Abstract
Substance-use disorders (SUDs) represent a major public health concern. The increased prevalence of SUDs within the general population has led to more patients with SUD being admitted to intensive care units (ICUs) for an SUD-related condition or with SUD as a relevant comorbidity. Multiprofessional providers of critical care should be familiar with these disorders and their impact on critical illness. Management of critically ill patients with SUDs is complicated by both acute exposures leading to intoxication, the associated withdrawal syndrome(s), and the physiologic changes associated with chronic use that can cause, predispose patients to, and worsen the severity of other medical conditions. This article reviews the epidemiology of substance use in critically ill patients, discusses the identification and treatment of common intoxication and withdrawal syndromes, and provides evidence-based recommendations for the management of patients exposed to chronic use.
Substance-use disorders (SUDs) have become a major public health concern, and among individuals aged 12 and older, the rates of SUD have nearly doubled from 21.6 million in 2013 to 48.7 million (14.4% of the population) in 2022. (https://www.samhsa.gov/data/sites/default/files/reports/rpt42731/2022-nnr-briefing-slides.pdf) This increase has paralleled a rise in deaths due to drug-related overdose from <20,000 in 1999 and 52,404 in 2015 to 109,000 in 2022 (https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm). Figure 1 depicts recent trends in substance use.
In a 2020 study of admissions to a medical intensive care unit (ICU) at a large county hospital, approximately 25% of all admissions to the ICU were SUD-related.1 Such patients require ICU care due to SUD-related acute overdose or withdrawal or are admitted for other reasons but have an underlying SUD. In a prospective 2020 study of a mixed medical and surgical ICU population in Norway, 25% had SUD, and 59% were admitted to the ICU for substance misuse-related issues.2 Critically ill patients with SUD have higher rates of multisystem organ failure, mechanical ventilation, utilization of other ICU level resources, and longer ICU lengths of stay (LOS).1,3 Also, the presence of an SUD may significantly complicate the management of a patients’ primary illness by masking or exacerbating the symptoms, as seen in patients with acute withdrawal, where excessive sympathetic activity may complicate the management of other medical conditions. Recognizing and treating substance misuse-related complications may thus play an important role in critical care even for an unrelated admission diagnosis. In this article, we discuss the epidemiology, management strategies for acute intoxication and withdrawal syndromes, and address general treatment considerations for critically ill patients with SUD.
ALCOHOL-USE DISORDER
Alcohol-use disorder (AUD) is among the most prevalent psychiatric disorders globally, affecting about 8.6% of men and 1.7% of women, and is more common in high-income countries.4 In the United States, AUD affects 7.6% of men and 4.1% of women older than 18 years, comprises 10% to 20% of ICU admissions, and results in an annual estimated cost of $249 billion.1 Patients with acute alcohol intoxication may require ICU care due to altered mental status and tracheal intubation to protect the airway. Traumatic injuries requiring ICU admission are also common in patients with AUD. A 2001 prospective cohort study found that trauma patients with positive blood alcohol concentration, even in nontoxic range, were sicker at admission and had an increased need for ICU admission than patients without alcohol intoxication (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.01–3.46).5 Similarly, in surgical patients, chronic alcohol use is associated with more postoperative (pneumonia, surgical site infections, sepsis, poor wound healing, etc) and cardiac complications (heart failure, ischemia, arrhythmias, etc), predisposing them to a higher likelihood of postoperative ICU admission. Once in the ICU, patients with AUD often require increased doses of sedatives and opioids, tend to have a longer ICU LOS, and have higher morbidity and mortality.6 Compared to patients without AUD, they are more likely to develop ICU-related complications, increased health care utilization, and worse outcomes.7
Alcohol-Withdrawal Syndrome
Alcohol is a central nervous system (CNS) depressant and acts via stimulation of gamma-aminobutyric acid (GABA) and inhibition of glutamate pathways. Such alterations in neurotransmission lead to many of the symptoms associated with alcohol withdrawal. While most individuals experience minor withdrawal symptoms that self-resolve, a small subgroup experience a more complicated syndrome including seizures, hallucinations, and delirium tremens. Approximately one-third of patients hospitalized for alcohol-withdrawal syndrome (AWS) require ICU admission to manage complications such as respiratory failure (due to alcohol-induced sedation), delirium tremens, infections, cirrhosis, or gastrointestinal bleeding.8 Patients with AUD may need ICU admission for reasons other than AWS, and manifest symptoms during their ICU stay. Although early identification and treatment for AWS reduces the risk of progressing to a more severe form, the symptoms of AWS are nonspecific, a clinical history can be difficult to obtain, and concurrent AWS may be difficult to diagnose and often attributed to other medical conditions such as ICU delirium. Patients with AWS have longer ICU stays, longer duration of mechanical ventilation, higher costs, and a higher mortality rate compared to ICU patients without AWS.8,9 In a 2010 study, the overall mortality rate in patients hospitalized with AWS was 6.6%, compared to 62% in those requiring ICU admission. The need for tracheal intubation was an independent variable associated with mortality, particularly in those requiring ICU care for pneumonia (OR, 8 [95% CI, 3–21.3], P < .001).10
Management of AWS in the ICU is similar to noncritically ill hospitalized patients and involves both supportive and pharmacologic therapy, but with important differences. Benzodiazepines are the cornerstone of pharmacologic management of autonomic and neurologic disturbances in AWS and are commonly administered in a symptom-triggered manner using scales such as the Revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). Benzodiazepines decrease symptom severity and the duration and frequency of seizures associated with AWS. In critically ill patients, benzodiazepine use predisposes patients to delirium and is associated with increased ICU and hospital LOS and overall increased morbidity and mortality.11 In some patients, withdrawal symptoms may not be controlled despite aggressive use of benzodiazepines, thus leading to benzodiazepine-resistant alcohol withdrawal (RAW).
To decrease complications and treat RAW, alternative treatments for AWS are often used. Phenobarbital is a guideline recommended for monotherapy in patients with contraindications to the use of benzodiazepines (patients with prior hypersensitivity reactions), or those with severe AWS, seizures, or hallucinations.12 In patients affected by severe AWS, the combination of benzodiazepines and barbiturates can decrease the need for mechanical ventilation and may decrease ICU LOS when compared to benzodiazepine therapy alone.13 Phenobarbital-based pathways may be more efficient and simpler to use, with requirements for mechanical ventilation noninferior to benzodiazepine-based pathways.14 However, a 2020 retrospective analysis showed no significant difference in adverse events in ICU patients with AWS receiving either phenobarbital adjunct to lorazepam or lorazepam alone.15 Prospective trials with standardized protocols are needed to better understand the role of phenobarbital in benzodiazepine-resistant and complicated AWS. To further complicate AWS treatment, a 2023 case report describes phenobarbital-resistant AWS, highlighting the role of adjunctive therapies.16
Dexmedetomidine is an attractive adjunct in nonintubated patients as it decreases autonomic hyperactivity and avoids respiratory compromise. Retrospective studies suggest a benzodiazepine-sparing effect and a lowering of alcohol severity scores.17,18 However, a lack of GABAergic effect, and hemodynamic instability due to bradycardia limits its use as a primary treatment. If used as an adjunct, dexmedetomidine therapy should always include additional GABAergic medications as it may mask withdrawal symptoms and predispose patients to life-threatening seizures. Ketamine attenuates N-methyl-D-aspartate (NMDA) receptor stimulation due to alcohol withdrawal and may also be an alternative when GABAergic agents such as benzodiazepine and/or barbiturates are inadequate in controlling symptoms. Two small studies have observed that adjunctive ketamine in patients with RAW improved symptom control, decreased benzodiazepine requirements, shortened ICU LOS, and reduced the likelihood of intubation.19,20 Baclofen, a GABAB receptor agonist has also been used as an adjunct although it has not been evaluated for safety in critically ill patients, and a 2015 Cochrane review on use of baclofen for AWS identified only 2 randomized clinical trials (RCTs) with a total of 81 participants.21 In addition, because the drug requires enteral access, it may be difficult to administer to ICU patients.
Data on the use of other anticonvulsants such as carbamazepine (CBZ), valproic acid (VPA), gabapentin, pregabalin, tiagabine, and vigabatrin are promising.22 However, none of these drugs have Food and Drug Administration (FDA) approval for the prophylaxis or treatment of AWS. Propofol has benefits in the management of RAW, as it works on a different binding site than benzodiazepines on the GABAa receptor. When propofol is used for sedation in mechanically ventilated patients with AWS, the need for additional administration of benzodiazepine or phenobarbital is still unclear.23 Future studies involving these adjunctive medications are needed to evaluate optimal dosing, timing of initiation, and utility in the therapy for RAW. Supplemental Digital Content 1, Supplemental Table 1, https://links.lww.com/AA/E877, lists some of the commonly used adjuvant drugs used in the management of AWS, and Figure 2 proposes a suggested algorithm for the management of AWS.
OPIOID-USE DISORDER
The prevalence of opioid-use disorder (OUD) in the United States is estimated to be between 2.04% and 2.77%, suggesting that about 6.7 to 7.6 million adults are currently living with OUD.24 Critical care specialists are challenged with not only managing acute opioid overdose, but also providing sufficient analgesia to patients impacted with OUD, and appropriately initiating medications for OUD (MOUD), and managing withdrawal. Minimizing ICU-acquired opioid dependence and chronic pain disorders after critical illness may also reduce the incidence of postintensive care syndrome (PICS) and improve outcomes in ICU survivors.
Acute Opioid Overdose
Patients with acute opioid overdose may require tracheal intubation and invasive mechanical ventilation if they cannot protect their airway or if the respiratory depression is severe. If intubation is needed, a rapid sequence technique is often applied due to an unclear fasting status and risk of aspiration. Volume resuscitation, vasopressor, and/or inotropic support may be required due to hemodynamic compromise resulting from negative inotropic and chronotropic effects, and opioid-induced vasodilation. Invasive hemodynamic monitoring and point-of-care ultrasound can help distinguish the etiology of cardiovascular collapse. Naloxone reverses μ-receptor–related effects of opioid intoxication and remains the cornerstone of treatment of acute opioid overdose in conjunction with supportive measures. High-dose naloxone and/or naloxone administration to opioid-dependent or opioid-tolerant patients may precipitate acute withdrawal, leading to pulmonary edema, and cardiac arrhythmias. Critical care specialists should also be cautious of possible xylazine inclusion in fentanyl, heroin, and other illicit drug overdoses. Xylazine is a nonopioid sedative used for analgesia and muscle relaxation exclusively in veterinary medicine. Its chemical structure resembles clonidine, and it acts as a central α-2 agonist. The addition of xylazine to opioids may potentiate the sedative effects of opioids, and accentuate opioid-induced hypotension, respiratory depression, and bradycardia. Xylazine effects are not reversible with naloxone. Xylazine exposure should be suspected if opioid-intoxicated patients are not responding to naloxone or when signs or symptoms of xylazine exposure (eg, severe, necrotic skin ulcerations) are present.25
Managing an Opioid-Tolerant Patient
With the increasing prevalence of OUD, critical care specialists are likely to encounter patients with varying degrees of opioid tolerance during treatment for other critical illnesses. Pain is ubiquitous in the ICU and most critically ill patients experience pain from routinely performed procedures and interventions during their ICU stay. Postoperative patients have additional pain related to their surgical incision, surgical drains, and tubes. Pain is often inadequately treated in the ICU, and is one of the most commonly recalled memories by patients of their ICU stay.26 Undertreatment of pain is common in patients with OUD due to fear of causing adverse effects when using higher doses of opioids, and difficulty in assessing the severity of opioid dependence.27 Patients with OUD must be closely monitored for inadequate pain control and for early signs and symptoms of opioid withdrawal. To appropriately treat pain in this complex patient population, a history of OUD is helpful but may be challenging in patients unable to communicate. Identifying OUD may require discussions with family members, and medicine reconciliation of prescription opioids. Once OUD is identified, the next step is to estimate the daily use of opioids before ICU admission. An equivalent amount of long-acting opioids should then be administered to address the baseline need, along with additional short-acting opioids to address acute pain. Patients with a history of chronic opioid use have a higher opioid requirement due to tolerance and require frequent reevaluation of their opioid needs and escalation of opioid doses as needed.
Some patients may be maintained on MOUD such as methadone, buprenorphine, and naltrexone. Temporarily discontinuing these medications in a previously stable patient, while concurrently prescribing an opioid agonist for pain may increase the risk for relapse.28 For this reason, patients who are receiving MOUD should continue their regimen if circumstances allow, with supplemental analgesia as indicated.29 Buprenorphine, a partial μ-opioid receptor agonist and antagonist at the kappa-opioid receptor, is a potent analgesic that may provide effective analgesia for acute pain. However, addition of short-acting full μ-agonists, at higher doses may be needed to improve analgesia. Similarly, patients receiving a combination of buprenorphine and naloxone would also require higher doses of pure μ-agonist opioids due to cross- tolerance and increased sensitivity to pain. Such patients should be closely monitored for the risks and potential side effects of additional opioid exposure. Methadone is a full μ-opioid receptor agonist and a weak agonist at the NMDA receptor. Before admission doses of methadone should be continued during the ICU stay if feasible. Temporarily increasing the methadone dose or dosing frequency may be effective for managing acute pain. Splitting the daily methadone dose across 3 to 4 doses per day is also an option, and can maximize the analgesic properties of this medication.30 Patients receiving methadone for OUD may experience increased pain levels and opioid requirements due to potential hyperalgesia and tolerance.31 Naltrexone, another MOUD, is a μ-opioid receptor antagonist and blocks μ-receptor effects, rendering exogenous opioids ineffective. Although acute pain in patients on naltrexone can be managed with opioids, higher doses may be required, necessitating heightened safety monitoring for adverse events. Multimodal treatment involving nonopioid interventions (eg, nonsteroidal anti-inflammatory agents, acetaminophen, gabapentin, regional anesthesia, etc) is recommended by consensus guidelines.11 However, many ICU patients may not be able to receive medications via the enteral route, and alterations in renal and hepatic function pose additional challenges. Supplemental Digital Content 2, Supplemental Table 2, https://links.lww.com/AA/E878, lists some of the opioid-sparing interventions and their limitations within the critically ill patient population.
Although very high doses of opioids may be needed in patients with OUD to control acute pain, managing pain and withdrawal is important in ensuring receipt of life-saving treatment for such patients in the ICU. Comprehensive reviews on acute pain management in critically ill patients with OUD and consensus guidelines on the management of postoperative pain in patients with chronic pain, opioid tolerance, and SUD are available.29,32,33 However, guidance addressing specific sedation needs in this patient population is lacking, and most centers do not have dedicated addiction care teams to help with short- and long-term management.34
Iatrogenic Opioid Withdrawal Syndrome
Critically ill patients, particularly those receiving mechanical ventilation, often receive continuous infusions of opioids to improve mechanical ventilation synchrony and minimize agitation. In a prospective, observational study in 44 ICUs in France, almost 90% of patients receiving mechanical ventilation received opioid infusions.35 Although current recommendations are to wean the sedative and analgesic infusions on a regular basis to test readiness for extubation,11 this strategy may not be always possible, and the use of opioid infusions for extended periods can lead to iatrogenic opioid withdrawal syndrome (IOWS). IOWS is defined as an opioid withdrawal syndrome in critically ill inpatients due to abrupt reduction or cessation in opioid administration initially prescribed during hospitalization.36 It occurs in about 15% to 40% of critically ill patients who receive opioid infusions, and has been reported in medical, trauma, surgical, and burn ICUs.37–39 Development of IOWS may be limited using light levels of sedation, daily spontaneous awakening trials, and opioid administration based on validated pain-assessment tools. Treatment of patients that develop IOWS includes reinstitution of the opioid infusion with slower reductions in the rate (25% per day if infusions are used for >7 days) and symptomatic management. The use of an α-2 agonist may be considered as an adjunct for symptom control.36
ICU-Acquired Opioid Dependence
A significant number of critically ill patients receive opioid infusions during their ICU stay,40,41 and scheduled enteral opioids are often utilized as a strategy for weaning from continuous opioid infusions.42,43 However, opioid use in the ICU may predispose patients to a new onset OUD on hospital discharge.41,44 Preadmission benzodiazepine use, a diagnosis of sepsis, receipt of an IV opioid infusion for >4 hours, and mechanical ventilation have been independently associated with new opioid prescriptions at hospital discharge.41 Similarly, patients with a longer hospital stay and more days between ICU and hospital discharge were more likely to be discharged on a new opioid prescription.41 These patients are also at risk of new persistent opioid use, the incidence of which was recently estimated at nearly 4% in postsurgical ICU survivors45 and 2.6% in those who received invasive mechanical ventilation in the ICU.46 Chronic opioid use amongst ICU survivors may also be independently associated with mortality, both in patients who did and did not have preadmission opioid use.47 While current evidence suggests that opioid prescription on hospital discharge is common among ICU survivors and can contribute to new persistent opioid use and mortality, further research into the factors that contribute to this phenomenon and the impact of interventions such as reducing ICU opioid use is needed.
CANNABIS-USE DISORDER
Cannabis is the third most used controlled substance worldwide (after alcohol and nicotine) and one 2018 report estimated that 3.9% of the global adult population had used cannabis in the previous year.48 In the United States, marijuana is the most widely used recreational drug with an estimated 49.6 million Americans 12 years or older reporting at least one use in 2020. This prevalence accounts for 17.9% of the population, an almost 2-fold increase from 11% in 2002.49 Cannabis-use disorder (CUD) is broadly defined as the inability to stop consuming cannabis even when it has caused physical or psychological harm.50 According to the most recent global estimate 22.1 million persons met diagnostic criteria for CUD in 2016 (289.7 cases per 100,000 people).51 Persons with CUD are more likely to have other SUDs,52 and clinicians should consider the possibility of polysubstance use when encountering a patient with CUD. The crossing or cousage of marijuana with amphetamines, synthetic cannabinoids (K2, spice), or alcohol is common and may account for physiologic symptoms not attributable to cannabis intoxication or withdrawal alone and may require alternative management.
Acute intoxication from cannabis use is rare. However, in some individuals, cannabis use has been associated with an immediate psychosis that can last longer than the period of acute intoxication. This cannabis-induced acute persistent psychosis is characterized by hallucinations, paranoia, delusions, depersonalization, emotional lability, amnesia, confusion, and disorientation, which follows the ingestion of large doses of cannabis.53 Symptoms of cannabis withdrawal include anxiety, irritability, anger or aggression, disturbed sleep/dreaming, depressed mood, and loss of appetite, but are typically mild and rarely cause physiologic derangements. Cannabis withdrawal treatment in the ICU typically consists of symptom management and/or agonist substitution or replacement therapy (ART).54 Substitution therapies involve the use of dronabinol or nabiximols that target the cannabinoid CB1 receptor. These drugs reduce the severity of cannabis withdrawal symptoms, and patients who previously reported severe withdrawal symptoms or failed attempts to quit because of withdrawal symptoms may benefit.54 Medications to address cannabis withdrawal symptoms have not shown clear benefit, and further studies are needed before their routine use can be recommended in the ICU.55Figure 3 depicts a proposed algorithm for the management of cannabis intoxication and withdrawal.
The increasing liberalization of cannabis for recreational use is likely to lead to more patients with CUD and chronic cannabis use presenting to the ICU. A review of the Trauma Quality Improvement Program database for 2017 found that 16% of critically ill trauma patients had a (+) cannabis screen and a similar study in Arizona found a 7% incidence.56,57 Overall, when compared to their negative drug screen-matched cohort, patients with a positive marijuana screen had a greater likelihood of requiring mechanical ventilation, but not an increase in ICU or hospital LOS.56–58 With respect to nonneurological effects of cannabis, Delta-9-THC, the primary psychoactive substance in marijuana, increases the risk of venous thromboembolism (VTE), possibly due to hypercoagulability from coagulation cascade modulation or endothelial lining disruption.59 While case reports suggest that marijuana use increases the risk of acute myocardial infarction (MI),60 systematic studies have not observed this increased risk.61 Further research is needed to examine the increased risk of coagulation-related complications in marijuana users who develop critical illness. Outpatients who regularly use cannabis also require a higher amount of procedural sedation,62 and it is likely that patients in the ICU may also require more sedation for procedures but whether sedation requirements are higher for cannabis users who require mechanical ventilation is not yet known. Long-term effects of inhaled cannabis on the pulmonary system may also be relevant to critical care. Current evidence does suggest that chronic marijuana users are more likely to develop cough, increased sputum production, and wheezing.63 A connection between marijuana use and increased risk of pneumonia has been suggested due to the destruction of ciliated epithelium and the immunosuppressive effects of tetrahydrocannabinol (THC) on alveolar macrophages.63
NICOTINE-USE DISORDER
Tobacco use continues to be the leading cause of preventable disease and death in the United States, accounting for approximately 20% of deaths64 and costing >$300 billion annually.65 The prevalence of tobacco use in critically ill patients varies, and it is estimated that approximately 25% to 47% of patients admitted to the ICU are active smokers.66,67 When compared to nonsmokers, smokers have an increased incidence of acute respiratory distress syndrome (ARDS), higher rates of postoperative complications, and on average, a longer ICU LOS, more ventilator-associated days, and higher mortality rates.68–71 During the COVID-19 pandemic, current smokers were at greater risk of severe complications and higher mortality rates compared to former and never smokers.72 While it is unclear if cigarette smoking is a risk factor for delirium,73 active smokers in the ICU present with more agitation, self-removal of devices, need for physical restraint, and receive higher doses of sedatives, neuroleptics, and analgesics.66
Nicotine-Withdrawal Syndrome
Abrupt cessation of nicotine in long-term users may cause withdrawal symptoms beginning as early as 4 to 24 hours after last consumption with symptoms peaking around the third day. Since nicotine acts on acetylcholine receptors, the symptoms reflect the ubiquitous influence of cholinergic transmission in the nervous system. The severity of withdrawal symptoms is largely determined by the duration, dose, and the form in which nicotine is consumed. In addition, certain genetic alterations predispose individuals to consume larger amounts of nicotine more frequently—as well as to develop more severe symptoms of withdrawal when trying to quit.74 Both the presence and withdrawal of nicotine increase the risk of delirium and agitation in critically ill patients resulting in adverse events including undesired removal of lines and tubes and an increased need for pharmacologic and physical restraints.75,76
Nicotine replacement therapy (NRT) has been effective in reducing withdrawal symptoms in the treatment of tobacco addiction in the community.77 However, research regarding the use of NRT in the critically ill population has yielded conflicting results. A 2018 randomized trial78 found that NRT did not affect mortality or the number of serious adverse events, but did increase the time alive with normal brain function (without delirium, sedation, or coma). In contrast, an older 2013 trial79 found nonsignificant trends toward decreased ICU LOS, ventilator days, and days on sedation. Both trials faced challenges with recruitment limiting statistical power and larger well-powered studies are needed to better assess the safety and utility of NRT in the ICU. No current risk versus benefit analysis exists regarding the use of α2-adrenergic receptor agonists to manage delirium or agitation in critically ill tobacco users, and the impact of α2 agonists on hemodynamics and other outcomes in critically ill smokers also needs further exploration. In the absence of concrete data, NRT should be considered on a case-by-case basis, preferably in consultation with an addiction medicine specialist.
STIMULANTS: COCAINE AND AMPHETAMINES
The prevalence of stimulant-use disorders in the United States has fluctuated over the past 20 years, with trends showing regional and demographic variability.80 Multiple single-center studies in trauma populations have demonstrated an association between illicit amphetamine use and higher rates of ICU admission, longer length of stay, and increased hospital costs.81–83 A single-center review of medical ICU admissions found that 13% of admissions were related to illicit drug use and that 27.4% were related to cocaine or amphetamines.1
Short- and long-term stimulant use can affect all organ systems. The most common presentations to the emergency department include (1) CNS stimulation (acute agitation, hallucinations, irritability, aggressiveness, and psychosis), (2) cardiovascular complaints (eg, chest pain), and (3) cerebrovascular disease. Though chest pain in this patient population is frequently related to vasospasm, 10% of stimulant users have evidence of ischemia and 6% have evidence of acute MI.84–86 Other cardiovascular manifestations include acute arrhythmia, hypertensive urgency and emergency, heart failure, myocarditis, and cardiomyopathy. The cardiomyopathy appears to develop rapidly, and when compared to patients with heart failure not related to illicit drug use, patients using stimulants have a higher risk of in-hospital complications.87 Chronic methamphetamine use can also lead to pulmonary arterial hypertension (PAH), especially in women.88 Compared to patients with idiopathic PAH, patients with methamphetamine-associated PAH have less favorable hemodynamics, greater right ventricular dilation, worse functional status, and reduced survival. Spontaneous intracranial hemorrhage (ICH) is also more common in psychostimulant users compared to the general population.89,90 Methamphetamine use is associated with earlier onset ICH, longer hospital length of stay, and greater change in functional ability.91
Management of CNS manifestations of stimulant use are symptom driven. Acute agitation is typically managed with benzodiazepines with or without an antipsychotic. Due to excessive CNS stimulation, it has been hypothesized that patients with a history of stimulant use who are mechanically ventilated would have higher sedation requirements; however, 2 single-center retrospective studies in trauma patients found no difference in opioid or sedative requirements compared to nonusers.92,93 In the perioperative setting, signs and symptoms of acute intoxication may be indistinguishable from malignant hyperthermia and neuroleptic malignant syndrome, thus requiring heightened awareness.
Withdrawal symptoms are typically short-lived, particularly for cocaine which has a shorter half-life than amphetamines, though cravings can persist for months or longer. Behavioral therapy and medications to prevent withdrawal have been studied in the outpatient setting but have limited clinical utility in the ICU. The optimal symptomatic management of acute stimulant withdrawal in critical illness is unknown but benzodiazepines, antipsychotics, clonidine, propranolol, and/or dexmedetomidine may be reasonable options. Antipsychotics and other medications used for acute withdrawal are not effective at maintaining abstinence after hospital discharge and should be discontinued as withdrawal symptoms resolve.94 Whether delirium occurrence, duration, or severity is worse for patients with a history of stimulant use is unknown. Nonpharmacologic delirium prevention measures should remain best practice. Many illicit stimulants may also contain fentanyl and, such patients should be monitored for opioid withdrawal.
Mechanical circulatory support (MCS) for stimulant-induced cardiomyopathy has been described in case reports for both cocaine and amphetamine users with acute MI,95 heart failure,96 and cardiogenic shock.97 As with other indications, the role of MCS in critical illness continues to expand and evolve and may have specific utility in this patient population.
TRANSITIONS OF CARE FOR PATIENTS WITH SUD
While acute management is often the primary focus of ICU providers, caregivers should also view hospitalization as an opportunity to “intervene” and “engage” with patients with SUD. Since most hospitalized patients with SUD are not seeking addiction treatment before admission, the ICU stay may enhance receptivity to intervention. Recent innovations in-hospital-based SUD care have been remarkably successful and clinicians should involve multidisciplinary addiction consult services during the ICU stay with follow-up at transitions of care.98 For example, pairing of hospital-initiated therapy with proactive case management and follow-up with outpatient addiction services, may help reduce overdose- and intoxication-related readmissions.99 Patients with SUD often have underlying psychiatric comorbidities, so screening for and treating such psychiatric disorders, and appropriately following-up are essential components of the holistic treatment of SUD.100
CONCLUSIONS
The increase in the admission of patients impacted by SUD to the ICU has posed novel challenges for critical care specialists. A thorough understanding of the pathophysiology of various SUDs and their respective impact on different organ systems is necessary to prevent negative outcomes in this at-risk patient population. Adequately managing withdrawal and decreasing the stigma of SUD are key priorities for helping patients with SUD receive the medical treatment they need and prevent “against medical advice” discharges. Better understanding how best to manage patients in acute withdrawal from alcohol, opioids, cannabis, and stimulants is a key area for future work. Also, the involvement of multidisciplinary addiction management during critical illness, with follow-up during transitions of care should be considered and its long-term impact on SUD should be explored.
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