Alcoholism is a prevalent medical and psychiatric disease, and, consequently, alcohol withdrawal is encountered frequently in the emergency department. This issue reviews the pathophysiology of the alcohol withdrawal syndrome, describes the 4 manifestations of alcohol withdrawal, and looks at the available evidence for optimal treatment of alcohol withdrawal in its diverse presentations. Patients commonly manifest hyperadrenergic signs and symptoms, necessitating admission to the intensive care unit, intravenous benzodiazepines, and, frequently, adjunctive pharmacotherapy. An aggressive front-loading approach with benzodiazepines is proposed and the management of benzodiazepine-resistant disease is addressed.
A 56-year-old alcoholic woman presents to the ED seeking detoxification from alcohol. Her reported consumption is 750 mL of vodka daily. Her last drink was 15 hours prior, at 4:30 PM the previous afternoon. Upon presentation to the ED, she is found to be tachycardic, with a heart rate of 139 beats/min; and hypertensive, with blood pressure of 172/84 mm Hg. She is diaphoretic and has a severe tremor. She is unable to hold a glass of water without spilling its contents. The patient denies any history of illicit drug use and states that she has no history of alcohol withdrawal seizures or delirium tremens. She receives 1 liter of intravenous normal saline and an intravenous dose of 5 mg of diazepam. Fifteen minutes later, her tremor is worsening and her vital signs have failed to improve. What treatment modalities should you choose for her worsening symptoms?
As you are returning to her room, a nurse asks for your assistance in an adjacent room where EMS has brought in a 62-year-old man with agitated delirium. You find a disheveled, malnourished-appearing man being restrained by 2 security guards. He is tachycardic, with a heart rate of 162 beats/min; and hypertensive, with blood pressure of 165/92 mm Hg. He is attempting to sit up in the stretcher and appears to be miming turning a key in a car ignition, repeating over and over, “I have to go.” He does not attend to you or the staff, and he appears to look off into space, tracking objects that are not there. He is diaphoretic and tremulous. The paramedics tell you they know him as a local alcoholic. He has a history of pancreatitis, and his wife told the paramedics that he has complained of abdominal pain and has been vomiting for the past 2 or 3 days. The paramedics were initially called for seizure-like activity. What are your priorities in the initial diagnosis and management of this patient?
Alcohol withdrawal syndrome (AWS) is a major cause of morbidity and mortality among alcoholics, and, for many medical centers, it creates a significant burden on resource utilization. Several studies have reported that alcohol withdrawal increases the morbidity and mortality of coexisting illness and prolongs the duration of hospital admissions.1-3
Alcohol withdrawal has been recognized since ancient times.4 Marked strides in recognition and management have occurred over the past century. The mortality rate of delirium tremens (DT), the most severe manifestation of AWS, was 52% in 1912, and had decreased to 10% to 12% by the 1930s.5 Mortality due to DT is now estimated to be 2% to 3%.6 Nonetheless, complications due to alcohol abuse remain important clinical problems, accounting for 21% of medical intensive care unit (ICU) admissions at one urban hospital.7 Alcohol withdrawal was the most common of these diagnoses. While seemingly straightforward, the diagnosis of AWS is often missed, or its signs and symptoms are erroneously attributed to another cause, such as sepsis or drug intoxication. The differential diagnosis is broad. There is no single laboratory or imaging test that can diagnose AWS, and the criteria are strictly historical and clinically based.8
An understanding of risk factors for progression to severe AWS as well as basic knowledge of the pathophysiology of alcohol withdrawal will aid the emergency clinician in the prompt recognition of AWS. Recognition of risk factors will allow for early empiric treatment as well as optimal choices for therapeutic interventions. In turn, unnecessary hospital and ICU admissions can be avoided and hospital lengths of stay shortened when alcohol withdrawal is recognized promptly and aggressive treatment is initiated early. This review will evaluate the limited available literature regarding the management of AWS in the emergency department (ED). It will also address the underlying pathophysiology of AWS and the treatment modalities available to emergency clinicians. Finally, it will introduce adjunctive and controversial therapeutic interventions.
Relevant primary literature was identified by a search of the Cochrane Database of Systematic Reviews, PubMed, and Ovid MEDLINE®. Search terms included alcohol withdrawal syndrome, alcohol withdrawal seizure, alcoholic hallucinosis, alcoholic hallucinations, and delirium tremens . We reviewed only reports available in the English language and excluded outpatient studies. Using the same search terms, relevant review literature was identified. Select case reports and case series were utilized where clinical trial literature was lacking. The bibliographies of major toxicology textbooks9,10 and review articles11-20 were also queried to ensure relevant literature was not overlooked.
A total of 87 randomized controlled studies of drug-versus-drug trials or drug-versus-placebo trials were identified. However, there was a paucity of trials pertaining directly to the ED management of AWS.21 The settings of most clinical trials were inpatient psychiatric alcohol detoxification units, predominantly in Europe, and the numbers of participants in these studies were small. In addition, the patient populations in these inpatient detoxification unit trials did not necessarily parallel the patient population seen in the ED with acute, severe alcohol withdrawal. The challenges of research directly pertaining to the ED diagnosis and management of AWS are numerous and include difficulty in obtaining informed consent (especially in the setting of delirium) and the lack of homogeneity of alcohol withdrawal. While the underlying principles of the management of the 4 stages of AWS are similar, studies focusing on a single presentation (such as alcohol withdrawal seizure) cannot necessarily be applied to alcohol withdrawal as a whole.
“The patient was hallucinating, so I gave him an antipsychotic.”
While antipsychotics are certainly indicated for psychotic hallucinations, the use of antipsychotics in alcohol withdrawal is associated with poorer outcomes.91 It is best to address the underlying pathophysiology of CNS hyperexcitability and utilize a GABAA receptor agonist such as a benzodiazepine.
“The patient’s withdrawal looked mild, so I discharged her with benzodiazepines.”
There are criteria for safe discharge of an alcoholic patient presenting with withdrawal or requesting detoxification: CIWA-Ar score < 8, no history of complicated alcohol withdrawal, no clinical alcohol or drug intoxication, no significant underlying medical or psychiatric comorbidities. Even in patients who develop DT, early symptoms may be mild.
“The patient was tachycardic; I presumed it was from alcohol withdrawal.”
Alcoholics are at high risk for multiple acute and chronic medical comorbidities. Furthermore, there is commonly an acute medical ailment that causes an alcoholic patient to decrease or cease alcohol consumption. Pulmonary embolus, myocardial infarction, sepsis, dehydration, and a number of other diagnoses should be considered in the tachycardic alcoholic patient.
“I thought the patient had straightforward alcohol withdrawal, so I didn’t check any labs.”
Alcoholics commonly present with a range of metabolic derangements, some of which can be life threatening. These generally stem from malnutrition and dehydration. All intoxicated patients or patients with altered mental status should have a capillary glucose checked. Alcoholic patients who require inpatient admission (for withdrawal or otherwise) should have basic chemistries performed (including checking the magnesium level), and should be checked for severe abnormalities such as hyponatremia or alcoholic ketoacidosis.
“The patient presented with alcohol withdrawal and was confused, but looked okay, so I admitted him to the floor.”
Even in the absence of agitation, the presence of confusion in the setting of alcohol withdrawal suggests DT and necessitates admission to a higher level of care such as the ICU or, at minimum, a step-down unit. Furthermore, the treating emergency clinician should consider Wernicke encephalopathy or an underlying concomitant medical cause.
“The patient is an alcoholic; I assumed his delirium was from alcohol withdrawal.”
Alcohol withdrawal is a diagnosis of exclusion; there is no available test that confirms a diagnosis of alcohol withdrawal delirium. Consideration must be taken for other causes of delirium including structural CNS pathology (eg, stroke, intracranial hemorrhage), metabolic derangements (eg, uremia, hyperammonemia), infectious sources (eg, sepsis, meningitis), and toxicologic causes (eg, antimuscarinic syndrome, sympathomimetic syndrome).
“I was afraid benzodiazepines would cause her to stop breathing.”
In the absence of structural airway abnormalities or drug co-intoxication, benzodiazepines should not have a significant effect on ventilation. While patients will become sedated with high-dose benzodiazepines, their respiratory drive should be maintained, provided they are not also toxic on opioids or other sedating medications and they are without obstructive upper airway pathology.
“The patient is an alcoholic; I assumed the seizure was from alcohol withdrawal.”
While alcohol withdrawal seizures are relatively uncommon, alcoholics are at high risk for structural CNS injury, putting them at high risk for the development of epilepsy. Furthermore, antecedent trauma and subsequent intracranial hemorrhage places that patient at high risk for seizure. A seizure in an adult alcoholic without a history of withdrawal seizures and without other objective signs of withdrawal should prompt a more complete neurologic workup and cranial imaging.
“The patient told me he only drink 2 beers per day, so I didn’t think his presentation could be alcohol withdrawal.”
Alcoholics commonly minimize their alcohol consumption, portraying to the clinician a vast underestimation of actual alcohol consumption. In the right clinical context, a social history of daily drinking or periodic heavy alcohol consumption should prompt the emergency clinician to further consider alcohol withdrawal in the presentation of the tachycardic tremulous patient and/or new-onset seizure.
“The patient was requesting detoxification, but had no history of severe withdrawal and had no symptoms in the ED, so I discharged her with outpatient follow-up.”
Psychiatric comorbidities, including depression, are common among alcoholics. Some drink alcohol due to an underlying psychiatric disorder, and others have a mood disorder due to alcohol consumption. It is imperative that patients presenting with alcohol-related complaints are screened for suicidality.
Evidence-based medicine requires a critical ap;praisal of the literature based upon study methodol;ogy and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study will be included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, will be noted by an asterisk (*) next to the number of the reference.
Joseph H. Yanta, MD; Greg S. Swartzentruber, MD; Anthony F. Pizon, MD
June 1, 2015