Resuscitation 91 (2015) A3–A4
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Editorial
Cognitive decline after cardiac arrest – It is more to the picture than hypoxic brain injury
Keywords: Cardiac arrest Outcome Rehabilitation Prognosis Cognitive impairment
Fellow researchers in the field of experimental and clinical resuscitation science would probably agree that the available information on brain injury due to cardiac arrest is conflicting. Despite brain injury being the predominating cause of death for hospitalized patients during the first weeks after successful resuscitation,1 as much as 90–95% of long-term survivors have a good neurological function according to the commonly used cerebral performance scale.2 The hypoxic-ischemic brain injury inflicted during the circulatory arrest appears to be either lethal or something that we recover from, at least to a substantial degree. Adding to the complexity, studies using neuropsychological tests report cognitive problems in as much as half of the survivors when assessed during the first year after the arrest.3,4 The degree of cognitive impairment appears relatively stable over time but a few small studies have reported improvement as well as decline during the first year5,6 leading to the frequent call for studies with longer observation times. In this issue of Resuscitation an interesting study of very longterm survivors is presented in which the authors offer yet another piece to this complicated puzzle.7 As survivors were tested 17 years after their arrest 7/8 had below-normal scores in the cognitive screening test, the Montreal Cognitive Assessment (MoCA). The results seem remarkable but it is consoling that the survivors in general were content with their life situation and their quality of life. The MoCA test was not available in the authors’ earlier assessments but was repeatedly found to be more sensitive than the commonly used Mini-Mental State Examination, MMSE,8,9 and may well be the preferable cognitive screening test for OHCA survivors. A major limitation with this Swedish study is that the authors’ description is limited to a very small fraction of the initially included study participants, the majority being either dead or missing. Lacking cognitive outcome data for 92% of the participants, the results become difficult to interpret and generalize from. This considered, the author’s interpretation of cardiac arrest induced cognitive impairment as permanent, with a long-term increased http://dx.doi.org/10.1016/j.resuscitation.2015.03.002 0300-9572/© 2015 Elsevier Ireland Ltd. All rights reserved.
risk of further decline seems plausible. An important question is whether this decline is caused by brain-injury attained during the arrest and finally taking its toll or whether there are other factors at play? In a similar long-term study, Harve et al. used three neuropsychological tests and reported that 5/10 patients were still cognitively intact 15 years after their cardiac arrest, the remainder having some degree of cognitive decline.10 Although cardiac arrest causes severe brain injury in a small group of survivors it may not be the only or even the predominant cause of the mild cognitive impairment seen among half of the survivors in neuropsychological studies.3 Recently we reported that similar levels of cognitive impairment were found in cardiac arrest survivors treated with target temperature management as in a matched control group of myocardial infarction patients who shared the same cardiovascular risk factors.4 Extensive literature supports the role of cardiovascular burden as the major determinant of age-related cognitive decline11 and such burden is likely to have affected the participants of the present study as well. Since cardiac arrest often is the dramatic effect of an underlying cardiovascular disease it is likely that the cardiac arrest population will be at increased risk for a cognitive decline both before and after the arrest. In further support of the impact of cardiovascular risk factors the majority of deaths in the Swedish study were caused by cardiovascular disease, thus the underlying disease that once caused the arrest continue to take its toll. Similar information comes from a study on OHCA-patients in Minnesota, US.2 Patients surviving to discharge from hospital in that cohort had an increased mortality during the next 5-year period compared to a matched control population. However, compared to a disease-matched population with similar cardiovascular risk factors the mortality curve was almost identical. In accordance, earlier studies of patients undergoing coronary artery bypass grafting (CABG) described an initial decline of cognitive function after the intervention. Later studies using a longer follow-up found a similar but later decline in a disease-matched control group without CABG.12 The interpretation of these findings has been that the intervention per se was not responsible for the cognitive impairment; rather the initial decline of cognitive function reflected a more severe stage of the underlying cardiac disease necessitating a CABG. Although it is beyond doubt that circulatory standstill leads to injury in vulnerable areas of the brain there are still other
A4
Editorial / Resuscitation 91 (2015) A3–A4
possible mechanisms shared by cardiac arrest patients and the general group of critically ill ICU patients in which the underlying causal factors for observed cognitive disability to a large extent remain unknown.13,14 In the present study, the possible long-term effects of cognitive impairment 17 years after a cardiac arrest is likely to be overshadowed by the fact that 87% of the patients initially included were dead at the time for the follow-up. Whether patients with an initial cognitive impairment had a higher risk of death is not described, and if the deceased patients had a cognitive decline is not known. One conclusion is therefore that further follow-up of a cardiac arrest cohort beyond 20 years is probably not meaningful. We conclude that survival and long-term cognitive outcome must be considered in the context of the underlying cardiovascular morbidity rather than as an effect merely of the cardiac arrest itself. To evaluate the effect of the cardiac arrest event on long-term survival or cognitive functioning a much larger study including disease-matched as well as healthy controls is warranted and an important challenge for the future. Meanwhile, the increased risk for death and cognitive decline in cardiac arrest survivors should not be neglected. Instead it highlights the importance to offer this high-risk group of patients a multi-disciplinary cardio-neurological follow-up including interventions to prevent, treat and help the patients adjust to their impairments in everyday life with the shared aim to decrease, prevent and delay future problems. Conflict of interest statement Tobias Cronberg and Gisela Lilja declare no conflicts of interest. References 1. Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation 2013;84:337–42. 2. Bunch TJ, White RD, Gersh BJ, et al. Long-term outcomes of out-of-hospital cardiac arrest after successful early defibrillation. N Engl J Med 2003;348:2626–33. 3. Moulaert VR, Verbunt JA, van Heugten CM, Wade DT. Cognitive impairments in survivors of out-of-hospital cardiac arrest: a systematic review. Resuscitation 2009;80:297–305.
4. Lilja G, Nielsen N, Friberg H, et al. Cognitive function in survivors of out-ofhospital cardiac arrest after target temperature management at 33 ◦ C versus 36 ◦ C. Circulation 2015. 5. Roine RO, Kajaste S, Kaste M. Neuropsychological sequelae of cardiac arrest. JAMA 1993;269:237–42. 6. Sauve MJ, Walker JA, Massa SM, Winkle RA, Scheinman MM. Patterns of cognitive recovery in sudden cardiac arrest survivors: the pilot study. Heart Lung 1996;25:172–81. 7. Andersson AE, Rosén H, Sunnerhagen KS. Life after cardiac arrest: A very long term follow up. Resuscitation 2015;91:99–103. 8. Van Heugten CM, Walton L, Hentschel U. Can we forget the Mini-Mental State Examination? A systematic review of the validity of cognitive screening instruments within one month after stroke. Clin Rehabil 2014 (Epub ahead of print). 9. Pendlebury ST, Mariz J, Bull L, Mehta Z, Rothwell PM. MoCA ACE-R, and MMSE versus the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery after TIA and stroke. Stroke 2012;43:464–9. 10. Harve H, Tiainen M, Poutiainen E, et al. The functional status and perceived quality of life in long-term survivors of out-of-hospital cardiac arrest. Acta Anaesthesiol Scand 2007;51:206–9. 11. Qiu C, Fratiglioni L. A major role for cardiovascular burden in age-related cognitive decline. Nat Rev Cardiol 2015;12:267–77. 12. Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N Engl J Med 2012;366:250–7. 13. Wilcox ME, Brummel NE, Archer K, Ely EW, Jackson JC, Hopkins RO. Cognitive dysfunction in ICU patients: risk factors, predictors, and rehabilitation interventions. Crit Care Med 2013;41:S81–98. 14. Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med 2013;369:1306–16.
Tobias Cronberg a,b,∗ Gisela Lilja a,b a Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden b Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, Lund, Sweden ∗ Corresponding
author at: Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden. E-mail address: [email protected] (T. Cronberg) 2 March 2015
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Editorial
Cognitive decline after cardiac arrest – It is more to the picture than hypoxic brain injury
Keywords: Cardiac arrest Outcome Rehabilitation Prognosis Cognitive impairment
Fellow researchers in the field of experimental and clinical resuscitation science would probably agree that the available information on brain injury due to cardiac arrest is conflicting. Despite brain injury being the predominating cause of death for hospitalized patients during the first weeks after successful resuscitation,1 as much as 90–95% of long-term survivors have a good neurological function according to the commonly used cerebral performance scale.2 The hypoxic-ischemic brain injury inflicted during the circulatory arrest appears to be either lethal or something that we recover from, at least to a substantial degree. Adding to the complexity, studies using neuropsychological tests report cognitive problems in as much as half of the survivors when assessed during the first year after the arrest.3,4 The degree of cognitive impairment appears relatively stable over time but a few small studies have reported improvement as well as decline during the first year5,6 leading to the frequent call for studies with longer observation times. In this issue of Resuscitation an interesting study of very longterm survivors is presented in which the authors offer yet another piece to this complicated puzzle.7 As survivors were tested 17 years after their arrest 7/8 had below-normal scores in the cognitive screening test, the Montreal Cognitive Assessment (MoCA). The results seem remarkable but it is consoling that the survivors in general were content with their life situation and their quality of life. The MoCA test was not available in the authors’ earlier assessments but was repeatedly found to be more sensitive than the commonly used Mini-Mental State Examination, MMSE,8,9 and may well be the preferable cognitive screening test for OHCA survivors. A major limitation with this Swedish study is that the authors’ description is limited to a very small fraction of the initially included study participants, the majority being either dead or missing. Lacking cognitive outcome data for 92% of the participants, the results become difficult to interpret and generalize from. This considered, the author’s interpretation of cardiac arrest induced cognitive impairment as permanent, with a long-term increased http://dx.doi.org/10.1016/j.resuscitation.2015.03.002 0300-9572/© 2015 Elsevier Ireland Ltd. All rights reserved.
risk of further decline seems plausible. An important question is whether this decline is caused by brain-injury attained during the arrest and finally taking its toll or whether there are other factors at play? In a similar long-term study, Harve et al. used three neuropsychological tests and reported that 5/10 patients were still cognitively intact 15 years after their cardiac arrest, the remainder having some degree of cognitive decline.10 Although cardiac arrest causes severe brain injury in a small group of survivors it may not be the only or even the predominant cause of the mild cognitive impairment seen among half of the survivors in neuropsychological studies.3 Recently we reported that similar levels of cognitive impairment were found in cardiac arrest survivors treated with target temperature management as in a matched control group of myocardial infarction patients who shared the same cardiovascular risk factors.4 Extensive literature supports the role of cardiovascular burden as the major determinant of age-related cognitive decline11 and such burden is likely to have affected the participants of the present study as well. Since cardiac arrest often is the dramatic effect of an underlying cardiovascular disease it is likely that the cardiac arrest population will be at increased risk for a cognitive decline both before and after the arrest. In further support of the impact of cardiovascular risk factors the majority of deaths in the Swedish study were caused by cardiovascular disease, thus the underlying disease that once caused the arrest continue to take its toll. Similar information comes from a study on OHCA-patients in Minnesota, US.2 Patients surviving to discharge from hospital in that cohort had an increased mortality during the next 5-year period compared to a matched control population. However, compared to a disease-matched population with similar cardiovascular risk factors the mortality curve was almost identical. In accordance, earlier studies of patients undergoing coronary artery bypass grafting (CABG) described an initial decline of cognitive function after the intervention. Later studies using a longer follow-up found a similar but later decline in a disease-matched control group without CABG.12 The interpretation of these findings has been that the intervention per se was not responsible for the cognitive impairment; rather the initial decline of cognitive function reflected a more severe stage of the underlying cardiac disease necessitating a CABG. Although it is beyond doubt that circulatory standstill leads to injury in vulnerable areas of the brain there are still other
A4
Editorial / Resuscitation 91 (2015) A3–A4
possible mechanisms shared by cardiac arrest patients and the general group of critically ill ICU patients in which the underlying causal factors for observed cognitive disability to a large extent remain unknown.13,14 In the present study, the possible long-term effects of cognitive impairment 17 years after a cardiac arrest is likely to be overshadowed by the fact that 87% of the patients initially included were dead at the time for the follow-up. Whether patients with an initial cognitive impairment had a higher risk of death is not described, and if the deceased patients had a cognitive decline is not known. One conclusion is therefore that further follow-up of a cardiac arrest cohort beyond 20 years is probably not meaningful. We conclude that survival and long-term cognitive outcome must be considered in the context of the underlying cardiovascular morbidity rather than as an effect merely of the cardiac arrest itself. To evaluate the effect of the cardiac arrest event on long-term survival or cognitive functioning a much larger study including disease-matched as well as healthy controls is warranted and an important challenge for the future. Meanwhile, the increased risk for death and cognitive decline in cardiac arrest survivors should not be neglected. Instead it highlights the importance to offer this high-risk group of patients a multi-disciplinary cardio-neurological follow-up including interventions to prevent, treat and help the patients adjust to their impairments in everyday life with the shared aim to decrease, prevent and delay future problems. Conflict of interest statement Tobias Cronberg and Gisela Lilja declare no conflicts of interest. References 1. Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation 2013;84:337–42. 2. Bunch TJ, White RD, Gersh BJ, et al. Long-term outcomes of out-of-hospital cardiac arrest after successful early defibrillation. N Engl J Med 2003;348:2626–33. 3. Moulaert VR, Verbunt JA, van Heugten CM, Wade DT. Cognitive impairments in survivors of out-of-hospital cardiac arrest: a systematic review. Resuscitation 2009;80:297–305.
4. Lilja G, Nielsen N, Friberg H, et al. Cognitive function in survivors of out-ofhospital cardiac arrest after target temperature management at 33 ◦ C versus 36 ◦ C. Circulation 2015. 5. Roine RO, Kajaste S, Kaste M. Neuropsychological sequelae of cardiac arrest. JAMA 1993;269:237–42. 6. Sauve MJ, Walker JA, Massa SM, Winkle RA, Scheinman MM. Patterns of cognitive recovery in sudden cardiac arrest survivors: the pilot study. Heart Lung 1996;25:172–81. 7. Andersson AE, Rosén H, Sunnerhagen KS. Life after cardiac arrest: A very long term follow up. Resuscitation 2015;91:99–103. 8. Van Heugten CM, Walton L, Hentschel U. Can we forget the Mini-Mental State Examination? A systematic review of the validity of cognitive screening instruments within one month after stroke. Clin Rehabil 2014 (Epub ahead of print). 9. Pendlebury ST, Mariz J, Bull L, Mehta Z, Rothwell PM. MoCA ACE-R, and MMSE versus the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery after TIA and stroke. Stroke 2012;43:464–9. 10. Harve H, Tiainen M, Poutiainen E, et al. The functional status and perceived quality of life in long-term survivors of out-of-hospital cardiac arrest. Acta Anaesthesiol Scand 2007;51:206–9. 11. Qiu C, Fratiglioni L. A major role for cardiovascular burden in age-related cognitive decline. Nat Rev Cardiol 2015;12:267–77. 12. Selnes OA, Gottesman RF, Grega MA, Baumgartner WA, Zeger SL, McKhann GM. Cognitive and neurologic outcomes after coronary-artery bypass surgery. N Engl J Med 2012;366:250–7. 13. Wilcox ME, Brummel NE, Archer K, Ely EW, Jackson JC, Hopkins RO. Cognitive dysfunction in ICU patients: risk factors, predictors, and rehabilitation interventions. Crit Care Med 2013;41:S81–98. 14. Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med 2013;369:1306–16.
Tobias Cronberg a,b,∗ Gisela Lilja a,b a Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden b Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, Lund, Sweden ∗ Corresponding
author at: Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden. E-mail address: [email protected] (T. Cronberg) 2 March 2015
