1. Acute Brain Dysfunction in the Critically Ill Patient : Data from recent delirium studies Pratik Pandharipande, MD, MSCI Anesthesiology/ Critical Care Vanderbilt University, Nashville, TN
2. … 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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7. 0 10 20 30 40 50 60 0 5 10 15 20 Days of ICU Delirium Cognitive Function at 12 months (predicted mean T-score) Girard TD, et al. 2008, unpublished data p =.005 Delirium and Long-Term Cognitive Outcomes
10. Probability of transitioning from normal to delirium after lorazepam Lorazepam Dose (mg) Delirium Risk Pandharipande et al. Anesthesiology 2006: 124:21-6 OR 1.2 (1.1-1.4), P=0.003
11. Midazolam and fentanyl as risk factors for delirium Pandharipande et al., J Trauma.2008:65;34-41 Surgical Trauma Users Non-Users Midazolam Daily Midazolam Use (Exc. Coma Days) % Days Delirious 0 20 40 60 80 100 p=0.014 p=0.031 Surgical Trauma Users Non-Users Fentanyl Daily Fentanyl Use (Exc. Coma Days) % Days Delirious 0 20 40 60 80 100 p=0.007 p=0.936
23. SBT- CONTROL SAT+SBT- INTERVENTION Treatment group No Yes Sepsis 0 10 20 Days of Delirium p =.74 Delirium duration in septic patients in ABC study Girard et al. Personal communication p =.02
27. MENDS Study Double blind randomized controlled trial Vanderbilt University Medical Center and Washington Hospital Center Pandharipande P et al. JAMA Dec 2007
28. Brain Dysfunction Delirium/Coma-Free Days 0 2 4 6 8 10 12 p =.01 Delirium-Free Days p =.09 p =.001 Coma-Free Days Dexmedetomidine Lorazepam Pandharipande PP, et al. JAMA 2007;298:2644-53
31. Pandharipande et al. Critical Care 2008, 12(Suppl 2):P275 0.016 67% (35,85) 35% (0,60) Days at Physician RASS goal Efficacy of sedation <0.03 68% 95% Prevalence of coma 0.52 79% 70% Prevalence of delirium <0.003 10 (9, 12) 7 (1,9) Coma free days 0.007 10 (8, 11) 7.5 (4, 8) Delirium free days 0.002 8 (4,10) 1.5 (1,4) Delirium and coma free days Brain Dysfunction (N=19) (N=20) P value Dexmedetomidine Lorazepam Outcome variable MENDS: Patients Outcomes in Septic subgroup
36. MIND Multicenter Double Blind RCT Girard T, Pandharipande P et al. in review MV Surgical, Medical and Trauma ICU patients PO haloperidol PO ziprasidone Placebo
Today, I am going to talk about a new frontier in critical care, brain injury, its prevalence, importance, methods of diagnosis, prognosis and opportunities for treatment.
Why should we be concerned? Delirium : disturbance of consciousness, rapid onset, fluctuating course, ability to receive, process, store and recall information is strikingly impaired Dementia : gradual onset, intellectual impairment, memory disturbance, no clouding of consciousness Psychosis : hallucinations/delusions, impaired reality testing, no clouding of consciousness
Predictors certainly include age and pre-existing impairment, but what else?
Studies such as these have generated interest in whether delirium caused patients to get increased sedation or vice versa
Note that the risk of delirium with no lorazepam was 60%, due to the other risk factors or other drugs. X axis is Lorazepam dose in mg. This is a univariate plot of delirium risk using LOWESS (locally weighted scatter plot smooth, which is derived using locally weighted linear regression to smooth data) versus lorazepam dose, though the odds ratios shown earlier are multivariate analysis
Histogram illustrating the proportion of time that patients were delirious in the surgical and trauma ICU while receiving midazolam, fentanyl or morphine (users) in comparison to those that were not exposed to the medications (non- users). Patients receiving midazolam spent a greater proportion of time with delirium than the non users in the surgical and trauma ICU.
Investigator initiated- D-RCT, with the investigators holding the FDA IND
Shifting gears slightly to the options available for treatment of delirium
