Dr. Gustin's Blog

Kratom Products from Southeast Asia are Contaminated with Heavy Metals

Final results of tests performed by the US Food and Drug Administration (FDA) on 30 kratom products confirm the presence of heavy metals, including lead and nickel, at concentrations not considered safe for human consumption, the FDA said Wednesday.

The FDA first warned of "disturbingly" high levels of heavy metals, including lead and nickel, last November, as reported by Medscape Medical News.  The FDA has posted a list of the kratom products and concentrations of heavy metals found in them on its website. Based on reported patterns of kratom use, heavy kratom users may be exposed to levels of lead and nickel many times greater than the safe daily exposure, the FDA warns in a statement.

Based on these test results, the typical long-term kratom user could potentially develop heavy metal poisoning, which could include nervous system or kidney damage, anemia, high blood pressure, and increased risk of certain cancers, the agency adds.

"Over the last year, the FDA has issued numerous warnings about the serious risks associated with the use of kratom, including novel risks due to the variability in how kratom products are formulated, sold and used both recreationally and by those who are seeking to self-medicate for pain or to treat opioid withdrawal symptoms," FDA Commissioner Scott Gottlieb, MD, said in the statement.

Gottlieb said the FDA has been "attempting to work" with the companies whose kratom products contain high levels of heavy metals.  The agency has released the final laboratory results to the public to "help make sure consumers are fully informed of these risks." "The data from these results support our public warning about the risk of heavy metals in kratom products. The findings of identifying heavy metals in kratom only strengthen our public health warnings around this substance and concern for the health and safety of Americans using it," he added.

No Approved Use Kratom is derived from the leaves of the kratom tree (Mitragyna speciosa), which is native to Thailand, Indonesia, and Papua New Guinea. The botanical's popularity has been increasing in the United States, with manufacturers — and those who take it — claiming it can help treat pain, anxiety, depression, and more recently, opioid withdrawal. Last year, an analysis of kratom by FDA scientists found that its compounds act like prescription-strength opioids. In addition to heavy metal contamination, kratom products have also been found to be contaminated with Salmonella, resulting in numerous illnesses and product recalls. Kratom has been linked to numerous deaths in the United States. There are currently no FDA-approved uses for kratom, and the agency has advised against using kratom or its psychoactive compounds mitragynine and 7-hydroxymitragynine in any form and from any manufacturer.

Health providers are encouraged to report any adverse reactions related to kratom products to MedWatch, the FDA's safety information and adverse event reporting program.

Exertional Heat Illness- Death While Running/Cycling

Exertional heat illness (EHI) is among the leading causes of death in young athletes each year.  A report by the United States Centers for Disease Control (CDC) found that EHI occurs both during practice and competition and noted a disturbing trend of increasing incidence [3]. Clinicians who care for athletes, both young and old, and others who exert themselves in the heat (eg, firefighters, soldiers, construction workers) need to be aware of the basic physiologic principles of thermoregulation, the spectrum of heat illness, strategies for prevention and treatment, and current guidelines for determining safe return to play or work.

The process of thermoregulation and the epidemiology, clinical presentation, and diagnosis of the different types of exertional heat illness, including exertional heat stroke, are reviewed here. The management of exertional heat stroke and other forms of exertional heat illness is discussed separately, as are exercise-associated hyponatremia, nonexertional heat stroke, malignant hyperthermia and other causes of severe hyperthermia, and heat illness in children. 


Exertional heat illness (EHI) is an ever present danger when athletes, military personnel, or laborers perform intense exercise in the heat. A table summarizing important functional, acquired, and congenital risk factors for EHI is provided.

Despite great progress educating athletes, coaches, and clinicians, deaths related to exertional heat stroke (EHS), the most severe form of EHI, appear to be on the rise. Deaths from EHS were higher during the period from 2005 to 2009 than any other five year period over the past 35 years. The United States Centers for Disease Control report a weighted average of 9237 cases of EHI among high school athletes per year for the period 2005 to 2009. The United States military, despite a continued focus on prevention, reported an increase in exertional heat stroke cases (344) in 2014 compared with 2013.

In the United States, the highest incidence of EHS is found among participants in American football, in whom the condition occurs at a rate of 4.5 cases per 100,000 athlete exposures. According to an annual survey of catastrophic American football injuries presented in 2008, 31 players have died from EHS since 1995. Most cases occurred during summer practice when players are less fit, and temperatures and humidity are often high. According to our data, only one death from EHS occurred among American collegiate football players between 2003 and 2011 during traditional August practices due to the adoption of heat acclimatization policies in 2003. However, problems persist in high school football and collegiate strength and conditioning training, during which a disproportionate number of deaths have occurred.

A comprehensive study of fatal episodes of EHS among military personnel provides further insight into important risk factors. According to this study, the absence of appropriate medical triage and physical effort beyond the fitness capacities of the victim were found in all deaths. Training in extreme heat was also common.

Other studies emphasize the importance of adverse environmental conditions in heat illness. Data from large-scale endurance events, such as marathons, show a strong correlation between the severity of environmental conditions and the incidence of heat illness, especially EHS.  According to annual surveillance studies of the Falmouth (Massachusetts, USA) Road Race (7 mile/11 km event), elevations in the temperature and heat index correlate with an increase in the incidence of exertional heat stroke.  A four-year study of collegiate American football players found the incidence of heat illness to be closely associated with rising wet bulb globe temperature (WBGT) and lack of heat acclimatization.  A study of high school football players reported similar results.


According to several large reviews and reports, common risk factors for all types of exertional heat illness (EHI) include the following:

-Strenuous exercise in high ambient temperature and humidity

-Lack of acclimatization 

-Poor physical fitness


-Acute illness

-External load, including clothing, equipment, and protective gear

Drugs and dietary supplements may increase the risk for EHI through a number of mechanisms, including impaired sweating, cardiovascular disturbances (eg, peripheral vasoconstriction or impaired cardiovascular performance), increased heat production, disturbances in water and electrolyte balance, and decreased perception of fatigue, which might hinder the voluntary termination of exercise. Drugs and supplements associated with an increased risk for EHI include but are not limited to [16,21,22]:

●Anticholinergic agents

●Antiepileptic agents

●Angiotensin-converting enzyme inhibitors

●Angiotensin II receptor blockers




●Tricyclic antidepressants


●Ergogenic stimulants (eg, ephedrine, dimethylamylamine)


●Beta blockers



Regulation of body temperature — Body temperature is regulated in the preoptic nucleus of the anterior hypothalamus, which carefully maintains a core temperature of 37°C±1° (98.6˚F±1.8°). The pathophysiology of heat illness is discussed separately.

While the human body has remarkable resilience against cold, it can tolerate only minor temperature elevations above normal (4.5°C, 9°F) without developing systemic dysfunction, which ultimately leads to multiorgan failure and death if body temperature cannot be lowered. Accordingly, the human body has multiple mechanisms to dissipate heat [21,30,31]:

Evaporation occurs when water vaporizes from the skin and respiratory tract. This is the body's most effective mechanism for dissipating excess heat and is the primary means for athletes exercising in hot environments.

●Radiation is the emission of electromagnetic heat waves. This energy transfer does not require direct contact or air motion.

Convection is the transfer of heat to a gas or liquid moving over the body. Heat transfer occurs when the gas or liquid is colder than the body.

 ●Conduction is direct heat transfer to an adjacent, cooler object.

During exercise, the human body acts to dissipate the excess heat generated by skeletal muscle. This requires an intact cardiovascular system that uses blood to transfer heat from the body core to the skin, where the mechanisms for dissipating heat can take effect. During high heat loads, blood flow to the skin increases many fold. However, when the ambient temperature is higher than the body's core temperature, convection, conduction, and radiation are no longer effective.

Environmental conditions also effect evaporative cooling. A water vapor pressure gradient must exist for sweat to evaporate and release heat into the environment. In high humidity (relative humidity >75 percent), evaporation becomes ineffective for transferring heat. Thus, in hot and humid conditions, athletes become susceptible to exertional heat illness.

Limitations on heat dissipation in hot and humid weather are exacerbated during intense exercise by a finite supply of blood that must fulfill multiple functions, including meeting the metabolic demands of active skeletal muscle and transporting heat to the skin surface for cooling. Further complicating matters is the dehydration that develops in most individuals during intense exercise in the heat, which decreases plasma volume.

Studies suggest that during intense exercise in the heat, for every one percent of body mass lost from dehydration, there is a concomitant increase in core body temperature of 0.22°C (0.4°F). In other words, other factors being equal, an athlete who lost only 1 percent of body mass from dehydration during intense exercise in the heat would be 1°C cooler compared to a teammate who lost 6 percent of body mass. This would equate to a temperature difference of approximately 39°C (102°F) versus 40°C (104°F) at the end of a training session.

A number of additional factors influence the rate at which a person's core body temperature rises during vigorous activity, including fitness level, degree of acclimatization to heat, clothing/equipment, and physiologic response (eg, degree of tachycardia).

Compensated and uncompensated heat stress — Heat stress refers to the environmental and host conditions that increase body temperature. Heat stress is further categorized as compensated or uncompensated. Heat strain is the physiological and psychological consequence of heat stress. Severe heat strain is associated with a decline in athletic performance and increases the risk for EHI.

During exercise, the body elevates its temperature in response to the increase in metabolic heat production; a modest rise in temperature is thought to represent a favorable adjustment that optimizes physiologic functions. With compensated heat stress (CHS), the body achieves a new steady-state core temperature that is proportional to the increased metabolic rate and available means for dissipating heat. Studies in runners describe exercise-induced hyperthermia, including athletes completing events successfully with significantly elevated core temperatures.

Uncompensated heat stress (UCHS) results when cooling capacity is exceeded and the athlete cannot maintain a steady temperature. Continued exertion in the setting of UCHS increases heat retention, causing a progressive rise in core body temperature and increasing the risk for severe heat illness.

Thermotolerance and acclimatization — Tolerance of extreme heat and humidity depends upon a number of functional, acquired, and congenital factors, of which acclimatization is of great importance .

Acclimatization is the body's ability to improve its response and tolerance of heat stress over time, and it is the most important factor determining how well an athlete withstands extreme heat. Thus, allowing sufficient time and using optimal training strategies that enable athletes to acclimatize is critical for improving performance and mitigating the risk for EHI. Observational studies have found that the first week of athletic practice in high heat and humidity is the period of greatest risk for developing EHI [3,41,45]. Acclimatization requires at least one to two weeks. However, any improved tolerance of heat stress generally dissipates within two to three weeks of returning to a more temperate environment. The attached tables provide guidelines for acclimatization.

The major physiologic adjustments that occur during heat and humidity acclimatization include [41]:

●Plasma volume expansion

●Improved cutaneous blood flow

●Lower threshold for initiation of sweating●

●Increased sweat output

●Lower salt concentration in sweat

●Lower skin and core temperatures for a standard exercise



Terminology — The classification of heat illness is controversial, as the precise pathophysiology of these disorders remains largely unknown. Accordingly, experts disagree about the general categories of illness, as well as the temperature and symptoms needed to define specific heat illnesses.

The International Classification of Diseases (ICD) published by the World Health Organization (WHO) offers one reasonable method for categorizing the various forms of exertional heat illnesses. The ICD contains 10 categories of heat disorders. Four of these diagnoses (heat cramps, heat syncope, heat exhaustion, and heat stroke), as well as heat injury, are the most common entities found in athletes and others who engage in vigorous activity in the heat (eg, soldiers, laborers). Although not recognized by the WHO, heat injury is a term used by the United States military to describe a condition that falls between heat exhaustion and heat stroke. These relatively common entities are described below.

"Heat cramps" (exercise associated muscle cramps)

Definition, clinical presentation, and risk factors — Although muscle cramps are common in athletes, their etiology and pathophysiology remain poorly understood. The term "heat cramps" is a misnomer, as heat has not been shown to directly trigger cramping. Nevertheless, nearly all cases of cramping in athletes involve exercise at a high intensity or to exhaustion. Muscle cramps occur more often when athletes perform strenuous exercise in the heat, but they can also occur in cooler environments (eg, ice hockey, swimming). Muscle cramps are also more common in athletes engaged in novel or rarely performed exercise regimens. The treatment of heat cramps is discussed separately. 

A number of factors are thought to contribute to the development of muscle cramps in athletes. Dehydration, loss of sodium and/or potassium, extreme environmental conditions, and neurogenic fatigue are suspected to play a role .

As a result of the controversy surrounding the etiology of muscle cramps, sports medicine researchers often refer to cramping that occurs during or after exercise as "exercise associated muscle cramping" (EAMC). Clinical criteria for establishing the diagnosis of muscle cramps generally include intense muscle pain (not associated with acute muscle strain or other injury) and spasm, and persistent contractions of the muscles primarily involved in the prolonged exercise. No signs of more severe illness, such as exertional hyponatremia or exertional heat stroke, may be present.

Factors that are thought to predispose to EAMC include:

●Sweat with high salt concentration (ie, "salty sweaters") [54,55]

●Heavy sweating


●Insufficient sodium intake prior to and during intense activity

●Lack of heat acclimatization

●Baseline (preactivity) fatigue

●History of heat cramps

Differential diagnosis — It is important to note that muscle cramps are not necessarily related to exercise. The differential diagnosis is extensive and includes medications (eg, diuretics), myopathies, and endocrine disorders. Another possible cause is sickle cell trait, which is thought to have played a role in several cases of exertional sudden death and severe rhabdomyolysis [56]. In some of these cases, reports describe antecedent cramping following brief periods of intense exercise characterized by intense pain and distinguishable from EAMC-related symptoms by the lack of spasm, suggesting the possibility of acute muscle ischemia.

Heat syncope and exercise associated collapse

Definitions, clinical presentation, and pathophysiology — Heat syncope is among the more confusing diagnoses identified by the International Classification of Diseases. Like heat cramps, heat syncope is a misnomer as heat does not directly cause the syncopal event (ie, core body temperature is not significantly elevated). The treatment of heat-related syncope is discussed separately. 

The syncopal event that occurs in the exercising athlete is more appropriately termed "exercise associated collapse" (EAC) [15]. EAC occurs when an athlete is unable to stand or walk as a result of lightheadedness or syncope. EAC usually occurs immediately after completing a race or workout and is commonly observed at endurance events (eg, marathon). The mechanism for collapse is an abrupt decrease in venous return once that athlete completes the event. Given the typical degree of vasodilatation seen with prolonged exertion, the sudden loss of the pressure exerted by the skeletal muscles on the vasculature leads to a precipitous decline in venous return, as well as postural tone, causing the athlete to collapse.

Heat is an indirect contributor to EAC as the body is dually tasked to provide blood to exercising muscle and the periphery, to assist in thermoregulation. In typical EAC, the athlete's core temperature is either normal or only marginally elevated and any alterations in mental status quickly resolve (within approximately 15 to 20 minutes) with appropriate treatment. These features help to distinguish EAC from heat stroke.

Heat syncope in those who are not exercising can be described as a transient loss or near-loss of consciousness due to the indirect effects of high ambient temperature. Heat syncope occurs most often during the first few days that someone is exposed to high environmental temperatures, before acclimatization is complete. Two common scenarios for heat syncope are:

●Prolonged standing in the heat with little movement

 ●Sudden standing after prolonged sitting in the heat

The signs and symptoms associated with these forms of heat syncope include light-headedness, tunnel vision, pale and sweaty skin, and decreased pulse rate. Most often the core temperature is normal or only mildly elevated. Patients generally recover rapidly with appropriate treatment.

The pathophysiology for each of these nonexertional events is related to the body's competing needs for thermoregulation and maintaining adequate blood pressure for an upright posture [41,57]. Thermoregulation requires increasing blood flow to the periphery through vasodilation in order to facilitate sweating. This increase in peripheral vasodilation can lead to peripheral pooling of blood, causing postural hypotension. Acclimatization eventually results in an increased circulating blood volume capable of accommodating both sweating and activity in the heat. In each scenario, the severity of illness is proportional to the rise in body temperature and the degree of dehydration.

Differential diagnosis — Particularly in older athletes and those with preexisting cardiac disease, all forms of heat-related syncope must be distinguished from general causes unrelated to exercise, including cardiac arrhythmia. The differential diagnosis and management of syncope is reviewed separately.

Heat exhaustion — Heat exhaustion is characterized by the inability to maintain adequate cardiac output due to strenuous physical exercise and environmental heat stress [49,58]. Acute dehydration may be present, but is not required for the diagnosis. The treatment of heat exhaustion is discussed separately. 

The clinical criteria for heat exhaustion generally include the following:

●Athlete has obvious difficulty continuing with exercise


●Core body temperature is usually 101 to 104ºF (38.3 to 40.0ºC) at the time of collapse


●No significant dysfunction of the central nervous system (eg, seizure, altered consciousness, persistent delirium) is present


If any central nervous system dysfunction develops (eg, mild confusion), it is mild and resolves quickly with rest and cooling.

Patients with heat exhaustion may also manifest:

●Tachycardia and hypotension

●Extreme weakness

●Dehydration and electrolyte losses

●Ataxia and coordination problems, syncope, light-headedness

●Profuse sweating, pallor, "prickly heat" sensations


●Abdominal cramps, nausea, vomiting, diarrhea

●Persistent muscle cramps

It is important to note that during exercise free water losses exceed electrolyte losses, leading to elevated serum sodium concentrations, unless these losses are replaced. However, sodium concentrations in sweat vary widely among athletes and there may be a subset with high concentrations (so-called "salty sweaters"). Some researchers speculate that the carrier trait for cystic fibrosis may lead to higher sodium concentrations in sweat, but this has not been clearly established.

Heat injury — Heat injury is defined as an exertional heat illness with evidence of both hyperthermia and end organ damage, but without any significant neurologic manifestations . The absence of neurologic findings distinguishes the diagnosis from exertional heat stroke. The treatment of heat injury is discussed separately. (

Organs commonly damaged with heat injury include the muscles, kidneys, and liver; clinical and laboratory manifestations of metabolic acidosis, rhabdomyolysis, acute kidney injury, and liver failure are often seen.

The diagnosis of heat injury is primarily based upon a history of collapse during strenuous activity, a core temperature above 104 to 105°F (40 to 40.5°C), and the absence of neurologic findings. Any alteration in mental function suggests the diagnosis of exertional heat stroke.

As noted earlier, exertional heat injury is not officially recognized as a heat illness by the World Health Organization. This term was created by United States military physicians to classify soldiers manifesting signs of severe heat-related injury (ie, more severe than heat exhaustion) but without significant CNS dysfunction, thus precluding use of the term heat stroke.

Exertional heat stroke — Heat stroke is a multisystem illness characterized by central nervous system (CNS) dysfunction (encephalopathy) and additional organ and tissue damage (eg, acute kidney injury, liver injury, rhabdomyolysis) in association with high body temperatures. Nonexertional heat stroke is reviewed in detail separately; exertional heat stroke in healthy adults and older adolescents is described here.

The two main criteria for diagnosing exertional heat stroke (EHS) are a core temperature above 104°F (40°C), measured immediately following collapse during strenuous activity, and CNS dysfunction. CNS dysfunction can manifest as a wide range of possible symptoms and signs, including: disorientation, headache, irrational behavior, irritability, emotional instability, confusion, altered consciousness, coma, or seizure.

Other clinical findings vary. Most patients are tachycardic and hypotensive. Symptoms and signs that may be present include hyperventilation, dizziness, nausea, vomiting, diarrhea, weakness, profuse sweating, dehydration, dry mouth, thirst, muscle cramps, loss of muscle function, and ataxia. Some texts describe the absence of sweating with heat stroke but this is incorrect.

The morbidity and mortality due to EHS are a direct result of ischemia and oxidative and nitrosative stress; the prognosis is worse when cooling is delayed and the core temperature is allowed to remain above the critical threshold of 40.5 to 41.0°C (105 to 106°F) for any period of time. The treatment of EHS is discussed separately.

The majority of deaths from EHS among athletes occur primarily in two settings: high school American football practices and strength and conditioning workouts. 


●The management of exertional heat stroke and other forms of exertional heat illness is discussed separately.

●Exertional heat illness (EHI) is an ever present danger when athletes or workers perform intense exercise in the heat. A table summarizing important functional, acquired, and congenital risk factors for EHI is provided.. Important risk factors include high ambient temperature and humidity, lack of acclimatization, dehydration, and poor physical fitness. A number of drugs and supplements, including alcohol and stimulants, increase the risk of EHI and are listed in the text. 

●High heat and humidity impair the body's capacity for dissipating heat, which is accomplished primarily through evaporation but also involves convection, conduction, and radiation. 

●Acclimatization is the body's ability to improve its response and tolerance of heat stress over time, and it is the most important factor determining how well an athlete can withstand extreme heat and humidity. General principles for heat acclimatization are listed in the accompanying table and described in the text.

●The wet bulb globe temperature (WBGT) is an important index for determining the environmental risk for heat illness and the need to modify activity. The specific WBGT that would warrant modifications and the types of modifications needed vary by region and individual. 

●The syncopal event that occurs in the exercising athlete is more appropriately termed "exercise associated collapse" (EAC). EAC occurs when an athlete is unable to stand or walk and usually occurs immediately after completing an endurance race or workout. 

●Heat injury is defined as an EHI with evidence of both hyperthermia (core temperature above 40 to 40.5°C) and end organ damage, but without any significant neurologic manifestations. Clinical and laboratory signs of metabolic acidosis, rhabdomyolysis, acute kidney injury, and/or liver failure are often seen. The absence of neurologic findings distinguishes the diagnosis from exertional heat stroke. 

●Exertional heat stroke (EHS) is a multisystem, life-threatening illness characterized by central nervous system (CNS) dysfunction (encephalopathy) and additional organ and tissue damage (eg, acute kidney injury, liver injury, rhabdomyolysis) in association with high body temperatures. The two main diagnostic criteria are a core (eg, rectal) temperature above 40°C and CNS dysfunction. CNS dysfunction can manifest as a wide range of possible symptoms and signs, including: disorientation, headache, irritability, emotional instability, confusion, altered consciousness, coma, or seizure. 

●The differential diagnosis for an athlete or worker who is presumed to have collapsed from an EHI includes exertional hyponatremia, malignant hyperthermia, and cardiac arrest. 


Drug Overdoses: Current Trends

Drug overdose remains a significant concern worldwide, with nearly half a million deaths annually. In the United States, drug overdoses are the leading cause of death for adults younger than 55 years. Drug-related deaths now outnumber those attributed to motor vehicle accidents and homicides. According to information from the Centers for Disease Control and Prevention (CDC), the drugs most commonly involved in overdose deaths include opioids (eg, fentanyl, heroin, oxycodone), cocaine, methamphetamines, and benzodiazepines. There are other drugs that can cause death including MDMA and various synthetic drugs.

Naloxone has been lifesaving in many scenarios, so the CDC recently issued recommendations regarding its use in patients taking opioids. The CDC recommends that clinicians strongly consider prescribing or coprescribing naloxone and providing education about its use in these types of patients taking opioids:

  • Those who are receiving opioids at a dosage of 50 morphine milligram equivalents per day or greater
  • Those who have respiratory conditions such as chronic obstructive pulmonary disease or obstructive sleep apnea (regardless of opioid dose)
  • Those who have been prescribed benzodiazepines (regardless of opioid dose)
  • Those who have a nonopioid substance use disorder, report excessive alcohol use, or have a mental health disorder (regardless of opioid dose)

The CDC also recommends naloxone in patients who are at high risk for experiencing or responding to an opioid overdose, including the following:

  • Those known to use heroin or illicit synthetic opioids or misuse prescription opioids
  • Those using other illicit drugs such as stimulants, including methamphetamine and cocaine
  • Those receiving treatment for opioid use disorder, including medication-assisted treatment with methadone, buprenorphine, or naltrexone
  • Those with a history of opioid misuse who were recently released from incarceration or other controlled settings where tolerance to opioids has been lost

Most of the deaths from synthetic opioids are from fentanyl. Most of the increases in fentanyl deaths in recent years do not involve prescription fentanyl but are related to illicitly made fentanyl mixed with or sold as heroin—with or without the users' knowledge—and increasingly sold as counterfeit pills.

In the event of an overdose, pertinent history may be obtained from bystanders, family, friends, or emergency medical services (EMS) providers. Pill bottles, drug paraphernalia, or eyewitness accounts may assist in the diagnosis of opioid toxicity. Occasionally, a trial of naloxone administered by an EMS provider is helpful to establish the diagnosis in the prehospital setting.

Patients with opioid toxicity characteristically have a depressed level of consciousness. Opioid toxicity should be suspected when the clinical triad of central nervous system (CNS) depression, respiratory depression, and pupillary miosis are present. Clinicians must be aware that opioid exposure does not always result in miosis (pupillary constriction), and that respiratory depression is the most specific sign. Drowsiness, conjunctival injection, and euphoria are frequently seen.

Drug screens are widely available but rarely alter clinical management in patients with uncomplicated overdoses. Drug screens are most sensitive when performed on urine. Positive results are observed up to 36-48 hours postexposure, but wide variations are possible depending on test sensitivity, dose, route of opioid administration, and the patient's metabolism. In patients with moderate to severe toxicity, performing these baseline studies is appropriate:

  • Complete blood cell (CBC) count
  • Comprehensive metabolic panel
  • Creatine kinase (CK) level
  • Arterial blood gas (ABG) determinations

According to American Heart Association guidelines, clear evidence suggests that cocaine can precipitate acute coronary syndrome, and that trying agents that show efficacy in the management of acute coronary syndrome may be reasonable in patients with severe cardiovascular toxicity. Agents that may be used as needed to control hypertension, tachycardia, and agitation include:

  • Alpha-blockers (eg, phentolamine)
  • Benzodiazepines (eg, lorazepam, diazepam)
  • Calcium channel blockers (verapamil)
  • Morphine
  • Sublingual nitroglycerin

The American Heart Association does not recommend any one of these agents over another in the treatment of cardiovascular toxicity due to cocaine; however, benzodiazepines are often used as first-line treatment.

Cardiopulmonary complaints are the most common presenting manifestations of cocaine abuse and include chest pain (frequently observed in long-term use or overdose), MI, arrhythmia, and cardiomyopathy. In individuals with cocaine-associated MI, median times to the onset of chest pain vary with the route or form of cocaine use: 30 minutes for intravenous use, 90 minutes for crack, and 135 minutes for intranasal use.

Temperature dysregulation is also a problem with cocaine intoxication. Hyperthermia is a marker for severe toxicity, and it is associated with numerous complications, including renal failure, disseminated intravascular coagulation, acidosis, hepatic injury, and rhabdomyolysis. Dopamine plays a role in the regulation of core body temperature, so increased dopaminergic neurotransmission may contribute to psychostimulant-induced hyperthermia in cocaine users, including those with excited delirium.

No laboratory studies are indicated if the patient has a clear history of cocaine use and mild symptoms.

If a history of cocaine use is absent or if the patient has moderate to severe toxicity, appropriate laboratory tests may include:

  • CBC count
  • Electrolytes, blood urea nitrogen, creatinine, and glucose levels (basic metabolic panel)
  • Glucose level
  • Pregnancy test
  • Calcium level
  • ABG analysis
  • CK level
  • Troponin level (cocaine use does not affect the specificity of troponin assays)
  • Urinalysis
  • Toxicology screens

Acute and long-term methamphetamine use may lead to abnormal findings on examination of the following organ systems:

  • Cardiovascular
  • CNS
  • Gastrointestinal
  • Renal
  • Skin
  • Dental

There are specific cardiovascular findings associated with acute and long-term methamphetamine use:

  • Tachycardia and hypertension is frequently observed
  • Atrial and ventricular arrhythmias may occur
  • Chest pain from cardiac ischemia and infarction following methamphetamine use has been reported, and patients are at risk because of accelerated atherosclerosis from chronic use; acute aortic dissection or aneurysm has been associated with methamphetamine abuse
  • Hypotension may be observed with methamphetamine overdose with profound depletion of catecholamines
  • Acute and chronic cardiomyopathy results directly from methamphetamine cardiac toxicity and indirectly from chronic hypertension and ischemia; intravenous use may result in endocarditis; patients may have dyspnea, edema, and other signs of acute congestive heart failure exacerbation

The euphoric effects produced by methamphetamine, cocaine, and various designer amphetamines are similar and may be difficult to clinically differentiate. A distinguishing clinical feature is the longer pharmacokinetic and pharmacodynamic half-life of methamphetamine, which may be as much as 10 times longer than that of cocaine.

Methamphetamine can cause significant CNS and psychiatric activation, so patients who present to emergency departments for acute intoxication often require physical restraint and pharmacologic intervention. Hyperactive or agitated patients can be treated with droperidol or haloperidol, which are butyrophenones that antagonize CNS dopamine receptors and mitigate the excess dopamine produced from methamphetamine toxicity. These medications should be administered intravenously, with doses adjusted based on the symptoms. Droperidol has been subject to a black box warning by the US Food and Drug Administration based on concerns of QT prolongation and the potential for torsades de pointes. As a result, some institutions restrict its use. However, it is important to note that the black box warning specifies dementia-related psychosis and is not supported by the literature for doses below 2.5 mg.

If sedation fails to reduce blood pressure, antihypertensive agents such as beta-blockers and vasodilators are effective in reversing methamphetamine-induced hypertension and tachycardia. With regard to choice of beta-blockers, labetalol is preferred because of its combined anti–alpha-adrenergic and anti–beta-adrenergic effects. Labetalol has been shown to safely lower mean arterial pressure in patients with positive cocaine test results. Carvedilol, like labetalol, is a nonselective beta-blocker with alpha-blocking activity and may also be effective for this indication. Esmolol is advantageous because of its short half-life but must be administered via intravenous drip. Metoprolol has excellent CNS penetration characteristics and may also ameliorate agitation.

Oral benzodiazepine overdoses, without co-ingestion of another drug, rarely result in significant morbidity (eg, aspiration pneumonia, rhabdomyolysis) or mortality; however, in mixed-drug overdoses, they can potentiate the effect of alcohol or other sedative-hypnotic agents. Overdose of ultrashort-acting benzodiazepines (eg, triazolam) is also more likely to result in apnea and death than overdose with longer-acting benzodiazepines. Of the individual benzodiazepines, alprazolam is relatively more toxic than others in overdose.

Immunoassay screening techniques are most commonly performed when benzodiazepine overdose is suspected. These tests typically detect benzodiazepines that are metabolized to desmethyldiazepam or oxazepam; thus, a negative screening result does not rule out the presence of a benzodiazepine.

As with any overdose, the first step is an assessment of the patient's airway, breathing, and circulation, and any issues should be addressed rapidly. In any patient with an altered mental status, blood glucose level should be checked immediately. The cornerstone of treatment in benzodiazepine overdoses is good supportive care and monitoring. Single-dose activated charcoal is not routinely recommended because the risks far outweigh the benefit. Altered mental status greatly increases the risk of aspiration following an oral activated charcoal dose.

Flumazenil is a competitive benzodiazepine receptor antagonist and the only available specific antidote for benzodiazepines. Its use in acute benzodiazepine overdose is controversial, however, and its risks usually outweigh any benefit. In long-term benzodiazepine users, flumazenil may precipitate withdrawal and seizures; in patients taking benzodiazepines for a medical condition, flumenazil may result in exacerbation of the condition. Flumazenil should not be used in patients with long-term benzodiazepine use or in any patient at an increased risk of having a seizure, including those with a seizure history, head injury, co-ingestion of a benzodiazepine and tricyclic antidepressant or other proconvulsant, or even a possible ingestion of a proconvulsant.

In general, when it is the sole agent used, the clinical presentation of heroin poisoning and its diagnosis hold little challenge for experienced healthcare practitioners. The diagnosis of heroin poisoning should be suspected in all comatose patients, especially in the presence of respiratory depression and miosis.

Respiratory depression, due to heroin's effect on the brain's respiratory centers, is a hallmark sign of overdose. However, the presence of tachypnea should prompt the search for complications of heroin use, such as pneumonia, acute lung injury, and pneumothorax, or an alternative diagnosis, such as shock, acidosis, or CNS injury. Tachypnea may also be seen in overdoses of pentazocine or meperidine.

Symptoms generally develop within 10 minutes of intravenous heroin injection. Patients who survive heroin poisoning commonly admit to using more than their usual dose, using heroin again after a prolonged period of abstinence, or using a more concentrated street sample. Coma, respiratory depression, and miosis are the hallmarks of opioid overdose.

Mild hypotension and mild bradycardia are commonly observed with heroin use. These are attributable to peripheral vasodilation, reduced peripheral resistance and histamine release, and inhibition of baroreceptor reflexes. In the setting of heroin overdose, hypotension remains mild. The presence of severe hypotension should prompt a search for other causes of hypotension, such as hemorrhage, hypovolemia, sepsis, pulmonary emboli, and other causes of shock.

Gastric lavage in the setting of oral heroin overdose is generally not recommended because it has no documented value. Furthermore, gastric lavage is contraindicated in "body packers" and "body stuffers," who have ingested packages of drugs, because the procedure may rupture a package. Activated charcoal is becoming increasingly controversial because of the risk of aspiration and charcoal pneumonitis. It may be indicated for orally ingested narcotics with large enterohepatic circulation (eg, propoxyphene, diphenoxylate) but is of no value in pure heroin overdose.

Toad Venom Psychedelics for Depression and Anxiety

A very interesting study has recently been done on the effects of a psychedelic substance in a small mitigated-psychedelic dose in the treatment of resistant depression and anxiety. The following is a synopsis of the key points from a recent Medscape article.  The relevance of this study to toxicology is that psychelics can have severe side-effects, some even long-lasting or permanent, even in customary doses, as noted below. Practitioners who treat their patients with these substances should be aware of the medicolegal liability and health risks.

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Fluoroquinolones are dangerous and can lead to a medical malpractice action

FDA Warns of Aortic Aneurysm Risk With Fluoroquinolones.

The US Food and Drug Administration (FDA) issued a warning today that fluoroquinolone use can increase the risk of aortic aneurysm.

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Cannabis-Linked ER Visits Increasing

The number of cannabis-associated emergency department (ED) visits has risen sharply since marijuana was legalized in Colorado. New data show that although inhalable cannabis use accounts for most of these visits, edible cannabis is tied to a disproportionate number of visits, and patients present with different symptoms.

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There are approximately 1.4 million fires each year in the United States.[1] In 2016, 81% of civilian fire-related deaths occurred in residences/homes (Table 1).[1] The National Fire Incident Reporting System (NFIRS) found that smoke inhalation was a factor in 85% of all residential fire fatalities between 2013 and 2015. 

Thus, personal injury cases that stem from residential or occupational fires must take into consideration the science behind smoke inhalation. The following article is an overview of the toxic gas produced when combustible materials ignite, how to treat it, and how Emergency Physicians can err in their evaluation and treatment of smoke inhalation victims. 

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Intoxication and ER deaths from Synthetic Cannabinoids

Synthetic cannabinoids are part of a group of drugs called new psychoactive substances (NPS). NPS are unregulated mind-altering substances that have become newly available on the market and are intended to produce the same effects as illegal drugs. Some of these substances may have been around for years but have reentered the market in altered chemical forms, or due to renewed popularity.

Individuals reported acquiring the contaminated synthetic cannabinoid products (i.e., K2, spice, synthetic marijuana, and legal weed) from convenience stores, dealers, and friends, in counties across the state.

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Update on EMTALA Law

Randy Strickland walked into the ER at North Metro Medical Center burning with fever and trembling. He told the nurse at the triage desk that he was nauseated and felt like he needed to throw up. The emergency room was nearly empty. Randy waited in the waiting room, yet repeated visits by his wife and son to the triage desk didn't bring Randy any closer to getting care. Over the next 2 hours, he lost his ability to speak or respond to questions. His breathing became labored. Finally, on a trip to the bathroom, his legs buckled as he held onto his wife and son for support. No one came out to help them so they dialed 911 but were told that the ambulance will not respond to a hospital.The 911 dispatcher told them to get Randy out to his car in the parking lot, where paramedics could pick him up and bring him in the ambulance door of the hospital. 

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