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The Clinical Implications of Subarachnoid Hemorrhage Volume
Perspectives Commentary on: How Large Is the Typical Subarachnoid Hemorrhage? A Review of Current Neurosurgical Knowledge by Whitmore et al. pp. 686-697.
E. Sander Connolly, Jr., M.D. Bennett M. Stein Professor of Neurological Surgery, Columbia University Department of Neurological Surgery, Neurological Institute
The Clinical Implications of Subarachnoid Hemorrhage Volume Brad E. Zacharia1, Santiago Ortega-Gutierrez 2, E. Sander Connolly Jr.1
T
he pathophysiology of aneurysmal subarachnoid hemorrhage is intimately related to the consequences of blood in the subarachnoid space. It stands to reason that the amount, that is, the volume, of subarachnoid blood would be critically important in understanding this disease process. Since the introduction of the Fisher scale in 1980, we have recognized that the presence of thick cisternal or sylvian clot on admission computed tomography (CT) is associated with the development of vasospasm, and modifications of this scale over the years have identified the presence of bilateral intraventricular hemorrhage as an independent risk factor for delayed cerebral ischemia (3, 4). Broderick et al. (2) demonstrated that volume of subarachnoid hemorrhage powerfully predicted 30-day mortality, and less than 10% of patients with 15 mL or less died within 30 days. Rosen et al. (6) went on to demonstrate a correlation between the volume of subarachnoid clot and severity of admission clinical status on the basis of the World Federation of Neurological Societies grade. Although the clinical implications of subarachnoid hemorrhage volume seem obvious, few investigators have accurately quantified the total hemorrhage volume, in fact, there is little consensus on what constitutes the total hemorrhage volume. In most of the earlier studies researchers focused solely on the burden of subarachnoid blood and did not take into account ventricular hemorrhage or erythrocytes circulating in the cerebrospinal fluid (CSF), relying instead solely on early CT imaging. The included report, “How large is the typical subarachnoid hemorrhage? A review of current neurosurgical knowledge,” from Whitmore et al. addresses the aforementioned deficit in the literature. The authors used an extensive literature search of almost 5000 articles to derive a mean quantitative total subarachnoid hemorrhage blood volume. The majority of studies reviewed derived subarachnoid clot volume from CT imaging, and only four publications reported quantitative estimates, with volumes ranging
Key words 䡲 Animal models 䡲 Blood volume 䡲 Cerebrospinal fluid 䡲 Quantifying hemorrhage 䡲 Subarachnoid hemorrhage
Abbreviations and Acronyms CIHV: Cisternal blood plus intraventricular hemorrhage volume CSF: Cerebrospinal fluid CT: Computed tomography
WORLD NEUROSURGERY 77 [5/6]: 613-614, MAY/JUNE 2012
from 0.2 to 170 mL. The mid-range estimate when combining these four studies was approximately 20 mL. Only a single study provided substantial quantitation of CSF red blood cell counts, and using a previously defined calculation, the authors estimated that approximately 15 mL of blood was dispersed in the CSF after aneurysmal subarachnoid hemorrhage. By combining these values, Whitmore et al. estimate the mean subarachnoid hemorrhage volume to be approximately 35 mL. Given the paucity of literature on this specific subtopic, the authors are to be commended for providing a thorough summation. Nevertheless, the retrospective nature and the inconsistent methodology between studies clearly limit the strength of the data and any true conclusions. The authors went on to poll members of the American Association of Neurosurgeons, asking them to estimate the volume of subarachnoid hemorrhage. Although the mean estimated volume of subarachnoid hemorrhage given by responders (33.9 mL) was in line with the authors’ estimated value (35 mL), less than 5% of neurosurgeons polled responded. Furthermore, it is unclear how such a poll contributes to the strength or validity of the authors’ estimate. The authors also reviewed all animal studies involving direct injection of blood into the subarachnoid space and demonstrated considerable variation in blood volume injected both within and between species. It has been difficult to develop a subarachnoid hemorrhage model that accurately reflects the human condition, and because cisternal injection models are most common, the data provided in this study could certainly serve as a guide to further standardize these experiments and bring them more in line with what is occurring in humans. Although the information gleaned from this study may help guide the development of more accurate animal models, it does not address the clinical implications of subarachnoid hemorrhage volume. Volumetric analysis of blood in subarachnoid hemor-
From the Departments of 1Neurological Surgery and 2Neurology, Columbia University, New York, New York, USA To whom correspondence should be addressed: E. Sander Connolly Jr., M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2012) 77, 5/6:613-614. DOI: 10.1016/j.wneu.2011.04.005
www.WORLDNEUROSURGERY.org
613
PERSPECTIVES
rhage has been reported by a number of groups, and with continued improvement in cranial imaging, more accurate estimates of blood volume will occur. Our group recently undertook an effort to quantitate hemorrhage in a large group of subarachnoid hemorrhage patients and correlate these values with outcome. As discussed previously, many early studies were limited by small sample sizes, varied timing of obtaining CT scans, exclusion of high-grade patients, and exclusion of intraventricular hemorrhage volume. By using a well-described single center, prospective, observational cohort study of adult patients with spontaneous subarachnoid hemorrhage, we analyzed 160 consecutive patients. CT scans were analyzed by the use of MIPAV software package (Medical Image Processing, Analysis, and Visualization, version 4.3; National Institutes of Health, Bethesda, Maryland, USA) (1). Regions of hemorrhage on CT scan were outlined slice-by-slice with the use of a semiautomatic threshold approach by a blinded rater. After measuring blood volume in each cistern, ventricle, parenchyma, and sulci near the cortex, we merged any blood in the cisterns or ventricles as a volume variable called cisternal blood plus intraventricular hemorrhage volume (CIHV) (5). The median CIHV of 16.5 mL, if added to the approximate volume of
REFERENCES 1. Bazin PL, Cuzzocreo JL, Yassa MA, Gandler W, McAuliffe MJ, Bassett SS, Pham DL: Volumetric neuroimage analysis extensions for the MIPAV software package. J Neurosci Methods 165:111-121, 2007. 2. Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A: Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke 25:1342-1347, 1994. 3. Claassen J, Bernardini GL, Kreiter K, Bates J, Du YE, Copeland D, Connolly ES, Mayer SA: Effect of cister-
614
www.SCIENCEDIRECT.com
circulating red blood cells in the CSF (15 mL), yields a similar total volume of subarachnoid hemorrhage as purported by Whitmore et al. Moreover, when dichotomized on the basis of the median CIHV of 16.5 mL, the group in the larger hemorrhage volume had a greater risk of delayed cerebral ischemia (odds ratio, 2.9; P ⫽ 0.03) (5). The greater blood burden group also developed delayed cerebral ischemia approximately 1.5 days earlier than the lower blood burden group when baseline clinical factors were controlled. Finally, patients in the greatest quartile of CIHV had an increased risk of death or severe disability when compared with the first quartile after we controlled for age, sex, hypertension, diabetes mellitus, smoking, and alcohol use. Further statistical analysis showed that CIHV was superior compared with the modified Fisher Scale in predicting death or severe disability at 3 months (P ⫽ 0.02). The measurement of quantitative blood burden may be more than a good research tool because it could serve as a strong predictor of delayed ischemia and outcome. As intracranial imaging and software to analyze it continues to improve, the task of measuring blood volume will become more accurate and rapid thus incorporating measurement of total subarachnoid hemorrhage volume into the initial analysis of these patients.
nal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited. Stroke 32:2012-2020, 2001. 4. Fisher CM, Kistler JP, Davis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6:1-9, 1980. 5. Ko SB, Choi HA, Carpenter AM, Helbok R, Schmidt JM, Badjatia N, Claassen J, Connolly ES, Mayer SA, Lee K: Quantitative analysis of hemorrhage volume for predicting delayed cerebral ischemia after subarachnoid hemorrhage. Stroke 42:669-674, 2011.
6. Rosen DS, Amidei C, Tolentino J, Reilly C, Macdonald RL: 2007. Subarachnoid clot volume correlates with age, neurological grade, and blood pressure. Neurosurgery 60:259-266; discussion 266-267, 2007. Citation: World Neurosurg. (2012) 77, 5/6:613-614. DOI: 10.1016/j.wneu.2011.04.005 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2012 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2011.04.005
E. Sander Connolly, Jr., M.D. Bennett M. Stein Professor of Neurological Surgery, Columbia University Department of Neurological Surgery, Neurological Institute
The Clinical Implications of Subarachnoid Hemorrhage Volume Brad E. Zacharia1, Santiago Ortega-Gutierrez 2, E. Sander Connolly Jr.1
T
he pathophysiology of aneurysmal subarachnoid hemorrhage is intimately related to the consequences of blood in the subarachnoid space. It stands to reason that the amount, that is, the volume, of subarachnoid blood would be critically important in understanding this disease process. Since the introduction of the Fisher scale in 1980, we have recognized that the presence of thick cisternal or sylvian clot on admission computed tomography (CT) is associated with the development of vasospasm, and modifications of this scale over the years have identified the presence of bilateral intraventricular hemorrhage as an independent risk factor for delayed cerebral ischemia (3, 4). Broderick et al. (2) demonstrated that volume of subarachnoid hemorrhage powerfully predicted 30-day mortality, and less than 10% of patients with 15 mL or less died within 30 days. Rosen et al. (6) went on to demonstrate a correlation between the volume of subarachnoid clot and severity of admission clinical status on the basis of the World Federation of Neurological Societies grade. Although the clinical implications of subarachnoid hemorrhage volume seem obvious, few investigators have accurately quantified the total hemorrhage volume, in fact, there is little consensus on what constitutes the total hemorrhage volume. In most of the earlier studies researchers focused solely on the burden of subarachnoid blood and did not take into account ventricular hemorrhage or erythrocytes circulating in the cerebrospinal fluid (CSF), relying instead solely on early CT imaging. The included report, “How large is the typical subarachnoid hemorrhage? A review of current neurosurgical knowledge,” from Whitmore et al. addresses the aforementioned deficit in the literature. The authors used an extensive literature search of almost 5000 articles to derive a mean quantitative total subarachnoid hemorrhage blood volume. The majority of studies reviewed derived subarachnoid clot volume from CT imaging, and only four publications reported quantitative estimates, with volumes ranging
Key words 䡲 Animal models 䡲 Blood volume 䡲 Cerebrospinal fluid 䡲 Quantifying hemorrhage 䡲 Subarachnoid hemorrhage
Abbreviations and Acronyms CIHV: Cisternal blood plus intraventricular hemorrhage volume CSF: Cerebrospinal fluid CT: Computed tomography
WORLD NEUROSURGERY 77 [5/6]: 613-614, MAY/JUNE 2012
from 0.2 to 170 mL. The mid-range estimate when combining these four studies was approximately 20 mL. Only a single study provided substantial quantitation of CSF red blood cell counts, and using a previously defined calculation, the authors estimated that approximately 15 mL of blood was dispersed in the CSF after aneurysmal subarachnoid hemorrhage. By combining these values, Whitmore et al. estimate the mean subarachnoid hemorrhage volume to be approximately 35 mL. Given the paucity of literature on this specific subtopic, the authors are to be commended for providing a thorough summation. Nevertheless, the retrospective nature and the inconsistent methodology between studies clearly limit the strength of the data and any true conclusions. The authors went on to poll members of the American Association of Neurosurgeons, asking them to estimate the volume of subarachnoid hemorrhage. Although the mean estimated volume of subarachnoid hemorrhage given by responders (33.9 mL) was in line with the authors’ estimated value (35 mL), less than 5% of neurosurgeons polled responded. Furthermore, it is unclear how such a poll contributes to the strength or validity of the authors’ estimate. The authors also reviewed all animal studies involving direct injection of blood into the subarachnoid space and demonstrated considerable variation in blood volume injected both within and between species. It has been difficult to develop a subarachnoid hemorrhage model that accurately reflects the human condition, and because cisternal injection models are most common, the data provided in this study could certainly serve as a guide to further standardize these experiments and bring them more in line with what is occurring in humans. Although the information gleaned from this study may help guide the development of more accurate animal models, it does not address the clinical implications of subarachnoid hemorrhage volume. Volumetric analysis of blood in subarachnoid hemor-
From the Departments of 1Neurological Surgery and 2Neurology, Columbia University, New York, New York, USA To whom correspondence should be addressed: E. Sander Connolly Jr., M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2012) 77, 5/6:613-614. DOI: 10.1016/j.wneu.2011.04.005
www.WORLDNEUROSURGERY.org
613
PERSPECTIVES
rhage has been reported by a number of groups, and with continued improvement in cranial imaging, more accurate estimates of blood volume will occur. Our group recently undertook an effort to quantitate hemorrhage in a large group of subarachnoid hemorrhage patients and correlate these values with outcome. As discussed previously, many early studies were limited by small sample sizes, varied timing of obtaining CT scans, exclusion of high-grade patients, and exclusion of intraventricular hemorrhage volume. By using a well-described single center, prospective, observational cohort study of adult patients with spontaneous subarachnoid hemorrhage, we analyzed 160 consecutive patients. CT scans were analyzed by the use of MIPAV software package (Medical Image Processing, Analysis, and Visualization, version 4.3; National Institutes of Health, Bethesda, Maryland, USA) (1). Regions of hemorrhage on CT scan were outlined slice-by-slice with the use of a semiautomatic threshold approach by a blinded rater. After measuring blood volume in each cistern, ventricle, parenchyma, and sulci near the cortex, we merged any blood in the cisterns or ventricles as a volume variable called cisternal blood plus intraventricular hemorrhage volume (CIHV) (5). The median CIHV of 16.5 mL, if added to the approximate volume of
REFERENCES 1. Bazin PL, Cuzzocreo JL, Yassa MA, Gandler W, McAuliffe MJ, Bassett SS, Pham DL: Volumetric neuroimage analysis extensions for the MIPAV software package. J Neurosci Methods 165:111-121, 2007. 2. Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A: Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke 25:1342-1347, 1994. 3. Claassen J, Bernardini GL, Kreiter K, Bates J, Du YE, Copeland D, Connolly ES, Mayer SA: Effect of cister-
614
www.SCIENCEDIRECT.com
circulating red blood cells in the CSF (15 mL), yields a similar total volume of subarachnoid hemorrhage as purported by Whitmore et al. Moreover, when dichotomized on the basis of the median CIHV of 16.5 mL, the group in the larger hemorrhage volume had a greater risk of delayed cerebral ischemia (odds ratio, 2.9; P ⫽ 0.03) (5). The greater blood burden group also developed delayed cerebral ischemia approximately 1.5 days earlier than the lower blood burden group when baseline clinical factors were controlled. Finally, patients in the greatest quartile of CIHV had an increased risk of death or severe disability when compared with the first quartile after we controlled for age, sex, hypertension, diabetes mellitus, smoking, and alcohol use. Further statistical analysis showed that CIHV was superior compared with the modified Fisher Scale in predicting death or severe disability at 3 months (P ⫽ 0.02). The measurement of quantitative blood burden may be more than a good research tool because it could serve as a strong predictor of delayed ischemia and outcome. As intracranial imaging and software to analyze it continues to improve, the task of measuring blood volume will become more accurate and rapid thus incorporating measurement of total subarachnoid hemorrhage volume into the initial analysis of these patients.
nal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited. Stroke 32:2012-2020, 2001. 4. Fisher CM, Kistler JP, Davis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6:1-9, 1980. 5. Ko SB, Choi HA, Carpenter AM, Helbok R, Schmidt JM, Badjatia N, Claassen J, Connolly ES, Mayer SA, Lee K: Quantitative analysis of hemorrhage volume for predicting delayed cerebral ischemia after subarachnoid hemorrhage. Stroke 42:669-674, 2011.
6. Rosen DS, Amidei C, Tolentino J, Reilly C, Macdonald RL: 2007. Subarachnoid clot volume correlates with age, neurological grade, and blood pressure. Neurosurgery 60:259-266; discussion 266-267, 2007. Citation: World Neurosurg. (2012) 77, 5/6:613-614. DOI: 10.1016/j.wneu.2011.04.005 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2012 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2011.04.005