Poor-grade aSAH Patients Research Articles

The Effectiveness of Target Temperature Management on Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

The effectiveness of target temperature management (TTM) in poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains a topic of debate. In order to assess the clinical efficacy of TTM in patients with poor-grade aSAH, we conducted a systematic review and meta-analysis. This research was registered in PROSPERO (CRD42023445582) and included all relevant publications up until October 2023. We compared the TTM groups with the control groups in terms of unfavorable outcomes (modified Rankin scale [mRS] score > 3), mortality, delayed cerebral ischemia (DCI), cerebral vasospasm (CVS), and specific complications. Subgroup analyses were performed based on country, study type, follow-up time, TTM method, cooling maintenance period, and rewarming rate. Effect sizes were calculated as relative risk(RR) using random-effect or fixed-effect models. The quality of the articles was assessed using the methodological index for non-randomized studies scale. Our analysis included a total of 5 clinical studies (including 1 randomized controlled trial) and 219 patients (85 in the TTM group and 134 in the control group). Most of the studies were of moderate quality. TTM was found to be associated with a statistically significant improvement in mortality (mRS score 6) rates compared with the control group (RR = 0.61, 95% confidence interval [CI]: 0.40-0.94, p = 0.026). However, there was no statistically significant difference in unfavorable outcomes (mRS 4-6) between the TTM and control groups (RR = 0.94, 95% CI: 0.71-1.26, p = 0.702). The incidence of adverse events, including DCI, CVS, pneumonia, cardiac complications, and electrolyte imbalance, did not significantly differ between the two groups. In conclusion, our overall results suggest that TTM does not significantly reduce unfavorable outcomes in poor-grade aSAH patients. However, TTM may decrease mortality rates. Preoperative TTM may cause patients to miss the opportunity for surgery, although it temporarily protects the brain. Furthermore, the incidence of adverse events was similar between the TTM and control groups.

Factors affecting 30-day mortality in poor-grade aneurysmal subarachnoid hemorrhage: a 10-year single-center experience.

The management of patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is burdened by an unfavorable prognosis even with aggressive treatment. The aim of the present study is to investigate the risk factors affecting 30-day mortality in poor-grade aSAH patients. We performed a retrospective analysis of a prospectively collected database of poor-grade aSAH patients (World Federation of Neurosurgical Societies, WFNS, grades IV and V) treated at our institution from December 2010 to December 2020. For all variables, percentages of frequency distributions were analyzed. Contingency tables (Chi-squared test) were used to assess the association between categorical variables and outcomes in the univariable analysis. Multivariable analysis was performed by using the multiple logistic regression method to estimate the odds ratio (OR) for 30-day mortality. A total of 149 patients were included of which 32% had WFNS grade 4 and 68% had WFNS grade 5. The overall 1-month mortality rate was 21%. On univariable analysis, five variables were found to be associated with the likelihood of death, including intraventricular hemorrhage (IVH ≥ 50 mL, p = 0.005), the total amount of intraventricular and intraparenchymal hemorrhage (IVH + ICH ≥ 90 mL, p = 0.019), the IVH Ratio (IVH Ratio ≥ 40%, p = 0.003), posterior circulation aneurysms (p = 0.019), presence of spot sign on initial CT scan angiography (p = 0.015).Nonetheless, when the multivariable analysis was performed, only IVH Ratio (p = 0.005; OR 3.97), posterior circulation aneurysms (p = 0.008; OR 4.05) and spot sign (p = 0.022; OR 6.87) turned out to be independent predictors of 30-day mortality. The risk of mortality in poor-grade aSAH remains considerable despite maximal treatment. Notwithstanding the limitations of a retrospective study, our report highlights some neuroradiological features that in the emergency setting, combined with leading clinical and anamnestic parameters, may support the multidisciplinary team in the difficult decision-making process and communication with family members from the earliest stages of poor-grade aSAH. Further prospective studies are warranted.

Length of Survival, Outcome, and Potential Predictors in Poor-Grade Aneurysmal Subarachnoid Hemorrhage Patients Treated with Microsurgical Clipping.

Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) has been associated with severe morbidity and high mortality. It has been demonstrated that early intervention is of paramount importance. The aim of our study is to evaluate the functional outcome and the overall survival of early microsurgically treated patients. Poor-grade aSAH patients admitted at our institution over fifteen years (January 2008 - December 2022) were included in our retrospective study. All participants underwent brain Computed Tomography Angiography (CTA). Fisher scale was used to assess the severity of hemorrhage. All our study participants underwent microsurgical clipping, and their functional outcome was assessed with the Glasgow Outcome Scale (GOS). We used logistic regression analysis to identify any parameters associated with a favorable outcome at 12 months. Cox proportional hazard analysis was also performed, identifying factors affecting the length of survival. Our study included 39 patients with a mean age of 54 years. Thirty of our participants (76.9%) were Hunt and Hess grade V, while the vast majority (94.9%) were Fisher grade 4. The observed six-month mortality rate was 48.6%. The mean follow-up time was 18.6 months. The functional outcome at six months was favorable in 6 patients (16.2%), increased to 23.5% at 12 months. Our data analysis showed that the age, as well as the employment of temporary clipping during surgery, affected the overall outcome. Management of poor-grade aSAH patients has been dramatically changed. Microsurgical clipping provides promising results in carefully selected younger patients.

Volatile Sedation With Isoflurane in Neurocritical Care Patients After Poor-grade Aneurysmal Subarachnoid Hemorrhage

Volatile sedation after aneurysmal subarachnoid hemorrhage (aSAH) promises several advantages, but there are still concerns regarding intracranial hypertension due to vasodilatory effects. We prospectively analyzed cerebral parameters during the switch from intravenous to volatile sedation with isoflurane in patients with poor-grade (World Federation of Neurosurgical Societies grade 4-5) aSAH. Eleven patients were included in this prospective observational study. Between day 3 and 5 after admission, intravenous sedation was switched to isoflurane using the Sedaconda Anesthetic Conserving Device (Sedana Medical, Danderyd, Sweden). Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), cerebral mean flow velocities (MFVs; transcranial Doppler ultrasound) and regional cerebral oxygen saturation (rSO2, near-infrared spectroscopy monitoring), as well as cardiopulmonary parameters were assessed before and after the sedation switch (-12 to+12 hours). Additionally, perfusion computed tomography data during intravenous and volatile sedation were analyzed retrospectively for changes in cerebral blood flow. There were no significant changes in mean ICP, CPP, and PBrO2 after the sedation switch to isoflurane. Mean rSO2 showed a non-significant trend towards higher values, and mean MFV in the middle cerebral arteries increased significantly after the initiation of volatile sedation. Isoflurane sedation resulted in a significantly increased norepinephrine administration. Despite an increase in mean inspiratory pressure, we observed a significant increase in mean partial arterial pressure of carbon dioxide. Isoflurane sedation does not compromise ICP or cerebral oxygenation in poor-grade aSAH patients, but the significant depression of CPP could limit the use of volatiles in case of hemodynamic instability or high vasopressor demand.

Early predictors of functional outcome in poor-grade aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

BackgroundPatients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) often receive delayed or no aneurysm treatment, although recent studies suggest that functional outcome following early aneurysm treatment has improved. We aimed to systematically review and meta-analyze early predictors of functional outcome in poor-grade aSAH patients. MethodsWe included studies investigating the association of early predictors and functional outcome in adult patients with confirmed poor-grade aSAH, defined as World Federation of Neurological Surgeons (WFNS) grade or Hunt and Hess (H–H) grade IV-V. Studies had to use multivariable regression analysis to estimate independent predictor effects of favorable functional outcome measured with the Glasgow Outcome Scale or modified Rankin Scale. We calculated pooled adjusted odds ratios (aOR) and 95% confidence intervals (CI) with random effects models. ResultsWe included 27 studies with 3287 patients. The likelihood of favorable outcome increased with WFNS grade or H–H grade IV versus V (aOR 2.9, 95% CI 1.9–4.3), presence of clinical improvement before aneurysm treatment (aOR 3.3, 95% CI 2.0–5.3), and intact pupillary light reflex (aOR 2.9, 95% CI 1.6–5.1), and decreased with older age (aOR 0.7, 95% CI 0.5–1.0, per decade), increasing modified Fisher grade (aOR 0.4, 95% CI 0.3–0.5, per grade), and presence of intracerebral hematoma on admission imaging (aOR 0.4, 95% CI 0.2–0.8).ConclusionsWe present a summary of early predictors of functional outcome in poor-grade aSAH patients that can help to discriminate between patients with favorable and with unfavorable prognosis and may aid in selecting patients for early aneurysm treatment.

Clinical condition of 120 patients alive at 3 years after poor-grade aneurysmal subarachnoid hemorrhage

BackgroundTo study the clinical condition of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients alive at 3 years after neurointensive care.MethodsOf the 769 consecutive aSAH patients from a defined population (2005–2015), 269 (35%) were in poor condition on admission: 145 (54%) with H&H 4 and 124 (46%) with H&H 5. Their clinical lifelines were re-constructed from the Kuopio Intracranial Aneurysm Database and Finnish nationwide registries. Of the 269 patients, 155 (58%) were alive at 14 days, 125 (46%) at 12 months, and 120 (45%) at 3 years.ResultsThe 120 H&H 4–5 patients alive at 3 years form the final study population. On admission, 73% had H&H 4 but only 27% H&H 5, 59% intracerebral hematoma (ICH; median 22 cm3), and 26% intraventricular blood clot (IVH). The outcome was favorable (mRS 0–1) in 45% (54 patients: ICH 44%; IVH clot 31%; shunt 46%), moderate (mRS 2–3) in 30% (36 patients: ICH 64%; IVH clot 19%; shunt 42%), and unfavorable (mRS 4–5) in 25% (30 patients: ICH 80%; IVH clot 23%; shunt 50%). A total of 46% carried a ventriculoperitoneal shunt. ICH volume was a significant predictor of mRS at 3 years.ConclusionsOf poor-grade aSAH patients, 45% were alive at 3 years, even 27% of those extending to pain (H&H 5). Of the survivors, 75% were at least in moderate condition, while only 2.6% ended in hospice care. Consequently, we propose non-selected admission to neurointensive care (1) for a possibility of moderate outcome, and (2), in case of brain death, possibly improved organ donation rates.

Scoring Model to Predict Functional Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

Background: Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as World Federation of Neurosurgical Societies (WFNS) grades IV–V have high rates of disability and mortality. The objective of this study was to accurately prognosticate the outcomes of patients with poor-grade aSAH by developing a new scoring model.Methods: A total of 147 poor-grade aSAH patients in our center were enrolled. Risk variables identified by multivariate logistic regression analysis were used to devise a scoring model (total score, 0–9 points). The scores were estimated on the basis of β coefficients. A cohort of 68 patients from another institute was used to validate the model.Results: Multivariate logistic regression analysis revealed that modified Fisher grade >2 [odds ratio [OR], 2.972; P = 0.034], age ≥65 years (OR, 3.534; P = 0.006), conservative treatment (OR, 5.078; P = 0.019), WFNS grade V (OR, 2.638; P = 0.029), delayed cerebral ischemia (OR, 3.170; P = 0.016), shunt-dependent hydrocephalus (OR, 3.202; P = 0.032), and cerebral herniation (OR, 7.337; P < 0.001) were significant predictors for poor prognosis [modified Rankin Scale [mRS] ≥3]. A scoring system was constructed by the integration of these factors and divided the poor-grade aSAH patients into three categories: low risk (0–1 points), intermediate risk (2–3 points), and high risk (4–9 points), with predicted risks of poor prognosis of 11, 52, and 87%, respectively (P < 0.001). The area under the curve in the derivation cohort was 0.844 (95% CI, 0.778–0.909). The AUC in the validation cohort was 0.831 (95% CI, 0.732–0.929).Conclusions: The new scoring model can improve prognostication and help decision-making for subsequent complementary treatment in patients with aSAH.

Circulatory dipeptidyl peptidase 3 (cDPP3) is a potential biomarker for early detection of secondary brain injury after aneurysmal subarachnoid hemorrhage

IntroductionDelayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) that can culminate in secondary brain damage. Although it remains one of the main preventable causes of aSAH-related morbidity, there is still a lack of prognostic criteria for identification of patients at risk of developing DCI. Because elevated circulatory levels of the enzyme dipeptidyl peptidase 3 (cDPP3) were recently identified as a potential biomarker for outcome prediction in critically ill patients, we evaluated the time-course of changes in cDPP3 levels after aSAH. Materials and methodscDPP3 levels were quantified in serum obtained from 96 confirmed aSAH patients during the early (EP: d1–4), critical (CP: d5–8, d9–12, d13–15) and late (LP: d16–21) phase after aSAH onset. Associations between cDPP3 levels and demographic or clinical parameters were evaluated. The relations between cDPP3 levels and DCI, DCI-related infarctions and long-term clinical outcomes were examined by receiver operating characteristics (ROC) curve analysis and multivariate logistic regression. ResultsSignificantly higher cDPP3 levels during CP (d5–8, d9–12, d13–15) were observed in patients with poor clinical (p < 0.001 to p = 0.033) or radiological (p = 0.012 to p = 0.039) status on admission, DCI (p < 0.001 to p = 0.001), DCI-related infarctions (p = 0.002 to p = 0.007), and poorer long-term outcome (p = 0.007 to p = 0.019). ROC curve analysis indicated that higher cDPP3 levels on d5–8 are predictive for a poor clinical outcome (area under the curve = 0.677, p = 0.007). In multivariate analysis, there was an independent association between cDPP3 levels on d5–8 and development of DCI-related infarctions (p = 0.038). ConclusionOur results provide first evidence that cDPP3 could serve as a promising biomarker for early diagnosis of DCI-related infarctions in poor grade aSAH patients.

Long-Term Outcomes of Elderly Patients with Poor-Grade Aneurysmal Subarachnoid Hemorrhage

Long-term outcomes after surgical treatment and intensive care have not been investigated in elderly patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to analyze 12-month outcomes and prognostic factors of patients with poor-grade aSAH who were at least age 70 years. We performed a single-center, retrospective study including poor-grade (World Federation of Neurological Societies [WFNS] grades IV and V) aSAH patients who were at least age 70 years, were admitted to our stroke center, and received aneurysmal treatment between April 2012 and September 2018. The clinical outcomes were evaluated at months 3 and 12. Univariate/multivariate analyses were performed to identify the independent prognostic factors of good neurologic outcomes (modified Rankin Scale score 0-3). These factors included sex, age, WFNS grade, Fisher group, delayed cerebral ischemia, aneurysm treatment, aneurysm size, aneurysm location, and blood examination data in the 14 days post subarachnoid hemorrhage. The proportion of patients with good outcomes (modified Rankin Scale score 0-3) was increased at 12 months compared with that at 3 months. No intracerebral hemorrhage was a significant predictor of good neurologic outcomes at 3 months (P= 0.03). The absence of delayed cerebral ischemia and small fluctuations in the average absolute daily difference from normal sodium levels were significant predictors of good neurologic outcomes at months 3 and 12 (P= 0.04 and P= 0.03, respectively). The absence of delayed cerebral ischemia and small fluctuations in the average absolute daily difference from the normal sodium levels were independently associated with good neurologic outcomes at 12 months in elderly patients. Intracerebral hemorrhage did not appear to affect long-term outcomes. These findings suggest that elderly patients with severe subarachnoid hemorrhage should not be excluded from receiving surgical treatment on the basis of their age alone.

Primary decompressive craniectomy in poor-grade aneurysmal subarachnoid hemorrhage: long-term outcome in a single-center study and systematic review of literature

Primary decompressive craniectomy (PDC) in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) in order to decrease elevated intracranial pressure (ICP) is controversially discussed. The aim of this study was to analyze the effect of PDC on long-term clinical outcome in these patients in a single-center cohort and to perform a systematic review of literature. Eighty-seven consecutive poor-grade SAH patients (World Federation of Neurosurgical Societies (WFNS) grades IV and V) were analyzed between October 2012 and August 2017 at the author’s institution. PDC was performed due to clinical signs of herniation or brain swelling according to the treating surgeon. Outcome was analyzed according to the modified Rankin Scale (mRS). Literature was systematically reviewed up to August 2019, and data of poor-grade aSAH patients who underwent PDC was extracted for statistical analyses. Of 87 patients with poor-grade aSAH in the single-center cohort, 38 underwent PDC and 49 did not. Favorable outcome at 2 years post-hemorrhage did not differ significantly between the two groups (26% versus 20%). Systematic literature review revealed 9 studies: Overall, a favorable outcome could be achieved in nearly half of the patients (49%), with an overall mortality of 24% (median follow-up 11 months). Despite a worse clinical status at presentation (significantly higher rate of mydriasis and additional ICH), poor-grade aSAH patients with PDC achieve favorable outcome in a significant number of patients. Therefore, treatment and PDC should not be omitted in this severely ill patient collective. Prospective controlled studies are warranted.

Intermediate surgical outcome in patients suffering poor-grade aneurysmal subarachnoid hemorrhage. A single center experience

Background It is known that patients suffering poor-grade aneurysmal subarachnoid hemorrhage (aSAH) have a dismal prognosis. The importance of early intervention is well established in the pertinent literature. Our aim was to assess the functional outcome and overall survival of these patients undergoing surgical clipping. Material and methods In the current retrospective study we included all consecutive poor-grade patients after spontaneous SAH who presented at our institution over an eight-year period. All participants suffering SAH underwent brain CT angiography (CTA) to identify the source of hemorrhage. We assessed the severity of hemorrhage according to the Fisher grade classification scale. All patients were surgically treated. The functional outcome was evaluated six months after the onset with the Glasgow Outcome Scale. Finally, we performed logistic and Cox regression analyses to identify potential prognostic risk factors. Results Our study included twenty-three patients with a mean age of 53 years. Five (22%) patients presented with Hunt and Hess grade IV, and eighteen (78%) with grade V. The mean follow-up was 15.8 months, while the overall mortality rate was 48%. The six-month functional outcome was favorable in 6 (26%) patients. The vast majority of our patients died between the 15th and the 60th post-ictal days. We did not identify any statistically significant prognostic factors related to the patient’s outcome and/or survival. Conclusions Poor-grade aSAH patients may have a favorable outcome with proper surgical management. Large-scale studies are necessary for accurately outlining the prognosis of this entity, and identifying parameters that could be predictive of outcome.

Elevated hemoglobin is associated with poor prognosis in Tibetans with poor-grade aneurysmal subarachnoid hemorrhage after clipping: A Retrospective Case-Control Study

ObjectivesHigh hemoglobin (HGB) concentration is frequently seen in Tibetans in clinical practice; however, the impact on postsurgical prognosis in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is not precisely known. Thus, we sought to understand the association between high HGB level and postoperative outcome in Tibetans with poor-grade aSAH. Patients and methodsResults of clipping in consecutive Tibetan patients with poor-grade aSAH were analyzed retrospectively for the period January 2012 to January 2017. Based on the upper limit (160g/L) of normal hemoglobin levels, patients were divided to a high (HHC) and a normal (NHC) HGB-level cohort according to the first routine blood result on admission. Propensity score matching was used for baseline matching in the 2 cohorts. Postoperative complications in the 2 groups were compared. Prognosis after ictus, including 6-month neurological functional status and mortality at 30 days and 6 months were also assessed. ResultsRisk of ischemia, pulmonary embolism and lower-limb deep venous thrombosis (DVT) was higher in HHC than NHC (62.88% vs. 21.64%; P<0.001; 10.30% vs. 1.31%, P<0.005; 24.74% vs. 7.21%, P<0.001, respectively). Hospital stay also differed significantly (15.82±3.86 vs. 10.37±4.80 days; P<0.001). Out of the 194 patients, 150 survived at 6 months. At 6-month neurological functional follow-up, 8 NHC patients had favorable modified Rankin scale (mRS) scores ≤2 at discharge, versus only 1 HHC patient, showing better outcome in NHC than HHC (8.25% vs. 1.03%; P=0.035). In-hospital mortality was significantly greater in HHC than NHC (17.52% vs. 7.22%; P=0.029). 30-day post-ictus mortality was 30.93% in HHC versus 14.43% in NHC (P<0.006). There was also a significant difference in mortality at 6 months post-ictus (47.42% vs. 18.56%; P<0.001). ConclusionHigh HGB level was associated with increased risk of postsurgical cerebral ischemia, pulmonary embolism and lower-limb DVT and poor prognosis in poor-grade aSAH patients. Preoperative hemodilution therapy might be beneficial in reducing operative complications, reducing hospital stay and improving short-term prognosis for neurological functional recovery in aSAH patients with high HGB concentration, but further detailed research is needed.

The path from ictus to Neurosurgery: chronology and transport logistics of patients with aneurysmal subarachnoid haemorrhage in the South-Eastern Norway Health Region.

Guidelines state that patients with aneurysmal subarachnoid haemorrhage (aSAH) require neurosurgical treatment as early as possible. Little is known about the time frame of transport from the ictus scene to Neurosurgery in large, partially remote catchment areas. We therefore analysed the chronology and transport logistics of aSAH patients in the South-Eastern Norway Health Region and related them to the frequency of aneurysm rebleed and 1-year mortality. Retrospective analysis of aSAH patients bleeding within our region admitted to Neurosurgery during a 5-year period. Date, time and site of ictus and arrival at Neurosurgery, distance and mode of transport and admission were obtained from our institutional quality register and the emergency medical communication centre log. We scored the patients' clinical condition, rebleeds and 1-year mortality. Five hundred forty-four patients were included. Median time from ictus to arrival Neurosurgery was 4.5h. Transport by road ambulance was most common at distances between the ictus scene and Neurosurgery below 50km, whereas airborne transport became increasingly more common at larger distances. Direct admissions, frequency of intubation and airborne transport to Neurosurgery increased with the severity of haemorrhage, leading to shorter transport times. The risk of rebleed was 0.8%/hour of transport. The rebleed rate was independent of distances travelled, but increased with the severity of aSAH, reaching up to 6.54%/hour in poor-grade patients. Distance and time of transport had no impact on 1-year mortality, whereas poor-grade aSAH and rebleed were strong predictors of mortality. Poor-grade aSAH patients have a high risk of rebleed independent of the distance between the ictus scene and Neurosurgery. As rebleeding triples 1-year mortality, patients with Glasgow Coma Score < 9 with suspected aSAH should be admitted directly to Neurosurgery without delay after best possible cardiovascular and airway optimisation on site by competent personnel.

Safety and feasibility of lumbar drainage in the management of poor grade aneurysmal subarachnoid hemorrhage

The use of lumbar drain (LD) in the aneurysmal subarachnoid hemorrhage (aSAH) has been described to reduce cerebral vasospasm and delayed cerebral ischemia (DCI), with a lack of studies referring to high grade population. The purpose of our study is to assess safety and feasibility of LD in the poor grade aSAH population subjected to endovascular aneurysm occlusion.Twenty-four consecutive poor grade aSAH patients, defined as grade IV and V according to World Federation of Neurological Surgeons (WFNS) classification, subjected to endovascular aneurysm occlusion, were retrospectively reviewed. Details of CSF drainage via LD and related complications were analyzed. Ventriculo-lumbar pressure gradient (VLPG) lower than 6 mmHg was considered in order to start LD use. Good outcome was defined as modified Rankin Scale (mRS) 0–2.LD was started within 72 h since aSAH in 17 cases (70.8%), and in 7 cases (29.2%) it was delayed due to contraindications. The mean LD length was of 13.8 days. The median VLPG during drainage was 2 mmHg (IQR: 0–4). No cases of brain or spinal hemorrhage, permanent neurological worsening due to brain herniation were noted. Three cases (12.5%) of CSF infection and a related death (4.2%) were reported.The use of LD, in association with external ventricular drain (EVD), seems to be safe and feasible in the poor grade aSAH population. VLPG monitoring seems to play a key role in avoiding potentially severe complications.

An Observational Study on the Use of Intravenous Non-Opioid Analgesics and Antipyretics in Poor-Grade Subarachnoid Hemorrhage: Effects on Hemodynamics and Systemic and Brain Temperature.

Intravenous nonsteroidal anti-inflammatory drugs and nonopioid analgesics are used to achieve normothermia or relieve pain in patients with aneurysmal subarachnoid hemorrhage (aSAH). We investigated the effects of paracetamol (1 g), diclofenac (75 mg) and metamizole (1 g) on systemic and cerebral hemodynamics and temperature during febrile and nonfebrile episodes after aSAH. Prospectively collected data from 77 consecutive poor-grade aSAH patients with invasive neuromonitoring were included. The burden and occurrence of hypotension (mean arterial pressure <70 mmHg), brain tissue hypoxia (PbtO2 < 20 mmHg), high intracranial pressure (>22 mmHg), low cerebral perfusion pressure (CPP <70 mmHg), and cerebral autoregulation pressure (pressure reactivity index [PRx]) during baseline (1 hour before) and 6 hours after medication were analyzed in febrile (core temperature; Tcore ≥ 38.3°C) and nonfebrile episodes. Nine hundred eighty-nine infusions (278 paracetamol, 542 diclofenac, and 169 metamizole) were administered resulting in significant reduction of core and brain temperature during febrile (49%) and nonfebrile (51%) episodes (p < 0.001). In febrile cases, temperature decreased for >1 hour below 37.5°C in 36% of interventions and ≤37°C in 11%. Hemodynamic side effects with hypotension and low CPP occurred in both febrile and nonfebrile episodes (p < 0.001) prompting increased vasopressor support in 31% of cases, even more pronounced during the vasospasm period (4-12 days postictus) (OR 5.4, 95% CI 1.8-16). The magnitude of PbtO2-decrease is directly correlated with the decrease in Tcore (p = 0.002) and higher baseline PbtO2 (p < 0.001). PRx decreased in febrile and nonfebrile episodes (p < 0.001), indicating improvement of cerebrovascular autoregulation. Antipyretics were insufficient to achieve sustained normothermia in poor-grade aSAH patients. Hemodynamic side effects were common even when given as analgesic drugs. Further studies are needed to weigh hemodynamic side effects to benefits (inter alia improved cerebral autoregulation).

Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Risk Factors Affecting Clinical Outcomes in Intracranial Aneurysm Patients in a Multi-Center Study.

Objective: Patients with poor-grade aneurysm subarachnoid hemorrhage (SAH) have commonly been considered to have a poor prognosis. The objective of this study was to investigate the independent risk factors affecting clinical outcomes in intracranial aneurysm patients with poor-grade aneurysm subarachnoid hemorrhage (aSAH) underwent different intervention therapies.Methods: A multicenter observational registry of 324 poor-grade aSAH patients treated at tertiary referral centers from October 2010 to March 2012 were enrolled in this study. The clinical data including patient characteristics on admission and during treatment course, treatment modality, aneurysm size and location, radiologic features, signs of cerebral herniation (dilated pupils), and functional neurologic outcome were collected. Clinical outcomes were assessed via a modified Rankin Scale at 12 months. Multivariate logistic regression models were used to develop prognostic models. The area under the receiver operator characteristic curves (AUC) and Hosmer-Lemeshow tests were used to assess discrimination and calibration. WAP score was developed to predict risk of poor outcome.Results: Older age, female gender, ventilated breathing status, non-reactive pupil response, pupil dilation, lower GCS score, a WFNS grade of V, intraventricular hemorrhage, a higher Fisher grade, a higher modified Fisher grade, and conservative treatment were calculated to be associated with a relatively poor outcome. Multivariate analyses revealed that older age, lower Glasgow coma scale score (GCS), the absence of pupillary reactivity, higher modified Fisher grade, and conservative treatment were independent predictors of poor outcome, showed good discrimination and calibration. Patients with WFNS grade V, older age and non-reactive pupillary reactivity were predicted to have a poor outcome by WAP risk score.Conclusions: A simple WAP risk score had good discrimination and calibration in the prediction of outcome. The risk score can be easily measured and may complement treatment decision-making.

Brain Extracellular Interleukin-6 Levels Decrease Following Antipyretic Therapy with Diclofenac in Patients with Spontaneous Subarachnoid Hemorrhage.

In patients with aneurysmal subarachnoid hemorrhage (aSAH), increased brain extracellular interleukin (IL)-6 levels measured by cerebral microdialysis (CMD) were associated with disease severity, early brain injury, delayed cerebral infarction, and axonal injury. In this study, we analyzed brain extracellular IL-6 levels of aSAH patients following parenteral diclofenac. Twenty-four mechanically ventilated poor-grade aSAH patients were included. Changes in cerebral metabolism, brain/body temperature, and CMD-IL-6 levels following intravenous diclofenac infusion (DCF; 75 mg diluted in 100 cc normal saline) were retrospectively analyzed from prospectively collected bedside data (at 1 hour before DCF = baseline; and at 2, 4, and 8 hours after DCF). Statistical analysis was performed using generalized estimating equations. Seventy-two events in 24 aSAH patients were analyzed. Median age was 60 years (interquartile range [IQR]: 52-67), admission Hunt & Hess grade was 4 (IQR: 3-5), and modified Fisher grade (mFisher) was 4 (IQR: 3-4). Higher CMD-IL-6 levels at baseline were linked to fever, higher mFisher, delayed cerebral infarction, and metabolic distress (p < 0.05). CMD-IL-6 levels at baseline were 281.4 pg/mL (IQR: 47-1866) and significantly (p < 0.001; Wald-X2 = 106) decreased at 2 hours to 86.3 pg/mL (IQR: 7-1946), at 4 hours to 40.9 pg/mL (IQR: 4-1237), and at 8 hours to 53.5 pg/mL (IQR: 5-1085), independent of probe location or day after bleeding. Parenteral diclofenac may attenuate brain extracellular proinflammatory response in poor-grade aSAH patients.

Neuroinflammation is Associated with Brain Extracellular TAU-Protein Release After Spontaneous Subarachnoid Hemorrhage.

Animal data suggest an association between neuroinflammation and secondary brain injury including axonal injury after aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between brain extracellular interleukin (IL)-6 and TAU-protein levels as a surrogate marker for neuroinflammation and axonal injury in patients with poor grade aSAH. Prospectively collected data from 26 consecutive poor-grade aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD) were retrospectively analyzed. IL-6 and TAU-protein levels were analyzed using ELISA from a single CMD-sample every 24 hours and correlated with brain metabolic and hemodynamic parameters. Patients were dichotomized to highgrade (N=10) or low-grade (N=16) neuroinflammation according to their median CMD-IL-6 levels. Data were analyzed using generalized estimating equations to account for multiple within-subject measurements. Perilesional probe location (P=0.02) and aSAH related intracerebral hemorrhage (aICH) volume (P=0.003) at admission were associated with high-grade neuroinflammation. Brain extracellular TAU-protein levels (P=0.001), metabolic distress and delayed cerebral infarction (DCI; P=0.001) were linked to high-grade neuroinflammation. Relative or absolute phosphor-TAU levels were not correlated with CMD-IL-6 levels. High-grade neuroinflammation was a predictor for worse outcome three months after ictus, independently from probe location, initial Hunt&amp;Hess grade and age (P=0.01). Neuroinflammation after aSAH is associated with intraparenchymal bleeding, deranged cerebral metabolism and TAU-protein release. The impact of potential anti-inflammatory treatment strategies on secondary brain injury after aSAH has to be investigated in future studies.

Management strategy and prognosis analysis for poor-grade aneurysmal subarachnoid hemorrhage

Objective To investigate the efficacy of microsurgery and predictors of outcome for poor-grade aneurysmal subarachnoid hemorrhage(aSAH). Methods Clinical data of 43 patients of poor-grade aSAH who performed microsurgery were retrospectively analyzed.There were 30 patients with Hunt-Hess grade IV and 13 patients with grade V.24 patients received emergency operation(within 6hours after onset), 16 patients received ultra-early operation(within first 24hours after onset).Outcome was assessed by Glascow Outcome Scale(GOS). Results Of 43 patients who received microsurgery, favorable outcome was achieved by 19 cases of 43 cases (44.2%), poor outcome was achieved by 16 cases of 43 cases (37.2%), the overall outcome of patients with Hunt-Hess grade IV was better than that with grade V(Z=-2.486, P=0.016).18 patients with intracerebral hematoma received ultra-early or emergency operation, effective surgical intervention(GOS≥3) achieved in 12 patients, there was no significant difference in prognosis between the patients and the others who without intracerebral hematomas(χ2=0.103, P=1.000). Conclusion The ultra-early or emergency surgery could avoid the risk of aneurysmal re-rupture, relieve malignant intracranial hypertension as soon as possible and decrease the mortality of poor-grade aSAH patients. Key words: Subarachnoid hemorrhage; Intracranial aneurysm; Microsurgery

Early brain injury after aneurysmal subarachnoid hemorrhage: a multimodal neuromonitoring study.

IntroductionThere is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Cerebral microdialysis (CMD) allows online measurement of brain metabolites, including the pro-inflammatory cytokine interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9), which is indicative for disruption of the blood-brain barrier.MethodsTwenty-six consecutive poor-grade aSAH patients with multimodal neuromonitoring were analyzed for brain hemodynamic and metabolic changes, including CMD-IL-6 and CMD-MMP-9 levels. Statistical analysis was performed by using a generalized estimating equation with an autoregressive function.ResultsThe baseline cerebral metabolic profile revealed brain metabolic distress and an excitatory response which improved over the following 5 days (P <0.001). Brain tissue hypoxia (brain tissue oxygen tension of less than 20 mm Hg) was common (more than 60% of patients) in the first 24 hours of neuromonitoring and improved thereafter (P <0.05). Baseline CMD-IL-6 and CMD-MMP-9 levels were elevated in all patients (median = 4,059 pg/mL, interquartile range (IQR) = 1,316 to 12,456 pg/mL and median = 851 pg/mL, IQR = 98 to 25,860 pg/mL) and significantly decreased over days (P <0.05). A higher pro-inflammatory response was associated with the development of delayed cerebral ischemia (P = 0.04), whereas admission disease severity and early brain tissue hypoxia were associated with higher CMD-MMP-9 levels (P <0.03). Brain metabolic distress and increased IL-6 levels were associated with poor functional outcome (modified Rankin Scale of more than 3, P ≤0.01). All models were adjusted for probe location, aneurysm securing procedure, and disease severity as appropriate.ConclusionsMultimodal neuromonitoring techniques allow insight into pathophysiologic changes in the early phase after aSAH. The results may be used as endpoints for future interventions targeting EBI in poor-grade aSAH patients.