Altered mental status is a change in level of consciousness (i.e., attentiveness) and/or cognition (i.e., mental processes or thoughts; orientation; memory loss).

It can range from confusion to complex, life-threatening coma.


Terminology for impaired levels of consciousness, in order of increasing severity1

Confusion, a mental and behavioral state of reduced comprehension, coherence, and capacity to reason,

Delirium is a special example of an acute confusional state in which impaired attention and reasoning are associated with agitation, hallucinations, and in some cases, tremor and convulsions.

Drowsiness: Inability to remain awake without external stimulation; often associated with some degree of confusion.

Stupor: State in which only vigorous external stimulation can arouse the patient; once aroused, responses remain markedly impaired.

Coma: Deep sleep-like state; patient cannot be aroused even with vigorous or repeated external stimulation.

Altered mental status stems from a not Intact or non-functioning brainstem reticular activating system and its cortical projections.




A 23-year-old woman is admitted to the hospital obtunded with slow respirations (7 breaths/min). Blood pressure is 90/60 mm Hg and the pulse is 90 beats/min. She was found at home in bed with empty bottles of diazepam, acetaminophen with codeine, and fluoxetine lying next to her.

How is the diagnosis of a drug overdose made?

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What are appropriate steps in managing this patient?

Regardless of the type of drug or poison ingested, the principles of initial supportive care are the same. Airway patency with adequate ventilation and oxygenation must be obtained. Unless otherwise contraindicated, oxygen therapy (100%) should be administered. Hypoventilation and obtunded airway reflexes require tracheal intubation and mechanical ventilation. Many clinicians routinely administer naloxone (up to 2 mg), dextrose 50% (50 mL), and thiamine (100 mg) intravenously to all obtunded or comatose patients until a diagnosis is established; this may help exclude or treat opioid overdose, hypoglycemia, and Wernicke-Korsakoff syndrome, respectively. The dextrose can be omitted if a glucose determination can be obtained by a fingerstick. In this case, intubation should be performed prior to naloxone because the respiratory depression is likely due to both the codeine and the diazepam.

Blood, urine, and gastric fluid specimens should be obtained and sent for drug screening. Blood is also sent for routine hematological and chemistry studies (including liver function). Urine is usually obtained by bladder catheterization, and gastric fluid can be aspirated from a nasogastric tube; the latter should be placed after intubation to avoid pulmonary aspiration. Alternatively, emesis material may be tested for drugs in conscious persons.

Hypotension should generally be treated with intravenous fluids unless the patient is obviously in pulmonary edema; an inotrope or vasopressor may be necessary in some instances. Seizure activity may be the result of hypoxia or a pharmacological action of a drug (tricyclic antidepressants) or poison. Seizure activity is unlikely in this patient because she ingested diazepam, a potent anticonvulsant.

Should flumazenil be administered?

Flumazenil should generally not be administered to patients who overdose on both a benzodiazepine and an antidepressant and those who have a history of seizures. Reversal of the benzodiazepine’s anticonvulsant action can precipitate seizure activity in such instances. Moreover, as is the case with naloxone and opioids, the half-life of flumazenil is shorter than that of benzodiazepines. Thus, it is often preferable to ventilate the patient until the benzodiazepine effect dissipates, the patient regains consciousness, and the respiratory depression resolves.

Should any other antidotes be given?

Because the patient also ingested an unknown quantity of acetaminophen (paracetamol) administration of N-acetylcysteine (NAC; Mucomyst) should be considered. Acetaminophen toxicity is due to depletion of hepatic glutathione, resulting in the accumulation of toxic metabolic intermediates. Hepatic toxicity is usually associated with ingestion of more than 140 mg/kg of acetaminophen. NAC prevents hepatic damage by acting as a sulfhydryl donor and restoring hepatic glutathione levels. If the patient is suspected of having ingested a toxic dose of acetaminophen, an initial dosage of NAC (140 mg/kg orally or by nasogastric tube) should be administered even before plasma acetaminophen levels are obtained; additional doses are given according to the measured plasma level. If the patient cannot tolerate oral or gastric administration of NAC, if the patient is pregnant, or if the risk of hepatotoxicity is high, NAC should be given intravenously.

What measures might limit drug toxicity?

Toxicity might be reduced by decreasing drug absorption or enhancing elimination. Gastrointestinal absorption of an ingested substance can be reduced by emptying stomach contents and administering activated charcoal. Both methods can be effective up to 12 h following ingestion. If the patient is intubated, the stomach is lavaged carefully to avoid pulmonary aspiration. Emesis may be induced in conscious patients with syrup of ipecac 30 mL (15 mL in a child). Gastric lavage and induced emesis are generally contraindicated for patients who ingest caustic substances or hydrocarbons because of a high risk of aspiration and worsening mucosal injury.

Activated charcoal 1-2 g/kg is administered orally or by nasogastric tube with a diluent. The charcoal irreversibly binds most drugs and poisons in the gut, allowing them to be eliminated in stools. In fact, charcoal can create a negative diffusion gradient between the gut and the circulation, allowing the drug or poison to be effectively removed from the body.

Alkalinization of the serum with sodium bicarbonate for tricyclic antidepressant overdose is beneficial because, by increasing pH, protein binding is enhanced; if seizures occur the alkalinization prevents acidosis-induced cardiotoxicity.

What other methods can enhance drug elimination?

The easiest method of increasing drug elimination is forced diuresis. Unfortunately, this method is of limited use for drugs that are highly protein bound or have large volumes of distribution. Mannitol or furosemide with saline may be used. Concomitant administration of alkali (sodium bicarbonate) enhances the elimination of weakly acidic drugs such as salicylates and barbiturates; alkalization of the urine traps the ionized form of these drugs in the renal tubules and enhances urinary elimination. Hemodialysis is usually reserved for patients with severe toxicity who continue to deteriorate despite aggressive supportive therapy.


A 74-year-old woman was admitted to the hospital for extreme confusion and agitation. She had been doing reasonably well until 1 to 2 weeks prior to admission; however, her family says that her memory has been getting worse over the last 3 years.

Initially, she had problems remembering recent events and people’s names and had a tendency to dwell in the past. She has gotten lost several times while driving, most recently in a familiar neighborhood.

She has stopped cooking because she can no longer work her electric oven. Sometimes, her words do not make sense. Her social graces have remained preserved, and she is still quite pleasant to be around, although she tends to interact less with her friends. Her family says her mood has been poor lately, with some tearful episodes. She still walks around the block every day, and her basic gait and coordination seem quite normal. Over the last week or so, her condition has acutely worsened. She is easily agitated to the point of aggression. She also appears to see and speak to her mother, who has been dead for many years. According to her family, she has developed frequent urination and incontinence, which is not normal for her. On physical examination, she was found to be inattentive and had difficulty keeping on task. She had numerous paraphasic errors but was otherwise fluent. Her neurologic examination was otherwise unremarkable.

: A 74-year-old woman was admitted to the hospital for extreme confusion and agitation. She has had short-term memory deficits over the last 3 years including becoming lost several times while driving, most recently in a familiar neighborhood. She now acutely displays confusion, memory loss, hallucinations, and urinary incontinence. She had numerous paraphasic errors but was otherwise fluent. Her neurologic examination was otherwise unremarkable.

  • Most likely diagnosis: Underlying dementia, probably Alzheimer disease (AD), with superimposed delirium from a urinary tract infection (UTI).

  • Next diagnostic step: Treat UTI with antibiotics, medical evaluation, and observation.

  • Next step in therapy: After observation and stabilization, consider treatment of the underlying dementia.



  1. Recognize the differential diagnosis of dementia.

  2. Understand the underlying pathophysiology of AD.

  3. Appreciate the special susceptibilities of patients with dementia.


This case has two main aspects to it: a several-year history of apparent cognitive decline, and a more recent, precipitous decline with agitation and inattention. The insidious onset and gradual progression in an older person is characteristic of degenerative disease (eg, Alzheimer), although other classes of diseases can sometimes mimic this time course. In this patient, there has been decline of cognition with profound deficits of short-term memory. Long-term memory is preserved. Other symptoms include getting lost in familiar areas, suggesting visuospatial deficits, and the use of tools like the oven, which is consistent with apraxia. She had no focal neurologic dysfunction, such as deficits in her cranial nerves, motor, sensation, coordination, gait, and station.

Dementia presents with decline in memory and at least one other cognitive domain that is severe enough to interfere with daily function and independence. The sudden decline and agitation is more consistent with delirium. Dementia needs to be distinguished from delirium, depression, and, more importantly, reversible organic causes of cognitive decline such as drugs or metabolic derangements.

The acute onset of agitation and delirium in this patient is likely caused by a UTI, given her simultaneous development of urinary symptoms (frequency and incontinence). Patients with underlying dementia or other brain disease (eg, stroke and multiple sclerosis [MS]) are particularly sensitive to infections, medication changes, or metabolic abnormalities. Infections are particularly common etiologies of delirium in these patients, though medications and basic laboratory values should also be reviewed.

In this patient, the first order of business is to ensure that she is medically stable. In addition, she should be checked for other causes of delirium, including metabolic and pharmacologic agents as well as vitamin and hormonal deficiencies. Urinalysis and urine culture should be obtained to confirm the diagnosis of UTI, and she should be treated appropriately. She should improve and reach a stable baseline, after which she can be examined more closely as to the nature of her dementia. Cognitive screening tests, such as the Montreal Cognitive Assessment (MoCA) or Mini-Mental State Examination (MMSE), imaging and cerebrospinal fluid (CSF) studies can be performed as indicated by the clinical picture.

If the patient does not have any reversible metabolic causes of cognitive decline, consider the more common dementia syndromes:

  1. Alzheimer disease (AD)

  2. Lewy body dementia

  3. Vascular dementia

  4. Parkinson disease (PD) with dementia

  5. Frontotemporal dementia (FTD)

In this case, there is neither history of tremor or gait disturbance suggestive of PD nor history of visual hallucinations suggestive of Lewy body dementia. This patient’s history is also not significant for a stepwise deterioration seen with neurologic deficits of stroke, nor is it characterized primarily by personality changes such as disinhibition and impaired judgment seen in FTD. AD is therefore the most probable diagnosis, given the predominant deficits of recent memory and visual-spatial function.

Treatment with an acetylcholinesterase inhibitor such as donepezil, which has been shown to delay symptom progression, would be appropriate at this point. Memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, can also be considered since it has benefit in moderate stages of AD. Dementia is a chronic, progressive disorder; it does not present or change acutely, and there is no need to treat it with the timing and urgency of a cardiac arrest. These patients can be very sensitive to the deleterious effect of medications. Medication should be titrated carefully, and two drugs should never be started at once unless absolutely necessary.

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A 38-year-old woman is brought to the emergency department by her spouse because of decreased mental status. She had knee surgery 2 days ago and was prescribed oral oxycodone for pain. Her spouse notes that she finished the entire 7-day supply during that day. He denies any seizure activity. They have no other drugs or medications in the house. She is afebrile with blood pressure of 130/75 mmHg, heart rate of 70 bpm, respiratory rate of 4 breaths/min, and SaO2 of 85% on room air. She barely responds to painful stimuli but moves all four extremities equally. Which of the following medications is most likely to improve her mental status?

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The correct answer is E. You answered E.

The answer is E.(Chap. 18) Opioids, such as oxycodone, work centrally and may cause significant respiratory depression and sedation. Because of the hypoventilation, hypoxemia is common although easily treated with supplemental oxygen. Naloxone is an opioid antagonist that may rapidly reverse the respiratory depression and sedation. Alvimopan is an oral opioid antagonist that is confined to the gut. It may be useful to counteract peripheral opioid side effects, such as constipation, but has no central actions. Albuterol is a β-agonist that may increase respiratory rate but will not reverse the opioid sedation. Flumazenil is a γ-aminobutyric acid (GABA) receptor antagonist that can be used for benzodiazepine overdose. N-Acetylcysteine is used for acetaminophen overdose. Many forms of oxycodone also include acetaminophen, so the clinician should be careful to elicit an accurate medication history because of the possibility of concurrent acetaminophen-induced liver toxicity.


A 46-year-old man is found by his wife unresponsive on the floor. She immediately calls 911. An interview with the wife by Emergency Medical Services reveals that her husband has complained of a headache for several months now, and that she has noticed some changes in his memory. However, despite her requests, he refused to see a physician. Physical examination reveals left-sided pupillary dilation. Which of the following might a CT scan of the head reveal?

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The correct answer is C. You answered A.

The patient has a rapidly growing, left-sided intracerebral neoplasm, which has resulted in left uncal herniation. Compression of the left oculomotor nerve, with subsequent involvement of the parasympathetic nerve fibers caused the pupillary dilation. Uncal herniation can also compress the posterior cerebral artery.


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