Evaluation and Treatment of Altered Mental Status in the Emergency Department

EXECUTIVE SUMMARY

• Altered mental status is a common presentation in the emergency department (ED). There are many causes of altered mental status, and often the exact cause is not apparent in the ED. The role of the ED provider is to stabilize the patient, treat causes that are rapidly reversible (hypoglycemia, hyperthermia/hypothermia) and initiate diagnostic testing and treatment for life-threatening causes (trauma, intracranial lesions, sepsis).

• Delirium is a transient alteration of sensorium that often waxes and wanes. When the underlying cause is treated, delirium may be reversible. However, dementia is a fixed deficit resulting from changes in the brain, such as those seen with Alzheimer’s disease.

• Alcohol withdrawal can be seen in patients with known chronic alcoholism. Some patients, especially the elderly and those who live alone, may be able to hide their addiction. Patients can be treated with benzodiazepines.

• A thorough history and physical examination are necessary to establish the cause of the altered mental state. However, these are not always available in the ED, and it may take some detective work to establish a diagnosis. Even with a good history, the underlying cause may not be determined for several days and, in some cases, may never be found.

Introduction and Definitions

The term “mental status” has a complex definition that involves the interplay between emotional and intellectual functioning. Mental status, simply put, is how well one’s brain and body are working in sync. When a patient presents to the emergency department (ED) with altered mental status, three broad categories of diagnosis should be considered: delirium, coma, and dementia.¹ Altered mental status has many definitions, but fundamentally it involves changes in a person’s alertness, attention, memory, and/or awareness.²

Delirium

Delirium, also known as an acute confusional state, is a transient disorder characterized by impaired attention, perception, thinking, memory, and cognition. Delirium can be thought of as acute brain failure and is the final common pathway of multiple mechanisms.³ According to the official definition in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), delirium involves a disturbance in attention and awareness that is acute and tends to fluctuate.⁴ This can include a disturbance in attention or a change in an additional cognitive domain. Delirium can be caused by either somatic or medication factors, and it usually develops over the course of a few days. Sleep-wake cycles may be disrupted, and symptoms tend to be worse at night. Levels of alertness may be reduced, and activity levels may fluctuate rapidly.¹

Delirium is present in 10% to 15% of older adults in the ED.⁵ The condition can be characterized further into three subtypes: hyperactive, hypoactive, and mixed. Hyperactive delirium is the most easily recognizable subtype because the patients usually are restless, agitated, and overall hyperactive. Hypoactive delirium is much harder to recognize and frequently goes unnoticed because patients demonstrate reduced motor activity, sluggishness, and abnormal drowsiness, and they may appear to be in a daze. Hypoactive delirium is believed to be the most common subtype, present in about 60% of delirium cases.⁶ Mixed delirium includes aspects of both the hyperactive and hypoactive types. The person may switch quickly back and forth between the two.⁷

Dementia

Dementia typically involves a loss of mental capacity over a prolonged time period.⁸ Dementia is a disorder characterized by a decline in cognition in many domains, including learning, memory, language, executive function, complex attention, perceptual-motor skills, and social cognition. The beginning stages of dementia can be classified as mild early dementia, when the majority of functional capabilities are still intact. Unfortunately, as the disease progresses, dementia can become severe and interfere with daily function and independence. The most common form of dementia in older adults is Alzheimer’s disease (AD), which accounts for 60% to 80% of dementia cases in older adults.⁹

Coma

Coma is defined as “unarousable unresponsiveness.”¹⁰ Colloquially, coma is referred to as a state of reduced alertness and responsiveness from which the patient cannot be aroused.¹ When patients are in a coma, they are said to be unresponsive to external stimulation, such as verbal stimuli, sternal rub, and other noxious stimuli. Coma is the most severe state of altered mental status. A common method used to quantify the depth of a coma is by implementing the Glasgow Coma Scale (GCS).¹¹ (See Table 1.)

Altered Mental Status Relevancy

Having a solid foundational approach for evaluating and treating people with altered mental status is crucial to every emergency medicine practitioner. Altered mental status is a common chief complaint that can present on every shift. The older adult age group is the fastest growing age group worldwide. Nearly 30% of older medical patients experience delirium at some time during hospitalization.¹² Delirium is missed in up to 75% of patients older than 65 years of age in the ED. In one study, patients whose delirium was missed in the ED had a 30% mortality rate at six months. In a study involving 1,934 patients with altered mental status, researchers determined that the total mortality rate was roughly 8.1%.¹³ This implies that close to one in 10 patients with altered mental status will die during a hospital visit. Hospitalized individuals older than 65 years of age with delirium have three times the risk of placement in a nursing home and about three times the functional decline as hospitalized patients without delirium at both discharge and three months later.¹⁴

An estimated 2% of ED patients will present with altered mental status. Altered mental status will be present in 10% of hospitalized patients and 50% of hospitalized older adult patients.¹⁵ More than 2.6 million older adults develop delirium each year, costing $164 billion in annual healthcare expenditures.¹⁶

Etiology

The etiology of altered mental status is vast, and it is beyond the scope of this article to address them all. This article will attempt to highlight the most clinically relevant and common etiologies that present to the ED. The five broad categories considered include infections, metabolic or toxic encephalopathies, neurologic causes, cardiopulmonary causes, and drug-related causes. (See Table 2.)

Infectious causes include pneumonia, urinary tract infection (UTI), meningitis and encephalitis, sepsis, cellulitis, and brain abscess. Metabolic and toxic causes of altered mental status include but are not limited to hypoglycemia, alcohol intoxication, electrolyte abnormalities, hepatic encephalopathy, renal failure/uremia, thyroid disorders, alcohol or drug withdrawal, hypothermia or hyperthermia, vitamin deficiencies, and anemia. Neurologic etiologies of altered mental status include stroke or transient ischemic attack, seizure or a postictal state, subarachnoid hemorrhage, intracranial hemorrhage, central nervous system mass lesion, epidural hematoma, and subdural hematoma. Cardiopulmonary causes of altered mental status include heart failure, myocardial infarction, pulmonary embolism (PE), hypoxia, and carbon dioxide narcosis. Finally, one of the largest and hardest to determine categories of altered mental status includes drug- and poison-related toxicity. Drug-related toxicities include anticholinergic drugs, alcohol or drug withdrawal, sedative-hypnotics, narcotic analgesics, selective serotonin reuptake inhibitors vs. selective serotonin norepinephrine inhibitors, polypharmacy, and drugs of abuse (ecstasy, lysergic acid diethylamide], gamma hydroxy-butyric acid, phencyclidine, ketamine, cocaine, bath salts, marijuana, and synthetic cannabinoids, sometimes known as K2). Poison toxicities include inhalants, carbon monoxide (CO), pesticides, and toxic alcohols. (See Table 2.)

Pathophysiology

The pathophysiology of altered mental status, including delirium, confusion, dementia, and coma, is poorly understood and likely is cause-specific. To date, an all-encompassing explanation of altered mental status does not exist. However, certain aspects have been studied. Neurobiology studies have shown that human attention is governed by the “non-dominant” parietal and frontal lobes. Thus, with confusion and inattention, there typically is some molecular, structural, chemical, or electrical dysfunction in these brain regions.¹⁷

Seminal work in the 1940s using electroencephalography (EEG) in acutely delirious patients demonstrated global cortical function disturbances. These disturbances were characterized by slowing of the dominant posterior alpha rhythm on EEG and the appearance of abnormal slow-wave activity.¹⁷ These EEG findings have proven to be consistent and reproducible and have been used to resolve uncertainty in patients when the diagnosis of delirium was in doubt.¹⁸ These findings tend to suggest a final common neural pathway for delirium.¹⁷ In addition, the neurotransmitter acetylcholine is believed to play a key role.^18,19 Furthermore, the reticular activating system appears to be involved in modulating alertness. This is evident in the fact that strokes or tumors in this region of the brainstem can directly induce a coma.

Clinical Features

Many chief complaints are present under the umbrella of altered mental status. Common chief complaints include altered mental status, the patient is not acting like his or her baseline, the person is confused and disoriented, something is off, or the person is not acting right. A patient can present with an impaired level of consciousness and may be lethargic, stuporous, or comatose. A partner who accompanies a patient to the ED may say that the patient has been speaking to himself or hallucinating. Perhaps a parent will bring in a 19-year-old child after he went to a rave and is complaining that he is hyper-alert, agitated, confused, or disoriented.

When evaluating a patient presenting with an altered mental state, it is important to obtain as much history as possible and to perform a complete head-to-toe physical exam. Since patients often are unable to provide a history because of their altered state, a history should be obtained from family members or the nursing home to determine the baseline mental status. Obtain a timeline of the change in mental status. Review the patient’s medication history in the electronic medical record (EMR) or call the pharmacy.

Unfortunately, most of the time when people present to the ED with altered mental status, the history is difficult to obtain, and physicians initially are limited to information from either a family member or emergency medical services (EMS).

Vital Signs

As soon as the patient is brought into the ED, intravenous (IV) access should be obtained and oxygen and monitoring should be started. Because hypoglycemia is one of the most common life-threatening and reversible conditions of altered mental status, a glucometer check often is referred to as the fifth vital sign.²⁰ A finger stick glucose level should be obtained immediately on arrival, and treatment should be administered if the level is less than 70 mg/dL. Adults should be given 1 to 2 grams/kg of dextrose, usually as D50, for symptomatic hypoglycemia. Remember that “one amp” of D50 is only equal to 25 grams of dextrose. Some adults might need multiple amps to improve their hypoglycemia.

A full set of vital signs, including rectal temperature, should be taken quickly. The presence of fever may suggest meningitis, encephalitis, or another cause of sepsis. If a patient’s temperature is greater than 104° F and primary hyperthermia is believed to be a cause of altered mental status, start lowering the patient’s core temperature, most commonly through evaporative techniques. Such techniques consist of applying cold water to the patient’s skin with either a sponge or spray bottle, and then applying fans to enhance evaporative cooling. Other common temperature-lowering techniques include applying cooling blankets or ice packs to the groin, axillae, and neck. A very effective yet often impractical method is simply placing the patient in an ice bath. The goal should be to lower the temperature to 101° F in the first 30 minutes and then stop active cooling to avoid overshoot.

In the setting of hypothermia, when a patient’s temperature is below 95° F, rewarming should be initiated with either a convective warming blanket, such as the commonly used Bair Hugger, or other techniques. In very cold patients, warmed IV fluids may be needed. Ideally, normal saline is better to use than lactated Ringer’s (LR) solution in a hypothermic patient since LR is metabolized poorly by the cold liver. In extreme cases of hypothermia, techniques such as warmed bladder irrigation, chest tubes with irrigation, peritoneal lavage, and even extracorporeal membrane oxygenation can be employed.

The esophagus is the most accurate place for continuous monitoring of a patient’s temperature since it lies very close to the core; however, esophageal temperature monitoring devices may not be available in most settings. Devices such as temperature Foley catheters may be more accessible and practical.

Other vital sign abnormality combinations, such as tachycardia and hypertension, may suggest alcohol withdrawal or a multitude of other toxicological ingestions and toxidromes. (See Table 3.) A low respiratory rate in a patient with pinpoint pupils and decreased level of consciousness could call for immediate naloxone administration.

Primary Survey

Airway, breathing, circulation, disability, exposure, Focused Assessment with Sonography for Trauma (FAST) (ABCDEF). Altered patients can be approached in much the same way as typical trauma patients. As always, start with the airway. Assume every patient is a trauma patient until proven otherwise. Be gentle with the head and support the cervical spine with appropriate precautions. If the patient is not breathing, start bagging the patient and prepare to possibly establish a definitive airway. Look for signs or historical points to rule out easily reversible causes, such as opioid overdose, hypoglycemia, hypothermia, or hyperthermia, before intubating the patient. If the patient is breathing spontaneously but hypoxic, apply a non-rebreather mask and attempt to maintain the oxygen saturation above 88% to 90%. If concern exists for a possible opioid overdose in a patient who is severely hypoxic or near arrest, a dose of 0.4 mg to 2 mg IV push of naloxone is warranted. If no response is obtained, consider pushing up to 10 mg of naloxone.

To assess the patient’s disability, a frequently used method is the GCS score. (See Table 1.) If the GCS is less than 8, consider intubating the patient to protect the airway in the absence of the aforementioned reversible causes.

If the patient has cool or mottled extremities and there is concern with circulation, start resuscitating with IV fluids for hypotension. Assess for focal neurological defects suggesting a stroke or cerebral hemorrhage.

Look for other clues while examining the patient, such as an odor suggesting a toxic substance, or a rash or ecchymosis suggesting an infection or trauma. Perform a thorough visual inspection to look for any occult injuries. Finally, perform a FAST in patients with any suggestion of trauma or intra-abdominal hemorrhage (hypotension) as the last part of the primary survey.

History of Present Illness

When obtaining a history from an altered patient, the initial goal should be to determine why the patient was brought to the ED. EMS can provide clues to the etiology. The more history EMS can provide, the better. Family members or caretakers can provide a timeline of when the patient was “normal” and the transition to the present altered state, in addition to any pertinent prior history.

It is crucial to look at the EMR for prior history of psychiatric illnesses, substance abuse, prior overdoses, delirium, or existing dementia. Look for a history of seizures, diabetes, frequent UTIs, cerebrovascular accidents, or metastatic cancers.

One important determination when evaluating an altered patient is to differentiate an acute medical/organic process from a worsening functional/psychiatric illness. (See Table 4.) Disorientation and memory problems suggest an organic or neurologic illness, while problems with thought content can imply an underlying functional illness.²¹ Visual hallucinations are more common with organic causes of confusion when compared to functional causes, which involve auditory hallucinations more often. Altered behavior from organic causes frequently is acute and can happen at any age. Functional causes often occur gradually in onset over the course of weeks to months and are more typical in patients between 12 and 40 years of age. Medical confusion frequently involves fluctuating levels of consciousness as well as disturbances in attention, while psychiatric patients tend to be more alert, anxious, and agitated.²²

Family members, bystanders, or EMS sometimes can identify suspected triggers of the altered mental status episode (i.e., recent stressors, bouts of depression, recent infections, etc.) or a history of similar episodes in the past. Many psychotic conditions, including exacerbations of underlying schizophrenia and manic attacks, may happen many times throughout a person’s lifetime, so a history of prior episodes can be enlightening. When considering the potential for new psychiatric diagnoses, the patient’s age can be an important clue. Schizophrenia and bipolar disorders tend to begin at earlier ages compared with dementia, which is mainly a disease of the elderly.²³

If family members, EMS, or bystanders are able to confirm an acute, immediate onset of the symptoms with or without an association of weakness or speech changes, this may suggest a possible stroke or other medical cause for the change in status. Lastly, one of the most important aspects of the history of an altered patient is the medication review.

Physical Exam

Vital signs can help differentiate medical from psychiatric conditions. Abnormal vital signs occur more often with medical causes, while vital signs may be normal with psychiatric causes. As previously discussed, a fever and/or systemic inflammatory response syndrome (SIRS) criteria frequently imply an infection as a source for confusion, especially in elderly patients. Abnormal temperatures also may highlight hyperthermia or hypothermia as a primary cause of altered mental status.

Nystagmus, focal neurologic deficits, and traumatic signs are medically related more often, while the absence of these findings is more typical of psychiatric illness. Psychiatric illnesses also might have some purposeful movements. On lung exam, focal wheezes or rales can hint at a respiratory infection, such as pneumonia, or a cardiac problem, both of which can cause hypoxia or hypercarbia leading to alterations in consciousness and stupor.

A thorough neurologic exam is paramount when examining any altered patient because focal findings suggest structural abnormalities. Pupils and extraocular movements also are important when assessing for various toxidromes. Asking the patient to walk when feasible is a valuable aspect to the physical exam, since different types of ataxia may suggest various differential diagnoses from stroke to toxicological causes, ingestions, and even toxic levels of therapeutic medications.

In addition to those already discussed, many other specific physical exam findings, such as signs of trauma, the presence of an arteriovenous fistula, asterixis, cardiac murmurs, painful bones, the presence of a goiter or proptosis, and petechial or ecchymotic rashes, can guide further investigations.

Mental Status Testing

When evaluating an altered patient in the ED, many tests are available to supplement the physical and neurologic exam to assess mental status.²⁴ Two quick and easy tests that can be done at the bedside are the WORLD and the Six-Item Screen (SIS) tests. To perform the WORLD test, simply ask the patient to spell the word “world” correctly forward and backward, and then to list the letters in the correct alphabetical order. Failure to perform this test accurately has a sensitivity of 85%, a specificity of 88%, and a positive predictive value of 95% that the patient has some degree of dementia.²⁵

To perform the SIS test, ask the patient to name three random objects (e.g., pen, orange, and cat) and ask them to repeat the items aloud. After the patient has successfully repeated the three items out loud, ask them to state the year, month, and day of the week. Following that, ask the patient to recall the three items aloud they had listed prior to the exam. Give one point for each correct answer. A score below 5 suggests cognitive impairment and the patient should be evaluated for an underlying medical ailment. This test was found to be 94% sensitive and 86% specific in identifying cognitive impairment in older ED patients.²⁰

Diagnostic Studies

Considering the vast differential for the altered mental status patient, it is impossible to have a reflex order set that would be relevant to every altered patient. Endless amounts of laboratory tests may be considered in a patient with altered mental status. Targeted testing is appropriate in most instances. The ED workup evaluation ultimately will be directed at identifying the underlying process contributing to the patient’s altered state.

Most patients with an altered mental status can benefit from an electrocardiogram (ECG). Standard blood laboratory tests often will include a finger stick glucose, complete blood count with differential, and a complete metabolic panel with hepatic studies. A urinalysis, point-of-care pregnancy, reflex culture, and urine toxicology screens can be helpful as well. Additional tests that can be appropriate based on the clinical presentation include an arterial blood gas, coagulation studies, type and screen, ammonia level, thyroid profile, ethanol, blood cultures, calcium, magnesium, and phosphorus. Additional labs can include vitamin levels, such as B12 or folic acid, thiamine, syphilis testing, erythrocyte sedimentation rate, C-reactive protein, and HIV screening.

Obtain a portable chest X-ray and possibly a pelvic X-ray if trauma is suspected, followed by a head computed tomography (CT) scan. If the patient is older than 60 years of age and there is concern for trauma, consider adding a cervical CT and possibly even performing a trauma survey “pan-scan” of the chest, abdomen, and pelvis. If concern exists for brain damage with a negative CT, the treating team may consider ordering an inpatient brain magnetic resonance imaging or even an EEG when nonconvulsive status epilepticus is on the differential. If the patient has a fever, is altered, and there is no source of infection, a lumbar puncture may be indicated after a CT has ruled out an intracranial mass lesion or bleed.

Differential Diagnosis

The differential diagnosis for altered mental status is vast. The most common causes of abnormal behavior, especially in elderly patients, are infectious, such as UTI and pneumonia. Medication overdoses, withdrawals, and drug-to-drug interactions also are among the most common causes of acute altered mental status and confusion in the ED. Many altered patients will have an obvious presenting situation, such as a recent inciting fall with suspected head trauma while on anticoagulants and alteration since the fall. Another situation suggesting altered mental status is a suspected overdose patient who was found with an empty pill bottle nearby.

Intracranial hemorrhage is a critical condition in which death can occur if the patient does not receive immediate intervention. When suspected, a rapid CT can be diagnostic, followed by immediate neuro-intervention. High blood pressure can support intracranial pathology and, in the setting of a negative head CT, hypertensive encephalopathy should be considered. However, this is a diagnosis of exclusion pending an otherwise negative workup. Generally speaking, when patients have critical conditions, associated vital sign abnormalities will be evident. Two critical diagnoses that must be made immediately, as previously stated, are hypoxia and hypoglycemia for which oxygen and dextrose should be administered rapidly. If two SIRS criteria are met, sepsis should be considered, and a 30 mL/kg bolus of LR should be given for hypotension, as well as consideration for antibiotic administration. If a patient is febrile, confused, and there is no obvious external source, serious consideration needs to be given to the possibility of meningitis, encephalitis, brain abscess, or another intracranial infection.

A practical way to group life-threatening reversible causes of altered mental status is by the following five categories that were established by Edlow et al in The Lancet in 2014:²⁶

• intracranial pathology requiring neuroimaging;
• toxicological ingestions requiring immediate antidotes;
• infectious conditions requiring lumbar puncture and antimicrobials;
• seizures, particularly nonconvulsive status epilepticus, requiring EEGs; and
• endocrine or metabolic abnormalities requiring prompt treatment with electrolytes, thiamine, steroids, or dextrose.

Management

If a patient has abnormal vital signs, act immediately to stabilize the patient. When managing acutely altered patients in the ED, the first priority should be deciphering “sick” or “not sick.” If the patient is critical, stabilize the patient before proceeding to imaging. The diagnosis often is not established until after multiple days of inpatient testing, monitoring, and therapeutic intervention.

If a CT scan shows an intracranial bleed, remember that only 5 mm of blood is necessary before radically increasing the intracranial pressure (ICP). When a patient exhibits signs of increased ICP, elevate the head of the bed to 30 degrees. Promptly consult a neurosurgeon, if possible, and discuss the pros and cons of hyperventilation, as this may transiently lower ICP. When using hyperventilation, be sure to monitor the partial pressure of carbon dioxide (PaCO₂), and avoid lowering the PaCO₂ below 35 mmHg. If nonpharmacologic measures are unsuccessful in lowering ICP, consider administering 0.5 to 1.0 g/kg of mannitol after discussion with the neurosurgeon. Dexamethasone, 10 mg IV, is another therapeutic option, which reduces vasogenic brain edema associated with a tumor.

Pharmacologic management of delirium in older patients is a common and difficult problem. Often, this problem is exacerbated at night when traditional “sundowning” occurs or in the chaotic environment of the ED. Patients can pose a risk to themselves since they often are a fall risk and pick at tubes and lines because they are confused and agitated. For many years, delirium in the inpatient and emergency setting has been treated with antipsychotic medications, such as haloperidol, quetiapine, ziprasidone, and other first- and second-generation antipsychotics. Pharmacological management is especially common at night and in the ED when there is not enough medical staff to watch patients and, therefore, medication is deemed necessary.

A frequently used sedative combination in the ED is referred to as a “B-52,” which is 25 mg of diphenhydramine, 5 mg of haloperidol, and 2 mg of either lorazepam or midazolam. This medication combination can be particularly dangerous in the elderly population because both benzodiazepines and anticholinergics are known to cause dangerous effects in elderly patients. Additionally, the full 5 mg dose of haloperidol is more likely to cause extrapyramidal side effects in the elderly compared to younger patients.

If treating delirium in a patient is deemed necessary with an antipsychotic such as haloperidol, it is recommended to start with only 2 mg IV and monitor for effect, especially in elderly patients. It is crucial to obtain an ECG before administering haloperidol because of the known QT-prolonging effect of antipsychotics and subsequent risk for dysrhythmias. Ideally, the patient should be placed on a continuous cardiac monitor with the capability to monitor continuous QT intervals when available. In the event that the QTc is prolonged (greater than 440 milliseconds [ms] in men or 460 ms in women), 1 to 2 grams of magnesium sulfate IV should be administered to shorten the QT interval. Magnesium administration improves the safety profile of antipsychotic medications and decreases the chances of the patient developing the deadly torsades de pointes dysrhythmia.

However, a recent study has challenged the utility of antipsychotic use in delirious patients at all. The authors of a systematic review analyzing 16 randomized controlled trials with 1,768 patients, as well as 10 observational studies, found no difference in sedation status, delirium duration, hospital length of stay, or mortality when comparing antipsychotic use to placebo in delirious older adult patients in the hospital setting. They also found no difference in delirium severity or cognitive function or mortality when comparing haloperidol use vs. second-generation antipsychotics. The authors concluded that current evidence does not support the use of antipsychotics to manage delirium in adult hospitalized patients, and more research is required to specifically look at the elderly population.²⁷

Be particularly aware of the possibility of alcohol withdrawal, even in the elderly and patients without a history of alcoholism. Alcohol abuse is prevalent in approximately 20% of men and 10% of women, and about 50% of those experience alcohol withdrawal. The disease also has significant morbidity and mortality.²⁸ The presentation of these patients can range from mild, requiring only one oral benzodiazepine, to life-threatening delirium tremens that may require benzodiazepines, barbiturates, propofol, and/or another atypical agent, such as dexmedetomidine or ketamine.

Benzodiazepines, namely diazepam, lorazepam, midazolam, oxazepam, and chlordiazepoxide, are first-line agents for alcohol withdrawal.²⁹ The three most commonly used benzodiazepines for alcohol withdrawal are typically IV diazepam 5 mg to 10 mg every 5 to 10 minutes, IV lorazepam 2 mg to 4 mg every 15 to 20 minutes, and oral chlordiazepoxide 20 mg to 100 mg every hour.³⁰ Usually IV lorazepam or diazepam is preferred in the acute setting and for more severe symptoms, and oral chlordiazepoxide is reserved for less severe symptoms and outpatient treatment regimens.

Although there is consensus that benzodiazepines are the first-line treatment, there is much debate as to which benzodiazepine is preferred. Although diazepam is sometimes preferred because of its quick onset of action and longer half-life due to active metabolites, consideration should be taken for underlying liver disease and/or cirrhosis. These active metabolites seen in longer-acting agents, such as diazepam and chlordiazepoxide, tend to result in a smoother clinical course with lower chances of recurrent withdrawal, seizures, and delirium tremens. However, these same metabolites of both can accumulate to quite a significant extent in the liver, causing unpredictable half-lives in advanced liver disease patients, and can be very dangerous.³¹

Therefore, in patients with liver disease, agents chosen should be those without active metabolites. A simple mnemonic “Out the Liver” can be used to remember which benzodiazepines are best used for advanced liver disease: oxazepam, temazepam, and lorazepam.³¹ Because of the absence of metabolites, their pharmacokinetics are much more favorable and predictable in this population, and their half-lives remain relatively constant.

A certain number of patients with severe symptoms may be resistant to benzodiazepines. In this situation, a well-studied, effective drug to use is phenobarbital at 130 mg to 260 mg IV, repeated every 15 to 20 minutes.³² Although not recommended as a monotherapy for alcohol withdrawal syndrome, many experts believe a single dose of phenobarbital on day 1 can decrease the hospital length of stay and improve outcomes when administered in conjunction with benzodiazepines.³³ In the intensive care unit (ICU) setting, the addition of phenobarbital to benzodiazepines was found to be more effective than benzodiazepines alone when treating acute alcohol withdrawal.³⁴ Other contradicting studies have concluded that adjunctive phenobarbital use in the ED for alcohol withdrawal syndrome did not result in decreased ICU admissions, severity of symptoms, or complication rates.³⁵

Another medication that has been used as a last resort in managing alcohol withdrawal is IV propofol infusion at 25 mcg/kg per minute. Propofol is typically started in withdrawal patients who do not respond to benzodiazepines and barbiturates. Propofol is a great option in mechanically ventilated patients, those who are not candidates for other adjuvant therapies, or those with seizure activity or refractory delirium tremens.³⁶

Disposition

Altered mental status has a relatively high mortality rate, as high as 30% at six months in many studies. Subsequently, the ED disposition for most patients will be admission to the hospital for further evaluation and management. Only patients with readily reversible causes of mental status changes and appropriate home care and physician follow-up can be discharged safely. There should be a clear cause of the episode that is treated and reversed, and patients should be back to baseline mental status.

Cost Considerations

More than 2.6 million older adults develop delirium each year, costing close to $164 billion in annual healthcare expenditures. Given the high mortality rate of altered mental status, especially when missed, it is no surprise that such a significant amount of money is spent on these patients. As discussed earlier in the section on diagnostic studies, a number of laboratory tests can be considered in altered mental status patients. Unfortunately, the desire for diagnostic completeness can dramatically increase costs and sometimes even delay the prompt treatment for more glaring and obvious disorders. As discussed earlier, targeted testing is important and should be allocated on a case-by-case basis.

New Technologies

One new technology that can be considered for use in an altered mental status patient is point-of-care ultrasound to diagnose increased ICP. Ultrasound is an easy and rapid way to diagnose increased ICP when more advanced tests are not available. Various causes of increased ICP, including head injury, spontaneous intracranial bleeds, metastatic tumors, and more, can contribute to altered mental status. Unfortunately, papilledema on physical exam is difficult to diagnose. Many emergency medicine physicians do not believe in their ability to perform this exam well, and it is even more difficult to perform on an unconscious, intubated, or paralyzed patient. Further, papilledema seen on funduscopic exam is a delayed PE manifestation of elevated ICP. A high-frequency, linear ultrasound probe can be used to measure a normal optic nerve sheath diameter (ONSD), which should be less than 5.0 mm, typically measured 3 mm posterior to the globe bilaterally. The average of two measurements should be used to correlate with ICP. When the ONSD average is greater than 5 mm, suspect elevated ICP.³⁷ While the bedside exam is very specific, it is not sufficiently sensitive to rule it out. Therefore, when positive, the diagnosis is made. When negative, further testing still is warranted.

Medical Legal Considerations

Informed Consent

When an emergency physician cares for a patient who is acutely confused, altered, violent, or presents a danger to himself/herself, family, or healthcare workers, the physician will need to treat without informed consent. This can present a potential legal issue if appropriate precautions are not taken. Proper documentation during these cases is essential. There have been numerous cases for which physicians were acting in the best interest of a patient, but because of failed documentation, the physician and hospital were sued. Having another physician present during these decisions and, further, having that physician document in the chart “I agree” with the necessary precautions taken, can be extremely supportive if legal action is taken at a later date.³⁸ When the patient’s family members are present, explaining to them the pros and cons, and need for intervention, and further documenting this discussion and their support are essential.³⁸ If the physician is unable to obtain consent for treatment for whatever reason, it is crucial to document three factors: the intervention is emergent; consent could not be obtained; and the intended treatment was specifically for the benefit of the patient.³⁹ A classic case in which the physician was protected by appropriate documentation is Craig L. Miller v. Rhode Island Hospital et al.⁴⁰ In this case, the patient was intoxicated, violent, and deemed to not have capacity to perform informed consent. He had an invasive diagnostic procedure performed, and then sued the hospital for acting against his wishes. The hospital was not held responsible.

Physical Restraints

Often, when dealing with altered mental status patients who are violent or a risk to others or themselves, restraints may be necessary. However, when applying four-point or two-point restraints on violent or delirious patients who repeatedly pull out their lines, there are significant medicolegal considerations involved. As stated earlier, appropriate documentation is essential. The American College of Emergency Physicians has a detailed policy on the appropriate use of restraints. When appropriate and safe, verbal de-escalation and standard treatment of underlying medical or psychiatric conditions should be attempted before restraints.⁴¹ However, some patients still will require restraints. When using restraints, the treating physician should recognize that it is the physician’s responsibility to watch over the health, safety, and well-being of the restrained patient. There are two case examples where restraints ultimately led to a patient’s death because proper monitoring was not performed — the Estate of Doe v. ABC Ambulance⁴² and Larry Gazda v. Pima County.⁴³ In both cases, the physician and hospital were successfully sued.

Side Effects of Opioids Causing Altered Mental Status in Older Patients

When addressing the difficult situation of an elderly patient who has significant pain, the ED physician is faced with the challenge of whether to give opioids for pain control. It is well-known that opioids cause confusion and delirium in older adults and increase falls. In addition, opioids themselves have been shown to cause delirium in older adults.

Unfortunately, older patients frequently are undertreated for their pain when compared to their younger counterparts. However, untreated pain can cause older adult patients to become more delirious as well.⁴⁴ The treatment of pain with opioid medications in older adult postoperative patients has been shown to result in an overall reduction in delirium compared to patients who did not receive narcotics for pain control.⁴⁵ Therefore, it is recommended that opioid medications be used for older patients in moderate to severe pain, using a smaller starting dose, and choosing medications with shorter half-lives to avoid medication stacking.⁴⁶ If an older adult patient has a hip fracture, the most ideal form of pain control is a fascia iliaca nerve block, but this can be technically difficult for practitioners who are not familiar with the procedure. There are excellent online video tutorials that teach how to perform a fascia iliaca block under ultrasound guidance. If the ED physician is unable to perform the block, it can be performed by anesthesia. If a nerve block cannot be performed, it is better to give opioids to elderly patients and adequately control their pain.

Another potential non-opioid option when trying to accomplish analgesia is ketamine. Ketamine has potential deleterious sympathomimetic effects and enhances the body’s natural secretion of catecholamines like norepinephrine and epinephrine. These catecholamines can be dangerous in elderly patients with underlying hypertension and atrial fibrillation. However, in subdissociative lower doses used for pain control, such as 0.15 mg/kg to 0.3 mg/kg, ketamine provides extremely effective pain control with minimal vital sign alterations. This often is ideal in trauma patients who have joint injuries or dislocations. There is moderate evidence from the surgical literature that ketamine administration is associated with a lower incidence of delirium.⁴⁷ Overall more research is needed, but this does provide a potential adjunct when opioids are not ideal.

Summary

When a patient presents to the ED in an altered state, the first step is to determine whether the patient has a critical condition requiring rapid assessment and treatment using the ABC algorithm. If the patient is critical, establish two large-bore IVs, and treat every patient as a trauma patient until proven otherwise. If the patient has stable vital signs, be sure to get the best ancillary history possible, including the EMS report, and perform a meticulous physical exam. Look for subtle clues to infection, such as a hidden decubitus ulcer or small areas of ecchymosis. Evaluate vital sign abnormalities that may suggest a toxidrome or ingestion or that point toward infectious causes.

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