Controlled transient hypercapnia: a novel approach for the treatment of delayed cerebral ischemia after subarachnoid hemorrhage?

2014 ◽  
Vol 121 (5) ◽  
pp. 1056-1062 ◽  
Author(s):  
Thomas Westermaier ◽  
Christian Stetter ◽  
Ekkehard Kunze ◽  
Nadine Willner ◽  
Judith Holzmeier ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Near Infrared ◽  
Therapeutic Potential ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Rebound Effect ◽  
Delayed Cerebral Ischemia ◽  
Physiological Mechanism ◽  
Tissue Oxygen Saturation ◽  
Poor Grade ◽  
Continuous Drainage

Object The authors undertook this study to investigate whether the physiological mechanism of cerebral blood flow (CBF) regulation by alteration of the arterial partial pressure of carbon dioxide (PaCO2) can be used to increase CBF after aneurysmal subarachnoid hemorrhage (aSAH). Methods In 6 mechanically ventilated patients with poor-grade aSAH, the PaCO2 was first decreased to 30 mm Hg by modification of the respiratory rate, then gradually increased to 40, 50 and 60 mm Hg for 15 minutes each setting. Thereafter, the respirator settings were returned to baseline parameters. Intracerebral CBF measurement and brain tissue oxygen saturation (StiO2), measured by near-infrared spectroscopy (NIRS), were the primary and secondary end points. Intracranial pressure (ICP) was controlled by external ventricular drainage. Results A total of 60 interventions were performed in 6 patients. CBF decreased to 77% of baseline at a PaCO2 of 30 mm Hg and increased to 98%, 124%, and 143% at PaCO2 values of 40, 50, and 60 mm Hg, respectively. Simultaneously, StiO2 decreased to 94%, then increased to 99%, 105%, and 111% of baseline. A slightly elevated delivery rate of cerebrospinal fluid was noticed under continuous drainage. ICP remained constant. After returning to baseline respirator settings, both CBF and StiO2 remained elevated and only gradually returned to pre-hypercapnia values without a rebound effect. None of the patients developed secondary cerebral infarction. Conclusions Gradual hypercapnia was well tolerated by poor-grade SAH patients. Both CBF and StiO2 reacted with a sustained elevation upon hypercapnia; this elevation outlasted the period of hypercapnia and only slowly returned to normal without a rebound effect. Elevations of ICP were well compensated by continuous CSF drainage. Hypercapnia may yield a therapeutic potential in this state of critical brain perfusion. Clinical trial registration no.: NCT01799525 (ClinicalTrials.gov).

scholarly journals Dose Optimization Study of Therapeutic Hypercapnia for Prevention of Secondary Ischemia After Severe Subarachnoid Hemorrhage

2021 ◽  
Author(s):  
Christian Stetter ◽  
Franziska Weidner ◽  
Nadine Lilla ◽  
Judith Weiland ◽  
Ekkehard Kunze ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Rebound Effect ◽  
Comparative Trial ◽  
Target Range ◽  
Tissue Oxygen Saturation ◽  
Enhancing Effect ◽  
Poor Grade ◽  
Arterial Blood

Abstract BackgroundAim of this study was to investigate the time point at which the cerebral blood flow (CBF) enhancing effect of controlled hypercapnia in patients with severe aneurysmal subarachnoid hemorrhage (SAH) starts to extenuate. This point is assumed to be the time at which buffer systems become active and annihilate a possible therapeutic effect. MethodsIn this prospective interventional study in a neurosurgical ICU the arterial partial pressure of carbon dioxide (PaCO2) was increased to a target range of 50 - 55 mmHg for 120 minutes by modification of the respiratory minute volume (RMV) one time a day between day 4 and 14 in 12 mechanically ventilated poor-grade SAH-patients. Arterial blood gases were measured every 15 minutes. CBF and brain tissue oxygen saturation (StiO2) were the primary and secondary end points. Intracranial pressure (ICP) was controlled by an external ventricular drainage. ResultsUnder continuous hypercapnia (PaCO2 of 53.17 ± 5.07), CBF was significantly elevated between 15 and 120 minutes after the start of hypercapnia. During the course of the trial intervention, cardiac output also increased significantly. To assess the direct effect of hypercapnia on brain perfusion, the increase of CBF was corrected by the parallel increase of cardiac output. The maximum direct CBF enhancing effect of hypercapnia of 31% was noted at 45 minutes after the start of hypercapnia. Thereafter, the CBF enhancing slowly declined. No relevant adverse effects were observed. Conclusion CBF and StiO2 reproducibly increased by controlled hypercapnia in all patients. After 45 minutes, the curve of CBF enhancement showed an inflection point when corrected by cardiac output. Temporary hypercapnia of 45 minutes is, thus, likely to be the optimum duration for a therapeutic use and for a controlled comparative trial. Longer intervals bear the risk of a negative rebound effect after return to normal ventilation parameters and may be counterproductive inducing ischemia in a state of critical perfusion after SAH. Trial registrationThe study was approved by the institutional ethics committee (AZ 230/14) and registered at ClinicalTrials.gov (Trial-ID: NCT01799525). Registered 01 January 2015. Retrospectively registered.

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

Neurosurgery ◽  
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.

scholarly journals Clinical evidence of efficacy of simvastatin for aneurysmal subarachnoid hemorrhage

2017 ◽  
Vol 45 (6) ◽  
pp. 2128-2138
Author(s):  
Jinghui Lin ◽  
Houxian Liu ◽  
Jianjun Jiang ◽  
Conglin Jia ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Therapeutic Potential ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Large Population ◽  
Delayed Cerebral Ischemia ◽  
Acute Stage ◽  
Cochrane Library ◽  
Eligibility Criteria ◽  
All Cause Mortality ◽  
The Cochrane Library

Objective The present study was performed to explore the therapeutic potential of simvastatin in subarachnoid hemorrhage (SAH) in the context of the Simvastatin in Aneurysmal Subarachnoid Hemorrhage (STASH) trial. Methods MEDLINE, EMBASE, and the Cochrane Library were searched for all randomized controlled trials (RCTs) investigating the therapeutic effect of simvastatin on aneurysmal SAH. We applied a random-effects model to calculate the data. Results Five RCTs involving 951 patients met the eligibility criteria. We found no statistically significant effects on vasospasm detected by transcranial cerebral Doppler (relative risk [RR], 0.91; 95% confidence interval [CI], 0.55–1.49), delayed cerebral ischemia (DCI) (RR, 0.85; 95% CI, 0.63–1.14), or all-cause mortality (RR, 1.02; 95% CI, 0.67–1.54). Subgroup analysis showed that these consolidated results were stable at different doses, different times to start of treatment, and different courses of treatment in all included RCTs. Sensitivity analysis showed that the STASH trial, which had a large population, did not influence the consolidated results of all three outcomes. Conclusions Simvastatin showed no benefits in decreasing the incidence of vasospasm, DCI, or all-cause mortality after aneurysmal SAH. We conclude that patients with SAH should not be treated routinely with simvastatin during the acute stage.

Assessment of lipoprotein-associated phospholipase A2 level and its changes in the early stages as predictors of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage

2020 ◽  
Vol 132 (1) ◽  
pp. 62-68 ◽  
Author(s):  
Chen-Yu Ding ◽  
Han-Pei Cai ◽  
Hong-Liang Ge ◽  
Liang-Hong Yu ◽  
Yuan-Xiang Lin ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Phospholipase A2 ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Poor Grade ◽  
Early Stages ◽  
Fisher Grade ◽  
The Relationship

OBJECTIVEThe relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and various cardiovascular and cerebrovascular diseases is inconsistent. However, the connection between Lp-PLA2 level and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. The objective of this study was to investigate the relationships between the Lp-PLA2 levels in the early stages of aSAH and the occurrence of DCI.METHODSThe authors evaluated 114 patients with aSAH who were enrolled into a prospective observational cohort study. Serum Lp-PLA2 level at admission (D0), on the first morning (D1), and on the second morning of hospitalization (D2) were determined using commercial enzyme-linked immunosorbent assay kits. The relationship between Lp-PLA2 levels and DCI was analyzed.RESULTSForty-three patients with aSAH (37.72%) experienced DCI. Mean serum Lp-PLA2 level decreased from 183.06 ± 61.36 μg/L at D0 (D0 vs D1, p = 0.303), to 175.32 ± 51.49 μg/L at D1 and 167.24 ± 54.10 μg/L at D2 (D0 vs D2, p = 0.040). The Lp-PLA2 level changes (D0-D1 and D0-D2) were comparable between patients with and without DCI. Multivariate model analysis revealed Lp-PLA2 level (D0) > 200 μg/L was a more significant factor of DCI compared with Lp-PLA2 (D1) and Lp-PLA2 (D2), and was a strong predictor of DCI (odds ratio [OR] 6.24, 95% confidence interval [CI] 2.05–18.94, p = 0.001) after controlling for World Federation of Neurosurgical Societies (WFNS) grade (OR 3.35, 95% CI 1.18–9.51, p = 0.023) and modified Fisher grade (OR 6.07, 95% CI 2.03–18.14, p = 0.001). WFNS grade (area under the curve [AUC] = 0.792), modified Fisher grade (AUC = 0.731), and Lp-PLA2 level (D0; AUC = 0.710) were all strong predictors of DCI. The predictive powers of WFNS grade, modified Fisher grade, and Lp-PLA2 (D0) were comparable (WFNS grade vs Lp-PLA2: p = 0.233; modified Fisher grade vs Lp-PLA2: p = 0.771). The poor-grade patients with Lp-PLA2 (D0) > 200 μg/L had significantly worse DCI survival rate than poor-grade patients with Lp-PLA2 (D0) ≤ 200 μg/L (p < 0.001).CONCLUSIONSThe serum level of Lp-PLA2 was significantly elevated in patients with DCI, and decreased within the first 2 days after admission. Lp-PLA2 in the early stages of aSAH might be a novel predictive biomarker for the occurrence of DCI.

scholarly journals Invasive and Noninvasive Multimodal Bedside Monitoring in Subarachnoid Hemorrhage: A Review of Techniques and Available Data

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Baback Arshi ◽  
William J. Mack ◽  
Benjamin Emanuel
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Near Infrared ◽  
Tissue Oxygenation ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Treatment Options ◽  
Delayed Cerebral Ischemia ◽  
Jugular Bulb ◽  
Accurate Diagnosis ◽  
Cerebral Vasculature ◽  
Brain Tissue Oxygenation

Delayed-cerebral ischemia is a major cause of morbidity and mortality in the setting of aneurysmal subarachnoid hemorrhage. Despite extensive research efforts and a breadth of collective clinical experience, accurate diagnosis of vasospasm remains difficult, and effective treatment options are limited. Classically, diagnosis has focused on imaging assessment of the cerebral vasculature. Recently, invasive and noninvasive bedside techniques designed to characterize relevant hemodynamic and metabolic alterations have gained substantial attention. Such modalities include microdialysis, brain tissue oxygenation, jugular bulb oximetry, thermal diffusion cerebral blood flow, and near-infrared spectroscopy. This paper reviews these modalities and examines data pertinent to the diagnosis and management of cerebral vasospasm.

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