Delirium is defined as fluctuation in mental status such as inattention, disorganized thinking, hallucinations, disorientation, and an altered level of consciousness. It occurs in up to 65% of hospitalized patients, and up to 87% of patients admitted to the ICU. The outcomes of delirium can be serious for the patient and should be considered as another organ failure that affects patient’s outcome. Delirium can increase the hospital stay and increase health care cost. There has been discussion of ICU delirium rates as being a possible quality measure. Delirium must be considered when assessing pain and sedation in the ICU. It can be further defined as (1) hyperactive delirium: previously referred to as ICU psychosis, includes such symptoms as hypervigilance, restlessness, anger, irritability, and uncooperativeness, and is associated with better overall outcomes; (2) hypoactive delirium: the more common and deleterious, characterized by a lack of awareness, decreased alertness, sparse or slow speech, lethargy, decreased motor activity, and apathy; (3) mixed delirium: apparent in patients with a mixed clinical picture and may occur in up to 54% of patients. Delirium occurs in patients typically 24–72 hours after admission to the ICU. Risk factors existing before hospitalization placing patients at risk for delirium include cognitive impairment, chronic illness (including hypertension), age over 65 years, depression, smoking, alcoholism, and severity of illness. Risk factors arising during hospitalization include congestive heart failure, sepsis, prolonged restraint use, immobility, withdrawal from substance abuse, seizures, dehydration, hyperthermia, head trauma, intracranial mass lesions, and the use of lorazepam, midazolam, morphine, fentanyl, and propofol. Assessment of delirium should be carried out in association with pain and sedation assessments and can be facilitated by the use of a validated delirium score such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC); these tools may be most usefully administered during a daily awakening.101,102 In addition, the patient should be assessed for QTc prolongation on EKG if therapy is being considered as many antidelirium agents are associated with QTc prolongation and risk of torsade de pointes. CAM-ICU and ISDSC allow rapid consistent assessment for altered level of consciousness, disorganized thinking, inattention, and other delirium features. Nonpharmacologic measures that can be used to manage delirium include daily awakening trials, continuous reorientation of the patient by nursing staff, clocks and calendars visible to the patient, promoting effective sleep/awake cycles, timely removal of restraints and catheters, ensuring use of glasses and hearing aids, minimizing ICU noise and stimulation, and avoiding excessive use of benzodiazepines. Pharmacologic agents used in the management of ICU delirium have not been supported by large clinical trials and agent selection should be based on patient-specific factors (Table 55-10). Intravenous drugs include dexmedetomidine, which may be especially useful in patients scaling spontaneous breathing trials secondary to agitation, and intravenous haloperidol. Intravenous haloperidol achieves peak levels 11 minutes after injection and the half-life of the drug is 10–24 hours. The dose required to control agitation and critically ill patients varies widely; a suggested maximum daily dose in the ICU is 35 mg per day; use of larger doses has been reported. Haloperidol has been associated with a reduced seizure threshold, extrapyramidal reactions (dyskinesia), and laryngeal dystonia. It has also been associated with malignant neuroleptic syndrome. Large doses of intravenous health care should only be administered in a monitored critical care setting and serial EKGs obtained to monitor QTc interval. In patients with hypoactive delirium, the dose of haloperidol may need to be reduced. Oral agents are longer acting and include aripiprazole, risperidone, or oral haloperidol. These agents are associated with QTc prolongation and should only be administered if the measured EKG QTc is less than 440 milliseconds. Another oral delirium agent with greater sedative properties is quetiapine; it is not associated with QTc prolongation.