1932

Abstract

A growing body of literature has shown that survivors of critical illness often struggle with cognitive impairment that persists months to years after hospital discharge. We describe the epidemiology of this form of cognitive impairment—which we refer to as critical illness brain injury—and review the history and maturation of the investigation of this previously unrecognized, yet common problem. We then review the characteristics of critical illness brain injury, which can vary in severity and typically affects multiple domains of cognition. Finally, we examine known risk factors for critical illness brain injury and, based on these data, suggest approaches to patient management.

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/content/journals/10.1146/annurev-med-050913-015722
2016-01-14
2024-06-24
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Literature Cited

  1. Kaukonen KM, Bailey M, Suzuki S. 1.  et al. 2014. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA 311:1308–16 [Google Scholar]
  2. Phua J, Badia JR, Adhikari NK. 2.  et al. 2009. Has mortality from acute respiratory distress syndrome decreased over time? A systematic review. Am. J. Respir. Crit. Care Med. 179:220–27 [Google Scholar]
  3. Iwashyna TJ. 3.  2010. Survivorship will be the defining challenge of critical care in the 21st century. Ann. Intern. Med. 153:204–5 [Google Scholar]
  4. Fried TR, Bradley EH, Towle VR, Allore H. 4.  2002. Understanding the treatment preferences of seriously ill patients. N. Engl. J. Med. 346:1061–66 [Google Scholar]
  5. Hopkins RO, Weaver LK, Pope D. 5.  et al. 1999. Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 160:50–56 [Google Scholar]
  6. Rothenhausler HB, Ehrentraut S, Stoll C. 6.  et al. 2001. The relationship between cognitive performance and employment and health status in long-term survivors of the acute respiratory distress syndrome: results of an exploratory study. Gen. Hosp. Psychiatry 23:88–94 [Google Scholar]
  7. Hopkins RO, Weaver LK, Chan KJ, Orme JF Jr. 7.  2004. Quality of life, emotional, and cognitive function following acute respiratory distress syndrome. J. Int. Neuropsychol. Soc. 10:1005–17 [Google Scholar]
  8. Hopkins RO, Weaver LK, Collingridge D. 8.  et al. 2005. Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 171:340–47 [Google Scholar]
  9. Christie JD, Biester RC, Taichman DB. 9.  et al. 2006. Formation and validation of a telephone battery to assess cognitive function in acute respiratory distress syndrome survivors. J. Crit. Care 21:125–32 [Google Scholar]
  10. Larson MJ, Weaver LK, Hopkins RO. 10.  2007. Cognitive sequelae in acute respiratory distress syndrome patients with and without recall of the intensive care unit. J. Int. Neuropsychol. Soc. 13:595–605 [Google Scholar]
  11. Mikkelsen ME, Christie JD, Lanken PN. 11.  et al. 2012. The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury. Am. J. Respir. Crit. Care Med. 185:1307–15 [Google Scholar]
  12. Needham DM, Dinglas VD, Morris PE. 12.  et al. 2013. Physical and cognitive performance of patients with acute lung injury 1 year after initial trophic versus full enteral feeding. EDEN trial follow-up. Am. J. Respir. Crit. Care Med. 188:567–76 [Google Scholar]
  13. Needham DM, Dinglas VD, Bienvenu OJ. 13.  et al. 2013. One year outcomes in patients with acute lung injury randomised to initial trophic or full enteral feeding: prospective follow-up of EDEN randomised trial. BMJ 346:f1532 [Google Scholar]
  14. 14. Acute Respiratory Distress Syndrome Network 2000. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.. N. Engl. J. Med. 342:1301–8 [Google Scholar]
  15. Girard TD, Kress JP, Fuchs BD. 15.  et al. 2008. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 371:126–34 [Google Scholar]
  16. Jackson JC, Hart RP, Gordon SM. 16.  et al. 2003. Six-month neuropsychological outcome of medical intensive care unit patients. Crit. Care Med. 31:1226–34 [Google Scholar]
  17. Sukantarat KT, Burgess PW, Williamson RC, Brett SJ. 17.  2005. Prolonged cognitive dysfunction in survivors of critical illness. Anaesthesia 60:847–53 [Google Scholar]
  18. Jones C, Griffiths RD, Slater T. 18.  et al. 2006. Significant cognitive dysfunction in non-delirious patients identified during and persisting following critical illness. Intensive Care Med. 32:923–26 [Google Scholar]
  19. Girard TD, Jackson JC, Pandharipande PP. 19.  et al. 2010. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit. Care Med. 38:1513–20 [Google Scholar]
  20. Ehlenbach WJ, Hough CL, Crane PK. 20.  et al. 2010. Association between acute care and critical illness hospitalization and cognitive function in older adults. JAMA 303:763–70 [Google Scholar]
  21. Sacanella E, Perez-Castejon JM, Nicolas JM. 21.  et al. 2011. Functional status and quality of life 12 months after discharge from a medical ICU in healthy elderly patients: a prospective observational study. Crit. Care 15:R105 [Google Scholar]
  22. Woon FL, Dunn CB, Hopkins RO. 22.  2012. Predicting cognitive sequelae in survivors of critical illness with cognitive screening tests. Am. J. Respir. Crit. Care Med. 186:333–40 [Google Scholar]
  23. Pandharipande PP, Girard TD, Jackson JC. 23.  et al. 2013. Long-term cognitive impairment after critical illness. N. Engl. J. Med. 369:1306–16 [Google Scholar]
  24. Iwashyna TJ, Ely EW, Smith DM, Langa KM. 24.  2010. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 304:1787–94 [Google Scholar]
  25. Jackson JC, Archer KR, Bauer R. 25.  et al. 2011. A prospective investigation of long-term cognitive impairment and psychological distress in moderately versus severely injured trauma intensive care unit survivors without intracranial hemorrhage. J. Trauma 71:860–66 [Google Scholar]
  26. 26. The National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network 2006. Comparison of two fluid-management strategies in acute lung injury. N. Engl. J. Med. 354:2564–75 [Google Scholar]
  27. Brummel NE, Girard TD, Ely EW. 27.  et al. 2014. Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial. Intensive Care Med. 40:370–79 [Google Scholar]
  28. Jackson JC, Ely EW, Morey MC. 28.  et al. 2012. Cognitive and physical rehabilitation of intensive care unit survivors: results of the RETURN randomized controlled pilot investigation. Crit. Care Med. 40:1088–97 [Google Scholar]
  29. Jackson JC, Girard TD, Gordon SM. 29.  et al. 2010. Long-term cognitive and psychological outcomes in the Awakening and Breathing Controlled trial. Am. J. Respir. Crit. Care Med. 182:183–91 [Google Scholar]
  30. Robinson KA, Dennison CR, Wayman DM. 30.  et al. 2007. Systematic review identifies number of strategies important for retaining study participants. J. Clin. Epidemiol. 60:757–65 [Google Scholar]
  31. Tansey CM, Matte AL, Needham D, Herridge MS. 31.  2007. Review of retention strategies in longitudinal studies and application to follow-up of ICU survivors. Intensive Care Med. 33:2051–57 [Google Scholar]
  32. Kurland BF, Johnson LL, Egleston BL, Diehr PH. 32.  2009. Longitudinal data with follow-up truncated by death: match the analysis method to research aims. Stat. Sci. 24:211 [Google Scholar]
  33. Randolph C, Tierney MC, Mohr E, Chase TN. 33.  1998. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J. Clin. Exp. Neuropsychol. 20:310–19 [Google Scholar]
  34. Hobson VL, Hall JR, Humphreys-Clark JD. 34.  et al. 2010. Identifying functional impairment with scores from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Int. J. Geriatr. Psychiatry 25:525–30 [Google Scholar]
  35. McKay C, Casey JE, Wertheimer J, Fichtenberg NL. 35.  2007. Reliability and validity of the RBANS in a traumatic brain injured sample. Arch. Clin. Neuropsychol. 22:91–98 [Google Scholar]
  36. Randolph C. 36.  1998. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Manual San Antonio, TX: Psychological Corp. [Google Scholar]
  37. Qin L, Wu X, Block ML. 37.  et al. 2007. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55:453–62 [Google Scholar]
  38. Semmler A, Hermann S, Mormann F. 38.  et al. 2008. Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism. J. Neuroinflamm. 5:38 [Google Scholar]
  39. Bossu P, Cutuli D, Palladino I. 39.  et al. 2012. A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-alpha and IL-18. J. Neuroinflamm. 9:101 [Google Scholar]
  40. Weberpals M, Hermes M, Hermann S. 40.  et al. 2009. NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits. J. Neurosci. 29:14177–84 [Google Scholar]
  41. Cardoso FL, Herz J, Fernandes A. 41.  et al. 2015. Systemic inflammation in early neonatal mice induces transient and lasting neurodegenerative effects. J. Neuroinflamm. 12:82 [Google Scholar]
  42. d'Avila JC, Santiago AP, Amancio RT. 42.  et al. 2008. Sepsis induces brain mitochondrial dysfunction. Crit. Care Med. 36:1925–32 [Google Scholar]
  43. Comim CM, Rezin GT, Scaini G. 43.  et al. 2008. Mitochondrial respiratory chain and creatine kinase activities in rat brain after sepsis induced by cecal ligation and perforation. Mitochondrion 8:313–18 [Google Scholar]
  44. Noh H, Jeon J, Seo H. 44.  2014. Systemic injection of LPS induces region-specific neuroinflammation and mitochondrial dysfunction in normal mouse brain. Neurochem. Int. 69:35–40 [Google Scholar]
  45. Hernandes MS, D'Avila JC, Trevelin SC. 45.  et al. 2014. The role of Nox2-derived ROS in the development of cognitive impairment after sepsis. J. Neuroinflamm. 11:36 [Google Scholar]
  46. Semmler A, Okulla T, Sastre M. 46.  et al. 2005. Systemic inflammation induces apoptosis with variable vulnerability of different brain regions. J. Chem. Neuroanat. 30:144–57 [Google Scholar]
  47. Gunther ML, Morandi A, Krauskopf E. 47.  et al. 2012. The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: the VISIONS cohort magnetic resonance imaging study. Crit. Care Med. 40:2022–32 [Google Scholar]
  48. Hopkins RO, Suchyta MR, Snow GL. 48.  et al. 2010. Blood glucose dysregulation and cognitive outcome in ARDS survivors. Brain Inj. 24:1478–84 [Google Scholar]
  49. Jackson JC, Gordon SM, Hart RP. 49.  et al. 2004. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol. Rev. 14:87–98 [Google Scholar]
  50. MacLullich AM, Beaglehole A, Hall RJ, Meagher DJ. 50.  2009. Delirium and long-term cognitive impairment. Int. Rev. Psychiatry 21:30–42 [Google Scholar]
  51. van den Boogaard M, Schoonhoven L, Evers AW. 51.  et al. 2012. Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. Crit. Care Med. 40:112–18 [Google Scholar]
  52. Wolters AE, van Dijk D, Pasma W. 52.  et al. 2014. Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study. Crit. Care 18:R125 [Google Scholar]
  53. Jackson JC, Hopkins RO, Miller RR. 53.  et al. 2009. Acute respiratory distress syndrome, sepsis, and cognitive decline: a review and case study. South. Med. J. 102:1150–57 [Google Scholar]
  54. 54. ICU Delirium and Cognitive Impairment Study Group 2015. Patient testimonials http://www.icudelirium.org/testimonials.html. Accessed May 18, 2015 [Google Scholar]
  55. Ely EW, Inouye SK, Bernard GR. 55.  et al. 2001. Delirium in mechanically ventilated patients: validity and reliability of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). JAMA 286:2703–10 [Google Scholar]
  56. Ely EW, Margolin R, Francis J. 56.  et al. 2001. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit. Care Med. 29:1370–79 [Google Scholar]
  57. Ely EW, Pun BT. 57.  2014. The Confusion Assessment Method for the ICU (CAM-ICU) training manual http://www.icudelirium.org/docs/CAM_ICU_training.pdf [Google Scholar]
  58. Bergeron N, Dubois MJ, Dumont M. 58.  et al. 2001. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 27:859–64 [Google Scholar]
  59. Barr J, Fraser GL, Puntillo K. 59.  et al. 2013. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit. Care Med. 41:263–306 [Google Scholar]
  60. Pandharipande P, Shintani A, Peterson J. 60.  et al. 2006. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 104:21–26 [Google Scholar]
  61. Pandharipande P, Cotton BA, Shintani A. 61.  et al. 2008. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J. Trauma 65:34–41 [Google Scholar]
  62. Agarwal V, O'Neill PJ, Cotton BA. 62.  et al. 2010. Prevalence and risk factors for development of delirium in burn intensive care unit patients. J. Burn Care Res. 31:706–15 [Google Scholar]
  63. McPherson JA, Wagner CE, Boehm LM. 63.  et al. 2013. Delirium in the cardiovascular ICU: exploring modifiable risk factors. Crit. Care Med. 41:405–13 [Google Scholar]
  64. Pandharipande PP, Pun BT, Herr DL. 64.  et al. 2007. Effect of sedation with dexmedetomidine versus lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 298:2644–53 [Google Scholar]
  65. Riker RR, Shehabi Y, Bokesch PM. 65.  et al. 2009. Dexmedetomidine versus midazolam for sedation of critically ill patients: a randomized trial. JAMA 301:489–99 [Google Scholar]
  66. Hager DN, Dinglas VD, Subhas S. 66.  et al. 2013. Reducing deep sedation and delirium in acute lung injury patients: a quality improvement project. Crit. Care Med. 41:1435–42 [Google Scholar]
  67. Balas MC, Vasilevskis EE, Olsen KM. 67.  et al. 2014. Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle. Crit. Care Med. 42:1024–36 [Google Scholar]
  68. Strom T, Martinussen T, Toft P. 68.  2010. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 375:475–80 [Google Scholar]
  69. Brook AD, Ahrens TS, Schaiff R. 69.  et al. 1999. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit. Care Med. 27:2609–15 [Google Scholar]
  70. Kress JP, Pohlman AS, O'Connor MF, Hall JB. 70.  2000. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N. Engl. J. Med. 342:1471–77 [Google Scholar]
  71. Pisani MA, Friese RS, Gehlbach BK. 71.  et al. 2015. Sleep in the intensive care unit. Am. J. Respir. Crit. Care Med. 191:731–38 [Google Scholar]
  72. Helton MC, Gordon SH, Nunnery SL. 72.  1980. The correlation between sleep deprivation and the intensive care unit syndrome. Heart Lung 9:464–68 [Google Scholar]
  73. Weinhouse GL, Schwab RJ, Watson PL. 73.  et al. 2009. Bench-to-bedside review: delirium in ICU patients—importance of sleep deprivation. Crit. Care 13:234 [Google Scholar]
  74. Van Rompaey B, Elseviers MM, Van Drom W. 74.  et al. 2012. The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients. Crit. Care 16:R73 [Google Scholar]
  75. Kamdar BB, King LM, Collop NA. 75.  et al. 2013. The effect of a quality improvement intervention on perceived sleep quality and cognition in a medical ICU. Crit. Care Med. 41:800–9 [Google Scholar]
  76. Inouye SK, Charpentier PA. 76.  1996. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 275:852–57 [Google Scholar]
  77. Van Rompaey B, Elseviers MM, Schuurmans MJ. 77.  et al. 2009. Risk factors for delirium in intensive care patients: a prospective cohort study. Crit. Care 13:R77 [Google Scholar]
  78. Schweickert WD, Pohlman MC, Pohlman AS. 78.  et al. 2009. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 373:1874–82 [Google Scholar]
  79. Needham DM, Korupolu R, Zanni JM. 79.  et al. 2010. Early physical medicine and rehabilitation for patients with acute respiratory failure: a quality improvement project. Arch. Phys. Med. Rehabil. 91:536–42 [Google Scholar]
  80. Girard TD, Pandharipande PP, Carson SS. 80.  et al. 2010. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit. Care Med. 38:428–37 [Google Scholar]
  81. Devlin JW, Roberts RJ, Fong JJ. 81.  et al. 2010. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit. Care Med. 38:419–27 [Google Scholar]
  82. Page VJ, Ely EW, Gates S. 82.  et al. 2013. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respir. Med. 1:515–23 [Google Scholar]
  83. 83. American Psychiatric Association 2013. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5 Washington, DC: Am. Psychiatr. Publ. [Google Scholar]
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