Cerebral Hemodynamic Changes After Wartime Traumatic Brain Injury Alexander Razumovsky, Teodoro Tigno, Sven M. Hochheimer, Fred L. Stephens, Randy Bell, Alexander H. Vo, Meryl A. Severson, Scott A. Marshall, Stephen M. Oppenheimer, Robert Ecker, and Rocco A. Armonda
Abstract Traumatic brain injury (TBI) is associated with the severest casualties from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). From October 1, 2008, the U.S. Army Medical Department initiated a transcranial Doppler (TCD) ultrasound service for TBI; included patients were retrospectively evaluated for TCD-determined incidence of post-traumatic cerebral vasospasm and intracranial hypertension after wartime TBI. Ninety patients were investigated with daily TCD studies and a comprehensive TCD protocol, and published diagnostic criteria for vasospasm and increased intracranial pressure (ICP) were applied. TCD signs of mild, moderate, and severe vasospasms were observed in 37%, 22%, and 12% of patients, respectively. TCD signs of intracranial hypertension were recorded in 62.2%; 5 patients (4.5%) underwent transluminal angioplasty for post-traumatic clinical vasospasm treatment, and 16 (14.4%) had cranioplasty. These findings demonstrate that cerebral arterial spasm and intracranial hypertension are frequent and significant complications of combat TBI; therefore, daily TCD monitoring is recommended for their recognition and subsequent management.
A. Razumovsky, Ph.D., FAHA (), S.M. Oppenheimer, M.D., Ph.D. Sentient NeuroCare Services, Inc, 11011 McCormick Rd, Suite 200, Hunt Valley, MD, USA e-mail:
[email protected] T. Tigno, M.D., S.M. Hochheimer, M.D., F.L. Stephens, M.D., R. Bell, M.D., M.A. Severson, and R.A. Armonda Department of Neurosurgery, Walter Reed National Military Medical Center, Bethesda, MD, USA
Keywords Combat-associated wartime traumatic brain injury • Wartime traumatic brain injury • Transcranial Doppler ultrasonography • Cerebral blood flow velocity • Vasospasm • Intracranial pressure
Introduction Cerebral vasospasm is a frequent complication after aneurysmal and traumatic subarachnoid hemorrhage (SAH) and carries significant morbidity and mortality [9, 11, 13, 19]. Armonda and co-authors indicated that vasospasm occurred in a substantial number of patients with wartime traumatic brain injury (TBI), and clinical outcomes were worse in such patients [2]. Cerebral angiography remains the standard diagnostic test in this setting; however, this procedure is invasive, expensive, not always available, and not without risk [8]. In contrast, transcranial Doppler (TCD) ultrasonography has been increasingly used over the past few years for diagnosis and monitoring cerebral vasospasm and implementing therapeutic interventions [21]. TBI and cerebrovascular injury are associated with the severest casualties from Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) [3]. From October 1, 2008, the U.S. Army Medical Department TBI program initiated a TCD protocol for examination of head-injured patients who were evacuated from the combat theater to receive care at the National Naval Medical Center, the San Antonio Military Medical Center, and the Walter Reed Army Medical Center. The purpose of this retrospective analysis was to evaluate the TCD determined incidence of post-traumatic cerebral vasospasm and intracranial hypertension after wartime TBI in these patients.
A.H. Vo, Ph.D. The University of Texas Medical Branch, Galveston, TX, USA S.A. Marshall, M.D. Uniformed Services University of the Health Sciences, Department of Neurology, Bethesda, MD, USA R. Ecker, M.D. Department of Neuroradiology, Maine Medical Center, Portland, ME, USA
Materials and Methods TCD data were retrospectively analyzed in 90 patients (two females) aged 18–50 years (mean 25.9 years) who had suffered wartime TBI (with Glasgow Coma Scale scores ranging from
M. Zuccarello et al. (eds.), Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage, Acta Neurochirurgica Supplementum, Vol. 115, DOI 10.1007/978-3-7091-1192-5_19, © Springer-Verlag Wien 2013
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3 to 15). The patients were categorized according to injury: 18 patients with closed head injury (CHI), 19 patients with CHI due to improvised explosive device (CHI/IED), 33 patients with penetrating head injury (PHI), and 20 patients with PHI due to IED (PHI/IED). A total of 567 TCD studies were made after admission. Patients were identified using a computerized registry and a prospective TCD database maintained in the Sentient NeuroCare Services. TCD recordings of mean cerebral blood flow velocities (CBFV, in cm/s) and Pulsatility Indices (PI) of the anterior and posterior circulation vessels were recorded using a 2-MHz transducer (Doppler Box, DWL/ Compumedics, USA). A comprehensive TCD protocol was applied in all cases [1]: If mean CBFV equaled or exceeded 100, 140, and 200 cm/s, the TCD signs of mild vasospasm, moderate vasospasm, and severe vasospasm, respectively, were considered present [20]. Lindegaard ratio was measured when the CBFV exceeded 100 cm/s [15]. On average, patients received 6.4 TCD examinations (range 1–30). The primary purpose of TCD methodology is to determine the CBFV by quantitative interpretation of Doppler spectrum waveforms. Although the qualitative contour of the TCD waveform during intracranial pressure (ICP) elevation falls into a recognizable pattern, their interpretation depends on the experience and expertise of the TCD examiner/interpreter. Objective, reproducible, and verifiable measures of TCD waveform changes are necessary for TCD findings to be used with certainty for evaluation of intracranial hypertension. One method of quantifying these changes is the utilization of the PI [4], which is a reflection of downstream resistance. The PI takes into account the peak systolic CBFV (pCBFV) and the end-diastolic CBFV (edCBFV) and compares changes in these variables against the change in the standard measure of the entire waveform, such as mean CBFV. Changes in arterial pulsatility, especially occurring during intracranial hypertension, will affect both pCBFV and edCBFV, which are easily identified in the TCD waveform and are reflected by the equation PI = pCBFV − edCBFV/ mean CBFV. The SAS statistical package was used for data analysis (SAS/STAT® 9.3 Software, SAS Institute, Inc., USA). All data were tested for normal distribution using the Shapiro Wilk test: Nonparametric statistics were used if determined appropriate. All data were described using median and interquartile range (25th and 75th percentiles). Spearman rank correlations of MAP (mean arterial pressure), Hct (hematocrit), ICP, and PaCO2 (arterial partial pressure of carbon dioxide) with measures of the CBFV were calculated. Anterior and posterior CBFV data were compared between groups defined by severity of vasospasm (mild, moderate, and severe) using the Wilcoxon rank sum test for each diagnostic group. General linear models were employed to test between diagnostic group differences, adjusting for severity of vasospasm. Statistical significance was assumed on the 5% level.
A. Razumovsky et al.
Study and analysis of the data were done according to the IRBNet protocol 363439-4.
Results TCD signs of vasospasm were observed in 57 cases (63.3%): 13 (14.4%) in CHI, 12 (13.3%) in CHI/IED, 21 (23.3%) in PHI, and 11 (12.3%) in PHI/IED groups (p = 0.732). Different degree of TCD signs of vasospasm presented in Table 1. In PHI patients, there were 75%, 35.7%, and 14.3% TCD signs of mild, moderate, and severe vasospasm, respectively. In the PHI/IED group, there were 36.8%, 5.2%, and 5.2% TCD signs of mild, moderate, and severe vasospasm, respectively. In the CHI group, there were 68.4%, 31.5%, and 15.7% TCD signs of mild, moderate, and severe vasospasm, respectively. Last, in the CHI/IED group, there were 29%, 23.5%, and 17.6% TCD signs of mild, moderate, and severe vasospasm, respectively. TCD evidence of intracranial hypertension was seen in 57.1% of PHI patients, in 63% of PHI/IED patients, in 63.1% of CHI patients, and in 50% of CHI/IED patients. While there were no overall differences in presence of vasospasm, there were statistically significant differences between frequency of degrees of TCD signs of vasospasm between different TBI groups (p < 0.001). Post hoc analysis revealed that PHI and CHI groups had higher frequency of mild vasospasm compared to both CHI/IED and PHI/IED (p < 0.05).The PHI/IED group had a higher frequency of moderate vasospasm compared to the CHI, PHI, and CHI/IED groups (p < 0.05).
Discussion These results suggest that abnormal TCD findings are frequent in patients with wartime TBI and indicate post-traumatic vasospasm and intracranial hypertension in a significant number of patients. In addition, delayed cerebral arterial spasm is a frequent complication of combat TBI, and severity of cerebral vasospasm is comparable to that seen in aneurysmal SAH. This confirms earlier data that traumatic SAH is associated with a high incidence of cerebral vasospasm with a higher probability in patients with severe TBI [2, 9, 19]. Another cause of abnormally high CBFVs could be reactive hyperemia after TBI; however, the literature suggests that global post-trauma malignant hyperemia is present primarily in the acute stage of TBI [18], although more recent data showed that post-TBI focal hyperemia can be present up to 3 weeks [7]. In our study, utilization of the Lindegaard ratio and qualitative evaluation of the Doppler spectrum were helpful in differentiating between hyperemia and vasospasm.
Cerebral Hemodynamic Changes After Wartime Traumatic Brain Injury
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Table 1 Different degree of transcranial Doppler (TCD) signs of vasospasm in wartime patients with traumatic brain injury (TBI) TBI groups TCD signs of vasospasm PHI PHI/IED CHI CHI/IED Mild vasospasm Anterior
114 (106,124)
112 (105,121)
114 (106,124)
116 (107,129)
Posterior
66 (63,71)
(63.5,71)
68 (63,74.5)
67 (62,72)
Anterior
159 (149,172)
162 (148,181)
154 (146,173)
150 (146,164)
Posterior
86 (83.5,90)
85.5 (83,89)
89 (85,97)
87 (85,92)
Anterior
220.5 (210,234)
216 (206,248)
214 (210,225)
214 (209,237)
Posterior
114 (108,124)
124 (104.5,161)
115 (107,132.5)
113 (106.5,124)
Moderate vasospasm
Severe vasospasm
Numbers represent median cerebral blood flow velocity (CBFV) in centimeters/second (interquartile range, 25th and 75th percentile) CHI closed head injury, IED improvised explosive device, PHI penetrating head injury
Of interest is the finding that the PHI/IED TBI group had a higher frequency of TCD signs of moderate vasospasm when compared to other TBI groups. This result emphasizes the point that explosive blast TBI is one of the more serious wounds suffered by U.S. service members injured in the current conflicts in Iraq and Afghanistan. Observations suggest that the mechanism by which explosive blast injures the central nervous system may be more complex than initially assumed [16]. The purpose of monitoring patients with TBI is to detect treatable and reversible causes of neurological deterioration. There are numerous causes of such deterioration after TBI, and frequent neurological examinations, the availability of urgent neuroimaging, and electroencephalograms (EEGs) are standards in the management of patients with traumatic SAH. Physiological monitoring modalities include TCD, electroencephalography, brain tissue oxygen monitoring, cerebral microdialysis, and near-infrared spectroscopy. TCD has long been used for monitoring patients with SAH, but studies of diagnostic accuracy for detection of vasospasm and cerebral angiography vary widely with regard to sensitivity and specificity of TCD. Ability of TCD to predict clinical deterioration and infarction from delayed cerebral ischemia is not yet validated in a prospective trial. In spite of this, TCD examination is noninvasive and inexpensive, and the pattern of CBFVs observed in patients after SAH of different etiology is very distinctive, enabling immediate detection of abnormally high CBFVs and it appears to be predictive of vasospasm [10, 14]. Recent evidence suggests TCD holds promise for the detection of critical elevations of ICP and decreases in cerebral perfusion pressure (CPP). Using the PI, Bellner et al. [4] demonstrated that an ICP of 20 mmHg can be determined with a sensitivity of 0.89 and specificity of 0.92. They concluded that the PI may provide guidance in those patients with suspected intracranial hypertension, and that repeated measurements may be of use in the neurocritical care unit.
There is significant evidence that independent of the type of intracranial pathology, a strong correlation between PI and ICP exists [4, 5, 12, 17]. A recent study indicated that TCD had 94% of sensitivity for identifying high ICP/low CPP at admission and a negative predictive value of 95% to identify normal ICP at admission; the sensitivity for predicting abnormal CPP was 80% [17]. In 2011, Bouzat and co-authors showed that in patients with mild-to-moderate TBI, the TCD test on admission, together with brain CT scan, could accurately screen patients at risk for secondary neurological damage [6]. At the same time, to the best of our knowledge, no one as yet has suggested using the PI as an accurate method to assess ICP quantitatively. Nevertheless, even at this juncture, quantitative and qualitative changes in CBFV values and TCD waveform morphologies may persuade physicians to undertake other diagnostic steps or change medical treatment that will improve care of these patients and their outcomes. At the moment, TCD appears to be useful for following PIs trends, and it is a practical ancillary technique for estimating the direction of CBFV changes in response to increasing ICP or falling CPP. It may also reveal whether there is a response to therapeutic interventions, although further sophistication of TCD data analysis is essential before it may be used with confidence to measure ICP and CPP in the intensive care unit (ICU). This study had some limitations. First, we were not able to correlate clinical vasospasm with angiographic vasospasm and combine TCD data with other neuroimaging methods that help to identify vasospasm and impaired cerebral perfusion in patients with traumatic SAH. Second, current data should be validated prospectively. In addition, the lack of established TCD criteria for vasospasm in younger patients presents interpretative issues. The high sensitivity of TCD to identify abnormally high CBFVs and PIs due to the onset of vasospasm and intracranial hypertension, respectively, demonstrates that TCD is an excellent first-line examination to determine those patients
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who may need urgent aggressive treatment and continuous invasive ICP monitoring. Because vasospasm and intracranial hypertension represent significant events in a high proportion of patients after wartime TBI, daily TCD monitoring is recommended for the management of such patients. Acknowledgements This chapter was supported in part by the U.S. Army Medical Research and Material Command’s Telemedicine and Advanced Technology Research Center (Fort Detrick, MD, USA). In addition, we would like to express our gratitude to Richard L. Skolasky, Jr., assistant professor, director of the Spine Outcomes Research Center at Johns Hopkins University (Baltimore, MD, USA), for his statistical assistance and guidance. Also, we need to thank neurosonographers A. Dzhanashvili and Mirkko Galdo, who were responsible for data collection. Conflicts of Interest We declare that we have no conflict of interest.
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