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for Medical Professionals — ABCDEFs of Prevention and Safety // Delirium Monitoring

Outcomes Associated with Delirium

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Numerous studies have found ICU delirium to be associated with many negative outcomes such as:

  • Increased time on the ventilator
  • Longer ICU and Hospital lengths of stay
  • Increased costs
  • Higher mortality –both in-hospital and after discharge
  • Greater long-term cognitive dysfunction

ICU Delirium and Mortality

Despite similar baseline characteristics in a cohort of 275 mechanically ventilated patients, delirium was an independent predictor of higher 6-month mortality and longer stay even after adjusting for relevant covariates including coma and sedative/analgesic medications. See the Figures below and the comment from the multivariable analysis.

Reference: Ely, E.W., Shintani, A., Truman, B., Speroff, T., Gordon, S.M., Harrell, F.E., Inouye, S.K., Bernard, G.R., Dittus, R.S. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 291(14): 1753-1762, 2004.

Figure A Figure B

Figure Legend: Delirium versus Six-month Survival. These Kaplan-Meier plots show the relationship between delirium and 6-month survival. (a) Never vs. Ever Delirium (according to whether or not the patient ever developed delirium in the ICU) (b) Clinical Severity (subdividing the never and ever delirium groups in order to better understand the phenomenology of delirium). The never delirium group, composed of those who were always normal and those who were coma-normal (e.g., deeply sedated and then normal when drugs stopped) had higher survival than the ever delirium group, which was composed of those with delirium only and delirium-coma.

NOTE: After using Cox proportional hazard regression models with time-dependent covariates (multivariable analysis) to adjust for covariates, delirium was independently associated with higher 6-month mortality [adjusted hazard ratio (HR) =3.2 (1.4-7.7), P=0.008], and longer hospital stay [adjusted HR=2.0 (1.4-3.0), P<0.001]. ICU Delirium was also independently associated a longer post-ICU (ward) stay (adjusted P=0.009), fewer days alive and free of mechanical ventilation (adjusted P=0.03), and a higher incidence of cognitive impairment at hospital discharge (adjusted P=0.002).

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ICU Delirium and Hospital Length of stay

In this patient cohort, the majority of patients developed delirium in the ICU, and delirium was the strongest independent determinant of length of stay in the hospital. Further study and monitoring in the ICU of this complication and modifiable risk factors for its development are warranted. (see table below)

Reference: Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T et al. The impact of delirium in the Intensive care unit on hospital length of stay. Intensive Care Med 2001; 27:1892-1900.

Multiple Linear Regression Model
Predictors of Lengths of Stay in ICU and Hospital*

Variable Length of Hospital Stay (days)
  Beta 95% C.I. P Value
Intercept 1.82 - -
Duration of Delirium ** 1.18 1.05 -1.32 0.006
APACHE II 1.01 0.98-1.03 0.61
Age 1.00 0.99 “ 1.00 0.38
Gender 1.22 0.84 “ 1.75 0.30
Drug Days 1.13 1.01 “1.26 0.04

 

Using multivariate analysis, delirium was the strongest predictor of length of stay in the hospital (P=0.006) even after adjusting for severity of illness, age, gender, race, and days of benzodiazepine and narcotic drug administration.

* Dependent variables were log transformed prior to analysis, but estimates have been back transformed into original scale for presentation. Beta coefficients can be interpreted as average stay in days (intercept) or expected difference in stay between patients with and without the listed condition; 95% C.I. = 95% confidence intervals; APACHE II = denotes Acute Physiology and Chronic Health Evaluation II score [21]; Drug Days = number of days that a patient received psychoactive medications designated in Methods

** Delirium with onset in the ICU (i.e., ICU-onset delirium), duration measured in days. The adjusted r2 for delirium in relation to the ICU stay was 0.37, and for the hospital stay the adjusted r2 was 0.55.

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ICU Delirium and Cost

Higher severity and duration of delirium were associated with incrementally greater costs (all p<0.001). Using multivariable analysis to adjust for age, comorbidity, severity of illness, degree of organ dysfunction, nosocomial infection, hospital mortality, and other potential confounders, delirium was associated with 39% higher ICU (95% CI, 12% to 72%) and 31% higher hospital (95% CI, 1% to 70%) costs. Therefore, we conclude that delirium is a common clinical event in mechanically ventilated medical ICU patients and is associated with significantly higher ICU and hospital costs. Future efforts to prevent or treat ICU delirium have the potential to improve patient outcomes and reduce costs of care.

REFERENCE: Milbrandt, E.B., Deppen, S., Harrison, P.L., Shintani, A.K., Speroff, T., Stiles, R.A., Truman, B., Bernard, G.R., Dittus, R.S., Ely, E.W. Costs Associated with Delirium in Mechanically Ventilated Patients. Crit. Care Med. 32 (4):955-962, 2004.

ICU Costs Increased Mostly Due to Length of Stay

Severity strata Without Delirium With Delirium
Low $ 12,000 $ 21,000
Medium $ 20,000 $ 35,000
High $ 34,000 $ 49,000

Milbrandt, E.B., et al Crit Care Med 2005; 32:955-62 Read on PubMed.gov

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ICU Delirium and Dementia Interaction

In this ICU cohort, delirium was a frequent complication in the 185 ICU patients 65 years and older who were studied, and we found that delirium often persisted beyond the ICU stay. Delirium in older ICU persons was a dynamic and complex process as shown in the manuscript. Dementia was an important predisposing risk factor for the development of delirium in this population during and after the ICU stay (see the Figure below).

Reference: McNicoll L, Pisani MA, Zhang Y, Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc 2003; 51:591-598.

Figure C

* Indicates statistical significance at p<0.05 for comparison of groups with and without dementia. NOTE: Patients with dementia were 40% more likely to be delirious (RR 1.4, 95% CI 1.1, 1.7), even after controlling for comorbidity, baseline functional status, severity of illness, and invasive procedures.

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Lorazepam Risk Factor for ICU Delirium

In this cohort study, the authors evaluated 198 mechanically ventilated patients to determine the probability of daily transition to delirium as a function of sedative and analgesic dose administration during the previous 24 hours. Lorazepam was an independent risk factor for daily transition to delirium (odds ratio, 1.2 [95% confidence interval, 1.1-1.4]; P = 0.003), whereas fentanyl, morphine, and propofol were associated with higher but not statistically significant odds ratios. Increasing age and Acute Physiology and Chronic Health Evaluation II scores were also independent predictors of transitioning to delirium (multivariable P values p< 0.05).

Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006 Jan;104(1):21-6.

Figure 1.
Lorazepam and the Probability of Transitioning to Delirium
Lorazepam 1
Figure 2.
Age and the Probability of Transitioning to Delirium
Lorazepam 2
Figure 3.
Severity of Illness and the Probability of Transitioning to Delirium
Lorazepam 3 Read on PubMed.gov

Management of Delirium in the ICU

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