Approach

Although AMS is common in presentation, its workup is challenging because there are many potential causes, ranging from less serious to life-threatening. Therefore, a thoughtful, comprehensive approach is essential, which involves clarifying the history and onset of symptoms with the patient and/or caregivers, and localizing specific signs or symptoms to narrow the differential.

Evaluating a patient with AMS is difficult because obtaining a reliable history from the patient is often impossible. Initially, it is imperative to establish basic life support.[6] Once the patient's airway, breathing, and circulation have been secured, a secondary emergency survey should be conducted. See Urgent considerations section for conditions requiring immediate management. 

After emergency treatment and stabilization of the patient, a directed differential diagnosis should be considered. Older patients often present with relatively common conditions in uncommon, subtle manners. For example, they may present with infections without fever or leukocytosis, or a perforated viscus without abdominal pain or tenderness. It is therefore important to adopt a logical, stepwise approach.

Healthcare professionals often fail to recognize and diagnose delirium in older patients.[26][27] There are multiple validated evaluation tools for delirium. 

  • The Confusion Assessment Method (CAM), the CAM Short Form (CAM-S), and the brief CAM (bCAM) can be used to diagnose delirium, focusing on four cardinal features:[28][29][30][31]

    • Acute onset and fluctuating course

    • Inattention

    • Disorganized thinking

    • Altered level of consciousness.

    CAM is a well-validated tool for evaluating delirium, with a reported sensitivity of 87% to 100% and specificity of 80% to 100%.[32] CAM is specific for evaluating incident delirium in critically ill older patients (although its sensitivity may be lower than that of some other screening tools), and it is commonly used to determine delirium severity (as are the Delirium Rating Scale [DRS] and the Memorial Delirium Assessment Scale).[33][34] 

  • The Observational Scale of Level of Arousal (OSLA) is a bedside evaluation tool, which has a sensitivity of over 90% and a specificity of over 80% for diagnosing delirium in older patients.[35] The evaluation is based on patient observations in four clinical areas: eye contact, eye opening, posture, and movement. 

  • 4AT is a brief tool that combines four elements:[8][36]​​

    • Alertness: anything less than A on the alert, voice, pain, unresponsive (AVPU) scale

    • AMT4: four questions from the Abbreviated Mental Test (age, date of birth, place, and current year)

    • Cognition: recite the months backward (December to July only)

    • Acute change or fluctuating course.

History

Initially determine a baseline level of mentation/cognition and establish the rapidity with which changes have occurred. This often requires the assistance of a third party, such as a relative, spouse, or friend.

Questions should be targeted at establishing recent events such as trauma, relevant past medical history, previous medication use, and use of alcohol or toxins. Every body system should be assessed in an attempt to localize the potential etiology.

Key historical considerations include the following:

  • Previous cognitive status: it is imperative to establish a baseline cognitive and functional status before the onset of symptoms. In most cases, a rough assessment of previous cognitive status can be obtained from the patient's family. A previously obtained assessment of cognition can also be compared with a current screen to determine whether symptoms related to cognitive changes are acute or chronic in nature. The Folstein Mini-Mental State Examination (MMSE) is still the most widely used cognitive screening test.[37] However, it has been increasingly shown in the literature to be poorly sensitive in differentiating mild cognitive impairment from a dementia syndrome, due largely to the MMSE’s lack of executive function testing.[38][39][40] There are several other tests available, including the 10-minute Montreal Cognitive Assessment Scale (MoCA).[41][42][43] Some instruments, such as the Mini-Cog test and Addenbrooke's Cognitive Examination-Revised (ACE-R), have been shown to perform as well as the MMSE in terms of detecting dementia.[40] Existing tools for evaluating delirium superimposed on dementia lack robust evidence to support their utility; however, results obtained with the CAM and CAM-ICU are promising.[44][45]

  • It is noteworthy that fluent aphasia (e.g., Wernicke encephalopathy) can sometimes be mistaken for delirium or AMS, particularly when other neurologic signs are not present. Therefore, short tests for aphasia (e.g., object naming, phrase repetition, following simple commands) should be conducted in differentiating this condition.

  • Previous functional status: care should be taken to determine whether the patient has deficiencies in activities of daily living, hearing impairment, or vision impairment.

  • Medication usage: medication lists should be carefully scrutinized. Potentially high-risk medications should be discontinued whenever possible. Herbal remedies, nonprescription medications, and illicit substances should also be considered in a medication review.

  • Comorbid conditions: particularly neurologic diseases (e.g., stroke, Parkinson disease, dementia), cardiovascular diseases (e.g., myocardial infarction [MI], angina), and a history of renal/metabolic diseases (e.g., hyponatremia, hypernatremia, chronic renal failure).

  • Pain levels: the presence of severe pain is often associated with AMS. Chest pain (often described as heavy, or tight) radiating to arms, back, neck, or jaw is typical with MI, although chest pain may be absent in older adults and people with diabetes.

  • Alcohol and drug use: alcohol intoxication and withdrawal are frequently associated with AMS.

  • Nonspecific irritability: together with typical symptoms of sweating, palpitations, weight loss, may suggest thyrotoxicosis.

  • Environmental factors: key issues such as sleep deprivation, multiple procedures or surgery, restraint use, and intensive care stay are associated with delirium and might be causative. Hypothermia may be suspected if there is a recent history of exposure to the cold for a prolonged period of time, or with inadequately warm clothing. This is more common in older adults, or in young children and infants. Alternatively, heat stroke may be suspected following intense exercise under hot, humid conditions.

Physical examination

Possible helpful findings include signs of head trauma, icterus, hydration status, dry mouth, a bitten tongue, nuchal rigidity, heart murmurs, and abdominal tenderness. Important considerations include the following.

  • Pupillary response: might suggest drug intoxication, drug withdrawal, or stroke.

  • Vital signs: may be particularly revealing, either in a toxidrome pattern, such as anticholinergic toxicity (e.g., fever, tachycardia, hypertension), or in a pattern of autonomic dysfunction, as in alcohol withdrawal, although this may be blunted in older people. Bradycardia and hypotension reflect possible myxedema coma or heart block. Bradycardia and hypertension can be signs of elevated intracranial pressure. Tachycardia and hypotension may suggest shock either from cardiogenic or hypovolemic etiologies.

  • Fever: may be helpful for distinguishing infection. Hyperthermia (e.g., with heat stroke) is generally associated with core temperatures >104°F (>40°C). Sweating, together with palpitations, weight loss, and irritability, may suggest thyrotoxicosis.

  • Core body temperature: lowered to <95°F (<35°C) if hypothermic. Low-reading infrared tympanic membrane thermometers should be used.

  • Neck stiffness: meningitis or encephalitis should be considered.

  • Lung exam: decreased breath sounds and rales might indicate infection (e.g., pneumonia) or diseases commonly associated with hypoxia such as congestive heart failure (CHF) and COPD.

  • Cardiovascular exam: physical findings evident with coronary disease or MI should be evaluated.

  • Abdominal exam: might suggest intra-abdominal infection. If the history and physical exam findings suggest constipation, secondary causes need to be ruled out. Features of intestinal obstruction may be present.

  • Suprapubic tenderness or palpable bladder: might suggest urinary tract infection (UTI) or obstruction.

  • Hip tenderness: might suggest occult hip fracture, a frequently missed trigger for delirium in frail older patients, particularly if they are bed-bound.

  • Neurologic findings: focal findings might suggest stroke or neurologic insult. The investigation should include cranial nerve testing (including visual fields); motor exam (to assess focality and possible parkinsonism); sensory (often difficult in a patient with AMS), cerebellar, and verbal abilities; and gait.

Investigations

Investigations should be guided by history and physical exam findings.[25] In the absence of definitive historic or physical findings, a preliminary workup should include the following:

  • Plasma glucose should be the first test in any patient presenting with AMS; it is quick and easy to perform, and abnormalities are readily treatable. If the test is not immediately available, empiric glucose should be given.

  • CBC to confirm suspected anemia and help in the diagnosis of infection.

  • Chemistry panel, including glucose levels, to rule out metabolic disturbances.

  • Thyroid function tests if thyrotoxicosis or myxedema coma is suspected.

  • Urinalysis to rule out UTI.

  • Chest x-ray to help detect pneumonia, CHF, or other potential causes of hypoxia.

  • Drug levels in patients on digoxin, lithium, quinidine, and alcohol (if a history of alcohol abuse is suspected).

  • ECG and cardiac enzymes to rule out MI.[6]

  • Arterial blood gas or pulse oximetry to evaluate for hypoxia and lactate, commonly found in sepsis, or hypercapnia.

  • If liver dysfunction is suspected, liver function tests, including bilirubin, are warranted; coagulation studies may be abnormal. Plasma ammonia measurement should be performed in patients with delirium/encephalopathy and liver disease.[46]

  • If infection is suspected, blood and urine culture should be obtained. Lumbar puncture is recommended in the presence of nuchal rigidity and fever, or if encephalitis is suspected.

  • If a hip fracture is suspected as a cause of AMS (e.g., with a history of a fall and age above 65 years), a pelvic x-ray and consideration of a hip computed tomography (CT) scan (e.g., in patients with persistent pain, concerning exam findings, no obvious fracture visible on x-ray) or bone scan may be helpful.

If no etiology is identified from preliminary testing, further investigations should be considered including the following:

  • Neurologic imaging (CT and/or magnetic resonance imaging).

  • Holter monitor, exercise testing, and/or cardiac electrophysiology studies to assess for arrhythmias.

  • Coronary angiography to rule out ischemic heart disease.

  • Echocardiography to assess for cardiac failure and cardiomyopathy.

  • B-type natriuretic peptide to assess for cardiac failure.

  • CT pulmonary angiogram or ventilation-perfusion scan to evaluate for pulmonary embolism as a cause of hypoxia.

  • Glomerular filtration rate may be useful in uremia.

  • Abdominal imaging and/or endoscopy if abdominal pathology such as acute appendicitis or bowel ischemia is suspected.

  • EEG to rule out seizure activity and encephalopathy. Diffuse slowing of the EEG may be helpful in highlighting delirium.[47]

  • A therapeutic trial of parenteral thiamine if Wernicke encephalopathy is suspected.

Urgent or emergent brain imaging is needed in the presence of rapid deterioration of mental status, and may be done simultaneously with or even before some laboratory tests under certain circumstances (e.g., suspected stroke or intracranial hemorrhage). If the diagnosis of dementia is being considered, a CT scan of the head is useful for excluding tumors, normal pressure hydrocephalus, and subdural hematoma. Investigations in patients with signs of hypertensive encephalopathy should focus on any signs of end-organ damage. In addition, spot urine or plasma metanephrine may be useful before initiation of drug therapy to rule out pheochromocytoma in these patients.

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