Neurocritical Care Has Matured and it is Time to Raise the Bar…Yet Again

Background

Management of delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is difficult and still carries controversies. In this study, the effect of therapeutic hypervolemia, hemodilution, and hypertension (HHH-therapy) on cerebral blood flow (CBF) was assessed by xenon-enhanced computerized tomography (XeCT) hypothesizing an increase in CBF in poorly perfused regions.

Methods

Bedside XeCT measurements of regional CBF in mechanically ventilated SAH patients were routinely scheduled for day 0–3, 4–7, and 8–12. At clinical suspicion of DCI, patients received 5-day HHH-therapy. For inclusion, XeCT was required at 0–48 h before start of HHH (baseline) and during therapy. Data from corresponding time-windows were also collected for non-DCI patients.

Results

Twenty patients who later developed DCI were included, and twenty-eight patients without DCI were identified for comparison. During HHH, there was a slight nonsignificant increase in systolic blood pressure (SBP) and a significant reduction in hematocrit. Median global cortical CBF for the DCI group increased from 29.5 (IQR 24.6–33.9) to 38.4 (IQR 27.0–41.2) ml/100 g/min (P = 0.001). There was a concomitant increase in regional CBF of the worst vascular territories, and the proportion of area with blood flow below 20 ml/100 g/min was significantly reduced. Non-DCI patients showed higher CBF at baseline, and no significant change over time.

Conclusions

HHH-therapy appeared to increase global and regional CBF in DCI patients. The increase in SBP was small, while the decrease in hematocrit was more pronounced, which may suggest that intravascular volume status and rheological effects are of importance. XeCT may be potentially helpful in managing poor-grade SAH patients.

     

Changes in Cerebral Perfusion with Induced Hypertension in Aneurysmal Subarachnoid Hemorrhage: A Pilot and Feasibility Study

Background

The effects of induced hypertension (IH) on cerebral perfusion after subarachnoid hemorrhage (SAH) are unclear. The objectives of this investigation are to: (1) determine whether there are differences in cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) measured with computed tomography perfusion (CTP) before and after IH; (2) evaluate differences in the presence of infarction and clinical outcome between patients with and without IH.

Methods

We performed a retrospective cohort analysis of 25 aneurysmal SAH patients. IH was initiated as per the standard institutional protocol when patients showed clinical symptoms of delayed cerebral ischemia (DCI). Differences in CBF, CBV, and MTT between early (<72 h after aneurysm rupture) and late (7–10 days after aneurysm rupture) CTP were quantified in patients with (n = 13) and without IH (n = 12). Outcome measures included cerebral infarction and clinical outcome at 3 months.

Results

Early MTT was significantly greater in the IH group compared to the no-IH group. There was no difference in early or late CBV or CBF between the two groups. In patients that received IH, there was a significant decrease in MTT between the early (7.0 ± 1.2 s) and late scans (5.8 ± 1.6 s; p = 0.005). There was no difference in the incidence of infarction (5/13 vs. 2/11) or poor outcome (3/11 vs. 6/13) between the IH and no-IH groups, respectively (p > 0.05).

Conclusions

Elevated MTT is a significant factor for the development of DCI in patients eventually requiring IH therapy and is improved by IH treatment. Therapies to prevent DCI and improve clinical outcome may need to be initiated earlier, when cerebral perfusion abnormalities are first identified.

     

SANGUINATE™ (PEGylated Carboxyhemoglobin Bovine) Improves Cerebral Blood Flow to Vulnerable Brain Regions at Risk of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Background

Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been linked to focal reductions in cerebral blood flow (CBF) and microvascular impairments in oxygen delivery. Effective therapies that restore flow and oxygen transport to vulnerable brain regions are currently lacking. SANGUINATE is a dual-action carbon monoxide-releasing and hemoglobin-based oxygen transfer agent with efficacy in animal models of focal brain ischemia and tolerability in patients with sickle cell disease.

Methods

We performed a safety and proof-of-principle study in 12 SAH patients at risk of DCI across three escalating doses (160, 240, and 320 mg/kg). We used ¹⁵O-PET (performed at baseline, after SANGUINATE and at 24 h) to evaluate efficacy for improving CBF and restoring flow–metabolism balance (assessed by oxygen extraction fraction [OEF]) to vulnerable regions (defined as baseline OEF ≥ 0.50).

Results

SANGUINATE resulted in a transient rise in mean arterial pressure (116 ± 15–127 ± 13 mm Hg, p = 0.001) that normalized by 24 h and allowed three patients with DCI to be weaned off vasopressors. No adverse events were noted during infusion. Global CBF did not rise (43 ± 8–46 ± 9 ml/100 g/min) although a trend was seen at the highest dose (45 ± 7–51 ± 9, p = 0.044). However, a significant 16% rise in regional CBF associated with reduction in OEF was seen in vulnerable regions, but did not persist at 24 h.

Conclusions

We demonstrated that this novel agent can improve regional CBF and may improve oxygen supply–demand balance. Clinical studies (likely with repeat dosing) are required to evaluate whether this effect can prevent DCI or cerebral infarction.

     

Default Mode Network Perfusion in Aneurysmal Subarachnoid Hemorrhage

Background

The etiology of altered consciousness in patients with high-grade aneurysmal subarachnoid hemorrhage (SAH) is not thoroughly understood. We hypothesized that decreased cerebral blood flow (CBF) in brain regions critical to consciousness may contribute.

Methods

We retrospectively evaluated arterial-spin labeled (ASL) perfusion magnetic resonance imaging (MRI) measurements of CBF in 12 patients with aneurysmal SAH admitted to our neurocritical care unit. CBF values were analyzed within gray matter nodes of the default mode network (DMN), whose functional integrity has been shown to be necessary for consciousness. DMN nodes studied were the bilateral medial prefrontal cortices, thalami, and posterior cingulate cortices. Correlations between nodal CBF and admission Glasgow Coma Scale (GCS) score, admission Hunt and Hess (HH) class, and GCS score at the time of MRI (MRI GCS) were tested.

Results

Spearman’s correlation coefficients were not significant when comparing admission GCS, admission HH, and MRI GCS versus nodal CBF (p > 0.05). However, inter-rater reliability for nodal CBF was high (r = 0.71, p = 0.01).

Conclusions

In this retrospective pilot study, we did not identify significant correlations between CBF and admission GCS, admission HH class, or MRI GCS for any DMN node. Potential explanations for these findings include small sample size, ASL data acquisition at variable times after SAH onset, and CBF analysis in DMN nodes that may not reflect the functional integrity of the entire network. High inter-rater reliability suggests ASL measurements of CBF within DMN nodes are reproducible. Larger prospective studies are needed to elucidate whether decreased cerebral perfusion contributes to altered consciousness in SAH.

     

Relationship Between Cardiac Dysfunction and Cerebral Perfusion in Patients with Aneurysmal Subarachnoid Hemorrhage

Introduction

Cardiac dysfunction may occur after aneurysmal subarachnoid hemorrhage (aSAH). Although it is associated with poor outcome, the pathophysiological mechanism of this association remains unclear. We investigated the relationship between cardiac function and cerebral perfusion in patients with aSAH.

Methods

We studied 72 aSAH patients admitted within 72 h after ictus with echocardiography and cerebral CT perfusion within 24 h after admission. Cardiac dysfunction was defined as myocardial wall motion abnormalities or positive troponin. In patients with and without cardiac dysfunction, we calculated the mean perfusion [cerebral blood flow (CBF) and time-to-peak (TTP)] in standard regions of interest and calculated differences with 95 % confidence intervals (95 % CI).

Results

In 35 patients with cardiac dysfunction minimal CBF was 15.83 mL/100 g/min compared to 18.59 in 37 without (difference of means ?2.76; 95 % CI ?5.43 to ?0.09). Maximal TTP was 26.94 s for patients with and 23.10 s for patients without cardiac dysfunction (difference of means 3.84; 95 % CI 1.63–6.05). Mean global CBF was 21.71 mL/100 g/min for patients with cardiac dysfunction and 24.67 mL/100 g/min for patients without cardiac dysfunction (?2.96; 95 % CI ?6.19 to 0.27). Mean global TTP was 25.27 s for patients with cardiac dysfunction and 21.26 for patients without cardiac dysfunction (4.01; 95 % CI 1.95–6.07).

Conclusion

aSAH patients with cardiac dysfunction have decreased focal and global cerebral perfusion. Further studies should evaluate whether this relation is explained by a direct effect of cardiac dysfunction on cerebral circulation or by an external determinant, such as a hypercatecholaminergic or hypometabolic state, influencing both cardiac function and cerebral perfusion.

     

The Role of Platelet Activation and Inflammation in Early Brain Injury Following Subarachnoid Hemorrhage

Background

Early brain injury (EBI) following aneurysmal subarachnoid hemorrhage (SAH) is an important predictor of poor functional outcome, yet the underlying mechanism is not well understood. Animal studies suggest that platelet activation and inflammation with subsequent microthrombosis and ischemia may be a mechanism of EBI.

Methods

A prospective, hypothesis-driven study of spontaneous, SAH patients and controls was conducted. Platelet activation [thromboelastography maximum amplitude (MA)] and inflammation [C-reactive protein (CRP)] were measured serially over time during the first 72 h following SAH onset. Platelet activation and inflammatory markers were compared between controls and SAH patients with mild [Hunt–Hess (HH) 1–3] versus severe (HH 4–5) EBI. The association of these biomarkers with 3-month functional outcomes was evaluated.

Results

We enrolled 127 patients (106 SAH; 21 controls). Platelet activation and CRP increased incrementally with worse EBI/HH grade, and both increased over 72 h (all P < 0.01). Both were higher in severe versus mild EBI (MA 68.9 vs. 64.8 mm, P = 0.001; CRP 12.5 vs. 1.5 mg/L, P = 0.003) and compared to controls (both P < 0.003). Patients with delayed cerebral ischemia (DCI) had more platelet activation (66.6 vs. 64.9 in those without DCI, P = 0.02) within 72 h of ictus. At 3 months, death or severe disability was more likely with higher levels of platelet activation (mRS4–6 OR 1.18, 95 % CI 1.05–1.32, P = 0.007) and CRP (mRS4–6 OR 1.02, 95 % CI 1.00–1.03, P = 0.041).

Conclusions

Platelet activation and inflammation occur acutely after SAH and are associated with worse EBI, DCI and poor 3-month functional outcomes. These markers may provide insight into the mechanism of EBI following SAH.

     

Biomarkers of Glycocalyx Injury are Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Case Series Supporting a New Hypothesis

Background

Delayed cerebral ischemia (DCI) contributes to morbidity following aneurysmal subarachnoid hemorrhage; however, its etiology remains poorly understood. DCI is not only a consequence of angiographic vasospasm, but also involves microthrombosis and neuroinflammation, two events with unexplained phenomenology. The vascular endothelial glycocalyx mediates platelet aggregation and endothelial cell-leukocyte interactions and may play an important role in DCI pathogenesis.

Methods

We present a case series in which we conducted multiplex and singlet enzyme-linked immunosorbent assays of endothelial, glycocalyx, inflammatory, and neuroinjury proteins in both CSF and plasma in three patients during active DCI following SAH. Samples were obtained at baseline following surgical repair of SAH, and again at DCI onset. CSF was sampled at the same time points from in situ external ventricular drains.

Results

DCI was associated with significant elevations of soluble markers of endotheliopathy, including vascular adhesion protein-1, soluble fractions of endothelial cell adhesion molecules (CAMs), procoagulant tissue factor, and specific markers of glycocalyx injury, including syndecan-1, and CD44. These phenomena were also associated with an elevation of both circulating and CSF matrix metalloproteinases, which are known to cleave components of the glycocalyx. Elevation of vascular CAM-1 in the CSF with DCI indicated these events were possibly associated with the breakdown of brain microvasculature integrity.

Conclusions

These preliminary data support the hypothesis that glycocalyx injury occurs in SAH, and might contribute to DCI by regulating cerebral microthrombosis and delayed neuroinflammation.

     

The Effect of Packed Red Blood Cell Transfusion on Cerebral Oxygenation and Metabolism After Subarachnoid Hemorrhage

Background

Anemia adversely affects cerebral oxygenation and metabolism after subarachnoid hemorrhage (SAH) and is also associated with poor outcome. There is limited evidence to support the use of packed red blood cell (PRBC) transfusion to optimize brain homeostasis after SAH. The aim of this study was to investigate the effect of transfusion on cerebral oxygenation and metabolism in patients with SAH.

Methods

This was a prospective observational study in a neurological intensive care unit of a university hospital. Nineteen transfusions were studied in 15 consecutive patients with SAH that underwent multimodality monitoring (intracranial pressure, brain tissue oxygen, and cerebral microdialysis). Data were collected at baseline and for 12 h after transfusion. The relationship between hemoglobin (Hb) change and lactate/pyruvate ratio (LPR) orbrain tissue oxygen (PbtO₂) was tested using univariate and multivariable analyses.

Results

PRBC transfusion was administered on the median post-bleed day 8. The average Hb concentration at baseline was 8.1 g/dL and increased by 2.2 g/dL after transfusion. PbtO₂ increased between hours 2 and 4 post-transfusion and this increase was maintained until hour 10. LPR did not change significantly during the 12-h monitoring period. After adjusting for SpO₂, cerebral perfusion pressure, and LPR, the change in Hb concentration was independently and positively associated with a change in PbtO₂ (adjusted b estimate = 1.39 [95 % confidence interval 0.09–2.69]; P = 0.04). No relationship between the change in Hb concentration and LPR was found.

Conclusions

PRBC transfusion resulted in PbtO₂ improvement without a clear effect on cerebral metabolism prior to SAH.

     

Controlled Hypercapnia Enhances Cerebral Blood Flow and Brain Tissue Oxygenation After Aneurysmal Subarachnoid Hemorrhage: Results of a Phase 1 Study

Background

This study investigated if cerebral blood flow (CBF) regulation by changes of the arterial partial pressure of carbon dioxide (PaCO₂) can be used therapeutically to increase CBF and improve neurological outcome after subarachnoid hemorrhage (SAH).

Methods

In 12 mechanically ventilated poor-grade SAH-patients, a daily trial intervention was performed between day 4 and 14. During this intervention, PaCO₂ was decreased to 30 mmHg and then gradually increased to 40, 50, and 60 mmHg in 15-min intervals by modifications of the respiratory minute volume. CBF and brain tissue oxygen saturation (StiO₂) were the primary and secondary endpoints. Intracranial pressure was controlled by an external ventricular drainage.

Results

CBF reproducibly decreased during hyperventilation and increased to a maximum of 141 ± 53 % of baseline during hypercapnia (PaCO₂ 60 mmHg) on all days between day 4 and 14 after SAH. Similarly, StiO₂ increased during hypercapnia. CBF remained elevated within the first hour after resetting ventilation to baseline parameters and no rebound effect was observed within this time-span. PaCO₂-reactivities of CBF and StiO₂ were highest between 30 and 50 mmHg and slightly decreased at higher levels.

Conclusion

CBF and StiO₂ reproducibly increased by controlled hypercapnia of up to 60 mmHg even during the period of the maximum expected vasospasm. The absence of a rebound effect within the first hour after hypercapnia indicates that an improvement of the protocol is possible. The intervention may yield a therapeutic potential to prevent ischemic deficits after aneurysmal SAH.

     

Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage

Background

Statins may promote vasodilation following subarachnoid hemorrhage (SAH) and improve the response to blood pressure elevation. We sought to determine whether simvastatin increases cerebral blood flow (CBF) and alters the response to induced hypertension after SAH.

Methods

Statin-naïve patients admitted <72 h after WFNS ≥2 aneurysmal SAH were randomly assigned to 80 mg simvastatin/day or placebo for 21 days. Regional CBF was measured with quantitative ¹⁵O PET on SAH day 7–10 before and after raising mean arterial pressure (MAP) 20–25 %. Autoregulatory index (AI) was calculated as the ratio of % change in resistance (MAP/CBF) to % change in MAP. Angiography was performed within 24 h of PET. Results are presented as simvastatin vs. placebo.

Results

Thirteen patients received simvastatin and 12 placebo. Clinical characteristics were similar. Moderate or severe angiographic vasospasm occurred in 42 vs. 45 % and delayed cerebral ischemia in 14 vs. 55 % (p = 0.074). During PET studies, MAP (110 ± 10 vs. 111 ± 12), global CBF (41 ± 12 vs. 43 ± 13), and CVR (2.95 ± 1.0 vs. 2.81 ± 1.0) did not differ at baseline. When MAP was raised to 135 ± 7 mm Hg vs. 137 ± 15, global CBF did not change. Global AI did not differ (107 ± 59 vs. 0. 89 ± 52 %, p = 0.68). CBF did not change in regions with low baseline flow or in regions supplied by vessels with angiographic vasospasm in either group. Six-month modified Rankin Scale scores did not differ.

Conclusions

Our data indicate that initiation of therapy with high-dose simvastatin does not alter baseline CBF or response to induced hypertension.

     

Continuous EEG Monitoring for Early Detection of Delayed Cerebral Ischemia in Subarachnoid Hemorrhage: A Pilot Study

Introduction

Early identification of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is a major challenge. The aim of this study was to investigate whether quantitative EEG (qEEG) features can detect DCI prior to clinical or radiographic findings.

Methods

A prospective cohort study was performed in aSAH patients in whom continuous EEG (cEEG) was recorded. We studied 12 qEEG features. We compared the time point at which qEEG changed with the time point that clinical deterioration occurred or new ischemia was noted on CT scan.

Results

Twenty aSAH patients were included of whom 11 developed DCI. The alpha/delta ratio (ADR) was the most promising feature that showed a significant difference in change over time in the DCI group (median ?62 % with IQR ?87 to ?39 %) compared to the control group (median +27 % with IQR ?32 to +104 %, p = 0.013). Based on the ROC curve, a threshold was chosen for a combined measure of ADR and alpha variability (AUC: 91.7, 95 % CI 74.2–100). The median time that elapsed between change of qEEG and clinical DCI diagnosis was seven hours (IQR ?11–25). Delay between qEEG and CT scan changes was 44 h (median, IQR 14–117).

Conclusion

In this study, ADR and alpha variability could detect DCI development before ischemic changes on CT scan was apparent and before clinical deterioration was noted. Implementation of cEEG in aSAH patients can probably improve early detection of DCI.

     

MRI Detection of Cerebral Infarction in Subarachnoid Hemorrhage

Objective

To investigate magnetic resonance imaging (MRI) detection of cerebral infarction (CI) in patients presenting with subarachnoid hemorrhage (SAH).

Background

CI is a well-known complication of SAH that is typically detected on computed tomography (CT). MRI has improved sensitivity for acute CI over CT, particularly with multiple, small, or asymptomatic lesions.

Methods

With IRB approval, 400 consecutive SAH patients admitted to our institution from August 2006 to March 2011 were retrospectively reviewed. Traumatic SAH and secondary SAH were excluded. Data were collected on demographics, cause of SAH, Hunt Hess and World Federation of Neurosurgical Societies grades, and neuroimaging results. MRIs were categorized by CI pattern as single cortical (SC), single deep (SD), multiple cortical (MC), multiple deep (MD), and multiple cortical and deep (MCD).

Results

Among 123 (30.8 %) SAH patients who underwent MRIs during their hospitalization, 64 (52 %) demonstrated acute CI. The mean time from hospital admission to MRI was 5.7 days (range 0–29 days). Among the 64 patients with MRI infarcts, MRI CI pattern was as follows: MC in 20 (31 %), MCD in 18 (28 %), SC in 16 (25 %), SD in 3 (5 %), MD in 2 (3 %), and 5 (8 %) did not have images available for review. Most infarcts detected on MRI (39/64 or 61 %) were not visible on CT.

Conclusions

The use of MRI increases the detection of CI in SAH. Unlike CT studies, MRI-detected CI in SAH tends to involve multiple vascular territories. Studies that rely on CT may underestimate the burden of CI after SAH.

     

Preventive Antibiotics and Delayed Cerebral Ischaemia in Patients with Aneurysmal Subarachnoid Haemorrhage Admitted to the Intensive Care Unit

Introduction

Delayed cerebral ischemia (DCI) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Development of DCI is multifactorial, and inflammation, with or without infection, is one of the factors independently associated with development of DCI and poor outcome. We thus postulated that preventive antibiotics might be associated with a reduced risk of DCI and subsequent poor outcome in aSAH patients.

Methods

We performed a retrospective cohort-study in intensive care units (ICU) of three university hospitals in The Netherlands. We included consecutive aSAH patients with minimal ICU stay of 72 h who received either preventive antibiotics (SDD: selective digestive tract decontamination including systemic cefotaxime or SOD: selective oropharyngeal decontamination) or no preventive antibiotics. DCI was defined as a new hypodensity on CT with no other explanation than DCI. Hazard ratio’s (HR) for DCI and risk ratio’s (RR) for 28-day case-fatality and poor outcome at 3 months were calculated, with adjustment (aHR/aRR) for clinical condition on admission, recurrent bleeding, aneurysm treatment modality and treatment site.

Results

Of 459 included patients, 274 received preventive antibiotics (SOD or SDD) and 185 did not. With preventive antibiotics, the aHR for DCI was 1.0 (95 % CI 0.6–1.8), the aRR for 28-day case-fatality was 1.1 (95 % CI 0.7–1.9) and the aRR for poor functional outcome 1.2 (95 % CI 1.0–1.4).

Conclusions

Preventive antibiotics were not associated with reduced risk of DCI or poor outcome in aSAH patients in the ICU.

     

SSRI/SNRI Use is Not Associated with Increased Risk of Delayed Cerebral Ischemia After aSAH

Background

To determine the effect of selective serotonin reuptake inhibitor (SSRI)/selective norepinephrine reuptake inhibitor (SNRI) use on the risk of symptomatic vasospasm and delayed cerebral ischemia (DCI) in patients hospitalized with aneurysmal subarachnoid hemorrhage (aSAH).

Methods

Retrospective review of consecutive patients with aSAH at Mayo Clinic, Rochester from January 2001 to December 2013. The variables collected and analyzed included age, sex, SSRI/SNRI use, active smoking, transfusion, modified Fisher score, WFNS grade, and outcome at discharge. Multivariate logistic regression analysis was used to evaluate factors associated with DCI, symptomatic vasospasm, and poor outcome (modified Rankin score 3–6) within 1 year.

Results

579 [females 363 (62.7 %)] patients with a median age of 55 (IQR 47–65) years were admitted with aSAH during the study period. WFNS at nadir was IV–V in 240 (41.5 %), and modified Fisher score was 3–4 in 434 (75.0 %). 81 (13.9 %) patients had been prescribed an SSRI or SNRI prior to admission and all continued to receive these medications during hospitalization. Symptomatic vasospasm was present in 154 (26.4 %), radiological infarction in 172 (29.5 %), and DCI in 250 (42.9 %) patients. SSRI/SNRI use was not associated with the occurrence of DCI (p = 0.458), symptomatic vasospasm (p = 0.097), radiological infarction (p = 0.972), or poor functional outcome at 3 months (p = 0.376).

Conclusions

The use of SSRI/SNRI prior to and during hospitalization is not associated with DCI or functional outcome in patients with aSAH.

     

Effect of Hydroxyethyl Starch Solution on Incidence of Acute Kidney Injury in Patients Suffering from Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Background

The application of third-generation hydroxyethyl starch (HES) solutions in critically ill patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) was often part of the treatment of delayed cerebral ischemia (DCI). However, there is increasing evidence showing a correlation between the application of HES and the incidence of acute kidney injury (AKI).

Methods

In a single-center retrospective analysis including 81 patients without a preexisting renal disorder suffering from aSAH who had received higher volumes of 6 % HES 130/0.4 due to standard treatment of DCI, the incidence of AKI during intensive care unit (ICU) stay was recorded using AKIN criteria. Furthermore, the course of serum creatinine after discharge from ICU was observed.

Results

6 % HES 130/0.4 was given over a period of 12.9 ± 7.1 days resulting in a cumulative dose of 12543.2 ± 7743.6 mL. Four patients (4.9 %) fulfilled AKIN criteria stage 1 during ICU stay. In two of these patients, serum creatinine was within normal range again on day of discharge. Five patients showed elevated levels of serum creatinine within 1 to 22 months after hospitalization. A correlation between the amount of HES given and the incidence of AKI could not be found.

Conclusion

The application of 6 % HES 130/0.4 did not lead to an elevated incidence of AKI in patients without an elevated baseline serum creatinine. However, there is still a lack of high-level evidence as prospective randomized trials are missing yet.

     

Spontaneous Elevation of Blood Pressure After SAH: An Epiphenomenon of Disease Severity and Demand,But Not a Surrogate for Outcome?

Background

Spontaneous blood pressure increase is frequently observed after aneurysmal subarachnoid hemorrhage (aSAH). These episodes of spontaneous blood pressure alterations are usually tolerated under the assumption of an endogenous response to maintain cerebral perfusion. The relevance of blood pressure variability and its relationship to disease severity and outcome, however, remain obscure.

Methods

A total of 115 consecutive patients with aSAH were included for this retrospective analysis of a continuously collected data pool. Demographics, initial clinical severity of aSAH (HH°, mFS), treatment modality, clinical course, and outcome (development of DCI, cerebral infarction, and GOS after 3 months) were recorded. Hemodynamic information—recorded automatically with a frequency of 1/15 min—was analyzed for spontaneous blood pressure increase (SBI) and endogenous persistent hypertension (EPH) after exclusion of iatrogenic factors and relevant co-medication. Subgroup analysis included stratification for day 0–3, 4–14, and 14–21.

Results

SBI and EPH incidence varied from 17 to 84% depending on detection threshold (15–35 mmHg) and time period under scrutiny. Incidence of blood pressure increase correlated with disease severity upon admission (p < 0.05), but the anticipated association with outcome was not observed. SBI and EPH were more likely to occur between day 4 and 14 (p < 0.001), but only early occurrence (day 0–3) was associated with higher incidence of DCI (p < 0.05). Persistent blood pressure elevation between day 4 and 21 was associated with fewer DCI. However, no influence of spontaneous upregulation on clinical outcome after three months was observed.

Conclusions

Spontaneous hemodynamic upregulation is a frequent phenomenon after aSAH. Our data support the hypothesis that spontaneous blood pressure alterations reflect an endogenous, demand-driven response correlating with disease severity. Early alterations may indicate an aggravated clinical course, while later upregulation in particular—if permitted—does not translate into a higher risk of unfavorable outcome.

     

Elevated C-reactive protein and white blood cell count at admission predict functional outcome after non-aneurysmal subarachnoid hemorrhage

Introduction

Patients with non-aneurysmal subarachnoid hemorrhage (SAH) are considered to have an overall benign course of disease compared to patients suffering from aneurysmal SAH. Nevertheless, a small but significant number of such patients might only achieve unfavorable outcome. Therefore, the purpose of the present study was to determine if routine laboratory markers of acute phase response are associated with unfavorable outcome in patients with non-aneurysmal SAH.

Methods

From 2006 to 2017, 154 patients suffering from non-aneurysmal SAH were admitted to our institution. Patients were stratified according to the distribution of cisternal blood into patients with perimesencephalic SAH (pSAH) versus non-perimesencephalic SAH (npSAH). C-reactive protein (CRP) and white blood cells (WBC) assessments were performed within 24 h of admission as part of routine laboratory workup. Outcome was assessed according to the modified Rankin Scale (mRS) after 6 months and stratified into favorable (mRS 0–2) vs. unfavorable (mRS 3–6).

Results

The multivariate regression analysis revealed “CRP?>?5 mg/l” (p?=?0.004, OR 143.7), “WBC count?>?12.1 G/l” (p?=?0.006, OR 47.8), “presence of IVH” (p?=?0.02, OR 13.5), “poor-grade SAH” (p?=?0.01, OR 45.2) and “presence of CVS” (p?=?0.003, OR 149.9) as independently associated with unfavorable outcome in patients with non-aneurysmal SAH.

Conclusion

Elevated C-reactive protein and WBC count at admission were associated with unfavorable outcome after non-aneurysmal SAH.

     

Acousto-Optic Cerebral Blood Flow Monitoring During Induction of Anesthesia in Humans

Background

Past transcranial Doppler (TCD) studies have documented the effects of the sequence of anesthesia induction followed by intubation on cerebral blood flow (CBF) velocity. The purpose of this study was to determine whether acousto-optic CBF monitoring would detect changes in CBF which are known to occur with propofol and subsequent endotracheal intubation.

Methods

Seventy-two patients scheduled for elective non-intracranial surgery were evaluated. A Cerox 3215F (Ornim Medical) acousto-optic CBF monitor was used. The acousto-optic transducers were applied bifrontally prior to induction. Baseline cerebral flow index (CFI) values were obtained for at least 2 min prior to induction, set to a unitless value of 100. Subsequent relative changes in CFI from baseline were determined at the lowest value over 3 min after propofol injection but before laryngoscopy; and the highest value over 5 min after the start of laryngoscopy. CFI data were evaluated using Friedman’s test.

Results

The median dose of propofol [interquartile range] given was 200 mg [160–250]. CFI decreased to 84 % of baseline after propofol and increased to 147 % of baseline after endotracheal intubation (both p < 0.001); MAP decreased after intravenous induction of anesthesia from 103 ± 15 to 86 ± 15 mmHg (p < 0.001) and then returned following endotracheal intubation to 104 ± 20 mmHg.

Conclusions

Our data are congruent with previous observations made with TCD under similar experimental conditions. Such observations support the notion that acousto-optic monitoring yields valid real-time measures of changes in CBF in humans. Further validation against other quantitative measures of CBF would be appropriate.

     

Hyperacute Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Background

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage typically occurs 3–14 days after aneurysm rupture. We describe a series of patients who developed vasospasm within minutes of aneurysm rupture. This phenomenon, which we term, “hyperacute vasospasm,” has been reported in animal models of SAH, but hitherto has been poorly described in humans.

Methods

Eleven patients were identified from an institutional registry who had aneurysmal rupture during catheter cerebral angiography between 1997 and 2009. We quantified the degree of vasoconstriction using vascular diameter index (VDI). The change in VDI (delta VDI or DVDI) was calculated by determining the difference in VDI before and after the procedure. We also examined the relationship between hyperacute vasospasm and delayed cerebral ischemia.

Results

Ten of eleven (91 %) patients with intraoperative aneurysm rupture had cerebral vasoconstriction within minutes of intra-procedural aneurysmal rupture. Six of eleven patients (55 %) with hyperacute vasospasm developed delayed cerebral infarction.

Conclusions

Hyperacute vasospasm is likely common in patients with intraoperative aneurysm rupture and may be an unrecognized element of the natural history of aneurysmal subarachnoid hemorrhage. In this limited series, there was an association between hyperacute vasospasm and delayed cerebral infarction.

     

Evaluation of a New Brain Tissue Probe for Intracranial Pressure,Temperature, and Cerebral Blood Flow Monitoring in Patients with Aneurysmal Subarachnoid Hemorrhage

Objective

To evaluate an intraparenchymal probe for intracranial pressure (ICP) and temperature (TEMP) monitoring as well as determination of cerebral hemodynamics using a near-infrared spectroscopy (NIRS) and indocyanine green (ICG) dye dilution method (NIRS-ICP probe).

Methods

The NIRS-ICP probe was applied after aneurysmal subarachnoid hemorrhage if multimodal monitoring was established due to poor neurological condition. ICP and TEMP values were obtained from ventricular catheters and systemic temperature sensors. Repeated NIRS-ICG measurements (2 injections within 30 min) were performed daily for determination of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time of ICG (mttICG). Secondary neurologic dysfunction was defined as brain tissue oxygen tension <20 mmHg and/or lactate/pyruvate ratio >35 obtained from cerebral probing.

Results

A total of 128 NIRS-ICG measurements were performed in ten patients. The correlation coefficients between ICP and TEMP values obtained with the NIRS-ICP probe and values from routine monitoring were r = 0.72 and r = 0.96, respectively. The mean values were 30.3 ± 13.6 ml/100 g/min for CBF, 3.3 ± 1.2 ml/100 g for CBV, and 6.8 ± 1.6 s for mttICG. The coefficients of variation from repeated NIRS-ICG measurements were 10.9 % for CBF, 11.7 % for CBV, and 3.8 % for mttICG. The sensitivity for detection of secondary neurologic dysfunction was 85 % and the specificity 83 % using a CBF-threshold of 25 ml/100 g/min.

Conclusion

Multimodal monitoring using the NIRS-ICP probe is feasible with high reproducibility of measurement values and the ability to detect secondary neurologic dysfunction. No safety concerns exist for the routine clinical use of the NIRS-ICP probe.