance after loperamide abuse. Clin Toxicol (Phila). 2014;52(9):952–957.

11. Krantz MJ, Kutinsky IB, Robertson AD, et al. Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes. Pharmacotherapy. 2003;23(6):802–805.

12. U.S. Department of Health and Human Services. (May 2013.) Drug abuse warning network, 2011: National estimates of drug-related emergency department visits. Substance Abuse and Mental Health Services Administration. Retrieved Nov. 20, 2017, from www.samhsa.gov/data/sites/default/files/DAWN2k11ED/DAWN2k11ED/DAWN2k11ED.pdf.

13. Hasegawa K, Espinola JA, Brown DF, et al. Trends in U.S. emergency department visits for opioid overdose, 1993-2010. Pain Med. 2014;15(10):1765–1770.

14. Ingraham C. (Dec. 8, 2016.) Heroin deaths surpass gun homicides for the first time, CDC data shows. The Washington Post. Retrieved Nov. 20, 2017, from www.washingtonpost.com/ news/wonk/wp/2016/12/08/heroin-deaths-surpass-gun-homicides-for-the-first-time-cdc- data-show.

15. Goodnough A. (Oct. 26, 2017.) Trump declares opioid crisis a ‘health emergency’ but requests no funds. The New York Times. Retrieved Dec. 4, 2017, from www.nytimes.com/2017/10/26/us/ politics/trump-opioid-crisis.html.

NAEMSP Endorses New Opioid Safety Guidelines for First Responders

In August of this year, the National Association of EMS Physicians (NAEMSP) announced that it was endorsing a recent document developed by the American College of Medical Toxicology (ACMT) and American Academy of Clinical Toxicology (AACT). The document outlines several recommendations for first responders who find themselves in an opioid overdose situation.

The document, developed by ACMT and AACT, was created in response to requests from first reponders for practical, evidence-based recommendations that allow providers to ensure their own safety while treating their patients. The need for these guidelines ultimately arose as a result of the ongoing and escalating public health crisis of opioid overdose in the United States.

NAEMSP’s Executive Board and Standards and Clinical Practice Committee voted unanimously to support the document.

In announcing their endorsement, NAEMSP also expressed their ongoing commitment to their members and their aim to keep all first responders aware of safety measures and guidelines.

NAEMSP’s Standards & Clinical Practice Committee has developed a group that will provide support to members with practical guidelines and best practices for specific scenarios.

Learn more at www.naemsp.org.