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The Role of Monitoring Cerebral Autoregulation After Subarachnoid Hemorrhage Karol P. Budohoski, MD, PhD
S
ubarachnoid hemorrhage (SAH) is a devastating disease with approximately 30% early case fatality. Of the 70% who survive Peter J. Kirkpatrick, FRCS, SN the ictus, despite early resuscitation and obliterDivision of Neurosurgery, Department of ation of the aneurysm in order to prevent the Clinical Neurosciences, Addenbrooke’s deleterious effects of a rebleed, 25% will subHospital, University of Cambridge, sequently deteriorate.1 Delayed deterioration Cambridge, United Kingdom may be due to hydrocephalus, electrolyte disturbances, seizures, as well as delayed cerebral Correspondence: Karol P. Budohoski, MD, PhD, ischemia (DCI). Box 167, Division of Neurosurgery, DCI, traditionally attributed to cerebral vasoAddenbrooke’s Hospital, spasm (ie, narrowing of large cerebral arteries), Hills Rd, CB2 0QQ, was first described in 1951.2 Vasospasm takes Cambridge, UK. E-mail: [email protected] some days to develop and peaks at 5 to 7 days, after which it slowly resolves,3 hence the Copyright © 2015 by the association with delayed deterioration. However, Congress of Neurological Surgeons. it has been documented clinically that the relationship between vasospasm and DCI is inconsistent. Some patients with severe vasospasm never deteriorate and some deteriorate without vasospasm.4 Current research suggests that a number of pathophysiological processes take place after SAH, all of which may contribute to delayed deterioration. In experimental settings, cerebral vasospasm does not reduce distal cerebral blood flow unless there is an additional insult such as a decrease in blood pressure,5 lending support to the Harper dual-control hypothesis.6-8 Clinical evaluation of cerebral autoregulation is being increasingly recognized as a factor requiring consideration in the management of patients with SAH. In this review, we present recent findings on the role of monitoring of cerebral autoregulation after SAH. Marek Czosnyka, PhD
CEREBRAL AUTOREGULATION Cerebral autoregulation describes the intrinsic ability of cerebral vasculature to maintain a stable blood flow despite changes in blood pressure or, more accurately, cerebral perfusion pressure.9 Cerebral blood flow is regulated primarily by changes in arteriolar diameter, which drive the changes in cerebrovascular resistance.10-12 Despite many pathways mediating the described vasomotor reactions,11,13-18 the exact mechanisms remain
180 | VOLUME 62 | NUMBER 1 | AUGUST 2015
elusive. Importantly, cerebral autoregulation is thought to be a mechanism distinct from CO2 reactivity and flow-metabolism coupling.19-22 Calculation of the static rate of autoregulation by assessing cerebral blood flow at 2 different blood pressure levels using direct perfusion methods is considered to be the best available technique for testing autoregulation. It is a quantitative method that is simple to interpret, but there are a number of drawbacks (such as the need for pharmacological interventions to alter the blood pressure levels or the effect of “false autoregulation” if the intracranial pressure follows induced changes in arterial blood pressure23) that limit its usefulness in clinical settings. Currently, numerous methods using surrogate markers of cerebral blood flow are being explored. Frequently, emphasis is placed on the dynamic process of autoregulatory reactions. These methods include transcranial Doppler, laser Doppler flowmetry, partial pressure of brain oxygen, thermal diffusion regional cerebral blood flow, and the tissue oxygenation index (derived from near-infrared spectroscopy). Methods using spontaneous fluctuations of blood pressure rather than external stimuli are gaining momentum because of their relative ease of implementation in clinical settings, particularly in the critical care unit. With these methods, various parameters can be calculated by assessing either the speed or direction of changes in the surrogate markers of blood flow in relation to the speed or direction of blood pressure changes. Although simple in principle, various algorithms are used, leading to significant heterogeneities and difficulties in clinical interpretation.24,25 In this study, we aimed to characterize the most recent data on the role of monitoring autoregulation after SAH, focusing solely on dynamic methods using continuous monitoring signals.
THE ROLE OF AUTOREGULATION MONITORING AFTER SAH Studies in which dynamic autoregulation was tested after SAH are summarized in the Table. Unambiguous interpretation of the results is
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MONITORING CEREBRAL AUTOREGULATION AFTER SAH
TABLE. Studies Investigating Dynamic Cerebral Autoregulation After Subarachnoid Hemorrhagea Study
n
CBF Measurement
Findings
Giller26 (1991)
25
TCD
Absence of a hyperemic response in all poor-grade patients (n = 14) but only in 60% of goodgrade patients.
Steinmeier et al27 (1996) Lam et al28 (2000)
10
TCD, ICP, ABP
20
TCD
Spontaneous fluctuations of blood pressure can be used for assessment of AR with the intracranial pressure signal. Patients with primary impairment of AR (n = 5) and CVS (n = 6) developed DCI. No patients without primary impairment of AR (n = 14) developed DCI.
Ra¨tsep and Asser29 (2001)
55
TCD
Lang et al30 (2001)
12
TCD
Soehle et al31 (2003) Soehle et al32 (2004) Tseng et al33,34 (2005 and 2006) Jaeger et al35,36 (2007 and 2012)
NN 32 80
PbtO2 TCD TCD
67
PbtO2
Christ et al37 (2007) Tseng et al38 (2007) Tseng et al39 (2009)
6 35 80
TCD TCD, ICP TCD
Zweifel et al40 (2010) 27 Bijlenga et al41 (2010) 25
CVS was associated with DCI only if hyperemic response was reduced (n = 14). In all cases, CVS and reduced hyperemic response were associated with delayed infarctions (n = 12) and poor outcome in 68%. Testing divided into early (days 1-6) and late (day 7-13); 88% of patients with intact dynamic AR (n = 8) had good outcome. Disturbed AR was predictive of GOS score of 1 and 2. Late-phase AR did not have predictive value. PbtO2 AR can be used to titrate CPP levels. CVS caused impairments in AR. AR was more affected ipsilateral to the spastic vessel. Shorter duration of AR impairment was associated with lower incidence of DCI in the pravastatin group (n = 40). Impaired AR on day 5-6 after SAH was an independent predictor of delayed infarction (n = 20). Impaired AR was an independent predictor of outcome at 6 mo (n = 56).
Dynamic autoregulation was impaired (n = 6) compared with healthy control subjects (n = 9). Impaired autoregulation ipsilaterally to the aneurysm. HTS improved blood flow but not AR (n = 35). Shorter-duration AR impairments, decreased incidence of severe CVS resulted in a reduced incidence of new infarctions in the EPO group: 40% vs 7.5% (n = 40). TCD, NIRS Dynamic AR assessed with NIRS correlates with TCD-based AR. ICP Intact AR had a 87.5% positive predictive value for survival (n = 16). Impaired AR in the first 48 h correlated with mRS score (n = 16). ICP, PbtO2, TD-rCBF No differences in dynamic AR between infarction (n = 8) and no-infarction groups (n = 13). ICP Duration of impaired AR was longer in patients with poor outcome (n = 14). Longer time spent below optimal CPP was associated with poor outcome (n = 14). PbtO2, TD-rCBF Improved correlation of dynamic indexes of AR after temporal synchronization. ICP ICP-ABP wave amplitude correlation was related to both the baseline status and outcome at 12 mo. TCD, NIRS Failure of AR in the first 5 d after SAH was an independent predictor of DCI. Benefit of multimodal assessment of autoregulation.
Barth et al42 (2010) Rasulo et al43 (2011)
21 29
Hecht et al23 (2011) Eide et al44 (2012) Budohoski et al45,46 (2012)
5 94 98
Budohoski et al47 (2015)
90
TCD
Otite et al48 (2014)
68
TCD
Unilateral failure of AR was related to DCI. Bilateral failure of AR was related to poor outcome (16/18 patients vs 17/72 patients with unfavorable vs favorable outcome, respectively, demonstrated bilateral failure of AR). Impaired AR predictive of CVS and DCI. Two clinical scoring models developed: SAGA score for predicting CVS (.90% specificity; unit increase in score 3-fold increase in risk of CVS) and WHAP for predicting DCI (.90% specificity; unit increase in score 3-fold increase in risk of DCI).
a
ABP, arterial blood pressure; AR, autoregulation; CBF, cerebral blood flow; CPP, cerebral perfusion pressure; CVS, cerebral vasospasm; DCI, delayed cerebral ischemia; EPO, erythropoietin; GOS, Glasgow Outcome Scale; HTS, hypertonic saline; ICP, intracranial pressure; mRS, modified Rankin Scale; NIRS, near-infrared spectroscopy; SAGA, smoking, age, gain, aneurysmal SAH; SAH, subarachnoid hemorrhage; TCD, transcranial Doppler; TD-rCBF, thermal diffusion regional cerebral blood flow; WHAP, World Federation of Neurosurgical Societies, hyperglycemia, arterial pressure, phase.
hampered by the variety of methods used both for estimating blood flow and for calculating autoregulatory parameters, as well as a lack of data on the relationship between different monitoring modalities used. Furthermore, the exact nature of post-SAH autoregulation failure is unclear. The change in the autoregulation curve is presumed to follow 1 of 3 patterns (Figure). Approximately 75% of the studies reported autoregulatory dysfunction as a result of SAH. Jaeger et al,35,36 in a prospective study using invasive brain tissue oxygenation measurements as an
CLINICAL NEUROSURGERY
estimate of cerebral blood flow, demonstrated impaired autoregulation on days 5 and 6 after the bleed to be predictive of delayed cerebral infarctions and poor neurological outcome at the 6-month follow up. Importantly, impaired cerebral autoregulation was found to be an independent predictor of outcome when multivariate models were used. Although the study included one of the largest series to date, because of the invasive nature of brain oxygen monitoring, it was performed only on poor-grade patients, precluding generalization.
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BUDOHOSKI ET AL
FIGURE. Possible effects of subarachnoid hemorrhage on the autoregulatory curve and autoregulatory (AR) capacity: shift of the autoregulatory curve to higher pressures (far left panel), narrowing of the autoregulatory plateau (middle panel), and complete loss of autoregulatory capacity with passive pressure flow transmission (far right panel). CBF, cerebral blood flow CPP, cerebral perfusion pressure.
Another large study by Otite et al48 included 68 patients (both good- and poor-grade patients) with SAH and used noninvasive methodology based on transcranial Doppler and transfer function analysis. They also found the state of autoregulation to be predictive of subsequent DCI. Furthermore, the authors developed 2 clinical scoring systems that included measurement of autoregulation: a smoking, age, gain, aneurysmal SAH score and a World Federation of Neurosurgical Societies, hyperglycemia, arterial pressure, phase score. Both scores had a specificity .90% for predicting vasospasm and DCI. The largest study by Budohoski et al45 using noninvasive technology, ie, transcranial Doppler and near-infrared spectroscopy, included 98 patients with all grades of SAH represented. Dynamic autoregulation was calculated with the well-established correlation coefficient methodology.24,25 Similar to the other studies, the authors found that early impairment of autoregulation (before the occurrence of vasospasm) was predictive of DCI, whereas identification of vasospasm alone was not. Those results indicated that autoregulatory failure is an independent predictor of DCI in all World Federation of Neurosurgical Societies grades, which can be identified as early as days 2 and 3 after ictus. In a follow-up study on the same cohort of patents, the authors analyzed the effect of the extent and spatial characteristics of autoregulatory failure with respect to outcome.47 They found that unilateral autoregulatory failure (commonly ipsilateral to the aneurysm, which is what is seen clinically) was related to DCI and seemed to occur first. However, they also demonstrated that bilateral autoregulatory failure, which typically is seen 1 or 2 days later, is related to poor neurological outcome at 3 months. Although the hemodynamic consequences of SAH are commonly regarded to be vascular in nature, a number of authors have investigated the changes in pressure reactivity using indexes that typically examine the dynamic relationship between intracranial pressure and arterial blood pressure and are commonly used in patients with head injury. Eide et al44 demonstrated in a prospective study that impaired pressure reactivity was predictive of outcome after SAH.
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AUTOREGULATION AND THERAPEUTIC INTERVENTIONS Although numerous authors support the role of autoregulation after SAH, it remains to be demonstrated that monitoring autoregulation can have beneficial therapeutic implications. To date, only 2 randomized controlled trials looking at the effect of pravastatin and erythropoietin on DCI and outcome after SAH have used autoregulation as an end point.33,39 It was demonstrated that indeed both statins and erythropoietin reduce the duration of impaired autoregulation. However, clinical benefit of simvastatin was ruled out in a recently completed large, multicenter study,49 whereas no further clinical studies of erythropoietin were performed. Nevertheless, in both cases (statins and erythropoietin), it was demonstrated that cerebral autoregulation is a process that can be pharmacologically influenced, at least in the acute stages. Optimal cerebral perfusion pressure (ie, the pressure at which cerebral autoregulation works best), a concept that has originated in the management of head injury,50,51 has been explored in SAH. Two retrospective studies demonstrated that indeed optimal cerebral perfusion pressure increases after SAH41,43 and that the duration of time spent below or above the calculated optimal cerebral perfusion pressure is related to worse outcome. Nevertheless, this concept has not been validated in a prospective fashion. In SAH, in which hemodynamic augmentation therapy is often implemented to prevent DCI, determination of specific blood pressure/cerebral perfusion pressure targets guided by the state of autoregulation is a plausible option and should be evaluated in prospective studies.
FUTURE DIRECTIONS In view of the existing literature on cerebral autoregulation after SAH, there seem to be several issues that should be addressed before definitive clinical evaluation. First, the literature documents a vast array of modalities for assessment of autoregulation. Although the diversity of modalities demonstrates that assessment of autoregulation is feasible in different clinical settings, it limits the generalizability of results.
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MONITORING CEREBRAL AUTOREGULATION AFTER SAH
Formulation of unified methodologies would aid in the design of future large-scale collaborative studies. The exact time course of autoregulatory impairment after SAH (in particular in good-grade patients) needs to be established, with emphasis on the temporal relationship between the large-vessel spasm, DCI, and autoregulatory failure. Although some work has already been done, it seems plausible that interrogation of autoregulation could be introduced into risk stratification models for patients with SAH. Furthermore, research is needed into the nature of autoregulation and the possibilities of influencing it either pharmacologically or though physical stimuli. Disclosures Dr Kirkpatrick is the principal investigator for the Simvastatin in Aneurysmal Subarachnoid Haemorrhage trial (STASH trial; http://www.clinicaltrials.gov; NCT00731627). Dr Czosnyka has a financial interest in a fraction of the licensing fee for ICM1 software (www.neurosurg.cam.ac.uk/icmplus) used for monitoring autoregulation. Dr Budohoski reports no conflict of interest.
REFERENCES 1. Hop JW, Rinkel GJ, Algra A, van Gijn J. Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke. 1997;28(3): 660-664. 2. Ecker A, Riemenschneider PA. Arteriographic demonstration of spasm of the intracranial arteries, with special reference to saccular arterial aneurysms. J Neurosurg. 1951;8(6):660-667. 3. Harders AG, Gilsbach JM. Time course of blood velocity changes related to vasospasm in the circle of Willis measured by transcranial Doppler ultrasound. J Neurosurg. 1987;66(5):718-728. 4. Dankbaar JW, Rijsdijk M, van der Schaaf IC, Velthuis BK, Wermer MJ, Rinkel GJ. Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology. 2009;51(12):813-819. 5. Rasmussen G, Hauerberg J, Waldemar G, Gjerris F, Juhler M. Cerebral blood flow autoregulation in experimental subarachnoid haemorrhage in rat. Acta Neurochir (Wien). 1992;119(1-4):128-133. 6. Harper AM, Glass HI. Effect of alterations in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial blood pressures. J Neurol Neurosurg Psychiatry. 1965;28(5):449-452. 7. Harper AM, Deshmukh VD, Sengupta D, Rowan JO, Jennett WB. The effect of experimental spasm on the CO2 response of cerebral bloodflow in primates. Neuroradiology. 1972;3(3):134-136. 8. Fitch W, Ferguson GG, Sengupta D, Garibi J, Harper AM. Autoregulation of cerebral blood flow during controlled hypotension in baboons. J Neurol Neurosurg Psychiatry. 1976;39(10):1014-1022. 9. Lassen NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959;39(2):183-238. 10. Fog M. The relationship between the blood pressure and the tonic regulation of the pial arteries. J Neurol Psychiatry. 1938;1(3):187-197. 11. Kontos HA, Wei EP, Navari RM, Levasseur JE, Rosenblum WI, Patterson JL Jr. Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol. 1978;234(4):H371-H383. 12. Symon L, Held K, Dorsch NW. A study of regional autoregulation in the cerebral circulation to increased perfusion pressure in normocapnia and hypercapnia. Stroke. 1973;4(2):139-147. 13. Andresen J, Shafi NI, Bryan RM Jr. Endothelial influences on cerebrovascular tone. J Appl Physiol (1985). 2006;100(1):318-327. 14. Bayliss WM. On the local reactions of the arterial wall to changes of internal pressure. J Physiol. 1902;28(3):220-231. 15. Kontos HA, Wei EP, Raper AJ, Rosenblum WI, Navari RM, Patterson JL Jr. Role of tissue hypoxia in local regulation of cerebral microcirculation. Am J Physiol. 1978;234(5):H582-H591. 16. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev. 1990;2(2):161-192.
CLINICAL NEUROSURGERY
17. Symon L, Held K, Dorsch NW. On the myogenic nature of the autoregulatory mechanism in the cerebral circulation. Eur Neurol. 1971-1972;6(1):11-18. 18. Wang Q, Pelligrino DA, Baughman VL, Koenig HM, Albrecht RF. The role of neuronal nitric oxide synthase in regulation of cerebral blood flow in normocapnia and hypercapnia in rats. J Cereb Blood Flow Metab. 1995;15(5):774-778. 19. Baron JC, Rougemont D, Soussaline F, et al. Local interrelationships of cerebral oxygen consumption and glucose utilization in normal subjects and in ischemic stroke patients: a positron tomography study. J Cereb Blood Flow Metab. 1984;4 (2):140-149. 20. Lundar T, Lindegaard KF, Froysaker T, Aaslid R, Grip A, Nornes H. Dissociation between cerebral autoregulation and carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass. Ann Thorac Surg. 1985;40(6):582-587. 21. Gordon E, Bergvall U. The effect of controlled hyperventilation on cerebral blood flow and oxygen uptake in patients with brain lesions. Acta Anaesthesiol Scand. 1973;17(1):63-69. 22. Kontos HA, Raper AJ, Patterson JL Jr. Mechanisms of action of CO2 on pial precapillary vessels. Eur Neurol. 1971-1972;6(1):114-118. 23. Sahuquillo J, Amoros S, Santos A, et al. False autoregulation (pseudoautoregulation) in patients with severe head injury: its importance in CPP management. Acta Neurochir Suppl. 2000;76:485-490. 24. Czosnyka M, Smielewski P, Kirkpatrick P, Menon DK, Pickard JD. Monitoring of cerebral autoregulation in head-injured patients. Stroke. 1996;27(10):1829-1834. 25. Czosnyka M, Smielewski P, Kirkpatrick P, Laing RJ, Menon D, Pickard JD. Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery. 1997;41(1):11-17. 26. Giller CA. A bedside test for cerebral autoregulation using transcranial Doppler ultrasound. Acta Neurochir (Wien). 1991;108(1-2):7-14. 27. Steinmeier R, Bauhuf C, Hübner U, et al. Slow rhythmic oscillations of blood pressure, intracranial pressure, microcirculation, and cerebral oxygenation: dynamic interrelation and time course in humans. Stroke. 1996;27(12):22362243. 28. Lam JM, Smielewski P, Czosnyka M, Pickard JD, Kirkpatrick PJ. Predicting delayed ischemic deficits after aneurysmal subarachnoid hemorrhage using a transient hyperemic response test of cerebral autoregulation. Neurosurgery. 2000;47(4):819-825. 29. Rätsep T, Asser T. Cerebral hemodynamic impairment after aneurysmal subarachnoid hemorrhage as evaluated using transcranial Doppler ultrasonography: relationship to delayed cerebral ischemia and clinical outcome. J Neurosurg. 2001;95(3):393-401. 30. Lang EW, Diehl RR, Mehdorn HM. Cerebral autoregulation testing after aneurysmal subarachnoid hemorrhage: the phase relationship between arterial blood pressure and cerebral blood flow velocity. Crit Care Med. 2001;29(1):158-163. 31. Soehle M, Jaeger M, Meixensberger J. Online assessment of brain tissue oxygen autoregulation in traumatic brain injury and subarachnoid hemorrhage. Neurol Res. 2003;25(4):411-417. 32. Soehle M, Czosnyka M, Pickard JD, Kirkpatrick PJ. Continuous assessment of cerebral autoregulation in subarachnoid hemorrhage. Anesth Analg. 2004;98(4): 1133-1139. 33. Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial. Stroke. 2005;36(8):1627-1632. 34. Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Effects of acute treatment with statins on cerebral autoregulation in patients after aneurysmal subarachnoid hemorrhage. Neurosurg Focus. 2006;21(3):E10. 35. Jaeger M, Schuhmann MU, Soehle M, Nagel C, Meixensberger J. Continuous monitoring of cerebrovascular autoregulation after subarachnoid hemorrhage by brain tissue oxygen pressure reactivity and its relation to delayed cerebral infarction. Stroke. 2007;38(3):981-986. 36. Jaeger M, Soehle M, Schuhmann MU, Meixensberger J. Clinical significance of impaired cerebrovascular autoregulation after severe aneurysmal subarachnoid hemorrhage. Stroke. 2012;43(8):2097-2101. 37. Christ M, Noack F, Schroeder T, et al. Continuous cerebral autoregulation monitoring by improved cross-correlation analysis: comparison with the cuff deflation test. Intensive Care Med. 2007;33(2):246-254. 38. Tseng MY, Al-Rawi PG, Czosnyka M, et al. Enhancement of cerebral blood flow using systemic hypertonic saline therapy improves outcome in patients with poorgrade spontaneous subarachnoid hemorrhage. J Neurosurg. 2007;107(2):274-282.
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39. Tseng MY, Hutchinson PJ, Richards HK, et al. Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a phase II randomized, double-blind, placebo-controlled trial: clinical article. J Neurosurg. 2009;111(1):171-180. 40. Zweifel C, Castellani G, Czosnyka M, et al. Continuous assessment of cerebral autoregulation with near-infrared spectroscopy in adults after subarachnoid hemorrhage. Stroke. 2010;41(9):1963-1968. 41. Bijlenga P, Czosnyka M, Budohoski KP, et al. “Optimal cerebral perfusion pressure” in poor grade patients after subarachnoid hemorrhage. Neurocrit Care. 2010;13(1):17-23. 42. Barth M, Woitzik J, Weiss C, et al. Correlation of clinical outcome with pressure-, oxygen-, and flow-related indices of cerebrovascular reactivity in patients following aneurysmal SAH. Neurocrit Care. 2010;12(2):234-243. 43. Rasulo FA, Girardini A, Lavinio A, et al. Are optimal cerebral perfusion pressure and cerebrovascular autoregulation related to long-term outcome in patients with aneurysmal subarachnoid hemorrhage? J Neurosurg Anesthesiol. 2012;24(1): 3-8. 44. Eide PK, Sorteberg A, Bentsen G, Marthinsen PB, Stubhaug A, Sorteberg W. Pressure-derived versus pressure wave amplitude-derived indices of cerebrovascular pressure reactivity in relation to early clinical state and 12-month outcome following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2012;116(5): 961-971.
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45. Budohoski KP, Czosnyka M, Smielewski P, et al. Impairment of cerebral autoregulation predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective observational study. Stroke. 2012;43(12):3230-3237. 46. Budohoski KP, Czosnyka M, Smielewski P, et al. Cerebral autoregulation after subarachnoid hemorrhage: comparison of three methods. J Cereb Blood Flow Metab. 2013;33(3):449-456. 47. Budohoski KP, Czosnyka M, Kirkpatrick PJ, et al. Bilateral failure of cerebral autoregulation is related to unfavorable outcome after subarachnoid hemorrhage. Neurocrit Care. 2015;22(1):65-73. 48. Otite F, Mink S, Tan CO, et al. Impaired cerebral autoregulation is associated with vasospasm and delayed cerebral ischemia in subarachnoid hemorrhage. Stroke. 2014;45(3):677-682. 49. Kirkpatrick PJ, Turner CL, Smith C, Hutchinson PJ, Murray GD; STASH Collaborators. Simvastatin in Aneurysmal Subarachnoid Haemorrhage (STASH): a multicentre randomised phase 3 trial. Lancet Neurol. 2014;13(7):666-675. 50. Steiner LA, Czosnyka M, Piechnik SK, et al. Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Crit Care Med. 2002;30(4):733-738. 51. Aries MJ, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit Care Med. 2012; 40(8):2456-2463.
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The Role of Monitoring Cerebral Autoregulation After Subarachnoid Hemorrhage Karol P. Budohoski, MD, PhD
S
ubarachnoid hemorrhage (SAH) is a devastating disease with approximately 30% early case fatality. Of the 70% who survive Peter J. Kirkpatrick, FRCS, SN the ictus, despite early resuscitation and obliterDivision of Neurosurgery, Department of ation of the aneurysm in order to prevent the Clinical Neurosciences, Addenbrooke’s deleterious effects of a rebleed, 25% will subHospital, University of Cambridge, sequently deteriorate.1 Delayed deterioration Cambridge, United Kingdom may be due to hydrocephalus, electrolyte disturbances, seizures, as well as delayed cerebral Correspondence: Karol P. Budohoski, MD, PhD, ischemia (DCI). Box 167, Division of Neurosurgery, DCI, traditionally attributed to cerebral vasoAddenbrooke’s Hospital, spasm (ie, narrowing of large cerebral arteries), Hills Rd, CB2 0QQ, was first described in 1951.2 Vasospasm takes Cambridge, UK. E-mail: [email protected] some days to develop and peaks at 5 to 7 days, after which it slowly resolves,3 hence the Copyright © 2015 by the association with delayed deterioration. However, Congress of Neurological Surgeons. it has been documented clinically that the relationship between vasospasm and DCI is inconsistent. Some patients with severe vasospasm never deteriorate and some deteriorate without vasospasm.4 Current research suggests that a number of pathophysiological processes take place after SAH, all of which may contribute to delayed deterioration. In experimental settings, cerebral vasospasm does not reduce distal cerebral blood flow unless there is an additional insult such as a decrease in blood pressure,5 lending support to the Harper dual-control hypothesis.6-8 Clinical evaluation of cerebral autoregulation is being increasingly recognized as a factor requiring consideration in the management of patients with SAH. In this review, we present recent findings on the role of monitoring of cerebral autoregulation after SAH. Marek Czosnyka, PhD
CEREBRAL AUTOREGULATION Cerebral autoregulation describes the intrinsic ability of cerebral vasculature to maintain a stable blood flow despite changes in blood pressure or, more accurately, cerebral perfusion pressure.9 Cerebral blood flow is regulated primarily by changes in arteriolar diameter, which drive the changes in cerebrovascular resistance.10-12 Despite many pathways mediating the described vasomotor reactions,11,13-18 the exact mechanisms remain
180 | VOLUME 62 | NUMBER 1 | AUGUST 2015
elusive. Importantly, cerebral autoregulation is thought to be a mechanism distinct from CO2 reactivity and flow-metabolism coupling.19-22 Calculation of the static rate of autoregulation by assessing cerebral blood flow at 2 different blood pressure levels using direct perfusion methods is considered to be the best available technique for testing autoregulation. It is a quantitative method that is simple to interpret, but there are a number of drawbacks (such as the need for pharmacological interventions to alter the blood pressure levels or the effect of “false autoregulation” if the intracranial pressure follows induced changes in arterial blood pressure23) that limit its usefulness in clinical settings. Currently, numerous methods using surrogate markers of cerebral blood flow are being explored. Frequently, emphasis is placed on the dynamic process of autoregulatory reactions. These methods include transcranial Doppler, laser Doppler flowmetry, partial pressure of brain oxygen, thermal diffusion regional cerebral blood flow, and the tissue oxygenation index (derived from near-infrared spectroscopy). Methods using spontaneous fluctuations of blood pressure rather than external stimuli are gaining momentum because of their relative ease of implementation in clinical settings, particularly in the critical care unit. With these methods, various parameters can be calculated by assessing either the speed or direction of changes in the surrogate markers of blood flow in relation to the speed or direction of blood pressure changes. Although simple in principle, various algorithms are used, leading to significant heterogeneities and difficulties in clinical interpretation.24,25 In this study, we aimed to characterize the most recent data on the role of monitoring autoregulation after SAH, focusing solely on dynamic methods using continuous monitoring signals.
THE ROLE OF AUTOREGULATION MONITORING AFTER SAH Studies in which dynamic autoregulation was tested after SAH are summarized in the Table. Unambiguous interpretation of the results is
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Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
MONITORING CEREBRAL AUTOREGULATION AFTER SAH
TABLE. Studies Investigating Dynamic Cerebral Autoregulation After Subarachnoid Hemorrhagea Study
n
CBF Measurement
Findings
Giller26 (1991)
25
TCD
Absence of a hyperemic response in all poor-grade patients (n = 14) but only in 60% of goodgrade patients.
Steinmeier et al27 (1996) Lam et al28 (2000)
10
TCD, ICP, ABP
20
TCD
Spontaneous fluctuations of blood pressure can be used for assessment of AR with the intracranial pressure signal. Patients with primary impairment of AR (n = 5) and CVS (n = 6) developed DCI. No patients without primary impairment of AR (n = 14) developed DCI.
Ra¨tsep and Asser29 (2001)
55
TCD
Lang et al30 (2001)
12
TCD
Soehle et al31 (2003) Soehle et al32 (2004) Tseng et al33,34 (2005 and 2006) Jaeger et al35,36 (2007 and 2012)
NN 32 80
PbtO2 TCD TCD
67
PbtO2
Christ et al37 (2007) Tseng et al38 (2007) Tseng et al39 (2009)
6 35 80
TCD TCD, ICP TCD
Zweifel et al40 (2010) 27 Bijlenga et al41 (2010) 25
CVS was associated with DCI only if hyperemic response was reduced (n = 14). In all cases, CVS and reduced hyperemic response were associated with delayed infarctions (n = 12) and poor outcome in 68%. Testing divided into early (days 1-6) and late (day 7-13); 88% of patients with intact dynamic AR (n = 8) had good outcome. Disturbed AR was predictive of GOS score of 1 and 2. Late-phase AR did not have predictive value. PbtO2 AR can be used to titrate CPP levels. CVS caused impairments in AR. AR was more affected ipsilateral to the spastic vessel. Shorter duration of AR impairment was associated with lower incidence of DCI in the pravastatin group (n = 40). Impaired AR on day 5-6 after SAH was an independent predictor of delayed infarction (n = 20). Impaired AR was an independent predictor of outcome at 6 mo (n = 56).
Dynamic autoregulation was impaired (n = 6) compared with healthy control subjects (n = 9). Impaired autoregulation ipsilaterally to the aneurysm. HTS improved blood flow but not AR (n = 35). Shorter-duration AR impairments, decreased incidence of severe CVS resulted in a reduced incidence of new infarctions in the EPO group: 40% vs 7.5% (n = 40). TCD, NIRS Dynamic AR assessed with NIRS correlates with TCD-based AR. ICP Intact AR had a 87.5% positive predictive value for survival (n = 16). Impaired AR in the first 48 h correlated with mRS score (n = 16). ICP, PbtO2, TD-rCBF No differences in dynamic AR between infarction (n = 8) and no-infarction groups (n = 13). ICP Duration of impaired AR was longer in patients with poor outcome (n = 14). Longer time spent below optimal CPP was associated with poor outcome (n = 14). PbtO2, TD-rCBF Improved correlation of dynamic indexes of AR after temporal synchronization. ICP ICP-ABP wave amplitude correlation was related to both the baseline status and outcome at 12 mo. TCD, NIRS Failure of AR in the first 5 d after SAH was an independent predictor of DCI. Benefit of multimodal assessment of autoregulation.
Barth et al42 (2010) Rasulo et al43 (2011)
21 29
Hecht et al23 (2011) Eide et al44 (2012) Budohoski et al45,46 (2012)
5 94 98
Budohoski et al47 (2015)
90
TCD
Otite et al48 (2014)
68
TCD
Unilateral failure of AR was related to DCI. Bilateral failure of AR was related to poor outcome (16/18 patients vs 17/72 patients with unfavorable vs favorable outcome, respectively, demonstrated bilateral failure of AR). Impaired AR predictive of CVS and DCI. Two clinical scoring models developed: SAGA score for predicting CVS (.90% specificity; unit increase in score 3-fold increase in risk of CVS) and WHAP for predicting DCI (.90% specificity; unit increase in score 3-fold increase in risk of DCI).
a
ABP, arterial blood pressure; AR, autoregulation; CBF, cerebral blood flow; CPP, cerebral perfusion pressure; CVS, cerebral vasospasm; DCI, delayed cerebral ischemia; EPO, erythropoietin; GOS, Glasgow Outcome Scale; HTS, hypertonic saline; ICP, intracranial pressure; mRS, modified Rankin Scale; NIRS, near-infrared spectroscopy; SAGA, smoking, age, gain, aneurysmal SAH; SAH, subarachnoid hemorrhage; TCD, transcranial Doppler; TD-rCBF, thermal diffusion regional cerebral blood flow; WHAP, World Federation of Neurosurgical Societies, hyperglycemia, arterial pressure, phase.
hampered by the variety of methods used both for estimating blood flow and for calculating autoregulatory parameters, as well as a lack of data on the relationship between different monitoring modalities used. Furthermore, the exact nature of post-SAH autoregulation failure is unclear. The change in the autoregulation curve is presumed to follow 1 of 3 patterns (Figure). Approximately 75% of the studies reported autoregulatory dysfunction as a result of SAH. Jaeger et al,35,36 in a prospective study using invasive brain tissue oxygenation measurements as an
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estimate of cerebral blood flow, demonstrated impaired autoregulation on days 5 and 6 after the bleed to be predictive of delayed cerebral infarctions and poor neurological outcome at the 6-month follow up. Importantly, impaired cerebral autoregulation was found to be an independent predictor of outcome when multivariate models were used. Although the study included one of the largest series to date, because of the invasive nature of brain oxygen monitoring, it was performed only on poor-grade patients, precluding generalization.
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FIGURE. Possible effects of subarachnoid hemorrhage on the autoregulatory curve and autoregulatory (AR) capacity: shift of the autoregulatory curve to higher pressures (far left panel), narrowing of the autoregulatory plateau (middle panel), and complete loss of autoregulatory capacity with passive pressure flow transmission (far right panel). CBF, cerebral blood flow CPP, cerebral perfusion pressure.
Another large study by Otite et al48 included 68 patients (both good- and poor-grade patients) with SAH and used noninvasive methodology based on transcranial Doppler and transfer function analysis. They also found the state of autoregulation to be predictive of subsequent DCI. Furthermore, the authors developed 2 clinical scoring systems that included measurement of autoregulation: a smoking, age, gain, aneurysmal SAH score and a World Federation of Neurosurgical Societies, hyperglycemia, arterial pressure, phase score. Both scores had a specificity .90% for predicting vasospasm and DCI. The largest study by Budohoski et al45 using noninvasive technology, ie, transcranial Doppler and near-infrared spectroscopy, included 98 patients with all grades of SAH represented. Dynamic autoregulation was calculated with the well-established correlation coefficient methodology.24,25 Similar to the other studies, the authors found that early impairment of autoregulation (before the occurrence of vasospasm) was predictive of DCI, whereas identification of vasospasm alone was not. Those results indicated that autoregulatory failure is an independent predictor of DCI in all World Federation of Neurosurgical Societies grades, which can be identified as early as days 2 and 3 after ictus. In a follow-up study on the same cohort of patents, the authors analyzed the effect of the extent and spatial characteristics of autoregulatory failure with respect to outcome.47 They found that unilateral autoregulatory failure (commonly ipsilateral to the aneurysm, which is what is seen clinically) was related to DCI and seemed to occur first. However, they also demonstrated that bilateral autoregulatory failure, which typically is seen 1 or 2 days later, is related to poor neurological outcome at 3 months. Although the hemodynamic consequences of SAH are commonly regarded to be vascular in nature, a number of authors have investigated the changes in pressure reactivity using indexes that typically examine the dynamic relationship between intracranial pressure and arterial blood pressure and are commonly used in patients with head injury. Eide et al44 demonstrated in a prospective study that impaired pressure reactivity was predictive of outcome after SAH.
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AUTOREGULATION AND THERAPEUTIC INTERVENTIONS Although numerous authors support the role of autoregulation after SAH, it remains to be demonstrated that monitoring autoregulation can have beneficial therapeutic implications. To date, only 2 randomized controlled trials looking at the effect of pravastatin and erythropoietin on DCI and outcome after SAH have used autoregulation as an end point.33,39 It was demonstrated that indeed both statins and erythropoietin reduce the duration of impaired autoregulation. However, clinical benefit of simvastatin was ruled out in a recently completed large, multicenter study,49 whereas no further clinical studies of erythropoietin were performed. Nevertheless, in both cases (statins and erythropoietin), it was demonstrated that cerebral autoregulation is a process that can be pharmacologically influenced, at least in the acute stages. Optimal cerebral perfusion pressure (ie, the pressure at which cerebral autoregulation works best), a concept that has originated in the management of head injury,50,51 has been explored in SAH. Two retrospective studies demonstrated that indeed optimal cerebral perfusion pressure increases after SAH41,43 and that the duration of time spent below or above the calculated optimal cerebral perfusion pressure is related to worse outcome. Nevertheless, this concept has not been validated in a prospective fashion. In SAH, in which hemodynamic augmentation therapy is often implemented to prevent DCI, determination of specific blood pressure/cerebral perfusion pressure targets guided by the state of autoregulation is a plausible option and should be evaluated in prospective studies.
FUTURE DIRECTIONS In view of the existing literature on cerebral autoregulation after SAH, there seem to be several issues that should be addressed before definitive clinical evaluation. First, the literature documents a vast array of modalities for assessment of autoregulation. Although the diversity of modalities demonstrates that assessment of autoregulation is feasible in different clinical settings, it limits the generalizability of results.
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MONITORING CEREBRAL AUTOREGULATION AFTER SAH
Formulation of unified methodologies would aid in the design of future large-scale collaborative studies. The exact time course of autoregulatory impairment after SAH (in particular in good-grade patients) needs to be established, with emphasis on the temporal relationship between the large-vessel spasm, DCI, and autoregulatory failure. Although some work has already been done, it seems plausible that interrogation of autoregulation could be introduced into risk stratification models for patients with SAH. Furthermore, research is needed into the nature of autoregulation and the possibilities of influencing it either pharmacologically or though physical stimuli. Disclosures Dr Kirkpatrick is the principal investigator for the Simvastatin in Aneurysmal Subarachnoid Haemorrhage trial (STASH trial; http://www.clinicaltrials.gov; NCT00731627). Dr Czosnyka has a financial interest in a fraction of the licensing fee for ICM1 software (www.neurosurg.cam.ac.uk/icmplus) used for monitoring autoregulation. Dr Budohoski reports no conflict of interest.
REFERENCES 1. Hop JW, Rinkel GJ, Algra A, van Gijn J. Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke. 1997;28(3): 660-664. 2. Ecker A, Riemenschneider PA. Arteriographic demonstration of spasm of the intracranial arteries, with special reference to saccular arterial aneurysms. J Neurosurg. 1951;8(6):660-667. 3. Harders AG, Gilsbach JM. Time course of blood velocity changes related to vasospasm in the circle of Willis measured by transcranial Doppler ultrasound. J Neurosurg. 1987;66(5):718-728. 4. Dankbaar JW, Rijsdijk M, van der Schaaf IC, Velthuis BK, Wermer MJ, Rinkel GJ. Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology. 2009;51(12):813-819. 5. Rasmussen G, Hauerberg J, Waldemar G, Gjerris F, Juhler M. Cerebral blood flow autoregulation in experimental subarachnoid haemorrhage in rat. Acta Neurochir (Wien). 1992;119(1-4):128-133. 6. Harper AM, Glass HI. Effect of alterations in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial blood pressures. J Neurol Neurosurg Psychiatry. 1965;28(5):449-452. 7. Harper AM, Deshmukh VD, Sengupta D, Rowan JO, Jennett WB. The effect of experimental spasm on the CO2 response of cerebral bloodflow in primates. Neuroradiology. 1972;3(3):134-136. 8. Fitch W, Ferguson GG, Sengupta D, Garibi J, Harper AM. Autoregulation of cerebral blood flow during controlled hypotension in baboons. J Neurol Neurosurg Psychiatry. 1976;39(10):1014-1022. 9. Lassen NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959;39(2):183-238. 10. Fog M. The relationship between the blood pressure and the tonic regulation of the pial arteries. J Neurol Psychiatry. 1938;1(3):187-197. 11. Kontos HA, Wei EP, Navari RM, Levasseur JE, Rosenblum WI, Patterson JL Jr. Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol. 1978;234(4):H371-H383. 12. Symon L, Held K, Dorsch NW. A study of regional autoregulation in the cerebral circulation to increased perfusion pressure in normocapnia and hypercapnia. Stroke. 1973;4(2):139-147. 13. Andresen J, Shafi NI, Bryan RM Jr. Endothelial influences on cerebrovascular tone. J Appl Physiol (1985). 2006;100(1):318-327. 14. Bayliss WM. On the local reactions of the arterial wall to changes of internal pressure. J Physiol. 1902;28(3):220-231. 15. Kontos HA, Wei EP, Raper AJ, Rosenblum WI, Navari RM, Patterson JL Jr. Role of tissue hypoxia in local regulation of cerebral microcirculation. Am J Physiol. 1978;234(5):H582-H591. 16. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev. 1990;2(2):161-192.
CLINICAL NEUROSURGERY
17. Symon L, Held K, Dorsch NW. On the myogenic nature of the autoregulatory mechanism in the cerebral circulation. Eur Neurol. 1971-1972;6(1):11-18. 18. Wang Q, Pelligrino DA, Baughman VL, Koenig HM, Albrecht RF. The role of neuronal nitric oxide synthase in regulation of cerebral blood flow in normocapnia and hypercapnia in rats. J Cereb Blood Flow Metab. 1995;15(5):774-778. 19. Baron JC, Rougemont D, Soussaline F, et al. Local interrelationships of cerebral oxygen consumption and glucose utilization in normal subjects and in ischemic stroke patients: a positron tomography study. J Cereb Blood Flow Metab. 1984;4 (2):140-149. 20. Lundar T, Lindegaard KF, Froysaker T, Aaslid R, Grip A, Nornes H. Dissociation between cerebral autoregulation and carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass. Ann Thorac Surg. 1985;40(6):582-587. 21. Gordon E, Bergvall U. The effect of controlled hyperventilation on cerebral blood flow and oxygen uptake in patients with brain lesions. Acta Anaesthesiol Scand. 1973;17(1):63-69. 22. Kontos HA, Raper AJ, Patterson JL Jr. Mechanisms of action of CO2 on pial precapillary vessels. Eur Neurol. 1971-1972;6(1):114-118. 23. Sahuquillo J, Amoros S, Santos A, et al. False autoregulation (pseudoautoregulation) in patients with severe head injury: its importance in CPP management. Acta Neurochir Suppl. 2000;76:485-490. 24. Czosnyka M, Smielewski P, Kirkpatrick P, Menon DK, Pickard JD. Monitoring of cerebral autoregulation in head-injured patients. Stroke. 1996;27(10):1829-1834. 25. Czosnyka M, Smielewski P, Kirkpatrick P, Laing RJ, Menon D, Pickard JD. Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery. 1997;41(1):11-17. 26. Giller CA. A bedside test for cerebral autoregulation using transcranial Doppler ultrasound. Acta Neurochir (Wien). 1991;108(1-2):7-14. 27. Steinmeier R, Bauhuf C, Hübner U, et al. Slow rhythmic oscillations of blood pressure, intracranial pressure, microcirculation, and cerebral oxygenation: dynamic interrelation and time course in humans. Stroke. 1996;27(12):22362243. 28. Lam JM, Smielewski P, Czosnyka M, Pickard JD, Kirkpatrick PJ. Predicting delayed ischemic deficits after aneurysmal subarachnoid hemorrhage using a transient hyperemic response test of cerebral autoregulation. Neurosurgery. 2000;47(4):819-825. 29. Rätsep T, Asser T. Cerebral hemodynamic impairment after aneurysmal subarachnoid hemorrhage as evaluated using transcranial Doppler ultrasonography: relationship to delayed cerebral ischemia and clinical outcome. J Neurosurg. 2001;95(3):393-401. 30. Lang EW, Diehl RR, Mehdorn HM. Cerebral autoregulation testing after aneurysmal subarachnoid hemorrhage: the phase relationship between arterial blood pressure and cerebral blood flow velocity. Crit Care Med. 2001;29(1):158-163. 31. Soehle M, Jaeger M, Meixensberger J. Online assessment of brain tissue oxygen autoregulation in traumatic brain injury and subarachnoid hemorrhage. Neurol Res. 2003;25(4):411-417. 32. Soehle M, Czosnyka M, Pickard JD, Kirkpatrick PJ. Continuous assessment of cerebral autoregulation in subarachnoid hemorrhage. Anesth Analg. 2004;98(4): 1133-1139. 33. Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial. Stroke. 2005;36(8):1627-1632. 34. Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Effects of acute treatment with statins on cerebral autoregulation in patients after aneurysmal subarachnoid hemorrhage. Neurosurg Focus. 2006;21(3):E10. 35. Jaeger M, Schuhmann MU, Soehle M, Nagel C, Meixensberger J. Continuous monitoring of cerebrovascular autoregulation after subarachnoid hemorrhage by brain tissue oxygen pressure reactivity and its relation to delayed cerebral infarction. Stroke. 2007;38(3):981-986. 36. Jaeger M, Soehle M, Schuhmann MU, Meixensberger J. Clinical significance of impaired cerebrovascular autoregulation after severe aneurysmal subarachnoid hemorrhage. Stroke. 2012;43(8):2097-2101. 37. Christ M, Noack F, Schroeder T, et al. Continuous cerebral autoregulation monitoring by improved cross-correlation analysis: comparison with the cuff deflation test. Intensive Care Med. 2007;33(2):246-254. 38. Tseng MY, Al-Rawi PG, Czosnyka M, et al. Enhancement of cerebral blood flow using systemic hypertonic saline therapy improves outcome in patients with poorgrade spontaneous subarachnoid hemorrhage. J Neurosurg. 2007;107(2):274-282.
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39. Tseng MY, Hutchinson PJ, Richards HK, et al. Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a phase II randomized, double-blind, placebo-controlled trial: clinical article. J Neurosurg. 2009;111(1):171-180. 40. Zweifel C, Castellani G, Czosnyka M, et al. Continuous assessment of cerebral autoregulation with near-infrared spectroscopy in adults after subarachnoid hemorrhage. Stroke. 2010;41(9):1963-1968. 41. Bijlenga P, Czosnyka M, Budohoski KP, et al. “Optimal cerebral perfusion pressure” in poor grade patients after subarachnoid hemorrhage. Neurocrit Care. 2010;13(1):17-23. 42. Barth M, Woitzik J, Weiss C, et al. Correlation of clinical outcome with pressure-, oxygen-, and flow-related indices of cerebrovascular reactivity in patients following aneurysmal SAH. Neurocrit Care. 2010;12(2):234-243. 43. Rasulo FA, Girardini A, Lavinio A, et al. Are optimal cerebral perfusion pressure and cerebrovascular autoregulation related to long-term outcome in patients with aneurysmal subarachnoid hemorrhage? J Neurosurg Anesthesiol. 2012;24(1): 3-8. 44. Eide PK, Sorteberg A, Bentsen G, Marthinsen PB, Stubhaug A, Sorteberg W. Pressure-derived versus pressure wave amplitude-derived indices of cerebrovascular pressure reactivity in relation to early clinical state and 12-month outcome following aneurysmal subarachnoid hemorrhage. J Neurosurg. 2012;116(5): 961-971.
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45. Budohoski KP, Czosnyka M, Smielewski P, et al. Impairment of cerebral autoregulation predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective observational study. Stroke. 2012;43(12):3230-3237. 46. Budohoski KP, Czosnyka M, Smielewski P, et al. Cerebral autoregulation after subarachnoid hemorrhage: comparison of three methods. J Cereb Blood Flow Metab. 2013;33(3):449-456. 47. Budohoski KP, Czosnyka M, Kirkpatrick PJ, et al. Bilateral failure of cerebral autoregulation is related to unfavorable outcome after subarachnoid hemorrhage. Neurocrit Care. 2015;22(1):65-73. 48. Otite F, Mink S, Tan CO, et al. Impaired cerebral autoregulation is associated with vasospasm and delayed cerebral ischemia in subarachnoid hemorrhage. Stroke. 2014;45(3):677-682. 49. Kirkpatrick PJ, Turner CL, Smith C, Hutchinson PJ, Murray GD; STASH Collaborators. Simvastatin in Aneurysmal Subarachnoid Haemorrhage (STASH): a multicentre randomised phase 3 trial. Lancet Neurol. 2014;13(7):666-675. 50. Steiner LA, Czosnyka M, Piechnik SK, et al. Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Crit Care Med. 2002;30(4):733-738. 51. Aries MJ, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit Care Med. 2012; 40(8):2456-2463.
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