Journal club: long-term cognitive impairment after critical illness [NEJM 369]
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Journal Club and some extra considerations, presented in April 2015 at Hadassah Ein Kerem Universitary Hospital, Jerusalem
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Journal club: long-term cognitive impairment after critical illness [NEJM 369]
- 1. JOURNAL CLUB LONG-TERM COGNITIVE IMPAIRMENT AFTER CRITICAL ILLNESS JOÃO MELO ALVES, MD LISBOA, PORTUGAL -- INTERNAL MEDICINE ICU DIRECTOR: PROF. VAN-HEERDEN VERNON, MD HADASSAH EIN KEREM UNIVERSITARY HOSPITAL JERUSALEM
- 2. PROLOGUE JOURNAL CLUB EPILOGUE THE STUDY BRAIN-ICU Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU survivors Pratik Pandharipande, MD American Board of Anesthesiology – Anesthesiology & Critical Care American College of Critical Care Medicine – Fellow Professor of Anesthesiology, Vanderbilt University School of Medicine Multicenter prospective cohort Nashville (Tennessee, USA) Vanderbilt University Medical Center Saint Thomas Hospital
- 3. PROLOGUE JOURNAL CLUB EPILOGUE DEFINITIONS “use of a correct terminology is a key factor to spread the knowledge on clinical conditions”
- 4. PROLOGUE JOURNAL CLUB EPILOGUE DEFINITIONS DELIRIUM MCI Dementia POCD (…) A. Morandi, PP Pandharipande et. al Best Pract Res Clin Anaesthesiol 26 (2012) 267-276 LTCI-CI
- 5. DELIRIUM Disturbance of consciousness with inattention Acute change in cognition (memory, disorientation, language, perception) Acute onset (hours to days) & fluctuating course Clinical evidence that it is secondary to a medical condition TIME COURSE Prevalent Incident Persistent MOTORIC SUBTYPES Hyperactive Hypoactive Mixed Subsyndromal Sumperimposed on dementia DSM-IV-TR Diagnostic and Statistical Manual 4th ed. American Psychiatric Association. APA Press, 2013. DEFINITIONS PROLOGUE JOURNAL CLUB EPILOGUE
- 6. LTCI-CI Long-term cognitive impairment after critical illness RBANS Repeatable Battery for the Assessment of Neuropsychological Status TWO TESTS < 2 S.D. THREE TESTS < 1.5 S.D. MCI AD (…) A. Morandi, PP Pandharipande et. al Best Pract Res Clin Anaesthesiol 26 (2012) 267-276 DEFINITIONS PROLOGUE JOURNAL CLUB EPILOGUE
- 7. LTCI-CI Long-term cognitive impairment after critical illness RBANS Repeatable Battery for the Assessment of Neuropsychological Status TWO TESTS < 2 S.D. THREE TESTS < 1.5 S.D. MCI AD (…) A. Morandi, PP Pandharipande et. al Best Pract Res Clin Anaesthesiol 26 (2012) 267-276 DEFINITIONS PROLOGUE JOURNAL CLUB EPILOGUE Reitan RM. Percept Mot Skills 1958 (8)
- 8. LTCI-CI Long-term cognitive impairment after critical illness RBANS Repeatable Battery for the Assessment of Neuropsychological Status TWO TESTS < 2 S.D. THREE TESTS < 1.5 S.D. MCI AD (…) A. Morandi, PP Pandharipande et. al Best Pract Res Clin Anaesthesiol 26 (2012) 267-276 DEFINITIONS PROLOGUE JOURNAL CLUB EPILOGUE
- 9. JOURNAL CLUB
- 10. LTCI-CI Small cohorts Individual disease processes Large studies lacking in-hospital RF assessment LIMITED EVIDENCE Multicenter prospective cohort study of a diverse critically ill population Prevalence of LTCI-CI Hypothesis: duration of delirium, doses of sedation/analgesia ? BACKGROUND PROLOGUE JOURNAL CLUB EPILOGUE
- 11. ADULTS medical or surgical ICU respiratory failure cardiogenic shock septic shock (…) DELIRIUM Number of hospital days SEDATION / ANALGESIA 3 MONTHS 12 MONTHS IN-HOSPITAL POST-DISCHARGE METHODS PROLOGUE JOURNAL CLUB EPILOGUE
- 12. ADULTS medical or surgical ICU respiratory failure cardiogenic shock septic shock (…) DELIRIUM Number of hospital days SEDATION / ANALGESIA 3 MONTHS 12 MONTHS IN-HOSPITAL POST-DISCHARGE METHODS PROLOGUE JOURNAL CLUB EPILOGUE Covariates Age Years of education Chronic disease burden (Charlson comorbidity index) Preexisting cognitive impairment (short IQCODE) Cerebrovascular disease (Framingham Stroke Risk Profile) Apolipoprotein E genotype Daily SOFA Mean daily dose Haloperidol Duration of severe sepsis, hypoxemia, coma Multiple linear regression adjustament for covariates separate models for 3 and 12 months
- 13. PROLOGUE JOURNAL CLUB EPILOGUE RESULTS March 2007 – May 2010 821 patients HOSPITAL MONTH 3 MONTH 12 74% had delirium 569 survivors 510 survirors COGNITIVE TESTING 448 382 467 patients underwent follow-up at 3 and/or 12 months
- 15. PROLOGUE JOURNAL CLUB EPILOGUE RESULTS 3m 12m Median RBANS global cognition score -1.5 σ ≤ moderate TBI 40% 34% ≤ mild Alzheimer’s (-2 σ) 26% 24%
- 16. PROLOGUE JOURNAL CLUB EPILOGUE RESULTS 3m 12m Median RBANS global cognition score -1.5 σ ≤ moderate TBI 40% 34% ≤ mild Alzheimer’s (-2 σ) 26% 24% Impairment not limited to older patients or those with coexisting conditions at baseline: <49 yo previously healthy, 12m 34% ≤ moderate TBI 20% ≤ mild Alzheimer’s Mild Alzheimer’s predominantly affects delayed memory, but… LTCI is multidomain
- 17. 3 MONTHS 12 MONTHS IN-HOSPITAL POST-DISCHARGE RESULTS – RISK FACTORS PROLOGUE JOURNAL CLUB EPILOGUE p=0.001 p=0.004 p=0.04 p=0.007 Global RBANS Executive function DELIRIUM SEDATION / ANALGESIA individual RBANS domains
- 18. 3 MONTHS 12 MONTHS IN-HOSPITAL POST-DISCHARGE RESULTS – RISK FACTORS PROLOGUE JOURNAL CLUB EPILOGUE p=0.001 p=0.004 p=0.04 p=0.04 p=0.007 Global RBANS Executive function DELIRIUM SEDATION / ANALGESIA individual RBANS domains Benzodiazepines Opiates PPF Dexmedetomidine
- 19. 3 MONTHS 12 MONTHS IN-HOSPITAL POST-DISCHARGE RESULTS – RISK FACTORS PROLOGUE JOURNAL CLUB EPILOGUE p=0.001 p=0.004 p=0.04 p=0.007 Global RBANS Executive function DELIRIUM SEDATION / ANALGESIA individual RBANS domains
- 21. Causal role? Mechanisms? Inflammation and neuronal apoptosis brain atrophy and loss of white matter integrity Van Gool WA et al. Lancet 2010 (375) Cunningham C. Biochem Soc Trans 2011 (39) Gunther ML et al. Crit Care Med 2012 (40) Morandi A et al. Crit Care Med 2012 (40) PROLOGUE JOURNAL CLUB EPILOGUE DISCUSSION ≤Alzheimer’s ≤ TBI These profound cognitive deficits were new in the majority of patients, and affected both old and young patients, regardless of the burden of coexisting illnesses at baseline Longer duration of delirium worse long-term global cognition and executive function Independent of sedation, analgesia, age, preexistent cognitive impairment, coexisting conditions and SOFA score
- 22. Groundbreaking study A role for interventions targeted at reducing delirium duration? Limitations Previous cognitive function not assessed Patients with incomplete data Unmeasured confounders? PROLOGUE JOURNAL CLUB EPILOGUE DISCUSSION
- 23. Reliability of delirium assessment Letter to the editor (NEJM 370;2 p184) PROLOGUE JOURNAL CLUB EPILOGUE BEYOND THE JOURNAL CLUB “sedation confounds delirium assessement, especially with the CAM-ICU” “patients who are awake in the ICU have a much lower prevalence of delirium than more sedated patients” “as sedation decreases and RASS increases, rate of delirium assessed by CAM-ICU drops precipitously”
- 24. “unequivocally establishes” “ a new standard of longitudinal cognitive-outcome studies” “herculean efforts to track patients and conduct blinded cognitive assessments” “prior observations suggesting drug exposures are clear risk factors were not supported” PROLOGUE JOURNAL CLUB EPILOGUE BEYOND THE JOURNAL CLUB Herridge M, Cameron JI. NEJM 369;14
- 25. “unequivocally establishes” “ a new standard of longitudinal cognitive-outcome studies” “herculean efforts to track patients and conduct blinded cognitive assessments” “prior observations suggesting drug exposures are clear risk factors were not supported” PROLOGUE JOURNAL CLUB EPILOGUE BEYOND THE JOURNAL CLUB Herridge M, Cameron JI. NEJM 369;14 “it would be important to gain an appreciation of how the brain-activity interface affects functional independence, quality of life and patient- centered outcomes (…) job loss, healthcare utilization, family caregivers” “risk stratification will help distinguish patients who can regain functional independence and those who have exhausted their organ reserve and rehabilitive potential and who live in the purgatory of critical illness only to have unacceptably poor outcomes” “should fuel an informed discussion about what it means for our patients to survive and episode of critical illness (…) when the degree of suffering and futility becomes unacceptable from a patient-centered and societal standpoint”
- 26. Duration of ICU delirium vs. disability and physical health status N=126 CAM-ICU vs. Katz activities of daily living (…) PROLOGUE JOURNAL CLUB EPILOGUE BEYOND THE JOURNAL CLUB Crit Care Med 2014 (42) worse activities of daily living scores at 12m (p=0.002) worse motor-sensory function (p=0.02)
- 27. PROLOGUE JOURNAL CLUB EPILOGUE BEYOND THE JOURNAL CLUB Lancet Resp Med 2014 (2) 3 months 12 months depression 37% 33% PTSD 7% 7% basic activities of daily living 32% 27% instrumental activities of daily living 26% 23% (no consistent association between delirium and outcomes…)
- 28. BEYOND THE JOURNAL CLUB PREVENT Orientation protocols Cognitive stimulation Physiologic sleep (e.g. lighting, earplugs) Early mobilization, avoid restraints Visual/hearing aids Monitor orders (e.g. bzd) Pain BUNDLES! TREAT THE CAUSE MANAGE SYMPTOMS Hyperactive only! Nonpharmacological interventions LOW DOSE, SHORT ACTING, PRN drugs Neuroleptics Atypical antipsichotics BZD CholE inhib? PROLOGUE JOURNAL CLUB EPILOGUE
- 29. (A FEW) FINAL WORDS
- 31. MANUEL DE OLIVEIRA (1908-2015)
- 32. 1. Pandharipande PP et al. Long-term cognitive impairment after critical illness. N Engl J Med 369 (2013);14, 1306-1316 2. Morandi A, Pandharipande PP et al. Understanding terminology of delirium and long-term cognitive impairment in critically ill patients. Best Pract Res Clin Anaesthesiol 26 (2012) 267-276 3. Herridge M, Cameron JI. Disability after critical illness (editorial). N Engl J Med 2013 (369:14) 4. Fraser GL, Riker RR, Coursin DC. (letter to the editor).N Engl J Med 2014 (370:2) 5. Brummel NE et al. Delirium in the ICU and subsequent long-term disability among survivors of mechanical ventilation. Crit Care Med 2014 (42:2) 6. Jackson JC et al. Depression, post-traumatic stress disorder and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study. Lancet Respir Med 2014 (2)