OVERVIEW: What every practitioner needs to know

Are you sure your patient has overdosed? What are the typical findings for this condition?

Stimulants

Stimulants are a class of compounds that accelerate neuronal and/or physical activity. These include a number of both prescription and recreational drugs such as cocaine, amphetamines, anticholinergics, and sympathomimetics. In general, they induce sympathetic neuronal discharge.

What is the mechanism of action of stimulants?

Stimulants act via a number of different mechanisms. In general, though, they increase overall sympathetic outflow – either directly or via inhibition of parasympathetic function. Cocaine exerts its effects by blocking the re-uptake of norepinephrine, serotonin, and dopamine from the synaptic cleft, increasing the time and amount of these excitatory neurotransmitters in the synaptic cleft. Methylenedioxypyrovalerone (MDPV), also known as “bath salts,” function in the same manner, blocking norepinephrine, dopamine, and serotonin re-uptake.

Likewise, amphetamines work in much the similar manner. Amphetamines are believed to block the re-uptake of norepinephrine. The mechanism by which amphetamines increase synaptic concentrations of dopamine and serotonin is not well understood. The outcome effect, though, is an increase in excitatory neurotransmitters in the synaptic cleft. Methamphetamines and MDMA (ecstasy) are amphetamine derivatives; the ratio of norepinephrine, dopamine, and serotonin increase varies with the type of amphetamine and accounts for the varying signs and symptoms of these drugs.

Typical findings:

Hallucinogen overdose

Hallucinogens are a class of compounds that alter perception and thought. They include a number of both synthetic and naturally-occurring drugs such as lysergic acid diethylamide (LSD), MDMA (ecstasy), psilocybin, phencyclidine (PCP), and ketamine. In general, they function by increasing central nervous system (CNS) serotonin levels. Overlap between stimulants and hallucinogens is common because many stimulants modulate CNS serotonin as well.

What is the mechanism of action of hallucinogens?

Hallucinogens act via a number of different mechanisms. In general, though, they increase overall CNS serotonin levels. Most hallucinogens directly stimulate serotonin (5-HT) receptors while others, like methamphetamines and MDMA, block re-uptake of serotonin from the synaptic cleft, increasing the time and amount of this excitatory neurotransmitter in the synaptic cleft. There are a number of 5-HT receptor subtypes and the specific receptor subtype, and location in the brain, accounts for the varying effects of these hallucinogens.

Typical findings:

Recognizing signs of a clinical toxidrome is the best way to identify potential overdoses. Co-ingestions can cloud the clinical picture and most intentional ingestions do, indeed, involve co-ingestions. Realistically, the practitioner must piece together the predominant signs. In mild hallucinogen abuse, users may only demonstrate alterations in normal perception. In moderate hallucinogen overdoses, the patient may manifest agitation, hypertension, and tachycardia. Severe overdoses involve hyperthermia, seizures, hemodynamic instability, and death. The signs of hallucinogen overdose fall, most commonly, into two broad categories: sympathomimetic or anticholinergic. Again, co-ingestants can cloud the picture and the practitioner must put together the predominant signs.

Sympathomimetic signs include tachycardia, mydriasis, hypertension, hyperthermia, altered mental status, and diaphoresis. They are adrenergic in nature and are the same “fight or flight” signs demonstrated in stressful situations. Amphetamines and amphetamine derivatives typically present in this manner. Additionally, ketamine and PCP both demonstrate sympathomimetic signs in overdose situations. They also commonly present with nystagmus.

Anticholinergic signs are very similar, with the exception of diaphoresis. Anticholinergics, much like sympathomimetics, cause tachycardia, mydriasis, hypertension, hyperthermia, and altered mental status. The biggest difference, and often the practitioner’s best clue for differentiating the two toxidromes, is the presence or absence of diaphoresis. Sweat gland function is elicited by stimulation of muscarinic receptors. Anticholinergic drugs block muscarinic receptors, leading to the inability to sweat. Also, anticholinergic drugs decrease bowel function by blocking vagal nerve stimulation. Realistically, decreased bowel sounds are an unreliable sign and vary depending on the timing and amount of anticholinergic drug ingested. Bowel sounds may or may not be present and their presence should not dissuade the practitioner from suspecting an anticholinergic-like hallucinogen.

Hyperthermia can be present in many hallucinogen overdoses and should be taken very seriously. It should be addressed emergently and has a poor prognosis. A review and literature search by Gowing et al. (2002) of MDMA-induced hyperthermia overdose cases demonstrated that, for temperatures >41.5 C, 17 of 25 (68%) died.

Sedative/hypnotic overdose

Sedatives are a class of medications that induce relaxation and treat agitation. The term hypnotics refers to medications that induce drowsiness and promote sleep. They are often discussed together because they demonstrate many similar signs and symptoms and most function via similar mechanisms.

What is the mechanism of action of sedatives/hypnotics?

Sedatives/hypnotics predominantly act via central type A gamma-aminobutyric acid (GABA-A) receptors. GABA-A receptors are post-synaptic pentameric receptors. Binding of benzodiazepines/barbiturates induces binding of gamma-aminobutyric acid (GABA) to its binding-site on the surface of the GABA-A receptor. The GABA-A receptor is a chloride channel, allowing chloride influx into the post-synaptic neuron and hyperpolarization of the cell membrane. Membrane hyperpolarization inhibits excitation. Binding of sedative/hypnotic medicines to the receptor can alter the function of the chloride channel. Barbiturates are believed to increase the time the chloride channel is open, while benzodiazepines are believe to increase the frequency of the channel opening.

Other sedatives/hypnotics include zolpidem (Ambien) and gamma-hydroxybutyric acid (GHB). Zolpidem is a non-benzodiazepine hypnotic, acting at the same receptor site as benzodiazepines and initiating sleep. GHB is an analog of GABA and its mechanism is not entirely understood. It is believed to be a GABA precursor and also acts via GHB receptors, causing extracellular chloride influx into the intracellular space. This influx causes inhibitory effects similar to those of other sedatives/hypnotics.

Typical findings:

Recognizing symptoms of a clinical toxidrome is the best way to identify potential overdoses. Co-ingestions will cloud the clinical picture and most intentional ingestions do, indeed, involve co-ingestions. Realistically, the practitioner must piece together the predominant signs. In moderate sedative/hypnotic overdoses, the patient may demonstrate slurred speech, somnolence, confusion, and ataxia. Severe overdoses involve CNS, cardiovascular, and respiratory depression. There is even a case of reported coma and absent brainstem reflexes following severe zolpidem overdose.

Respiratory depression manifests as hypoventilation and hypoxia, resulting in acidosis and, if left untreated, cardiopulmonary arrest. Barbiturates also demonstrate direct effects on the myocardium and vasculature, inducing hypotension. Benzodiazepines produce milder respiratory effects compared to barbiturates, but still should not be overlooked or forgotten. Some textbooks/literature may argue that benzodiazepine overdose will not cause respiratory compromise but, frankly, this is untrue. Respiratory depression simply occurs to a lesser extent with benzodiazepines when compared to barbiturates.

Miosis has been reported with barbiturates and can resemble an opioid overdose. Additionally, sedative/hypnotic overdoses may demonstrate hypothermia, resulting directly from poor cardiac output and hypoperfusion or secondary to altered mental status and poor decision-making capacity.

Ethanol exposure

Ethanol, or ethyl alcohol, is a widely used inebriant found not only in alcoholic beverages, but also in a variety of household items like perfume, colognes, and mouthwash. Intentional ingestion is a common clinical occurrence, especially in preteens and adolescents, presenting as both acute intoxication, and more rarely, dependency and addiction.

The diagnosis of alcohol ingestion is based on clinical history, signs of CNS depression, serum ethanol levels, and careful exclusion of other potential causes for a patient’s motor and cognitive impairment.

Accidental ingestion, especially in young children, can cause potentially fatal hypoglycemia even at low serum concentrations and must be evaluated and either excluded or treated following exposure. While non-fatal ethanol levels in adults are typically above 500mg/dL, young children can develop CNS depression, hypoglycemia, and hypothermia at blood levels of 50-100mg/dL, and have been reported with levels as low as 20mg/dL

Treatment of acute alcohol ingestion is focused on supportive care, as no antidote exists to reverse the clinical effects. Typical interventions include airway protection and monitoring, fluid, glucose and electrolyte replacement, control of nausea/vomiting, and rewarming. Protecting the patient from accidental self-harm while intoxicated is mandatory and disposition may involve referral to an appropriate treatment program for those with addiction.

In any patient demonstrating signs and symptoms not entirely consistent with isolated ethanol exposure or in those with an unexpectedly low serum ethanol level for their level of impairment, the differential diagnosis should be broadened. In a patient with an anion gap acidosis or an osmolar gap (which should include an ethanol level in it’s calculation), toxic alcohols should be considered.

Signs of ethanol exposure:

The degree of ethanol intoxication occurs along a spectrum and individuals may manifest certain features more prominently than others (i.e. being extremely disinhibited or being a “mean drunk”). Generally, the degree of intoxication can be categorized according to the following clinical signs:

Mild Intoxication: euphoria, relaxation, impaired ability to concentrate, disinhibition, impaired judgment, and a decrease in fine motor control.

Moderate Intoxication: slurred speech, staggering gait, emotional lability, impaired reaction time.

Severe Intoxication: significant CNS depression or unresponsiveness (“blacking out”), loss of bladder control, vomiting, respiratory depression, and failure to adequately protect their airway.

In those who have not developed a tolerance to it, the symptoms of ethanol intoxication are largely proportional to the amount consumed. However, in regular users, the clinical signs of intoxication may not be apparent even at high serum ethanol concentrations. In these individuals, failure to maintain an elevated blood alcohol level may produce signs of alcohol withdrawal including agitation, diaphoresis, tachycardia, hypertension, vomiting, and possibly seizures.

Inhalant exposure

Inhalant abuse is a potentially lethal form of recreational drug abuse involving the purposeful inhalation of everyday chemicals for the purpose of achieving feelings of euphoria and psychoactive effects.

Many methods of exposure exist including:

“Huffing”: Breathing deeply through as absorbent material that has been soaked in a volatile liquid.

“Sniffing”: Direct inhalation of fumes from a bottle or container. This is how “poppers” and “snappers” (glass ampules that are broken open) are used.

“Dusting”: Inhalation of keyboard or electronic dust-removing propellant that is sprayed directly into the oropharynx.

“Bagging”: Placing a volatile substance into a plastic bag and then inhaling the fumes.

There are almost an innumerable number of chemicals that can be used as inhalants, but a common property of all inhalants is a high degree of lipophilicity that promotes rapid CNS penetration and almost immediate onset. The duration of action is similarly brief and is typically limited to the time of direct exposure.

Certain inhalants of abuse can cause specific clinically important conditions:

Alkyl nitrates can result in methemoglovinemia.

Methylene chloride can cause carboxyhemoglobinemia (carbon monoxide poisoning).

Carburetor cleaners/degreasers can induce methanol toxicity

While long-term abuse can cause multiple chronic illnesses, acute treatment of these patients is focused largely on the management of hypoxia, aspiration, airway injury, cardiac arrest, and trauma.

“Sudden Sniffing Death Syndrome” results from hydrocarbon-induced cardiac myocyte sensitization to adrenergic surges and can precipitate ventricular fibrillation. Case reports suggest the use of beta-blockers such as Esmolol and Propranolol may inhibit the adrenergic trigger

Freezing temperatures from spraying inhalants directly into the oropharyn can produce sufficient inflammation and edema to create airway obstruction.

See Figure 1 for Inhalants Table.

Signs of inhalant exposure:

Following use, the immediate signs of inhalant abuse include stimulation, disinhibition, impulsivity, euphoria, motor excitation, and hallucinations. Prolonged use results in slurred speech, emotional lability, ataxia, disorientation, sedation, seizures, respiratory depression, headache, and nausea with vomiting. CNS depression to the point of coma is uncommon because the user becomes too anesthetized to continue actively manipulating the container.

Unique Exam Findings:

“Glue Sniffer’s Rash”:A contact dermatitis around the nose and mouth caused by prolonged chemical irritation of the skin. Some patients will present with paint on their face, skin, and clothes from spray paint propellant abuse.

Perioral Pyoderma:A collection of pustular sores around the user’s mouth as the result of skin breakdown due to chemical irritation that is secondarily colonized by bacteria.

Odor: A significant amount of ingested inhalants are excreted unchanged via the lungs, producing a strong and persistent chemical odor on the user’s breath. Similar smells may come from their clothes and personal belongings.

Thermal Injuries:Burns and edema from freezing propellant being sprayed directly into the oropharynx should be detected early.

Opiate exposure

Opiate overdose is a common clinical problem as a result of both accidental and intentional use. Narcotic ingestion typically produces the classic signs of the “opiate toxidrome” including depressed mental status, bradypnea, miotic or “pinpoint” pupils, and hypoactive bowel sounds. It should be noted, however, that these symptoms represent the textbook opiate toxicity, and certain features such as miosis may not be seen with the use of specific opiates such as merperidine and propoxyphene, or with simultaneous use of other drugs such as sympathomimetics or organophosphates.

Mechanism of action:

Binding of an opiate to the three main opiate neurotransmitter receptors (mu, kappa, and delta) results in the inhibition of pain preception and causes sedation, euphoria, and respiratory depression via their effects on g-proteins and cyclic AMP.

Domaminergic activity mediated by mu receptor binding plays a role in addiction and dependence by affecting the brain’s reward and reinforcement pathways.

The duration of opiate poisoning is highly variable and depends on the route of ingestion, patient tolerance, and drug formulation. While single doses of Fentanyl may only last a few hours and require a single Naloxone bolus for full reversal, longer-acting opiates like Methadone may require prolonged monitoring and treatment on the order of days.

Typical symptoms:

Typical symptoms of an opiate ingestion include analgesia, euphoria, sedation, and GI complaints such as nausea, vomiting, constipation, and anorexia.

Numerous methods for exposure exist including intradermal, transdermal, intramuscular or subcutaneous injection, transdermal update, swallowing, smoking, per rectum, and intranasally.

There are innumerable colloquialisms used to refer to various narcotics. Examples include “Hillbilly heroin, Monkey, TNT, Dillies, O-Bombs, Jackpot, etc” making it difficult for a practitioner to determine the specific ingestions, especially in the patient with altered mental status who may not know themselves which drug they took. Assistance should be sought from a poison control specialist regarding diagnosis, management, and disposition.

Respiratory support is the mainstay of narcotic overdose treatment and control of the airway alone is typically sufficient to manage an opiate overdose until the drug is fully metabolized. A single dose of Naloxone may be sufficient to reverse the clinical effects of some short-acting narcotics such as heroin or morphine, but longer-acting preparations require maintenance drips and admission for hemodynamic and respiratory monitoring.

Confirming the diagnosis:

A respiratory rate of less than 12 breaths per minutes has been shown to be a highly sensitive clinical sign for detecting narcotic overdose and is thus predictive of a favorable response to Naloxone.

All poisonings/overdoses should prompt a call to the regional poison control center (1-800-222-1222) for diagnostic, management, and surveillance purposes.

Frequently, the patient is only aware of the street name of the substance they ingested, and both a poison control specialist and an internet database search may be helpful in determining which particular drug was ingested.

Carefully consider the possibility of coingestions that have significant morbidity and mortality if missed like acetaminophen, toxic alcohols, tricyclic antidepressants, salicylates, and antihypertensives. Prompt detection and treatment of these conditions can be life-saving if instituted early.

What other diseases/conditions share some of these symptoms?

Stimulants

Many of the same signs of tachycardia, altered mental status, and hypertension seen in stimulant overdoses can be seen in other settings. Thyroid storm demonstrates tachycardia, hyperthermia, altered mental status, and hypertension. Furthermore, it presents acutely, much like a potential stimulant overdose and has been shown to be pharmacologically induced by other drugs. Serotonin syndrome and neuroleptic malignant syndrome may present similarly with altered mental status, tachycardia, and hyperthermia. These syndromes may present almost identically to stimulant overdose. Their etiologies involve elevated intra-synaptic concentrations of serotonin and dopamine, respectively, much like that seen during stimulant overdose.

Other potential mimics of stimulant overdose include heat exhaustion and heat stroke. The history, if the practitioner is able to obtain it, is extremely important and may differentiate between these other potential causes of the patient’s signs and symptoms.

Stimulant overdoses demonstrate sympathomimetic-like or anticholinergic-like signs. These include tachycardia, hypertension, hyperthermia, and altered mental status. Miosis, mydriasis, or normal pupils may be present depending upon the type of stimulant and the presence of co-ingestants. Co-ingestions will complicate the toxidrome picture. In severe stimulant overdose settings, patients may demonstrate seizures, coma, hemodynamic instability, and death.

Hallucinogens

Many of the same signs of tachycardia, altered mental status, and hypertension seen in hallucinogen exposures can be seen in other settings. Thyroid storm demonstrates tachycardia, hypertension, altered mental status, and hyperthermia. Furthermore, it presents acutely, much like a potential hallucinogen overdose and has been shown to be pharmacologically induced by other drugs. Serotonin syndrome and neuroleptic malignant syndrome may present similarly with altered mental status, tachycardia, and hyperthermia. These syndromes may present almost identically to hallucinogen overdose, particularly since hallucinogens produce known serotinergic effects. Their etiologies involve elevated intra-synaptic concentrations of serotonin and dopamine, respectively, much like that seen during hallucinogen overdose.

Other potential mimics of hallucinogen overdose include heat exhaustion and heat stroke. The history, if the practitioner is able to obtain it, is extremely important and may differentiate between these other potential causes of the patient’s signs and symptoms.

Many hallucinogen overdoses demonstrate sympathomimetic-like or anticholinergic-like signs and may be indistinguishable from stimulant overdoses. Many of the hallucinogenic drugs are, in fact, amphetamine derivatives or anticholinergics. Signs include tachycardia, hypertension, hyperthermia, and altered mental status. The extent of these sympathomimetic-like symptoms and signs varies with the specific hallucinogen. For instance, LSD demonstrates milder autonomic dysfunction – in general – compared to other hallucinogens such as MDMA. Miosis, mydriasis, or normal pupils may be present depending upon the type of hallucinogen and the presence of co-ingestants. Co-ingestions can complicate the toxidrome picture. In severe hallucinogen overdose settings, patients may demonstrate seizures, coma, hemodynamic instability, and death.

Sedative/hypnotic overdose

Many of the same symptoms of drowsiness, altered mental status, and respiratory depression seen in sedative/hypnotic overdoses can be seen in opiate overdoses as well as ethanol intoxication and hypoglycemia. Opiate overdoses demonstrate respiratory depression and, often, altered mental status, frequently with pinpoint pupils in cases of pure opioid overdose. Co-ingestions will complicate the toxidrome picture. A study of pediatric comatose patients by Mitchell et al. (1976) showed that barbiturates can cause miosis as well. Ethanol intoxication presents similarly to the sedative/hypnotics with sedation and altered mental status. In higher doses, ethanol intoxication induces respiratory depression. Similar signs/symptoms occur with ethanol intoxication since ethanol acts at the same central GABA-A receptors as most sedatives/hypnotics.

Ethanol exposure

While considering the diagnosis of ethanol ingestion, it is important to consider other conditions that may mimic the signs and symptoms but have a less benign prognosis if not detected early and treated appropriately.

Exposures: benzodiazepines, barbiturates, toxic alcohols (including methyl alcohol, ethylene glycol, and isopropyl alcohol), sleep aids (“Z-Drugs”), and antihistamines, hypothermia.

Trauma: concussion, intracranial hemorrhage, diffuse axonal injury, internal bleeding leading to hemorrhagic shock.

Metabolic: hypoglycemia or diabetic ketoacidosis, seizures from abnormal sodium levels, dysrhythmias from abnormal potassium levels, thyrotoxicosis, uremia.

Infectious: meningitis, encephalitis, sepsis.

Isolated ethanol ingestions will typically self-resolve with supportive care and airway monitoring. The majority of small children with accidental exposure have a benign course with complete recovery.

The major factors affecting long-term prognosis include traumatic injury, coingestions, aspiration, hypoxic brain injury, and addiction.

Dependence and tolerance following chronic exposure can lead to difficulty with work, school, and social relationships, motor vehicle accidents, hepatic injury, pancreatitis, diabetes, and accelerated rates of cardiovascular and cerebrovascular disease.

Hypoglycemia in children, like CNS depression, will resolve as ethanol metabolism occurs, though ongoing monitoring until serum levels stabilize is critical to prevent seizures and CNS injury.

Assumption that a patient’s symptoms are due entirely to ethanol intoxication without a thorough search for other etiologies can produce delays in diagnosis of critical diseases and conditions which require early detection and treatment to achieve therapeutic success.

Inhalant exposure

While considering the diagnosis of inhalant exposure, it is important to consider other conditions that may mimic the signs and symptoms but have a less benign prognosis if not detected early and treated appropriately.

Exposures: benzodiazepines, barbiturates, toxic alcohols (including methyl alcohol, ethylene glycol, and isopropyl alcohol), sleep aids (“Z-Drugs”), and antihistamines, hypothermia.

Trauma: concussion, intracranial hemorrhage, diffuse axonal injury, internal bleeding leading to hemorrhagic shock.

Metabolic: hypoglycemia or diabetic ketoacidosis, seizures from abnormal sodium levels, dysrhythmias from abnormal potassium levels, thyrotoxicosis, uremia.

Infectious: meningitis, encephalitis, sepsis.

Other: Dysrhythmias

Opiate exposure

While considering the diagnosis of opiate ingestion, it is important to consider other conditions that may mimic its signs and symptoms but have a less benign prognosis if not detected and treated.

Depressed Mental Status: Cerebrovascular accident, alcohol use, hypoglycemia, diabetic ketoacidosis, sedative/hypnotic use, post-ictal phase, nonconvulsive status epilepticus, conversion disorder, post-traumatic coma, uremia, sepsis, shock.

Bradypnea: Respiratory failure from pulmonary diseases such as COPD, pneumonia and asthma, alcohol intoxication, sedative ingestion, sleep apnea, increased intracranial pressure, CNS injury and infection.

Miosis: Cholenergic or organophosphate ingestion, brainstem stroke, neurosyphilis.

Hypoactive Bowel Sounds: Ileus, mechanical obstruction, trauma, hypokalemia, decreased intestinal blood supply resulting in ischemia.

Clonidine: a centrally acting alpha agonist used to treat high blood pressure is worth special mention as large dosages can mimic opiate overdose and it has shown a mixed response to Naloxone therapy.

What caused this disease to develop at this time?

Stimulants

According to “Monitoring the Future,” a University of Michigan based study surveying 8th-12th graders on substance abuse, the prevalence of “cocaine” use in 2010 by 12th graders was 2.9% (MTF 2010). The prevalence of “ecstasy” was 4.5% and “amphetamines” was 7.4% in this same survey. Whether students correctly identified the difference between “ecstasy” and other amphetamines is unknown. It is important to note, though, that there is a significant percentage of 12th graders using stimulant drugs.

Stimulant overdoses can be either accidental or intentional and an accurate ingestion history is extremely important. Accidental overdoses can occur in patients who take these drugs regularly for such issues as attention-deficit hyperactivity disorder (ADHD) or narcolepsy. Two common ADHD medicines include methylphenidate (Ritalin or Concerta) and dextroamphetamine (Adderall). Drug-drug interactions may cause inadvertent overdoses as well.

Intentional non-prescription use of these medications are common too. They are common drugs of abuse and “party drugs” like cocaine, amphetamines, ecstasy, and “bath salts” (MDPV). To complicate the picture, stimulant use is often combined with sedative/hypnotic drugs to counter-balance the undesirable side-effects of the stimulant, such as tachycardia. While not always the case, stimulants are often mixed or “cut” with other stimulants such as caffeine or ephedrine to increase profit margin. Again, an accurate ingestion history is extremely important for the safety and disposition of your patient.

Hallucinogens

According to “Monitoring the Future,” a University of Michigan based study surveying 8th-12th graders on substance abuse, the prevalence of “hallucinogens” use in 2010 by 12th graders was 5.5% (MTF 2010). The prevalence of “ecstasy” was 4.5% and “salvia” was 5.5% in this same study.

Hallucinogen overdoses result from intentional ingestions and an accurate ingestion history is extremely important. These medications are not regularly used as outpatient medicines. Ketamine is used frequently in monitored procedural sedation settings. They are common drugs of abuse and party drugs referred to as “Special K” (ketamine), “Molly” (MDMA), and “wets” (marijuana joints dipped in liquid PCP), to name a few. Again, an accurate ingestion history is extremely important for the safety and disposition of your patient.

Sedative/hypnotic overdose

According to “Monitoring the Future,” a University of Michigan based study surveying 8th-12th grader on substance abuse, the prevalence of “tranquilizers” in 2010 by 12th graders was 5.6% (MTF 2010) and the prevalence of “sedatives/barbiturates” was 4.8%. Flunitrazepam (Rohypnol) prevalence in 2010 by 12th graders was 1.5% and GHB was 1.4% in this same study. Whether students correctly identified the difference between “tranquilizers” and “sedatives” is unknown. Nevertheless, it is interesting that 18.4% of 12th graders felt it was “fairly easy” or “very easy” to get “tranquilizers” and 38.6% felt it was “fairly easy” or “very easy” to get “sedatives.”

As reported by the Drug Abuse Warning Network (DAWN) and summarized in an article by Cai et al. (2010), the estimated number of emergency department (ED) visits for non-medical use (abuse) of benzodiazepines increased 89% from 2004 to 2008. The total number of ED visits in 2008 reported for benzodiazepines was 271,700 with alprazolam being the biggest contributor at 104,800 visits. The age, according to DAWN data, with the largest abuse of benzodiazepines was the 21-29 year old group.

Sedative/hypnotic overdoses can be either accidental or intentional and an accurate ingestion history is extremely important. Accidental overdoses can occur in patients who take these drugs regularly for such issues as seizure or anxiety disorders. Drug-drug interactions may cause inadvertent overdoses as well. Intentional overdoses of these medications are common too. They are commonly involved in suicide attempts and are also used for the “downer” effects when used in combination with stimulants. The sedative properties of these medications counter-balance the undesirable side-effects of stimulants and “take the edge off”. Additionally, flunitrazepam (also known as “roofies”) and GHB have been reportedly involved in instances of date rape. Again, an accurate ingestion history is extremely important for the safety and disposition of your patient.

Ethanol exposure

According to the University of Michigan’s Monitoring the Future study, approximately 90% of high school seniors and 80% of 10th graders report ethanol as being “fairly easy” or “very easy” to get as of 2010. This same study found that “use in the last 30 days” has been steadily declining amongst 12th graders from 70% in 1980 to just over 40% in 2010. Binge drinking (5+ drinks in a row) within the last 30 days was reported by approximately 25% of those seniors surveyed as of 2010.

According to the 2009 National Poison Control data, ethanol caused only 1 reported fatality in 2009 in a child less than 5, representing only 2.13% of poisoning-related fatalities in that age group. That same year, 27,087 exposures involving ethanol occurred in children less than 5. This represented only 2.02% of all exposures in that age group. This indicates that of all reported substance exposures in children less than 5, alcohol is quite uncommon and fatal outcomes even more rare. This data is limited, however, by the passive method of collection and is unlikely to reflect the true incidence of ethanol exposures.

Multiple factors, both intrinsic and extrinsic, determine the severity of symptoms and the rapidity of onset when a given amount of ethanol is consumed.

Intrinsic Factors:

• Body Composition: As ethanol is hydrophilic, it is poorly distributed in tissues with a higher fat content. Overweight individuals and women (who tend to have a higher percentage of body fat than men) are therefore more susceptible to the effects of alcohol and will develop higher serum ethanol levels compared to individuals with a smaller amount of body fat who consume an equal quantity of ethanol.

• Race and Ethnicity:Variants of the alcohol dehydrogenase enzyme appear to play a role in both the rate of alcohol metabolism and the risk of developing alcoholism. Various racial and ethnic groups express different subtypes with a significant effect on individual response to ethanol.

• Physical Tolerance:Up-regulation of hepatic alcohol dehydrogenase in those who are chronic ethanol users leads to more rapid metabolism and clearance of ethanol in these individuals.

• Functional Tolerance:The user’s brain adapts to chronic exposure and is able to maintain normal function at higher ethanol levels than an occasional user can.

• Rate of Metabolism:An adult occasional consumer will metabolize approximately 15-20mg/dL/hr and regular users can metabolize up to 30mg/dL/hr. In children, this rate is estimated to be between 18-29mg/dL/hr.

Extrinsic Factors:

• Food:Ethanol is readily absorbed from the stomach, and consumption of ethanol with food will delay uptake.

• Rate of Ingestion:Rapid consumption of ethanol at a rate greater than the body can metabolize it results in rapidly increasing blood-alcohol levels with a more sudden onset of symptoms.

• Coingestants:Consumption of other sedatives like benzodiazepines, barbiturates, sleep aids, antihistamines, and opiates may compound the degree of CNS impairment and depression.

Ethanol acts as a GABAergic agonist that, by acting on the GABA
_Areceptor, enables transmembrane flux of chloride ions resulting in hyperpolarization of the transmembrane electrical potential. This hyperpolarization inhibits cellular depolarization and acts to decrease neurotransmission. The primary outcome with sufficient blood-alcohol levels is CNS depression. Direct effects of ethanol are also directed at NMDA receptors. Tolerance develops with chronic use as excitatory NMDA receptors are upregulated and inhibitory GABA receptors are down-regulated.

Inhalant exposure

Inhalants pose a special danger to pediatric patients. They are readily accessible, common in many household products, have no legal restrictions on their purchase, and are inexpensive. They also rapidly produce a euphoric and dissociative “high” which resolves shortly after active inhalation has ceased.

According to the National Poison Data System, between 1993 and 2088 inhalant exposure occurred starting in children as young as 6 years old, and followed a bell-shaped curve to a peak incidence at age 14 of approximately 57 cases per million people. Use then gradually declined with age and by the late 20’s, the incidence of exposure had decreased to less than 5 cases per million. This data reflects only those cases reported to Poison Centers and while it likely provides a reasonably accurate portrait of age distribution, it undoubtedly underestimates actual use rates due to its passive data collection.

The University of Michigan’s Monitoring the Future study showed that in 2010, use of inhalants among 8th, 10th, and 12th graders surveyed was greatest in the youngest students with approximately 9% reporting usage within the last 12 months. That percentage declined moving into the 10th and 12th grade down to about 4% in high school seniors.

As of 2008, the National Survey on Drug Use and Health (NSDUH) found that the majority of inhalant abusers were between the ages of 12-17 years old. Of 729,000 individuals aged 12 years and older who were asked about first time inhalant usage in the past year, 67% were less than 18 years old.

While inhalant abuse is seen throughout all socioeconomic and ethnic groups, those at especially high risk include the impoverished, Native Americans, Hispanics, and children raised in rural areas.

Familial dysfunction and immersion in settings where substance abuse is commonplace increase a child’s likelihood of experimenting and abusing drugs themselves. Peer pressure among children is also a common factor in inhalant experimentation as it is in many drugs. Contributing to the problem is the ongoing misperception by children that because inhalants aren’t frequently-discussed drugs of abuse such as cocaine and heroin they are somehow safe or free from consequences.

Acute Ingestions:

Asphyxia: Displacement of oxygen by the inhalant results in hypoxic brain injury.

Suffocation: Impaired mentation and motor control while inhaling through a bag, or with a bag over the user’s head, leads to airway obstruction.

Acute Lung Injury: Accidental aspiration and direct chemical injury to the lung is not uncommon in these patients.

Edema: Both pulmonary and cerebral edema can occur acutely following inhalant abuse.

Trauma: Indirect injuries secondary to euphoria and disinhibition are common including motor vehicle accidents, falls, exposure, drowning, and suicide.

Cardiac Arrest can be precipitated by two mechanisms:

• “Sudden Sniffing Death Syndrome”occurs when ingested hydrocarbons cause myocardial sensitization to epinephrine. Vivid hallucinations or surprise by parents or authorities produces a release of epinephrine that causes a fatal dysrhythmia, typically ventricular fibrillation. The hydrocarbons, in particular the halogenated hydrocarbons, inhibit the delayed rectifier potassium channel and prolong the QT interval. This prolonged QT interval in the setting of an acute adrenergic release results in an R on T and an early afterdepolarization which causes the dysrhythmia.

• Freezing temperatures from propellant gases sprayed directly into the oropharynx can cause vagal stimulation to the point of asystolic cardiac arrest.

Chronic Exposure:

CNS Injury: CT and MRI findings have found evidence of accelerated volume loss and white matter degeneration while autopsies have shown cerebral and cerebellar atrophy.

Psychiatric Symptoms: Insomnia, psychosis, anxiety, depression, delirium, dementia, and memory loss may develop.

Addiction: Recovery is complicated, expensive, and with variable rates of success. Failures in academics, truancy, and impaired social skills are seen. Few treatment programs are available which are geared specifically toward inhalant abuse. Inhalants, often seen as innocuous by the user, may also act as a gateway drug to even more addictive and dangerous substance abuse.

Withdrawal: Symptoms of withdrawal can occur after a relatively short period of use and include nausea, vomiting, sweating, chills, muscle cramping, irritability, insomnia and cravings.

Specific Diseases:

Toluene can produce deafness, injury to the fetus, and metabolic acidosis.

Paint pigment inhalation can result in chronic lung disease.

Pathophysiology of Inhalant Exposure:

The effects of inhalants are thought to be mediated by their actions on NMDA, GABA, and serotonin receptors in a manner similar to other CNS depressants like alcohol.

While aerosols, gases and solvents act directly on the CNS, nitrates exert their clinical effects by smooth muscle dilation.

“Sudden Sniffing Death Syndrome” is thought to be caused predominantly by aromatic and halogenated hydrocarbons inhibiting the sodium and inwardly rectifying potassium channels of cardiac myocytes. This sensitizes the myocardium to epinephrine released by sudden startling. Sufficient adrenal output can precipitate a lethal arrhythmia, particularly ventricular fibrillation.

The duration of action of most inhalants is generally short and resolves shortly after discontinuation of active inhalation. Onset and elimination show variability amongst different chemicals largely due to their lipophilicity. While highly lipophilic drugs like nitrous oxide are eliminated almost immediately, chemicals like acetone are more hydrophilic have a longer time to onset, and a prolonged duration of action due to slow elimination.

The interplay of inhalants with dopamine signaling is thought to play a role in the reward and reinforcement pathways that promotes ongoing use and addiction.

Opiate exposure

While accidental ingestion due to a failure in keeping medications out of the reach of children is an important and avoidable cause of opiate poisoning, intentional ingestion related to addiction and recreational use is the predominant reason for exposure. Its abuse represents a growing problem globally and accounts for a huge number of poisoning deaths in the United States each year. Addiction is a complicated disease process resulting in both physical and psychological dependence and recovery is especially difficult to achieve and maintain because of this. The pleasurable effects of the drug as well as the need to continue its use to avoid withdrawal both reinforce ongoing use and abuse.

Among factors contributing to prescription narcotic abuse is the perception that because it is a medicine it is somehow “safer” than street drugs, and also more socially acceptable. In 1991 there were 76 million prescriptions for narcotic-containing medications in the United States. By 2001 this number had almost tripled to 210 million. The presence of incompletely used narcotic medications in the home facilitates abuse by minors.

Epidemiology:According to data from the Monitoring the Future Survey, of 14,400 12th-graders polled in 2010, 1.6% had tried heroin, and 13% had tried narcotics other than heroin. That represents a 0.8% decline in heroin use and a 2.4% increase in non-heroin narcotic use over a 10-year period. There was also a major increase in the number of students reporting having used opiates in the last 12 months from approximately 6.5% in 2001 to 9% in 2002. These percentages remained stable through 2010.

According to the CDC, 40% of poisoning deaths in 2006 were due to opiates, and deaths due to abuse of opiate pain medication quadrupled between 1999 and 2007.

The National Institutes for Drug Abuse estimate that 1 in 12 high school seniors have abused Vicodin and 1 in 20 have used Oxycontin, making these the most abused drugs by adolescents.

Though heroin is an important contributor to opiate-related poisonings, heroin deaths have remained around 2000 per year since before 1999, while deaths due to methadone and other opiates have nearly tripled since that time up to 5000, and 7000 deaths per year respectively as of 2006. Also, while heroin use did spike in the mid-to-late ’90’s to between 1-1.5% of school-aged children, it has since fallen back to just below 1%.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Stimulants

A urine drug screen (UDS) can be sent in cases where the practitioner has limited information but, again, is unlikely to help in the acute setting. Specific stimulant testing can be ordered through consultation with the hospital laboratory and/or the poison control center. These specific tests usually require gas chromatography-mass spectrometry and can take days for results. Furthermore, there are a number of medications that can cause urine drug screen false-positives and it is important to be familiar with your laboratory’s UDS and its sensitivity for certain drug classes.

A review article by Brahm et al. (2010) investigated urine drug screen false-positives and noted that amphetamine and methamphetamine were the most commonly reported false-positive UDS results. In their study, they noted that a number of antihistamines and antidepressants, including trazadone and bupropion, were causes of amphetamine false-positive results. A study by Casey et al. (2011) also demonstrated 41% of amphetamine false-positive results are found in patients who are therapeutically prescribed bupropion. In summary, laboratories are useful in ruling out significant co-ingestions but serve little aid or function in the acute recognition and management of stimulant overdoses.

Hallucinogens

Symptomatic treatment is the hallmark of care and confirmatory lab studies can be drawn but are minimally helpful in the acute overdose setting. Laboratory studies are more helpful for addressing co-ingestions that require urgent action such as elevated acetaminophen or aspirin levels. A urine drug screen (UDS) can be sent in cases where the practitioner has limited information but, again, is unlikely to help in the acute setting.

Specific hallucinogen testing can be ordered through consultation with the hospital laboratory and/or poison control center. These specific tests usually require gas chromatography-mass spectrometry and can take days for results. Furthermore, there are a number of medications that can cause urine drug screen false-positives and it is important to be familiar with your laboratory’s UDS and its sensitivity for certain drug classes.

A review article by Brahm et al. (2010) investigated urine drug screen false-positives and noted that venlafaxine, dextromethorphan, and even ibuprofen had been documented to cause a false-positive PCP result. Instances of tramadol and dextromethorphan causing PCP false-positives have also been reported. In summary, laboratories are useful in ruling out significant co-ingestions, but will rarely assist in the recognition and management of acute hallucinogen overdoses.

Sedative/hypnotic overdose

Specific benzodiazepine/barbiturate testing can be ordered through consultation with the hospital laboratory and/or poison control center. These specific tests usually require gas chromatography-mass spectrometry and can take days for results. Furthermore, there are a number of medications that can cause urine drug screen false-positives and it is important to be familiar with your laboratory’s UDS and its sensitivity for certain drug classes.

A review article by Brahm et al. (2010) investigated urine drug screen false-positives and noted that therapeutic levels of ibuprofen and naproxen had been documented to cause a false-positive barbiturate result. Likewise, sertraline (Zoloft) had been recognized to cause a false-positive benzodiazepine result on UDS in that same study. In summary, laboratories are useful in ruling out significant co-ingestions but will rarely assist in the recognition and management of acute hallucinogen overdoses.

Ethanol exposure

Serum Ethanol Level:Levels of 80-150mg/dL usually result in symptomatic intoxication in children.

Rapid Glucose Finger-stick: An altered mental status or seizure should prompt immediate determination of blood glucose concentration via a bedside finger-stick. If the patient is mentating normally and is hemodynamically stable, it is appropriate to wait for the basic metabolic panel if one is being obtained. Whichever method is used, a glucose level is mandatory in all pediatric patients given the small ethanol concentrations capable of inducing hypoglycemia.

Toxic Alcohol Workup:If coingestion of a toxic alcohol is suggested by the history, additional useful diagnostic labs include a basic metabolic panel to calculate the anion gap, a measured serum osmols to determine the osmol gap, a lactic acid level, an arterial blood gas analysis, and specific toxic alcohol levels as indicated. While not particularly reliable, using a Wood’s lamp on urine to look for the Fluorescein added to antifreeze and a microscopic examination of the urine for calcium oxalate crystals may suggest ethylene glycol exposure.

Pregnancy Testing:A serum pregnancy test should be performed in all females of child-bearing age.

Acetaminophen and Salicylate Levels:Plasma levels of these medications must be obtained if suicidal intent is suspected to aid in the diagnosis of these potentially lethal and treatable coingestions.

Inhalant exposure

Standard urine and serum drug screens are not designed to detect inhalants, and unless organ dysfunction is suspected from chronic use, no specific laboratory test will suggest their presence, which is a clinical and historical diagnosis. A hepatic function panel may indicate toxicity from long-standing inhalant abuse.

Abuse of alkyl nitrates can produce methemoglobinemia. A pulse oximetry reading of 85-90%, cyanosis, and a normal PO₂on an ABG revealing a “saturation gap” are suggestive of this condition. Confirmation is made by obtaining a methemoglobin level.

Methylene chloride inhalation produces carbon monoxide poisoning. Normal oximetry in a patient with signs of hypoxia (fatigue, dyspnea, tachycardia) suggests this condition as does an elevated lactic acid level and an ABG with metabolic acidosis. Confirmation is made with a carboxyhemoglobin level.

Methanol poisoning can occur from abuse of certain carburetor cleaners/degreasers. An ethanol level, methanol level, measured serum osmols, a basic metabolic panel, and a lactic acid will help in the diagnosis of methanol, ethyl alcohol and other toxic alcohol ingestions.

Opiate exposure

Urine Drug Screen: This test screens for opiates but requires further testing to determine the specific type. Also, false positives can occur with more benign substances such as fluoroquinolones. The main life-threatening feature of opiate poisoning, respiratory depression, demands attention and management long before results will return from the lab, and a careful history and the clinical response to Naloxone will be far more valuable from a diagnostic standpoint in the acute setting.

Dextrose Level: Chronic liver disease, hepatitis, poor diet and coingestions may all contribute to hypoglycemia as a cause of depressed mental status and should be checked in every patient with an altered sensorium.

Basic Metabolic Panel: Useful to help identify electrolyte-induced conditions such as seizures due to sodium abnormalities, potassium-related arrhythmias, uremia from renal failure, and acidosis from prolonged hypoxia or co-ingestion.

Acetaminophen Level: While the history and information obtained from family, friends, bystanders, EMS, and police is most helpful for determining a potentially lethal (and treatable) levels caused by either suicide-directed ingestions or exposure to combined opiate-acetaminophen preparations.

Creatinine Kinase: Trauma or prolonged immobilization may produce rhabdomyolysis and result in kidney injury if not recognized early and addressed.

Ammonia: Elevated levels from liver failure due to advanced cirrhosis or infectious hepatitis can produce depressed mental status.

Pregnancy Test: This should be routinely performed on every female of reproductive age to assist in both diagnostic and management decisions.

Lumbar Puncture: In patients with mental status changes who are febrile or exhibit meningismus, consider performing an LP to diagnose CNS infection. Subarachnoid bleeding not seen on unenhanced CT may also be detected by this study and may prompt further investigation with contrast-enhanced CT or MRI.

Ethanol Level: Impaired mentation and loss of a patient’s ability to protect their own airway may be due to consumption of alcohol alone or as a coingestant.

Would imaging studies be helpful? If so, which ones?

Stimulants

With the exception of an EKG, imaging studies are unlikely to be helpful unless the patient has developed chest pain after a stimulant ingestion. An EKG is strongly recommended for all suspected overdose patients. Reported cocaine-induced EKG changes include QRS widening, ST elevation, QTc prolongation, atrial fibrillation, and ventricular tachycardia. In patients with co-ingestions, an EKG will additionally help evaluate for any AV blocks, QRS widening, or QTc prolongation that may be associated with co-ingestants.

In the setting of chest pain or shortness of breath, additional imaging is warranted. This includes a chest x-ray and, potentially, a CT of the thorax with contrast if the practitioner has a suspicion for aortic or pulmonary catastrophe. As mentioned earlier, stimulant overdose is associated with hypertension, a known risk factor for aortic dissection. Westover and Nakonezny (2010) retrospectively evaluated the relationship between amphetamine abuse and aortic dissection, finding a statistically significant increased adjusted odds ratio of 3.33 in the amphetamine abuse population. Other potential intrathoracic injuries requiring CT imaging include pneumomediastinum and pneumothorax.

In the setting of body stuffers and body packers of illicit drugs, further abdominal CT imaging is also required. Body stuffers are individuals who swallow or rectally insert bags of illicit drugs in an effort to conceal them from authorities. Body packers are individuals with the intention of transporting or smuggling illicit drugs. The concentration of drugs ingested by body packers is typically higher, but more meticulously wrapped with a lower likelihood of rupture.

Hallucinogens

With the exception of an EKG, imaging studies are unlikely to be helpful unless the patient has developed chest pain after a hallucinogen overdose. It is inexpensive, rapid, and non-invasive. In the overdose setting, there is a single case report of presumed ketamine-induced Brugada pattern on EKG (Rollin, 2011). Otherwise, the most common finding following hallucinogen ingestion is sinus tachycardia. In patients with coingestions, an EKG will additionally help evaluate for any AV blocks, QRS widening, or QTc prolongation that may be associated with coingestants.

In the setting of chest pain or shortness of breath, additional imaging is warranted. This includes a chest x-ray and, potentially, a CT thorax with contrast if the practitioner has a suspicion for aortic or pulmonary catastrophe. As mentioned earlier, many hallucinogens demonstrate sympathomimetic or anticholinergic signs like amphetamines. Overdose can be associated with hypertension, a known risk factor for aortic dissection.

Westover and Nakonezny (2010) retrospectively evaluated the relationship between amphetamine abuse and aortic dissection, finding a statistically significant increased adjusted odds ratio of 3.33 in the amphetamine abuse population. In cases such as “wets,” where a marijuana cigarette is dipped in liquid PCP, chest pain complaints require evaluation with a chest x-ray or CT thorax for pneumothorax or pneumomediastinum. Patients valsalva against a closed glottis and pneumothoraces are not uncommon.

A non-contrast head and neck CT may be warranted; head trauma can cause similar signs of altered mental status, hypertension, and tachycardia. The setting and circumstances surrounding the ingestion are often vague and an intracranial bleed is a life-threatening issue.

Sedative/hypnotic overdose

With the exception of an EKG, imaging studies are unlikely to be helpful unless the patient has developed cardiopulmonary arrest. In these instances, imaging studies are more helpful in addressing and ruling out other etiologies of the arresting patient. An EKG is strongly recommended for all suspected overdose patients. It is non-invasive, inexpensive, and quick.

In the overdose setting, there are case reports of benzodiazepine-associated first-degree atrioventricular block. In a single case series by Li et al. (1998), 5 of 7 GHB overdose patients demonstrated U-waves on EKG, although each of the patients had taken other coingestants and this could have contributed to the EKG finding. In patients with coingestions, an EKG will additionally help evaluate for any AV blocks, QRS widening, or QTc prolongation that may be associated with coingestants.

Ethanol exposure

AP and Lateral Chest X-ray:If the patient exhibits signs of respiratory distress (tachypnea, tripoding, retractions, hypoxia), a chest x-ray will be helpful in detecting causes such as pneumonia or pneumonitis from aspiration. Be aware that the findings on chest x-ray may not be present for many hours following a clinically significant aspiration event.

CT Scan of the Head and Neck:These imaging studies should be obtained in any patient with signs of head injury or focal neurological impairment. It may be reasonable to consider expectant management of minimal CNS depression in an otherwise neurologically intact patient without obtaining a CT only if consumption of the offending substance was witnessed by a reliable bystander in the complete absence of any trauma. Providers should have a low threshold for obtaining these studies, even in children, if the clinical picture is unclear in any way given the potential for devastating morbidity and mortality from missed CNS and spinal injuries.

EKG: A cheap and easily obtained study, an EKG is useful for the diagnosis of dysrhythmias or detecting a prolonged QRS or QTc if a suicide attempt using QTc-prolonging drugs is suspected. Congenital pro-arrhythmic syndromes such as Brugada, Wolff-Parkinson-White, and Lown-Ganong-Levine may also be detected.

Inhalant exposure

AP and Lateral Chest X-ray: This study is indicated if a patient exhibits signs of respiratory depression or impaired oxygenation.

CT Scan of the Head and Neck: An important part of the work-up of altered mentation that does not improve with correction of hypoglycemia or naloxone administration. Accidental injuries are common in those with an altered sensorium and missed spinal and intracranial injuries can cause significant morbidity and mortality.

EKG: An EKG should be obtained if the history or physical exam suggests a cardiac dysrhythmia, or if coingestion of a tricyclic antidepressant or other QTc-prolonging drug is suspect.

Opiate exposure

CT of the Head and Neck: An important study in those who fail to respond rapidly and fully to Naloxone administration to rule out CNS abnormalities such as epidural or subdural hematomas, subarachnoid hemorrhage, masses, diffuse axonal injury, or ventriculomegally.

EEG: If non-convulsive status epilepticus is suspected as a cause of depressed mental status an EEG must be performed to either diagnose or exclude this clinical entity. Physical exam findings that suggest this condition include facial twitching, oral automatisms (lip smacking, chewing) eye blinking, hypersalivation, aphasia, neglect, hippus (rhythmic contraction and dilation of the pupils) or a prolonged confusional state resistant to Naloxone lasting greater than 30 minutes.

AP and Lateral Chest X-ray: Signs of respiratory distress should prompt the acquisition of a chest x-ray to help evaluate the cause. Noncardiogenic pulmonary edema (from Naloxone or the opiate itself) and pneumonitis from aspiration are important etiologies that may be detected. Findings on x-ray may lag behind the clinical manifestations of exposure that can present within minutes to hours.

EKG: An EKG is a rapid and inexpensive test that can identify arrhythmias, myocardial infarction, QRS widening due to propoxyphene or other coingestions like tricyclic antidepressants and possible QT prolongation due to a possible methadone ingestion or coingestion of other drugs like atypical antipsychotics.

Are clinical decision algorithms available for suspecting/confirming the diagnosis?

Stimulants

There are no clinical decision algorithms available to confirm the diagnosis in the acute overdose setting of stimulants. The best algorithm to confirm the diagnosis is a good history from the patient, family, or friends, coupled with a good physical examination.

If the patient demonstrates signs of altered mental status, it is important to evaluate for reversible causes like hypoglycemia and hypoxia. This can be done easily and quickly at the bedside via a dextrostick and pulse oximeter, respectively. A urine drug screen can be performed in the acute setting but offers little in regards to the acute management of the patient. As mentioned earlier, there are a number of UDS false-positive results and these can distract the practitioner from the overall clinical picture.

Hallucinogens

There are no clinical decision algorithms available to confirm the diagnosis in the acute overdose setting of hallucinogens. The best algorithm to confirm the diagnosis is a good history from the patient, family, or friends, coupled with a good physical examination.

If the patient demonstrates signs of altered mental status, it is important to evaluate for reversible causes like hypoglycemia and hypoxia. This can be done easily and quickly at the bedside via a dextrostick and pulse oximeter, respectively. A urine drug screen can be performed in the acute setting but offers little in regards to the acute management of the patient. As mentioned earlier, there are a number of medications that may cause UDS false-positive results and these can distract the practitioner from the overall clinical picture.

Sedative/hypnotic overdose

With the exception of the benzodiazepine antagonist flumazenil, there are no clinical decision algorithms available to confirm the diagnosis in the acute overdose setting of sedatives/hypnotics. The best algorithm for treatment is to rule out correctable causes of the patient’s signs/symptoms. If the patient demonstrates signs of altered mental status, it is important to evaluate for hypoglycemia and hypoxia. This can be done easily and quickly at the bedside via a dextrostick and pulse oximeter, respectively. If your patient demonstrates respiratory depression and miosis, consider administering a dose of naloxone.

If you patient shows signs of hypoventilation and hypoxia suggestive of respiratory depression – and you are considering administration of naloxione – make sure to preoxygenate the patient via bag-valve-mask. There are multiple case reports demonstrating the development of acute lung injury manifesting as pulmonary edema after administration of naloxone to respiratory-depressed patients. These episodes appear to be associated with catecholamine release and negative intrapulmonary pressures, induced by inhalation against a closed glottis. They are believed to be preventable with securing a patent airway prior to administration of naloxone with simple maneuvers such as head tilt and chin lift and bag-valve-masking.

For known pure benzodiazepine overdoses, a trial of flumazenil can be considered by the practitioner. Flumazenil is a competitive benzodiazepine receptor antagonist and reversal of benzodiazepine overdose with flumazenil can precipitate seizure activity. It should be avoided in chronic benzodiazepine users. Potential induction of seizures with administration of flumazenil further complicates the overdose patient’s clinical picture and transitions the patient from potentially stable to unstable. While the rate of precipitating benzodiazepine-withdrawal seizures is low, it may do more harm than good for your patient.

With regard to the general use of flumazenil, the only indication for its use is in cases of known pure benzodiazepine overdose – as seen in situations involving procedural sedation. The use of this reversal agent is contraindicated in unknown overdoses, which commonly involve poly-pharmacy.

If you are able to confirm that the patient has overdosed, what treatment should be initiated?

Stimulants

Treatment for stimulant overdoses is symptomatic. This begins with immediate evaluation of the patient’s circulation, airway, and breathing.

In regards to circulation, stimulant overdoses often present with hypertension and tachycardia. Benzodiazepines are the mainstay of therapy and function via activation of gamma-aminobutyric acid type A (GABA-A) receptors in the central nervous system. Activation of these GABA-A receptors induces neuronal membrane hyperpolarization and inhibits excitation. This resultant inhibition of CNS neurons counters the excitatory effects of stimulant overdose.

Aside from the cardiovascular signs of hypertension and tachycardia, benzodiazepines also treat the agitation that often accompanies stimulant overdose. Very large doses of benzodiazepines may be required to adequately control the patient’s signs of hypertension and tachycardia. The amount of benzodiazepine administered should be enough to control hemodynamics and agitation without respiratory compromise or loss of airway reflexes.

Beta-blockers are not recommended for control of hypertension, especially in the setting of potential cocaine overdose (Beta-blockers and cocaine are addressed below). If the patient is unstable and presents in shock, boluses with normal saline or lactated Ringer’s solution are the first method of addressing hypotension.

While addressing circulatory issues, it is important to quickly assess the airway and breathing. Respiratory compromise is less common than in overdoses of other drugs such as ethanol or sedatives/hypnotics. Tachypnea is a common finding in stimulant overdose. As mentioned previously, it is important to continue to reassess the airway after administration of benzodiazepines. If the patient demonstrates respiratory difficulty or hypoxia, be sure to assess for pneumothorax or pneumomediastinum, as these complications have been well described in stimulant abuse cases.

If the patient requires endotracheal intubation for medical or safety reasons, it is important to consider initially hyperventilating these patients. The tachypnea demonstrated prior to intubation is a response to the metabolic acidosis caused by their overdose. Before intubating the patient, the practitioner should quickly rule out hypoglycemia as the cause of altered mental status and failure to protect the airway. This can quickly and easily be done at the bedside via a dextrostick.

Immediately after addressing life-threatening issues, the practitioner needs to elicit a good history and perform an all-inclusive physical examination. This should involve EMS providers, if available, who were at the scene and could identify any specific pill bottles or drugs of abuse. This should also involve questioning family or friends that are present. Questions aside from time of ingestion and drug ingestion type are also important. A non-contrast head and neck CT may be warranted; head trauma can cause similar signs of altered mental status, hypertension, and tachycardia.

For potential agitation, benzodiazepines are considered the best therapy for sedation. As mentioned above, very large doses of benzodiazepines may be required to appropriately control the patient’s signs of agitation, hypertension, and tachycardia. Phenothiazines – such as haloperidol and droperidol – are generally considered contraindicated for treatment of acute agitation in overdose patients, as they both are known to cause QT prolongation.

Benzodiazepines have a wider therapeutic range and better safety profile. Since many stimulants in overdose settings are known to cause EKG changes such as QRS widening and QTc prolongation, administration of medicines known to cause QTc prolongation is felt to be contraindicated. Recent literature by Isbister et al. (2010) suggests that there is no significant difference in adverse outcomes when comparing droperidol versus midazolam for all causes of acute agitiation in the ED setting. While interesting, this article should not change your practice until more definitive data on this topic is produced. Current recommendations for agitation control are benzodiazepines titrated to effect.

Laboratory studies mostly involve testing for coingestants that will change your clinical management. An EKG is strongly recommended for all overdoses, especially with stimulant overdose and chest pain. Approximately 6% of cocaine abuse patients who present with chest pain will have evidence of an acute myocardial infarction (MI), as indicated by positive cardiac enzymes. Another reported abnormal laboratory value involves serum sodium. Cases associated with MDMA abuse and the syndrome of inappropriate anti-diuretic hormone (SIADH) have been reported. Hyponatremia should be corrected acutely if the patient is actively seizing – slowly if the patient is asymptomatic. Also, frank hepatic injury is well described with MDMA toxicity and should be evaluated.

Rhabdomyolysis and acidosis are commonly reported in the literature for many stimulants. Treatment involves supportive care with copious intravenous fluids of normal saline or lactated Ringer’s solution. Hemodialysis may be needed for treatment of the acidosis. The stimulant, itself, though cannot be removed via dialysis. Urine output goals should be 2 mL/kg/hour.

Gastrointestinal decontamination with activated charcoal (AC) can be given if the ingestion occurred within one hour and the patient demonstrates no altered mental status and no airway compromise. There is no definitive data in humans regarding AC and mortality, but methamphetamine toxicity and AC have been examined in a mouse model (McKinney, 1994). In that study, there was a statistically significant decrease in mortality at 24 hours, but not at 48 hours.

Hyperthermia can be present in all stimulant overdoses and should be taken very seriously. It should be addressed emergently and has a poor prognosis. A review and literature search by Gowing et al. (2002) of MDMA-induced hyperthermia overdose cases demonstrated that, for temperatures >41.5 C, 17 of 25 patients (68%) died. Initial hyperthermia treatment involves administration of room temperature intravenous fluids. As circumstances dictate, ice water packs can be placed in the groin and axilla. Additionally, evaporation is very effective and can be performed with simple tools such as a spray bottle with tepid water and large fans. Large industrial fans can often be found by the maintenance team and can be very effective.

Hallucinogens

Treatment for hallucinogen overdoses is symptomatic. This begins with immediate evaluation of the patient’s circulation, airway, and breathing.

In regards to circulation, hallucinogen overdoses often present with hypertension and tachycardia. Benzodiazepines are the mainstay of therapy and function via activation of gamma-aminobutyric acid type A (GABA-A) receptors in the central nervous system. Activation of these GABA-A receptors induces neuronal membrane hyperpolarization and inhibits excitation. This resultant inhibition of CNS neurons counters the excitatory effects of hallucinogen overdose. Aside from the cardiovascular signs of hypertension and tachycardia, benzodiazepines also treat the agitation that may often accompany hallucinogen overdose.

Very large doses of benzodiazepines may be required to adequately control the patient’s signs of hypertension and tachycardia. The amount of benzodiazepine administered should be enough to modulate hemodynamics and agitation without respiratory compromise or loss of airway reflexes. Beta-blockers are not recommended for control of hypertension, especially in the setting of an undifferentiated overdose and potential cocaine coingestion. For a discussion of beta-blockers and cocaine, please refer to the section on stimulant overdose. If the patient is unstable and presents in shock, boluses with normal saline or lactated Ringer’s solution are the first method of addressing hypotension.

While addressing circulatory issues, it is important to quickly assess the airway and breathing. Respiratory compromise is less common than overdoses of other drugs such as ethanol or sedatives/hypnotics. Tachypnea is a common finding in hallucinogen overdose. If the patient demonstrates respiratory difficulty or hypoxia, be sure to assess for pneumothorax or pneumomediastinum, as these complication have been well described in hallucinogen and stimulant abuse cases.

Immediately after addressing life-threatening issues, the practitioner needs to elicit a good history and perform an all-inclusive physical examination. This should involve EMS providers – if available – who were at the scene and could identify any specific pill bottles or drugs of abuse. This should also involve questioning family or friends that are present. Questions aside from time of ingestion and drug ingestion type are also important.

Phenothiazines such as haloperidol and droperidol are generally best avoided in the treatment of acute agitation in overdose patients, as they both are known to cause QT prolongation.

Benzodiazepines have a wider therapeutic range and better safety profile. Many hallucinogen overdoses are mixed overdoses or unknown undifferentiated overdoses. There are a number of recreational drugs that are known to cause EKG changes such as QRS widening and QTc prolongation and, for this reason, administration of medicines known to cause QTc prolongation is felt to be contraindicated. As a side note, recent literature by Isbister et al. (2010) suggests that there is no significant difference in adverse outcomes when comparing droperidol versus midazolam for all causes of acute agitation in the ED setting. While interesting, this article should not change your practice until more definitive data on this topic is produced. Current recommendations for agitation control are benzodiazepines titrated to effect.

Laboratories for hallucinogen overdose are useful, as there are a number of reported abnormalities that can change your clinical management. Hyponatremia, hepatic dysfunction, and significant acidosis are the major laboratories to investigate. Cases associating MDMA abuse and syndrome of inappropriate anti-diuretic hormone (SIADH) have been reported.

Hyponatremia should be corrected acutely if the patient is actively seizing – slowly if the patient is asymptomatic. While the hallucinogen is the most likely cause of altered mental status in hallucinogen overdoses, hyponatremia may also be contributing to this clinical picture. Also, frank hepatic injury is well described with MDMA toxicity and should be evaluated. Rhabdomyolysis and acidosis are commonly reported in the literature for MDMA and should be evaluated in other hallucinogen overdoses. Treatment involves supportive care with copious intravenous fluids of normal saline or lactated Ringer’s solution. Hemodialysis may be needed for treatment of the acidosis in severe cases. Urine output goals should be 2mL/kg/hour.

An EKG is strongly recommended for all overdoses, especially with undifferentiated overdoses and chest pain. In the overdose setting, there is a single case report of presumed ketamine-induced Brugada pattern on EKG. Otherwise, the most common finding following hallucinogen ingestion is sinus tachycardia. In patients with coingestions, an EKG will additionally help evaluate for any AV blocks, QRS widening, or QTc prolongation that may be associated with coingestants.

Gastrointestinal decontamination with activated charcoal (AC) can be given if the ingestion occurred within one hour and the patient demonstrates no altered mental status and no airway compromise. With ingestion of known psychoactive mushroom species such as Psilocyba and Amanita, treatment is supportive. Clinical presentation of mushroom species varies considerably and involvement of your local poison control center is important. Amanita and psilocybin mushrooms are psychoactive and amanita species have been associated with hepatorenal failure.

Hyperthermia can be present in overdoses and should be taken very seriously. It should be addressed emergently and has a poor prognosis. A review and literature search by Gowing et al. (2002) of MDMA-induced hyperthermia overdose cases demonstrated that, for temperatures >41.5 C, 17 of 25 patients (68%) died. Initial hyperthermia treatment involves administration of room temperature intravenous fluids. As circumstances dictate, ice water packs can be placed in the groin and axilla. Additionally, evaporation is very effective and can be performed with simple tools such as a spray bottle with tepid water and large fans. Large industrial fans can often be found by the maintenance team and can be very effective.

Sedative/hypnotic overdose

Treatment for sedative/hypnotic overdoses is symptomatic. This begins with immediate evaluation of the patient’s circulation, airway, and breathing.

In regards to circulation, sedative/hypnotic overdoses can often present with hypotension, requiring intravenous fluids. Benzodiazepines, in general, demonstrate less hemodynamic instability compared to barbiturate overdoses. Boluses with normal saline or lactated Ringer’s solution are the first method of addressing hypotension. If hypotension persists, additional intravenous fluid boluses may be needed followed by pressor therapy. In one study, GHB specifically, resulted in bradycardia and hypotension in 38% and 6%, respectively, of overdose patients who presented to a single urban emergency department. Another study by Chin et al. (2006) demonstrated hypotension in 11% of GHB overdose patients in a single urban ED over a 3-year period.

While addressing circulatory issues, it is important to quickly assess the airway and breathing. Simple maneuvers like head tilt and chin lift with the addition of supplemental oxygen may be all that is needed. In moderate-to-severe overdoses, endotracheal intubation may be needed if the patient is unable to protect his/her own airway or demonstrates inadequate ventilatory effort. Before intubating the patient, the practitioner should quickly rule out hypoglycemia as the cause of altered mental status and failure to protect the airway. This can quickly be done at the bedside via a dextrostick.

In the event of miosis with respiratory depression, it is reasonable for the physician to consider using the opiate antagonist naloxone to reverse a suspected opiate overdose. Polysubstance ingestions are the majority of overdoses. Interestingly, though, a study by Mitchell et al. (1976) showed that 31% of barbiturate-induced comatose children demonstrated miosis. If a benzodiazepine is known to be the causative agent of respiratory depression, the practitioner can also consider using flumazenil.

Flumazenil is a competitive benzodiazepine receptor antagonist and reversal of benzodiazepine overdose with flumazenil can precipitate seizure activity. It should be avoided in chronic benzodiazepine users. Potential induction of seizures with administration of flumazenil further complicates the overdose patient’s clinical picture and transitions the patient from potentially stable to unstable. While the rate of precipitating benzodiazepine-withdrawal seizures is low, it may do more harm than good for your patient.

A non-contrast head and neck CT may be warranted; head trauma can cause similar signs of altered mental status, respiratory depression, and hypotension. Intrathoracic and intra-abdominal trauma can present similarly with hypotension and may have occurred secondary to the drug ingestion.

Laboratory studies are addressed above and involve testing for coingestants. An EKG is strongly recommended, as stated above.

Gastrointestinal decontamination with activated charcoal (AC) should be given if the ingestion occurred within one hour and the patient demonstrates no altered mental status and no airway compromise. A recent meta-analysis by Roberts and Buckley (2011) investigated the use of multiple-dose AC for acute phenobarbital poisoning and identified two prospective controlled clinical trials. They concluded that multiple-dose AC did, in fact, increase the half-life elimination of phenobarbital from 80 hours to 40 hours. The authors mention, though, that only one of the two studies identified clinical benefit.

Hypothermia in the sedative/hypnotic overdose patient needs to be corrected. GHB, specifically, resulted in hyothermia in 48% of overdose patients who presented to a single urban emergency department. Another study by Chin et al. (2006) demonstrated hypothermia in 31% of GHB overdose patients in a single urban ED over a 3-year period. Hypothermia can be addressed with both passive external (warm blankets) and/or passive internal (warm intravenous fluids) rewarming techniques.

Hemodialysis may be necessary in instances of refractory hypotension following barbiturate overdose. Its use, though, is not routinely recommended.

Ethanol exposure

Airway Control:

Maintain a patent airway by suctioning, and upright position (if not spinal injury), and the jaw thrust maneuver. In those patients with sonorous respirations, a nasopharyngeal airway may be required and is less likely to induce vomiting than an oropharyngeal airway. If supplemental O₂is required due to bradypnea, consider continuous waveform capnometry to evaluate for hypoventilation.

A patient who is unable to maintain their own airway with the aforementioned interventions will require bag valve mask ventilation to support their breathing. If the patient can be temporized using this technique, quickly evaluate for hypoglycemia and opiate toxicity as treatment of these two conditions may obviate the need for endotracheal intubation.

If a patient requires mechanical ventilation to maintain respiratory function despite treatment of reversible causes, cricoid pressure during intubation may help reduce the risk of aspiration, and an NG or OG tube should be placed after the airway is secure to decompress the stomach and reduce the risk of vomiting. This may also help with GI decontamination.

Fluids, Electrolytes, and Glucose:

Prolonged vomiting and ethanol-induced diuresis may contribute to dehydration necessitating parenteral replacement. Vomiting can also lead to electrolyte imbalances and failure to maintain PO intake may contribute to significant hypoglycemia.

Hypoglycemia, typically defined as a serum glucose level below 40mg/dL in infants and young children, requires urgent treatment. Levels just above this should not be considered benign and require further monitoring until levels can be maintained without intervention between 70-120mg/dL.

Treatment of significant hypoglycemia includes administration of parenteral administration of dextrose according to the “Rule of 50”, where the concentration of the dextrose solution multiplied by the volume per kilogram equals 50.

• 0-1 year old:5ml/kg of D10W

• 1-12 years old: 2ml/kg of D25W

• 12+ years old: 1ml/kg of D50W

Thiamine administration is a standard therapy in the resuscitation of adults with chronic alcohol abuse and poor dietary intake to prevent and treat Wernicke-Korsakoff Syndrome (symptoms include ataxia, ophthalmoplegia, and confabulation). It should be administered prior to dextrose in at-risk patients to prevent precipitation of this syndrome. This entity is unlikely to be present in the ethanol-naive pediatric population, though providers should be aware of this disease process.

Dialysis:

Peak serum ethanol levels greater than 450-500mg/dL are highly toxic in pediatric patients and should prompt consideration of dialysis and consultation from a nephrologist.

Ongoing Monitoring:

Consider 1:1 monitoring for those patients who have moderate to severe intoxication. Impaired judgment, impulse control, depth perception, reaction time, and motor control make these patients prone to accidental falls resulting in facial fractures, lacerations, and CNS injuries.

Potentially Harmful Therapies:

GI decontamination is not indicated in acute ethanol exposure unless a potentially life-threatening coingestion has also occurred. Activated charcoal does not appear to bind ethanol in human subjects and only increases the potential for aspiration both during administration and secondary to vomiting from gastric distention. Nasogastric tubes may also precipitate vomiting and subsequent aspiration of stomach contents and are of little utility given that ethanol is rapidly absorbed from the stomach (20%) and the small intestine (80%) within 60 minutes of ingestion.

Poison Control Consultation:

All potential toxic ingestions should be discussed with a regional poison control specialist (1-800-222-1222) for diagnostic, management, and surveillance purposes.

Inhalant exposure

As with any acute resuscitation, patient management begins with control of the airway by suctioning, positioning, bag valve mask ventilation and airway adjuncts if needed. If manual assisted-ventilation is successful in temporizing the patient’s airway consider, and if appropriate treat, hypoglycemia and narcotic overdose. Intubation is indicated in all patients with hypoxemia, hypercapnea, and failure to maintain their own airway.

Follow standard decontamination procedures if the patient’s clothing is contaminated with chemicals as the fumes will act as a continuing source of toxicity.

Beta blockers such as Esmolol and Propranolol have been used to manage inhalant-induced ventricular dysrhythmias, though untoward effects including bradycardia and hypotension may develop. While no specific dosage guidelines are available, case studies involving trichloroethylene poisoning found improvement in cardiac dysrhythmias using 20mg of Esmolol IV over 5 minutes followed by a 2mg/min continuous infusion, or a 5mg bolus of Propranolol followed by a 0.5mg/hr drip.

Correct electrolyte abnormalities (including magnesium and phosphorus) and dehydration if present.

Agitation can be effectively treated with benzodiazepines in conjunction with a calming environment to minimize adrenergic stimulation. Acute psychosis can be treated with Haldol or Rispridal, though these medications themselves can cause pro-arrhythmic QTc prolongation.

All poisonings and chemical exposures should be discussed with a poison control specialist (Nationwide number is 1-800-222-1222) for diagnostic, management and surveillance purposes.

Opiate exposure

The mainstay of opiate poisoning is airway management and a thorough evaluation of other potentially life-threatening ingestions or injuries. Vital signs, especially respiratory rate and oxygen saturation should be obtained immediately, and airway interventions including suctioning, airway maneuvers, bag-valve-mask ventilation and possibly even endotracheal intubation may be necessary. Continuous waveform capnography may also be helpful for patients who are able to maintain their oxygen saturations with the assistance of supplemental oxygen but may not be ventilating adequately to prevent hypercapnea.

When a patient’s airway can be controlled temporarily by less invasive methods such as basic airway maneuvers or bag-valve-mask assistance, rapidly reversible causes of a depressed mental status such as hypoglycemia and opiate overdose should be addressed with a bedside glucose measurement and a trial dose of Naloxone prior to intubation. This has the potential to spare the patient a trip to the ICU and the complications associated with mechanical ventilation.

A careful examination of the patient and their belongings should be undertaken to detect remaining drugs or pill bottles, hidden transdermal patches, sites of infection, and indicators of chronic abuse (track marks). Extreme care must be taken to avoid accidental needle sticks during this examination.

Naloxone Dosing:

Neonates

Full Reversal: 0.1mg/kg/dose IO/IV/IM/SQ every 20-60 minutes. Current recommendations for endotracheal administration are 2-3x the IV dosing.

Partial Reversal: 0.01mg/kg/dose IO/IV/IM/SQ every 2-3 minutes as needed titrated to the desired level of reversal.

Infants and Children <5 and <20kg

Full Reversal: 0.1mg/kg/dose IO/IV/IM/SQ every 2-3 minutes as needed to achieve the desired effect. May repeat every 20-60 minutes. Current recommendations for endotracheal administration are 2-3x the IV dosing.

Infants and Children >5 and >20kg

Full Reversal: 2mg/dose IO/IV/IM/SQ every 2-3 minutes as needed to achieve the desired effect. May repeat every 20-60 minutes. Current recommendations for endotracheal administration are 2-3x the IV dosing.

Maintenance Drip for Children

Determine the sum of the doses that resulted in an effective response, and based on the duration of that response, extrapolate to a dose/hour infusion rate. Titration will likely be required. (Example: If two 2mg boluses (4mg total) were given to maintain a 30 minute period of adequate respiratory function, begin the patient on an 8mg/hour continuous infusion, titrating as needed).

Adult (or Adult-Sized) Dosing

Full Reversal: 0.4-2mg IO/IV/IM/SQ every 2-3 minutes to achieve the desired effect. May repeat every 20-60 minutes.

Partial Reversal: 0.04-0.4mg IO/IV/IM/SQ. Repeat and/or escalate dose up to 2mg as needed until the desired effect is acheived.

Maintenance Drip for Adults (or Adult-Sized Children)

2/3 of the total effective bolus dose given over 1 hour. If respiratory depression reoccurs despite this, administer 1/2 of the bolus amount and repeat until reversal is achieved and titrate the drip up by 1/2 the initial rate.

Disposition:

When a patient does respond promptly to Naloxone and is able to maintain their airway and respiratory rate, extreme caution must be exercised when deciding on a disposition. Many opiate-containing prescription medications come in long-acting preparations, and may produce profound respiratory depression after the initial treatment of Naloxone has worn off. Because of this, a careful history regarding the exact formulation and an observation period to watch for rebound is critical.

The effects of Naloxone last approximately 45-70 minutes and certain opiates such as morphine and heroin may be amenable to single dose Naloxone therapy with discharge after observation. If the patient requires multiple doses of Naloxone to maintain their respiratory drive, admission to a telemetry unit for continuous IV infusion is appropriate. HIV testing should be offered to these patients who are at a higher risk of infection due to sharing needles and trading drugs for sex.

Potentially Harmful Therapies:

CPAP and BiPAP are not appropriate methods of respiratory support for opiate-intoxicated patients. These therapies require that an adequate respiratory rate, often lost in opiate-poisoned patients, be maintained in order to function properly.

GI decontamination with charcoal or gastric lavage should not be used unless there is a life-threatening coingestion as these can precipitate vomiting, aspiration and airway obstruction and are unlikely to alter the clinical course.

What are the adverse effects associated with each treatment option?

Stimulants/Hallucinogens

Benzodiazepines can cause respiratory depression, manifesting as hypoventilation and hypoxia. This can result in acidosis and, if left untreated, cardiopulmonary arrest. Some textbooks/literature may argue that benzodiazepine overdose will not cause respiratory compromise but, frankly, this is untrue. Coupled with the hypermetabolic lactic acidosis from a stimulant overdose, induction of hypoventilation and a respiratory acidosis can quickly convert a stable patient to an unstable patient.

Sedative/hypnotic overdose

Flumazenil administration is discussed above and can precipitate benzodiazepine withdrawal and seizure activity. A recent retrospective 2-year study in the United Kingdom by Veiraiah et al. (2011) demonstrated 80 cases of administration of flumazenil with one precipitated brief seizure and one episode of acute agitation. Seventy percent of the patients in that study showed improved symptoms. This is consistent with other studies that show a low rate of precipitating seizures following flumazenil administration.

Activated charcoal (AC) adverse events, while uncommon, have been reported. A review article by Seger (2004) discusses these adverse events. Most are associated with depressed mental status and aspiration with resultant pneumonitis and hypoxia. The risks and benefits need to be addressed before administering charcoal to a sedative/hypnotic overdose. Current mental status of the patient and ability to protect the airway must be assessed. Another recent meta-analysis by Roberts and Buckley (2011) investigated the use of multiple-dose AC for acute phenobarbital poisoning and identified two prospective controlled clinical trials. They concluded that multiple-dose AC did, in fact, increase the half-life elimination of phenobarbital from 80 hours to 40 hours. The authors mention, though, that only one of the two studies identified clinical benefit.

Hemodialysis adverse events include bleeding, bruising, and catheter-related complications. Hemodialysis is usually used as a late attempt to correct refractory hypotension. According to a systematic review by Roberts and Buckley (2011), there is not sufficient data to recommend this method of treatment regularly for barbiturates. We were unable to identify any studies in the literature addressing benzodiazepine overdose requiring hemodialysis. Benzodiazepines have milder effects on hemodynamic stability than barbiturates and this is the likely cause of this paucity of reports in the literature.

Opiate exposure

Naloxone’s duration of action is brief in comparison with some of the longer-acting opiate formulations. Careful determination of the type of opiate ingested and observation of the patient until after the reversal effects of Naloxone have dissipated is critical to ensure the patient remains alert and can maintain their own airway.

Opiate withdrawal can be precipitated by Naloxone administration in those who have developed a tolerance through chronic use. In these patients, excessive amounts of Naloxone may precipitate a rapid withdrawal manifesting as anxiety, tachycardia, abdominal cramps, restlessness, vomiting and diarrhea. Careful titration of Naloxone in these patients is important to reverse the life-threatening respiratory depression without causing clinically significant withdrawal.

Both Naloxone and narcotics use itself have been linked to noncardiogenic pulmonary edema. The current theory for this complication is a sudden increase in sympathetic output with epinephrine levels rising 30-fold (even in barbiturate-sedated patients). This results in sudden fluid shifts from the high-pressure peripheral vasculature to the low-pressure pulmonary vasculature causing pulmonary edema. This effect has been found to be even more pronounced in hypercapnic animal models which suggests that in the obtunded, hypercapnic, opiate-intoxicated patient, ventilatory support with a bag-valve-mask prior to Naloxone use may be helpful.

Intubation and mechanical ventilation is not a benign intervention and exposes the patient to complications such as pulmonary barotrauma, pneumothorax, ventilator-associated pneumonia, aspiration, and complications with the intubation process resulting in hypoxic brain injury.

Tolerance and addiction complicate the long-term treatment of those who abuse opiates, and referral for specialist assistance with rehabilitation and detoxification should be sought.

Case studies have linked Naloxone use to sudden pulmonary edema, hypertension, seizures, cadiac arrhythmias and even cardiac arrest. However, given its widespread use and success, it is considered to have an excellent safety profile.

Withdrawal may occur in those using opiates on a chronic basis, and these individuals typically display drug-seeking behavior between use and can suffer significant physical withdrawal symptoms if not appropriately managed.

The delayed-release formulations of many prescription opiates combined with the decrease in GI motility they cause may result in a significant delay in the presentation of the full clinical severity of an exposure leading to an underestimation of the treatment required. A thorough history and high index of suspicion should be had when determining the duration of treatment and appropriateness for discharge.

What are the possible outcomes of overdose?

Opiate exposure

Brain Injury: Prolonged respiratory depression without prompt correction by either mechanical ventilation or antidotal therapy results in decreased oxygen intake and delivery to the brain resulting in permanent injury.

Respiratory Arrest: Lethal doses of narcotic may precipitate full respiratory arrest, which is quickly followed by cardiac arrest and death.

Hypotension: Most opioids trigger some degree of histamine release which in turn results in hypotension. Fentanyl produces very little histamine release, which makes it a useful analgesic in hypotensive trauma patients. On the other end of the spectrum, Merperidine can produce a much more pronounced drop in blood pressure.

Trauma: Due to the euphoric and sedating effects of narcotics, those exposed engage in increased risk-taking behavior, have impaired judgment and motor coordination, and are at increased risk of suffering traumatic injury.

Tolerance: Frequent use of narcotics cause an up-regulation in the secondary messenger cAMP, which in turn blunts the effects of opiate receptor agonists. This causes a decrease in the physical and psychological effects of the same narcotic dose over time. All opiate-induced effects do not decrease equally with chronic usage, however, which increases the risk of an adverse response such as respiratory depression with dose escalation.

Infection: Needle-sharing and trading sex for drugs increases a user’s chance of acquiring diseases such as HIV and hepatitis, and of developing cutaneous abscesses at injection sites. Endocarditis can also develop when unsterilized needles introduce bacteria into the blood stream, which then leads to seeding of the valves and inner lining of the heart. These clinical entities should be considered in those patients presenting with a history of opiate abuse, especially in the setting of fever or chronic constitutional symptoms.

Other clinical manifestations that might help with diagnosis and management

Stimulants

There is a single case report (Jakkala-Saibaba, 2011) in the literature of successful treatment of cocaine toxicity with lipid emulsion therapy. Successful local anesthetic toxicity treatment with lipid emulsion has been well described in the literature. Cocaine can be used as a local anesthetic as well and has similar structural moieties.

How can overdose be prevented?

Ethanol exposure

Alcoholic beverages and dangerous chemicals should be locked up and kept out of the reach of children at all times to prevent accidental exposure in young children.

It is important to talk to children about the dangerous of ethanol abuse before they begin experimentation and to convey the parental expectations about use as they reach adulthood.

Disfulram is a prescription aid used to help ensure compliance with ethanol abstinence. Those taking this medication who consume ethanol experience headache, flushing, sweating, nausea and vomiting for an hour or more. This medication is not part of initial management and should not be given to those who are intoxicated.

For those who have become addicted/dependant on ethanol, both inpatient and outpatient treatment programs exist but availability varies by location. Social workers are generally familiar with local resources and can assist with patient disposition.

Inhalant exposure

Due to the ubiquitous nature of household materials that can be used as recreational inhalants, regulatory control similar to those imposed on alcohol and tobacco is unrealistic. Laws prohibiting abuse of these chemicals impose a societal standard and create deterring consequences for those participating in this form of drug abuse. Age restrictions on sales of the most dangerous or frequently abuse inhalants may help reduce availability.

Prevention, rather than treatment, must be the primary goal and should be instituted early by parents, teachers, and healthcare providers. With the mean age of inhalant abuse reported to poison control centers being 14 years old, and with some exposures occurring in children as young as 6, discussions with kids about the dangers of drug abuse should be started early in life.

Parents may be naive to the frequency of inhalant drug abuse in school-aged children and should also be educated as to the signs, symptoms, and behaviors associated with inhalant abuse to facilitate early recognition and intervention.

Encouraging manufacturers to create products with less potential for abuse or that contain chemical deterrents (noxious smells/tastes) is complicated as the alteration may detract from the intended function of the product.

Mandated labeling of products with an emphasis on the dangers of inhalation may have the unintended side-effect of making the identification of inhalable chemicals easier.

Opiate exposure

Maintain careful control of prescription narcotics and proper disposal of unused medication by the patient to whom they’re prescribed helps reduce accessibility for recreational and accidental overdose.

Careful instructions by providers to their patients to who they are prescribing narcotic pain medications regarding the side-effects, and precautions to take during their use will minimize chances of an accidental overdose or drug-drug interaction.

“Detox” and “Rehab” help minimize withdrawal symptoms and improve the chance of a successful recovery from addiction when compared to an individuals’ attempt to wean off these highly addictive substances.

Long-acting opiate receptor agonists with low euphoric effects such as methadone and buprenorphine can be prescribed as part of a treatment program to help prevent the withdrawal symptoms.

What is the evidence?

Stimulants

Kalivas, PW. “Cocaine and amphetamine-like psychostimulants: neurotoxicity and glutamate neuroplasticity”. Dialogues Clin Neurosci.. vol. 9. 2007. pp. 389-397.

Ross, EA, Watson, M, Goldberger, B. “”Bath salts” intoxication”. N Engl J Med. vol. 365. 2011 Sep 8. pp. 967-8.

Spiller, HA, Ryan, L, Weston, RG, Jansen, J. “Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States”. Clin Tox (Phila). vol. 49. 2011 Jul. pp. 499-505.

Wilson, BE, Hobbs, WN. “Case Report: pseudoephedrine-associated thyroid storm: thyroid hormone-catecholamine interactions”. Am J Med Sci. vol. 306. 1993 Nov. pp. 317-9.

Al-Anazi, KA, Inam, S, Jeha, SMT, Judzewitch, R. “Thyrotoxic crisis induced by cytotoxic chemotherapy”. Support Care Cancer. vol. 13. 2005 Mar. pp. 196-8.

Rusyniak, DE, Sprague, JE. “Toxin-induced hyperthermic syndromes”. Med Clin North Am. vol. 89. 2005 Nov. pp. 1277-96.

June, R, Aks, SE, Keys, N, Wahl, M. “Medical outcome of cocaine bodystuffers”. J Emerg Med. vol. 18. 2000 Feb. pp. 221-4.

Greene, SL, Kerr, F, Braitberg, G. “Review article: amphetamines and related drugs of abuse”. 2008 Oct. vol. 20. pp. 391-402.

Kaye, S, Darke, S, Duflou, J, McKetin, R. “Methamphetamine-related fatalities in Australia: demographics, circumstances, toxicology, and major organ pathology”. Addiction. vol. 103. 2008 Aug. pp. 1353-60.

Gowing, LR, Henre-Edwards, SM, Irvine, RJ, Ali, RL. “The health effects of ecstasy: a literature review”. Durg Alcohol Re. vol. 21. 2002 Mar. pp. 53-63.

Brahm, NC, Yeager, LL, Fox, MD, Farmer, KC, Palmer, TA. “Commonly prescribed medications and potential false-positive urine drug screens”. Am J Health Syst Pharm. vol. 67. 2010 Aug 15. pp. 1344-50. (This article describes the numerous medications that can result in a false positive urine toxicology screen performed by immunoassay and the limitations of the urine drug screen testing.)

Casey, ER, Scott, MG, Tang, S, Mullins, ME. “Frequency of false positive amphetamine screens due to bupropion using the Syva EMIT II immunoassay”. J Med Toxicol. vol. 7. 2011 Jun. pp. 105-8.

Hollander, JE, Henry, TD. “Evaluation and management of the patient who has cocaine-associated chest pain”. Cardiol Clin. vol. 24. 2006 Feb. pp. 103-14.

Karch, SB. “Cocaine cardiotoxicity”. South Med J. vol. 98. 2005 Aug. pp. 794-9.

Mohamad, T, Kondur, A, Vaitkevicius, P, Bachour, K, Thatai, D, Afonso, L. “Cocaine-induced chest pain and beta-blockade: an inner city experience”. Am J Ther. vol. 15. 2008 Nov-Dec. pp. 531-5.

Westover, AN, Nakonnezny, PA. “Aortic dissection in young adults who abuse amphetamines”. Am Heart J. vol. 160. 2010 Aug. pp. 315-321.

Alnas, M, Altayeh, A, Zaman, M. “Clinical course and outcome of cocaine-induced pneumomediastinum”. Am J Med Sci. vol. 339. 2010 Jan. pp. 65-67.

Devlin, RJ, Henry, JA. “Clinical review: Major consequences of illicit drug consumption”. Crit Care. vol. 12. 2008. pp. 202

Blom, MT, Bardai, A, van Munster, BC. “Differential changes in QTc duration during in-hospital haloperidol use”. PLoS One. vol. 6. 2011. pp. e23728

Stepkovitch, K, Heagle Bahn, C, Gupta, R. “Low-dose haloperidol-associated QTc prolongation”. J Am Geriatr Soc. vol. 56. 2008 Oct. pp. 1963-4.

Isbister, GK, Calver, LA, Page, CB, Stokes, B, Bryant, JL, Downes, MA. “Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study”. Ann Emerg Med. vol. 56. 2010 Oct. pp. 392-401.

Weber, JE, Chudnofsky, CR, Boczar, M. “Cocaine-associated chest pain: how common is myocardial infarction”. Acad Emerg Med. vol. 7. 2000 Aug. pp. 873-7.

Ghatol, A, Kazory, A. “Ecstasy-associated acute severe hyponatremia and cerebral edema: A role for osmotic diuresis”. J Emerg Med. 2009 Jun 3.

Holden, R, Jackson, MA. “Near-fatal hyponatremia coma due to vasopressin over-secretion after “ecstasy” (3,4-MDMA)”. Lancet. vol. 347. 1996 Apr 13. pp. 1052

Walubo, A, Seger, D. “Fatal multi-organ failure after suicidal overdose with MDMA ‘ecstasy’: case report and review of the literature”. Hum Exp Toxicol. vol. 18. 1999 Feb. pp. 119-25.

Eilert, RJ, Kliewer, ML. “Methamphetamine-induced rhabdomyolysis”. Int Aesthesiol Clin. vol. 49. 2011 Spring. pp. 52-6.

McKinney, PE, Tomaszewski, C, Phillips, S, Brent, J, Kulig, K. “Methamphetamine toxicity prevented by activated charcoal in a mouse model”. Ann Emerg Med. vol. 24. 1994 Aug. pp. 220-3.

Seger, D. “Single-dose activated charcoal-backup and reassess”. J Toxicol Clin Toxicol.. vol. 42. 2004. pp. 101-110.

Jakkala-Saibaba, R, Morgan, PG, Morton, GL. “Treatment of cocaine overdose with lipid emulsion”. Anaesthesia. vol. 66. 2011 Dec. pp. 1168-70.

Cave, G, Harve, M, Graudins, A. “Intravenous lipid emulsion as antidote: a summary of published human experience”. Emerg Med Australas. vol. 23. 2011 Apr. pp. 123-41.

Rangel, C, Shu, RG, Lazar, LD, Vittinghoff, E, Hsue, PY, Marcus, GM. “Beta-blockers for chest pain associated with recent cocaine use”. Arch Intern Med. vol. 170. 2010 May 24. pp. 874-9.

Hallucinogens

Passie, T, Halpern, JH, Stichtenoth, DO, Emrich, HM, Hintzen, A. “The pharmacology of lysergic acid diethylaminde: a review”. CNS Neurosci Ther. vol. 14. 2008 Winter. pp. 295-314.

Greene, SL, Kerr, F, Braitberg, G. “Review article: amphetamines and related drugs of abuse”. vol. 20. 2008 Oct. pp. 391-402.

Walubo, A, Seger, D. “Fatal multi-organ failure after suicidal overdose with MDMA ‘ecstasy’: case report and review of the literature”. Hum Exp Toxicol. vol. 18. 1999 Feb. pp. 119-25.

Wilson, BE, Hobb, WN. “Case report: pseudoephedrine-associated thyroid storm: thyroid hormone-catecholamine interactions”. Am J Med Sci. vol. 306. 1993 Nov. pp. 317-9.

Al-Anazi, KA, Inam, S, Jeha, MT, Judzewitch, R. “Thyrotoxic crisis induced by cytotoxic chemotherapy”. Support Care Carcer. vol. 13. 2005 Mar. pp. 196-8.

Rusyniak, DE, Sprague, JE. “Toxin-induced hyperthermic syndromes”. Med Clin North Am. vol. 89. 2005 Nov. pp. 1277-96.

June, R, Aks, SE, Keys, N, Wahl, M. “Medical outcomes of cocaine bodystuffers”. J Emerg Med. vol. 18. 2000 Feb. pp. 221-4.

Kaye, S, Darke, S, Duflou, J, McKetin, R. “Methamphetamine-related fatalities in Australia: demographics, circumstances, toxicology and major organ pathology”. Addiction. vol. 103. 2008 Aug. pp. 1353-60.

Wolff, K, Winstock, AR. “Ketamine: from medicine to misuse”. CNS Drugs. vol. 20. 2006. pp. 199-218.

Gowing, LR, Henre-Edwards, SM, Irvine, RJ, Ali, RL. “The health effects of ecstasy: a literature review”. Drug Alcohol Rev. vol. 21. 2002 Mar. pp. 53-63.

Ly, BT, Thornton, SL, Buono, C, Stone, JA, Wu, AH. “False-Positive Urine Phencyclidine Immunoassay Screen Result Caused by Interference by Tramadol and its Metabolites”. Ann Emerg Med. 2011 Sept 14.

Rollin, A, Maury, P, Guilbeau-Frugier, C, Brugada, J. “Transient ST elevation after ketamine intoxication: a new cause of acquired brugada ECG pattern”. J Cardiovasc Electrophysiol. vol. 22. 2011 Jan. pp. 91-4.

Westover, AN, Nakonnezny, PA. “Aortic dissection in young adults who abuse amphetamines”. Am Heart J. vol. 160. 2010 Aug. pp. 315-21.

Beshay, M, Kaiser, H, Niedhart, D, Reymond, MA, Schmid, RA. “Emphysema and secondary pneumothorax in young adults smoking cannabis”. Eur J Cardiothorac Surg. vol. 32. 2007 Dec. pp. 834-8.

Alnas, M, Altayeh, A, Zaman, M. “Clinical course and outcome of cocaine-induced pneumomediastinum”. Am J Med Sci. vol. 339. 2010 Jan. pp. 65-7.

Devlin, RJ, Henry, JA. “Clinical review: Major consequences of illicit drug consumption”. Crit Care. vol. 12. 2008. pp. 202

Blom, MT, Bardai, A, van Munster, BC. “Differential changes in QTc duration during in-hospital haloperidol use”. PLoS One. vol. 6. 2011. pp. e23728

Stepkovitch, K, Heagle Bahn, C, Gupta, R. “Low-dose haloperidol-associated QTc prolongation”. J Am Geriatr Soc. vol. 56. 2008 Oct. pp. 1963-4.

Hollander, JE, Henry, TD. “Evaluation and management of the patient who has cocaine-associated chest pain”. Cardiol Clin. vol. 24. 2006 Feb. pp. 103-14.

Karch, SB. “Cocaine cardiovascular toxicity”. South Med J. vol. 98. 2005 Aug. pp. 794-9.

Mohamad, T, Kondur, A, Vaitkevicius, P, Bachour, K, Thatai, D, Afonso, L. “Cocaine-induced chest pain and beta-blockade: an inner city experience”. Am J Ther. vol. 15. 2008 Nov-Dec. pp. 531-5.

Ghatol, A, Kazory, A. “Ecstasy-associated acute severe hyponatremia and cerebral edea: A role for osmotic diuresis”. J Emerg Med. 2009 Jun 3.

Holden, R, Jackson, MA. “Near-fatal hyponatremia coma due to vasopressin over secretion after “ecstasy” (3,4-MDMA)”. Lancet. vol. 347. 1996 Apr 13. pp. 1052

Eilert, RJ, Kliewer, ML. “Methamphetamine-induced rhabdomyolysis”. Int Aesthesiol Clin. vol. 49. 2011 Spring. pp. 52-6.

Unverir, P, Soner, BC, Dedeoglu, E, Karcioglu, O, Boztok, K, Tuncok, Y. “Renal and hepatic injury with elevated cardiac enzymes in Amanita phalloides poisoning: a case report”. Hum Exp Toxicol. vol. 26. 2007 Sep. pp. 757-61.

Seger, D. “Single-dose activated charcoal-backup and reassess”. J Toxicol Clin Toxicol. vol. 42. 2004. pp. 101-110.

Sedative/hypnotic overdose

Kuzniar, TJ, Balagani, R, Radigan, KA, Factor, P, Mutlu, GM. “Coma with absent brainstem reflexes resulting from zolpidem overdose”. Am J Ther. vol. 17. 2010 Sep-Oct. pp. e172-4.

Mason, PE, Kerns, WP. “Gamma hydroxybutyric acid (GHB) intoxication”. Acad Emerg Med. vol. 9. 2002 Jul. pp. 730-9.

Mitchell, AA, Lovejoy, FH, Goldman, P. “Drug ingestions associated with miosis in comatose children”. J Pediatr. vol. 89. 1976 Aug. pp. 303-5.

Coupey, SM. “Barbiturates”. Pediatr Rev. vol. 18. 1997 Aug. pp. 260-4.

Syed, T, Cruz, M. “In brief: barbiturate overdosage”. Pediatr Rev. vol. 27. 2006 Dec. pp. e81-2.

Angelini, G, Ketzler, JT, Coursin, DB. “Use of propofol and other nonbenzodiazepine sedatives in the intensive care unit”. Crit Care Clin. vol. 17. 2001 Oct. pp. 863-80.

Cai, R, Crane, E, Poneleit, K, Paulozzi, L. “Emergency department visits involving nonmedical use of selected prescription drugs in the United States, 2004-2008”. J Pain Palliat Care Pharmacother. vol. 24. 2010 Sep. pp. 293-7.

Mullins, ME. “First-degree atrioventricular block in alprazolam overdose reversed by flumazenil”. J Pharm Pharmacol. vol. 41. 1999 Mar. pp. 367-70.

Plasencia, AM, Ballentine, LM, MOwry, JB, Kao, LW. “Benzodiazepine-associated atrioventricular block”. Am J Ther. 2010 Jun 9.

Li, J, Stokes, SA, Woechener, A. “A tale of novel intoxication: seven cases of gamma-hydroxybutyric acid overdose”. Ann Emerg Med. vol. 31. 1998 Jun. pp. 723-8.

Horng, HC, Ho, MT, Huang, CH, Yeh, CC, Cherng, CH. “Negative pressure pulmonary edema following naloxone administration in a patient with fentanyl-induced respiratory depression”. Acta Anaesthesiol Taiwan. vol. 48. 2010 Sep. pp. 155-7.

van Dorp, EL, Yassen, A, Dahan, A. “Naloxone treatment in opioid addiction: the risks and benefits”. Expert Opin Drug Saf. vol. 6. 2007 Mar. pp. 125-32.

Liechti, ME, Kunz, I, Greminger, P, Speich, R, Kupferschmidt, H. “Clinical features of gamma-hydroxybutyrate and gamma-butyrolactone toxicity and concomitant drug and alcohol use”. Drug Alcohol Depend. vol. 81. 2006 Feb 28. pp. 323-6.

Chin, RL, Sporer, KA, Cullison, B, Dyer, JE, Wu, TD. “Clinical course of gamma-hydroxybutyrate overdose”. Ann Emerg Med. vol. 31. 1998 Jun. pp. 716-22.

Roberts, DM, Buckley, NA. “Enhanced elimination of acute barbiturate poisoning-a systematic review”. Clin Toxicol (Phila). vol. 49. 2011 Jan. pp. 2-12.

Weinbroum, A, Rudick, V, Sorkine, P, Nevo, Y, Halpern, P, Geller, E, Niv, D. “Use of flumazenil in the treatment of drug overdose: a double-blind and open clinical study in 110 patients”. Crit Care Med. vol. 24. 1996 Feb. pp. 199-206.

Seger, D. “Single-dose activated charcoal-backup and reassess”. J Toxicol Clin Toxicol.. vol. 42. 2004. pp. 101-10.

Ethanol exposure

Edenberg, H.J. “The Genetics of Alcohol Metabolism: Role of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Variants”. Alcohol Research and Health. vol. 30. 2007. pp. 5-13. (A detailed review of the genetic polymorphisms of alcohol dehydrogenase and aldehyde dehydrogenase and the impact this variability has on the clinical effects of ethanol in individuals and specific ethnic groups.)

Bronstein, A.C, Spyker, D.A, Cantilene, L.R, Green, J.L, Rumack, B.H, Griffen, S.L. “2009 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 27th Annual Report”. Clinical Toxicology. vol. 48. 2010. pp. 979-1178. (A portion of this data report and analysis focuses on the rates of exposures and fatalities in children less than 5 years of age.)

Iyer, S.S, Haupt, A, Henretig, F.M. “Straight from the Spring?”. Pediatric Emergency Care. vol. 25. 2009. pp. 193-195. (A case report of a 3 month old with accidental ethanol poisoning producing significant blood-alcohol levels with discussion on clinical presentation, pediatric metabolism, and medical management.)

Fine, J.S, Goldfrank, L.R, Nelson, L.S, Hoffman, R.S, Lewin, N.A, Howland, M.A, Flomenbaum, N.E. “Pediatric Principles”. (A portion of this online book chapter details the current knowledge and management of ethanol-induced hypoglycemia and its pathophysiology.)

Wiener, S.W, Goldfrank, L.R, Nelson, L.S, Hoffman, R.S, Lewin, N.A, Howland, M.A., Flomenbaum, N.E. “Toxic Alcohols”. (This online book chapter details the current knowledge and management of toxic alcohol exposure including pathophysiology, clinical manifestations, laboratory evaluation, and medical management.)

Minocha, A, Herold, D.A, Barth, J.T, Gideon, D.A, Spyker, D.A. “Activated Charcoal in Oral Ethanol Absorbtion: Lack of Effect in Humans”. Clinical Toxicology. vol. 24. 1986. pp. 225-234. (Volunteers were given ethanol, or activated charcoal and ethanol, and absorption rates and maximal plasma concentrations were not found to be significantly different between the two groups.)

“Monitoring the Future: A Continuing Study of American Youth”. (Graphic presentation of ethanol use, and perception on use, among 8th, 10th, and 12th graders as part of an ongoing study of drug and alcohol abuse by the University of Michigan in conjunction with the National Institute on Drug Abuse.)

McKeon, M, Frye, M.A, Delanty, N. “The Alcohol Withdrawal Syndrome”. J Neurol Neurosurg Psychiatry. vol. 79. 2008. pp. 854-862. (A detailed discussion of ethanol withdrawal which includes discussions on epidemiology, pathophysiology, diagnosis, monitoring, treatment, and complications.)

Inhalant exposure:

Marsolek, M.R, White, N.C, Litovitz, T.L. “Inhalant Abuse: Monitoring Trends by Using Poison Control Data, 1993-2008”. Pediatrics. vol. 125. 2010. pp. 906-913. (Information from the National Poison Data System is used to monitor and detect trends in drug abuse among pediatric patients.)

Ridenour, T.A. “Inhalants: Not to be Taken Lightly Anymore”. Curr Opin Psychiatry. vol. 18. 2005. pp. 243-247. (A review of the epidemiology, pathophysiology, risk factors and clinical outcomes of inhalant abuse by children.)

“Committee on Substance Abuse and Committee on Native American Child. Inhalant Abuse”. Pediatrics. vol. 97. 1996. pp. 420-423. (A review of inhalant abuse in pediatric patients including discussions on detection and prevention.)

Long, H, Goldfrank, L.R, Nelson, L.S, Hoffman, R.S, Lewin, N.A, Howland, M.A, Flomenbaum, N.E. “Inhalants”. (This book chapter details current knowledge and management of inhalant abuse including pathophysiology, clinical manifestations, laboratory evaluation, and medical management.)

Opiate exposure

Nelson, L.S, Olsen, D, Goldrank, L.R, Nelson, L.S, Hoffman, R.S, Lewin, N.A, Howland, M.A., Flomenbaum, N.E. “Opioids”. 2011. (This online book chapter details the current knowledge and management of opiate abuse including pathophysiology, clinical manifestations, laboratory evaluation and medical management.)

Kaplan, P.W. “The Clinical Features, Diagnosis, and Prognosis of Nonconvulsive Status Epilepticus”. The Neurologist. vol. 11. 2005. pp. 348-361. (This article provides a detailed review of the features of nonconvulsive status epilepticus with historical references, classifications, differential diagnosis, diagnostic workup, and management.)

Mills, C.A, Flacke, J.W, Flacke, W.E, Bloor, B.C, Liu, M.D. “Narcotic Reversal in Hypercapnic Dogs: Comparison of Naloxone and Nalbuphine”. Can J Anaesth. vol. 37. 1990. pp. 238-244. (A side-by-side comparison of two opiate reversal medications to determine the hemodynamic effects of a pure opiate antagonist against a partial agonist/antagonist in a hypercapnic, opiate-medicated, animal model.)

“Monitoring the Future: A Continuing Study of American Youth”. (Data and graphic presentations of use, and perceptions of use, among 8th-, 10th-, and 12th-graders as part of an ongoing study of drug abuse by the University of Michigan in conjunction with the National Institute of Drug Abuse.)

“Drugs of Abuse Information: Prescription Drugs of Abuse Chart”. 2011. (A National Institutes for Health website providing information about various prescription opiates include street names, DEA scheduling, clinical effects, and epidemiology of abuse.)

Warner, M, Chen, L.H, Makuc, D.M. “Increase in Fatal Poisonings Involving Opioid Analgesics in the United States, 1999-2006”. (A epidemiological-focused report on opiate related morbidity and mortality in the US published by the National Center for Health Statistics.)

Hoffman, J.R, Schringer, D.L, Luo, J.S. “The Empiric Use of Naloxone in Patients with Altered Mental Status: A Reappraisal”. Ann Emerg Med. vol. 20. 1991. pp. 246-252. (A retrospective review of Naloxone administration to determine if selective criteria [respiratory rate <12, miotic pupils, and circumstantial history of use] could predict response to Naloxone. Use of the criteria reduced Naloxone use by >75% while maintaining a high sensitivity for detecting responders to Naloxone therapy.)

“American Academy of Pediatrics Committee on Drugs. Naloxone Dosage and Route of Administration for Infants and Children: Addendum to Emergency Drug Dosages for Infants and Children”. Pediatrics. vol. 86. 1990. pp. 484-485. (A committee statement regarding Naloxone dosing in pediatric patients with scientific references to support their conclusions.)

Kienbaum, P, Thurauf, N, Micheal, M.C, Scherbaum, N, Gastpar, M, Peters, J. “Profound Increase in Epinephrine Concentration in Plasma and Cardiovascular Stimulation after Mu-opioid Receptor Blockade in Opiate-addicted Patients During Barbiturate-induced Anesthesia for Acute Detoxification”. Anesthesiology. vol. 99. 1998. pp. 1154-1161. (An evaluation of patients undergoing detoxification during barbiturate-induced sedation showed 30-fold increase in plasma epinephrine levels and significant elevation in markers of cardiovascular stress after Naloxone administration.)

Flacke, J.W, Flacke, W.E, Williams, G.D. “Acute Pulmonary Edema Following Naloxone Reversal of High-dose Morphine Anesthesia”. Anesthesiology. vol. 47. 1977. pp. 376-378. (A discussion of Naloxone dosing and cardiovascular response based around a dramatic case of acute Naloxone-induced pulmonary edema.)

Chamberlain, J.M. “A Comprehensive Review of Naloxone for the Emergency Physician”. American Journal of Emergency Medicine. vol. 12. 1994. pp. 650-660. (A highly detailed review of Naloxone’s pharmacology, clinical effects, and proposed uses including nearly 200 scientific citations.)

Ongoing controversies regarding etiology, diagnosis, or treatment

Stimulants

Beta-blockade in the setting of stimulant use, especially cocaine, is currently viewed as a contraindication. It is argued that beta-blockade results in unopposed alpha-adrenergic stimulation, leading to increased peripheral arterial vasoconstriction. In the setting of chest pain, it is believed to contribute to coronary vasospasm and resultant myocardial infarction.

A retrospective cohort study by Rangel et al. (2010) suggests that there was no difference in the endpoints of death, ventricular fibrillation/ventricular tachycardia, MI, or EKG changes from baseline when comparing patients exposed and unexposed to beta-blockers. Conversely, though, a study by Mohamad et al. (2008) found that continuation or initiation of a beta-blocker on admission increased the risk of developing troponin-positive myocardial infarction (23.3%) compared to patients who did not receive beta-blockers (10.7%). Currently, beta-blockade in the presence of cocaine-induced cardiac chest pain should be avoided until further data strongly suggests a benefit with beta-blockers.

Sedative/hypnotic overdose

While not controversial, there is potential theoretical benefit to the use of intralipid emulsion for long-acting barbiturates such as phenobarbital in patients with refractory hypotension and hemodynamic instability. Long-acting barbiturates such as phenobarbital are more lipid soluble than shorter-acting barbiturates such as secobarbital or pentobarbital.

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OVERVIEW: What every practitioner needs to know

Are you sure your patient has overdosed? What are the typical findings for this condition?

Stimulants

Hallucinogen overdose

Sedative/hypnotic overdose

Ethanol exposure

Inhalant exposure

Figure 1.

Opiate exposure

What other diseases/conditions share some of these symptoms?

Stimulants

Hallucinogens

Sedative/hypnotic overdose

Ethanol exposure

Inhalant exposure

Opiate exposure

What caused this disease to develop at this time?

Stimulants

Hallucinogens

Sedative/hypnotic overdose

Ethanol exposure

Inhalant exposure

Opiate exposure

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Stimulants

Hallucinogens

Sedative/hypnotic overdose

Ethanol exposure

Inhalant exposure

Opiate exposure

Would imaging studies be helpful? If so, which ones?

Stimulants

Hallucinogens

Sedative/hypnotic overdose

Ethanol exposure

Inhalant exposure

Opiate exposure

Are clinical decision algorithms available for suspecting/confirming the diagnosis?

Stimulants

Hallucinogens

Sedative/hypnotic overdose

If you are able to confirm that the patient has overdosed, what treatment should be initiated?

Stimulants

Hallucinogens

Sedative/hypnotic overdose

Ethanol exposure

Inhalant exposure

Opiate exposure

What are the adverse effects associated with each treatment option?

Stimulants/Hallucinogens

Sedative/hypnotic overdose

Opiate exposure

What are the possible outcomes of overdose?

Opiate exposure

Other clinical manifestations that might help with diagnosis and management

Stimulants

How can overdose be prevented?

Ethanol exposure

Inhalant exposure

Opiate exposure

What is the evidence?

Stimulants

Hallucinogens

Sedative/hypnotic overdose

Ethanol exposure

Inhalant exposure:

Opiate exposure

Ongoing controversies regarding etiology, diagnosis, or treatment

Stimulants

Sedative/hypnotic overdose

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