INTRODUCTION The International Statistical Classification of Diseases and Related Health Problems, revision 10 (ICD-10) describes intoxication as “a transient condition following the administration of alcohol or other psychoactive substance, resulting in disturbances in level of consciousness, cognition, perception, affect or behavior, or other psychophysiological functions and responses.”[1] Intoxication is generally an acute phenomenon, the intensity and effects of which wear off with time and disappear completely in the absence of further use of the substance. While most episodes of intoxication do not need medical attention, intoxicated patients may sometimes present to the emergency department.[1] The reasons for seeking medical attention may either be due to the substance use itself (e.g., extreme agitation or violent behavior that may endanger the patient or others around them) or due to an adverse consequence of substance use (e.g., head injury in a road traffic accident that occurred due to driving while intoxicated). Common substances of intoxication encountered in the emergency setting in India are alcohol, cannabis, opioids, and benzodiazepines. Cases of intoxication from other substances like inhalants, stimulants, hallucinogens, and newer psychoactive substances including synthetic cannabinoids and club drugs may also present to the emergency unit. Often the substance of intoxication may be unknown or falsely reported due to fear of legal ramifications or there may be use of more than one intoxicating substance, thereby complicating the clinical picture. Patients may present with decreased levels of consciousness, vomiting, seizures, or other symptoms that may resemble other medical or surgical emergencies. It is, thus, imperative that psychiatrists attending to patients in the emergency department be well-versed with identification, assessment, and management of patients with substance intoxication.[2] Caring for intoxicated patients in the emergency department comes with various other issues that require a psychiatrist’s time and effort. These patients may be brought into the emergency department against their wishes and refuse medical care. They may also be brought in for medical attention by law enforcement authorities with no available identification details and reliable history or even in association with an alleged crime or illegal activity, making it essential for the emergency care provider to be competent in dealing with the medicolegal aspects of intoxication and providing optimum medical services to the patient along with safeguarding the legal procedures. The present clinical practice guidelines deal with the assessment and management of patients with substance intoxication presenting to the emergency department. The guidelines present the general considerations while attending to a substance intoxicated patient, followed by general signs of intoxication. Thereafter, details of intoxication with specific substances are discussed, namely, alcohol, cannabis, opioids, benzodiazepines, and other substances. Features of intoxication, assessment, and management are discussed for each of these substances. Multiple substance intoxication is also discussed in the guidelines. Special populations are referred to in the guidelines, including children and adolescents, women, and the elderly population. The guidelines do not cover nicotine or caffeine intoxication (these are unlikely to be encountered in a clinical setting). Accidental ingestion of substances of use is not catered to in these guidelines. We also do not go into details of intoxication presenting with additional psychiatric and/or medical illnesses and each such case is likely to be unique with its own specific constraints and challenges in management. General considerations while attending to a substance intoxicated patient Patients with intoxication with a substance of abuse present several challenges during assessment and management [Figure 1]. One of the foremost concerns is the potential unreliability of history. Patients with substance intoxication may give inaccurate or unreliable history. This may be partly attributable to patients trying to minimize their substance use, not recollecting details adequately due to cognitive impact of the substance, concealment of the details of substance use from the family, or avoiding sharing details to prevent legal ramifications. Thus, multiple sources of information can be referred to obtain a more comprehensive account of the patient’s condition. Friends, family, and previous treatment records can be useful sources of collateral information about the patient. In some circumstances, physical examination and mental status examination of an uncooperative patient can be helpful to get a clearer clinical picture of the patient (e.g., injection track marks can hint at opioid overdose in an otherwise comatose patient).Figure 1: Challenges in assessment and management of patients with substance intoxicationAnother challenge that comes across in patients with intoxication is the occurrence of agitation or violence. Some of the intoxications with substances like alcohol and stimulants like cocaine may be associated to aggression. Aggression may be due to disinhibition and impaired judgement associated with substance use. Furthermore, substance use disorder may be associated with other psychiatric or medical illnesses that may individually contribute to the state of agitation or aggression. Addressing aggression promptly is required to prevent harm to the self and others. Other relevant guidelines of the Indian Psychiatric Society may be referred to while addressing aggression and violence when patients with substance intoxication present to the emergency department. A related issue is the consumption of substances or presentation with substance intoxication when the patient intends to kill themself. This may be a presenting feature in patients with overdose of opioids or sedative-hypnotics. Sometimes, patients may also consume large amounts of alcohol when they have an intent to die. Thus, self-harm should be considered as a possibility when patients present with substance intoxication, and suitable assessment measures should ascertain risk to self and the presence of concurrent psychiatric disorder. If required, additional treatment should be instituted for the patient. A relevant aspect of consideration is to determine the line between simply the use of a substance or substance intoxication. Description in the ICD-11 mentions substance intoxication as occurrence of “clinically significant disturbances in consciousness, cognition, perception, affect, behavior, or coordination that develop during or shortly after the consumption or administration.”[3] Hence there is a leeway for the clinician to determine what is considered as “clinically significant”. One way to simply operationalize is to consider any clinical encounter with a patient having a recent history of substance use which has resulted in the abovementioned mental or neuropsychiatric disturbances and are brought to the emergency/clinical setting as “clinically significant” (those situations where these disturbances are expected by the person and are found to be pleasurable would be considered simply as use). The disturbances are described as transient and reversible, and hence they are expected to abate with time. Patients with substance intoxication may have an issue related to their mental competence. Substance use may result in impairment of judgement or consciousness. This may result in impairment of competence, that is, the ability of the person to comprehend choices, decide a course of action, and communicate their choice back. This lack of competence has a bearing on treatment choices that should be instituted and promulgation of coerced treatment. It is generally accepted that when a person is not found to be competent, the nominated representative can be the proxy decisionmaker for the person. The treatment providers can also institute emergency treatment in the best interests of the patient. Furthermore, substance intoxication is a reversible process, so if emergency treatment is not required, then one can wait for the patient to re-attain competence as the substance intoxication wanes. A clinical consideration for patients with substance use disorders is the concurrent use of many substances together. This may lead to the clinical picture being altered or complicated by features of intoxication or withdrawal from different substances. For example, a patient with opioid dependence may experience sedation during intoxication. If benzodiazepines or alcohol are used concurrently with opioids, then the sedation may be accentuated. In such a patient, reversal using naloxone may offset the features of intoxication from opioids, but not reverse the effects of benzodiazepines. Similarly, intoxication from cocaine and other stimulants may lead to paranoia, which may be accentuated by the consumption of higher than usual amounts of cannabis. Thus, a clinician needs to be open to the idea of multiple substance consumption in a patient with substance intoxication. Another issue in the clinical management of patients with substance intoxication in the emergency setting is the potential lack of social support in the treatment process. Patients may be consuming substances alone, or it is possible that casual acquaintances do not intend to help or are not in a position to help (due to their own intoxication as well). Family and friends may be disinclined or burnt out due to the substance use disorder and hence may not be forthcoming in engaging with the care process. Thus, the ancillary supports available in the treatment process of patients with substance intoxication may be few. Sometimes, police or other bystanders may bring a patient with substance intoxication to the emergency unit and the identity of the patient may be unknown to them. Thus, clinicians may have to work with limited information on occasions. There may be legal concerns with the consumption of certain substances considered illegal under the Narcotic Drugs and Psychotropic Substances Act, 1985. This may make patients hesitant to disclose use of some of the substances; for example, heroin. Treating psychiatrists might also be apprehensive about documentation. However, it should be reiterated that clinicians can help patients better if they are able to get a reliable history of the patient. Thus, it would be preferable to gather detailed information and document suitably while ensuring confidentiality of the treatment records and providing reassurance about this to the patient. It might also be prudent to perform urine or blood testing for substance abuse, ensuring a safe chain of custody of the sample. It is unlikely that such treatment records are referred to by the legal process, but a psychiatrist may need to present the relevant information to courts when requested through due processing. General signs of intoxication As specified in the ICD-11,[3] intoxication from one or more psychoactive substances may be suspected in cases where the following features are present: Transient, but clinically significant disturbances occur in consciousness, coordination, perception, cognition, affect, or behavior that develop during or shortly after the consumption/administration of the substance(s) The symptoms are in accordance with the known pharmacological effects of the substance. The intensity of the symptoms is closely related to the amount of substance consumed/administered. The symptoms are time-limited and subside as the substance is cleared away from the body. The symptoms cannot be better explained by another medical condition or another psychiatric disorder. Table 1 enumerates signs and symptoms of intoxication with different substances.Table 1: Features of intoxication with common psychoactive substancesGeneral management of intoxicated patients in the emergency setting As mentioned earlier, patients presenting with intoxication may prove challenging to manage. Intoxicated behavior may often be confused with other disease conditions and vice versa. A brief outline on general management of a patient presenting with intoxication is given in Figure 2.Figure 2: General management of intoxicated patients in an emergency settingALCOHOL INTOXICATION IN THE EMERGENCY SETTING Alcohol (primarily) is a widely used psychoactive substance globally and in India. In people aged 20–39 years, approximately 13.5% of global deaths are attributable to alcohol. More than 200 disease and injury conditions are related to alcohol use. Data from the National Syndromic Surveillance Program of United States, which included non-fatal emergency department visits from facilities in 49 states and Washington, DC, indicated that in 2020 1.8% of the total annual emergency visits were related to alcohol use. Of the many alcohol related disorders presenting to the emergency department in India, a vast majority presents with road traffic accidents due to driving under intoxication followed by acute alcohol poisoning, which is defined as ingestion of a large amount of alcohol in a short duration of time.[4] Clinical features of alcohol intoxication Alcohol is a global central nervous system (CNS) depressant. Acute ingestion generally results in elevation of mood, disinhibition, and increased confidence, leading to argumentative or combative behavior. In addition to those mentioned in Table 1, some features of alcohol intoxication seen with increasing blood alcohol concentration (BAC) are discussed in Table 2. In naïve drinkers, BAC of 150–250 mg per 100 ml result in clinically apparent intoxication; BAC of 350 mg per 100 ml cause stupor and coma; while levels more than 450 mg per 100 ml can be fatal. Regular users of alcohol often develop tolerance and are significantly less likely to manifest symptoms/signs of intoxication at the same BAC than non-regular drinkers.[5] Effects can last from 2 to 3 hours after a few drinks to up to 24 hours after heavy drinking.Table 2: Effects of increasing blood alcohol concentrationAssessment of alcohol intoxication An asssessment of a patient presenting with alcohol intoxication aims at identifying the immediate risks to the patient and attendants and uncovering maladaptive patterns of alcohol use that may require specialized management and care. Acute alcohol intoxication may result in several metabolic abnormalities, like hypoglycemia, lactic acidosis, hypokalemia, hypomagnesemia, hypophosphatemia, and hypocalcemia. Thus, these may be required on an urgent basis. Alcohol can cause acute effects on the cardiovascular system, such as atrial and ventricular tachy-dysrhythmias. Hence, an urgent electrocardiogram (ECG) may be required. Further discussed are the assessment measures for alcohol intoxication: Clinical history Elicit details of current episode of alcohol use: amount, preparation, duration, mixing with other substances, etc. Ask for similar details about previous drinking episodes. Elicit, wherever possible, events of high-risk behavior under intoxication: driving, operating heavy machinery, self-harm, or violence toward others. Attempt should be made, wherever possible, to identify alcohol dependence or harmful use pattern. Physical Examination Assess levels of consciousness (the Glasgow Coma Scale may be used), cardiac and respiratory parameters (heart rate, blood pressure, cardiac rhythm, respiratory rate), and urine output, if possible, with hourly intervals until parameters begin to normalize. Unresponsive patients may suffer from an occult head injury that may be identified from increased intracranial pressure. It is thus advised to perform a direct ophthalmoscopy looking for papilledema, which is a clinical sign for increased intracranial pressure. Papilledema without increased intracranial pressure may also be seen in methyl alcohol poisoning. Thus, imaging (CT/MRI) may be required to determine definitive management. In responsive patients, rule out diplopia and assess eye movements in all cardinal positions, any muscle weakness, and sensory deficits. Observe for any abnormal or involuntary movements. Check for other physical injuries and bleeding from the ear, nose, or mouth. Mental status examination Assess for speech and behavioral abnormalities; pay special attention to aggressive behaviors, and ensure patient and staff safety. Assess thought and perceptual disturbances. Assess orientation to time and place: immediate, recent, and remote memory, insight, and reality testing. Rule out other causes of altered sensorium: Metabolic causes such as hypoglycemia, electrolyte imbalance, hyperosmolar hypoglycemic state, diabetic ketoacidosis, and metabolic acidosis may be detected by laboratory investigations including blood glucose, renal function tests, and arterial blood gases. Cerebral trauma, cerebrovascular events, and meningitis may be identified by computed tomography (CT), magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis. Encephalopathies and toxicity from other substances (methanol, lithium, barbiturates, benzodiazepines, and isoniazid) may be identified through laboratory investigations for serum ammonia, and levels of suspected agents in the blood. Higher serum levels than the therapeutic window indicates toxicity. The abovementioned assessments and investigations are based on individual case considerations and clinical suspicion. MANAGEMENT OF ALCOHOL INTOXICATION IN THE EMERGENCY SETTING Individuals with some symptoms of alcohol intoxication (mild and moderate cases, i.e., without impairment of consciousness or significant medical issues) can be managed in relatively simple surroundings without much medical intervention. Those who are severely intoxicated should be admitted and further managed in a setting where high-dependency or intensive care can be provided.[4,6] Treatment for acute alcohol toxicity is largely supportive. The first priority is airway protection and maintenance of breathing as respiratory depression due to alcohol intoxication may result in death. Alcohol acts as a diuretic; thus, patients with signs of dehydration (dry lips and mucosae and poor urine output) may be provided with intravenous fluids. Checking glucose is important, as many individuals with alcohol use disorder may have depleted glycogen stores. Hypoglycemia needs to be corrected with 5% dextrose intravenously. Routine use of vitamins is not necessary for all cases of alcohol intoxication. However, thiamine supplementation is needed for patients with alcohol dependence to prevent the occurrence of Wernicke encephalopathy. Thus, prophylactic thiamine may be administered to patients who appear at risk of developing thiamine deficiency (prolonged use of alcohol, poor nutritional status, confused mental state, gait abnormalities, and ophthalmoplegia).[7] Usual dose should be at least 250 mg of thiamine daily intramuscularly for 3–5 days, followed by oral thiamine 100 mg daily.[8] It is important to remember that in an emergency setting, thiamine is to be administered before glucose replenishment so that the glucose is utilized in ATP generation (which utilizes thiamine as a co-factor), preventing sequestration of the already limited thiamine which may precipitate Wernicke’s encephalopathy. A brief schematic flowchart for management of alcohol intoxication in the emergency setting is presented in Figure 3.Figure 3: Management of alcohol intoxication in an emergency setting General management Maintain airway, breathing, and circulation. Provide intravenous fluids to counter dehydration and maintain urine output. Hypoglycemia should be corrected with oral glucose, if conscious level permits, or else with 5% or 10% intravenous (IV) dextrose. Maintain ambient room temperature, with quiet surroundings and minimal disturbance. At least one electrocardiogram (ECG) should be obtained for all heavily intoxicated patients and for those with known cardiovascular conditions. “Holiday heart syndrome” characterized by new-onset arrhythmias/atrial fibrillation can occur following alcohol ingestion. Serial ECG monitoring should be done if arrhythmia is detected. As intoxication abates, ECG changes should resolve, but if the changes persist an alternate cause should be considered. In the case of altered mental status, when a full history cannot be elucidated from the patient, a CT scan of the head can be considered for detecting intracranial pathology contributing to the patients’ mental status (e.g., subdural hematoma). MRI can also be considered for select cases. If suicidality is expressed, then psychiatric evaluation should be considered. Laboratory investigations Blood glucose, plasma electrolytes, and blood gases should be measured as frequently as possible in patients with altered sensorium until recovery is assured. Urine toxicology may be performed, if needed, to check for presence of narcotics and sedatives, if suspected. Complete blood counts can be done to detect megaloblastic anemia. Liver function tests should be done when prolonged harmful pattern of alcohol use is suspected. Renal function tests should be done in cases of altered sensorium, poor urine output, or if behavioral features are out of proportion to the amount of alcohol consumed. Blood alcohol levels may be required in medicolegal cases when reliable history is not available or when behavioral features are out of proportion to the amount of alcohol consumed. Whole blood thiamine levels may be measured in patients at risk of or suspected to develop Wernicke’s encephalopathy. Symptomatic management Control aggression by adopting a concerned and non-threatening demeanor. Sedatives should be used judiciously to avoid over-sedation. Metadoxine (given as a single IV/intramuscular [IM] injection of 300–600 mg) may be used to accelerate the elimination of alcohol in adults leading to faster recovery from intoxication. In cases of agitation or violence, antipsychotics (haloperidol 5 mg with promethazine 50 mg) should be considered. In-patient admission of a patient with alcohol intoxication can be considered when there is severe intoxication, medical complications such as Wernicke’s encephalopathy, alcoholic hepatitis, dysrhythmias or convulsions, persistent disorientation, continued abnormality in cardiopulmonary parameters, known chronic systemic illnesses that require medical attention independently, prolonged aggressive behavior, or perceptual abnormalities. The specialty under which the patient needs to be admitted can be determined according to the indication for admission. CANNABIS INTOXICATION IN THE EMERGENCY SETTING Cannabis is the most common illicit substance of abuse in India. Cannabis intoxication sometimes presents to the emergency setting after consumption (either inhalational or oral) of high amounts of cannabis. It usually presents in those who have never tried cannabis before and experience severe psychiatric or medical manifestation of cannabis consumption. Sometimes, regular cannabis users may also experience symptoms and signs of cannabis intoxication when they are introduced to a cannabis product of higher potency. Cannabis intoxication manifests with several symptoms as mentioned in Table 3.[9] There can be several physical symptoms of cannabis intoxication. These include tachycardia, tachypnea, increased blood pressure, dry mouth, nystagmus, increased appetite, and, rarely, precipitation of arrhythmias, angina, or myocardial infarction. Rarely, deep inhalation or breath holding may lead to pneumomediastinum or pneumothorax. Marked perceptual and mental status changes can be observed in cases of cannabis intoxication. These can include alteration in perception of time, with the perceived time being faster than clock time. Music is perceived as more engrossing and colors may appear brighter. There may be hallucinations, primarily auditory ones. There can be a sense of depersonalization. One may become more self-conscious, and may manifest paranoid thinking or delusions (persecutory, referential, or grandiose). Cannabis intoxication affects cognition and psychomotor performance as well. There may be motor incoordination and impaired attention and concentration. Judgment may be impaired due to cannabis intoxication.Table 3: Features of cannabis intoxicationThe cognitive and psychomotor features of intoxication may not be immediately apparent and may manifest up to three hours after consumption of the cannabis product. This may lead novice users to consume higher amounts and experience dysphoria, anxiety, perceptual alterations, and cognitive changes to a higher than anticipated extent. These features of intoxication may last even for 12 to 24 hours after the consumption of cannabis due to accumulation in the adipose tissue and gradual release afterwards. Assessment of patients with cannabis intoxication The assessment of cannabis intoxication is through elaboration of the history and conduct of the examination, supplemented with urine drug screening. Patients presenting to the emergency department with panic attacks or psychotic symptoms after cannabis usage can describe their psychopathology. Attempts should be made to assess the consumption of cannabis products prior to occurrence of such symptoms. Sometimes, friends and family members can provide corollary information. A physical examination that reveals bilateral conjunctival injection without itchiness or pain may indicate cannabis intoxication. A high degree of suspicion may be necessary as the patient may not be forthcoming with proper history, fearing legal or social repercussions. Urine enzyme-linked immunodorbet assay (ELISA) tests might provide objective information about consumption of cannabis, as cannabis remains in the body and is excreted in the urine for at least three days in infrequent consumers and for an even longer duration for regular users. One has to be cautious about urine false positives for cannabis due to efavirenz and non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen and naproxen. Differential diagnosis of cannabis intoxication may include intoxication with other substances of use like cocaine, lysergic acid diethylamide (LSD), MDMA (ecstasy), amphetamines, and synthetic cannabinoids. When a patient presents with psychiatric symptoms like hallucinations, delusions, or panic attacks, one should evaluate for the exacerbation of a preexisting psychiatric illness like schizophrenia, acute and transient psychotic disorder, or panic disorder. Management of cannabis intoxication in the emergency setting Management of cannabis intoxication in the emergency setting can be initiated with placing the patient in a dimly lit space, reassuring them, and decreasing stimulation. In most cases, the intoxication would fade in a few hours. The patient may be given benzodiazepine orally if the patient is accepting the medication orally. Clonazepam 0.5 mg or lorazepam 1 mg can be given in such a situation. If the patient is agitated or violent, then appropriate measures should be taken for the management of agitation or violence. This may include use of antipsychotics (like haloperidol 5 mg with promethazine (Phenergan) 25 mg, given intravenously or intramuscularly), or cautious and limited use of restraints. In cases of chest pain, the patient should be evaluated for cardiac or pulmonary etiological causes. These may focus on myocardial infarction, angina, arrhythmia, pneumothorax, or pneumomediastinum, or evaluation of exacerbation of asthma. ECG or X-rays coupled with referral to cardiologists/pulmonologists or medicine specialists would be useful. Once the patient recovers from cannabis intoxication, they should be debriefed and offered counseling, providing information about harms associated with cannabis use. If a cannabis use disorder is identified (harmful use or dependence), then the patient should be suitably referred for further treatment of substance use disorder. OPIOID INTOXICATION IN THE EMERGENCY SETTING Opioids are highly dependence-producing substances. Opioids used commonly include both pharmaceutical ones (used generally in the form of medications such as methadone, buprenorphine, tramadol, and pentazocine), and non-pharmaceutical ones (generally used for recreational purposes like heroin and raw opium). Intoxication with opioids can be intentional (a patient may be taking increased amounts of opioids to experience a more intense high or as an attempt to harm oneself) or unintentional (a patient may be unable to know the potency of street heroin and hence may inject higher doses of it). There are several risk factors for opioid intoxication or overdose that have been reported in the literature.[10] These include escalating doses of opioids, combination of opioids and sedative drugs, use of opioids after a period of cessation, and presence of comorbid conditions like HIV, depression, and liver disease. Opioid intoxication is defined as a condition of transient and clinically significant disturbances in consciousness, perception, behavior, cognition, affect, or coordination that develop during or shortly after the consumption or administration of opioids. Presenting features include somnolence, stupor, psychomotor retardation, slurred speech, mood changes (euphoria followed by dysphoria), respiratory depression, and impaired memory and attention. Pupillary constriction is generally present. The intensity of these symptoms is related to the amount of opioids consumed, and in severe intoxication, coma may occur. These symptoms are not better accounted by the presence of another medical condition or presence of intoxication or withdrawal of another substance. Opioid intoxication can be classified as mild, moderate, or severe on the basis of the level of psychophysiologi