Pulmonary Edema Following Opioid Overdose


Opioid overdoses have become a serious problem in this country. In fact, the United States Department of Health and Human Services declared that we are facing an opioid epidemic. In hopes of reversing this trend, the Department launched its Opioid Initiative to support state efforts in addressing this crisis.1

Nineteen states saw a significant increase (greater than 10 percent) in overdose deaths between 2014 and 2015. Massachusetts saw the greatest increase at 35.3 percent. New Hampshire, Connecticut, Florida, and Kentucky followed closely behind with increases of between 20 and 30 percent. Other states saw either slight increases or slight decreases.2

Emergency medical responders will always be on the front lines to treat patients who overdose on opioids. To save lives, we must be able to handle the increased call volume, understand the nature of opioid overdose on the human body, and be able to effectively treat these patients. But sometimes we are called to the scene after the patient has died.

By the Numbers

The sad fact is that more people are dying in the United States from opioid abuse than at any other time in the history of this country. The Centers for Disease Control and Prevention (CDC) reports that the number of overdose deaths has quadrupled between 1999 and 2015.3 In 2015 alone, more than 33,000 people died from overdosing on legally prescribed or illegally bought opioids such as heroin, morphine, oxycodone, hydrocodone, fentanyl, and codeine. (2) The CDC also reports that the driving force behind the 15-year increase in overdose deaths is the increase in prescription opioids. (3)

Between 1997 and 2007, prescriptions for opioids in this country increased by 700 percent, and the number of grams of methadone prescribed increased by more than 1,200 percent.4 This growing availability may be the reason nearly 75 percent of overdoses are unintentional.5 Not only is the number of people dying from opioid overdoses growing, it is the leading cause of injury deaths in the United States. Statistics from 2013 show that more people died from opioids (46,471) than from motor vehicle accidents (35,369) or firearms (33,636).6

With more people overdosing on opioids, opioid-related visits to emergency departments (EDs) have also skyrocketed. Between 2005 and 2014, the rate of opioid-related ED visits increased by 99.4 percent. (1) More than 1,000 people are treated daily in EDs across the country. (5) More visits to the ED mean more people are being treated and transported by emergency medical services (EMS). With this growing trend, EMS must understand the challenges it may face while responding to these patients and know how to overcome them.

The Signs and Symptoms

The signs and symptoms of acute opioid intoxication are drowsiness, euphoria, miosis (pinpoint pupils), and respiratory depression. The respiratory depression can sometimes take up to one to three hours to develop; in many cases, it can be reversed effectively with the antidote naloxone (Narcan®) prior to cardiac arrest. (5) Naloxone is the first line medication given by first responders to reverse narcotic intoxication and has been used as an antidote for in-hospital opioid reversal since the 1960s.7 Obviously, with the growing trend of opioid overdose, first responders are using naloxone more frequently. In 2014, naloxone was administered by EMS personnel nearly 153,000 times.8 What makes naloxone so effective is its ability to work as an antagonist at the receptor sites that opioids occupy; it ultimately blocks and displaces the opioid from the receptor site. This effect lasts approximately 20 to 60 minutes. (5)

Naloxone can be administered intravenously (IV), intramuscularly, subcutaneously, endotracheally, and intranasally. The recommended route, IV, begins to work within one to two minutes. (5) The initial recommended adult dose for suspected narcotic overdose is between 0.4 and two milligrams; this can be repeated up to a total dose of 10 milligrams. (5) The amount of naloxone required to reverse an overdose depends on the number of receptors that are being occupied by the narcotic. (7) Because this number is unknown, EMS must continue to administer naloxone as needed to restore spontaneous respirations. In some cases, it has taken more than 20 milligrams of naloxone to counteract a massive overdose. (7) In general, if an overdose has not been reversed after 15 milligrams, it is unlikely to be an opioid overdose. (4)

Side effects have been reported with naloxone administration. The major side effects of naloxone are acute withdrawal symptoms that include nausea, vomiting, agitation, diarrhea, yawning, lacrimation (excess secretion of tears), and rhinorrhea (runny nose). (5)

A study of 453 patients treated with naloxone found that 1.3 percent suffered more severe side effects, which included noncardiogenic pulmonary edema (NCPE), later found to be the primary cause of a massive release of catecholamines after naloxone administration. (5) Also seen was a moderate increase in heart rate and blood pressure.9 Although naloxone-induced NCPE is rare, it can occur in young, healthy patients.10

In two cases, NCPE edema resulted in young healthy males after naloxone administration postsurgery. Both were given 100 micrograms (0.1 milligram) of naloxone IV. Neither had a history of drug use or any other medical history. (9) In another case, after a young male was given 80 micrograms (0.8 milligram) of naloxone postsurgery, he developed NCPE. His physicians concluded that naloxone contributed to the NCPE. (10)

Between 1996 and 1999, 13 male heroin overdose patients developed NCPE after prehospital administration of naloxone. These individuals were all reported to be less experienced heroin users (2.9 years).11 Although each of these cases happened following naloxone administration, the medical community is not convinced that NCPE is caused by naloxone. Studies have shown that patients who received large doses of naloxone, through continuous infusion, did not develop NCPE. (4)

Many believe that using naloxone does not cause pulmonary edema but rather reveals pulmonary edema that was masked by the respiratory depression. (7) Once respirations return to a more normal rate, pulmonary edema becomes more noticeable. Studies have found that NCPE is present in nearly all fatal cases of opioid overdose. (11)

NCPE was first described as a complication of a fatal heroin overdose in 1880 during an autopsy by William Osler. In 1953, NCPE was first found to be a complication of a nonfatal heroin overdose.12

A study conducted at San Francisco General Hospital found that of 1,278 patients who arrived at the hospital with a diagnosis of heroin overdose, 74 percent were hypoxic on arrival, 22 percent developed severe hypoxia within the first hour, and 2.1 percent were found to have NCPE. All but one patient had received prehospital naloxone. (12)

The hospital also looked at earlier case studies before naloxone became readily available and found that heroin overdose patients developed NCPE at a rate of 0.8 percent to 2.4 percent, which was within the range of their study. (12) Although the chances of patients developing NCPE in the field are low, we must recognize and treat it quickly and effectively if it happens. The first step is to recognize that the patient has overdosed on opioids.

Rapid recognition can make a difference in the patient’s survival. The first obvious determinants of opioid overdose are consciousness level and breathing effectiveness. Respirations of 12 breaths or less per minute in a patient who is not sleeping is a strong indicator (along with miosis and stupor) of opioid overdose. (4)

Our first priority is restoring oxygenation. Providing adequate ventilation is an easy way to prevent the sympathetic surge that triggers pulmonary edema following apnea reversal with naloxone. (10) The risk of respiratory arrest and/or aspiration is significant in these cases, especially when alcohol or benzodiazepines have also been consumed. Advanced life support (ALS) providers must be prepared to insert an advanced airway if the patient’s condition does not improve or worsens.13

Administer naloxone simultaneously with ventilation and oxygenation because it can be lifesaving. (5) Continue to administer naloxone at appropriately spaced intervals (to the limit of your local protocols) until the patient begins to self-oxygenate and ventilate on his own. Our goal is to improve breathing and restore airway reflexes, not to restore a full level of consciousness. During the physical exam, EMS should look for clues to explain the patient’s presentation. Look for pills, pill bottles, syringes, or fentanyl patches on or around the patient. If the patient begins to breathe on his own, the provider should administer oxygen through a nasal cannula or a nonrebreather mask until the oxygen saturation level reaches at least 94 percent. (13) Perform a limb lead EKG and a 12-lead EKG, check blood glucose level, and establish IV access (if one has not already been done). It is crucial to continuously monitor the patient because his breathing could once again become ineffective.

If the patient’s oxygen saturation level is below 90 percent, whether he is breathing on his own with oxygen or the rescuer is assisting ventilation with a bag-valve mask, pulmonary edema is often the cause after opioid overdose. (4) On auscultation of the lungs, the first responder will most likely hear crackles (rales).

NCPE results from an increased permeability – or leaking – of pulmonary capillaries followed by alveolar flooding; this decreases pulmonary oxygenation.14 Recognizing and treating this early will provide the best outcome for the patient. Although NCPE, uncomplicated by gastric aspiration, usually resolves itself within 24 hours, EMS providers must take quick action to treat it as we would cardiogenic pulmonary edema. (4)

If the patient is breathing, continuous positive airway pressure (CPAP) therapy is one of the most beneficial and effective treatments EMS providers can deliver. CPAP can improve work of breathing and reduce the feeling of dyspnea. CPAP use significantly reduces the need for endotracheal intubation in pulmonary edema patients as well as improves their outcomes.15 If the patient does not regain respirations, the ALS provider must provide a protected airway through intubation.

When treating pulmonary edema, other prehospital treatments such as nitroglycerin and furosemide may be appropriate per local protocols. Nitroglycerin works quickly and provides excellent preload reduction, but it can be used only if the patient is not hypotensive.16

Furosemide helps the body excrete water and reduces preload like nitroglycerin. However, unlike nitroglycerin, furosemide takes a little longer to work (approximately 20 to 60 minutes). (16)

Continuous observation of the patient, especially the airway and breathing, is critical in opioid overdose calls. Just because naloxone restored the patient’s consciousness and ability to breathe does not mean it is time to let down our guard. Being vigilant and prepared will give the patient the best outcome possible.


1. Weiss, Ph. D; Audrey J; Elixhauser, Ph.D; Anne, Barrett; et al. Opioid-Related Inpatient Stays and Emergency Department Visits by State, 2009-2014. Healthcare Cost and Utilization Project. December 2016. Retrieved from https://www.hcup-us.ahrq.gov/reports/statbriefs/sb219-Opioid-Hospital-Stays-ED-Visits-by-State.jsp.

2. Centers for Disease Control and Prevention. Drug Overdose Death Data. December 16, 2016. Retrieved from https://www.cdc.gov/drugoverdose/data/statedeaths.html.

3. Centers for Disease Control and Prevention. Understanding the Epidemic. Retrieved June 15, 2017, from https://www.cdc.gov/drugoverdose/epidemic/index.html.

4. Boyer, Ph.D; MD, Edward W. Management of Opioid Analgesic Overdose. PMC, August 9, 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739053.

5. Insys Development Company, Inc. Advisory Committee of October 5, 2016. FDA. Retrieved May 10, 2017. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AnestheticAndAnalgesic DrugProductsAdvisoryCommittee/UCM522690.pdf.

6. 2015 National Drug Threat Assessment Summary. U.S. Department of Justice, DEA. October 2015. Retrieved from https://www.dea.gov/docs/2015%20NDTA%20Report.pdf.

7. Clarke SFJ and D Jones. Naloxone in opioid poisoning: walking the tightrope. Emergency Medicine Journal. September 1, 2005. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1726910/pdf/v022p00612.pdf.

8. Federal EMS Advisory Board Asked to Address Response to Opioid Overdoses. NHTSA. Retrieved June 15, 2017, from https://www.ems.gov/newsletter/marapr2016/opioid-overdose.html.

9. Praugh MD; Donald Roy, MD, Ph.D; Bumgarner R, MD; et al. Acute Pulmonary Edema in Healthy Teenagers Following Conservative Doses of Intravenous Naloxone. Anesthesiology. (pp 485-486) May 1984.

10. Horng, Huei-Chi; Ho, Min-Tzung; Huang, Chih-Hung; et al. Negative Pressure Pulmonary Edema Following Naloxone Administration in a Patient with Fentanyl-induced Respiratory Depression. (pp 155-157). Taiwan Society of Anesthesiologists. November 12, 2009.

11. Mégarbane B and L Chevillard. The large spectrum of pulmonary complications following illicit drug use: Features and mechanisms. Chemical-Biological Interactions. (pp 444-451). October 18, 2013.

12. Sporer, MD; Karl A; Dorn E, MD. Heroin-Related Noncardiogenic Pulmonary Edema, A Case Series. Chest Journal. Vol. 120 Issue 5 (pp 1628 – 1632) November 2001. http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21969/1628.pdf.

13. National Model EMS Clinical Guidelines. National Association of State EMS Officials. Retrieved June 1, 2017. https://nasemso.org/Projects/ModelEMSClinicalGuidelines/documents/National-Model-EMS-Clinical-Guidelines-23Oct2014.pdf.

14. Kakoutros, NS and SN Kakoutros. Non-Cardiogenic Pulmonary Edema. Hellenic Journal of Cardiology. October 18, 2002, retrieved from http://www.hellenicjcardiol.org/archive/full_text/2003/6/2003_6_385.pdf.

15. Warner, MD, FACP, FCCP; G. Scott. Evaluation of the Effect of Prehospital Application of Continuous Positive Airway Pressure Therapy in Acute Respiratory Distress. Prehospital and Disaster Medicine. July 1, 2009, retrieved from https://pdfs.semanticscholar.org/f53b/11cd390b26d998e841fd0919f4fac06dc8c5.pdf.

16. Sovari, MD, FACP, FACC; Ali A. Cardiogenic Pulmonary Edema Medication. Medscape. December 22, 2016, retrieved from http://emedicine.medscape.com/article/157452-medication#2.

CONNIE PIGNATARO is a lieutenant for Oakland Park (FL) Fire Rescue (OPFR), where she has been a member since 2002. In 2011, she became the first woman to be promoted as an officer in the OPFR. Pignataro has a bachelor of applied science degree in public safety administration. She is a certified instructor III, live fire instructor, and vehicle and machine rescue technician. She began her career as a volunteer for her local community emergency response team in 1998.

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