Delirium/Alcohol Withdrawal Case File

Delirium/Alcohol Withdrawal Case File

Eugene C. Toy, MD, Gabriel M. Aisenberg, MD

Case 59

A 57-year-old man was admitted to the hospital 2 days ago following a motor vehicle accident. He suffered multiple contusions and a femur fracture that was surgically repaired 24 hours ago. He also had a laceration on his forehead; a computed tomography (CT) scan of his head on admission showed no intracranial bleeding. His hospital course has been uncomplicated, and he currently is taking morphine as needed for pain and subcutaneous enoxaparin for prophylaxis of deep venous thrombosis. This evening he has been agitated and combative and pulled out his intravenous (IV) line. He is cursing at the nurses and is trying to get out of bed to leave the hospital. When you see him, he is febrile with a temperature of 100.8 °F, heart rate of 122 beats per minute, blood pressure of 168/110 mm Hg, respiratory rate of 28 breaths per minute, and oxygen saturations of 98% on room air. He is awake and fidgety, staring around the room nervously. He is disoriented to place and time; he seems to be having auditory hallucinations and is brushing off unseen objects from his arms. On examination, his forehead wound is bandaged, his pupils are dilated but reactive, and he is mildly diaphoretic. His lung sounds are clear to auscultation, his heart rhythm is tachycardic but regular, his abdomen is benign, and he is tremulous. You are able to contact family members by phone. They confirm that prior to his car accident, the patient had no medical problems, had no dementia or psychiatric illness, and was employed as an attorney. They report that he took no medications at home, did not smoke or use illicit drugs, and drank three to four mixed drinks every day after work, sometimes more on the weekends.

▶ What is the most likely diagnosis?

▶ What should be your next step?

ANSWERS TO CASE 59:

Delirium/Alcohol Withdrawal

Summary: A 57-year-old man hospitalized for 2 days for multiple contusions presents with

• Surgery performed 24 hours ago for a femur fracture sustained in a motor vehicle accident
• Report from family members that the patient had no medical problems, dementia, or psychiatric illness; no medications; no history of smoking or illicit drugs; alcohol intake of three to four mixed drinks every day after work
• Sudden onset of agitation and combativeness
• Normal CT scan of the head
• Current medications of morphine and subcutaneous enoxaparin
• Tachycardia, hypertension, and temperature of 100.8 °F
• Fidgeting, disorientation, and suspected auditory and tactile hallucinations
• Dilated pupils, mild diaphoresis, and tremors

Most likely diagnosis: Delirium as a result of an acute medical illness or possibly alcohol withdrawal.

Next step: Look for serious or reversible underlying medical causes for the delirium. If no other medical problems are identified, based on the patient’s daily alcohol use, a possible diagnosis is alcohol withdrawal syndrome.

ANALYSIS

Objectives

1. Recognize delirium in a hospitalized patient. (EPA 1)
2. List the most common causes of delirium. (EPA 2)
3. Understand the management of an agitated, delirious patient. (EPA 4)
4. Recognize the special considerations applicable to an older demented patient with delirium. (EPA 1, 3)
5. Describe the stages, treatment, and complications of alcohol withdrawal syndrome. (EPA 1, 4)

Considerations

This 57-year-old man had been in a normal physical and mental state prior to hospitalization. He then developed an acute change in mental status, with fluctuating consciousness and orientation, the hallmark of delirium. There are many possible causes for his delirium: hypoxia, pulmonary embolism, acute electrolyte disturbances, hypoglycemia, occult infection, central nervous system hemorrhage or infection, or drug intoxication or withdrawal. These conditions require investigation before ascribing the symptoms to alcohol withdrawal because they are potentially very serious or even fatal. In addition, further investigation to quantify his alcohol intake is necessary. Rapid diagnosis and treatment are vital since this patient has findings of significant autonomic instability based on the hyperthermia, tachycardia, and high blood pressure. Mortality if untreated can approach 20%. The use of a benzodiazepine such as lorazepam is a fundamental part of the treatment regimen.

APPROACH TO:

Delirium and Alcohol Withdrawal

DEFINITIONS

DELIRIUM: An acute, fluctuating confusional state that is one of the most common mental disorders encountered in hospitalized or otherwise medically ill patients.

DEMENTIA: Significant loss of intellectual abilities, such as memory capacity, severe enough to interfere with social or occupational functioning, usually over a long period of time.

CLINICAL APPROACH TO DELIRIUM

Pathophysiology

• The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) defines delirium as a clinical diagnosis. It has the following features:
• Disturbance in attention (eg, reduced ability to direct, focus, sustain, and shift attention) and awareness.
• Change in cognition (eg, memory deficit, disorientation, language disturbance, perceptual disturbance) that is not better accounted for by a preexisting, established, or evolving dementia.
• The disturbance develops over a short period (usually hours to days) and tends to fluctuate during the course of the day.
• Evidence that the aforementioned features are caused by a medical condition, medications, or intoxicants.

Delirium can be a manifestation of an underlying medical disorder. Sometimes, the underlying condition is apparent. At other times, especially in elderly demented patients, delirium may be the first or the only sign of an acute illness, or it may be a serious decompensation or complication of a stable medical condition. Table 59–1 lists conditions that should be considered as causes of delirium. Of these conditions, the most common are drug toxicity (especially anticholinergics, sedatives, or narcotics in elderly patients), infection, electrolyte disturbances (most commonly hyponatremia or hypoglycemia), and withdrawal from alcohol or other sedatives.

Abbreviations: CNS, central nervous system; SSRI, selective serotonin reuptake inhibitor.

Delirium in the Geriatric Population. Delirium in the geriatric population can be the presenting manifestation of any acute illness, with an incidence of up to 10% on admission and up to 30% during an acute hospitalization. Causes of delirium in the elderly include pneumonia, urinary tract infection, myocardial infarction, gastrointestinal hemorrhage, traumatic injury, or virtually anything else that precipitates an acute hospitalization. This is even more of a problem after major surgery; nearly half of individuals (usually elderly) who suffer hip fractures develop delirium postoperatively. Urinary retention and constipation may also precipitate delirium and must be evaluated in all patients, especially given its high incidence in the elderly population.

Persons at any stage of dementia may develop delirium during an acute illness or injury or with additional pharmaceutical agent(s). Additionally, an acute delirium may “unmask” an early underlying, undetected dementia. The confused and disoriented geriatric patient cannot be dismissed as having one or the other, and the history should concentrate on any changes in the behavioral status of the patient since the acute event.

Clinical Presentation

Regardless of etiology, delirium produces a profound disturbance of brain function, and all etiologies are serious and potentially fatal illnesses. Delirium must be approached as an acute medical emergency. A detailed history, aggressively pursued, is mandatory, and because the responses from these patients cannot be relied upon, information from family, friends, or other caregivers is essential. A thorough physical examination with emphasis on neurologic status, clarity of speech, level of awareness, attention span, facial droop, and weakness of an extremity must be established because such changes must be carefully and frequently assessed. Basic laboratory studies should focus on chemical abnormalities (glucose, creatinine, bilirubin, serum sodium levels), drug intoxication, and evidence of hypoxia. The two threatening and potentially easily reversible conditions—hypoxia and hypoglycemia—should be immediately investigated and treated.

One of the earliest signs of a disturbance of consciousness is an inability to focus or sustain attention, which may be evident as distractibility in conversation.

Usually, there also is disturbance of the sleep-wake cycle. In alcohol withdrawal, signs of autonomic hyperactivity predominate, and patients may become hypervigilant and agitated. As symptoms progress, patients may become lethargic or even stuporous (arousable only to painful stimuli). Determining the time of the patient’s last drink is key to diagnosing withdrawal delirium, as symptoms of delirium typically present 72 to 96 hours after the patient’s last alcoholic beverage.

To diagnose and monitor a delirious patient, it is important to utilize the Confusion Assessment Method (or CAM) score. The CAM is a four-part screening tool used to differentiate delirium and other causes of altered mental status and is described as follows:

1. Acute onset and fluctuating course
2. Inattention
3. Disorganized thinking
4. Altered level of consciousness

The patient must have features 1 and 2 PLUS either 3 or 4 in order to meet criteria for delirium. Questions concerning the patient’s mental state should be directed to either the family or the nursing staff to assess for changes. Specifically, it is important to ascertain from family members whether these impairments were chronic, as in dementia, or developed acutely over hours to days and whether their symptoms are fluctuating throughout the day. Not uncommonly, hospitalized patients appear relatively lucid on morning rounds, especially if mental status is only superficially assessed, but then the night staff reports severe confusion and agitation. Delirious patients may hallucinate or have vague delusions of harm, but hallucinations are not a mandatory feature of the condition. Delirium more commonly manifests with hypoactive symptoms such as lethargy and inactivity and often goes unrecognized by medical staff.

Treatment

The management of delirium needs first and foremost the identification and treatment of the acute underlying illness. Adequate hydration, oxygenation, good nursing care, and around-the-clock careful supervision are always the initial measures. Management of agitation and disruptive behavior is the most challenging aspect of care of the delirious patient. Nonpharmacologic interventions should be attempted first, including frequent reassurance and orientation from familiar persons or constant supervision. A delirious patient is reoriented by sensory input, so it is important that they be provided with glasses and/or hearing aids if required. Agitation with psychotic symptoms (hallucinations and delusions) can be treated with a neuroleptic such as low-dose haloperidol. However, older patients are more likely to experience extrapyramidal side effects, so newer atypical antipsychotics such as risperidone may be used. Benzodiazepines have a rapid onset of action but may worsen confusion and sedation. Physical restraint should be used as a last resort. Restraints are often important and necessary in delirious patients to prevent removal of IV lines, nasogastric tubes, and the like.

There is limited evidence that antipsychotics improve delirium, and recent studies have shown that use of antipsychotics does not shorten the amount of time a patient is delirious when compared to placebo. Therefore, antipsychotics in delirious patients should be used cautiously and in the right circumstance because of variable efficacy and potential side effects.

CLINICAL APPROACH TO ALCOHOL WITHDRAWAL

Epidemiology

It is estimated that 5% to 10% of the population has alcoholism, and a fair proportion will have withdrawal symptoms upon cessation. Excessive alcohol use is defined in men as 15 or more drinks per week and 5 or more drinks on a single occasion. In women, this is reduced to 8 drinks or more per week and 4 or more drinks on any single occasion. It is difficult to predict who specifically will suffer from alcohol withdrawal, but excessive, daily drinkers are more likely to experience symptoms. Many Americans are also habituated to benzodiazepines, and the withdrawal syndrome is similar to alcohol withdrawal.

Pathophysiology

The withdrawal findings of alcohol or benzodiazepine cessation are complex and can be explained largely due to the interaction of ethanol to the postsynaptic gamma-aminobutyric acid (GABA) A receptors, which are inhibitory neurons. Long-term alcohol use leads to downregulation of the GABA-A receptors; the brain compensates for this chronic loss of excitatory neurotransmission by increasing excitatory neurotransmitters such as norepinephrine, serotonin, and dopamine. Thus, with the sudden cessation of alcohol, these excitatory neurotransmitters are unopposed, leading to profound effects.

Clinical Presentation

Alcohol withdrawal manifests as a spectrum of symptoms, ranging from minor tremulousness and insomnia to the most severe form, delirium tremens (DT), characterized by delirium, tremor, and autonomic hyperactivity. The severity of withdrawal can be assessed using a validated assessment tool, the Clinical Institute Withdrawal Assessment (CIWA) scale. However, the CIWA is labor intensive for caregivers and especially tedious for nursing staff to conduct, so shorter assessments can be used.

Risk factors for the development of DTs include a history of sustained drinking, prior withdrawal symptoms, age older than 30, and a concurrent medical illness. Withdrawal can coexist with or mimic other conditions, such as infection, intracranial bleeding, hepatic failure, gastrointestinal bleeding, or drug overdose. DT is a diagnosis of exclusion; other serious diagnoses must be excluded before the patient’s mental status and autonomic signs are attributed to withdrawal.

It is important to understand the temporal course of the spectrum of alcohol withdrawal syndromes (Table 59–2). A key component of assessing alcohol withdrawal is therefore determining the time of the patient’s last drink.

Treatment

In contrast to other causes of delirium, benzodiazepines are the drugs of choice in alcohol withdrawal. They can be given on a fixed schedule in high-risk patients (previous history of DT or withdrawal seizures) to prevent withdrawal symptoms. If symptoms have already developed, benzodiazepines can be given according to one of two strategies. Long-acting benzodiazepines such as diazepam or chlordiazepoxide can be given in high doses until withdrawal symptoms cease, and then the slow clearance of the drug is allowed to prevent further withdrawal symptoms. However, these medications are metabolized by the liver and should be used with caution in cirrhotic patients since many alcoholics have some form of impaired liver function. Alternatively, benzodiazepines not metabolized in the liver, such as lorazepam, oxazepam, and temazepam may be used in these patients. These are shorter acting medications and must be given as needed when the patient has symptoms. Both strategies are effective.

In either case, the key to successful management is initially aggressive upward titration of dosage until the patient is heavily sedated but responsive, followed by rapid downward titration as agitation decreases, usually over 48 to 72 hours. Supportive measures are also important, such as adequate hydration, replacement of electrolytes (eg, magnesium and phosphate), and early supplementation with thiamine and other B vitamins in malnourished, chronic alcoholics to prevent the development of Wernicke encephalopathy.

CASE CORRELATION

• See also Case 53 (Thyrotoxicosis/Graves Disease).

COMPREHENSION QUESTIONS

59.1 A 35-year-old man is brought into the emergency department after a motor vehicle collision. He is intoxicated due to alcohol. In assessing the effect of alcohol on cognitive function, the emergency physician notes some similarities to the effects of an other substance use. Which of the following agents most closely resembles the action of alcohol in the brain?

A. Amphetamines

B. Marijuana

C. Cocaine

D. Benzodiazepine

E. Acetaminophen

59.2 A 56-year-old man is brought into the emergency center for being disoriented and combative. He looks around the room with a wild look in his eyes and does not follow directions. His wife states that his baseline is alert and oriented with intact memory. He is diagnosed to have delirium. Compared with dementia, which of the following is a characteristic of delirium?

A. A fluctuating level of consciousness

B. Slow onset

C. Can be due to deficiencies of thiamine or cyanocobalamin

D. Decreased memory ability

59.3 A 34-year-old man is brought to the emergency department by his friends for “freaking out.” They state that he is usually in good health and has had no head trauma or injuries but that he does drink a lot of alcohol each day. He is noted to have marked tremors of his extremities and states that he is seeing large scorpions skittering across the walls of the room and hearing the scorpions talking to him. Which of the following statements is the most accurate description related to this patient?

A. Auditory hallucinations are unique to alcohol withdrawal and cannot be caused by a brain tumor.

B. If the serum blood alcohol level is higher than the legal limits of intoxication, these symptoms cannot be alcohol withdrawal.

C. This patient should immediately receive glucose intravenously for possible hypoglycemia.

D. If the patient also has hypertension, fever, and tachycardia, he has a 5% to 10% chance of mortality.

ANSWERS

59.1 D. Alcohol and benzodiazepines both interact with the GABA system; thus, benzodiazepines are the drugs of choice for treatment of acute alcohol withdrawal. Answer C (cocaine) and answer A (amphetamines) both act as stimulants in the brain, increasing levels of dopamine. Answer B (marijuana) acts on the cannabinoid receptor in the brain, a typical G protein-coupled receptor.

59.2 A. Fluctuating levels of alertness and consciousness are typical of delirium. Remember that delirium is usually acute in onset and fluctuates, whereas dementia (the other answers) is slower and more gradual in onset and consistent in alteration of cognition, such as memory issues.

59.3 D. This patient likely is suffering from alcohol withdrawal. DT with autonomic instability and sympathetic overactivity is associated with a 5% to 10% mortality. Auditory hallucinations (answer A) can occur from a number of illicit agents or even brain tumors. The fall in serum blood alcohol level and not the absolute level may induce symptoms of withdrawal. Thus, even if the patient’s serum alcohol level is elevated, he can still have withdrawal (answer B). An individual who abuses alcohol should first be given thiamine before glucose (answer C) is administered to prevent acute Wernicke encephalopathy.

CLINICAL PEARLS

▶ Delirium is characterized by acute onset of impaired attention and cognition and fluctuating levels of consciousness, often with psychomotor and autonomic hyperactivity.

▶ Delirium requires urgent investigation to search for serious underlying systemic or metabolic causes.

▶ Frequent reassurance and orientation and constant observation are useful in managing the agitated delirious patient. Low-dose haloperidol can be used to control agitation or psychotic symptoms. Physical restraint is used as a last resort.

▶ Delirium tremens is the most severe and dramatic form of alcohol withdrawal, with abrupt onset from 2 to 4 days after cessation of drinking and sudden resolution several days later, and is associated with a mortality rate of 5% to 10%.

▶ Therapy for alcohol withdrawal syndromes includes benzodiazepines, hydration, electrolyte replacement, and B vitamins to prevent Wernicke encephalopathy.

▶ The mechanism of alcohol withdrawal is due to excitatory neurotransmitters due to sudden cessation of alcohol, which binds to GABA-A (inhibitory) receptors.

REFERENCES

Cassidy EM, O’Sullivan I, Bradshaw P, Islam T, Onovo C. Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen. Emerg Med J. 2012;29(10):802-804. 

Goodson CM, Clark BJ, Douglas IS. Predictors of severe alcohol withdrawal syndrome: a systematic review and meta-analysis. Alcohol Clin Exp Res. 2014;38(10):2664-2677. 

Inouye SK. Delirium in older persons. N Engl J Med. 2006;354:1157-1165. 

Josephson SA, Miller BL. Confusion and delirium. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 19th ed. New York, NY: McGraw Hill; 2015:196-201. 

Shuckit MA. Alcohol and alcoholism. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 19th ed. New York, NY: McGraw Hill; 2015:3546-3556.

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