Neurocritical Care

17. Acute Delirium

A 72-year-old man with history of hypertension, diabetes mellitus, and a right subcortical ischemic stroke three years before was admitted with acute abdominal pain. Exploratory laparotomy revealed perforated diverticulitis. He underwent partial colectomy and colostomy without complications. In the surgical ICU he was treated with fluids, vasopressors, and antibiotics for sepsis. Complications included acute kidney injury and mild elevation of liver transaminases. He was kept on mechanical ventilation and sedated with a midazolam infusion. Three days after the surgery we are consulted because the patient is agitated every time the nurses try to diminish the sedation. On examination he fluctuates between drowsiness and agitation and he has multifocal adventitious movements.

What do you do now?

Delirium is a very common complication in the ICU. It can follow critical medical or surgical illness. It may be seen in 15% to 80% of critically ill patients depending on the severity of the underlying illness, the age, and the previous cognitive status. Another factor that explains the wide variation of reported rates of ICU delirium is that it is often underrecognized. Some clinicians seem to accept a certain degree of drowsiness, agitation, or confusion in elderly critically ill patients. However, delirium is a form of brain dysfunction associated with poor clinical outcomes and potentially persistent cognitive decline.

The raving, raging patient is obvious, but many patients with ICU delirium do not have pure or even predominant hyperactivity. Instead, mixed and hypoactive forms of delirium are more common. Monitoring tools sensitive to hyperactive and hypoactive manifestations of delirium have to be used to prevent cases from going unnoticed. Using a validated scale for monitoring the level of sedation, such as the Richmond Agitation Sedation Scale (RASS) (Table 17.1), is advisable.


FIGURE 17.1 Assessment of level of sedation and delirium in the ICU. RASS, Richmond Agitation Sedation Scale (see Table 17.3); CAM-ICU, Confusion Assessment Method for the ICU: delirium is diagnosed by the presence of 3 of the 4 diagnostic features.

TABLE 17.1 The Richmond Agitation Sedation Scale for the Assessment of Depth of Sedation


Very combative, violent, dangerous to staff


Pulling catheters and tubes, aggressive


Frequent nonpurposeful movements, fights ventilator


Anxious but movements not aggressive or vigorous


Alert and calm


Awakes (eye contact) for > 10 seconds in response to voice


Awakes (eye contact) for < 10 seconds in response to voice


Eye opening or movement to voice without eye contact


No response to voice, but eye opening or movement to physical stimulation


No response to voice or physical stimulation

Sedation holidays (stopping all sedatives at regular intervals) have been shown to decrease the duration of mechanical ventilation and the length of ICU stay. They also decrease the incidence of delirium. Still, the need for sedation holidays is not sufficiently appreciated. In fact, it has been our experience that precisely the sickest patient is the one at highest risk for delirium and in whom sedation holidays are less frequently used.

We still know little about the causes and mechanisms of delirium in critically ill patients, but there is emerging research. Studies have definitively demonstrated that prolonged exposure to psychoactive drugs in general and sedative drugs in particular increase the risk and severity of delirium. Benzodiazepines are particularly prone to exacerbate delirium and they are only indicated for the treatment of delirium related to alcohol withdrawal. Dexmedetomidine may be a safer option. Antidopaminergic agents are the best medications for agitation; the relative value of haloperidol versus atypical antipsychotics (such quetiapine or olanzepine) is not well studied in the ICU population. The risk of delirium with opiates has been less studied, but we often find them to be a major contributing factor. The general principle is that we should be using all sedatives very judiciously, prescribing the lowest possible doses and stopping them as soon as they are no longer truly necessary. In fact, a good first step would be to ensure that we avoid sedating critically ill patients who are already drowsy (when not stuporous or comatose), an everyday error in many ICUs today.

As neurologists we are often consulted to evaluate these patients in the medical or the surgical ICU and we can be very useful. Table 17.2 lists some of the diagnoses to consider when evaluating “encephalopathic” patients in general ICUs. The experienced clinician will look for brainstem or lateralizing signs, subtle manifestations of seizures, and features of major toxidromes (see chapter 14). Adventitious movements such as multifocal myoclonus (more common with uremia) and asterixis (more common with liver failure) are good markers of a metabolic derangement, albeit nonspecific. Severe muscle rigidity with clonus should raise suspicion for serotonin syndrome, neuroleptic malignant syndrome, and when accompanied by high fever, malignant hyperthermia.

Our approach to the evaluation of patients with ICU delirium is summarized in Table 17.3. In essence, after reviewing the history and examining the patient, we try to answer the following questions:

· Do I have a diagnosis?

· Should the patient have more blood tests?

· Should the patient have brain imaging? If so, which one?

· Should the patient have a lumbar puncture?

· Should the patient have an electroencephalogram? If so, is there a need for continuous monitoring?

· Are there any medications in the regimen that should be reduced or stopped?

· Do I need to recommend specific treatment for agitation?

In the case presented, we found that the patient had mixed delirium with multifocal myoclonus, but normal brainstem reflexes and no lateralizing signs on examination. Muscle tone was normal. Deep tendon reflexes were decreased in the legs, consistent with his long history of diabetes. He had no meningeal signs or clinical manifestations of seizures. We requested a serum ammonia level, which was normal, and decided to follow his clinical evolution without recommending further testing. We did ask the primary team to stop the infusion of midazolam and to use intravenous haloperidol (2–5 mg every 4 hours) for the patient’s episodic agitation. We also strongly advised to stop the infusion of fentanyl that the patient had been receiving since surgery. With these simple changes, the patient began to improve despite further increase in his BUN for two more days (to reach a peak of 58 mg/dL) before it started to decline. Once off sedatives, he was extubated without complications. Upon discharge 2 weeks later, his intellectual function was nearly normal.

TABLE 17.2 Differential Diagnoses in ICU Patients with Encephalopathy



*Only within 30 minutes to 24 hours after exposure to inhalational anesthesia or succinylcholine.

† Presented as an example of drug withdrawal syndrome.

BUN, blood urea nitrogen; CK, creatine kinase; CTV, CT venography; CMV, cytomegalovirus; EEG, electroencephalogram; HSV, herpes virus simplex; MRV, magnetic resonance venography

TABLE 17.3 Approach to the Patient with ICU Delirium



History (including preadmission functional and cognitive status)

All patients

Physical examination

All patients

Blood tests

Metabolic panel including BUN, liver transaminases, and serum ammonia in all cases. CK level if rigidity. Lactic acid if sepsis or acidosis. Toxicological screen in any case of coma or delirium at presentation with no known cause.

Brain imaging

If lateralizing signs, brainstem signs.

Lumbar puncture

Unexplained fever/sepsis. Meningeal signs.


Rhythmic abnormal movements. Staring, not tracking finger. Consider in any case of unexplained coma.

The evaluation of delirium may seem overwhelming, but a simple checklist including the questions listed above may help avoid oversights and focus the consultation.


· Altered level and content of consciousness is never a normal finding in a patient in the ICU. If present, it deserves careful attention.

· ICU delirium is a common complication of medical and surgical critical illness and it is associated with worse short-term and long-term clinical outcomes.

· Delirium does not always mean agitation. Some patients with delirium are actually hypoactive.

· Standardized tools, such as the CAM-ICU score, should be used for the timely recognition of ICU delirium.

· Sedatives (especially benzodiazepines) and opiates worsen delirium, and their use should be minimized as much as possible.

· Always exclude primary neurological diseases in any critical patient with evidence of brain dysfunction.

Further Reading

Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001; 286:2703–2710.

Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA 2003; 289:2983–2991.

Frontera JA. Delirium and sedation in the ICU. Neurocrit Care. 2011;14:463–474.

Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, Gordon SM, Canonico AE, Dittus RS, Bernard GR, Ely EW. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med 2010; 38:1513–1520.

Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Crit Care 2008; 12 Suppl 3:S3.

Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002; 30:119–141.

Kress JP, Pohlman AS, O’Connor MF, Hall JB . Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342:1471–1477.

Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, Shintani AK, Thompson JL, Jackson JC, Deppen SA, Stiles RA, Dittus RS, Bernard GR, Ely EW. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007; 298:2644–2653.

Wong CL, Holroyd-Leduc J, Simel DL, Straus SE. Does this patient have delirium? value of bedside instruments. JAMA. 2010;304:779–786.