Version July 2025
INTRODUCTION —
Trauma surgery is the most common indication for surgery and therefore, anesthesia in an acutely intoxicated individual. Other types of surgical emergencies include vascular dissection and hemorrhagic complications associated with certain stimulants.
This topic reviews perioperative and anesthetic considerations for patients who are acutely intoxicated with one or multiple substances including alcohol, cannabinoids, opioids, benzodiazepines, stimulants such as cocaine or amphetamines, or hallucinogens. This topic also discusses perioperative management of patients who are not acutely intoxicated but have a history of chronic substance use disorder or dependency.
IDENTIFYING PREOPERATIVE SUBSTANCE USE DISORDERS
History and physical examination
●History – As perioperative physicians, we routinely inquire about alcohol and other substances [1]. Information regarding current and past history of alcohol, tobacco and other recreational drug use should be obtained [1,2]. Since some patients may be hesitant to disclose their drug use due to fear of stigma or legal consequences, it is important to clearly explain the medical "need to know" to ensure safe perioperative care [3]. Individuals often refer illicit substances by street names. [4]. Knowing common names of various street drugs is helpful in asking specific queries about specific drugs.
Studies have suggested that surgical patients are reasonably honest about their drug use when asked directly. One study conducted in trauma patients in Colorado and Texas noted 80 percent agreement in self-reported use of any one drug compared with results of a standard urine toxicology screen [5]. Furthermore, negative predictive values greater than 90 percent were reported in this study (ie, nearly all patients who denied drug use tested negative on the urine toxicology screen). In another study, 53 percent of trauma patients able and willing to complete a routine drug use questionnaire who tested positive for cannabis on a toxicology screen had also self-reported its use [6].
Single-question screens for possible misuse of alcohol or other drugs have been well-validated in primary care and can be adopted for use in the preoperative period. For example, asking a patient, "Do you sometimes drink beer, wine, or other alcoholic beverages?" and following up a positive response with the question: "How many times in the past year have you had five or more drinks (four for women) in a day?" These two queries have a high sensitivity and specificity for identifying unhealthy alcohol use [7]. Other sensitive and specific screening methods use a questionnaire that can be rapidly administered in a conscious patient to estimate alcohol use (eg, the Alcohol Use Disorders Identification Test [AUDIT] or Substance Use Brief Screening [SUBS] questionnaire) (table 1 and table 2) [8]. (See "Identification and management of unhealthy alcohol use in the perioperative period", section on 'Screening and initial assessment'.)
Similarly, high sensitivity and specificity for identifying misuse of other substances can be obtained with the question: "How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons?" [9]. Adding the explanation: "for instance, because of the experience or feeling it caused" is helpful if asked to clarify the meaning of "nonmedical reasons". Screening tools are discussed in detail in a separate topic. (See "Screening for unhealthy use of alcohol and other drugs in primary care".)
●Physical examination – A thorough physical exam may uncover clues regarding possible acute intoxication or chronic substance misuse:
•Acute intoxication is frequently associated with trauma, and multiple substances can be involved [10]. Signs suggesting acute intoxication include otherwise unexplained tachycardia, diaphoresis, pupillary changes, agitation, or lethargy.
•Signs suggesting chronic substance use disorder include hypertrophic scarring over veins (track marks) or poor dentition.
Testing — For patients appearing to be acutely intoxicated, rapid urine screening tests are readily available at most hospitals for commonly misused substances including opioids (with a fentanyl-specific screen in some institutions), benzodiazepines, cocaine, tetrahydrocannabinol (the psychoactive substance in marijuana), amphetamines and similar agents, and certain hallucinogens. Typically, results are available within one hour. In one study of >10,000 traumatically injured patients, a urine drug screen revealed that nearly 60 percent tested positive for at least one substance that can be misused, while 12 percent tested positive for multiple substances [11]. Details regarding testing for drugs of abuse are available in separate topics. (See "Urine drug testing" and "Substance use disorders: Clinical assessment".)
However, the availability of a biochemical screen for alcohol and other drug intoxication does not reduce the value of directly asking patients about drug and alcohol use (see 'History and physical examination' above). One study reported that sensitivity and positive predictive values for a standard urine toxicology screen were quite poor, suggesting that a negative toxicology screen may not accurately recognize a patient who is a current drug user [5]. Specific challenges in ordering and interpreting these tests include the following:
●Since insurance companies in some states are allowed to deny reimbursement for hospital care of injured patients if the injury resulted from alcohol and drug use, routine ordering screening tests may be disincentivized [12].
●False positives are possible with screening assays. For example, the hallucinogen phencyclidine (PCP) is structurally like dextromethorphan (an over-the-counter cough suppressant). One study noted that most positive screening results for phencyclidine could be explained by the ingestion of a drug other than PCP [13].
●A true positive result does not mean an individual is acutely intoxicated. Examples include:
•Cannabinoids – The cannabis plant from which marijuana is made contains other compounds besides delta-9-tetrahydrocannabinol (THC); an example is cannabidiol (CBD), which is frequently used in legal consumer products (see 'Cannabidiol' below). Trace amounts of THC in these products can result in a positive result on a urine drug screening test. However, neither CBD nor trace amounts of THC would have any psychotropic or physiologic effects, and are irrelevant for anesthetic management. Furthermore, THC and other drugs can cause a positive test for many days after last ingestion when the patient is no longer intoxicated and has no residual effects relevant for anesthetic management. (See "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment", section on 'Drug testing'.)
•Cocaine – A urine screen for cocaine metabolites may remain positive for up to three days after acute intoxication.
•Amphetamines – Amphetamines may be sampled from urine for up to six days after taking the drug [14].
•Opioids – False-positive opioid drug screens have been reported in patients who recently consumed poppy seeds, and in those taking rifampin or quinolones [15]. (See "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment", section on 'Opioid detection'.)
Preoperative management — Before elective surgical procedures in a patient with a known substance use disorder [1]:
●Ensure abstinence in the preoperative period. Elective surgery should be postponed if acute intoxication is suspected, and referral to an expert in substance use disorders may be appropriate.
●Evaluate for specific drug-related comorbidities (eg, liver dysfunction, heart murmur suggesting cardiac valve lesion).
●Assess risk for withdrawal symptoms and plan for appropriate postoperative monitoring for patients at risk for later withdrawal.
●Plan for adequate postoperative pain control, particularly in patients with opioid use disorder - (See 'Opioids' below.)
●Discuss commitment to postoperative follow-up care, including management of the specific substance use disorder.
ETHANOL AND OTHER ALCOHOLS —
We screen for unhealthy alcohol use in all perioperative adult patients, as discussed separately. (See "Identification and management of unhealthy alcohol use in the perioperative period", section on 'Screening and initial assessment'.)
The most common acute intoxicant in trauma patients is ethanol from beer, wine, or spirits [16]. Ethanol has an overall effect as a central nervous system (CNS) depressant. However, the initial dopamine surge that accompanies acute ethanol ingestion may result in agitation rather than sedation.
Potential adverse effects — Pathophysiologic changes that may affect intraoperative care of patients with ethanol intoxication are summarized in the table (table 3), and in a separate topic. (See "Risky drinking and alcohol use disorder: Epidemiology, clinical features, adverse consequences, screening, and assessment", section on 'Morbidity'.)
Perioperative considerations are described below.
Acute intoxication
●Elective surgery – For elective cases, surgery should be delayed until the effects of acute intoxication are no longer present, so that adequate informed consent can be obtained and to allow time for gastric emptying to occur since alcohol delays gastric emptying in a non-dose-dependent fashion [17]. Ideally, patients with unhealthy alcohol use can receive education about alcohol-associated risks and alcohol use disorder treatment with the goal of abstinence prior to surgery. (See "Identification and management of unhealthy alcohol use in the perioperative period", section on 'Treatment of alcohol use disorder'.)
●Urgent surgery
•Rapid sequence induction and intubation (RSII) should be employed to prevent aspiration pneumonitis since ethanol causes delayed gastric emptying [17] and the stomach may be full of both ethanol and food. (See "Rapid sequence induction and intubation (RSII) for anesthesia".)
•Dose requirements of anesthetic agents are decreased in acutely intoxicated individuals due to additive CNS depression, even in patients with chronic alcohol use disorder [18]. This occurs because ethanol is a CNS depressant that alters the function of ion channels at several receptor sites including those for N-methyl-D-aspartate (NMDA), serotonin 5-hydroxytryptamine [5-HT3], glycine, and gamma-aminobutyric acid (GABAA) [18,19]. Thus, doses of induction agents such as propofol should be decreased, especially in patients with hypotension or shock (eg, due to traumatic injury). During maintenance of anesthesia, volatile agents should be carefully titrated since the minimum alveolar concentration (MAC) requirements are typically lower than those for patients who are not intoxicated (table 4) [18].
Chronic misuse
●Dose requirements for general anesthetics and adjuvant sedative and opioid agents may be increased in those patients with chronic excessive consumption of ethanol in the absence of acute intoxication. This occurs due to development of enzyme induction or cross-tolerance [20,21].
●Liver dysfunction impacts anesthetic management in the following ways:
•Doses of neuromuscular blocking agents (NMBAs) should be titrated to effect, with guidance using a peripheral nerve stimulator monitor. The onset, metabolism, and duration of action of NMBAs may be affected by liver insufficiency. (See "Anesthesia for the patient with liver disease", section on 'Neuromuscular blocking agents'.)
•Acetaminophen use should be limited because of the possibility of acute hepatic failure associated with even moderate therapeutic doses of acetaminophen [18,22,23]. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and evaluation".)
•Bleeding tendency may be associated with severe liver disease with thrombocytopenia and/or clotting factor deficiencies. (See "Hemostatic abnormalities in patients with liver disease", section on 'Impaired hemostasis'.)
●Patients with a recent history of known or suspected frequent heavy alcohol use require ongoing postoperative monitoring for symptoms of alcohol withdrawal (nausea and vomiting, headache, disorientation, agitation, anxiety, tremors, sweating) that may occur during the postoperative period (table 5). Management is described in separate topics. (See "Identification and management of unhealthy alcohol use in the perioperative period", section on 'Alcohol withdrawal syndrome' and "Management of moderate and severe alcohol withdrawal syndromes".)
Further details regarding the epidemiology, consequences, identification, and management of unhealthy alcohol use in patients presenting for surgical procedures are discussed separately. (See "Identification and management of unhealthy alcohol use in the perioperative period".)
Other alcohols — Other toxic alcohols include ethylene glycol, methanol, and isopropyl alcohol [24].
●Ethylene glycol and methanol – Ethylene glycol is a sweet-tasting, odorless substance found in antifreeze solutions. Methanol is a colorless, odorless, highly volatile chemical found in jellied cooking fuel or “canned heat” products such as Sterno, windshield washer fluid, and homemade or adulterated alcohols. If ethylene glycol or methanol ingestion is suspected, laboratory studies should be performed including an arterial blood gas (to look for metabolic acidosis), serum lactate, serum osmolality, blood chemistries, and ethanol and ethylene glycol levels. Details regarding management of ethylene glycol poisoning are discussed in a separate topic. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis".)
Intraoperative considerations include:
•Since ethylene glycol and methanol are very rapidly absorbed from the gastrointestinal tract, intraoperative attempts at orogastric-tube aspiration or gastric lavage do little to reduce the ethylene glycol load.
•Ingestion initially manifests as CNS depression, and dose requirements for anesthetic agents will likely be decreased similar to intoxication with ethanol [25]. (See 'Ethanol and other alcohols' above.)
•Hyperventilation may be present as a physiologic response compensating for the severe metabolic acidosis that may occur with acute ethylene glycol poisoning. It is usually prudent to continue hyperventilation during the perioperative period, and sodium bicarbonate is administered when necessary [26]. (See "Bicarbonate therapy in lactic acidosis".)
●Isopropyl alcohol – Isopropyl alcohol, most commonly found in rubbing alcohol and hand sanitizers, is more potent than ethylene glycol or methanol. Like methanol, isopropyl alcohol is very rapidly absorbed from the gastrointestinal tract; thus, intraoperative aspiration via an orogastric-tube or gastric lavage is unlikely to be beneficial. Depression of the CNS peaks at approximately 30 minutes after ingestion; however, isopropyl alcohol is quickly metabolized to acetone and does not cause prolonged sedation [27]. Therefore, dosing requirements for anesthetic agents should not be decreased. Details regarding management of isopropyl alcohol poisoning are discussed in a separate topic. (See "Isopropyl alcohol poisoning".)
CANNABINOIDS
Cannabis (marijuana) and synthetic cannabinoids — Marijuana is a product of the plant Cannabis sativa containing substantial amounts of the potent psychoactive agent delta-9-tetrahydrocannabinol (THC). Details regarding general management of acute intoxication with cannabis are discussed in a separate topic. (See "Cannabis (marijuana): Acute intoxication".)
Synthetic cannabinoids are lab-made chemicals intended to have similar psychoactive effects to those from THC or other products of the cannabis plant [28,29]. These include legally manufactured pharmaceutical agents such as dronabinol and nabilone, as well synthetic designer drugs with street names such as "spice" and "K2”. These products are typically dissolved in either ethanol or acetone, and the resulting liquid is smoked in e-cigarettes, sprayed on plant material that is then smoked, or burned and inhaled as incense or potpourri. Manufacture and ingredients of illegal synthetic cannabinoid products are not standardized [28]. Synthetic cannabinoids may be undetectable in routine serum and urine toxicology testing [30]. Details regarding general management of patients acutely intoxicated with synthetic cannabinoids are discussed separately. (See "Synthetic cannabinoids: Acute intoxication".)
The prevalence of cannabis use has increased steadily in the past several decades and in 2022 worldwide, 22 percent of people reported using cannabis in the past year, while 15 percent reported using it in the past 30 days [31]. However, since the actual prevalence of cannabinoid usage is unknown due to underreporting, we routinely screen all patients for cannabis use before surgery [28,32]. We also agree with the guidelines published by the American Society of Regional Anesthesia and Pain Medicine (ASRA) recommending that all patients reporting chronic use of cannabinoids should be counseled regarding the potential risks of continued use during the perioperative period [32].
Potential adverse effects — Cannabis (marijuana) and synthetic THC products affect multiple organ systems. These agents have important potential adverse effects which are summarized in the table (table 6) [33,34]:
●Pulmonary effects
•Although the isolated compound THC itself causes bronchodilation, smoking or vaping marijuana airway irritation, bronchospasm, and exacerbation of underlying pulmonary disease such as asthma or bronchitis, as well as upper airway edema and resultant airway obstruction during laryngoscopy and endotracheal intubation [28,29,33-44]. There is radiographic evidence suggesting that smoking marijuana causes a lung injury similar to smoking tobacco [45]. Also, smoking cannabis increases levels of carboxyhemoglobin, thereby reducing oxygen-carrying capacity, like smoking conventional cigarettes [46]. These risks are similar to those seen after smoking or vaping nicotine or inhaling other irritants, as described in a separate topic. (See "Smoking or vaping: Perioperative management".)
•Acute intoxication with synthetic cannabinoids has been associated with respiratory depression [47].
●Cardiovascular and cerebrovascular effects
•Sympathetic activation and increased circulating catecholamines, with increased heart rate (HR) and blood pressure (BP), as well as arrhythmias [48] in some patients, can occur with either acute or chronic use [28,34,49-51]. Cannabis use also impairs vascular endothelial function [52]. Acute intoxication or recent use therefore increases risk of perioperative myocardial infarction (MI), ischemic stroke, or transient ischemic attack [28,32,34,46,53-58]. In a retrospective study that included more than 27,000 patients, the incidence of postoperative MI was 0.7 percent in patients who reported active cannabis use compared with 0.3 percent in those without (adjusted odds ratio [OR] 1.88, 95% CI 1.31-2.69) [53].
•Reduced parasympathetic activity with resultant tachycardia can occur in patients with acute intoxication with moderate doses of THC [35,59]. However, at high doses, enhanced parasympathetic tone with dose-dependent bradycardia and hypotension may occur [28,34].
•Myocardial depression and peripheral vasodilation may also occur [60].
●Neuropsychiatric effects
•Acute administration impairs cognitive performance, and may produce sedation and dizziness, as well as euphoria [28,61,62].
•Chronic use can result in dependence, and memory impairment [28].
•Acute administration or acute withdrawal in chronic users may cause anxiety and/or psychotic symptoms in some patients [28,62-65].
•Cannabis may have anticonvulsant properties [66,67].
●Gastrointestinal effects
•Delayed gastric emptying, recurrent nausea and vomiting, or abdominal pain may occur [28,34,68].
•Some patients with long-standing daily use of marijuana may present with cannabinoid hyperemesis syndrome [28,69,70]. This syndrome is characterized by severe nausea, vomiting, abdominal pain, and possibly dehydration and/or electrolyte abnormalities (eg, metabolic alkalosis, hypokalemia) if episodes of nausea and vomiting are protracted. Patients with cannabinoid hyperemesis syndrome may have a paradoxical response to propofol by reducing elimination of endogenous cannabinoids [70].
●Disturbances in thermoregulation – Limited data suggests that cannabis may affect thermoregulation with resultant hypothermia [28,34].
●Other severe adverse effects of synthetic cannabinoids – Unlike cannabis, severe intoxication with synthetic cannabinoids may cause serious life-threatening toxicity including coma, seizures, severe or malignant hyperthermia, rhabdomyolysis, and acute kidney injury [30,71]. (See "Synthetic cannabinoids: Acute intoxication", section on 'Severe intoxication'.)
In rare cases, coagulopathy and prolonged international normalized ratio (INR) or prothrombin time has occurred, with severe bleeding unresponsive to administration of phytonadione (vitamin K) or fresh frozen plasma [72]. (See "Synthetic cannabinoids: Acute intoxication", section on 'Life-threatening coagulopathy (brodifacoum adulteration)'.)
Perioperative considerations are described below.
Acute intoxication
●Elective surgery – Elective surgery should be postponed in patients with altered mental status or impaired decision-making capacity due to acute intoxication [28]. Even in the absence of overt intoxication, a delay of at least two hours after cannabis consumption is recommended to avoid increased risk of MI [32,53,54]. For patients with cannabinoid hyperemesis syndrome, a delay of 24 to 48 hours may allow resolution of these symptoms [73].
Also, we advise patients to abstain from smoking or vaping for as long as possible before and after surgery, similar to abstaining from conventional cigarette smoking (see "Smoking or vaping: Perioperative management", section on 'Treatment of vaping in the perioperative period'). Compared with inhaling nicotine, patients inhaling other substances are at greater risk for development of perioperative lung injury [74]. Other products consumed with THC include additive substances [33,75-79]. The potential for adverse effects has been highlighted by the onset of acute e-cigarette or vaping product use-associated lung injury (EVALI) in some patients in the United States [74,80-84]. Severity of symptoms and physiologic derangements can range from mild (not requiring hospitalization) to severe (requiring noninvasive ventilation, endotracheal intubation with mechanical ventilation, or extracorporeal membrane oxygenation [ECMO]) [44,74,85]. Although causes are not completely understood, most cases are associated with vaping THC together with the added solvent vitamin E acetate. (See "E-cigarette or vaping product use-associated lung injury (EVALI)".)
For patients with recent consumption of cannabinoids via other routes of administration (eg, sublingual, oral, transdermal) rather than smoking or vaping, risks are weighed against benefits of proceeding with elective surgery.
●Urgent surgery
•Rapid sequence induction and intubation (RSII) is employed to prevent aspiration pneumonitis for patients with cannabinoid hyperemesis syndrome [73] (see "Rapid sequence induction and intubation (RSII) for anesthesia"). However, RSII probably is not necessary for acutely intoxicated patients without hyperemesis.
•Close perioperative monitoring of electrolytes is prudent in patients with hyperemesis syndrome.
•Cannabis can cause respiratory depression that is additive to the depressant effects of anesthetic agents [86].
•Anesthetic dose requirements are variable [28,34]. Acutely high levels of cannabis may decrease the minimum alveolar concentration (MAC) value of inhalation agents [87], and may have synergistic effects with dexmedetomidine [28].
•Due to sympathetic activation with increased circulating catecholamines and reduced parasympathetic activity, anesthetic or other agents that increase HR (eg, ketamine, atropine, epinephrine, ephedrine) should be used cautiously in acutely intoxicated patients to avoid marked tachycardia [29].
Chronic use
•Chronic cannabis use may be associated with higher dose requirements for anesthetic agents such as propofol and sevoflurane [28,35,36,88-92]. In one study of 976 endoscopy patients, 22 percent stated that they used marijuana [92]. These patients had higher requirements for propofol (OR 1.77, 95% CI 1.00-3.12) and midazolam (OR 1.57, 95% CI 1.02-2.42) during their procedures.
•Patients who consume cannabis routinely should be monitored for cannabis withdrawal symptoms in the postoperative period [28].
•Patients may have increased postoperative pain and opioid requirements [28,35,93-99]. In a retrospective cohort study that included 34,521 patients undergoing elective surgery with general anesthesia (without neuraxial or regional anesthetic techniques), 1683 had used cannabis within 30 days and 32,838 had never used cannabis [99]. Cannabis users had higher opioid consumption (adjusted ratio of geometric means of 1.30, 95% CI 1.22-1.38) and higher pain scores (time-weighted average score of 0.57, 95% CI 0.46-0.67) during the first 24 postoperative hours. When possible, we use multimodal analgesia incorporating regional analgesic techniques to control perioperative pain in patients with cannabis use disorder (or acute cannabis intoxication) [28,32]. Opioids are reserved for use as rescue medication.
•In some retrospective studies, patients with current cannabis use disorder have a higher risk for postoperative complications including respiratory failure, acute kidney injury (AKI), MI, stroke, or other thromboembolic events (table 7) [28]. Increased hospital length of stay and hospital readmission are also more likely [28].
Cannabidiol — Various legal consumer products derived from the cannabis plant contain components other than THC, with the nonintoxicating extract cannabidiol (CBD) being the most studied [28,100]. CBD and many other cannabis-derived compounds may cause somnolence, but not intoxication or other psychotropic or physiologic changes relevant for anesthetic management [100].
Potential beneficial effects include anticonvulsant properties, and possible efficacy in reducing severity of neuropathic pain, acute pain due to inflammation, anxiety, depression, and sleep disturbances [100]. However, some formulations of CBD products contain contaminants such as dextromethorphan or synthetic cannabinoids, which can have mild adverse hemodynamic effects including hypotension and decreased myocardial contractility which may require the use of direct acting pressors to resolve [101].
OPIOIDS —
Opioids have appropriate uses in the management of chronic cancer and noncancer pain. (See "Use of opioids in the management of chronic pain in adults" and "Cancer pain management with opioids: Optimizing analgesia".)
Appropriate perioperative uses of opioids are discussed in separate topics:
●(See "Perioperative uses of intravenous opioids in adults: General considerations".)
●(See "Perioperative uses of intravenous opioids: Specific agents".)
●(See "Approach to the management of acute pain in adults", section on 'Opioids'.)
However, opioid use disorder is an increasingly common problem that has become a public health crisis in the United States and worldwide [1,102]. Heroin use disorder nearly doubled between 2002 and 2018, and overdose deaths from synthetic opioids such as fentanyl are increasing 2.5 times faster than heroin overdose [102]. In a 2018 retrospective analysis of >16 million patients undergoing major surgical procedures, almost 95,000 had a diagnosis of opioid dependence or abuse (0.6 percent) [103]. These patients had longer lengths of stay in the hospital and higher readmission rates than those without any history of opioid misuse. Such patients are more likely to have inadequate relief from acute pain after a surgical procedure, higher risk of premature discharge from the hospital, and subsequent overdose [102].
Identification and general management of patients with opioid use disorder are discussed in separate topics. (See "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment" and "Opioid use disorder: Treatment overview".)
Potential adverse effects — Pathophysiologic changes that may affect perioperative care of patients with opioid use disorder include effects on gastrointestinal motility (eg, constipation, bloating, early satiety, pain) and opioid-induced hyperalgesia (OIH), characterized by an increased sensitivity to pain. These and other health consequences are discussed in a separate topic. (See "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment", section on 'Health consequences'.)
Perioperative considerations are described below.
Acute opioid intoxication — It is helpful to determine the opioid agent, likely dose, and time of most recent administration to estimate duration of effect, and to consider whether other intoxicant agents may have been ingested. (See "Acute opioid intoxication in adults".)
●Elective surgery – Elective surgery should be postponed if acute intoxication is suspected [102], and when possible, the patient should be referred to an expert in substance use disorders.
●Urgent surgery
•Since patients may be at increased risk for aspiration due to decreased gastric emptying [102], rapid sequence induction and intubation is employed. (See "Rapid sequence induction and intubation (RSII) for anesthesia".)
•Respiratory depression is typically present and can be exacerbated by synergism with other sedative agents taken in the preoperative period or administered in the intraoperative period. It is particularly important to ensure that respiratory effort is adequate before and for at least six to eight hours after liberation from mechanical ventilation [102]. There are no guidelines providing explicit instructions regarding the duration of monitoring for respiratory depression after co-administration of other sedative medications or anesthetics during surgery, so we tailor the duration of monitoring to the opioid that was used. For example, for patients overdosing on a high-affinity opioid such as carfentanil, the opioid receptor antagonist naloxone may be inadequate to achieve reliable and prolonged reversal of respiratory depression [104]; thus, prolonged intubation may be appropriate.
•Profound analgesia after acute opioid use decreases dose requirements for intraoperative anesthetic agents.
•Hypotension may be present due to central and peripheral vasodilatory effects and is exacerbated in hypovolemic patients. Bradycardia may be present with higher opioid doses [102]. Use of naloxone to treat opioid-induced hypotension and bradycardia during the intraoperative period may precipitate risk acute withdrawal or reversal analgesic effects, hence should be used judiciously. Furthermore, naloxone may be appropriate to treat life-threatening cardiopulmonary depression during the preoperative and postoperative periods.
•Noncardiogenic pulmonary edema may be present due to heroin overdose, or as a rare consequence of naloxone administration in the emergency department [105]. (See "Noncardiogenic pulmonary edema".)
•In the postoperative period, persistent opioid effects may exacerbate delirium, nausea and vomiting, ileus, and constipation. Once the analgesic effects of opioids are no longer present, patients are at high risk for withdrawal, tolerance, and OIH, as noted below. (See 'Chronic opioid use' below.)
Chronic opioid use
●Medical comorbidities that may impact anesthetic care or be exacerbated during the perioperative period include renal insufficiency (heroin-associated nephropathy) and hypoxic respiratory insufficiency due to granulomatous infiltrations in intravenous opioid users.
●Long-term use of heroin (or other injected drugs) often results in difficult vascular access due to severe scarring and sclerosis that renders usually accessible veins such as those in the antecubital fossa unusable [106].
●Tolerance, a phenomenon whereby administration of opioids has a diminishing effect over time, is typically present in patients who have received prolonged or high daily opioid doses [102]. This can be partially overcome with higher doses of opioids, although the risk of opioid-related adverse effects is increased with this strategy [107-110]. Opioid agonists with high binding affinity for the mu opioid receptor (eg, hydromorphone, fentanyl, sufentanil) are typically preferred.
Also, multimodal, opioid-sparing techniques should be used during the intraoperative and postoperative periods whenever feasible [102]. Options include continuous neuraxial or peripheral regional analgesia techniques, nonopioid analgesics such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase (COX)-2 specific inhibitors, gabapentinoids, and/or adjuvant inhalation or intravenous agents with analgesic properties (eg, nitrous oxide, ketamine, dexmedetomidine). Adjuvant intravenous agents such as ketamine and dexmedetomidine may be continued through the postoperative period. For example, the American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine, and the American Society of Anesthesiologists have published joint consensus guidelines on the use of ketamine for acute pain management, including for patients with opioid dependence or opioid tolerance [111]. Dosing recommendations are variable, but typically, are less than 1 mg/kg per hour.
●OIH in patients chronically exposed to opioids is caused by nociceptive sensitization and is characterized by greater than expected sensitivity to painful stimuli and/or a paradoxical hyperalgesic response when an opioid is administered [102,112,113]. Thus, nonopioid techniques and agents are employed to provide adequate perioperative analgesia when possible, similar to management of opioid tolerance.
●Overall dose requirements for anesthetic agents may be increased [102].
●Careful monitoring for opioid withdrawal is necessary during the postoperative period (table 8) [102]. Opioid withdrawal symptoms can be assessed with a validated scale such as the Clinical Opiate Withdrawal Scale (COWS) in the perioperative period (table 9) [114,115].
Acute opioid withdrawal is likely when opioids are abruptly discontinued, particularly if high daily doses have been administered over a prolonged period. Withdrawal symptoms can begin as soon as six to eight hours after abstinence in chronic opioid users (table 8 and table 9). Classic symptoms due to rebound increases in neurotransmitter release may be exacerbated by inadequate relief of surgical pain. These include sweating, lacrimation, tachycardia, and hypertension (as well as anxiety, nausea, and vomiting in an awake patient) [107,116]. The excessive sympathetic stimulation is associated with increased risk for perioperative cardiovascular complications including myocardial infarction, arrhythmias, or acute heart failure [102].
Patients in active opioid withdrawal may be treated with buprenorphine [102] (see "Opioid withdrawal in adults in the emergency setting", section on 'Buprenorphine'). In addition, an alpha2 agonist, typically dexmedetomidine, may be administered to reduce the undesirable physiologic effects of opioid withdrawal [107,117,118].
●Patients with chronic opioid misuse should also be monitored for central sleep apnea during the postoperative period [102]. The pathophysiology of opioid-induced central sleep apnea in patients using opioids chronically is based on dysfunction in respiratory rhythm generation and ventilatory chemoreflexes [119]. (See "Central sleep apnea: Risk factors, clinical presentation, and diagnosis".)
●Postoperative pain management is challenging since patients with chronic opioid exposure typically present with tolerance and may have OIH. Even those enjoying good analgesic effect from neuraxial, or regional anesthetic blockade will require maintenance administration of an opioid agent to prevent withdrawal [120]. In many cases, standard opioids and opioid escalation alone are unlikely to provide adequate analgesia [102]. Thus, multimodal, opioid-sparing techniques are employed [102]. Details regarding management of acute postoperative pain in patients with opioid use disorder are discussed in a separate topic, including management for those taking methadone, buprenorphine, or naltrexone. (See "Management of acute pain in patients with opioid use disorder".)
OTHER SEDATIVE AGENTS
Benzodiazepines — Benzodiazepines bind GABAA receptors in the central nervous system (CNS) and reduce the excitability of neurons. They are highly lipid-soluble agents with rapid onset of action. Typical indications for long-term prescription of benzodiazepines include insomnia, seizure disorders, anxiety or panic disorders, and treatment of muscle spasms. However, one report notes that benzodiazepines are the third most misused illicit or prescription drug in the United States (approximately 2.2 percent of the population) [121]. (See "Benzodiazepine use disorder" and "Benzodiazepine poisoning".)
Potential adverse effects — Pathophysiologic changes that may affect perioperative care of patients with benzodiazepine use disorder include cognitive impairment, incoordination, and unsteady gait. These and other manifestations are discussed in a separate topic. (See "Benzodiazepine use disorder", section on 'Clinical manifestations'.)
Potential beneficial effects include perioperative anxiolysis. (See "General anesthesia: Intravenous induction agents", section on 'Benzodiazepines'.)
Perioperative considerations are described below.
Acute intoxication — Acute benzodiazepine use results in sedation, hyperadrenergic effect, reduced centrally mediated tachycardia and hypertension, and respiratory depression [122]. (See "Benzodiazepine use disorder", section on 'Clinical manifestations'.)
●Elective surgery – Elective surgery is postponed if acute intoxication is suspected. The patient is referred to an expert in substance use disorders [28].
●Urgent surgery
•Respiratory depression may be present.
•Dose requirements for anesthetic agents will likely be decreased, similar to other CNS depressants.
•Although benzodiazepines typically do not cause significant hemodynamic changes, mild hypotension and myocardial depression may occur, especially if used concomitantly with opioids [123].
•In the postoperative period, severe withdrawal symptoms can be evident (eg, delirium, agitation, psychosis, seizures). Milder withdrawal symptoms include anxiety, diaphoresis, irritability, headaches, myalgias, nausea and vomiting, tremors, hypertension, tachycardia, and hyperthermia. Recognition and management of benzodiazepine withdrawal are discussed in a separate topic. (See "Benzodiazepine withdrawal".)
Chronic use
●Patients receiving prescribed benzodiazepine medication during the perioperative period should continue to take the agent or its intravenous equivalent to avoid withdrawal. Furthermore, the anxiolytic effects are likely to be useful. (See "Perioperative medication management", section on 'Antianxiety agents'.)
●Dose requirements for general anesthetics and adjuvant sedatives may be increased due to development of enzyme induction or cross-tolerance, similar to chronic ethanol use. (See 'Chronic misuse' above.)
●Postoperative opioid requirements may be increased, and adverse events after surgery are more likely [124,125].
Gamma hydroxybutyrate — Gamma hydroxybutyrate (GHB) or its metabolic precursors (gamma butyrolactone and 1,4-butanediol [1,4-BD]) are CNS depressants used recreationally. This agent is usually manufactured as a colorless, odorless liquid with a slightly salty taste. Although its primary effect is dose-related CNS depression, stimulant effects such as agitation can occur. Since GHB lowers inhibitions and typically causes antegrade memory loss, it has been used surreptitiously as a date-rape drug to facilitate sexual assault. Details regarding intoxication with this agent are found in a separate topic. (See "Gamma hydroxybutyrate (GHB) intoxication".)
Significant anesthetic implications for chronic users of GHB are unlikely unless the patient is acutely intoxicated. However, GHB is often ingested with other CNS depressants (eg, alcohol), which increases the likelihood of the following adverse effects:
●Reduction of dose requirements for anesthetic agents
●Respiratory depression
●In rare cases, seizures or coma
In the postoperative period, severe withdrawal symptoms can occur; these are similar to those noted with ethanol or benzodiazepine withdrawal [126]. (See "Gamma hydroxybutyrate (GHB) withdrawal and dependence".)
PSYCHOSTIMULANTS AND HALLUCINOGENS —
Estimates of the lifetime prevalence of psychostimulant use is seven to eleven percent, and much higher in different racial and ethnic groups [122,127,128]. Recreationally used psychostimulants increase catecholamine levels by increasing release or blocking reuptake. Some compounds have both psychostimulant and hallucinogenic activity (eg, 4-methylenedioxymethamphetamine [MDMA], lysergic acid diethylamide [LSD]) (table 10) [122].
Cocaine — Cocaine can be smoked, snorted, or injected as a recreational drug.
Potential adverse effects — Cocaine has stimulant and potent vasoconstrictive properties because of its effects as a presynaptic reuptake inhibitor of monoamines (eg, dopamine, norepinephrine, epinephrine, serotonin) [122]. Acute cocaine use can cause hypertensive medical or surgical emergencies such as intracranial hemorrhage, stroke, seizure-related trauma, myocardial infarction, aortic dissection, arterial vasoconstriction or thrombus formation with subsequent peripheral arterial infarction, and ischemic bowel. Details regarding management of acute intoxication and sequelae are available in other topics. (See "Cocaine: Acute intoxication" and "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine use".)
Cocaine is also a local anesthetic acting via blockade of sodium channel blockade.
Perioperative considerations are described below.
Acute intoxication
●Elective surgery – Elective surgery should be postponed if acute intoxication is suspected [122]. The patient is referred to an expert in substance use disorders.
●Urgent surgery – Perioperative considerations for urgent surgery include:
•Severe hypertension and cardiac dysrhythmias may be precipitated during laryngoscopy with endotracheal intubation or by noxious surgical stimuli [29]. Prevention and/or treatment includes increasing anesthetic depth with intravenous or inhalation agents. Administration of vasodilators may be necessary (eg, hydralazine 5 mg to 10 mg bolus doses or a continuous infusion of nitroglycerin, nicardipine, or clevidipine for patients with persistent hypertension) (table 11) [29,129]. However, beta-blockers (metoprolol, propranolol, esmolol) are relatively contraindicated because unopposed alpha-adrenergic stimulation may be detrimental [29,130]. (See "Cocaine: Acute intoxication", section on 'Cardiovascular complications'.)
•Ketamine is avoided since it may potentiate cocaine's cardiovascular toxicity or cause myocardial depression if the patient has depleted catecholamine reserves due to hemorrhagic shock [131]. (See "General anesthesia: Intravenous induction agents", section on 'Disadvantages and adverse effects' and "General anesthesia: Intravenous induction agents", section on 'Drug-drug interactions'.)
•Although increasing anesthetic depth may help mitigate hypertensive responses to noxious stimuli, overall anesthetic requirements are not predictable [129,132].
•Succinylcholine is avoided when early postoperative tracheal extubation is planned. Plasma cholinesterase metabolizes both succinylcholine and cocaine; therefore, administration of succinylcholine may result in prolonged effects of cocaine as well as prolonged neuromuscular blockade [29,133,134]. Furthermore, in patients who develop hyperthermia and rhabdomyolysis (see "Cocaine: Acute intoxication", section on 'Other organ systems and complications'), succinylcholine may worsen hyperkalemia and cause life-threatening arrhythmias.
Rocuronium is a reasonable alternative to produce a more reliable neuromuscular blockade. (See "Rapid sequence induction and intubation (RSII) for anesthesia", section on 'Alternatives to succinylcholine'.)
•Severe hyperthermia and rhabdomyolysis may occur [135-139]. (See "Cocaine: Acute intoxication", section on 'Other organ systems and complications'.)
This syndrome may be confused with malignant hyperthermia during anesthesia. (See "Malignant hyperthermia: Diagnosis and management of acute crisis".)
Chronic use — Chronic cocaine use may result in friability of airway tissue, even in the absence of acute intoxication. Nasal intubation or insertion of a nasogastric tube should be performed cautiously [122].
Amphetamines and similar agents — Amphetamines and related agents (eg, methamphetamine, methylphenidate) have similar effects on the patient, although specific pharmacologic properties differ among these agents. Amphetamines and methylphenidate are readily available as prescription medications for attention deficit hyperactivity disorder but also have high abuse potential [122]. Methamphetamine is easily synthesized from over-the-counter medicines such as ephedrine and pseudoephedrine. The United States Department of Health and Human Services estimates that more than one million individuals use illicit methamphetamine each month, and an additional 1.5 million misuse stimulants such as amphetamines or methylphenidate [140].
Entactogens are recreational drugs that include the synthetic amphetamine 3, MDMA (“ecstasy”), and other novel amphetamine-based synthetic molecules, as well as the cathinone (eg, “bath salts”) [122]. In addition to stimulant effects, these agents also act as hallucinogens that enhance euphoria.
Potential adverse effects — Increased release of norepinephrine, dopamine, epinephrine, serotonin, and histamine, with stimulation of alpha- and beta-adrenergic receptors, causes the acute effects of amphetamines and similar-acting agents [122]. Common symptoms include hyper-alertness, pupillary dilation, increased body temperature, diaphoresis, and severe tachycardia with or without increased blood pressure (BP) may be present. Vascular compromise including vascular dissection, ischemic bowel or acute bleeding can occur [122]. Inhaling methamphetamines vapor (smoking “crack” cocaine) may result in thermal pulmonary injury, pulmonary edema, or pulmonary hypertension [122]. (See "Methamphetamine: Acute intoxication", section on 'Examination findings associated with intoxication and complications'.)
Perioperative considerations are described below.
Acute intoxication
●Elective surgery – Elective surgery is postponed if acute intoxication is suspected [122]. The patient is referred to an expert in substance use disorders.
●Urgent surgery
•Check serum electrolytes preoperatively and closely monitor electrolytes throughout the perioperative period. Severe hyponatremia associated with cerebral edema and seizures may occur in users who have ingested excessive water to compensate for profound sweating. Overly rapid correction of marked hyponatremia can lead to central pontine myelinolysis (now referred to as osmotic demyelination syndrome). Other electrolyte disturbances (eg, hypokalemia, hypermagnesemia, elevated anion gap acidosis) may also be present. Details regarding management of these abnormalities are discussed in separate topics:
-(See "MDMA (ecstasy) intoxication", section on 'Hyponatremia'.)
-(See "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia".)
•Severe increases in heart rate (HR) and BP may occur. Due to potential for an exaggerated hypertensive response or life-threatening dysrhythmias, sympathomimetic drugs such as ephedrine are avoided or administered with extreme caution (small incremental doses of 2.5 mg to 5 mg). Treat hypotension by administering direct-acting vasopressors in small incremental doses (phenylephrine, epinephrine, norepinephrine, or vasopressin for refractory hypotension).
-(See "Methamphetamine: Acute intoxication", section on 'Hypertension'.)
-(See "Methamphetamine: Acute intoxication", section on 'Tachycardia'.)
-(See "MDMA (ecstasy) intoxication", section on 'Cardiac effects'.)
•Regional anesthesia is not contraindicated. Possible advantages include better monitoring of neurological status [122]. Possible disadvantages include poor cooperation or development of acute agitation.
•General anesthesia may aid in controlling central nervous system (CNS) stimulation-related problems, reduce metabolic demand, and facilitate treatment of hyperthermia [122]. Acutely patients typically have increased anesthetic requirements [122]. However, overall anesthetic requirements are variable, and minimal alveolar concentration (MAC) requirements for volatile inhalation agents may be decreased [132,141].
-Ketamine is avoided, since the patient may have exaggerated increases in HR and BP. Conversely, some patients may be catecholamine depleted and more likely to experience the cardiac depressant effects of this agent [122].
-Succinylcholine is avoided to reduce the likelihood of precipitating hyperkalemic arrest due to muscle-injury-related rhabdomyolysis.
•Severe hyperthermia is possible and may be associated with rhabdomyolysis, disseminated intravascular coagulation, and hepatic and renal failure [122]. Active cooling measures such as cooling blankets and allowing evaporative loss may be necessary. In the perioperative setting, this syndrome may be confused with malignant hyperthermia during anesthesia (see "Malignant hyperthermia: Diagnosis and management of acute crisis"). Further details are available in other topics:
-(See "Methamphetamine: Acute intoxication", section on 'Hyperthermia'.)
-(See "MDMA (ecstasy) intoxication", section on 'Hyperthermia'.)
-(See "Acute amphetamine and synthetic cathinone ("bath salt") intoxication", section on 'Hyperthermia' and "Acute amphetamine and synthetic cathinone ("bath salt") intoxication", section on 'Musculoskeletal system'.)
•Postoperative care in a monitored setting (eg, prolonged post-anesthesia care unit [PACU] stay or intensive care unit [ICU]) is necessary to detect metabolic derangements and organ dysfunction including myocardial ischemia [122]. Monitoring for signs of withdrawal. These include anxiety, agitation, confusion, and psychosis, as well as lethargy, somnolence, and fatigue.
Chronic use — Chronic use of psychostimulants can lead to peripheral catecholamine depletion.
●Elective surgery – For patients who chronically and appropriately take prescription medications, continuation during the perioperative period is reasonable.
However, for those who chronically misuse recreational agents, elective surgery is postponed, and the patient is referred to an expert in substance use disorders [122].
●Intraoperative management – As with acute intoxication, hypotension is treated by administering direct-acting vasopressors (eg, phenylephrine, epinephrine, norepinephrine, or vasopressin for refractory hypotension) in small incremental doses. Ephedrine may not have the desired response.
●Postoperative management – Withdrawal after chronic amphetamine use can result in variable effects on sensitivity to anesthetic agents, as well as fatigue, lethargy, or other symptoms of withdrawal in the postoperative period [122].
Hallucinogens and dissociative drugs — Acute intoxication with hallucinogens (eg, LSD, phencyclidine [PCP], ketamine [eg, “vitamin K”,] mescaline) can have physiologic effects similar to the amphetamine-like stimulants described above (see 'Amphetamines and similar agents' above); however, these effects are usually less severe. These agents also have hallucinogenic activity through a combination of pharmacologic activities [122]. Details regarding management of acute intoxication with these agents are described in other topics. (See "Intoxication from LSD and other common hallucinogens" and "Phencyclidine (PCP) intoxication in adults".)
LSD and PCP — Perioperative considerations for patients acutely intoxicated with LSD or PCP includes:
●Elective surgery – Elective surgery is postponed [122]. The patient is referred to an expert in substance use disorders.
●Urgent surgery
•Anesthetic requirements are variable; however, MAC requirements for volatile inhalation agents are typically decreased [132,141].
•PCP or LSD intoxication may cause prolonged neuromuscular blocking effects after administration of succinylcholine due to inhibition of plasma cholinesterase activity; thus, succinylcholine is avoided if early postoperative extubation is planned [29]. Rocuronium is a reasonable alternative, producing a more reliable neuromuscular blockade. (See "Rapid sequence induction and intubation (RSII) for anesthesia", section on 'Alternatives to succinylcholine'.)
Ketamine — Perioperative considerations for patients acutely intoxicated with ketamine includes:
•Elective surgery – Elective surgery is postponed [122]. The patient is referred to an expert in substance use disorders.
•Urgent surgery
-Profound analgesia – (See "General anesthesia: Intravenous induction agents", section on 'Advantages and beneficial effects'.)
-Although ketamine causes little respiratory depression when appropriately used as a sedative-hypnotic anesthetic agent, higher "street" doses may cause respiratory depression [142]. Also, there are synergistic anesthetic and respiratory depressant effects when ketamine is concomitantly administered with a volatile inhalation anesthetic agent. (See "General anesthesia: Intravenous induction agents", section on 'Ketamine' and "Ketamine poisoning".)
-Hypertension may occur in patients who are taking chronically administered medications with noradrenergic effects such as amphetamines or norepinephrine reuptake inhibitors (eg, tricyclic antidepressants) if ketamine has also been administered [143]. (See "General anesthesia: Intravenous induction agents", section on 'Drug-drug interactions'.)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately:
●(See "Society guideline links: Alcohol consumption".)
●(See "Society guideline links: Alcohol use disorders and withdrawal".)
●(See "Society guideline links: Benzodiazepine use disorder and withdrawal".)
●(See "Society guideline links: Cannabis use disorder and withdrawal".)
●(See "Society guideline links: Cocaine use and cocaine use disorder".)
●(See "Society guideline links: General measures for acute poisoning treatment".)
●(See "Society guideline links: Opioid use disorder and withdrawal".)
●(See "Society guideline links: Stimulant use disorder and withdrawal".)
●(See "Society guideline links: Substance misuse in pregnancy".)
SUMMARY AND RECOMMENDATIONS
●Identifying preoperative substance use
•History – We ask all conscious preoperative patients about current or past history of alcohol and/or recreational drug use (table 1 and table 2). (See 'History and physical examination' above.)
•Testing – For patients suspected to be acutely intoxicated, rapid urine screening tests for opioids, benzodiazepines, cocaine, delta-9-tetrahydrocannabinol (THC; the psychoactive substance in marijuana), amphetamines, and certain hallucinogens are readily available at most hospitals. (See 'Testing' above.)
●Preoperative management – Before elective surgical procedures in patients with known substance use disorder (see 'Preoperative management' above):
-Ensure preoperative abstinence. Postpone elective surgery if acute intoxication is suspected. Refer the patient to an expert in substance use disorders.
-Evaluate for specific drug-related comorbidities (eg, liver dysfunction).
-Assess risk for withdrawal symptoms. Plan for postoperative monitoring for later withdrawal.
-Plan for adequate postoperative pain control, particularly in patients with opioid use disorder - (See 'Opioids' above.)
●Anesthetic considerations for specific substances – The tables summarize key considerations for anesthetic management of individuals with acute or chronic use of specific substances (table 3 and table 10). Additional details are provided above and in separate topics:
•Ethanol
-(See 'Ethanol and other alcohols' above.)
-(See "Identification and management of unhealthy alcohol use in the perioperative period".)
-(See "Management of moderate and severe alcohol withdrawal syndromes".)
•Cannabinoids
-(See 'Cannabinoids' above.)
-(See "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment".)
-(See "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects".)
-(See "Smoking or vaping: Perioperative management".)
-(See "Cannabis (marijuana): Acute intoxication".)
-(See "Synthetic cannabinoids: Acute intoxication".)
•Opioids
-(See 'Opioids' above.)
-(See "Acute opioid intoxication in adults".)
-(See "Opioid withdrawal: Clinical features, assessment, and diagnosis" and "Opioid withdrawal in adults in the emergency setting".)
•Benzodiazepines
-(See 'Benzodiazepines' above.)
-(See "Benzodiazepine use disorder".)
-(See "Benzodiazepine withdrawal".)
•Gamma hydroxybutyrate
-(See 'Gamma hydroxybutyrate' above.)
-(See "Gamma hydroxybutyrate (GHB) intoxication".)
-(See "Gamma hydroxybutyrate (GHB) withdrawal and dependence".)
•Cocaine
-(See 'Cocaine' above.)
-(See "Cocaine: Acute intoxication".)
•Amphetamines and similar agents
-(See 'Amphetamines and similar agents' above.)
-(See "Acute amphetamine and synthetic cathinone ("bath salt") intoxication".)
-(See "Methamphetamine: Acute intoxication".)
-(See "MDMA (ecstasy) intoxication".)
•Lysergic acid diethylamide (LSD) and phencyclidine (PCP)
-(See 'LSD and PCP' above.)
-(See "Intoxication from LSD and other common hallucinogens".)
-(See "Phencyclidine (PCP) intoxication in adults".)
•Ketamine
-(See 'Ketamine' above.)
-(See "General anesthesia: Intravenous induction agents", section on 'Ketamine'.)
-(See "Ketamine poisoning".)
