A presentation on Delirium in ICU: Nomenclature, definition and Diagnostic tools used in ICU

1. 15° Congresso Nazionale
Associazione Nazionale Psicogeriatria
FIRENZE
PALAZZO DEI CONGRESSI
16/18 APRILE 2015
Dipartimento di Anestesia, Rianimazione Emergenza Urgenza, AO Spedali Civili di Brescia
www.anestbs.com

2. Key points: What I wold like to talk
about
 Definition  just to repeat
 Epidemiology
 Key points  why delirium is important in ICU’s
 Delirium and Mortality in ICU
 Risk factors for Delirium
 The relation between sedatives and delirium
 Diagnosis of delirium in ICU
 Key points for discussion and further studies

3. Fundamentally, the syndrome represents a decompensation of
cerebral function in response to one or more pathophysiological
stressors.
Therefore, understanding how to identify delirium can be central
to recognising acute illness in patients of all ages.
European Delirium Association and American Delirium Society. BMC Medicine 2014, 12:141
It may or may not be accompanied by agitation.
Devlin JW, et al. Intensive Care Med 2007; 33:929–940

4. …The biggest problem is that “doctors are
focused only on the organs that got
patients into the hospital, ignoring newly
acquired brain problems…”

5.  Disturbance of consciousness
 Rapid onset
 Fluctuating course
 Inattention
 Impaired ability to receive, process, store and recall information
 Perceptual disturbances- illusions, hallucinations

6. Epidemiology: Delirium in ICU
 Prevalence of delirium at admission ranges from 10% to 31%.
 Incidence of new delirium per admission ranges from 3% to 29%
 Occurrence rate per admission varies between 11% and 42%.
 Delirium may be prevented in up to a third of older patients; hence, early
recognition is vital.
Ahmed S, et al. Age Ageing 2014 May;43(3):326-33

7. Prevalence  presence of
delirium on admission
Incidence  New onset of
delirium

8. Hosie A, et al. Palliative Med 2013; 27(6) 486-498

10. Why delirium is important in ICU’s
 $15k to $25k higher hospital costs
 Longer hospital stays and ICU stays
 3 times higher risk of death by 6 months
 Prolonged neuropsychological dysfunction
Milbrandt E et al, Crit Care Med 2004;32:955-962
Ely EW et al, JAMA 2004;291-1753-1762
Ouimet S, ICM 2007;33(1):66-73
Lin et al, Crit Care Med 2004;32:2254-59

11. Why delirium is important in ICU’s
It is unquestionably a
marker for vulnerability,
and is associated with
adverse outcomes in a
number of settings.
European Delirium Association and American Delirium Society.
BMC Medicine 2014, 12:141

12. Delirium and Mortality
Depends on
1- Setting
2- Definition of delirium

14. CGA
Comprehensive
Geriatric
Assessmen

15.  The primary analysis with adjusted hazard ratios
(HRs) showed that delirium is associated with
an increased risk of death compared with
controls after an average follow-up of 22.7
months (271/714 patients [38.0%] with delirium,
616/2243 controls [27.5%]; HR 1.95 [95% CI 1.51-
2.52]; I2, 44.0%).
 Patients who had experienced delirium were
also at increased risk of institutionalization
(average follow-up, 14.6 months; 176/527
patients [33.4%] with delirium and 219/2052
controls [10.7%]; OR 2.41 [95% CI, 1.77-3.29]; I2,
0%).

16. Delirium and mortality in ICU
 lthough most studies have
identified delirium as an independent
predictor of death in the intensive
care unit, several others found no
association with mortality.
Klouwenberg PMCK, et al. BMJ 2014;349:g6652

17. Delirium and Mortality in ICU
Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and
consequences
of ICU delirium. Intensive Care Med 2007;33:66-73.
Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, et al. Delirium as a
predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA
2004;291:1753-62.
Lin SM, Liu CY, Wang CH, Lin HC, Huang CD, Huang PY, et al. The impact of delirium
on the survival of mechanically ventilated patients. Crit Care Med 2004;32:2254-9.
Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium
are associated with 1-year mortality in an older intensive care unit population. Am J
Respir
Crit Care Med 2009;180:1092-7.
Van den Boogaard M, Schoonhoven L, van der Hoeven JG, van Achterberg T, Pickkers
P. Incidence and short-term consequences of delirium in critically ill patients: a
prospective
observational cohort study. Int J Nurs Stud 2012;49:775-83.
Van den Boogaard M, Peters SA, van der Hoeven JG, Dagnelie PC, Leffers P,
Pickkers
P, et al. The impact of delirium on the prediction of in-hospital mortality in
intensive care
patients. Crit Care 2010;14:R146.
Lin SM, Huang CD, Liu CY, Lin HC, Wang CH, Huang PY, et al. Risk factors for the
development of early-onset delirium and the subsequent clinical outcome in
mechanically
ventilated patients. J Crit Care 2008;23:372-9.
Salluh JI, Soares M, Teles JM, Ceraso D, Raimondi N, Nava VS, et al. Delirium
epidemiology in critical care (DECCA): an international study. Crit Care 2010;14:R210.
Tomasi CD, Grandi C, Salluh J, Soares M, Giombelli VR, Cascaes S, et al. Comparison
of CAM-ICU and ICDSC for the detection of delirium in critically ill patients focusing on
relevant clinical outcomes. J Crit Care 2012;27:212-7.
Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit:
a study of risk factors. Intensive Care Med 2001;27:1297-304.
Kishi Y, Iwasaki Y, Takezawa K, Kurosawa H, Endo S. Delirium in critical care unit patients
admitted through an emergency room. Gen Hosp Psychiatry 1995;17:371-9.
Thomason JW, Shintani A, Peterson JF, Pun BT, Jackson JC, Ely EW. Intensive care
unit delirium is an independent predictor of longer hospital stay: a prospective analysis
of 261 non-ventilated patients. Crit Care 2005;9:R375-81.
Klein Klouwenberg et al., The attributable mortality of delirium in critically ill
patients: prospective cohort study. BMJ 2014; 349: g6652
Canadian Critical Trial Group. Prevalence, risk factors and outcome of delirium in
mechanically ventilated patients. Crit Care Med 2015; 43(3)

18. No minimization Of sedation
1740 patients
OR of delirium within the first 24 hours
was 3.22
Adding delirium to APACHE II
Score did not improve accuracy
of the model in predicting
Mortality
Delirium as a severity index?

20. None of the previous studies have adequately adjusted for disease
progression before the start of delirium, or for competing events (such as
discharge) that may preclude observation of mortality in the intensive care
unit.

21. TIME DEPENDENT COVARIATES
Daily SOFA score
sepsis status
core temperature
mechanical ventilation status
use of sedative and analgesic drugs
and plasma sodium
urea
acidosis
haematocrit levels
TIME INDEPENDENT COVARIATES
has been decided upon literature  age
Sex
history of dementia
history of alcohol misuse
Charlson comorbidity index
acute physiology and chronic health evaluation IV score
admission type
readmission status
presence of sepsis on admission to the intensive care unit

22.  Logistic regression with time dependent and independent covariates
 Cox proporzional hazard analysis: delirium become a time dependent variable
 Competing Risk analysis:
 cause specific hazard ratio: which in this case estimates the direct effects of delirium on
outcome (mortality)
 subdistribution hazard ratio: which describes the instantaneous risk of dying from delirium
given that the patient has not died from delirium
Firstly, the severity of disease on the day of
admission to the intensive care unit may not be representative
of the health state at the time of delirium onset
Secondly, bias might
occur when a time dependent covariable is not only a risk factor
for death but also predicts subsequent delirium, and when
delirium status at a previous time point predicts the risk factor

23. Marginal Structural Model
 A marginal structural model
analysis deals with these limitations by adjusting for the changes
in disease severity before delirium onset, while preventing
bias. It enables assessment of what the mortality in the
intensive care unit would have been in a hypothetical population
in which all patients remained delirium-free, and is therefore
called a counterfactual analysis
 In this analysis the authors take into account for 2 factors:
1. bias caused by time varying disease severity until the onset of delirium
2. competing risk factor of discharge

24. Evolution of disease severity before onset of delirium in two hypothetical patients admitted to the intensive care
unit. Both patients have similar severity of disease, but the condition of patient A worsens, whereas that of patient
B improves.
As delirium preferentially develops in more severely ill patients, confounding occurs when disease severity after
baseline is not adjusted for in the analysis. Logistic regression and survival analysis adjusts for baseline variables at
t=0 only. A marginal structural model adjusts for changes in disease severity until the onset of delirium (area to left
of arrow), but not thereafter (area to right of arrow)

25. Using this approach, the population attributable mortality in
the intensive care unit was estimated at 7.2% by day 30,
implying that absolute case fatality can be reduced by no
more than 0.9% if we were able to completely prevent
delirium in all patients.

26. What are the conclusions
 Many patients on the intensive care unit die with delirium.
 We now know delirium may not cause death directly but it does result in
longer hospital stays, complications, and anguish to patients, families, and
carers in both homes and hospitals.
 Good evidence suggests that many patients are left with delirium related
cognitive impairment

27. Critical Care Medicine Issue: Volume 43(3), March 2015, p 557–566
SLEAP TRIAL:
Sedation Tritation HOURLY to SAS (3 or 4) or RASS (0; -3)
Switch to iv infusion to bolus ASAP
Weaning ASAP daily assessment of SBT
Daily screening for delirium w ICDSC

28. 430 pazienti randomizzati delirium in 226 (53.8%)
BUT in non-delirium patients 90% had at least once an
ICDSC of 1-3 indicating subsyndromal delirium

29. Delirium in ICU: Risk Factors

33. we should view the admirable efforts of Zaal et al. not as a defiitive assessment of risk
factors for ICU delirium but rather as a reflction of severe limitations in our current
understanding that are driven by heterogeneity in methodologies and outcome
measurement
standardized outcome measures (including delirium) and increasing momentum to
synthesize diverse studies through collaborative analysis rather than relying on
systematic review

34. The COMET Initiative: search for «delirium»

35. The COMET Initiative: search for «delirium»

36. How to do that?
 An essential fist step would be the development of minimum data
collection sets and agreement on essential elements of the delirium
assessment with accurate reporting on how the assessment was
operationalized.

38. DELIRIUM(S)
 D Drugs, dementia
 E Eyes & ears (poor vision and hearing)
 L Low O2 states (CHF, COPD, ARDS, MI, PE)
 I Infection
 R Retention (urine and stool)
 I Ictal states
 U Underhydration/undernutrition
 M Metabolic upset
 (S) Subdural, sleep deprivation

39. I WATCH DEATH
 I Infection
 W Withdrawal (alcohol, sedatives, barbiturates etc.)
 A Acute metabolic (acidosis, alkalosis, electrolytes)
 T Trauma (closed head injury, haematoma etc.)
 C CNS pathology (seizures, stroke, encephalitis)
 H Hypoxia
 D Deficiencies (thiamine, niacin, B12, folate)
 E Endocrinopathies (thyroid, glucose, adrenal)
 A Acute vascular (hypertensive crisis, arrhythmia)
 T Toxins/drugs
 H Heavy metals

40. A fist-order Markov model

42. Crit Care Med 2015; 43:135–141
1- No correlation between delirium
and Sedation in more recent studies
2- Sedation and ventilation  reflect
the severity

43. The proportion of CAM-ICU-positive evaluations
decreased from 53 to 31% (p<0.001) if assessments from
patients at RASS -2/-3 (22 % of all assessments) were
excluded. Similarly, the number of positive ICDSC results
decreased from 51 to 29% (p<0.001).
Apparent prevalence of delirium is dependent on how
a depressed level of consciousness after sedation stop
is interpreted (delirium vs persisting sedation).
We suggest that any reports on delirium using these
assessment tools should be stratified for a sedation
score during the assessment.

45. CAM-ICU: Confusion Assessment Method for the ICU
ASSESS THE LEVEL OF SEDATION (RASS)Step 1:
If RASS is -4 or -5, then STOP and reassess
patient later, otherwise proceed to step 2
ASSESS THE DELIRIUM (CAM-ICU)Step 2:
1: Acute onset of mental status
changes or a fluctuating course
and
2: Inattention
and
3: Disorganized
Thinking
4: Altered Level of
Consciousness

47. ICDSC
1- 8 items, 1 point for each one
2- The 8 syntoms are:
3- evaluation over 8 to 24 hrs
4- ICDSC ≥ 4 indicates a positive
ICDSC and the presence of
delirium

48.  1- DURATION: CAM-ICU spot of 1 minute vs ICDSC in 8-24 hrs
 2- ICDSC: can better detect the fluctuation of delirium  increase the number of evaluation with
CAM-ICU
 3- The longer assessment period of the ICDSC may lead to increased false-positive screens for
delirium if a patient exhibited signs of delirium in the last 24 hours, but currently exhibits no signs.
 4- CAM-ICU uses specifically defined and validated measures requiring interaction with the
patient to determine the presence or absence of each delirium feature, providing a
reproducible measure. A potential disadvantage is that the diagnostic performance may be
dependent on patient characteristics such as age, premorbid cognition, and severity of illness.
 5- The ICDSC relies on observational methods to detect inattention, disorientation, hallucinations,
presence of sleep, and inappropriate speech or mood. Detection of these symptoms may be
particularly difficult in nonverbal mechanically ventilated patients, yet the ICDSC allows
subjective interpretation with those more difficult circumstances. For this reason, the ICDSC relies
more on clinical experience.
Sensitivity Specificity
CAM ICU 76%-80% 96%-96%
ICDSC 74%-80% 75%-82%

52. The Brain Road Map

53. When Delirium Is Present, “THINK” About “Dr. DRE”

54. Conclusions
 Delirium is a frequent condition in ICU and it is related to important
outcomes
 ICU LOS
 H LOS
 Mortality : open issue
 Costs
 Many risk factors has been related to ICU-Delirium development
 We should work on each items to avoid delirium development
 The relation between Sedation and Delirium is an open issue
 CAM-ICU and ICDSC could be indifferently used to diagnose delirium in ICU