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11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019
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Adapted image from Bouquie R, Wainstein L, Pilet P, et al. PLoS One. 2014;9(12):e113991. [Open access.] PMID: 25474108, PMCID: PMC4256378.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
As the opiate epidemic expands in the United States,[1] more patients battle addiction, and the rate of opiate-related overdose deaths continues to climb—almost tripling from 2000 to 2015.[2,3] Moreover, life expectancy in the United States has begun to drop for the first time this century.[2] Although these substance use disorders can lead to death, the most grave outcome, they can also result in a myriad of neurologic, cardiovascular, musculoskeletal, and pulmonary complications.[4] Emergency department [ED] clinicians and other healthcare providers must be prepared to quickly diagnose and appropriately treat the litany of potentially fatal conditions that can be precipitated by opiate abuse, especially intravenous (IV) drug abuse (IVDA)/injection drug use (IDU).
The image shows a livedo-like dermatitis with necrotic lesion caused by self-injection of a generic buprenorphine. The red arrow indicates the injection site.
Image depicting heroin-related noncardiogenic pulmonary edema courtesy of Medscape.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Respiratory Failure
The toxidrome that develops following opiate ingestion includes analgesia, sedation, slowing of the gastrointestinal tract and, most dangerously, respiratory depression. Stimulation of the mu receptors in the brain reduces the body's response to hypercarbia and hypoxia, resulting in a decreased incentive to breathe and a progression to apnea.[5] Thus, the most common cause of death following an opiate overdose is respiratory depression. Patients with previous history of lung disease have an even higher mortality risk. Co-ingestion of opiates with other respiratory depressants, such as gabapentin, further raises the risk of death.[5]
Image from Wikimedia Commons / Evilleavenger.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Use of naloxone
The treatment for an opiate overdose is naloxone, whose main purpose is to reverse respiratory depression. It is a competitive opioid antagonist with a high affinity for the mu-opioid receptor that can be administered IV, through an intraosseous (IO) line, intranasally (IN), subcutaneously (SC), or intramuscularly (IM).[6] Dosing should be titrated on the basis of an improvement in respiratory effort, but not to the point of opiate withdrawal, which endangers both the patient and medical staff.
After patients receive and respond to naloxone, they should be observed in the ED for at least 1-2 hours.[6] Prior to discharge, it is recommended that the patient have a Glasgow Coma Scale of 15, no need for repeat dosing of naloxone, and a return to normal vital signs. Ideally, a ride would be procured to take the patient home, with monitoring for 12-24 hours.[6]
Image courtesy of Nicole Cimino-Fiallos, MD, FAAEM.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
A 35-year-old male injection heroin user required resuscitation with both IN and IM naloxone. He subsequently developed noncardiogenic pulmonary edema (shown) and was intubated due to hypoxia.
Pulmonary Edema
Although naloxone can be lifesaving and there are no absolute contraindications to its use (except for documented anaphylaxis), complications can develop from its administration.[6] In addition to the risks of acute withdrawal syndrome precipitated by too much naloxone, naloxone can also cause noncardiogenic pulmonary edema. This condition, which develops in up to 4% of patients receiving naloxone, is likely caused by the adrenergic response to opiate withdrawal.[6] The sudden increase in plasma concentrations of catecholamines after naloxone therapy is thought to cause a shift in blood volume to the pulmonary vasculature, which triggers pulmonary vasoconstriction and resultant pulmonary hypertension.[7]
Image courtesy of Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Symptoms of noncardiogenic pulmonary edema can include persistent hypoxia despite reversal of respiratory depression, cough, and pink, frothy sputum. Chest x-ray is likely to show bilateral patchy infiltrates consistent with pulmonary edema (shown). Although most cases will develop within 4 hours of naloxone administration, case reports exist that detail delayed onset for up to 8 hours after its use.[6]
Image from Wikimedia Commons / James Heilman, MD.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Anoxic Brain Injury
Central nervous system (CNS) depression is a common outcome of opiate ingestion. It can range from mild somnolence to coma. Some opiates (eg, tramadol, tapentadol, propoxyphene) not only cause CNS depression, but they can also lead to the development of seizures after prolonged hypoxia secondary to brain injury and subsequent electrical instability. The respiratory depression classically caused by opiate toxicity can end in hypoxic brain injury (shown) if not reversed quickly.
Toxic leukoencephalopathy
Although most patients "found down" after an overdose likely have compromised mental status due to anoxia, clinicians should be aware of the diagnosis of toxic leukoencephalopathy (TLE).[8] This disease process, associated with heroin inhalation, can be diagnosed on magnetic resonance imaging (MRI) and occasionally has a better prognosis than most anoxic brain injuries. Patients with a history of heroin inhalation and no history of prolonged hypoxemia may benefit from additional evaluation for TLE prior to withdrawal of life-sustaining measures.[8]
Image of Staphylococcus aureus endocarditis with perforation of, and vegetation on, the aortic valve courtesy of Janet Jones, MD, Laboratory Service, Wichita Veterans Administration Medical Center.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Endocarditis
Many of the complications of IVDA/IDU result from the use of nonsterile needles.[5] The presence of S aureus on the skin, concomitant infection with human immunodeficiency virus (HIV), application of saliva to lubricate needles, and use of nonsterile ingredients in drug formulations all compound the risk of infections in this patient population.[9]
A difference between other causes of endocarditis and that associated with IVDA/IDU is that IVDA/IDU-related endocarditis typically results in infections on the right side of the heart.[5] The most commonly affected valve is the tricuspid valve. Patients may complain of malaise and fever. Clinicians may detect a new murmur on cardiac auscultation.[5]
Image courtesy of Nicole Cimino-Fiallos, MD, FAAEM.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
The hand of a patient who uses IV drugs is shown. She was diagnosed with endocarditis and septic emboli, in which an arterial embolus resulted in ischemic disease of her left fifth digit. Although right-sided endocarditis and septic emboli to the pulmonary vasculature are more common, left-sided disease and subsequent emboli through the arterial system are possible.
Septic emboli
Once bacterial vegetations grow on the cardiac valves, septic emboli can disperse to any organ system.[9] Occasionally, the presence of multiple infections or signs of embolic disease are the only clue(s) pointing to a diagnosis of endocarditis. The valves themselves can become compromised and develop regurgitation or insufficiency, or complete destruction of the valve can occur. Mortality ranges from 25% to 50% at 1 year after diagnosis, worsened by a frequent lack of compliance with long-term antibiotic regimens.[4] The modified Duke criteria for infective endocarditis can be used to make the diagnosis. If the patient is not septic or hemodynamically unstable, consider holding antibiotics until a series of blood cultures can be obtained.
Adapted image from Chan JJ, Oh JJ. Int J Emerg Med. 2016;9(1):22. [Open access.] PMID: 27456667, PMCID: PMC4960080.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
The image reveals compression of the thecal sac and the cauda equina by an abscess in the posterior epidural space and a posterior disc bulge.
Spinal Epidural Abscess
Spinal epidural abscess is a feared IVDA/IDU complication.[10] Bacteria seeded into the epidural space forms an abscess, which causes a mass effect on the spinal cord, conus medullaris, or cauda equina (shown). Left untreated, the compression of blood flow to the spinal cord can result in muscle weakness, sensory loss, bowel and bladder dysfunction, sepsis, or mortality. Less than 20% of patients will develop the classic triad of fever, back pain, and neurologic deficit.[10]
Although early detection leads to improved outcomes, symptoms/signs can be vague, making the diagnosis elusive.[10,11] The increasing prevalence of spinal epidural abscesses can likely be attributed to the increase in IVDA/IDU,[11] as hematogenous spread from bacteremia or endocarditis are common causes. Most infections are caused by S aureus, including methicillin-resistant S aureus (MRSA).[11]
Adapted image from Smids C, Kouijzer IJ, Vos FJ, et al. 2017;45(1):41-9. [Open access.] PMID: 27317050, PMCID: PMC5306365.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Physical examination in a person with a suspected spinal epidural abscess may detect spinal tenderness, radicular paresthesia or weakness, decreased rectal tone, or saddle anesthesia. Laboratory workup should include a white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level, as well as blood cultures.
Performance of a lumbar puncture is contraindicated if an epidural abscess is suspected. An MRI with gadolinium of the entire spine is the preferred diagnostic study, although computed tomography (CT) myelography is an option for non-MRI candidates.[11] Surgery is typically recommended; however, medical management may be pursued in patients with early disease, normal neurologic status, or poor surgical candidacy. Postoperative antibiotics are usually required for 4-6 weeks.
Adapted image from pxhere.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Mediastinitis
Prolonged use of IV drugs causes sclerosis and scarring of the involved peripheral veins; thus, many people with substance use disorders will attempt to inject into the deep veins of the neck.[12] Known as a "pocket shot,"[13] injection into this region (supraclavicular fossa) (shown) is fraught with danger: Patients can develop jugular venous thrombophlebitis, pseudoaneurysms of the carotid artery, Horner syndrome, septic arthritis of the sternoclavicular joint, and/or mediastinitis.[5]
Adapted image from van der Weg G, Wikkeling M, van Leeuwen M, Ter Avest E. Int J Emerg Med. 2014;7:27. [Open access.] PMID: 25364474, PMCID: PMC4215748.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
This CT scan reveals mediastinitis (induration of the mediastinal fat) and extensive left-sided pleural effusion with air pockets.
Mediastinitis is known for its rapid progression and high mortality. The infection can result in the development of an abscess, the creation of an esophagopleural fistula, or involvement of the pericardium.[4] CT scanning with IV contrast can be used for the diagnosis and may show lymphadenopathy, myositis, vascular thrombosis, fluid collections, free air, or increased density of the adipose tissues.[14] Initiate early administration of antibiotics, and obtain surgical consultation because debridement is often indicated.
Left image from the Centers for Disease Control and Prevention / Gregory Moran, MD. Right image courtesy of Medscape.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Skin Infections
In addition to using the neck veins as alternative sites when peripheral veins are inaccessible from sclerosis/scarring, individuals who inject drugs may advance to the use of a technique known as "skin popping," wherein drugs are injected into subcutaneous tissues.[13] Superficial infections such as cellulitis and abscess formation (left image) can occur. If users inject into deeper structures with dirty needles or without cleaning their skin, they can develop myositis, rhabdomyolysis, necrotizing fasciitis (right image), and/or compartment syndrome.[4]
Illustration courtesy of Sam Shlomo Spaeth.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Reports also exist of clostridial skin infections, which can cause necrotizing infections and gas gangrene, but these conditions are more common in individuals who use black tar heroin.[15]
Clinicians also need to be aware of illicit desomorphine, often referred to as "krokodil." This semisynthetic opioid causes a green reptilian appearance of the skin (shown) following injection. In addition, additives in the drug—such as paint thinners, lighter fluid, and heavy metals—frequently cause ulceration of the soft tissues around the injection site.[15]
Image courtesy of Nicole Cimino-Fiallos, MD, FAAEM.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
The photograph shows a mycotic pseudoaneurysm that developed after the patient injected heroin into his left radial artery. Operative repair and a prolonged course of IV antibiotics were required.
Pseudoaneurysm
If IV drug users unintentionally inject into an arterial structure, they are at high risk for the formation of a pseudoaneurysm,[16,17] a collection of blood that forms between the two outer layers of an artery. Patients may describe the development of an expanding pulsatile mass. Although the overlying skin may be warm and red, pseudoaneurysms should not be confused with abscesses—Bedside drainage should not be attempted.[16] Pseudoaneurysms most commonly occur after injection into the groin,[16,17] but they have also been reported to develop after accidental injection in the carotid, radial, and other vessels.[16]
Image courtesy of Nicole Cimino-Fiallos, MD, FAAEM.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
This sonogram was obtained in the same injection heroin patient discussed on the previous slide.
Pseudoaneurysms that develop after IDU are typically infected, and patients are often hemodynamically unstable.[17] These factors combined with a frequent lack of suitable autologous graft material due to patient's history of IVDA/IDU often make the patient a poor candidate for a native graft. Prosthetic grafts are also at high risk for infection in this patient population. Thus, excision and subsequent ligation of the pseudoaneurysm is often the treatment of choice, despite the risks of claudication and amputation.[17]
Image from Powell AG, Crozier JE, Hodgson H, Galloway DJ. BMC Infect Dis. 2011;11:21. [Open access.] PMID: 21251266, PMCID: PMC3033829.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
This preoperative photograph shows the left groin of an IV drug user with septicemic anthrax.
Sepsis/Bacteremia
IV drug users are frequently bacteremic and can develop sepsis.[15] Most patients become infected because they use nonsterile needles and do not clean their skin prior to injection. Sharing needles with other drug users also raises the risk of infection. S aureus and Streptococcus pyogenes are the most common causes of bacteremia, but oral flora (from licking needles) can cause a similar presentation.
Patients with a history of IVDA/IDU who present to the ED with fever and tachycardia should have blood cultures drawn, and clinicians should recognize the possibility of bacteremia and sepsis.[15]
Image from Wikimedia Commons / James Heilman, MD.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
The radiograph shows a retained needle fragment in the arm of a person who used IV drugs.
Needle Fragment Foreign Body
Another complication that can result from the reuse of needles for IDU is the risk of the needle breaking while the person is injecting.[13,18] The most common cause of a broken needle is the separation of the needle from its hub,[18] which occurs more frequently in needles that are being reused.
When the needle breaks, the distal fragment can remain in the subcutaneous/soft tissues around the injection site (shown) or it can become an embolus (see the next slide).[18] Patients often develop local infection and inflammation around the retained fragment.
Adapted images from Fu X, Chen K, Liao X, Shen K. Subst Abuse Treat Prev Policy. 2017;12(1):51. [Open access.] PMID: 29216882, PMCID: PMC5721468.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
The images reveal a needle fragment that migrated to the right ventricle of a person who injected heroin into the right groin. (a) Transthoracic echocardiography. (b, c) CT scans. (d) Intraoperative photograph. (e) The retrieved needle fragment.
Less frequently, the needle fragment migrates and can result in endocarditis, a pulmonary abscess, cardiac perforation (shown), or other complications.[13,18] Ideally, once identified, the needle fragment is removed to prevent further problems. Surgical consultation can aid in assessing the risks versus the benefits of retrieving the needle fragment.[18]
Image from Wikimedia Commons / Jer5150.
11 Opiate-Related Emergencies: When Highs May Become Fatal
Nicole Cimino-Fiallos, MD, FAAEM | July 25, 2019 | Contributor Information
Loperamide Overdose
Many patients addicted to opiates who are unable to afford the drugs they crave often turn to inexpensive and readily available substitutes, such as loperamide (Imodium). This over-the-counter anti-diarrheal agent works by acting on the opioid receptors in the large intestine.[19] Loperamide also has some activity against calcium channels.
When loperamide is used as prescribed, it has no effect on the CNS because it does not cross the blood brain barrier.[19] However, using this medication at significantly higher dosages can result in opiate intoxication. Unfortunately, at the larger dosages required to "get high," patients are at risk for QT prolongation, QRS widening, ventricular arrhythmias, and torsades de pointes (shown). These cardiac effects can result in syncope and death.[19]
The neurologic, psychosocial, and medicolegal consequences of substance abuse are well documented. However, excessive use of drugs of abuse can also demonstrate visible physical signs. Learn about such manifestations for the nine drugs of abuse.Slideshows, January 2017
Opioids are powerful pain killers that are highly addictive. Opioid dependence affects nearly 5 million people in the United States and leads to approximately 17,000 deaths annually. According to the CDC, the death rate from overdoses tripled from 6.1 per 100,000 people in 1999 to 19.8 in 2016 and rose 20% from 2015 to 2016.Diseases/Conditions, June 2018
Mediastinitis is a life-threatening condition with an extremely high mortality rate if recognized late or treated improperly. Although long recognized as a complication of certain infectious diseases, most cases of mediastinitis are associated with cardiac surgery (>300,000 cases per year in the United States).Diseases/Conditions, Procedures, February 2018
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Contributor Information
Author
Nicole Cimino-Fiallos, MD, FAAEM
Emergency Medicine Specialist
Carroll Hospital Center
Westminster, Maryland
Disclosure: Nicole Cimino-Fiallos, MD, FAAEM, has disclosed no relevant financial relationships.
Editor
Olivia Wong, DO
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: Olivia Wong, DO, has disclosed no relevant financial relationships.
Mehta AB, Weinstein Z, Walkey AJ. The untold toll of the opioid crisis on intensive care units in the United States. Ann Am Thorac Soc. 2017 Dec;14(12):1763-5. PMID: 29192818
Centers for Disease Control and Prevention (CDC). Opioids portal. Reviewed: July 17, 2019. Available at: https://www.cdc.gov/opioids/index.html. Accessed July 17, 2019.
Hossain R, Almeida RR, Natcheva H, et al. Complications of intravenous substance use disorders (SUDs): a multimodality pictorial essay for cardiothoracic radiologists. J Thorac Imaging. 2018 Mar;33(2):W1-12. PMID: 29257030
Schiller EY, Mechanic OJ. Opioid overdose. StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2019-. 2019 Mar 2. PMID: 29262202
Jordan MR, Morrisonponce D. Naloxone. StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2019 Jan-. 2019 Feb 19. PMID: 28722939
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DiGiorgio AM, Stein R, Morrow KD, Robichaux JM, Crutcher CL, Tender GC. The increasing frequency of intravenous drug abuse-associated spinal epidural abscesses: a case series. Neurosurg Focus. 2019 Jan 1;46(1):E4. PMID: 30611170
Abu-Omar Y, Kocher GJ, Bosco P, et al. European Association for Cardio-Thoracic Surgery expert consensus statement on the prevention and management of mediastinitis. Eur J Cardiothorac Surg. 2017 Jan;51(1):10-29. PMID: 28077503
Wurcel AG, Merchant EA, Clark RP, Stone DR. Emerging and underrecognized complications of illicit drug use. Clin Infect Dis. 2015 Dec 15;61(12):1840-9. PMID: 26270683
Rammell J, Kansal N, Bhattacharya V. Management options in the treatment of femoral pseudoaneurysms secondary to intravenous drug abuse: a case series. Int J Surg Case Rep. 2017;36:30-3. PMID: 28528282
Fu X, Chen K, Liao X, Shen K. Case report: surgical removal of a migrated needle in right ventricle of an intravenous drug user. Subst Abuse Treat Prev Policy. 2017 Dec 8;12(1):51. PMID: 29216882
Katselou M, Papoutsis I, Nikolaou P, et al. "Poor man's methadone" can kill the poor man. Extra-medical uses of loperamide: a review. Forensic Toxicol. 2017 July;35(2):217-31.
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