Simone Piva

15° Congresso NazionaleAssociazione Nazionale Psicogeriatria

FIRENZE PALAZZO DEI CONGRESSI

16/18 APRILE 2015

DIAGNOSI E NOSOGRAFIA DELIRIUM IN ICU

Dipartimento di Anestesia, Rianimazione Emergenza Urgenza, AO Spedali Civili di Bresciawww.anestbs.com

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

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

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

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

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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.

Why this Variability?Ahmed S, et al. Age Ageing 2014 May;43(3):326-33

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Prevalence presence of delirium on admission

Incidence New onset of delirium

More frequent in ICU with an overall occurence of 29-64%.

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

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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;291-1753-1762Ouimet S, ICM 2007;33(1):66-73Lin et al, Crit Care Med 2004;32:2254-59

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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

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Delirium and Mortality

Always Related?Depends on

1- Setting

2- Definition of delirium

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CGAComprehensive Geriatric Assessmen

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%).

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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.

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Klouwenberg PMCK, et al. BMJ 2014;349:g6652

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Delirium and Mortality in ICUOuimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequencesof 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 apredictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA2004;291:1753-62.

Lin SM, Liu CY, Wang CH, Lin HC, Huang CD, Huang PY, et al. The impact of deliriumon 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 deliriumare associated with 1-year mortality in an older intensive care unit population. Am J RespirCrit Care Med 2009;180:1092-7.

Van den Boogaard M, Schoonhoven L, van der Hoeven JG, van Achterberg T, PickkersP. Incidence and short-term consequences of delirium in critically ill patients: a prospectiveobservational cohort study. Int J Nurs Stud 2012;49:775-83.

Van den Boogaard M, Peters SA, van der Hoeven JG, Dagnelie PC, Leffers P, PickkersP, et al. The impact of delirium on the prediction of in-hospital mortality in intensive carepatients. Crit Care 2010;14:R146.

Lin SM, Huang CD, Liu CY, Lin HC, Wang CH, Huang PY, et al. Risk factors for thedevelopment of early-onset delirium and the subsequent clinical outcome in mechanicallyventilated patients. J Crit Care 2008;23:372-9.

Salluh JI, Soares M, Teles JM, Ceraso D, Raimondi N, Nava VS, et al. Deliriumepidemiology 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. Comparisonof CAM-ICU and ICDSC for the detection of delirium in critically ill patients focusing onrelevant 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 patientsadmitted through an emergency room. Gen Hosp Psychiatry 1995;17:371-9.

Thomason JW, Shintani A, Peterson JF, Pun BT, Jackson JC, Ely EW. Intensive careunit delirium is an independent predictor of longer hospital stay: a prospective analysisof 261 non-ventilated patients. Crit Care 2005;9:R375-81.

Klein Klouwenberg et al., The attributable mortality of delirium in critically illpatients: 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)

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No minimization Of sedation1740 patientsOR of delirium within the first 24 hourswas 3.22

Adding delirium to APACHE II Score did not improve accuracy of the model in predicting Mortality

Delirium as a severity index?

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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.

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TIME DEPENDENT COVARIATES Daily SOFA score sepsis statuscore temperaturemechanical ventilation statususe of sedative and analgesic drugsand plasma sodiumureaacidosishaematocrit levels

TIME INDEPENDENT COVARIATES has been decided upon literature ageSexhistory of dementiahistory of alcohol misuseCharlson comorbidity indexacute physiology and chronic health evaluation IV score admission type readmission statuspresence of sepsis on admission to the intensive care unit

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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 ofadmission to the intensive care unit may not be representative

of the health state at the time of delirium onset

Secondly, bias mightoccur when a time dependent covariable is not only a risk factor

for death but also predicts subsequent delirium, and whendelirium status at a previous time point predicts the risk factor

Marginal Structural Model

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Marginal Structural Model A marginal structural model

analysis deals with these limitations by adjusting for the changesin disease severity before delirium onset, while preventing

bias. It enables assessment of what the mortality in theintensive care unit would have been in a hypothetical population

in which all patients remained delirium-free, and is thereforecalled 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

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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)

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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.

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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

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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 ASAPWeaning ASAP daily assessment of SBTDaily screening for delirium w ICDSC

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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

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Delirium in ICU: Risk FactorsRi

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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 currentunderstanding 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 onsystematic reviewRi

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The COMET Initiative: search for «delirium»

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The COMET Initiative: search for «delirium»

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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.

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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

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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

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A fist-order Markov model

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Crit Care Med 2015; 43:135–141

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1- No correlation between delirium and Sedation in more recent studies

2- Sedation and ventilation reflect the severity

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.Se

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CAM-ICUvs

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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

and2: Inattention

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3: Disorganized Thinking

4: Altered Level of Consciousness

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ICDSC

1- 8 items, 1 point for each one2- The 8 syntoms are:3- evaluation over 8 to 24 hrs4- ICDSC ≥ 4 indicates a positive ICDSC and the presence ofdelirium

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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%

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The Brain Road Map

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

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