CC

A 35-year-old White male presents to the emergency department (ED), stating, “I was hit in the face, and I think that my jaw is broken.”

HPI

The patient was involved in a bar fight several hours earlier, and another male punched him in the face, causing a displaced left mandibular angle fracture (confirmed with a panoramic radiograph). On arrival at the ED, the patient appeared intoxicated and had a strong odor of alcohol on his breath. However, he was alert and oriented ×3 (person, place, and time) and denied any loss of consciousness. He was admitted to the oral and maxillofacial surgery service in preparation for open reduction with internal fixation of the mandibular fracture. The admitting resident did not include delirium tremens precautions in his admission orders because the patient denied any history of excessive alcohol use or abuse or previous withdrawal symptoms. (Patients frequently describe the tremulousness, agitation, and anxiety of alcohol withdrawal as the “shakes.”) The patient had an uneventful first night, but his operation was postponed because of problems with operating room availability. On the second hospital day, early symptoms of alcohol withdrawal were noted (agitation, anxiety, tremulousness, nausea, and vomiting). Later that evening, the patient wandered the halls of the ward, mumbling to himself and unable to sleep (insomnia). He became progressively more agitated, exhibiting aggressive behavior toward the nursing staff.

You are called to evaluate the patient in the middle of the night. You find him trembling in his bed, yelling incoherently at the television, and claiming that there are spiders in the room (visual hallucinations). He will not cooperate with an examination and does not respond to questions. Detailed questioning of the available family members reveals that the patient has been a heavy drinker for several years and had been on a binge for the past several days.

PMHX/PDHX/medications/allergies/SH/FH

The patient drinks at least a six pack of beer and half a pint of gin a day (alcohol dependence or addiction). His last drink was 2 nights ago, just before he was assaulted.

The diagnostic criteria for alcohol dependence and abuse listed in the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition, is beyond the scope of this chapter. To summarize, alcohol dependence is based on tolerance to alcohol, the presence of withdrawal symptoms, and excessive time spent to obtain and use alcohol along with persistent and increased use despite alcohol-related problems. Alcohol abuse manifests as the recurrent use of alcohol despite disruptions at home or work, physical hazards, or legal problems, occurring over a 12-month period. Alcoholism is 2.5 times more prevalent in males.

The CAGE questionnaire is a simple verbal test composed of four questions that can be quickly administered to identify patients at risk for alcoholism. Patients with two affirmative answers are seven times more likely to be alcohol dependent. The sensitivity of the CAGE questionnaire is 75% to 90% in most studies. Other questionnaires used in the clinical setting are the AUDIT and TWEAK questionnaires.

The CAGE questionnaire for detecting alcoholism is well described. A positive response to two of the four questions is highly suggestive of alcohol dependence. C: Have you ever felt the need to cut down on drinking? A: Have you ever been annoyed with criticism about your drinking? G: Have you ever felt guilty about something you did while drinking? E: Have you ever had a morning eye -opener to get you going or to address your withdrawal symptoms?

Examination

General. The patient is extremely agitated, sweating, and shaking and is moving about restlessly in bed (signs of sympathetic overdrive).

Vital signs. Blood pressure is 180/90 mm Hg (hypertensive), heart rate is 130 bpm (tachycardia), respirations are 22 per minute (tachypnea), and temperature is 37.8°C (rules out fever as the cause of altered mental status).

Neurologic. The patient is awake but extremely agitated and is not oriented to place, time, or situation. His speech is slurred, his pupils are dilated (mydriasis secondary to sympathetic overdrive) but equal and reactive to light (dilated pupils that are not reactive may indicate intracranial injury and elevated intracranial pressures), his extraocular eye movements are intact, and his face is symmetric. (Facial asymmetry during animation may indicate an upper or lower motor neuron lesion of cranial nerve VII.) He is uncooperative with the motor and sensory examination but is moving all extremities well and is very tremulous. (The grossly normal and symmetric strength examination of the extremities and symmetric facial movement make a focal cerebral lesion unlikely.)

Reflexes. Findings reveal +2/4 in all extremities, and the his are downgoing bilaterally. (Upgoing toes is an abnormal finding in the adult patient and is termed a Babinski sign . A nonfocal motor examination with downgoing toes is supportive of the absence of a focal upper motor neuron lesion.)

Maxillofacial. The examination is consistent with a left mandibular angle fracture.

Cardiovascular. The patient is tachycardic with no murmurs, gallops, or rubs. (Patients with chronic alcoholism may have significant cardiac comorbidities.)

Abdominal. The patient has a soft, nontender, slightly enlarged liver (hepatomegaly caused by chronic alcohol consumption) and no ascites. (Intraperitoneal serous fluid or ascites would be seen in advanced hepatic dysfunction.)

Imaging

Imaging studies for evaluating a trauma patient with altered mental status should include a noncontrast head computed tomography (CT) scan. Altered mental status can be caused by acute drug or alcohol intoxication or withdrawal, electrolyte disturbances, hypoxia, infection or sepsis, or metabolic derangements. Altered mental status can also be a manifestation of a closed head injury, particularly intracranial bleeding in the current trauma patient. Any acute changes in mental status warrant a head CT scan to rule out an undetected or blossoming intracranial injury.

For the current patient, an initial head CT scan was not ordered upon admission because of the absence of focal neurologic signs or loss of consciousness. Although this patient is most likely experiencing alcohol withdrawal syndrome and delirium tremens, a head CT scan was ordered after the onset of his altered mental status to evaluate for closed head injury; the scan was normal.

Plain radiographic studies of the mandible confirmed the diagnosis of a left mandibular angle fracture.

Labs

During the initial evaluation of an intoxicated trauma patient with maxillofacial injuries, a blood alcohol level and urine drug screen, in conjunction with a head CT scan, are recommended to account for altered or decreased mental status. Liver function tests (including aspartate aminotransferase [AST], alanine aminotransferase [ALT], albumin, bilirubin, prothrombin time [PT], partial thromboplastin time [PTT], and international normalized ratio [INR]) are indicated for patients with liver cirrhosis to evaluate for possible coagulopathies if the patient will or may undergo surgery. A complete blood count (including platelets) is warranted because anemia (particularly macrocytic) and thrombocytopenia (caused by liver dysfunction) are common in people with alcoholism. A complete metabolic panel (CMP) is mandatory to rule out electrolyte derangements as the source of altered mental status and to monitor the electrolyte abnormalities associated with chronic alcohol abuse and malnutrition (e.g., hypomagnesemia). A baseline electrocardiogram (ECG) is recommended, especially in older patients, because cardiac disorders are commonly associated with alcohol consumption.

The current patient presented with an initial blood alcohol level of 250 mg/dL (the legal intoxication level is 0.08%, or 80 mg/dL, in most states) and a negative urine drug screen result. AST and ALT levels were 110 U/L and 50 U/L, respectively. (AST and ALT are typically double or triple the normal values in patients with chronic alcoholism.) His hemoglobin was 11 g/dL, hematocrit was 34%, and mean corpuscular volume was 110 μm ³ (macrocytic anemia caused by malnutrition and likely vitamin B ₁₂ deficiency). The ECG showed sinus tachycardia. The remainder of the laboratory values were within normal limits.

Assessment

A 35-year-old male with a left mandibular fracture, now complicated by alcohol withdrawal syndrome and delirium tremens, presenting with altered mental status and agitation (hyperexcitable state).

Alcohol withdrawal syndrome and delirium tremens describe a spectrum of symptoms observed after a relative or absolute withdrawal from alcohol in susceptible individuals (especially those who are chronic consumers of large amounts of alcohol). The physiologic mechanisms of alcohol withdrawal are based on the inhibitory γ-aminobutyric acid (GABA) and excitatory (glutamate) neurotransmitters of the brain. Alcohol increases the effects of GABA on the GABAA receptor, thus increasing its inhibitory effects. Also, it inhibits the excitatory effects of glutamate at the N-methyl-D-aspartate (NMDA) receptor, thereby decreasing neuronal excitability. During alcohol withdrawal, a state of hyperexcitability and autonomic dysfunction becomes apparent (hypermetabolic state).

Treatment

Identification of patients who are at risk for developing alcohol withdrawal syndrome or delirium tremens is the most important step for prevention of these two conditions. Patients with a recent history of significant alcohol consumption (chronic or binge drinkers) and those with a history of alcohol withdrawal or delirium tremens are at risk for alcohol withdrawal syndrome and delirium tremens. Older patients with other medical comorbidities are at greater risk. With hospitalization, patients do not have access to alcohol and may develop a range of signs and symptoms consistent with alcohol withdrawal syndrome, withdrawal seizures, and delirium tremens. (Some hospital facilities have alcoholic beverages available for delirium tremens prevention.)

Preventive measures should be taken to reduce the risk of the development of alcohol withdrawal syndrome and delirium tremens. Benzodiazepines are the first-line agents for treatment and prevention; they are used either as needed or on a fixed schedule to prevent the development of the symptoms based on the patient’s history and the severity of symptoms. Scheduled dosing is recommended for patients considered to be at moderate or high risk; this also allows for a smoother withdrawal. With scheduled dosing of medications, doses high enough to relieve symptoms are given over the first 24 to 48 hours, and the patient is slowly weaned (by ∼20% a day) over the next 3 to 5 days. Longer acting benzodiazepines, such as diazepam (Valium), starting at 5 to 10 mg by mouth (PO), intravenously (IV), or intramuscularly (IM) every 6 to 8 hours, or chlordiazepoxide (Librium), starting at 25 to 100 mg PO, IV, or IM every 4 to 6 hours, may be used to reduce rebound effects and significantly decrease withdrawal symptoms. In patients with significant comorbidities (e.g., liver failure with associated decreased hepatic metabolism), shorter acting benzodiazepines may be used, such as lorazepam (Ativan), 1 to 4 mg PO, IV, IM every 4 to 8 hours, or oxazepam (Serax), starting with 15 to 30 mg PO every 6 to 8 hours. Nonpharmacologic measures include maintaining a calm, tranquil environment and a nonconfrontational interaction to help reduce the patient’s anxiety. Patients presenting with symptoms of anxiety, tremulousness, and agitation after recent cessation of alcohol use should be treated promptly (with longer acting benzodiazepines).

Intravenous fluids, replacement of electrolytes (e.g., magnesium), folic acid, and IV thiamine (given before administration of glucose to prevent the development of Wernicke’s encephalopathy) are essential to rehydrate the patient and correct any possible vitamin deficiencies. Standard “delirium tremens precautions and prophylaxis” orders include thiamine 100 mg IM or IV daily, folate 1 mg PO or IV daily, multivitamins PO or IV, magnesium sulfate 1 g IM or IV daily, and benzodiazepines as needed or scheduled, as discussed earlier.

With the onset of full-blown delirium tremens, the patient should be admitted to the intensive care unit, with administration of scheduled benzodiazepines to ameliorate delirium symptoms and reduce the incidence of seizures. For the autonomic symptoms (e.g., tachycardia and hypertension), antihypertensive medications may become necessary. Beta-blockers may be used to treat tachycardia and hypertension, but caution should be used because these drugs may precipitate delirium. Clonidine (a central α-agonist) may also be used to treat autonomic symptoms without any adverse effects on mental status. If withdrawal symptoms are severe and refractory despite benzodiazepine therapy, the patient may require endotracheal intubation for airway protection and administration of a general anesthetic, such as a propofol. (Propofol has been shown to be effective in refractory delirium tremens.) Usual supportive care is included throughout delirium tremens. (This may include four-point restraints.)

The differential diagnosis of altered mental status can be extensive, particularly in the absence of an appropriate history and examination. Broad categories include toxic (drug overdose or toxicity), metabolic (hypoglycemia, hepatic encephalopathy, or uremia), infectious (systemic or central nervous system [CNS]), inflammatory (demyelinating disease or CNS vasculitis), vascular (large vessel infarction or intracranial hemorrhage), and traumatic causes (increased intracranial pressure secondary to closed head injury); hypoxemia, hypercarbia, or both; and acute psychotic episodes secondary to underlying psychiatric disorders. The differential diagnosis should be categorically narrowed to the most likely cause given the clinical setting. Head imaging to rule out traumatic brain injuries, vascular accidents (e.g., intracranial hemorrhage), infectious processes (e.g., cerebral abscesses), and other cerebral lesions should be obtained early. If an infectious cause involving the CNS is suspected, a lumbar puncture (after checking the PT, PTT, and INR) is essential to rule out meningitis and encephalitis. Urine and serum toxicology screens can rule out drug or alcohol abuse. ACMP, including liver function tests, calcium, magnesium, ammonia, vitamin B ₁₂ level, and thyroid function tests, can help identify certain metabolic derangements. Urinalysis and blood cultures should be obtained in cases of suspected urinary or hematogenous infectious processes contributing to mental status changes. In an obtunded patient, subclinical seizure activity should be considered. This can be evaluated using an electroencephalogram.

For the current patient, failure to identify the patient’s risk factors and poor communication among staff members contributed to the lack of preventive measures for alcohol withdrawal syndrome and delirium tremens. At the onset of symptoms of delirium tremens, scheduled lorazepam 2 mg IV and chlordiazepoxide 50 mg IV every 4 hours were initiated followed by replacement of fluids, electrolytes, and multivitamins. The patient’s condition progressively improved over the course of the day, with resolution of the tachycardia and normalization of the blood pressure. Librium was continued on a scheduled basis for the next 2 days and subsequently slowly tapered (25 mg PO every 4 hours on day 3 followed by 10 mg PO every 4 hours on day 4) to prevent benzodiazepine withdrawal. Clonidine was not used because the patient’s autonomic dysfunction normalized. The patient underwent open reduction with internal fixation of the mandibular fracture without complications. (Closed reduction is frequently not well tolerated by patients who are poorly compliant.) The patient was counseled about the importance of drinking cessation and the long-term effects of heavy alcohol use and was assisted to obtain help via support groups such as Alcoholics Anonymous or from professional counselors (psychiatrists or psychologists), with the help of the hospital social worker.

Complications

Inherent to the diagnosis of delirium tremens is the autonomic instability (fluctuating blood pressure, heart, and respiratory rates) that is life threatening if not appropriately managed. Withdrawal seizures rarely require aggressive antiepileptic pharmacologic interventions. (Benzodiazepines are usually sufficient.) Rarely, the seizure may become prolonged, leading to status epilepticus, a neurologic emergency characterized by continuous seizures (clinical or subclinical) lasting longer than 5 minutes or multiple seizures with a 30-minute period during which the patient does not return to baseline between seizures. This may lead to permanent cerebral damage or death if not managed aggressively. The mortality rate for untreated alcohol withdrawal syndrome and delirium tremens is about 15%, mostly secondary to cardiovascular and respiratory collapse.

Discussion

Alcohol withdrawal syndrome and delirium tremens characterize the spectrum of symptoms observed after cessation or reduction in heavy and chronic alcohol use. Delirium primarily involves alterations of attention and is characterized by a fluctuating course, difficulty with concentration, and altered mental status. Tremens refers to the tremors seen in patients with delirium tremens. Most patients who stop alcohol use acutely do not develop withdrawal symptoms, or they simply experience minor symptoms that do not require medical attention. Clinically significant alcohol withdrawal symptoms occur in up to 20% of patients. If the symptoms go untreated, 10% to 15% of these patients progress to withdrawal seizures. Delirium tremens is the last stage of alcohol withdrawal; it occurs in 5% to 10% of alcohol-dependent individuals, with a mortality rate of 5% to 15% when left untreated.

The physiologic mechanism of alcohol withdrawal is based on the inhibitory and excitatory neurotransmitters of the brain. Alcohol increases the effects of the GABAA receptor by increasing its inhibitory effects. In contrast, glutamate (excitatory neurotransmitter that acts on the NMDA receptor) is inhibited, thereby decreasing neuronal excitability. The presence of alcohol has an inhibitory effect by enhancing GABAA and depressing the NMDA receptor. On withdrawal of alcohol, an abrupt cessation of the neuronal inhibition and a subsequent state of hyperexcitability occur.

There are multiple stages of withdrawal based on the chronology of symptoms occurring after the cessation of alcohol use. These stages, from least to most severe, include acute intoxication, alcohol withdrawal, withdrawal seizures, and delirium tremens. Withdrawal may be apparent as early as 6 hours after the last drink but may last up to 12 to 24 hours; symptoms include depression, anxiety, tremulousness, and insomnia. Withdrawal seizures, which have a 2% to 5% incidence in alcohol withdrawal syndrome and delirium tremens, typically occur approximately 48 hours after cessation of alcohol use and present as generalized tonic-clonic seizures. Delirium tremens peak at 48 to 72 hours after the last drink. The patient may present with delirium, hallucinations (visual, auditory, or tactile, with awareness that he or she is hallucinating), psychomotor agitation, diaphoresis, or fever, but the key feature of delirium tremens is autonomic instability. Scales such as the Clinical Institute Withdrawal Assessment for Alcohol may help determine the severity of alcohol withdrawal symptoms.

Wernicke-Korsakoff syndrome encompasses two different syndromes associated with chronic alcohol use and severe malnutrition. Wernicke’s encephalopathy is primarily a clinical diagnosis involving the classic triad of encephalopathy, ophthalmoplegia, and ataxia. Confusion is usually of a subacute to chronic nature and is characterized by inattention, memory loss, and apathy. Ophthalmoplegia (weakness or paralysis of one or more of the extraocular muscles) mostly involves the lateral recti but may also involve any of the extraocular muscles. Nystagmus (rhythmic oscillation of the eyes) is commonly present in the lateral or vertical gaze (or both). Ataxia is the unsteady, clumsy motion of the extremities and, more commonly, the trunk. Left untreated, Wernicke’s encephalopathy has a mortality rate of 10% to 20%. It is treated with the administration of thiamine 50 to 100 mg IV once a day (this should be given before glucose, because glucose further depletes thiamine and accelerates the development of Wernicke’s encephalopathy). Korsakoff syndrome primarily involves memory impairment without significant deficits of other cognitive functions, such as attention or social behavior. It is also characterized by both anterograde and retrograde amnesia, along with confabulation, in which the patient’s recall is distorted in relation to reality (a prominent feature). This condition is also treated with thiamine, but the prognosis is less favorable.