Impact of Goal-Directed Therapy on Delayed Ischemia After Aneurysmal Subarachnoid Hemorrhage

Background and Purpose: Delayed cerebral ischemia (DCI) is the most important cause for a poor clinical outcome after a subarachnoid hemorrhage. The aim of this study was to assess whether goal-directed hemodynamic therapy (GDHT), as compared to standard clinical care, reduces the rate of DCI after subarachnoid hemorrhage. Methods: We conducted a prospective randomized controlled trial. Patients >18 years of age with an aneurysmal subarachnoid hemorrhage were enrolled and randomly assigned to standard therapy or GDHT. Advanced hemodynamic monitoring and predefined GDHT algorithms were applied in the GDHT group. The primary end point was the occurrence of DCI. Functional outcome was assessed using the Glasgow Outcome Scale (GOS) 3 months after discharge. Results: In total, 108 patients were randomized to the control (n=54) or GDHT group (n=54). The primary outcome (DCI) occurred in 13% of the GDHT group and in 32% of the control group patients (odds ratio, 0.324 [95% CI, 0.11–0.86]; P =0.021). Even after adjustment for confounding parameters, GDHT was found to be superior to standard therapy (hazard ratio, 2.84 [95% CI, 1.18–6.86]; P =0.02). The GOS was assessed 3 months after discharge in 107 patients; it showed more patients with a low disability (GOS 5, minor or no deficits) than patients with higher deficits (GOS 1–4) in the GDHT group compared with the control group (GOS 5, 66% versus 44%; GOS 1–4, 34% versus 56%; P =0.025). There was no significant difference in mortality between the groups. Conclusions: GDHT reduced the rate of DCI after subarachnoid hemorrhage with a better functional outcome (GOS=5) 3 months after discharge. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01832389.

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Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience

Neurosurgical Review ◽

10.1007/s10143-021-01477-6 ◽

2021 ◽

Author(s):

Claudia Ditz ◽

Björn Machner ◽

Hannes Schacht ◽

Alexander Neumann ◽

Peter Schramm ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Functional Outcome ◽

Antiplatelet Therapy ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Control Group ◽

Lesion Volume ◽

Single Center ◽

Single Center Experience

AbstractPlatelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19–0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.

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High-Dose Nadroparin Following Endovascular Aneurysm Treatment Benefits Outcome After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1093/neuros/nyx381 ◽

2017 ◽

Vol 83 (2) ◽

pp. 281-287 ◽

Cited By ~ 1

Author(s):

Rene Post ◽

IJsbrand A.J Zijlstra ◽

Rene van den Berg ◽

Bert A Coert ◽

Dagmar Verbaan ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Dose Group ◽

Low Dose ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Controlled Trial ◽

Delayed Cerebral Ischemia ◽

Neurological Status ◽

High Dose ◽

Aneurysm Treatment ◽

Significant Difference

Abstract BACKGROUND Delayed cerebral ischemia (DCI) is one of the major causes of delayed morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE To evaluate the effect of high-dose nadroparin treatment following endovascular aneurysm treatment on the occurrence of DCI and clinical outcome. METHODS Medical records of 158 adult patients with an aSAH were retrospectively analyzed. Those patients treated endovascularly for their ruptured aneurysm were included in this study. They received either high-dose (twice daily 5700 AxaIE) or low-dose (once daily 2850 AxaIE) nadroparin treatment after occlusion of the aneurysm. Medical charts were reviewed and imaging was scored by 2 independent neuroradiologists. Data with respect to in-hospital complications, peri-procedural complications, discharge location, and mortality were collected. RESULTS Ninety-three patients had received high-dose nadroparin, and 65 patients prophylactic low-dose nadroparin. There was no significant difference in clinical DCI occurrence between patients treated with high-dose (34%) and low-dose (31%) nadroparin. More patients were discharged to home in patients who received high-dose nadroparin (40%) compared to low-dose (17%; odds ratio [OR] 3.13, 95% confidence interval [95% CI]: 1.36-7.24). Furthermore, mortality was lower in the high-dose group (5%) compared to the low-dose group (23%; OR 0.19, 95% CI: 0.07-0.55), also after adjusting for neurological status on admission (OR 0.21, 95% CI: 0.07-0.63). CONCLUSION Patients who were treated with high-dose nadroparin after endovascular treatment for aneurysmal SAH were more often discharged to home and showed lower mortality. High-dose nadroparin did not, however, show a decrease in the occurrence of clinical DCI after aSAH. A randomized controlled trial seems warranted.

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Phase 1/2a Trial of ISPASM

Stroke ◽

10.1161/strokeaha.121.034578 ◽

2021 ◽

Author(s):

Mario Zanaty ◽

Lauren Allan ◽

Edgar A. Samaniego ◽

Anthony Piscopo ◽

Eleanor Ryan ◽

...

Keyword(s):

Computed Tomography ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Intravenous Infusion ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Controlled Trial ◽

Phase 1 ◽

External Ventricular Drain ◽

Delayed Cerebral Ischemia ◽

Unique Identifier

Background and Purpose: Microthrombosis could play a role in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Tirofiban has shown promising results in reducing delayed cerebral ischemia in retrospective studies. However, the safety of using tirofiban in aneurysmal subarachnoid hemorrhage is not rigorously established. Methods: A phase 1/2a double-blinded randomized controlled trial (2:1 randomization) to assess the safety of a 7-day intravenous infusion of tirofiban compared with placebo, in patients with aneurysmal subarachnoid hemorrhage treated with ventriculostomy placed in the operative room and coiling was conducted. The primary end point was any intracranial hemorrhage during the hospital stay. The secondary end points were: incidence of radiographic and clinical vasospasm, incidence of delayed cerebral ischemia, and incidence of cerebral ischemic changes noted on magnetic resonance imaging or computed tomography. Results: Eighteen patients received intravenous tirofiban and 12 received placebo. There was no difference in baseline characteristics except for higher male proportions in the tirofiban group. There was no difference in death, in development of new or change in existing intracranial hemorrhages, in thrombocytopenia, and need for shunts in the two arms. However, the tirofiban arm had a lower incidence of delayed cerebral ischemia compared with placebo (6% [1/18] versus 33% [4/12]; P =0.04), and less radiographic vasospasm as detected by catheter angiogram or computed tomography angiography ( P =0.01) and computed tomography perfusion ( P =0.01). Conclusions: The above preliminary results support proceeding with further testing of the safety and efficacy of 7-day intravenous infusion of tirofiban in a pragmatic (placing external ventricular drain by the bedside), multicenter setting, and using a larger population. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03691727.

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Arginase-1 Released into CSF After Aneurysmal Subarachnoid Hemorrhage Decreases Arginine/Ornithine Ratio: a Novel Prognostic Biomarker

Translational Stroke Research ◽

10.1007/s12975-021-00944-y ◽

2021 ◽

Author(s):

Julian Zimmermann ◽

Johannes Weller ◽

Sven Grub ◽

Sied Kebir ◽

Felix Lehmann ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Functional Outcome ◽

Prognostic Biomarker ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Disease Onset ◽

Delayed Cerebral Ischemia ◽

Clinical Event ◽

Unique Identifier ◽

Clinical Trial Registration ◽

Arginase 1

AbstractWe hypothesized that the enzyme arginase-1 is released into the cerebrospinal fluid (CSF) during red blood cell lysis and contributes to dysregulated metabolism of the nitric oxide (NO) precursor L-arginine during aneurysmal subarachnoid hemorrhage (SAH). This prospective case–control study included 43 patients with aneurysmal SAH and ventricular drainage for clinical reasons. Longitudinal CSF samples (99) were obtained in the course of SAH. Patients were dichotomized regarding the occurrence of cerebral vasospasm syndrome (CVS) (N = 19). Arginase-1 and the amino acids L-arginine and L-ornithine were quantified in CSF. Outcome assessments included delayed cerebral ischemia (DCI) and functional status after 3 months using the modified Rankin Scale (mRS). Arginase-1 was released into the CSF of SAH patients whereas this enzyme was undetectable in controls. Compared to patients without CVS, arginase-1 levels were higher in CVS patients until day 14 after clinical event. The well-known surrogate parameter for arginase acitivity, the L-arginine to L-ornithine ratio (Arg/Orn), correlated with CSF arginase-1 levels. Arg/Orn was reduced in patients with CVS from disease onset (days 1–3, p = 0.0009) until day 14. Logistic regression analysis of early Arg/Orn was predictive for CVS (p = 0.008) and DCI (p = 0.035), independent of age, Hunt and Hess grade, and intraventricular blood. Arg/Orn < 2.71 at disease onset predicted CVS with a sensitivity of 86.7% and specificity of 72.2%. Arg/Orn ≥ 2.71 predicted excellent functional outcome. We propose a novel mechanism contributing to NO deprivation during SAH: arginase-1 is released from erythrocytes into the CSF, leading to L-arginine consumption and reduced NO bioavailability. Furthermore, Arg/Orn is a robust predictor for occurrence of CVS, DCI, and functional outcome 3 months after aneurysmal SAH. Our data provide a novel prognostic biomarker and may contribute to the development of novel therapeutic strategies in SAH. Clinical Trial Registration-URL: http://www.drks.de. Unique identifier: DRKS00015293, date of registration: 13.09.2018.

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Associations between endothelin polymorphisms and aneurysmal subarachnoid hemorrhage, clinical vasospasm, delayed cerebral ischemia, and functional outcome

Journal of Neurosurgery ◽

10.3171/2016.12.jns162594 ◽

2018 ◽

Vol 128 (5) ◽

pp. 1311-1317 ◽

Cited By ~ 6

Author(s):

Christoph J. Griessenauer ◽

Robert M. Starke ◽

Paul M. Foreman ◽

Philipp Hendrix ◽

Mark R. Harrigan ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Functional Outcome ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Multivariate Logistic Regression Analysis ◽

Renin Angiotensin System ◽

Nucleotide Polymorphisms ◽

Endothelin 1 ◽

Potent Vasoconstrictor

OBJECTIVEEndothelin-1, a potent vasoconstrictor, and its receptors may be involved in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH), clinical vasospasm, delayed cerebral ischemia (DCI), and functional outcome following aSAH. In the present study, common endothelin single nucleotide polymorphisms (SNPs) and their relation to aSAH were evaluated.METHODSBlood samples from all patients enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study were used for genetic evaluation. The CARAS study prospectively enrolled patients with aSAH at 2 academic institutions in the US from 2012 to 2015. Common endothelin SNPs were detected using 5′ exonnuclease (TaqMan) genotyping assays. Analysis of associations between endothelin SNPs and aSAH and its clinical sequelae was performed.RESULTSSamples from 149 patients with aSAH and 50 controls were available for analysis. In multivariate logistic regression analysis, the TG (odds ratio [OR] 2.102, 95% confidence interval [CI] 1.048–4.218, p = 0.036) and TT genotypes (OR 7.884, 95% CI 1.003–61.995, p = 0.05) of the endothelin-1 T/G SNP (rs1800541) were significantly associated with aSAH. There was a dominant effect of the G allele (CG/GG genotypes; OR 4.617, 95% CI 1.311–16.262, p = 0.017) of the endothelin receptor A G/C SNP (rs5335) on clinical vasospasm. Endothelin SNPs were not associated with DCI or functional outcome.CONCLUSIONSCommon endothelin SNPs were found to be associated with presentation with aSAH and clinical vasospasm. Further studies are required to elucidate the relevant pathophysiology and its potential implications in the treatment of patients with aSAH.

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Correlation between angiographic transit times and neurological status on admission in patients with aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2015.4.jns15134 ◽

2016 ◽

Vol 124 (4) ◽

pp. 1093-1099 ◽

Cited By ~ 9

Author(s):

Alexander Ivanov ◽

Andreas Linninger ◽

Chih-Yang Hsu ◽

Sepideh Amin-Hanjani ◽

Victor A. Aletich ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Artery ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Clinical Information ◽

Control Group ◽

Angiography Suite ◽

Transit Times ◽

Significant Difference ◽

Group A ◽

Group B

OBJECT The use of digital subtraction angiography (DSA) for semiquantitative cerebral blood flow(CBF) assessment is a new technique. The aim of this study was to determine whether patients with aneurysmal subarachnoid hemorrhage (aSAH) with higher Hunt and Hess grades also had higher angiographic contrast transit times (TTs) than patients with lower grades. METHODS A cohort of 30 patients with aSAH and 10 patients without aSAH was included. Relevant clinical information was collected. A method to measure DSA TTs by color-coding reconstructions from DSA contrast-intensity images was applied. Regions of interest (ROIs) were chosen over major cerebral vessels. The estimated TTs included time-to-peak from 0% to 100% (TTP0–100), TTP from 25% to 100% (TTP25–100), and TT from 100% to 10% (TT100–10) contrast intensities. Statistical analysis was used to compare TTs between Group A (Hunt and Hess Grade I-II), Group B (Hunt and Hess Grade III-IV), and the control group. The correlation coefficient was calculated between different ROIs in aSAH groups. RESULTS There was no difference in demographic factors between Group A (n = 10), Group B (n = 20), and the control group (n = 10). There was a strong correlation in all TTs between ROIs in the middle cerebral artery (M1, M2) and anterior cerebral artery (A1, A2). There was a statistically significant difference between Groups A and B in all TT parameters for ROIs. TT100–10 values in the control group were significantly lower than the values in Group B. CONCLUSIONS The DSA TTs showed significant correlation with Hunt and Hess grades. TT delays appear to be independent of increased intracranial pressure and may be an indicator of decreased CBF in patients with a higher Hunt and Hess grade. This method may serve as an indirect technique to assess relative CBF in the angiography suite.

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Cerebrospinal fluid macrophage migration inhibitory factor: a potential predictor of cerebral vasospasm and clinical outcome after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2019.6.jns19613 ◽

2020 ◽

Vol 133 (6) ◽

pp. 1786-1791 ◽

Cited By ~ 1

Author(s):

Kevin Kwan ◽

Orseola Arapi ◽

Katherine E. Wagner ◽

Julia Schneider ◽

Heustein L. Sy ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Vasospasm ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Significant Difference

OBJECTIVEIn patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration.METHODSIn this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures.RESULTSTwenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119).CONCLUSIONSPreliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

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Abstract T P352: Dantrolene for the Prevention and Treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage - A Randomized Placebo-Controlled Trial to Assess Safety, Tolerability and Feasibility

Stroke ◽

10.1161/str.45.suppl_1.tp352 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Susanne Muehlschlegel ◽

Raphael Carandang ◽

Wiley Hall ◽

Kini Nisha ◽

Saef Izzy ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Liver Toxicity ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Controlled Trial ◽

Statistical Significance ◽

Delayed Cerebral Ischemia ◽

Double Blind ◽

Outcome Differences ◽

Infusion Period

Introduction: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) after aneurysmal subarachnoid hemorrhage (aSAH) in humans. We evaluated safety/tolerability and feasibility of intravenous dantrolene (IV-D) after aSAH. Methods: In this single-center, randomized, double-blind, placebo-controlled trial, 31 patients with acute aSAH were randomized to IV-D 1.25 mg IV every 6 hours x 7 days (n=16) or placebo (n=15). Primary endpoint was incidence of hyponatremia (sNa ≤ 134 mmol/L) and liver toxicity (% patients with ALT, AST and AlkPhos >5x upper limit of normal). Secondary safety endpoints included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored by clinical, transcranial Doppler (TCD) or angiographic cVSP occurrence, delayed cerebral ischemia (DCI) and 3-month modified-Rankin-Scale, Glasgow Outcome Scale and Barthel Index. Statistical analysis was performed using non-parametric tests, generalized estimating equations and mixed models. Results: Between IV-D vs. placebo, no differences were observed in the primary outcome (hyponatremia: 44% vs. 67% [p=0.29]; liver toxicity 6% vs. 0% [p=1.0]). Numerically more AEs and SAEs were seen in the IV-D group, but did not reach statistical significance (16 vs. 5 AEs, of which 5 vs. 2 were severe; RR 2.2; 95% CI 0.7-6.7; p=0.16). Three IV-D vs. two placebo patients reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain edema requiring osmotherapy. No differences in angiographic, TCD, clinical cVSP, DCI, or 3-month functional outcomes were seen. Quantitative angiogram analysis revealed a trend towards increased vessel diameters in the IV-D group after the 7-day infusion-period (p=0.05). Conclusion: In this small trial, IV-Dantrolene after aSAH was feasible, tolerable and safe, but was underpowered to show efficacy or outcome differences.

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Randomized, placebo-controlled, double-blind, pilot trial to investigate safety and efficacy of Cerebrolysin in patients with aneurysmal subarachnoid hemorrhage

BMC Neurology ◽

10.1186/s12883-020-01908-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Peter Y. M. Woo ◽

Joanna W. K. Ho ◽

Natalie M. W. Ko ◽

Ronald P. T. Li ◽

Leo Jian ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Adverse Effects ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Pilot Trial ◽

Delayed Cerebral Ischemia ◽

Trial Registration ◽

Study Group ◽

Double Blind ◽

Link Type ◽

Significant Difference

Asbtract Background There are limited neuroprotective treatment options for patients with aneurysmal subarachnoid hemorrhage (SAH). Cerebrolysin, a brain-specific proposed pleiotropic neuroprotective agent, has been suggested to improve global functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of administering Cerebrolysin for SAH patients. Methods This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. Fifty patients received either daily Cerebrolysin (30 ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Scale (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the modified Ranking Scale (mRS), the Montreal Cognitive Assessment (MOCA) score, occurrence of adverse effects and the occurrence of delayed cerebral ischemia (DCI). Results No severe adverse effects or mortality attributable to Cerebrolysin were observed. No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 1.49; 95% confidence interval (CI): 0.43–5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79–15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28–2.59). Conclusions Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients. Clinical trial registration Name of Registry: ClinicalTrials.gov Trial Registration Number: NCT01787123. Date of Registration: 8th February 2013.

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Deviation from Dynamic and Personalized Optimal Blood Pressure Targets is Associated With Worse Functional Outcomes After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1093/neuros/nyz310_186 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Andrew Silverman ◽

Sreeja Kodali ◽

Sumita Strander ◽

Emily Gilmore ◽

Alexandra Kimmel ◽

...

Keyword(s):

Blood Pressure ◽

Subarachnoid Hemorrhage ◽

Functional Outcome ◽

Functional Outcomes ◽

Near Infrared ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Time Correlation ◽

Blood Pressure Targets ◽

Percent Time

Abstract INTRODUCTION Effective blood pressure (BP) management after aneurysmal subarachnoid hemorrhage (aSAH) is critical for maintaining optimal cerebral perfusion and protecting the brain from further injury. How to best manage BP during the early stages of aSAH remains uncertain. In this study, we calculated individualized BP thresholds at which cerebral autoregulation was best preserved. We analyzed how deviating from these limits correlates with functional outcome. METHODS We prospectively enrolled 31 patients with aSAH. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy (NIRS)-derived tissue oxygenation – a surrogate for cerebral blood flow – as well as intracranial pressure (ICP) in response to changes in mean arterial pressure (MAP) using time-correlation analysis. The resulting autoregulatory indices were used to trend BP ranges at which autoregulation was most preserved. The percent time that MAP exceeded limits of autoregulation (LA) was calculated for each patient. Functional outcome was assessed using the modified Rankin Scale (mRS) at discharge and 90 d. Associations with outcome were analyzed using ordinal multivariate logistic regression. RESULTS Personalized LA were computed in all patients (age 57.5, 23F, mean WFNS 2, monitoring time 67.8 h). Optimal BP and LA were calculated on average for 89.5% of the total monitoring period. ICP- and NIRS-derived optimal pressures and LA strongly correlated with one another (P < .0001). Percent time that MAP deviated from LA significantly associated with worse functional outcome at discharge (NIRS P = .001, ICP P = .004) and 90 d (NIRS P = .002, ICP P = .003), adjusting separately for age, WFNS, vasospasm, or delayed cerebral ischemia. CONCLUSION Both invasive (ICP) and non-invasive (NIRS) determination of personalized BP thresholds for aSAH patients is feasible, and these 2 approaches revealed significant collinearity. Exceeding individualized autoregulatory thresholds may increase the risk of poor functional outcomes.

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