Anesthesia for patients with substance use disorder or acute intoxication

INTRODUCTION — The most common indication for surgery and anesthesia of an acutely intoxicated individual is trauma. Other types of surgical emergencies resulting from drug misuse 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 (eg, alcohol, opioids benzodiazepines, cannabinoids, cocaine, amphetamines, hallucinogens) or have a recent history of substance use disorder or dependency.

Screening and management of chronic alcohol use disorder is discussed in a separate topic. (See "Identification and management of unhealthy alcohol use in the perioperative period".)

Specific challenges for management of acute pain in patients with chronic opioid use disorder are discussed separately. (See "Management of acute pain in adults with opioid use disorder" and "Pain control in the critically ill adult patient", section on 'Tolerance, withdrawal, and hyperalgesia'.)

SCREENING FOR SUBSTANCE USE DISORDER

●History – As part of the routine preanesthesia evaluation, we ask all conscious preoperative patients about a current or past history of alcohol and/or recreational drug use. Individuals often refer to misused or illicit substances by street names, and these sometimes don't contain the expected agent [1]. Notably, acute intoxication is frequently associated with trauma, and multiple substances may be involved [2]. 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 [3]. Patients presenting for certain case types such as bariatric surgery [4], organ transplantation [5], and certain cardiovascular procedures [6,7] may also be statistically more likely to have a history of substance use disorder.

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. Knowing common names of various street drugs is helpful in asking specific queries about particular drugs. Studies have suggested that patients are reasonably honest about their drug use when asked directly. For example, a 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. Furthermore, negative predictive values were 90 to 95 percent in this study (ie, nearly all patients who denied drug use tested negative on the urine toxicology screen) [8]. In another study, 53 percent of trauma patients able and willing to respond to a routine drug use questionnaire who tested positive for cannabis on a toxicology screen had also self-reported their use [9].

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 [10]. 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) [11]. 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?" and by adding the explanation: "For instance, because of the experience or feeling it caused" if asked to clarify the meaning of "nonmedical reasons" [12]. A detailed discussion of screening tools for alcohol and other substance use disorders can be found separately. (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. Signs suggesting acute intoxication may 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 suspected 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 ([THC], the psychoactive substance in marijuana), amphetamines and similar agents, and certain hallucinogens. Typically, results are available within one hour. Details regarding testing for substance use disorders are available in separate topics. (See "Testing for drugs of abuse (DOAs)" and "Substance use disorders: Clinical assessment".)

Notably, 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. 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 [8]. 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 [13].

•False positives are possible with screening assays. For example, the hallucinogen phencyclidine (PCP) is structurally similar to compounds such as dextromethorphan (an over-the-counter cough suppressant). One study noted that the majority of positive screening results for phencyclidine could be explained by the ingestion of a drug other than PCP [14].

•A true positive result does not mean an individual is acutely intoxicated. For example, the cannabis plant from which marijuana is made contains other compounds besides THC (eg, cannabidiol [CBD]), which is frequently used in legal consumer products. Many CBD products contain trace amounts of THC that 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 relevant to the patient’s anesthetic management.

Also, THC and other drugs can cause a positive test days after last ingestion when the patient is no longer intoxicated and has no residual effects relevant for anesthetic management. Another example is a urine screen for cocaine metabolites that may remain positive for up to three days after acute intoxication. Also, amphetamines may be sampled from urine for up to six days after last taking the drug [15].

SEDATIVES

Alcohols

Ethanol — The most common acute intoxicant in trauma patients is the ethanol from fermented fruit or grains that causes the intoxicating effects of alcoholic beverages such as beer, wine, and 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 presentation with agitation rather than sedation. Pathophysiologic changes that may affect intraoperative care of patients with ethanol intoxication are summarized in the table (table 3). Details regarding general management of patients with acute ethanol intoxication are discussed separately (see "Ethanol intoxication in adults"). Also, severe withdrawal symptoms can occur. (See "Management of moderate and severe alcohol withdrawal syndromes".)

Considerations for anesthetic management of patients with known or suspected alcohol misuse include:

●Acute intoxication

•For elective cases, surgery is 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. Alcohol is known to delay gastric emptying in a non-dose-dependent fashion [17].

•For emergency cases, 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".)

●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 (GABA_A) [18,19]. During acute intoxication, dose requirements of anesthetic agents are decreased due to additive CNS depression, even in patients with chronic alcohol use disorder [18]. For this reason, doses of induction agents such as propofol should be decreased or avoided, especially in patients with hypotension or shock. During maintenance of anesthesia, volatile agents are carefully titrated since the minimum alveolar concentration (MAC) requirements are typically lower than those for nonintoxicated patients [18].

●Chronic misuse

•With chronic excessive consumption of ethanol, dose requirements for general anesthetics and adjuvant sedative and opioid agents may be increased in a patient who is not acutely intoxicated due to development of enzyme induction or cross-tolerance [20,21].

•Longstanding alcoholism may lead to liver dysfunction. The following considerations are prudent:

-Limit acetaminophen use in patients with chronic alcohol use disorder due to 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".)

-Titrate doses of neuromuscular blocking agents (NMBAs) 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'.)

Ethylene glycol — Ethylene glycol is a sweet-tasting, odorless substance found in antifreeze solutions. It may be ingested intentionally because of its sweet taste or for its intoxicating effects, which initially manifest as CNS depression similar to ethanol [24]. However, ethylene glycol is metabolized by alcohol dehydrogenase (ADH) to glycolaldehyde, and then by aldehyde dehydrogenase to glycolic acid, which causes the metabolic acidosis of acute ethylene glycol poisoning. Further metabolism into oxalic acid occurs, which can accumulate in renal tissue. Severe cardiopulmonary and renal toxicity with elevated osmolar gap, profound metabolic acidosis, and acute kidney injury can occur hours or days after acute intoxication.

Suspected or known ingestion of ethylene glycol should prompt thorough evaluation with laboratory studies including arterial blood gases and blood chemistries, as well as serum lactate, osmolality, and ethanol and ethylene glycol levels. A high osmolal or anion gap in the correct clinical context indicates ethylene glycol intoxication. The osmolal gap increases secondary to the initial accumulation of unionized alcohols, followed by an increase in the anion gap secondary to the formation of ionized metabolites. However, a normal/low osmolal gap or anion gap does not rule out ethylene alcohol intoxication. Details regarding general management of ethylene glycol poisoning are discussed in a separate topic. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis".)

Regarding anesthetic considerations:

●Dose requirements for anesthetic agents will likely be decreased similar to intoxication with ethanol or other CNS depressants. (See 'Ethanol' above.)

●Hyperventilation may be present as a physiologic response compensating for the severe metabolic acidosis that may occur with acute ethylene glycol poisoning. In most cases, it is prudent to continue hyperventilation during the perioperative period, and sodium bicarbonate is administered when necessary [25]. (See "Intraoperative management of shock in adults", section on 'Initial interventions' and "Bicarbonate therapy in lactic acidosis".)

●Since ethylene glycol is very rapidly absorbed from the gastrointestinal tract, intraoperative attempts at orogastric-tube aspiration or gastric lavage do little to reduce the ethylene glycol load.

Methanol — Methanol is a colorless, odorless, highly volatile chemical found in Sterno, windshield washer fluid, and homemade or adulterated alcohols. Intoxication may be achieved through ingestion, inhalation, or dermal absorption. Methanol is metabolized by ADH into a toxic metabolite, formic acid, that is responsible for the signs of methanol poisoning. Other than inebriation, these signs include headache, ataxia, and visual disturbances, which typically occur 6 to 24 hours following ingestion [26]. Details regarding general management of methanol poisoning are discussed in a separate topic. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis".)

Regarding anesthetic considerations, as with ethanol and other CNS depressants, dose requirements for anesthetic agents will likely be decreased. (See 'Ethanol' above.)

Isopropyl alcohol — Isopropyl alcohol, most commonly found in rubbing alcohol and hand sanitizers, is more potent than ethylene glycol or methanol. Unlike these other agents, isopropyl alcohol is a secondary alcohol that is metabolized to acetone and causes only mild acidemia. A key feature in isopropyl alcohol intoxication is an elevated osmolal gap with a normal anion gap. Therefore, if an elevated anion gap is noted in a surgical patient with known isopropyl alcohol intoxication, alternative explanations should be sought (eg, co-intoxication with another alcohol such as ethylene glycol or end-organ hypoperfusion causing lactic acidosis).

Details regarding general management of isopropyl alcohol poisoning are discussed in a separate topic. (See "Isopropyl alcohol poisoning".)

Regarding anesthetic considerations:

●Isopropyl alcohol poisoning does not cause prolonged sedation since it is quickly metabolized to acetone. CNS depression peaks at approximately 30 minutes after ingestion [27]. Therefore, dosing requirements for anesthetic agents should not be decreased unless emergency surgery is necessary immediately after ingestion or co-intoxicants were ingested.

●Since isopropyl alcohol is very rapidly absorbed from the gastrointestinal tract, intraoperative aspiration via an orogastric-tube or gastric lavage is unlikely to be beneficial.

Cannabinoids

Cannabis (marijuana) — Marijuana is a product of the plant Cannabis sativa containing substantial amounts of the potent psychoactive agent delta-9-tetrahydrocannabinol (THC). The prevalence of cannabis use disorder among surgical patients is estimated to be approximately 6 percent [28,29]. Details regarding general management of acute intoxication with cannabis are discussed in a separate topic. (See "Cannabis (marijuana): Acute intoxication".)

Use of cannabis or cannabinoids is increasingly common in patients presenting for surgery [30]. Some centers routinely screen all patients for cannabis use before surgery [30]. Perioperative considerations for management of patients with known or suspected cannabis use include:

●Preoperative management – We agree with 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 on the potential risks of continued perioperative use [30]. Elective surgery is postponed in patients with altered mental status or impairment of decision-making capacity due to acute cannabis intoxication. Even in the absence of overt intoxication, a delay of at least two hours after smoking cannabis is recommended to avoid increased risk of myocardial infarction (MI) [30-32]. For patients with recent consumption of cannabinoids via other routes of administration, risks are weighed against benefits of proceeding with elective surgery.

Various legal consumer products contain components other than THC such as cannabidiol (CBD) that are derived from the cannabis plant. CBD and many other cannabis-derived compounds may cause somnolence, but are unlikely to cause significant psychotropic or physiologic changes relevant for anesthetic management. However, some formulations of CBD products contain contaminants such as dextromethorphan or synthetic cannabinoids, which can have adverse hemodynamic effects [33]. (See 'Synthetic cannabinoids' below.)

●Anesthetic requirements – Some studies suggest that preoperative cannabis use is associated with increased tolerance to general anesthesia with sevoflurane [34], sedation with propofol and other agents [35,36], and increased postoperative opioid requirements [37,38]. However, acutely high levels of cannabis may decrease the MAC value of inhalation agents [39].

●Cardiovascular effects

•Acute intoxication or recent use may increase risk of perioperative MI [30-32].

•Acute intoxication with moderate doses of THC reduces parasympathetic activity with resultant tachycardia [38,40]. Thus, anesthetic drugs that increase heart rate such as ketamine, atropine, epinephrine, or ephedrine are avoided or used with caution [41].

•Myocardial depression and peripheral vasodilation may also occur. Thus, doses of anesthetic agents with myocardial depressant effects (eg, volatile inhalation agents) are titrated to avoid hypotension.

●Respiratory effects

•Cannabis can cause respiratory depression that is additive to the depressant effects of other anesthetic agents.

•Although the isolated compound THC itself causes bronchodilation, smoking or vaping marijuana may cause 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 [38,41-43]. These risks are similar to those seen after smoking or vaping nicotine or inhaling other irritants, as described in separate topics:

-(See "Smoking or vaping: Perioperative management", section on 'Perioperative risks of smoking'.)

-(See "Smoking or vaping: Perioperative management", section on 'Perioperative risks of vaping'.)

-(See "E-cigarette or vaping product use-associated lung injury (EVALI)".)

●Gastrointestinal effects

•Although cannabis is used to treat refractory nausea and vomiting in selected patients (see "Cannabis (marijuana): Acute intoxication", section on 'Medicinal use'), rare patients with long-standing daily use of marijuana may present with cannabinoid hyperemesis syndrome (CHS). 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. Since symptoms of CHS usually readily resolve within 24 to 48 hours after abstinence from marijuana [44], elective surgery is delayed. For emergency procedures, RSII is employed to prevent aspiration pneumonitis (see "Rapid sequence induction and intubation (RSII) for anesthesia"). Also, close perioperative monitoring of electrolytes is prudent.

●Postoperative management – If appropriate for the surgical procedure, multimodal analgesia incorporating regional analgesia is typically used for patients with acute cannabis intoxication or cannabis use disorder, and opioids are used as rescue medication [30]. Postoperatively, patients who consume cannabis routinely should be monitored for cannabis withdrawal symptoms.

Synthetic cannabinoids — Synthetic cannabinoids (eg, "spice", "K2") are artificially manufactured chemicals that affect the same receptors as THC and tend to produce similar psychoactive effects [45]. These agents may be undetectable in routine serum and urine toxicology testing [46]. Notably, manufacture and ingredients of synthetic cannabinoid products are not standardized. They 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. Details regarding general management of patients acutely intoxicated with synthetic cannabinoids are discussed separately. (See "Synthetic cannabinoids: Acute intoxication".)

Anesthetic considerations in patients using synthetic cannabinoids include:

●Cardiovascular, respiratory, and gastrointestinal effects are similar to those in cannabis use. (See 'Cannabis (marijuana)' above.)

●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 [46,47]. (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 [48]. (See "Synthetic cannabinoids: Acute intoxication", section on 'Life-threatening coagulopathy (brodifacoum adulteration)'.)

Gamma hydroxybutyrate — Gamma hydroxybutyrate (GHB) or its metabolic precursors (gamma butyrolactone and 1,4-butanediol [1,4-BD]) are CNS depressants used recreationally as an intoxicant. This agent is usually manufactured as a colorless, odorless liquid with a slightly salty taste. 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"). Severe withdrawal symptoms can occur, similar to those noted with alcohol or benzodiazepine withdrawal [49]. (See "Gamma hydroxybutyrate (GHB) withdrawal and dependence".)

Significant anesthetic implications for chronic users of GHB are unlikely if they are not 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

●Seizures or coma in rare cases

Benzodiazepines — Benzodiazepines bind GABA_A receptors in the 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 commonly misused illicit or prescription drug in the United States (approximately 2.2 percent of the population) [50]. (See "Benzodiazepine use disorder" and "Benzodiazepine poisoning".)

Anesthetic considerations in patients taking a benzodiazepine include:

●Acute benzodiazepine use

•Dose requirements for anesthetic agents will likely be decreased, similar to other CNS depressants.  

•Although benzodiazepines use typically does not cause significant hemodynamic changes, administration may result in mild hypotension or myocardial depression, especially if opioids are coadministered [51].

•Respiratory depression may be present.

●Chronic benzodiazepine use

•Dose requirements for general anesthetics and adjuvant sedative may be increased due to development of enzyme induction or cross-tolerance, similar to chronic ethanol use (see 'Ethanol' above). Also, postoperative opioid use and adverse events after surgery are more likely [52,53].

Nevertheless, we recommend continuing prescribed benzodiazepine medication during the perioperative period to avoid risk of withdrawal and because the anxiolytic effects are likely to be useful.

Opioids — Details regarding general management of patients with acute or chronic opioid use are discussed in separate topics:

●(See "Acute opioid intoxication in adults".)

●(See "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment".)

●(See "Opioid use disorder: Treatment overview".)

Perioperative appropriate 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'.)

Considerations for anesthetic management of patients with opioid use disorders include:

●Acute opioid intoxication

•Profound analgesia decreases dose requirements for anesthetic agents. In 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 [54]. (See "Perioperative uses of intravenous opioids in adults: General considerations", section on 'Acute opioid intoxication'.)

•Respiratory depression is typically present.

●Chronic opioid use

•Opioid tolerance and/or opioid-induced hyperalgesia (OIH) may be present in chronic opioid users, making perioperative pain control difficult to achieve [55,56]. Use of multimodal, opioid-sparing techniques is recommended. 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, clonidine). Adjuvant intravenous agents are continued through the postoperative period. (See "Perioperative uses of intravenous opioids in adults: General considerations", section on 'Chronic opioid use' and "Management of acute pain in the patient chronically using opioids for non-cancer pain", section on 'Options for pain management'.)

•Withdrawal symptoms can begin as soon as 6 to 18 hours after abstinence in chronic opioid users (table 4 and table 5). Even those enjoying good analgesic effect from neuraxial or regional anesthetic blockade will require maintenance administration of an opioid agent. For such patients, opioid agonists with high binding affinity for the mu opioid receptor (eg, hydromorphone, fentanyl, sufentanil) are typically preferred. (See "Opioid withdrawal in the emergency setting".)

•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 [57].

•Considerations for specific opioids and opioid antagonists

-Transdermal fentanyl patches – These patches typically need replacement every three days. However, transdermal absorption of fentanyl is affected by skin temperature, and forced air warming devices over the patches may cause unexpectedly high uptake or overdose [58]. Also, intraoperative fluid shifts may affect fentanyl distribution. Therefore, we remove fentanyl patches during surgery [59]. However, transcutaneous fentanyl patches are replaced or an equivalent "basal" narcotic is administered in the early postoperative period to avoid risk of withdrawal symptoms.

-Buprenorphine and buprenorphine/naloxone combinations – Buprenorphine is a long-acting partial opioid agonist that has an extremely high affinity for mu opioid receptors in the CNS, resulting in displacement of other opioid agonists from these receptors [54,60]. Buprenorphine is also an antagonist at the kappa opioid receptor and is an agonist at the nociception protein receptor. The partial opioid agonism at the mu receptor minimizes risk of development of opioid withdrawal symptoms during abstinence from use of other opioids and prevents full development of respiratory depression, while acting together with nociception protein receptor activation to stimulate breathing [54,61].

Formulations combining buprenorphine with naloxone are used to treat opioid use disorder. Notably, it may be extremely difficult to achieve adequate perioperative analgesia for patients taking this combination. Management of acute pain in such patients is discussed in detail in other topics. (See "Opioid use disorder: Pharmacologic management", section on 'Buprenorphine: Opioid agonist' and "Management of acute pain in adults with opioid use disorder".)

STIMULANTS

Cocaine — Cocaine is a local anesthetic with potent vasoconstrictive properties that can be smoked, snorted, or injected. Acute cocaine use can cause hypertensive medical or surgical emergencies such as intracranial hemorrhage; stroke; seizure-related trauma; aortic dissection; arterial vasoconstriction or thrombus formation with subsequent myocardial, pulmonary, or peripheral arterial infarction; or ischemic bowel. (See "Cocaine: Acute intoxication".)

Considerations for anesthetic management of patients acutely intoxicated with cocaine include:

●Severe hypertension and cardiac dysrhythmias may be precipitated during laryngoscopy with endotracheal intubation or by noxious surgical stimuli [41]. 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 6) [41,62]. However, beta-blockers (eg, metoprolol, propranolol, esmolol) are relatively contraindicated due to risk of inducing unopposed alpha-adrenergic stimulation [41,63]. (See "Cocaine: Acute intoxication", section on 'Cardiovascular complications'.)

●Although increasing anesthetic depth may help mitigate hypertensive responses to noxious stimuli, overall anesthetic requirements are variable and may not be increased [62,64].

●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 [65]. (See "General anesthesia: Intravenous induction agents", section on 'Disadvantages and adverse effects' and "General anesthesia: Intravenous induction agents", section on 'Drug-drug interactions'.)

●Succinylcholine is avoided when early postoperative 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 [41,66,67]. 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 [68-72]. (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".)  

Amphetamines and similar agents — Methamphetamine, amphetamine, methylphenidate, and 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") have similar effects on the patient, although there are pharmacologic differences among these agents. Amphetamines and methylphenidate are readily available as prescription medications for attention deficit hyperactivity disorder. 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 amphetamine and methylphenidate [73].

Stimulation of alpha- and beta-adrenergic receptors is primarily responsible for the acute effects of these agents. Common symptoms include hyper-alertness, pupillary dilation, increased body temperature, diaphoresis, and severe tachycardia with or without increased blood pressure (BP) may be present. Details regarding management of acute intoxication from these agents are available in other topics. (See "Methamphetamine: Acute intoxication" and "Acute amphetamine and synthetic cathinone ("bath salt") intoxication" and "MDMA (ecstasy) intoxication".)

Considerations for anesthetic management of patients acutely intoxicated with amphetamines include:

●Serum electrolytes should be checked preoperatively and closely monitored 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 "Acute amphetamine and synthetic cathinone ("bath salt") intoxication", section on 'Electrolyte disturbances and other effects'.)

•(See "MDMA (ecstasy) intoxication", section on 'Hyponatremia'.)

•(See "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia".)

•(See "Manifestations of hyponatremia and hypernatremia in adults", section on 'Osmolytes and cerebral adaptation to hyponatremia'.)

●Severe increases in heart rate 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 (eg, in small incremental doses of 2.5 mg to 5 mg). (See "Methamphetamine: Acute intoxication", section on 'Hypertension' and "Methamphetamine: Acute intoxication", section on 'Tachycardia' and "Acute amphetamine and synthetic cathinone ("bath salt") intoxication", section on 'Cardiovascular system' and "MDMA (ecstasy) intoxication", section on 'Cardiac effects'.)

●Severe hyperthermia is possible and may be associated with rhabdomyolysis, disseminated intravascular coagulation, and hepatic and renal failure, as noted in separate 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'.)

This syndrome may be confused with malignant hyperthermia during anesthesia. (See "Malignant hyperthermia: Diagnosis and management of acute crisis".)

●Overall anesthetic requirements are variable, but minimal alveolar concentration (MAC) requirements for volatile inhalation agents are typically decreased [64,74].

Hallucinogens and dissociative drugs — Acute intoxication with hallucinogens (eg, lysergic acid diethylamide [LSD], phencyclidine [PCP], ketamine, 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. Details regarding management of acute intoxication with these agents are described in other topics:

●(See "Intoxication from LSD and other common hallucinogens".)

●(See "Phencyclidine (PCP) intoxication in adults".)

●(See "Ketamine poisoning".)

Considerations for anesthetic management of acutely intoxicated patients include:

●LSD and PCP

•Anesthetic requirements are variable, but MAC requirements for volatile inhalation agents are typically decreased [64,74].

•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 [41]. 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

•Although ketamine causes little respiratory depression when appropriately used as a sedative-hypnotic anesthetic agent, higher "street" doses may cause respiratory depression [75]. Also, there are synergistic anesthetic and respiratory depressant effects when ketamine is coadministered with a volatile inhalation anesthetic agent. (See "General anesthesia: Intravenous induction agents", section on 'Ketamine'.)

•Hypertension may occur in patients taking chronically administered medications with noradrenergic effects such as amphetamines or norepinephrine reuptake inhibitors (eg, tricyclic antidepressants) [76]. (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".)

●(See "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

●Preanesthesia screening – As part of the routine preanesthesia evaluation, we ask all conscious preoperative patients about a current or past history of alcohol and/or recreational drug use (table 1 and table 2). For patients suspected to be acutely intoxicated, rapid urine screening tests for opioids, benzodiazepines, cocaine, tetrahydrocannabinol (THC; the psychoactive substance in marijuana), amphetamines and similar agents, and certain hallucinogens are readily available at most hospitals. Although not always helpful, results are usually available within one hour. (See 'Screening for substance use disorder' above.)

●Ethanol – (table 3) (see 'Ethanol' above)

•Acute intoxication

-For elective cases, delay surgery until the effects of acute intoxication are no longer present, and to allow time for gastric emptying to occur.

-For emergency cases, we typically employ rapid sequence induction and intubation (RSII) to prevent aspiration pneumonitis since ethanol causes delayed gastric emptying of both alcohol and food.

-Likely reduction in dose requirements for anesthetic agents.

•Chronic misuse

-Possible increases in dose requirements for general anesthetics and adjuvant sedative and opioid agents due to development of enzyme induction or cross-tolerance.

-Liver insufficiency such that doses of neuromuscular blocking agents (NMBAs) should be titrated, and doses of acetaminophen should be limited.

●Cannabinoids – Considerations for anesthetic management include:  

•Cannabis (marijuana) – (see 'Cannabis (marijuana)' above):

-Cardiovascular effects including tachycardia, myocardial depression, and peripheral vasodilation.

-Respiratory effects including respiratory depression, as well as bronchospasm if marijuana is smoked or vaped.  

-Gastrointestinal effects including antiemetic effects in most patients. Rarely, development of cannabinoid hyperemesis syndrome (CHS) necessitates RSII to prevent aspiration pneumonitis, as well as close monitoring of electrolytes.

•Synthetic cannabinoids – (see 'Synthetic cannabinoids' above)

-Cardiovascular, respiratory, and gastrointestinal effects similar to cannabis.

-Unlike cannabis, serious life-threatening toxicity including coma, seizures, severe or malignant hyperthermia, rhabdomyolysis, and acute kidney injury that may occur with severe intoxication.

-In rare cases, coagulopathy and severe bleeding unresponsive to vitamin K or fresh frozen plasma.

●Gamma hydroxybutyrate – (see 'Gamma hydroxybutyrate' above)

•Likely reduction in dose requirements for anesthetic agents

•Respiratory depression

•Seizures or coma in rare cases

●Benzodiazepines − (see 'Benzodiazepines' above)

•Acute use

-Decreased dose requirements for anesthetic agents

-Mild hypotension

-Respiratory depression

•Chronic use

-Possible increase in dose requirements for general anesthetics and adjuvant sedative agents due to development of enzyme induction or cross-tolerance. Nevertheless, we continue any prescribed benzodiazepine medication during the perioperative period to alleviate anxiety and avoid withdrawal.

●Opioids – (see 'Opioids' above)

•Acute intoxication

-Decreased dose requirements for anesthetic agents due to profound analgesia

-Respiratory depression

•Chronic use

-Difficulties with perioperative pain control due to development of tolerance or opioid-induced hyperalgesia (OIH). We employ multimodal, opioid-sparing techniques. These may 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 (IV) agents with analgesic properties (eg, nitrous oxide, ketamine, dexmedetomidine, clonidine).

-Withdrawal symptoms, which can begin as soon as 6 to 18 hours after abstinence (table 4 and table 5). Opioid agonists with high binding affinity for the mu opioid receptor (eg, hydromorphone, fentanyl, sufentanil) are typically preferred.  

●Cocaine – (see 'Cocaine' above)

•Severe hypertension and cardiac dysrhythmias during laryngoscopy or noxious surgical stimuli. Prevention or treatment includes increasing anesthetic depth with IV or inhalation agents and/or administering vasodilators (table 6). Beta-blockers (eg, metoprolol, propranolol, esmolol) are avoided to avoid unopposed alpha-adrenergic stimulation.

•Avoid ketamine which may potentiate cocaine's cardiovascular toxicity.

•Avoid succinylcholine if early postoperative extubation is planned since plasma cholinesterase metabolizes both succinylcholine and cocaine with prolongation of neuromuscular blockade. Also, hyperthermia and rhabdomyolysis may be exacerbated.

•Severe hyperthermia and rhabdomyolysis.

●Amphetamines – (see 'Amphetamines and similar agents' above)

•Serum electrolytes are closely monitored since hyponatremia if excessive water was ingested to compensate for profound sweating. Other electrolyte disturbances (eg, hypokalemia, hypermagnesemia, elevated anion gap acidosis) may also be present.

•Severe increases in heart rate and blood pressure. Avoid sympathomimetic drugs such as ephedrine (or administer with extreme caution) due to potential for an exaggerated hypertensive response or life-threatening dysrhythmias.

•Severe hyperthermia and associated rhabdomyolysis, disseminated intravascular coagulation, and hepatic and renal failure.

●Hallucinogens – (see 'Hallucinogens and dissociative drugs' above)

•Lysergic acid diethylamide (LSD) and phencyclidine (PCP)

-Avoid succinylcholine if early postoperative extubation is planned since plasma cholinesterase is inhibited by LSD or PCP.

•Ketamine

-Although ketamine causes little respiratory depression when appropriately used as a sedative-hypnotic anesthetic agent, higher "street" doses and coadministration with other anesthetic agents may cause respiratory depression.

-Hypertension may occur in patients taking chronically administered medications with noradrenergic effects (eg, amphetamines or norepinephrine reuptake inhibitors such as tricyclic antidepressants).