Delirium occurs frequently in intensive care units (ICUs), and complicates treatment and patient outcomes. This article reviews risk factors, diagnosis, and guidelines for treatment of delirium in the ICU setting.

There are many complications that may arise with a patient in the critical care setting. Infection, arrhythmias, ventilator-induced barotrauma, and hemorrhage are just a few. Because these are life threatening conditions that worsen patient outcomes, prevention and monitoring is in place for each along with a course of action if they develop. Delirium should be considered on the list of intensive care unit (ICU) life threatening complications. According to the DSM-IV-TR, delirium is defined as a syndrome characterized by confusion and loss of short-term memory.1 Symptoms may fluctuate throughout the course of the disorder, even through the course of a day, and may present on a continuum from psychomotor retardation to excitation. Presenting symptoms are often confused with other psychiatric disorders and may be attributed to a variety of causes such as medical illness or medications. Unfortunately, the underlying pathophysiology is poorly understood. Because delirium has been associated with a higher mortality risk and long-term cognitive impairment, education and awareness about recognition and prevention is essential.2 This year's CPNP Annual Meeting, held in Colorado Springs, addressed this area of need. Robert MacLaren, Pharm.D., MPH, FCCM, FCCP discussed risk factors, recognition, and treatment in his presentation entitled “The Recognition and Management of Delirium in the Critically Ill.”

Delirium occurs frequently in ICU patients in a variety of settings. This is a fragile patient population already at increased risk for complications and mortality. Development of delirium further complicates the course of treatment and patient outcomes. In a study conducted by Ely et al., the mean onset of delirium occurred within 2.6 days and mean duration was 3.4 days. The duration of delirium was positively correlated with length of stay within the ICU and in the hospital.3 Delirium was the strongest predictor for length of stay in the hospital despite being adjusted for severity of illness, age, gender, race, and days of benzodiazepine and narcotic drug administration.

Lat et al. also found comparable results looking at patients who developed delirium in the ICU. Delirium was significantly associated with more mechanically ventilated days, longer ICU stay, and longer hospital stay.4 In this study, significantly greater cumulative lorazepam and fentanyl dose were administered in the delirium group. Similarly, a meta-analysis of 16 studies by Zhang et al. indicated delirious patients had a higher mortality rate, higher rate of complications, and longer length of stay in both ICU and hospital as well as spent more time on mechanical ventilation. When looking at long-term outcomes, patients with delirium were more likely to be discharged to skilled placement when compared to patients without delirium.5 In addition, van den Boogaard, et al. demonstrated an association with long-term cognitive impairment in patients after discharge who experienced delirium.6 

Given the array of deleterious patient outcomes associated with delirium, identification of risk factors to help detection and prevention would be beneficial to patients. In agreement with the Lat et al. study, Dubois et al. identified use of analgesics as a risk factor for delirium in addition to patient history of hypertension, nicotine or alcohol use, laboratory abnormalities and non-orienting environmental factors.7 However, a look at the system in place for recognition of delirium is crucial.

ICUs are filled with a variety of medical personnel who interact with patients on an hourly basis. In a range from physicians to nurses' aides, who is responsible for monitoring for delirium? This is often a debated subject. During his presentation, Dr. MacLaren discussed a study which surveyed 250 pharmacists who reported they spent 25% or more of their time in the ICU.8 From this survey, 7% reported using a delirium screening tool routinely. Thirty four percent cited lack of time as a reason for not conducting screens as well as 24 % indicated screening was a nursing role. In actuality, patient care is everyone's role. In the Annual Meeting presentation, MacLaren advocated delirium screening is a role pharmacists could fill within the treatment team and should be done every shift.

A commonly utilized screening tool is the Confusion Assessment Method (CAM) – ICU.9 The CAM-ICU was developed at Yale University through consensus and found to have high predictive accuracy for the features of delirium, convergent agreement with other mental status tests, and high inter-rater reliability.9 Through this tool, patients would be positive for delirium if they had (1) and (2) and either (3) or (4) below.

  • Acute onset or fluctuating mental status (present if either answer yes)

    • Different from baseline or

    • Sedation score fluctuation over 24 hours (Richmond Agitation Sedation Scale)

  • Inattention (present if >2 errors)

    • Ask patient to squeeze hand for every A in “SAVEAHAART”

  • Altered level of consciousness

    • Use sedation score (present if >0) lcist;

    • Disorganized thinking (present if errors >1)

      • Four yes/no questions

        • Example: Will a stone float on water?

      • Command (score 1 point if unable to do with both hands)

        • Example: Hold up x number of fingers

Another screening tool is the Intensive Care Delirium Screening Checklist (ICDSC). This tool was developed at the Université de Montréal as another alternative for delirium screening. In a study by Bergeron et al., the ICDSC was found to have predictive sensitivity of 99% but specificity of 64%, emphasizing its utility as a screening tool and not a diagnostic tool.10 This tool is based on information collected from each eight hour shift or within the previous 24 hours. A patient receives one point for each obvious manifestation of the below criteria. Any criterion that could not be assessed or exhibited no manifestation receives no points. A score of four or more points would indicate the presence of delirium.

  1. Altered level of consciousness

    • No response (1 point)

    • Need for vigorous stimulation needed for response (1 point)

    • Drowsiness or mild to moderate stimulation needed for response (1 point)

    • Wakefulness or easily aroused (no point)

    • Hypervigilance (1 point)

  2. Inattention (1 point)

    • Different from baseline

  3. Disorientation (1 point)

    • Obvious mistake in time, place, or person

  4. Hallucination, delusion, or psychosis (1 point)

  5. Psychomotor agitation or retardation (1 point)

  6. Inappropriate speech or mood (1 point)

  7. Sleep/wake cycle disturbance (1 point)

  8. Symptom fluctuation (1 point)

Regardless of the tool used, routine screening for delirium is crucial when considering the short and long term complications. Given the importance of screening and recognition, various training and informational sites have been developed to aid medical personnel in improving care. Icudelirium.org contains many resources, including information on delirium, outcomes, sedation and training. It is developed by the Vanderbilt University Medical Center and is becoming a major source of delirium information for medical professionals.

New guidelines for the management of delirium were released in January 2013 by the Society for Critical Care Medicine.11 These guidelines cite delirium as a major health problem affecting up to 80% of mechanically ventilated patients and costing between $4 billion and $16 billion in the United States alone. The deleterious patient outcomes were also stressed including increased mortality, length of hospital and ICU stay, cost, and long-term cognitive impairment. Routine monitoring was recognized as feasible and necessary in every day practice. Non-pharmacologic strategies were endorsed in prevention of delirium. Early mobilization was found to reduce the incidence of delirium, depth of sedation, and hospital and ICU length of stay.12–13 Early and aggressive physical and occupational therapy during sedation holidays was not harmful but, in fact, very helpful. However, the guidelines make no recommendations for pharmacologic therapy for prevention of delirium. Research reviewing haloperidol or atypical antipsychotics as a preventative measure against delirium has been limited by small sample size, poor design, and inconclusive results.11 In terms of pharmacologic treatment of delirium, the guidelines indicate atypical antipsychotics may reduce the duration of delirium in the ICU. This is based off a study by Devlin et al. where delirious patients were randomized to receive quetiapine or placebo. The quetiapine group was associated with shorter time to first resolution of delirium, reduced duration of delirium, less agitation, an increased likelihood of discharge to home or rehabilitation, and reduced number of days in which as needed haloperidol was required.14 Haloperidol was not endorsed as a treatment of delirium by the guidelines, citing a lack of published evidence that indicates haloperidol reduces duration of delirium in ICU patients.11 Pharmacologic therapy should be considered only after the underlying cause of delirium is addressed as this may affect response to antipsychotic therapy. The guidelines also do not endorse the use of cholinesterase inhibitors such as rivastigmine due to greater mortality and lower efficacy in resolving delirium when compared to placebo.15 

Also discussed during MacLaren's presentation was the utilization of dexmedetomidine for continuous IV infusion for mechanically ventilated patients with delirium. Riker et al. looked at light sedation with dexmedetomidine versus midazolam in mechanically ventilated ICU patients. At comparable sedation levels, dexmedetomidine patients spent less time mechanically ventilated, experienced less delirium, and developed less tachycardia and hypertension.16 Similarly, Pandharipande et al. compared lorazepam versus dexmedetomidine for sedation in mechanically ventilated patients in the ICU. The dexmedetomidine group resulted in more days alive without delirium or coma and more time at the targeted level of sedation when compared to the lorazepam group.17 The studies could not conclude if dexmedetomidine use reduced delirium or benzodiazepine use increased incidence of delirium. However, this supports benzodiazepine use as a risk factor for delirium and the use of dexmedetomidine over benzodiazepines for IV sedation in mechanically ventilated patients.11 

Overall, delirium is a major health problem with deleterious patient outcomes. It has been associated with increased length of stay, cost, mortality, and long-term cognitive impairment. Due to its prevalence, routine screening with tools such as the CAM-ICU or ICDSC should take place every shift. This is an ideal intervention for pharmacists to improve patient outcomes. Attempts should be made to minimize risk factors for delirium such as limiting sedation, utilizing dexmedetomidine, and early mobilization. Currently, the guidelines do not endorse pharmacologic prevention of delirium but do endorse atypical antipsychotic use for the treatment of delirium. Quetiapine in particular has evidence to support its use. Haloperidol does not have empirical evidence to support its use in prevention or treatment of delirium. However, this is still an area of debate given the years of previous and continued use of haloperidol for the prevention and treatment of delirium. Overall, further investigation is needed for the diagnosis, prevention, and treatment of delirium.

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