Perspective

Altered mental status is a spectrum of disease ranging from sleepiness and confusion to frank coma. Approximately 3% of patients arrive at the emergency department (ED) in a altered state.

Epidemiology

Roughly 85% of cases of altered mental status are caused by metabolic or systemic derangements, whereas 15% are caused by structural lesions. Once the ABCs (airway, breathing, and circulation) have been controlled and the patient stabilized, it is the role of the emergency physician (EP) to quickly distinguish structural from metabolic and systemic causes.

Pathophysiology

Consciousness is collectively made up of arousal and cognition. Arousal is defined as the awareness of self and the surroundings. The neuroanatomic structure primarily responsible for arousal is the ascending reticular activating system, which is located in the dorsal part of the brainstem. It controls the input of somatic and sensory stimuli to the cerebral cortex and functions to initiate arousal from sleep. Cognition is the combination of orientation (accurate perception of what is experienced), judgment (the ability to process input data to generate more meaningful information), and memory (the ability to store and retrieve information). The brain’s cognition centers are located primarily in the cerebral cortex.

Coma can be caused by damage to the brainstem (Fig. 94.1), the cerebral cortex, or both. These structures are vulnerable to toxins, metabolic derangements, and mechanical injury. Localized, unilateral lesions in the cerebral cortex do not usually induce altered mental status or coma, even with other cognitive functions being impaired. However, if both cerebral hemispheres are affected, altered mental status or coma can occur, depending on the size of the insult and its speed of progression. The ascending reticular activating system can also be vulnerable to small, focal lesions in the brainstem, which can result in coma.^1,2

Fig. 94.1 Cerebral insults leading to a depressed level of consciousness.

A, Ascending reticular activating system; B, bilateral cerebral cortex.

Presenting Signs and Symptoms

The chief complaints of patients and their family members are highly variable along the spectrum of altered mental status. Patients may report increased sleepiness or periods of confusion and disorientation. They may have trouble concentrating or maintaining focus on tasks that were previously performed without difficulty. Family members may describe the patient as being less interactive or more difficult to arouse from sleep.

Regardless of the circumstance, the EP will frequently need to use alternative sources of information to answer key historical questions that may alter the breadth and speed of the diagnostic work-up undertaken. Common sources of information include family members, neighbors, prehospital personnel, law enforcement, and nursing home staff.³ They may know of preceding symptoms such as headache, nausea, vomiting, or fever. It is important to determine the rate of symptom onset and whether the patient had any history of trauma, exposure to drugs or toxins, or new medications or change in dosage. Family members usually have some knowledge regarding the patient’s past medical history. Additionally, previous medical records should be reviewed whenever possible to confirm or augment the information provided. If the patient’s historical baseline mental status cannot be established, the current findings must be assumed to be an acute change.⁴

The age of the patient can be a key historical tool that may focus the physician on the most probable cause of the patient’s symptoms (Box 94.1).

In infants, infectious causes of altered mental status are most common; however, nonaccidental trauma and metabolic derangements from inborn errors of metabolism are also possible causes.⁵ Toxic ingestions are commonly seen in young children. Adolescents and young adults are often seen in the ED after recreational drug use. The elderly are particularly susceptible to infectious causes and to disorders related to changes in medications or drug doses, use of over-the-counter medications, and alterations in their living environment. Psychiatric illness should be considered in the adolescent through elderly population and must be distinguished from medical illness as a cause of the patient’s symptoms.

As with all patients, specific attention should first be paid to assessment of the ABCs and specific vital signs. Alterations in respiratory patterns such as hyperventilation, Kussmaul or Cheyne-Stokes breathing, agonal breathing, or apnea should be noted and may suggest toxic or metabolic derangements or primary central nervous system abnormalities. Marked hypotension or hypertension should be addressed immediately even if the underlying cause is unknown. Bradycardia may be the result of increased intracranial pressure as seen in the Cushing response and suggests a state of hypoperfusion. Tachycardia may also result in hypoperfusion and can be the result of toxic, metabolic, or primary cardiac causes. Assessment of temperature is crucial because both hypothermia and hyperthermia can cause altered mental status from infectious, structural (Box 94.2), environmental exposure, or toxic or metabolic causes (Box 94.3).

Any signs of trauma should be sought immediately. Scalp lacerations or hematomas, depressed skull fractures, hemotympanum, raccoon eyes, Battle sign, cerebrospinal fluid otorhinorrhea, cervical spine step-offs, and crepitus all suggest a traumatic cause. Other signs of trauma include lesions on the chest, abdomen, or pelvis; long-bone deformities; and gross blood in the rectum or vagina or at the urethral meatus.

In the absence of trauma, breath odors may be helpful, including the smell of alcohol, ketones (diabetic or alcoholic ketoacidosis), and bitter almonds (cyanide toxicity). Abdominal findings include ascites, hepatosplenomegaly, ecchymosis, and striae. Lesions on the skin such as rashes, signs of drug use (needle tracks, medication patches), and embolic phenomena can be telling.

Neurologic Evaluation

A systematic neurologic examination is a key tool in determining whether the cause is structural, systemic, or metabolic. The basic examination includes evaluation of the patient’s level of alertness, cranial nerves, strength, sensation, reflexes, gait, and cerebellar function.

The Glasgow Coma Scale (GCS) can be used to assess the patient’s level of consciousness. The GCS does not differentiate between causes of altered mental status or coma or assess cognition. However, it is useful in monitoring changes in mental status when serial examinations are performed and serves as an objective reference when communicating with consultants (Table 94.1).⁶

Table 94.1 Glasgow Coma Scale

A focal neurologic deficit usually suggests a structural cause. Pupillary findings such as unilateral dilation or a “blown pupil” and loss of reactivity indicate uncal herniation, which is a neurosurgical emergency. Funduscopic examination can demonstrate hemorrhage in the setting of trauma or papilledema, which suggests increased intracranial pressure.²

Testing of eye movements is a hallmark in the neurologic examination of patients with altered mental status or coma. Eye movements are coordinated by ocular centers in the cerebral cortex and the medial longitudinal fasciculus located in the brainstem. The extraocular muscles are innervated primarily by cranial nerves III, IV, and VI. Disconjugate gaze in the horizontal plane is common and can be associated with sedated or drowsy states or alcohol intoxication. Disconjugate gaze in the vertical plane is more ominous and points to pontine or cerebellar lesions. A persistently adducted eye is caused by cranial nerve VI paresis, whereas a persistently abducted eye is caused by cranial nerve III paresis. These are nonlocalizing lesions; however, elevated intracranial pressure or mass effects from trauma, for example, can compromise cranial nerve functions via extrinsic compression. In the absence of contraindications, oculocephalic (doll’s eyes) or oculovestibular reflex testing can be very helpful. If intact, these reflexes demonstrate functional integrity of a significant majority of the brainstem, thus making it exceedingly unlikely as the anatomic location for the cause of the patient’s altered mental status.^1,2,5,7

Differential Diagnosis and Medical Decision Making

The differential diagnosis of altered mental status and coma is extensive and can be daunting for the busy EP (see Boxes 94.1 to 94.3). Fortunately, there are many distinguishing features in the physical examination that, when combined with information gleaned from the patient’s history of the present illness, past medical history, and response to therapy (i.e., dextrose, naloxone), point to a particular cause and are frequently of greater diagnostic value than imaging, electrocardiograms (ECGs), and laboratory tests.¹ However, a systematic approach is best and reduces the likelihood of missing an important clue.^1,2,8

Diagnostic Testing

Diagnostic testing in patients with altered mental status or coma is based on information gathered from the history and physical examination, which in most cases will point toward a structural versus systemic or metabolic cause. Extensive metabolic work-ups should not precede neuroimaging studies in patients with altered mental status or coma that may be due to structural causes. Similarly, treatment of suspected narcotic overdose or hypoglycemia should not be delayed in favor of imaging studies. However, in undifferentiated patients, diagnostic tests should be performed in parallel whenever possible to avoid unnecessary delays in initiating treatment. A general approach to the diagnostic work-up of patients with altered mental status or coma is shown in Figure 94.2.

Fig. 94.2 Diagnostic approach to altered mental status and coma.

BP, Blood pressure; CT, computed tomography; CVA, cerebrovascular accident; ECG, electrocardiography; GCS, Glasgow Coma Scale; HR, heart rate; ICU, intensive care unit; MRI, magnetic resonance imaging; OR, operating room; RR, respiratory rate; RSI, rapid-sequence intubation.

Treatment

Initial stabilization and quick control of the ABCs are paramount in patients with altered mental status. Patients should be placed immediately on telemetry with concomitant administration of oxygen and initiation of intravenous access. Definitive airway control with endotracheal intubation is critical in patients without a gag reflex or with a GCS score lower than 8. Lidocaine premedication should be used for rapid-sequence intubation in patients with suspected elevated intracranial pressure. In the setting of trauma, maintaining spinal precautions with a backboard in addition to initiation of intravenous fluid therapy is mandatory.

Once initial stabilization has been addressed, reversible causes must be sought. A bedside ECG and capillary blood glucose test should be obtained immediately. Blood and urine should be sent to the laboratory for studies early after the patient’s arrival, and the patient should be scheduled for emergency head CT. Empiric administration of a “coma cocktail” consisting of dextrose, thiamine, and naloxone is controversial but may bring immediate results and significantly narrow the differential diagnosis.

Physical examination with specific attention to brainstem function dictates further work-up and therapy. Patients whose brainstem function is compromised with evidence of brain herniation require immediate evaluation by neurosurgery. Empiric therapy with mannitol may be indicated in this setting. Elevating the head of bed to 30 degrees (if not contraindicated) and hyperventilation to a PCO₂ of 35 mm Hg are additional temporizing measures. Evidence of brain herniation secondary to a traumatic cause may necessitate the use of burr holes on the side of the dilated pupil as a last resort. Ventriculostomy and monitoring of intracranial pressure are often performed by a neurosurgeon in the ED.

Patients with compromised brainstem function but no evidence of herniation should have immediate consideration for basilar artery or bilateral vertebral artery occlusion and undergo CT or magnetic resonance angiography while receiving supportive care with a concomitant toxic and metabolic work-up. Patients are considered to have unsalvageable brain tissue if they have no brainstem reflexes, have not received neuroactive medications, and are normothermic.

In patients whose brainstem function is intact, supportive care is provided while the work-up proceeds. Lesions discovered on brain CT require immediate evaluation by neurosurgery. In general, patients with operable lesions are transferred immediately to the operating room; patients with inoperable lesions continue to receive supportive care. In cases in which an infectious cause is suspected, empiric antibiotic coverage should not be delayed for lumbar puncture or other diagnostic modalities.

In the setting of suspected toxic ingestion, activated charcoal with or without sorbitol is indicated. Gastric lavage has been used in patients with recent (less than 60 minutes since ingestion), potentially lethal toxic ingestion (e.g., tricyclic antidepressants, beta-blockers); however, this intervention is somewhat controversial and associated with potential complications, including aspiration and esophageal damage. Specific antidotes, if applicable based on the history and physical examination, should be initiated early. Finally, early hemodialysis should be considered in patients who have ingested substances amenable to this therapeutic modality.¹⁰

Admission and Discharge

The majority of patients who have significant alterations in mental status require admission for further work-up and treatment. The exception is patients with an easily reversible cause, such as opiate overdose or hypoglycemia, who may be discharged after a period of observation during which there is a return to baseline mental status. In addition, patients with alcohol intoxication and no other cause of altered mental status may be discharged once they are deemed clinically sober. Placement in an intensive care unit setting is usually appropriate for patients whose mental status is persistently altered.

Immediate consultation with the neurosurgical service is paramount for patients with potentially operable lesions. After definitive airway control and stabilization of vital signs, rapid transfer to a center with neurosurgical diagnostic and therapeutic capabilities should be sought if the necessary resources are not available locally.