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Medical Complications After Aneurysmal Subarachnoid Hemorrhage: An Emerging Contributor to Poor Outcome
Perspectives Commentary on: Acute Lung Injury in Patients with Subarachnoid Hemorrhage: A Nationwide Inpatient Sample Study by Veeravagu et al. World Neurosurg 82:E235-E241, 2014
Medical Complications After Aneurysmal Subarachnoid Hemorrhage: An Emerging Contributor to Poor Outcome Nima Etminan1 and R. Loch Macdonald2
D
uring the past 3 decades, mortality after aneurysmal subarachnoid hemorrhage (SAH) has been effectively reduced by approximately 50% (6), mainly as the consequence of early repair of ruptured aneurysms and significant advances in aneurysm repair modalities but also improved neurocritical care. Nevertheless, the incidence of poor neurologic outcome has basically remained unchanged and ranges between 25% and 50% (1). The underlying pathophysiologic mechanisms that contribute to poor neurologic outcome, i.e., the extent of early brain injury and the incidence of delayed cerebral ischemia (DCI), and, moreover, their effective pharmaceutical treatment, are the focus of intensive research. Nevertheless, with increasing overall survival rates after aneurysmal SAH, medical or noncerebral complications increasingly are recognized as an additional determinant for neurologic outcome in the course of SAH. Indeed, there is evidence that primary critical medical illnesses, including sepsis and respiratory failure requiring intensive care support, are associated with cognitive impairment (12). In one study of 821 patients with respiratory failure or shock who were in the intensive care unit, 40% had cognitive scores similar to the scores of patients who suffer moderate traumatic brain injury (12). Why and how systemic illness causes cognitive dysfunction is not clear and is the subject of experimental study (9), but it points out that the high rate of cognitive dysfunction in patients with SAH may be contributed to by delirium and systemic illness. The prevention of medical complications may be even more important than previously thought.
Key words Acute lung injury - Acute respiratory distress syndrome - Nationwide Inpatient Sample Database - Subarachnoid hemorrhage -
Abbreviations and Acronyms ALI: Acute lung syndrome ARDS: Acute respiratory distress syndrome DCI: Delayed cerebral ischemia PE: Pulmonary edema SAH: Subarachnoid hemorrhage
Naturally, the incidence of such complications increases with increasing patient age and is reported to be twice as high in patients older than 70 years of age compared with patients younger than 40 (5). Studies also clearly illustrate that medical complications are the only complication of SAH that are increasing in terms of contribution to outcome after SAH (4). Furthermore, although there are few good randomized studies of medical treatment, there is a suggestion that earlier and more active treatment of cardiopulmonary complications in poor-grade SAH patients is associated with better functional outcome (4, 10). In view of these data as discussed by Lovelock et al., it is evident that the aforementioned reduction of case fatality after SAH also is related to the increasing collaborative efforts of neurosurgeons and neurointensivists to treat this complex disease and especially its complications. The most common medical complications are of cardiocirculatory, i.e., acute heart or renal failure of pulmonary nature, i.e., acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) (2, 4). It is likely that the incidence of cardiocirculatory and pulmonary complications is somewhat related to the incidence of risk factors for SAH, which suggests that if a patient has been smoking and suffering from untreated hypertension for decades, one should expect that these patients are more prone to systemic complications. Nevertheless, especially for good-grade SAH patients, it can be difficult to anticipate early after SAH ictus which patient requires more vigilant care or aggressive hemodynamic monitoring. Electrocardiographic alterations and cardiac enzyme (troponin T) elevations are quite frequent after SAH but, depending on their
From the 1Department of Neurosurgery, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; and 2Division of Neurosurgery, St. Michael’s Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, and the Department of Surgery, University of Toronto, Toronto, Ontario, Canada To whom correspondence should be addressed: Nima Etminan, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015) 83, 3:303-304. http://dx.doi.org/10.1016/j.wneu.2014.06.031
WORLD NEUROSURGERY 83 [3]: 303-304, MARCH 2015
www.WORLDNEUROSURGERY.org
303
PERSPECTIVES
severity, also are significant surrogates for clinical outcome (8, 11). The exact pathomechanisms behind acute myocardial injury or neurogenic myocardial are incompletely understood but clinically this may manifest as left ventricular failure, with subsequent impaired cardiac output, hypotension, and pulmonary edema (PE). The evident relation between impaired cardiac output, decreased cerebral perfusion pressure, or brain tissue oxygenation underlines the necessity of intensive noninvasive and invasive hemodynamic monitoring in such patients, to avoid an additive effect of such complications on DCI and neurologic outcome after SAH. The heterogeneous previous definitions for ALI (usually defined as partial pressure of oxygen in the blood [i.e., PaO2] to fraction of inspired oxygen [FiO2] ratio <300), which is now usually summarized in the revised definition of ARDS (mild, moderate, severe), make it difficult to accurately estimate their incidence in patients with SAH but they are reported to constitute 27% (for ALI) and up to 23% (for ARDS) (3, 13). In the setting of SAH, ARDS is commonly associated with pulmonary edema and/or pneumonia due to prolonged ventilation or aspiration. PE frequently is caused by fluid overload in patients with SAH for prevention or reduction of DCI, which warrants the use of hemodynamic monitoring (e.g., based on pulmonary artery catheters or thermodilution-guided measurement of cardiac output), in such patients to maintain euvolemia. Neurogenic PE after SAH or traumatic brain injury also is incompletely understood pulmonary complication and a rather seldom cause for ARDS, estimated to occur in 2%e8% of patients with SAH. In the current study by Veeravagu et al. (14), the authors investigated the prevalence, risk factors, and outcome for patients with ARDS and ALI after SAH using the Nationwide Inpatient Sample Database. The prevalence of ARDS among
REFERENCES 1. Al-Khindi T, Macdonald RL, Schweizer TA: Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke 41:e519-e536, 2010. 2. Beseoglu K, Holtkamp K, Steiger HJ, Hanggi D: Fatal aneurysmal subarachnoid haemorrhage: causes of 30-day in-hospital case fatalities in a large single-centre historical patient cohort. Clin Neurol Neurosurg 115:77-81, 2013. 3. Bruder N, Rabinstein A: Cardiovascular and pulmonary complications of aneurysmal subarachnoid hemorrhage. Neurocrit Care 15:257-269, 2011. 4. Komotar RJ, Schmidt JM, Starke RM, Claassen J, Wartenberg KE, Lee K, Badjatia N, Connolly ES Jr, Mayer SA: Resuscitation and critical care of poorgrade subarachnoid hemorrhage. Neurosurgery 64:397-410, 2009. 5. Lanzino G, Kassell NF, Germanson TP, Kongable GL, Truskowski LL, Torner JC, Jane JA: Age and outcome after aneurysmal subarachnoid hemorrhage: why do older patients fare worse? J Neurosurg 85:410-418, 1996. 6. Lovelock CE, Rinkel GJ, Rothwell PM: Time trends in outcome of subarachnoid hemorrhage: population-based study and systematic review. Neurology 74:1494-1501, 2010.
304
www.SCIENCEDIRECT.com
patients with SAH was as high as 38% in 2008. The most important risk factors for ARDS in patients with SAH were ethnic background, cardiac arrest and cardiovascular dysfunction, reduced neurologic status and, interestingly, larger hospital size. Although the latter finding is likely related to selection bias, this study suggests that socioeconomic background and comorbid diseases as well SAH grade are significant cofactors in the development of ARDS and poor neurologic outcome, which suggests the need for closer monitoring in such patient cohorts. Importantly, the basically unchanged high incidence of pulmonary complications during the course of SAH highlights the need for dedicated neurocritical management via the use of standardized hemodynamic monitoring or even more novel techniques to compensate ALI or ARDS, e.g., interventional lung assist devices. Ultimately, poor outcome after SAH is multifactorial, and its effective reduction is not only likely to be improved by reducing the usual complications, such as early brain injury, rebleeding, complications from aneurysm repair and DCI but, as highlighted in the present study, also to medical and especially pulmonary complications, which deserve our distinct attention to achieve better outcomes. This is also underlined by the findings of the CONSCIOUS-1 (i.e., Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid hemorrhage) study, in which the pulmonary side effects of the experimental drug may have diluted its beneficial effect on DCI and that did not result in improved outcome for patients (7). Moving forward, future clinical studies should identify and prospectively validate early markers as well as the beneficial effect of more aggressive monitoring and treatment in patient cohorts, which are at increased risk for developing medical complications after SAH.
7. Macdonald RL, Kassell NF, Mayer S, Ruefenacht D, Schmiedek P, Weidauer S, Frey A, Roux S, Pasqualin A: Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dosefinding trial. Stroke 39:3015-3021, 2008. 8. Manavalan P, Richardson D, Rayford R, Talley JD: ECG and cardiac enzymes changes associated with subarachnoid hemorrhage. J Arkansas Med Soc 93:592-593, 1997. 9. Mina F, Comim CM, Dominguini D, Cassol-Jr OJ, Dall Igna DM, Ferreira GK, Silva MC, Galant LS, Streck EL, Quevedo J, Dal-Pizzol F: IL1-beta involvement in cognitive impairment after sepsis. Mol Neurobiol 49:1069-1076, 2014. 10. Mocco J, Ransom ER, Komotar RJ, Schmidt JM, Sciacca RR, Mayer SA, Connolly ES Jr: Preoperative prediction of long-term outcome in poorgrade aneurysmal subarachnoid hemorrhage. Neurosurgery 59:529-538, 2006. 11. Naidech AM, Kreiter KT, Janjua N, Ostapkovich ND, Parra A, Commichau C, Fitzsimmons BF, Connolly ES, Mayer SA: Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation 112:2851-2856, 2005.
12. Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW: Long-term cognitive impairment after critical illness. N Engl J Med 369:1306-1316, 2013. 13. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS: Acute respiratory distress syndrome: the Berlin Definition. JAMA 307: 2526-2533, 2012. 14. Veeravagu A, Chen YR, Ludwig C, Rincon F, Maltenfort M, Jallo J, Choudhri O, Steinberg GK, Ratliff JK: Acute lung injury in patients with subarachnoid hemorrhage: a nationwide inpatient sample study. World Neurosurg 82:e235-e241, 2014.
Citation: World Neurosurg. (2015) 83, 3:303-304. http://dx.doi.org/10.1016/j.wneu.2014.06.031 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2014.06.031
Medical Complications After Aneurysmal Subarachnoid Hemorrhage: An Emerging Contributor to Poor Outcome Nima Etminan1 and R. Loch Macdonald2
D
uring the past 3 decades, mortality after aneurysmal subarachnoid hemorrhage (SAH) has been effectively reduced by approximately 50% (6), mainly as the consequence of early repair of ruptured aneurysms and significant advances in aneurysm repair modalities but also improved neurocritical care. Nevertheless, the incidence of poor neurologic outcome has basically remained unchanged and ranges between 25% and 50% (1). The underlying pathophysiologic mechanisms that contribute to poor neurologic outcome, i.e., the extent of early brain injury and the incidence of delayed cerebral ischemia (DCI), and, moreover, their effective pharmaceutical treatment, are the focus of intensive research. Nevertheless, with increasing overall survival rates after aneurysmal SAH, medical or noncerebral complications increasingly are recognized as an additional determinant for neurologic outcome in the course of SAH. Indeed, there is evidence that primary critical medical illnesses, including sepsis and respiratory failure requiring intensive care support, are associated with cognitive impairment (12). In one study of 821 patients with respiratory failure or shock who were in the intensive care unit, 40% had cognitive scores similar to the scores of patients who suffer moderate traumatic brain injury (12). Why and how systemic illness causes cognitive dysfunction is not clear and is the subject of experimental study (9), but it points out that the high rate of cognitive dysfunction in patients with SAH may be contributed to by delirium and systemic illness. The prevention of medical complications may be even more important than previously thought.
Key words Acute lung injury - Acute respiratory distress syndrome - Nationwide Inpatient Sample Database - Subarachnoid hemorrhage -
Abbreviations and Acronyms ALI: Acute lung syndrome ARDS: Acute respiratory distress syndrome DCI: Delayed cerebral ischemia PE: Pulmonary edema SAH: Subarachnoid hemorrhage
Naturally, the incidence of such complications increases with increasing patient age and is reported to be twice as high in patients older than 70 years of age compared with patients younger than 40 (5). Studies also clearly illustrate that medical complications are the only complication of SAH that are increasing in terms of contribution to outcome after SAH (4). Furthermore, although there are few good randomized studies of medical treatment, there is a suggestion that earlier and more active treatment of cardiopulmonary complications in poor-grade SAH patients is associated with better functional outcome (4, 10). In view of these data as discussed by Lovelock et al., it is evident that the aforementioned reduction of case fatality after SAH also is related to the increasing collaborative efforts of neurosurgeons and neurointensivists to treat this complex disease and especially its complications. The most common medical complications are of cardiocirculatory, i.e., acute heart or renal failure of pulmonary nature, i.e., acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) (2, 4). It is likely that the incidence of cardiocirculatory and pulmonary complications is somewhat related to the incidence of risk factors for SAH, which suggests that if a patient has been smoking and suffering from untreated hypertension for decades, one should expect that these patients are more prone to systemic complications. Nevertheless, especially for good-grade SAH patients, it can be difficult to anticipate early after SAH ictus which patient requires more vigilant care or aggressive hemodynamic monitoring. Electrocardiographic alterations and cardiac enzyme (troponin T) elevations are quite frequent after SAH but, depending on their
From the 1Department of Neurosurgery, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; and 2Division of Neurosurgery, St. Michael’s Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, and the Department of Surgery, University of Toronto, Toronto, Ontario, Canada To whom correspondence should be addressed: Nima Etminan, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015) 83, 3:303-304. http://dx.doi.org/10.1016/j.wneu.2014.06.031
WORLD NEUROSURGERY 83 [3]: 303-304, MARCH 2015
www.WORLDNEUROSURGERY.org
303
PERSPECTIVES
severity, also are significant surrogates for clinical outcome (8, 11). The exact pathomechanisms behind acute myocardial injury or neurogenic myocardial are incompletely understood but clinically this may manifest as left ventricular failure, with subsequent impaired cardiac output, hypotension, and pulmonary edema (PE). The evident relation between impaired cardiac output, decreased cerebral perfusion pressure, or brain tissue oxygenation underlines the necessity of intensive noninvasive and invasive hemodynamic monitoring in such patients, to avoid an additive effect of such complications on DCI and neurologic outcome after SAH. The heterogeneous previous definitions for ALI (usually defined as partial pressure of oxygen in the blood [i.e., PaO2] to fraction of inspired oxygen [FiO2] ratio <300), which is now usually summarized in the revised definition of ARDS (mild, moderate, severe), make it difficult to accurately estimate their incidence in patients with SAH but they are reported to constitute 27% (for ALI) and up to 23% (for ARDS) (3, 13). In the setting of SAH, ARDS is commonly associated with pulmonary edema and/or pneumonia due to prolonged ventilation or aspiration. PE frequently is caused by fluid overload in patients with SAH for prevention or reduction of DCI, which warrants the use of hemodynamic monitoring (e.g., based on pulmonary artery catheters or thermodilution-guided measurement of cardiac output), in such patients to maintain euvolemia. Neurogenic PE after SAH or traumatic brain injury also is incompletely understood pulmonary complication and a rather seldom cause for ARDS, estimated to occur in 2%e8% of patients with SAH. In the current study by Veeravagu et al. (14), the authors investigated the prevalence, risk factors, and outcome for patients with ARDS and ALI after SAH using the Nationwide Inpatient Sample Database. The prevalence of ARDS among
REFERENCES 1. Al-Khindi T, Macdonald RL, Schweizer TA: Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke 41:e519-e536, 2010. 2. Beseoglu K, Holtkamp K, Steiger HJ, Hanggi D: Fatal aneurysmal subarachnoid haemorrhage: causes of 30-day in-hospital case fatalities in a large single-centre historical patient cohort. Clin Neurol Neurosurg 115:77-81, 2013. 3. Bruder N, Rabinstein A: Cardiovascular and pulmonary complications of aneurysmal subarachnoid hemorrhage. Neurocrit Care 15:257-269, 2011. 4. Komotar RJ, Schmidt JM, Starke RM, Claassen J, Wartenberg KE, Lee K, Badjatia N, Connolly ES Jr, Mayer SA: Resuscitation and critical care of poorgrade subarachnoid hemorrhage. Neurosurgery 64:397-410, 2009. 5. Lanzino G, Kassell NF, Germanson TP, Kongable GL, Truskowski LL, Torner JC, Jane JA: Age and outcome after aneurysmal subarachnoid hemorrhage: why do older patients fare worse? J Neurosurg 85:410-418, 1996. 6. Lovelock CE, Rinkel GJ, Rothwell PM: Time trends in outcome of subarachnoid hemorrhage: population-based study and systematic review. Neurology 74:1494-1501, 2010.
304
www.SCIENCEDIRECT.com
patients with SAH was as high as 38% in 2008. The most important risk factors for ARDS in patients with SAH were ethnic background, cardiac arrest and cardiovascular dysfunction, reduced neurologic status and, interestingly, larger hospital size. Although the latter finding is likely related to selection bias, this study suggests that socioeconomic background and comorbid diseases as well SAH grade are significant cofactors in the development of ARDS and poor neurologic outcome, which suggests the need for closer monitoring in such patient cohorts. Importantly, the basically unchanged high incidence of pulmonary complications during the course of SAH highlights the need for dedicated neurocritical management via the use of standardized hemodynamic monitoring or even more novel techniques to compensate ALI or ARDS, e.g., interventional lung assist devices. Ultimately, poor outcome after SAH is multifactorial, and its effective reduction is not only likely to be improved by reducing the usual complications, such as early brain injury, rebleeding, complications from aneurysm repair and DCI but, as highlighted in the present study, also to medical and especially pulmonary complications, which deserve our distinct attention to achieve better outcomes. This is also underlined by the findings of the CONSCIOUS-1 (i.e., Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid hemorrhage) study, in which the pulmonary side effects of the experimental drug may have diluted its beneficial effect on DCI and that did not result in improved outcome for patients (7). Moving forward, future clinical studies should identify and prospectively validate early markers as well as the beneficial effect of more aggressive monitoring and treatment in patient cohorts, which are at increased risk for developing medical complications after SAH.
7. Macdonald RL, Kassell NF, Mayer S, Ruefenacht D, Schmiedek P, Weidauer S, Frey A, Roux S, Pasqualin A: Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dosefinding trial. Stroke 39:3015-3021, 2008. 8. Manavalan P, Richardson D, Rayford R, Talley JD: ECG and cardiac enzymes changes associated with subarachnoid hemorrhage. J Arkansas Med Soc 93:592-593, 1997. 9. Mina F, Comim CM, Dominguini D, Cassol-Jr OJ, Dall Igna DM, Ferreira GK, Silva MC, Galant LS, Streck EL, Quevedo J, Dal-Pizzol F: IL1-beta involvement in cognitive impairment after sepsis. Mol Neurobiol 49:1069-1076, 2014. 10. Mocco J, Ransom ER, Komotar RJ, Schmidt JM, Sciacca RR, Mayer SA, Connolly ES Jr: Preoperative prediction of long-term outcome in poorgrade aneurysmal subarachnoid hemorrhage. Neurosurgery 59:529-538, 2006. 11. Naidech AM, Kreiter KT, Janjua N, Ostapkovich ND, Parra A, Commichau C, Fitzsimmons BF, Connolly ES, Mayer SA: Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation 112:2851-2856, 2005.
12. Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW: Long-term cognitive impairment after critical illness. N Engl J Med 369:1306-1316, 2013. 13. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS: Acute respiratory distress syndrome: the Berlin Definition. JAMA 307: 2526-2533, 2012. 14. Veeravagu A, Chen YR, Ludwig C, Rincon F, Maltenfort M, Jallo J, Choudhri O, Steinberg GK, Ratliff JK: Acute lung injury in patients with subarachnoid hemorrhage: a nationwide inpatient sample study. World Neurosurg 82:e235-e241, 2014.
Citation: World Neurosurg. (2015) 83, 3:303-304. http://dx.doi.org/10.1016/j.wneu.2014.06.031 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2014.06.031