Boris Garber, DO, Attending Physician, MetroHealth Medical Center, Assistant Professor, Case Western Reserve University School of Medicine, Cleveland, OH.
Jonathan Glauser, MD, MBA, FACEP, Professor of Emergency Medicine; Faculty, Residency Program, Emergency Medicine, Case Western Reserve University, Cleveland, OH.
Larissa I. Velez, MD, FACEP, Professor and Program Director, Emergency Medicine, Michael P. Wainscott Professorship in Emergency Medicine, Department of Emergency Medicine, University of Texas Southwestern Medical Center, Dallas.
Statement of Financial Disclosure
To reveal any potential bias in this publication, and in accordance with Accreditation Council for Continuing Medical Education guidelines, we disclose that Dr. Farel (CME question reviewer) owns stock in Johnson & Johnson. Dr. Stapczynski (editor) owns stock in Pfizer, Johnson & Johnson, AxoGen, Walgreens Boots Alliance Inc., and Bristol Myers Squibb. Ms. Mark’s spouse (executive editor) works for a company that creates advertising for Uroplasty. Dr. Schneider (editor), Dr. Garber (author), Dr. Glauser (author), Dr. Velez (peer reviewer), Mr. Landenberger (editorial and continuing education director), and Jonathan Springston (associate managing editor) report no financial relationships with companies related to the field of study covered by this CME activity.
- Injection drug users with a fever and no obvious source should be hospitalized for work-up for endovascular infection, including endocarditis.
- Injection drug use compromises one’s immune system.
- Back pain in an injection drug user with fever should raise concern for epidural abscess or discitis.
- Injection drug users are at higher risk for suicide than the general population.
- Drug use has been a factor in a variety of negative social behaviors: traffic accidents, unemployment, homelessness, and violence.
- Intra-arterial injection may be associated with pseudoaneurysm, limb ischemia, and necrosis.
- Clostridium species are heat-resistant, making them a unique problem to users of black tar heroin.
- S. aureus is the most common organism causing endocarditis in injection drug users.
- Echocardiography and blood cultures remain the mainstays of endocarditis diagnosis.
- Mycotic pseudoaneurysms may require CT scan, ultrasound, or angiography for diagnosis.
- Approach any mass near an artery in an injection drug user with caution and exclude the diagnosis of pseudoaneurysm.
Recreational drug use is a major problem in the United States and around the world. This is a separate problem from drugs of abuse during pregnancy, which may be associated with abruptio placenta, growth retardation, and birth defects. As of 2006, it was estimated that there were approximately 13.2 million intravenous drug users in the world. Most were living in developing nations.1 In the United States, a 2005 survey showed that approximately 8% of adults had used an illicit drug within the previous month.2 Injecting drugs rather than ingesting them by other means adds further health risks that are important for emergency physicians to recognize to properly care for their patients.
Among those with abuse and dependency problems, people who inject substances place their health and lives at a greater risk, and frequently present a high financial burden to society due to chronic ill health.3 Even a single incidence of injecting drugs of abuse can lead to long-term health disorders, while an ongoing injection habit potentially places every organ system at risk. Injection drug abuse results in heavy use of emergency department (ED) services.3,4 These patients are frequently quite difficult to treat due to medical noncompliance, comorbid psychiatric issues, and, frequently, chaotic social situations.1,2,3 This article will examine unique emergencies that occur as a result of recreational injection drug use.
The Nature of the Problem and of the Substances Injected
The most commonly injected drugs in the United States as of this writing include heroin and other opioids, powder or crack cocaine, a combination of heroin and cocaine (speedball), synthetic cathinones (“bath salts”) under names such as Ivory Wave, Vanilla Sky, White Lightning, and others,5 and other stimulants including methamphetamines. (See Table 1.) Phencyclidine, gamma-hydroxybutyric acid (GHB), and MDMA (“ecstasy”) are abused less frequently. There are reports of injection abuse of ketamine,6 methoxitamine (a ketamine analog),7 anabolic androgenic steroids,8 desomorphine (Krokodil)9 and other home synthesized concoctions,10 as well as various psychoactive crushed tablets.11 Given the erratic character of production and supply, the precise nature of injected substance is at times unclear to the user,12 and, in the case of synthetic cannabinoids, essentially undetectable by standard testing. Furthermore, many users inject more than one type of drug. The drugs are typically obtained from the dealer in the form of powder. The drugs are commonly “cut” (adulterated) many times before being consumed, with multiple different substances, some of which may have local irritant or systemic toxicity. Adulterants such as strychnine, clenbuterol (a long-acting beta-2 agonist), or methamphetamine may have their own toxicity. Additives may be contaminated with infectious agents. Other substances used to dilute drugs include, but are not limited to: quinine, lactose, starch, procaine, mannitol, inositol, caffeine, and magnesium silicate (talc).13 It is not uncommon for the drugs to be simply contaminated with dirt. At times, pharmacologically active components such as acetaminophen or caffeine appear as adulterants.14 Levamisole, a common adulterant in U.S. samples of cocaine, is a known cause of agranulocytosis and vasculitis.75
Before a drug can be injected, it has to be reconstituted. Depending on the substance (white powder or black tar heroin, cocaine) different diluents are used. The resulting suspension is usually heated and sometimes filtered through cotton prior to use.15
Heroin is worthy of special mention, as it accounts for such a large share of morbidity and mortality related to drug abuse, and is at the center of a current epidemic. It was first synthesized in 1874 and advertised as a cough suppressant in 1898.16 It is notable that different global sources of heroin produce different products. Heroin historically came from three different regions: Mexico, Southeast Asia, and Southwest Asia, with Colombia emerging as a fourth source in the 1990s. Low solubility “black tar” heroin is associated with reduced HIV prevalence relative to the cold-water soluble heroin produced in Asia and Colombia, but has been associated with wound botulism, tetanus, and necrotizing fasciitis.15
Some users crush various psychoactive tablets17 and inject them; others may inject oral liquid medication formulations. An individual is typically “initiated” into the practice of injecting drugs by an established user who commonly performs the first several initial injections.18 Needle exchange programs, where they exist, supply both clean needles/syringes and, at times, sterile solution for drug reconstitution. Sharing the drug solution or cooker among several people (indirect syringe sharing) is a common practice. When a syringe is used to draw from a communal container, there is a risk of spreading bloodborne infections.19
The drugs are usually injected into hand and forearm veins, with the occasional inadvertent arterial or subcutaneous injection. As substance abusers’ veins are damaged and become unusable, skin popping is more common, as well as use of veins of the upper arms, neck, legs, and groin. There are reports of some users preferentially injecting in groin veins, believing it to be more discreet and easier to hide from family members.20,21 Injecting cocaine appears to lead to especially rapid vein damage.22 Some users develop chronic ulcers and vascular granulation tissue and resort to injecting these alternative sites.
Medical emergencies stemming from drug abuse can be a function of the substance used, the adulterants present, and also the means of delivery. Injection drug users either attempt to inject intravenously, into soft tissue subcutaneously (skin pop) (see Figure 1), or intramuscularly. If the drug is delivered into a blood vessel, it acts quickly, resulting in a strong and quickly developing high, but also placing the user at a high risk of overdose and dependence.23 The amount of drug needed to achieve the desired effect is typically less if it’s injected than if it is ingested, smoked, or snorted.
Recognizing Injection Drug Abuse in Patients in the ED
Certain syndromes and complaints trigger a different work-up, treatment, and disposition once it is established that the patient injects drugs. Many times the patient volunteers the information. Talking to the patient in private and obtaining information from family members when appropriate can be very helpful. A soft-tissue abscess that only requires incision and drainage may require an X-ray to locate a broken needle in the IV drug user. Acute febrile illness in a drug user without an obvious source for fever usually mandates an admission and work-up for endocarditis. Injection drug use is a red flag for epidural abscess in a patient with back pain and fever. Certain past medical history features, such as frequent skin abscesses, infectious endocarditis, or epidural abscess, may prompt the physician to question the patient more carefully regarding injection drug use. On physical examination, the physician should note any recent injection marks, track marks, or scars from skin infections. Findings consistent with puffy hand syndrome16,24 should also raise suspicion for active or prior injection drug abuse. Some drug abusers choose to place elaborate tattoos in an attempt to hide telltale skin changes.
Injection drugs users may have difficult vascular access; once access is established, they may use the new line to inject drugs of abuse and may be tempted to elope with an intravenous line in situ, an especially dangerous situation if a central line was placed for access. It is not unusual for these patients to continue to inject drugs while undergoing treatment in the hospital, resulting in seemingly puzzling fluctuations in their mental status.25,26
Infectious Disease in Users
Infectious agents may be introduced by the drug itself, or from solvents used to reconstitute the drug, contaminants from the patient’s own skin, organisms contaminating drug paraphernalia, or other people in the case of needle-sharing.15 (See Tables 2 and 3.) The resulting infectious complications vary from local bacterial infections (abscess and cellulitis, necrotizing fasciitis) to bacteremia. (See Figure 2.) This may cause sepsis or seeding of distant sites resulting in endocarditis, osteomyelitis, endophthalmitis (see Figure 3), and brain, splenic, or epidural abscess.
Non-bacterial infections and otherwise uncommon bacterial infections may result from injection drug use. These include viral diseases such as human immunodeficiency virus (HIV), and bloodborne forms of hepatitis, notably hepatitis B and C, as well as fungal infections, most commonly systemic candidiasis. Hepatitis C and injection drug use go hand in hand. There is evidence that more than 60% of new hepatitis C patients injected drugs during the prior 6 months. Conversely, perhaps 70-90% of illicit drug users are infected with the hepatitis C virus.27,28 Community-acquired pneumonia and pulmonary tuberculosis are common in drug users. This may be the result of a variety of factors, such as crowded living conditions, residence in homeless shelters, sharing smoke, and noncompliance with treatment. Notably, patients may not have contracted viral infections via drug use; one study from Baltimore indicated that 60% of injection drug users reported a history of a sexually transmitted disease, highlighting other high-risk behaviors present in habitual drug users.29
Drug users may fail to clean injection sites, predisposing them to infection from skin flora such as Staphylococcus aureus or Streptococcus species. In one report, abscesses were twice as likely to occur among those injection drug users who never cleaned the skin before shooting up.30
HIV infection may manifest itself as oral thrush or cervical adenopathy. Otherwise unusual bacterial infections that can be contracted as a result of injection drug use include tetanus,31 wound botulism,32 and syphilis. Approximately 40% of identified cases of tetanus, in one report from a 1997 California epidemic, occurred in injection heroin users.33 Malaria transmission via injection drug use has been reported, although not in the United States.34
A new form of anthrax, injectional anthrax, was recently seen in Northern Europe in people who inject heroin. Notable features included frequent absence of eschar or pus when early incision and drainage were attempted. Bacillus anthracis is a common pathogen in southwest Asia, which is the source for most of Europe’s heroin, and represents a potential danger to someone examining skin lesions without protective gloves.35 The disease is characterized by high mortality, and to date has not been reported in the United States.36
The combination of local irritant effect and vasoconstriction, especially from cocaine and inflammation, can result in the formation of chronic skin ulcers. Extensive venous and lymphatic damage can lead to venous insufficiency with dependent edema and ulcerations which may be or become infected. Endovascular infections apart from infective endocarditis include septic thrombophlebitis (see Figure 4), mycotic aneurysms, and sepsis. In a bacteremic injection-drug user, an endovascular source should be sought.2
Many drugs of abuse appear to weaken the immune system,37,38,39 and as noted earlier, injection drug users have high rates of HIV infection. Furthermore, the lifestyle of drug abusers often is associated with marginalization in society, along with problems with personal hygiene, which may make drug users’ predisposition to infections even greater. Fever in injection drug users, by history or as documented in the ED, usually mandates an admission and work-up for sepsis unless there is an obvious source for the fever. Injecting drugs increases the risk of osteomyelitis and septic arthritis both by contiguous and hematogenous spread,40 as well as for infective endocarditis.
The incidence of suppurative infections in general is high in injection drug users.13 While Gram-positive infections are common, injection at heavily colonized sites such as the femoral vein predisposes to infection with Gram-negative flora. Licking needles prior to injection may increase the risk of anaerobic infections.2
Botulism, Clostridium necrotizing fasciitis in black tar heroin users, and malaria are some of the examples of unusual infectious complications in injection drug users. Black tar heroin may protect against certain infections during preparation, since it is heated in water before use, but clostridial spores survive boiling. Botulism may be difficult to diagnose, not simply because of its rarity, but also because it can masquerade as intoxication if the patient presents with slurred speech, nausea and vomiting, and no evident bulbar palsy or dilated pupils.2
Apart from commonly encountered immune-compromising infections such as hepatitis C or HIV, there is evidence that injection drug use per se compromises one’s immune system. There are receptors in the central nervous system as well as in the immune system for marijuana and opiates, which may play a role in immune modulation.41 Amphetamines, cocaine, and opiates may perturb the homeostatic balance of pro-inflammatory and anti-inflammatory cytokines. Cocaine may alter immune function via sigma-1 receptors, as well as impair polymorphonuclear leukocyte chemotaxis. Marijuana and its more than 60 cannabinoids have been shown to alter functional activities of both B and T lymphocytes, and macrophages. Increased recurrence of genital viral lesions, as well as progression of fibrosis due to hepatitis C, has been associated with cannabis smoking.41 A direct link between drug-induced immune dysfunction and greater susceptibility to infection with bacteria, protozoa, and viruses has been demonstrated.42 It seems, therefore, that cocaine, marijuana, opioids, and amphetamines induce a decrease in host resistance to infection in a broad sense. Endocarditis, osteomyelitis, and epidural abscess are discussed below.
Cutaneous and Musculoskeletal Manifestations of Drug Abuse
The appearance of skin-popping, cutaneous abscess, and cellulitis can be self-evident, as is scarring, making IV access for therapeutic purposes extremely difficult.
In one study, the two most common reasons for admission in intravenous drug users were cellulitis and abscess, respectively. Soft-tissue necrosis, osteomyelitis, and compartment syndrome from inadvertent arterial injection were unusual.10 Infection in unusual places, such as the sternoclavicular or sacroiliac joints, should raise suspicion for injection drug abuse with hematogenous seeding. Organisms involved commonly are staphylococci and streptococci. The presence of anaerobic species and Eikenella corrodens is postulated to be from the practice of licking needles prior to injection.10
The substance desomorphine, the presumed active drug in “krokodil,” has received attention in the media. Drug injection in Russia became widespread after the social and economic disintegration that followed the collapse of the Soviet Union in 1991.9 Injecting liquid poppy straw adulterated with pseudo-ephedrine or other ephedrine-based stimulants from shared drug-mixing solutions, apart from being an obvious source of HIV spread, was associated with phlebitis and gangrene. Codeine, available in Russia inexpensively and over-the-counter, was boiled with a diluting agent such as paint thinner, but also with gasoline, hydrochloric acid, and red phosphorus from the striking surfaces of matches, and injected intravenously without using any filter. This resulted in abscesses, large-scale necrosis, and crocodile bite-like skin lesions, earning the name “the drug that eats junkies.”12 The presence of krokodil outside of the former Soviet Union has not been substantiated.43
Narcotic drug users are at risk for rhabdomyolysis, metaboloic derangements, and acute kidney injury. There may be complications from lying in the same position for hours, but there may also be a myotoxic effect of heroin.44 Compartment syndrome with hyperkalemia has been described.5 Rhabdomyolysis, cardiac and hepatic injury with renal failure, agitation, hyperthermia, and tachycardia have been reported with injection of 3,4-methylenedioxypyrovalerone (MDPV).45
Deep venous thrombosis is a recognized complication of injection drug use, especially when groin area veins are injected.46 As noted earlier, a state of unconsciousness combined with direct muscle toxicity places users at risk for muscle and nerve compression injuries with risk of rhabdomyolysis and renal failure.5,10,44 A broken needle imbedded in soft tissue can cause pain, may serve as a nidus for infection, or can migrate locally or intravascularly. (See Figure 5.) Musculoskeletal infections such as osteomyelitis or discitis may be indolent, causing pain without fever.2
Vascular Complications of Drug Injection
Injecting at sites where an artery lies in close proximity to the skin places patients at risk of inadvertent intra-arterial injection. Potential complications include pseudoaneurysm formation, mycotic pseudoaneurysm, arteritis with subsequent vasospasm and thrombosis, compartment syndrome, and tissue necrosis including amputation of a forearm or fingertips17 and distal particle embolization.47 Among common drugs of abuse, cocaine is especially damaging to arteries.1 Pseudoaneurysm is a rare48 but potentially fatal complication. A pseudoaneurysm is a collection of blood in soft tissue that communicates with the arterial lumen. It presents as a painful pulsatile or non-pulsatile mass, at times mimicking an abscess. The mass is prone to spontaneous free rupture.48 Most pseudoaneurysms develop in the femoral artery due to its close proximity to the femoral vein. Incision and drainage can result in disastrous consequences. Liberal use of duplex ultrasound or arteriography is advisable in cases of “red abscess” in the vicinity of a major artery.1,46 Arteriography has the theoretical risk of rupture of an aneurysm during injection. In addition to bleeding, local nerve compression by the psuedoaneursym can produce characteristic distal praxis.1 There are reports of upper and lower extremity arterial involvement.21,49 Prompt vascular surgery consultation is necessary. Temporizing measures in case of bleeding include direct pressure and proximal arterial tourniquet application.
Arteritis induced by endothelial damage or particle injection can produce extensive distal soft-tissue damage in cases of acute arterial insufficiency caused by either thrombosis or distal embolization.1 If this complication is suspected, systemic anticoagulation with heparin and vascular surgery consultation are suggested. CT angiogram is the imaging modality of choice.1 Nervous plexus block for pain control has been described. Peripheral pulses may be present initially, leading to false reassurance and premature discharge.50
Alternative imaging may include duplex ultrasonography, which may demonstrate femoral artery occlusion, arteriovenous fistula, or deep venous thrombosis. Even if the duplex scan is negative, it may be necessary to re-image using duplex or magnetic resonance angiography (MRA), depending upon one’s clinical suspicion for pseudoaneurysm. Management of pseudoaneurysms may include excision or ligation, saphenous vein interposition, or primary axial reanastamosis with arterial reconstruction. There is significant risk for graft infection and eventual amputation.1
Pulmonary Complications of Injecting Drugs
The lungs serve as a filter for impurities in drugs administered intravenously, and for venous emboli. Pyrogens injected may cause fever, tachycardia, and tachypnea within 10-20 minutes of injection, the so-called “cotton fever.” This tends to be a self-limited phenomenon.
The so called “pocket shot” attempt to access the internal jugular vein can result in a pneumothorax. Pneumomediastinum and air embolism have been described in injection drug users.51 Injected foreign particulate material can lead to perivascular pulmonary granuloma formation26 in drug users and eventually may result in pulmonary hypertension52 and cor pulmonale.11,53 Crushing and injecting tablets gives intravascular entry not just to the intended drug, but possibly to talc (magnesium trisilicate), potato starch, crospovidone, cornstarch, sugars, local anesthetics, or cellulose, some of which are insoluble. Embolization of foreign bodies may cause not only pulmonary embolization, pulmonary hypertension, and granulomatosis, but arterial embolization as well due to systemic shunts.52
Pulmonary edema is a well-known complication of heroin overdose associated with potential for requiring intubation and mechanical ventilation. This presents similarly to non-cardiogenic pulmonary edema from other causes.
The above considerations assume increased need for clinical awareness when evaluating the drug user. Dyspnea, cough, or sputum production may be attributed by the patient and caregiver to nicotine abuse, as most patients who abuse intravenous drugs are smokers.54
Drug users have a 10-fold higher risk of contracting community-acquired pneumonia than the general population.2 How much of this is attributable to concomitant cigarette smoking and poor nutrition is unclear.2 Eosinophilic pneumonia, pneumonitis, and pulmonary fibrosis may result from chronic substance use. Injecting particulate matter can result in venous and arterial thromboembolism.
Acute Infective Endocarditis in the Injection Drug User
Acute endocarditis, especially affecting the right side of the heart, commonly afflicts injection drug users and should be one of the primary concerns in an injection drug user with a fever without another obvious source. Infective endocarditis has an incidence of 1.5-3.3 cases per 1000 injection drug users annually, and up to 20% of injection drug users hospitalized with fever will turn out to have endocarditis.2,55 In injection drug users, the tricuspid valve is the most commonly involved, followed by the mitral, then the aortic valve, with pulmonic and eustachian valve involvement relatively uncommon.56,57 Tricuspid endocarditis is most commonly caused by S. aureus. Patients with endocarditis may present with fever, cough, pleuritic chest pain, and dyspnea.2 (See Table 4.)
Multivalve disease also occurs, and the incidence of left-sided involvement appears to be rising; these two conditions are associated with a more severe clinical course.58 The most common causative agent in infective endocarditis in the injection drug user is Staphylococcus aureus, with a high proportion of isolates being community-acquired methicillin resistant S. aureus (MRSA), followed by Streptococcus species. A multitude of other bacteria, including human oropharyngeal flora, Pseudomonas species, Acinetobacter, and Candida, have been isolated. Polymicrobial infections have also been described.59,60 Prior endocarditis, AIDS, and cocaine abuse place the injection drug user at even greater risk for infection. Mortality is higher in HIV-infected individuals whose CD4 cell count is below 200 per mm3.61
The diagnosis of infective endocarditis commonly relies on the Duke Criteria62 (see Table 5) and can be easy when a classic combination of sepsis, valvular damage, and peripheral immunological changes and embolic phenomena are apparent. However, early in the course, especially if a history of injection drug use is not apparent, the diagnosis can be difficult. The emergency physician should use caution in the evaluation of any drug user, and should be especially careful about discharging home a febrile patient who is found to have telltale skin infection, petechiae or vasculitis, a pulmonary infiltrate, an unexplained internal abscess, white blood cells in urine without dysuria, or when a young patient presents with new-onset heart failure or multilobar pneumonia consistent with tricuspid endocarditis.
Extreme caution should be exercised before giving antithrombotic medications to patients known to inject drugs and who present with symptoms of acute stroke or acute myocardial infarction, as these medications are generally contraindicated in infectious endocarditis. These patients should be admitted and have multiple blood cultures obtained.60,62 Echocardiography should be performed as soon as possible, usually with a transthoracic echocardiogram first followed by transesophageal echocardiogram as necessary.63
As with other forms of severe sepsis, broad-spectrum antibiotics and appropriate supportive measures should be instituted. Emergent cardiac surgery is indicated for patients with intractable heart failure or cardiogenic shock.63 Many of the complications of endocarditis will require collaboration among many specialists in managing these sick patients. The emergency physician should consider transferring these patients early if the institution lacks the ability to perform the necessary testing and consultations.
Other Cardiovascular Complications of Drug Use
A transient drug-linked cardiomyopathy may be precipitated by the intense stress of sympathetic overstimulation, which is a form of Takotsubo cardiomyopathy. The condition is characterized by a transient decrease in ejection fraction, classically with apical ballooning noted on echocardiogram, without significant coronary artery disease. Patients may present with chest pain, dyspnea, pulmonary edema, and, more unusually, cardiogenic shock. Reported drugs associated with this syndrome include opioids and drugs with adrenergic properties.64 This is not a rare disease, occurring in perhaps 1% of cases of presentation as acute coronary syndrome or ST-elevation myocardial infarction (STEMI) mimic, and has been attributed to drug withdrawal as well, notably withdrawal from oxycodone or from beta blockers such as metoprolol.65
Cocaine use has been associated with thoracic aortic dissection, renal artery dissection, and intestinal ischemia.1 Maternal cocaine use has been associated with aortic arch thrombosis in a neonate.1
Buerger’s disease, otherwise known as thromboangiitis obliterans, an inflammatory occlusive vascular disorder usually associated with tobacco smoking, has been reported with cannabis use.66 This may cause Raynaud’s phenomenon, painful ulcerations, gangrene, or amputation.
Psychosocial Aspects of Injection Drug Use in the ED
Injection drug users have high prevalence of comorbid major psychiatric disorders and a much higher risk of attempted and completed suicide than the general population.67-69 The incidence of personality disorders is also high, as well as precarious living situations, impulsiveness, and risk-taking behaviors.70 Most of these patients abuse multiple substances and may misuse or seek various psychoactive substances. They may not know what substances or contaminants they have smoked, ingested, or injected. In fact, a high percentage of street samples may lack the alleged drug entirely. Multiple factors make these patients poor historians and highly non-compliant patients. Often the emergency department is their only source of care.3,71
Patients may have problems at school or at work, interpersonal problems with partners or children, violence, and trauma. High-risk sexual behavior, legal problems for intoxication, driving under the influence, and altercations are common. Bizarre behavior, anxiety, agitation, and psychosis may result from a variety of substances, including some substances which are not injected, as with synthetic cannabinoids such as K2 and spice. Negative social and health consequences of drug abuse include, but are not limited to: unemployment, homelessness, violence, and mental health disorders. Whether these social issues stem from underlying psychosocial issues or from the substances themselves may be difficult to discern in the emergency setting.
Central Nervous System (CNS) Complications of IV Drug Use
Injecting drugs is considered to be a risk factor for stroke.72 Heroin-related stroke has been associated with large vessel arteritis,73 and amphetamine use has been linked to cerebral vasculitis as a cause for ischemic stroke.74 Strokes associated with cannabis use classically have been ischemic in nature,75 although vasospasm has been proposed as a mechanism for cannabis-associated stroke.76 Amphetamine, cocaine, and the related ecstasy have become important causes of thoracic aortic dissection and of intracranial hemorrhage among young adults.77 More recently, the synthetic cannabinoid spice has been linked to subarachnoid hemorrhage and hemorrhagic stroke.78
Persistent unexplained headache in an injection drug user should raise concern for intracerebral abscess80 in addition to other life-threatening processes.
Of special concern are infectious CNS complications such as spine spondylitis, discitis, and epidural abscess of the cranium and spine.79,80 Localized back pain in a patient with a history of injecting drugs and without another obvious explanation should prompt appropriate imaging. Standard diagnosis entails magnetic resonance imaging (MRI) with pre- and post-gadolinium contrast imaging to exclude these complications.79 There is no predictable level at which the spine may be involved in the injection drug user; one survey found the lumbar level to be the most common level; another found the most common level to be cervical.71,79 (See Figure 6.)
Both white blood cell count and inflammatory markers are normal in some patients with a spinal abscess,71 although one report cited a mean erythrocyte sedimentation rate (ESR) and mean C-reactive protein (CRP) of 61 mg/dL and 88 mg/dL, respectively, in IV drug users with pyogenic infections of the spine.79 Distal neurological deficits, while usually absent on presentation, signify cord compression and are associated with severe permanent neurologic sequelae and death.70 Systemic signs of inflammation and sepsis eventually develop, but early on are commonly lacking, and their absence cannot be relied upon to rule out this complication. Timely diagnosis followed by emergent neurosurgical or spine consultation and aggressive treatment offers the best chance of recovery.71 While Staphylococcus species are most commonly the culprit, a variety of other organisms have been isolated, necessitating broad antibiotic coverage until culture results become available. Viral as well as bacterial infections may exist concomitantly. One study of pyogenic infections of the spine in intravenous drug users noted that more than 40% had hepatitis C, 12-13% had hepatitis B, and 22-23% were positive for HIV, and that nearly one-third had an identifiable organism on blood cultures.40,79
Transverse myelitis is an unusual but well-described complication of heroin overdose. Symptoms may include extremity paresis, sensory loss, incontinence, or urinary retention. MRI of the spine shows characteristic findings, including effacement of ventral and dorsal subarachnoid spaces with patchy increased intramedullary signal.72
Injection drug users are subject to a wide variety of behavioral, cutaneous, immunologic, infectious, cardiac, neurologic, vascular, renal, musculoskeletal, and psychiatric disorders. It is prudent to treat these patients as any other immunocompromised patients. A history of substance use may be inaccurate, as these substances are illicit, and the people who consume them may not be fully aware of what they were taking, necessitating supportive care regardless of the agent. Behavioral disorders can make this group of patients particularly challenging to manage.
- Coughlin PA, Mayor AID. Arterial consequences of recreational drug use. Eur J Vasc Endovasc Surg 2006;32:389-396.
- Gordon RJ, Lowy FD. Bacterial infections in drug users. N Engl J Med 2005;353:1945-1954.
- O’Connor G, McGinty T, Yeung SJ, et al. Cross-sectional study of the characteristics, healthcare usage, morbidity and mortality of injecting drug users attending an inner city emergency department. Emerg Med J 2014;31:625-629.
- Aitken C, Kerr T, Hickman M, et al. A cross-sectional study of emergency department visits by people who inject drugs. Emerg Med J 2013;30:421-422.
- Borek HA, Holstege CP. Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3, 4-methylenedioxypyrovalerone. Ann Emerg Med 2012;60:103-105.
- Lankenau SE, Clatts MC. Drug injection practices among high-risk youths: The first shot of ketamine. J Urban Health 2004;81:232-248.
- Hofer KE, Grager B, Muller DM, et al. Ketamine-like effects after recreational use of methoxetamine. Ann Emerg Med 2012;60:97-99.
- Parkinson AB, Evans NA. Anabolic androgenic steroids: A survey of 500 users. Med Sci Sports Exerc 2006;38:644-651.
- Gahr M, Freundenmann RW, Hiemke C, et al. “Krokodil”: Revival of an old drug with new problems. Subst Use Misuse 2012;47:861-863.
- Booth RE. “Krokodil” and other home-produced drugs for injection: A perspective from Ukraine. Int J Drug Policy 2013;24:277-278.
- Darke S, Duflou J, Torok M. The health consequences of injecting tablet preparations: Foreign body pulmonary embolization and pulmonary hypertension among deceased injecting drug users. Addiction 2015;110:1144-1151.
- Mullins ME, Schwarz ES. ‘Krokodil’ in the United States is an urban legend and not a medical fact. Am J Med 2014;127:e25.
- Del Giudice P. Cutaneous complications of intravenous drug abuse. Br J Dermatol 2004;150:1-10.
- Brunt TM, Rigter S, Hoek J, et al. An analysis of cocaine powder in the Netherlands: Content and health hazards due to adulterants. Addiction 2009;104:798-805.
- Ciccarone D. Heroin in brown, black and white: Structural factors and medical consequences in the US heroin market. Int J Drug Policy 2009;20:277-282.
- Dinis-Oliveira RJ, Carvalho F, Moreira R, et al. Clinical and forensic signs related to opioids abuse. Curr Drug Abuse Rev 2012;5:273-290.
- Bruggisser M, Bodmer M, Liechti ME. Severe toxicity due to injected but not oral or nasal abuse of methylphenidate tablets. Swiss Med Wkly 2011;141:w13267.
- Bluthenthal RN, Wenger L, Chu D, et al. Factors associated with being asked to initiate someone into injection drug use. Drug Alcohol Depend 2015;149: 252-258.
- Koester S, Glanz J, Baron A, et al. Drug sharing among heroin networks: Implications for HIV and hepatitis B and C prevention. AIDS Behav 2005;9:27-39.
- Miller PG, Lintzeris N, Forzisi L. Is groin injecting an ethical boundary for harm reduction? Int J Drug Policy 2008;19:486-491.
- Salimi J, Shojaeefar A, Khashayar P. Management of infected femoral pseudoaneurysms in intravenous drug abusers: A review of 57 cases. Arch Med Res 2008;39:120-124.
- Rhodes T, Briggs D, Kimber J, et al. Crack–heroin speedball injection and its implications for vein care: Qualitative study. Addiction 2007;102:1782-1790.
- McKetin R, Ross J, Kelly E, et al. Characteristics and harms associated with injecting versus smoking methamphetamine among methamphetamine treatment entrants. Drug Alcohol Rev 2008;27:277-285.
- Buckland A, Barton R, McCombe D. Upper limb morbidity as a direct consequence of intravenous drug abuse. Hand Surg 2008;13:73-78.
- Hicks CW, Sweeney DA, Cui X, et al. An overview of anthrax infection including the recently identified form of disease in injection drug users. Intensive Care Med 2012;38:1092-1104.
- Darke S, Ross J. Suicide among heroin users: Rates, risk factors and methods. Addiction 2002;97:1383-1394.
- Gish RG, Afdhal NH, Dieterich DT, et al. Management of hepatitis C virus in special populations: Patient and treatment considerations. Clin Gastroenterol Hepatol 2005;3:311.
- Weaver MF, Cropsey KL, Fox SA. HCV prevalence in methadone maintenance: Self-report versus serum test. Am J Health Behav 2005;29:387-389.
- Nelson KE, Vlahov D, Cohn S, et al. Sexually transmitted diseases in a population of intravenous drug users: Association with seropositivity to the human immunodeficiency virus. J Infect Dis 1991;164:457-463.
- Vlahov D, Sullivan M, Astemborski J, et al. Bacterial infections and skin cleaning prior to injection among intravenous drug users. Public Health Rep 1992;107:595-598.
- Palmateer NE, Hope VD, Roy K, et al. Infections with spore-forming bacteria in persons who inject drugs, 2000–2009. Emerg Infect Dis 2013;19:29.
- Johnson EA, Montecucco C. Botulism. Handb Clin Neurol 2008;91:333-368.
- Centers for Disease Control and Prevention. Tetanus among injecting-drug users — California, 1997. Morbid Mortal Wkly Rep 1998;47:149-151.
- Alavi SM, Alavi L, Jaafari F. Outbreak investigation of needle sharing-induced malaria, Ahvaz, Iran. Int J Infect Dis 2010;14:e240-e242.
- Centers for Disease Control and Prevention. Anthrax: How people are infected. Available at http://www.cdc.gov/anthrax/basics/how-people-are-infected.html. Accessed Oct. 19, 2015.
- Roy S, Ninkovic J, Banerjee S, et al. Opioid drug abuse and modulation of immune function: Consequences in the susceptibility to opportunistic infections. J Neuroimmune Pharmacol 2011;6:442-465.
- Friedman H, Newton C, Klein TW. Microbial infections, immunomodulation, and drugs of abuse. Clin Microbiol Rev 2003;16:209-219.
- Sahni V, Garg D, Garg S, et al. Unusual complications of heroin abuse: Transverse myelitis, rhabdomyolysis, compartment syndrome, and ARF. Clin Toxicol 2008;46:153-155.
- Allison D, Holtom PD, Patzakis MJ, et al. Microbiology of bone and joint infections in injecting drug abusers. Clin Orthop Rel Res 2010;468:2107-2112.
- Cabral GA. Drugs of abuse, immune modulation, and AIDS. J Neuroimmune Pharmacol 2006;1:280-295.
- Friedman H, Newton C, Klein TW. Microbial infections, immunomodulation, and drugs of abuse. Clin Microbiol Rev 2003;16:209-219.
- Del Giudice P, Durant J, Dellamonica P. Hand edema and acrocyanosis: ‘Puffy hand syndrome.’ Arch Dermatol 2006;142:1084–1085.
- Kosmadakis G, Michail O, Filiopoulos V, et al. Acute kidney injury due to rhabdomyolysis in narcotic drug users. Int J Artif Organs 2011;34:584-588.
- Pescatore R, Robidoux M, Cole R, et al. Compartment syndrome and rhabdomyolysis presenting with the rare pseudo-infarction pattern of hyperkalemia. AJMCR 2014;2:262-265.
- Smith WB, Campbell KA, Zierler RE. Duplex ultrasound findings in intravenous drug users with femoral vein injection. Journal for Vascular Ultrasound 2013;37:14-20.
- Georgiadis GS, Bessias NC, Pavlidis PM, et al. Infected false aneurysms of the limbs secondary to chronic intravenous drug abuse: Analysis of perioperative considerations and operative outcomes. Surg Today 2007;37:837-844.
- Lardi C, Fracasso T. Spontaneous external rupture of femoral pseudoaneurysm: Fatal hemorrhage related to drug abuse. Am J Forensic Med Pathol 2012;33:319-321.
- Tsao JW, Marder SR, Goldstone J, et al. Presentation, diagnosis, and management of arterial mycotic pseudoaneurysms in injection drug users. Ann Vasc Surg 2002;16:652-662.
- Partanen TA, Vikatmaa P, Tukiainen E, et al. Outcome after injections of crushed tablets in intravenous drug abusers in the Helsinki University Central Hospital. Eur J Vasc Endovasc Surg 2009;37:704-711.
- Shrestha B, McLemore JL, Mils MC. Sudden death by acute cor pulmonale from intravenous drug abuse during an inpatient admission: Implications for unexplained in-hospital death. Clin Pulm Med 2013;20:192-195.
- Stoove MA, Dietze PM, Campbess CK, et al. Mortality among injecting drug users in Melbourne: A 16-year follow-up of the Victorian Injecting Cohort Study (VICS). Drug Alcohol Depend 2008;96:281-285.
- Wolff AJ, O’Donnell AE. Pulmonary effects of illicit drug use. Clin Chest Med 2004;25:203-216.
- Pare JA, Fraser RG, Hogg JC, et al. Pulmonary “mainline” granulomatosis: Talcosis of intravenous methadone abuse. Medicine 1979;58:229-239.
- Wilson LE, Thomas DL, Astemborski J, et al. Prospective study of endocarditis among injection drug users. J Infect Dis 2002;185:1761-1766.
- Moss R, Munt B. Injection drug use and right sided endocarditis. Heart 2003;89:577-581.
- Jain V, Yang MH, Kovacicova-Lezcano G. Infective endocarditis in an urban medical center: Association of individual drugs with valvular involvement. J Infection 2008;57:132-138.
- Sousa C, Botelho C, Rodrigues D, et al. Infective endocarditis in intravenous drug abusers: An update. Eur J Clin Microbiol Infect Dis 2012;31:2905-2910.
- Chung-Esaki H, Rodriguez RM, Alter H, et al. Validation of a prediction rule for endocarditis in febrile injection drug users. Am J Emerg Med 2014;32:412-416.
- Cicalini S, Forcina G, DeRosa FG. Infective endocarditis in patients with human immunodeficiency virus infection. J Infect 2001;42:267-271.
- Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633.
- Hoen B, Duval X. Infective endocarditis. N Engl J Med 2013;368:1425-1433.
- Habib G, Hoen B, Tornos P, et al; ESC Committee for Practice Guidelines. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009). The Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J 2009;30:2369-2413.
- Amariles P. A comprehensive literature search: Drugs as possible triggers of Takotsubo cardiomyopathy. Curr Clin Pharmacol 2011;6:1-11.
- Izumi Y. Drug-induced Takotsubo cardiomyopathy. Heart Failure Clin 2013;9:225-231.
- Disdier P, Granel B, Serratrice J, et al. Cannabis arteritis revisited- ten new case reports. Angiology 2001;52:1-5.
- Mackesy-Amiti ME, Donenberg GR, Ouellet LJ. Prevalence of psychiatric disorders among young injection drug users. Drug Alcohol Depend 2012;124:70-78.
- Darke S, Ross J. Suicide among heroin users: Rates, risk factors and methods. Addiction 2002;97:1383-1394.
Havens JR, Strathdee SA, Fuller CM, et al. Correlates of attempted suicide among young injection drug users in a multi-site cohort. Drug Alcohol Depend 2004;75:
- Fuller CM, Vlahov D, Ompad DC, et al. High-risk behaviors associated with transition from illicit non-injection to injection drug use among adolescent and young adult drug users: A case-control study. Drug Alcohol Depend 2002;66:189-198.
- Sahni V, Garg D, Garg S, et al. Unusual complications of heroin abuse: Transverse myelitis, rhabdomyolysis, compartment syndrome and ARF. Clin Toxicology 2008;46:153-155.
- Yeung M, Bhalla A, Birns J. Recreational drug misuse and stroke. Curr Drug Abuse Rev 2011;4:286-291.
- Brust JCM, Richter RW. Stroke associated with addiction to heroin. J Neurol Neurosurg Psychiatry 1976;39:194-199.
- Schteinschneider A, Lemme-Plaghos L, Garbugino S, et al. Cerebral arteritis following methylphenidate use. J Child Neurol 2000;15:265-267.
- Mateo I, Pinedo A, Gomez-Beldarrain, et al. Recurrent stroke associated with cannabis use. J Neurol Neurosurg Ps 2005;76:435-437.
- Mesec A, Rot U, Grad A, et al. Cerebrovascular disease associated with marijuana abuse: A case report. Cerebrovasc Dis 2001;11:284-285.
- McEvoy AW, Kitchen ND, Thomas DG. Intracerebral haemorrhage and drug abuse in young adults. Br J Neurosurg 2000;14:449-454.
- Rose DZ, Guerrero WR, Molin HV, et al. Hemorrhagic stroke following use of the synthetic marijuana “spice.” Neurology 2015;85:1177-1779.
Wang, Z, Lenehan B, Itshayek E, et al. Primary pyogenic infection of the spine in intravenous drug users: A prospective observational study. Spine 2012;37:
- Pradilla G, Ardila GP, Hsu W, et al. Epidural abscesses of the CNS. Lancet Neurol 2009;8:292-300.
- Ziu M, Dengler B, Cordell D, et al. Diagnosis and management of primary pyogenic spinal infections in intravenous recreational drug users. Neurosurg Focus 2014;37:E3 1-8.
- Del Giudice P. Cutaneous complications of intravenous drug abuse. Br J Dermatol 2004;150:1-10.