Poor-grade Subarachnoid Hemorrhage Patients Research Articles

Three Month Functional Outcomes in Poor Grade Subarachnoid Hemorrhage Patients Undergoing Endovascular Treatment of Cerebral Vasospasm (P7-5.032)

Three Month Functional Outcomes in Poor Grade Subarachnoid Hemorrhage Patients Undergoing Endovascular Treatment of Cerebral Vasospasm (P7-5.032)

Size of Craniectomy Predicts Approach-Related Shear Bleeding in Poor-Grade Subarachnoid Hemorrhage

Decompressive craniectomy is an option to decrease elevated intracranial pressure in poor-grade aneurysmal subarachnoid hemorrhage (SAH) patients. The aim of the present study was to analyze the size of the bone flap according to approach-related complications in patients with poor-grade SAH. We retrospectively analyzed poor-grade SAH patients (WFNS 4 and 5) who underwent aneurysm clipping and craniectomy (DC or ommitance of bone flap reinsertion). Postoperative CT scans were analyzed for approach-related tissue injury at the margin of the craniectomy (shear bleeding). The size of the bone flap was calculated using the De Bonis equation. Between 01/2012 and 01/2020, 67 poor-grade SAH patients underwent clipping and craniectomy at our institution. We found 14 patients with new shear bleeding lesion in postoperative CT scan. In patients with shear bleeding, the size of the bone flap was significantly smaller compared to patients without shear bleeding (102.1 ± 45.2 cm2 vs. 150.8 ± 37.43 cm2, p > 0.0001). However, we found no difference in mortality rates (10/14 vs. 23/53, p = 0.07) or number of implanted VP shunts (2/14 vs. 18/53, p = 0.2). We found no difference regarding modified Rankin Scale (mRS) 6 months postoperatively. In poor-grade aneurysmal SAH, the initial planning of DC-if deemed necessary -and enlargement of the flap size seems to decrease the rate of postoperatively developed shear bleeding lesions.

Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage.

Subarachnoid haemorrhage is a devastating disease that results in neurocognitive deficits and a poor functional outcome in a considerable proportion of patients. In this study, we investigated the prognostic value of microtubule-associated tau protein measured in the cerebral microdialysate for long-term functional and neuropsychological outcomes in poor-grade subarachnoid haemorrhage patients. We recruited 55 consecutive non-traumatic subarachnoid haemorrhage patients who underwent multimodal neuromonitoring, including cerebral microdialysis. Mitochondrial dysfunction was defined as lactate-to-pyruvate ratio >30 together with pyruvate >70 mmol/L and metabolic distress as lactate-to-pyruvate ratio >40. The multidimensional 12-month outcome was assessed by means of the modified Rankin scale (poor outcome: modified Rankin scale ≥4) and a standardized neuropsychological test battery. We used multivariable generalized estimating equation models to assess associations between total microdialysate-tau levels of the first 10 days after admission and hospital complications and outcomes. Patients were 56 ± 12 years old and presented with a median Hunt & Hess score of 5 (interquartile range: 3-5). Overall mean total microdialysate-tau concentrations were highest within the first 24 h (5585 ± 6291 pg/mL), decreased to a minimum of 2347 ± 4175 pg/mL on Day 4 (P < 0.001) and remained stable thereafter (P = 0.613). Higher total microdialysate-tau levels were associated with the occurrence of delayed cerebral ischaemia (P = 0.001), episodes of metabolic distress (P = 0.002) and mitochondrial dysfunction (P = 0.034). Patients with higher tau levels had higher odds for a poor 12-month functional outcome (adjusted odds ratio: 2.61; 95% confidence interval: 1.32-5.17; P = 0.006) and impaired results in the trail making test-B (adjusted odds ratio: 3.35; 95% confidence interval: 1.16-9.68; P = 0.026) indicative of cognitive flexibility. Total microdialysate-tau levels significantly decreased over the first 10 days (P < 0.05) in patients without delayed cerebral ischaemia or good functional outcomes and remained high in those with delayed cerebral ischaemia and poor 12-month outcomes, respectively. Dynamic changes of total tau in the cerebral microdialysate may be a useful biomarker for axonal damage associated with functional and neurocognitive recovery in poor-grade subarachnoid haemorrhage patients. In contrast, ongoing axonal damage beyond Day 3 after bleeding indicates a higher risk for delayed cerebral ischaemia as well as a poor functional outcome.

Early and Prolonged Mild Hypothermia in Patients with Poor-Grade Subarachnoid Hemorrhage: A Pilot Study.

We assessed the feasibility of therapeutic early and prolonged mild hypothermia (MH) in patients with poor-grade subarachnoid hemorrhage (SAH). A retrospective pilot study was conducted for poor-grade SAH patients at two university hospitals from March 2015 to December 2018 who had received MH immediately after coil embolization and maintained a target temperature of 34-35°C for 5 days. A matched controlled design at a 1:2 ratio was used to compare MH therapy outcomes. The primary goal was to assess the two groups' severe functional outcomes at discharge defined as a modified Rankin Scale score of 4-6. The secondary aim was to assess mortality and severe vasospasm depending upon MH. A binary logistic regression analysis was performed to identify relevant risk factors for the outcomes. A total of 54 patients (18 with MH treatment and 36 without MH treatment) were included. Severe functional outcome was significantly decreased in poor-grade SAH patients with MH (n = 7, 38.9%) than those without MH (n = 25, 69.4%; p = 0.031). In patients treated with MH, mortality and severe vasospasm tended to be less common, although the difference was not statistically significant. A binary logistic regression analysis revealed that early and prolonged MH (odds ratio [OR] = 0.156, 95% confidence intervals [CI]: 0.037-0.644) and severe vasospasm (OR = 5.593, 95% CI: 1.372-22.812) were risk factors for severe functional outcomes. This study shows potential therapeutic effect of early and prolonged MH treatment in poor-grade SAH patients. A randomized controlled study with a large number of patients is warranted in the future.

Cerebrospinal fluid metabolic profiling reveals divergent modulation of pentose phosphate pathway by midazolam, propofol and dexmedetomidine in patients with subarachnoid hemorrhage: a cohort study

BackgroundAgitation is common in subarachnoid hemorrhage (SAH), and sedation with midazolam, propofol and dexmedetomidine is essential in agitation management. Previous research shows the tendency of dexmedetomidine and propofol in improving long-term outcome of SAH patients, whereas midazolam might be detrimental. Brain metabolism derangement after SAH might be interfered by sedatives. However, how sedatives work and whether the drugs interfere with patient outcome by altering cerebral metabolism is unclear, and the comprehensive view of how sedatives regulate brain metabolism remains to be elucidated.MethodsFor cerebrospinal fluid (CSF) and extracellular space of the brain exchange instantly, we performed a cohort study, applying CSF of SAH patients utilizing different sedatives or no sedation to metabolomics. Baseline CSF metabolome was corrected by selecting patients of the same SAH and agitation severity. CSF components were analyzed to identify the most affected metabolic pathways and sensitive biomarkers of each sedative. Markers might represent the outcome of the patients were also investigated.ResultsPentose phosphate pathway was the most significantly interfered (upregulated) pathway in midazolam (p = 0.0000107, impact = 0.35348) and propofol (p = 0.00000000000746, impact = 0.41604) groups. On the contrary, dexmedetomidine decreased levels of sedoheptulose 7-phosphate (p = 0.002) and NADP (p = 0.024), and NADP is the key metabolite and regulator in pentose phosphate pathway. Midazolam additionally augmented purine synthesis (p = 0.00175, impact = 0.13481) and propofol enhanced pyrimidine synthesis (p = 0.000203, impact = 0.20046), whereas dexmedetomidine weakened pyrimidine synthesis (p = 0.000000000594, impact = 0.24922). Reduced guanosine diphosphate (AUC of ROC 0.857, 95%CI 0.617–1, p = 0.00506) was the significant CSF biomarker for midazolam, and uridine diphosphate glucose (AUC of ROC 0.877, 95%CI 0.631–1, p = 0.00980) for propofol, and succinyl-CoA (AUC of ROC 0.923, 95%CI 0.785–1, p = 0.000810) plus adenosine triphosphate (AUC of ROC 0.908, 95%CI 0.6921, p = 0.00315) for dexmedetomidine. Down-regulated CSF succinyl-CoA was also associated with favorable outcome (AUC of ROC 0.708, 95% CI: 0.524–0.865, p = 0.029333).ConclusionPentose phosphate pathway was a crucial target for sedatives which alter brain metabolism. Midazolam and propofol enhanced the pentose phosphate pathway and nucleotide synthesis in poor-grade SAH patients, as presented in the CSF. The situation of dexmedetomidine was the opposite. The divergent modulation of cerebral metabolism might further explain sedative pharmacology and how sedatives affect the outcome of SAH patients.

The effect of the volemic and cardiac status on brain oxygenation in patients with subarachnoid hemorrhage: a bi-center cohort study

BackgroundFluid management in patients after subarachnoid hemorrhage (SAH) aims at the optimization of cerebral blood flow and brain oxygenation. In this study, we investigated the effects of hemodynamic management on brain oxygenation by integrating advanced hemodynamic and invasive neuromonitoring.MethodsThis observational cohort bi-center study included data of consecutive poor-grade SAH patients who underwent pulse contour cardiac output (PiCCO) monitoring and invasive neuromonitoring. Fluid management was guided by the transpulmonary thermodilution system and aimed at euvolemia (cardiac index, CI ≥ 3.0 L/min/m2; global end-diastolic index, GEDI 680–800 mL/m2; stroke volume variation, SVV < 10%). Patients were managed using a brain tissue oxygenation (PbtO2) targeted protocol to prevent brain tissue hypoxia (BTH, PbtO2 < 20 mmHg). To assess the association between CI and PbtO2 and the effect of fluid challenges on CI and PbtO2, we used generalized estimating equations to account for repeated measurements.ResultsAmong a total of 60 included patients (median age 56 [IQRs 47–65] years), BTH occurred in 23% of the monitoring time during the first 10 days since admission. Overall, mean CI was within normal ranges (ranging from 3.1 ± 1.3 on day 0 to 4.1 ± 1.1 L/min/m2 on day 4). Higher CI levels were associated with higher PbtO2 levels (Wald = 14.2; p < 0.001). Neither daily fluid input nor fluid balance was associated with absolute PbtO2 levels (p = 0.94 and p = 0.85, respectively) or the occurrence of BTH (p = 0.68 and p = 0.71, respectively). PbtO2 levels were not significantly different in preload dependent patients compared to episodes of euvolemia. PbtO2 increased as a response to fluid boluses only if BTH was present at baseline (from 13 ± 6 to 16 ± 11 mmHg, OR = 13.3 [95% CI 2.6–67.4], p = 0.002), but not when all boluses were considered (p = 0.154).ConclusionsIn this study a moderate association between increased cardiac output and brain oxygenation was observed. Fluid challenges may improve PbtO2 only in the presence of baseline BTH. Individualized hemodynamic management requires advanced cardiac and brain monitoring in critically ill SAH patients.

Profiling of T Cell Receptor β-Chain Complimentary Determining Regions 3 Repertoire in Subarachnoid Hemorrhage Patients Using High-Throughput Sequencing.

ObjectiveThe adaptive immune response following subarachnoid hemorrhage (SAH) is not well understood. We evaluated and compared the T cell receptor (TCR) immune repertoire of good-grade and poor-grade SAH patients to elucidate the T cell immunology after ictus. MethodsPeripheral blood from six SAH patients was collected at two different times, admission and at the 7-day follow-up. Composition and variation of the TCR β-chain (TCRB) complimentary determining regions (CDR) 3 repertoire was examined using high-throughput sequencing; the analysis was based on sampling time and disease severity (good vs. poor-grade SAH). ResultsClonality at admission and follow-up were 0.059 (0.037–0.038) and 0.027 (0.014–0.082) (median, 25th–75th percentile). Poor-grade SAH (0.025 [0.011–0.038]) was associated with significantly lower clonality than good-grade SAH (0.095 [0.079–0.101]). Poor-grade SAH patients had higher diversity scores than good-grade SAH patients. CDR length was shorter in good-grade SAH vs. poor-grade SAH. Differences in clonotype distribution were more prominent in TCRBV gene segments than TCRBJ segments. TCRBV19-01/TCRBJ02-04 and TCRBV28-01/TCRBJ02-04 were the most increased and the most decreased V-J pairs in the 7-day follow-up compared to admission in good-grade SAH. The most increased and decreased V-J pairs in poor-grade SAH patients were TCRBV28-01/TCRBJ02-06 and TCRBV30-01/TCRBJ02-04, respectively. ConclusionThe TCRB repertoire is dynamic in nature following SAH. TCRB repertoire may facilitate our understanding of adaptive immune response according to SAH severity.

Time course of outcome in poor grade subarachnoid hemorrhage patients: a longitudinal retrospective study

BackgroundNeurological outcome and mortality of patients suffering from poor grade subarachnoid hemorrhage (SAH) may have changed over time. Several factors, including patients’ characteristics, the presence of hydrocephalus and intraparenchymal hematoma, might also contribute to this effect. The aim of this study was to assess the temporal changes in mortality and neurologic outcome in SAH patients and identify their predictors.MethodsWe performed a single center retrospective cohort study from 2004 to 2018. All non-traumatic SAH patients with poor grade on admission (WFNS score of 4 or 5) who remained at least 24 h in the hospital were included. Time course was analyzed into four groups according to the years of admission (2004–2007; 2008–2011; 2012–2015 and 2016–2018).ResultsA total of 353 patients were included in this study: 202 patients died (57 %) and 260 (74 %) had unfavorable neurological outcome (UO) at 3 months. Mortality tended to decrease in in 2008–2011 and 2016–2018 periods (HR 0.55 [0.34–0.89] and HR 0.33 [0.20–0.53], respectively, when compared to 2004–2007). The proportion of patients with UO remained high and did not vary significantly over time. Patients with WFNS 5 had higher mortality (68 % vs. 34 %, p = 0.001) and more frequent UO (83 % vs. 54 %, p = 0.001) than those with WFNS 4. In the multivariable analysis, WFNS 5 was independently associated with mortality (HR 2.12 [1.43–3.14]) and UO (OR 3.23 [1.67–6.25]). The presence of hydrocephalus was associated with a lower risk of mortality (HR 0.60 [0.43–0.84]).ConclusionsBoth hospital mortality and UO remained high in poor grade SAH patients. Patients with WFNS 5 on admission had worse prognosis than others; this should be taken into consideration for future clinical studies.

The Role of Consecutive Plasma Copeptin Levels in the Screening of Delayed Cerebral Ischemia in Poor-Grade Subarachnoid Hemorrhage.

The prognostic value of copeptin in subarachnoid hemorrhage (SAH) has been reported, but the prognosis was largely affected by the initial clinical severity. Thus, the previous studies are not very useful in predicting delayed cerebral ischemia (DCI) in poor-grade SAH patients. Here, we first investigated the feasibility of predicting DCI in poor-grade SAH based on consecutive measurements of plasma copeptin. We measured copeptin levels of 86 patients on days 1, 3, 5, 7, 9, 11, and 13 using ELISA. The primary outcome was the association between consecutive copeptin levels and DCI development. The secondary outcomes were comparison of copeptin with C-reactive protein (CRP) in predicting DCI. Additionally, we compared the prognostic value of transcranial Doppler ultrasonography (TCD) with copeptin using TCD alone to predict DCI. Increased copeptin (OR = 1.022, 95% CI: 1.008–1.037) and modified Fisher scale IV (OR = 2.841; 95% CI: 0.998–8.084) were closely related to DCI. Consecutive plasma copeptin measurements showed significant differences between DCI and non-DCI groups (p < 0.001). Higher CRP and DCI appeared to show a correlation, but it was not statistically significant. Analysis of copeptin changes with TCD appeared to predict DCI better than TCD alone with AUCROC differences of 0.072. Consecutive measurements of plasma copeptin levels facilitate the screening of DCI in poor-grade SAH patients.

Management of poor grade sub-arachnoid haemorrhage – clinical judgement v/s a formal model

Objective The poor grade subarachnoid haemorrhage patients represent a unique cohort with lack of clear treatment protocol. Most neurosurgical units in the UK will manage them at local hospital until they make a significant recovery, this period can put them at higher risk of rebleed while with aggressive treatment a significant subset can achieve a favourable outcome. Identification of this subset is difficult and decision to treat them is associated with significant commitment of neurosurgical and ITU resources. Recent paper by Szklener has come up with a scale for prognostication in this subgroup of patients. We wanted to check the validity of this scale in our patient population and see if this scale can be used to guide early patient transfer and aggressive management at the Neurosurgical unit. Methods We retrospectively reviewed our referral database for all poor grade subarachnoid patients referred over 2 years. Demographic information, Fisher and WFNS scores, admitting leucocyte count and outcome information as per MRS were obtained. These were scored as per the scale suggested by Szklener. Results A total of 115 poor grade subarachnoid patients were referred over the study time frame. 47 of them were accepted for admission . 18/47 patients achieved a favourable outcome (GOS4-5). Only 1 patient managed in peripheral hospital had a good outcome. There was a significant association between Szklener’s score and achieving a favourable outcome p = 0.002. Conclusion A selective admission policy could work specially with current economic climate, achieving outcomes comparable to admit-all. However, to optimise outcomes for all patients an aggressive standardised management at peripheral hospitals and a uniform admission policy assisted by Szklener score may be adopted. Szklener’s model predicts the outcome better than WFNS and age but more validation is needed.

Double hemispheric Microdialysis study in poor-grade SAH patients

Delayed cerebral ischemia (DCI) is a dreadful complication present in 30% of subarachnoid hemorrhage (SAH) patients. DCI prediction and prevention are burdensome in poor grade SAH patients (WFNS 4–5). Therefore, defining an optimal neuromonitoring strategy might be cumbersome. Cerebral microdialysis (CMD) offers near-real-time regional metabolic data of the surrounding brain. However, unilateral neuromonitoring strategies obviate the diffuse repercussions of SAH. To assess the utility, indications and therapeutic implications of bilateral CMD in poor grade SAH patients. Poor grade SAH patients eligible for multimodal neuromonitoring were prospectively collected. Aneurysm location and blood volume were assessed on initial Angio-CT scans. CMD probes were bilaterally implanted and maintained, at least, for 48 hours (h). Ischemic events were defined as a Lactate/Pyruvate ratio >40 and Glucose concentration <0.7 mmol/L. 16 patients were monitored for 1725 h, observing ischemic events during 260 h (15.1%). Simultaneous bilateral ischemic events were rare (5 h, 1.9%). The established threshold of ≥7 ischemic events displayed a specificity and sensitivity for DCI of 96.2% and 83.3%, respectively. Bilateral CMD is a safe and useful strategy to evaluate areas at risk of suffering DCI in SAH patients. Metabolic crises occur bilaterally but rarely simultaneously. Hence, unilateral neuromonitoring strategies underestimate the risk of infarction and the possibility to offset its consequences.

Brain temperature regulation in poor-grade subarachnoid hemorrhage patients – A multimodal neuromonitoring study

Elevated body temperature (Tcore) is associated with poor outcome after subarachnoid hemorrhage (SAH). Brain temperature (Tbrain) is usually higher than Tcore. However, the implication of this difference (Tdelta) remains unclear. We aimed to study factors associated with higher Tdelta and its association with outcome. We included 46 SAH patients undergoing multimodal neuromonitoring, for a total of 7879 h of averaged data of Tcore, Tbrain, cerebral blood flow, cerebral perfusion pressure, intracranial pressure and cerebral metabolism (CMD). Three-months good functional outcome was defined as modified Rankin Scale ≤2. Tbrain was tightly correlated with Tcore (r = 0.948, p < 0.01), and was higher in 73.7% of neuromonitoring time (Tdelta +0.18°C, IQR −0.01 – 0.37°C). A higher Tdelta was associated with better metabolic state, indicated by lower CMD-glutamate (p = 0.003) and CMD-lactate (p < 0.001), and lower risk of mitochondrial dysfunction (MD) (OR = 0.2, p < 0.001). During MD, Tdelta was significantly lower (0°C, IQR −0.2 – 0.1; p < 0.001). A higher Tdelta was associated with improved outcome (OR = 7.7, p = 0.002). Our study suggests that Tbrain is associated with brain metabolic activity and exceeds Tcore when mitochondrial function is preserved. Further studies are needed to understand how Tdelta may serve as a surrogate marker for brain function and predict clinical course and outcome after SAH.

CBF changes and cerebral energy metabolism during hypervolemia, hemodilution, and hypertension therapy in patients with poor-grade subarachnoid hemorrhage.

Despite the multifactorial pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), augmentation of cerebral blood flow (CBF) is still considered essential in the clinical management of DCI. The aim of this prospective observational study was to investigate cerebral metabolic changes in relation to CBF during therapeutic hypervolemia, hemodilution, and hypertension (HHH) therapy in poor-grade SAH patients with DCI. CBF was assessed by bedside xenon-enhanced CT at days 0-3, 4-7, and 8-12, and the cerebral metabolic state by cerebral microdialysis (CMD), analyzing glucose, lactate, pyruvate, and glutamate hourly. At clinical suspicion of DCI, HHH therapy was instituted for 5 days. CBF measurements and CMD data at baseline and during HHH therapy were required for study inclusion. Non-DCI patients with measurements in corresponding time windows were included as a reference group. In DCI patients receiving HHH therapy (n = 12), global cortical CBF increased from 30.4 ml/100 g/min (IQR 25.1-33.8 ml/100 g/min) to 38.4 ml/100 g/min (IQR 34.2-46.1 ml/100 g/min; p = 0.006). The energy metabolic CMD parameters stayed statistically unchanged with a lactate/pyruvate (L/P) ratio of 26.9 (IQR 22.9-48.5) at baseline and 31.6 (IQR 22.4-35.7) during HHH. Categorized by energy metabolic patterns during HHH, no patient had severe ischemia, 8 showed derangement corresponding to mitochondrial dysfunction, and 4 were normal. The reference group of non-DCI patients (n = 11) had higher CBF and lower L/P ratios at baseline with no change over time, and the metabolic pattern was normal in all these patients. Global and regional CBF improved and the cerebral energy metabolic CMD parameters stayed statistically unchanged during HHH therapy in DCI patients. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was a common occurrence, possibly explained by mitochondrial dysfunction despite improved microcirculation.

Hyperemia in subarachnoid hemorrhage patients is associated with an increased risk of seizures

The association between impaired brain perfusion, cerebrovascular reactivity status and the risk of ictal events in patients with subarachnoid hemorrhage is unknown. We identified 13 subarachnoid hemorrhage (SAH) patients with seizures and 22 with ictal-interictal continuum (IIC), and compared multimodality physiological recordings to 38 similarly poor-grade SAH patients without ictal activity. We analyzed 10,179 cumulative minutes of seizure and 12,762 cumulative minutes of IIC. Cerebrovascular reactivity (PRx) was not different between subjects with seizures, IIC, or controls. Cerebral perfusion pressure (CPP) was higher in patients with seizures [99 ± 6.5, p = .005] and IIC [97 ± 8.5, p = .007] when compared to controls [89 ± 12.3]. DeltaCPP, defined as actual CPP minus optimal CPP (CPPopt), was also higher in the seizure group [8.3 ± 7.9, p = .0003] and IIC [8.1 ± 10.3, p = .0006] when compared to controls [−0.1 ± 5]. Time spent with supra-optimal CPP was higher in the seizure group [342 ± 213 min/day, p = .002] when compared to controls [154 ± 120 min/day]. In a temporal examination, a supra-optimal CPP preceded increased seizures and IIC in SAH patients, an hour before and continued to increase during the events [p < .0001].

Protocolized Brain Oxygen Optimization in Subarachnoid Hemorrhage

BackgroundBrain tissue hypoxia (PbtO2 < 20 mmHg) is common after subarachnoid hemorrhage (SAH) and associated with poor outcome. Recent data suggest that brain oxygen optimization is feasible and reduces the time spent with PbtO2 < 20 mmHg from 45 to 16% in patients with severe traumatic brain injury. Here, we intended to quantify the brain tissue hypoxia burden despite implementation of a protocolized treatment approach in poor-grade SAH patients and to identify the simultaneous occurrence of pathologic values potentially amenable to treatment.MethodsWe present a bi-centric observational cohort study including 100 poor-grade SAH patients admitted to two tertiary care centers who underwent multimodal brain monitoring and were managed with a PbtO2-targeted protocolized approach. PbtO2 optimization (≥ 20 mmHg) included a stepwise neuro-intensive care approach, aiming to prevent low cerebral perfusion pressure (CPP), and blood hemoglobin, and to keep normocapnia, normoxemia,and normothermia. Based on routine blood gas analysis, hemoglobin, PaCO2, and PaO2 data were matched to 2-h averaged data of continuous CPP, PbtO2, core temperature, and to hourly cerebral microdialysis (CMD) samples over the first 11 days.ResultsPatients had a Glasgow Coma Scale of 3 (IQR 3–4) and were 58 years old (IQR 48–66). Overall incidence of brain tissue hypoxia was 25%, which was not different between both sites despite differences in the treatment approach. During brain tissue hypoxia, episodes of CPP < 70 mmHg (27%), PaCO2 < 35 mmHg (19%), PaO2 < 80 mmHg (14%), Hb < 9 g/dL (11%), metabolic crisis (CMD-lactate/pyruvate ratio > 40, and CMD-glucose < 0.7 mmol/L; 7%), and temperature > 38.3 °C (4%) were common.ConclusionsOur results demonstrate that brain tissue hypoxia remains common despite implementation of a PbtO2-targeted therapy in poor-grade SAH patients, suggesting room for further optimization.

Temporal Dynamics of Cerebral Blood Flow During the Acute Course of Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT

BackgroundCompromised cerebral blood flow (CBF) is a crucial factor in delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Repeated measurement of CBF may improve our understanding of the temporal dynamics following SAH. The aim of this study was to assess CBF at different phases of the acute course in poor-grade SAH patients, hypothesizing more pronounced disturbances at day 4–7, and that the initial level of CBF determines the following course of CBF.MethodsMechanically ventilated SAH patients were scheduled for bedside measurement of regional and global cortical CBF at day 0–3, 4–7, and 8–12, using xenon-enhanced computed tomography in a mobile setup. Patients were dichotomized depending on high or low initial global cortical CBF and cutoff level 30 ml/100 g/min.ResultsEighty-one patients were included, and 51 had measurements at day 0–3 and 4–7. In patients with high initial CBF, the level was unchanged at day 4–7; 37.7 (IQR 32.6–46.7) ml/100 g/min versus 36.8 (IQR 29.5–44.8). The low-CBF group showed a slight increase from 23.6 (IQR 21.0–28.1) ml/100 g/min to 28.4 (IQR 22.7–38.3) (P = 0.025), still markedly lower than the high-CBF group (P = 0.016). In the low-CBF group, CBF increased in patients who received hypertension, hypervolemia, and hemodilution (HHH therapy) but remained low in standard treated patients. For the subset of 27 patients examined also at day 8–12, the differences depending on initial CBF level were no longer statistically significant. Among patients with still low CBF at day 4–7, the proportion who had poor short-term outcome was 55% compared to 35% (n.s.) for patients with high CBF.ConclusionsCBF studied in poor-grade SAH patients at large did not show any statistically significant changes over time. Stratifying patients by high or low initial CBF and whether HHH therapy was given revealed an association between low initial CBF and persistent low CBF at day 4–7. These findings may be of clinical relevance in managing SAH patients with low early CBF.

Abstract TP537: Jugular Bulb Microdialysis in Subarachnoid Hemorrhage

Introduction: Metabolic perturbations are common in patients with subarachnoid hemorrhage (SAH) and contribute to patient outcome. Cerebral microdialysis (CMD), used for monitoring of poor grade SAH patients, is intracranial invasive and highly regional, depending on proximity to lesions. Microdialysis of jugular bulb venous drainage has not been attempted in this patient group and it may give a measure of global cerebral metabolism detecting critical events potentially missed by regional monitoring. Methods: Adult SAH patients were included at admission when local clinical guidelines prompted extended multimodal neuromonitoring (impaired consciousness and poor grade SAH). Patients were monitored using non-dominant frontal CMD combined with an intracranial pressure (ICP) and brain oxygen tension (PbtO 2 ) probe in a double lumen bolt (Raumedic®) as well as dominant jugular bulb microdialysis for a mean period of 5 days. Jugular bulb lactate/pyruvate ratio (LPR) and intracranial derived measurements were analysed for correlation. 6 month modified Rankin scale (mRs) was assessed. Results: Twelve patients were included (mean age 62 years, mean mRs 3.7). There were no complications related to jugular bulb access. Of 1218 monitoring hours, 131 displayed elevated jugular bulb LPR (&gt;20), 133 elevated ICP (&gt;20 mmHg) and 287 reduced PbtO 2 (&lt;20 mmHg). Periods of co-variation were seen in selected patients, but no significant correlations between jugular bulb LPR vs. cerebral LPR (r=-0.07, p=0.014), jugular bulb LPR vs. ICP (r=-0.03, p=0.72) or jugular bulb LPR vs. PbtO 2 (r=0.08, p=0.16) were found in Spearman analysis of critical periods. Concerning jugular LPR vs. mRs the study was underpowered (r=-0.36, p=0.27). Conclusions: Intracranial regional monitoring events were not mirrored in jugular bulb LPR and periods of metabolic perturbations seen in jugular bulb LPR passed without consistent indication from regional modalities. Metabolic disturbances are potentially missed by regional monitoring in SAH.

The Timing of Tracheostomy and Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Nationwide Inpatient Sample Analysis.

The goal of this study was to investigate the association of tracheostomy timing with outcomes after aneurysmal subarachnoid hemorrhage (SAH) in a national population. Poor-grade aneurysmal SAH patients were extracted from the Nationwide Inpatient Sample (2002-2011). Multivariable linear regression was used to analyze predictors of tracheostomy timing and multivariable logistic regression was used to evaluate the association of timing of intervention with mortality, complications, and discharge to institutional care. Covariates included patient demographics, comorbidities, severity of subarachnoid hemorrhage (measured using the NIS-SAH severity scale), hospital characteristics, and other complications and length of stay. The median time to tracheostomy among 1380 poor-grade SAH admissions was 11 (interquartile range: 7-15) days after intubation. The mean number of days from intubation to tracheostomy in SAH patients at the hospital (p < 0.001) was the strongest predictor of tracheostomy timing for a patient, while comorbidities and SAH severity were not significant predictors. Mortality, neurologic complications, and discharge disposition did not differ significantly by tracheostomy time. However, later tracheostomy (when evaluated continuously) was associated with greater odds of pulmonary complications (p = 0.004), venous thromboembolism (p = 0.04), and pneumonia (p = 0.02), as well as a longer hospitalization (p < 0.001). Subgroup analysis only found these associations between tracheostomy timing and medical complications in patients with moderately poor grade (NIS-SAH severity scale 7-9), while there were no significant differences by timing of intervention in very poor-grade patients (NIS-SAH severity scale > 9). In this analysis of a large, national data set, variation in hospital practices was the strongest predictor of tracheostomy timing for an individual. In patients with moderately poor grade, later tracheostomy was independently associated with pulmonary complications, venous thromboembolism, pneumonia, and a longer hospitalization, but not with mortality, neurological complications, or discharge disposition. However, tracheostomy timing was not significantly associated with outcomes in very poor-grade patients.

Diagnostic accuracy of quantitative EEG to detect delayed cerebral ischemia after subarachnoid hemorrhage: A preliminary study

ObjectiveDelayed cerebral ischemia (DCI) is the most important and preventable morbidity cause after subarachnoid hemorrhage (SAH). Therefore, DCI early detection is a major challenge. Yet, neurological examination can be unreliable in poor grade SAH patients. EEG provides information from most superficial cortical area, with ischemia-related changes. This study aims at defining an alpha-theta/delta (AT/D) ratio decrease thresholds to detect DCI. MethodsWe used EEG with a montage matching vascular territories (right and left anterior central and posterior) and compared them to follow-up brain imaging. Results15 SAH patients (Fischer ≥ 3, World Federation of Neurological Surgeons scale ≥4, 9 DCI) were monitored during 6.4 [4–8] days (min = 2d, max = 13d). AT/D changes could follow three different patterns: (1) prolonged or (2) transient decrease and (3) no decrease or progressive increase. A regional 30% decrease outlasting 3.7 h reached 100% sensitivity and 88.9% specificity to detect DCI. Only 22.6% were in a zone of uncertain diagnosis (3.7–8.04 h). These prolonged decreases, with a loss of transient changes, started in cortical areas evolving toward DCI, and preceded intracranial changes when available. ConclusionAlthough this study has a small sample size, prolonged AT/D decrease seems to be a reliable biomarker of DCI. SignificancecEEG changes are likely to precede cerebral infarction and could be useful at the bedside to detect DCI before irreversible damage.

Cerebral Autoregulation in the Prediction of Delayed Cerebral Ischemia and Clinical Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage Patients.

Pressure reactivity index and oxygen reactivity index are used to assess cerebral autoregulation after acute brain injury. The value of autoregulation indices in the prediction of delayed cerebral ischemia and outcome in patients with subarachnoid hemorrhage is still inconclusive. In this study, we aimed to focus on the predictive value of the first 72 hours commonly referred to as "early brain injury" in comparison to the overall monitoring period. Retrospective observational cohort study. Neurocritical care unit at a tertiary academic medical center. Forty-three consecutive poor-grade patients with nontraumatic subarachnoid hemorrhage admitted between 2012 and 2016 undergoing continuous high-frequency monitoring. High-frequency monitoring includes arterial blood pressure, intracranial pressure, and brain tissue oxygen tension. Pressure reactivity index and oxygen reactivity index were evaluated as moving correlation coefficient between mean arterial pressure/intracranial pressure and cerebral perfusion pressure/brain tissue oxygen tension, respectively. Median autoregulation monitoring time was 188 ± 91 hours per patient. Initial pressure reactivity index was 0.31 ± 0.02 and decreased significantly to 0.01 ± 0.01 (p < 0.001) 3 days after admission with a second peak 10 days after admission (0.18 ± 0.14; p = 0.001). Admission oxygen reactivity index was high, 0.25 ± 0.03, and decreased to a minimum of 0.11 ± 0.02 eight days after admission (p = 0.008). Patients with delayed cerebral ischemia had significantly higher overall mean pressure reactivity index values (p < 0.04), which were more pronounced during the first 72 hours, reflecting early brain injury (p < 0.02). High pressure reactivity index during the first 72 hours was associated with poor functional outcome (p < 0.001). No association between oxygen reactivity index and delayed cerebral ischemia or clinical outcome was observed (p = 0.8/0.78). High initial pressure reactivity index, presumably reflecting early brain injury, but not oxygen reactivity index, was associated with delayed cerebral ischemia and worse clinical outcome in poor-grade subarachnoid hemorrhage patients. Our data indicate that autoregulation indices should be interpreted cautiously when used in these patients and that timing is crucial when autoregulation indices are evaluated as predictor for delayed cerebral ischemia and outcome.