We hope that this web site will serve as a valuable resource for both medical and lay readers interested in learning about delirium in critically ill patients, neurological monitoring instruments for use in the hospital setting, newly recommended patient-oriented (goal-directed) sedation practices, and the under-recognized problem of long-term cognitive impairment following critical illness. In addition to overview narratives, the web site provides many training materials and resources for well-validated neurological monitoring instruments including the Confusion Assessment Method for the ICU (CAM-ICU) and the Richmond Agitation-Sedation Scale (RASS), the CAM-ICU Training Manual PDF, frequently asked questions (FAQs) PDF, a printable Pocket Card for medical personnel use, instructional videos, and a list of links to selected references from the peer reviewed literature. We believe that increased awareness and monitoring of delirium and improvements in the delivery of potent psychoactive medications including analgesics and sedatives will lead to better care of critically ill patients and ultimately improve patient outcomes.

Delirium Treatment

The most important step in delirium management is early recognition. If delirium is not diagnosed, it is doubtful that any efforts will be made to reverse it. Once delirium is detected, efforts should focus on identifying the etiology. Often this can be done by assessing for the presence of known risk factors. Both prevention and treatment should focus on the minimization and/or elimination of predisposing and precipitating factors. The theoretical goals of management are to improve the patient’s cognitive status and reduce the risk of adverse outcomes such as aspiration, prolonged immobility, increased length of acute care, institutionalization, and death.

Delirium Management Protocol
Protocols and evidence-based strategies for prevention and treatment of delirium will no doubt emerge as more evidence becomes available from ongoing randomized clinical trials of both nonpharmacological and pharmacological strategies. Our group has deliberately put off publishing a delirium management algorithm because it would necessitates incorporation of “expert opinion” and thus aspects that have yet to be adequately tested or proven. However, the requests for such an approach continue to flood our experiences at national and international forums and numerous emails we receive from website visitors. Therefore, we have developed the following Sedation and Delirium Management Protocol, which basically and succinctly summarizes our approach at the current time. We want to emphasize that this approach, which is largely based on the current SCCM Clinical Practice Guidelines, (VUMC Sedation Protocol) is one which needs to be updated regularly with new data and also personalized at each medical center according to thought leaders at that center. This is not a “one-shoe-fits-all” protocol. We hope that this draft protocol helps you form your own integrated approach to CNS monitoring, sedation targeting, and delirium management in critically ill ICU patients.

Nonpharmacologic
Primary prevention is preferred; however, some degree of delirium is inevitable in the ICU. Although there are no data on primary prevention (nonpharmacologic) trials in the ICU, the data in non-ICU settings focuses on minimizing risk factors. The strategies include the following interventions: repeated reorientation of patients, provisions of cognitively stimulating activities for the patients multiple times a day, a nonpharmacological sleep protocol, early mobilization activities, range of motion exercises, timely removal of catheters and physical restraints, use of eye glasses and magnifying lenses, hearing aids and earwax disimpaction, early correction of dehydration, use of a scheduled pain management protocol, minimization of unnecessary noise/stimuli. Strategies for the prevention and management of delirium in the ICU are important areas for future investigation.

Pharmacologic
The first step in pharmacologic treatment of delirium is to assess the patient’s current medications for any offending agents that may be causing or exacerbating the delirium. Inappropriate use of sedatives or analgesics may exacerbate delirium symptoms. Delirious patients may become more obtunded and confused when treated with sedatives, causing a paradoxical increase in agitation as the sedative effects wear off. In fact, benzodiazepines and narcotics that are often used in the ICU to treat “confusion” (delirium) actually worsen cognition and exacerbate the problem. A thorough review of a patient’s medications will help identify any sedatives, analgesics and/or anticholinergic drugs that may be removed or decreased in dose.

There are currently no drugs with FDA-approval for the treatment of delirium. The American Psychiatric Association and the Society of Critical Care Medicine clinical practice guidelines (Jacobi J, et al., Crit Care Med 2002; 30:119-141) recommend haloperidol for the treatment of delirium, though it is acknowledged that this is based on sparse outcomes data from nonrandomized case series and anecdotal reports (i.e., level C data). Haloperidol is a dopamine receptor antagonist that works by inhibiting dopamine neurotransmission, with resultant improvement in the positive symptomatology (hallucinations, agitated and combative behavior, etc) and often results in a sedative effect. Haloperidol and similar agents (e.g., droperidol) have not been extensively studied in the ICU, though they are widely used anecdotally. In addition to haloperidol, other candidate antipsychotics/neuroleptic agents (e.g., risperidol, ziprasidone, quetiapine, and olanzapine) may prove to be helpful for both hyperactive and hypoactive delirium, especially with their broader receptor affinities. Patients receiving all of these antipsychotics should be monitored for adverse side effects such as QT prolongation, arrhythmias and extrapyramidal side effects. Prospective randomized controlled trials are needed to evaluate the effectiveness and safety of these agents relative to one another.

Etiology

Most patients with delirium in the ICU likely have multiple causes, though these causes are often very difficult to determine with clinical precision. In fact, in our past work, we have determined that on average, ICU patients have greater than 10 risk factors for delirium which places them at a very high risk for this complication. The exact pathophysiological mechanisms involved in the development and progression of delirium are a point of controversy. However, these mechanisms are thought to be related both to (a) anatomic deficits and (b) imbalances in the neurotransmitters which modulate the control of cognitive function, behavior and mood. We will elaborate very briefly on these two categories of mechanism.

(a) Anatomic Deficits: Higher cortical areas of the brain such as the prefrontal and non-dominant posterior parietal regions are implicated by CT/MRI or SPECT scans in delirium. Other regions touted as important in such studies include the anterior thalamus, basal ganglia, and the temporal-occipital cortex. A nice review of this work is found in Trzepacz P, Sem Clin Neuropsychiatry 2000;5: 132-48.

(b) Neurotransmitter Imbalance: Derangements in levels of serotonin, acetylcholine deficiency and dopamine excess (to name 3) are thought to contribute to delirium, but there are many other neurotransmitters that may be involved. Such derangements could be secondary to a number of causal factors that include reduction in cerebral metabolism, primary intracranial disease, systemic diseases, secondary infection of the brain, exogenous toxic agents, withdrawal from substances of abuse such as alcohol or sedative-hypnotics agents, hypoxemia and metabolic disturbances, and the administration of psychoactive medications such as benzodiazepines and narcotics. A recent study from our group (Pandharipande P et al, Anesthesiology. 2006;104:21-26) documented, for example, that three important risk factors for transitioning to delirium were patient age (Figure 2), severity of illness (Figure 3), and the administered dose of the sedative lorazepam (Figure 1). It is important to emphasize that these data should not indicate a need to avoid lorazepam, as it has an important role in the management of ICU patients, and it is also true that other sedative and analgesic medications are deliriogenic as well. We would emphasize, however, that avoiding the use of any more of these medications than is absolutely necessary is likely an area of focus that may reduce either the onset or duration of delirium. This is a point of ongoing study in the medical field.

Prevalence and Clinical Relevance

Critically ill patients are at great risk for the development of delirium in the ICU. With more than 8 out of 10 ventilated patients experiencing delirium, this is one of the most frequent forms of organ dysfunction experienced by critically ill patients. Despite this prevalence, delirium (usually in the hypoactive state) remains unrecognized in 66% to 84% of patients whether they be in the ICU, hospital ward, or emergency department. Delirium in the non-ICU setting has repeatedly been associated with prolonged hospital stay, medical complications that can increase mortality, greater dependency of care on discharge, and higher nursing home disposition rates. In medical and coronary ICU patients, delirium has been reported to be an independent predictor of prolonged ICU and hospital lengths of stay, as well as a higher 6 month mortality rates. Importantly these findings were present even after adjusting for age, gender, race and severity of illness. Delirium may also predispose ICU survivors to prolonged neuropsychological deficits.