IM Board Review

Postoperative delirium in a 64-year-old woman

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2. What is most likely cause of the patient’s declining mental status, and what is the next appropriate step?

  • Acute stroke: repeat MRI with contrast
  • Urinary tract infection: order blood and urine cultures, and start empiric antibiotics
  • Neuroleptic malignant syndrome: start dantrolene
  • Seizures: order electroencephalography (EEG)

Acute stroke

Acute stroke can affect mental status and consciousness through several pathways. Stroke syndromes can vary in presentation depending on the level of cortical and subcortical involvement, with clinical manifestations including confusion, aphasia, neglect, and inattention. Wakefulness and the ability to maintain consciousness is impaired, with disruption of the ascending reticular activating system, often seen in injuries to the brainstem. Large territorial or hemispheric infarcts, with subsequent cerebral edema, can also disrupt this system and lead to cerebral herniation and coma.

MRI without contrast is extremely sensitive for ischemia and can typically detect ischemia in acute stroke within 3 to 30 minutes.18–20 Repeating the study with contrast is unlikely to provide additional benefit.

In our patient’s case, the lack of localizing neurologic symptoms, in addition to her recent negative neuroimaging workup, makes the diagnosis of acute stroke unlikely.


The role of severe infection in patients with altered mental status is well documented and likely relates to diffuse cerebral dysfunction caused by an inflammatory cascade. Less well understood is the role of occult infection, especially urinary tract infection, in otherwise immunocompetent patients. Urinary tract infection has long been thought to cause delirium in otherwise asymptomatic elderly patients, but few studies have examined this relationship, and those studies have been shown to have significant methodologic errors.21 In the absence of better data, urinary tract infection as the cause of frank delirium in an otherwise well patient should be viewed with skepticism, and alternative causes should be sought.

Although the patient has a nonspecific leukocytosis, her benign urinalysis and lack of corroborating evidence makes urinary tract infection an unlikely cause of her frank delirium.

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome is defined as fever, rigidity, mental status changes, and autonomic instability after exposure to antidopaminergic drugs. It is classically seen after administration of typical antipsychotics, though atypical antipsychotics and antiemetic drugs may be implicated as well.

Patients often exhibit agitation and confusion, which when severe may progress to mutism and catatonia. Likewise, psychotropic drugs such as quetiapine and venlafaxine, used in combination, have the additional risk of serotonin syndrome.

Additional symptoms include hyperreflexia, ataxia, and myoclonus. Withdrawal of the causative agent and supportive care are the mainstays of therapy. Targeted therapies with agents such as dantrolene, bromocriptine, and amantadine have also been reported anecdotally, but their efficacy is unclear, with variable results.22

As noted earlier, the addition of quetiapine to the patient’s already lengthy medication list could conceivably cause neuroleptic malignant syndrome or serotonin syndrome and should be considered. However, additional neurologic findings to confirm this diagnosis are lacking.


Nonconvulsive seizure, particularly nonconvulsive status epilepticus (NCSE), is not well recognized and is particularly challenging to diagnose without EEG. In several case series of patients presenting to the emergency room with altered mental status, NCSE was found in 16% to 28% of patients in whom EEG was performed after an initial evaluation failed to show an obvious cause for the delirium.23,24 Historical features are unreliable for ruling out NCSE as a cause of delirium, as up to 41% of patients in whom the condition is ultimately diagnosed have only confusion as the presenting clinical symptom.25

Likewise, alternating ictal and postictal periods may mimic the typical waxing and waning course classically associated with delirium of other causes. Physical findings such as nystagmus, anisocoria, and hippus may be helpful but are often overlooked or absent. EEG is thus an essential requirement for the diagnosis.26

Given the lack of a clear diagnosis, a workup with EEG should be considered in this patient.


In the ICU, our patient is evaluated by the intensivist team. Her vital signs are stable, and while she is now awakening, she is unable to follow commands and remains mute. She does not initiate movement spontaneously but offers slight resistance to passive movements, holding and maintaining postures her extremities are placed in. She keeps her eyes closed, but when opened by the examining physician, dysconjugate gaze and anisocoria are noted.

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Bedside manners: How to deal with delirium

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