Tag: Vasospasm

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Low-Dose Intravenous Heparin Infusion After Aneurysmal Subarachnoid Hemorrhage is Associated With Decreased Risk of Delayed Neurological Deficit and Cerebral Infarction

Neurosurgery 88 (3)2021: 523–530

Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily).

OBJECTIVE: To assess the safety and efficacy of LDIVH in aSAH patients.

METHODS: We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome datawere compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW).

RESULTS: The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTWshowed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts.

CONCLUSION: This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.

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Reliable Identification of Benign Clinical Course in Aneurysmal Subarachnoid Hemorrhage

Neurosurgery 83:948–956, 2018

A reliable method to specifically identify low vasospasm risk in aneurysmal subarachnoid hemorrhage (aSAH) patients has not been previously proposed.

OBJECTIVE: To develop a clinical algorithm using admission aSAH clinical severity and subarachnoid blood distribution to identify patients at low risk of clinical vasospasm.

METHODS: Clinical severities, admission noncontrasted head computerized tomography (CT) scan, and incidences of vasospasm among 291 aSAH patients treated at our institutionwere evaluated. Admission head CTswere assessed for distributions of cisternal and ventricular blood. Patients with the following 4 criteria experienced considerably lower risk of vasospasm: (1) Hunt Hess grade 1 to 2, (2) Lack of thick subarachnoid blood filling 2 adjacent cisterns, (3) Lack of thick interhemispheric blood, and (4) Lack of biventricular intraventricular hemorrhage.

RESULTS: One hundred thirty-three patients (45.7%) developed cerebral vasospasm. Hunt Hess grade greater than 2 (odds ratio [OR] 4.52, 95% confidence interval [CI] 2.74-7.46), adjacent cistern blood (OR 4.1, 95% CI 2.51-6.7), interhemispheric thick blood (OR 5.72, 95% CI 3.41-9.59), and biventricular intraventricular hemorrhage (OR 1.92, 95% CI 1.19-3.02) were significant risk factors. Application of our algorithm yielded a sensitivity of 29%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 54.5%, which was superior compared to metrics from current institutional practice criteria. Inter-rater agreement was substantial at mean kappa = 0.75.

CONCLUSION: Application of our novel clinical algorithm produced successful identification of aSAH patients who experience zero risk of clinical vasospasm. Our algorithm is simple to apply with high reliability and is superior to currently available clinical and radiographic metrics.

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Effect of statin treatment on vasospasm-related morbidity and functional outcome in patients with aneurysmal subarachnoid hemorrhage

J Neurosurg 127:291–301, 2017

The efficacy of statin therapy in treating aneurysmal subarachnoid hemorrhage (SAH) remains controversial. In this meta-analysis, the authors investigated whether statin treatment significantly reduced the incidence of cerebral vasospasm and delayed neurological deficits, promoting a better outcome after aneurysmal SAH.

METHODS: A literature search of the PubMed, Ovid, and Cochrane Library databases was performed for randomized controlled trials (RCTs) and prospective cohort studies investigating the effect of statin treatment. The end points of cerebral vasospasm, delayed ischemic neurological deficit (DIND), delayed cerebral infarction, mortality, and favorable outcome were statistically analyzed.

RESULTS Six RCTs and 2 prospective cohort studies met the eligibility criteria, and a total of 1461 patients were included. The meta-analysis demonstrated a significant decrease in the incidence of cerebral vasospasm (relative risk [RR] 0.76, 95% confidence interval [CI] 0.61–0.96) in patients treated with statins after aneurysmal SAH. However, no significant benefit was observed for DIND (RR 0.88, 95% CI 0.70–1.12), delayed cerebral infarction (RR 0.66, 95% CI 0.33–1.31), mortality (RR 0.69, 95% CI 0.39–1.24) or favorable outcome, according to assessment by the modified Rankin Scale or Glasgow Outcome Scale (RR 0.99, 95% CI 0.92–1.17).

CONCLUSIONS Treatment with statins significantly decreased the occurrence of vasospasm after aneurysmal SAH. The incidence of DIND, delayed cerebral infarction, and mortality were not affected by statin treatment. Future research should focus on DIND and how statins influence DIND.

 

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Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage

Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage

J Neurosurg 125:128–136, 2016

This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI).

Methods: Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)–measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated.

Results: Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD–measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI.

Conclusions: Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD–measured BFV increase or persisting coma, do not contribute to information gain.

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Continuous cisternal irrigation with Mg solution for vasospasm

Mg sulfate irrigation

J Neurosurg 124:18–26, 2016

Although cerebral vasospasm (CV) is one of the most important predictors for the outcome in patients with subarachnoid hemorrhage (SAH), no treatment has yet been established for this condition. This study investigated the efficacy of continuous direct infusion of magnesium sulfate (MgSO4) solution into the intrathecal cistern in patients with an aneurysmal SAH.

Methods An SAH caused by a ruptured aneurysm was identified on CT scans within 72 hours after SAH onset. All patients were treated by surgical clipping and randomized into 2 groups: a control group of patients undergoing a standard treatment and a magnesium (Mg) group of patients additionally undergoing continuous infusion of 5 mmol/L MgSO4 solution for 14 days. The Mg2+ concentrations in serum and CSF were recorded daily. Neurological examinations were performed by intensive care clinicians. Delayed cerebral ischemia was monitored by CT or MRI. To assess the effect of the Mg treatment on CV, the CVs were graded on the basis of the relative degree of constriction visible on cerebral angiograms taken on Day 10 after the SAH, and transcranial Doppler ultrasonography was performed daily to measure blood flow velocity in the middle cerebral artery (MCA). Neurological outcomes and mortality rates were evaluated with the Glasgow Outcome Scale and modified Rankin Scale at 3 months after SAH onset.

Results Seventy-three patients admitted during the period of April 2008 to March 2013 were eligible and enrolled in this study. Three patients were excluded because of violation of protocol requirements. The 2 groups did not significantly differ in age, sex, World Federation of Neurosurgical Societies grade, or Fisher grade. In the Mg group, the Mg2+ concentration in CSF gradually increased from Day 4 after initiation of the continuous MgSO4 intrathecal administration. No such increase was observed in the control group. No significant changes in the serum Mg2+ levels were observed for 14 days, and no cardiovascular complications such as bradycardia or hypotension were observed in any of the patients. However, bradypnea was noted among patients in the Mg group. The Mg group had a significantly better CV grade than the control group (p < 0.05). Compared with the patients in the Mg group, those in the control group had a significantly elevated blood flow velocity in the MCA. Both groups were similar in the incidences of cerebral infarction, and the 2 groups also did not significantly differ in clinical outcomes.

Conclusions Continuous cisternal irrigation with MgSO4 solution starting on Day 4 and continuing to Day 14 significantly inhibited CV in patients with aneurysmal SAH without severe cardiovascular complications. However, this improvement in CV neither reduced the incidence of delayed cerebral ischemia nor improved the functional outcomes in patients with SAH.

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Intraoperative rerupture during surgical treatment of aneurysmal subarachnoid hemorrhage is not associated with an increased risk of vasospasm

aneurysm

J Neurosurg 120:409–414, 2014

Intraoperative rerupture during open surgical clipping of cerebral aneurysms in subarachnoid hemorrhage (SAH)is a relatively frequent and potentially catastrophic occurrence. Patients who suffer rerupture have been shown to have worse outcomes at discharge compared with those who do not have rerupture. Perioperative injury likely plays a large part in the clinical worsening of these patients. However, due to the increased vessel manipulation and repeat exposure to acute hemorrhage, it is possible that secondary injury from increased incidence of vasospasm also contributes. Identifying an increased rate of vasospasm in these patients would justify early aggressive treatment with measures to prevent delayed cerebral ischemia. The authors investigated whether patients who suffer intraoperative rerupture during surgical treatment of ruptured cerebral aneurysms are at increased risk of developing vasospasm.

Methods. Five hundred consecutive patients treated with open surgical clipping for SAH were reviewed, and clinical and imaging data were collected. Angiographic vasospasm was defined as vessel narrowing believed to be consistent with vasospasm on angiography. Symptomatic vasospasm was defined as angiographic vasospasm in the setting of a clinical change attributable to vasospasm. Rates of angiographic and symptomatic vasospasm among patients with and without intraoperative rerupture were compared.

Results. There were no significant differences between the groups with and without rupture with respect to age, sex, modified Fisher grade, history of hypertension, or smoking. The group with intraoperative rupture had more patients with Hunt and Hess Grade I. Angiographic vasospasm was noted in 279 (66%) of the 425 patients without rerupture compared with 49 (65%) of the 75 patients with rerupture (p = 1.0, Fisher’s exact test). Symptomatic vasospasm was noted in 154 (36%) of the 425 patients without rerupture, compared with 31 (41%) of the 75 patients with rerupture (p = 0.44, Fisher’s exact test). In multivariate analysis, higher modified Fisher grade was significantly predictive of vasospasm, whereas older age and male sex were protective.

Conclusions. This study found no significant influence of intraoperative rerupture during open surgical clipping on the rate of angiographic or symptomatic vasospasm. Brief exposure to acute hemorrhage and vessel manipulation associated with rerupture events did not affect the rate of vasospasm. Risk of vasospasm was related to increased modified Fisher grade, and inversely related to age and male sex. These results do not justify early, targeted vasospasm therapy in patients with intraoperative rerupture.

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Intraventricular Tissue Plasminogen Activator for the Prevention of Vasospasm and Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery 67:110-117, 2010 DOI: 10.1227/01.NEU.0000370920.44359.91

The sequelae of aneurysmal subarachnoid hemorrhage (SAH) include vasospasm and hydrocephalus.

OBJECTIVE: To assess whether intraventricular tissue plasminogen activator (tPA) results in less vasospasm, fewer angioplasties, or fewer cerebrospinal fluid shunting procedures.

METHODS: 41 patients (tPA group, Hunt and Hess 3, 4, 5) from 2007 to 2008 received intraventricular tPA and lumbar drainage for a minimum of 5 days (range 5-7 days) and were compared to a matched group of 35 patients from 2006 to 2007 (Control, HH 3, 4, 5). Statistical comparison was done by t test analysis or Fisher exact tests and data are expressed as average ± standard error of the mean.

RESULTS: There were no significant differences in demographic data, although the tPA group had a trend toward more surgical patients. The tPA group of patients had a significantly higher modified Fisher grade than controls (P < .001) and had a significantly better Hunt and Hess grade than controls (P < .03). The angioplasty rate was significantly lower among the tPA patients (15.0% ± 5.6) than controls (40.0% ± 8.5, P = .019). The number of days spent in severe vasospasm normalized over the 14-day monitoring period by transcranial Doppler was significantly lower in the tPA group (0.09 ± 0.02) than controls (0.17 ± 0.03). The shunt rate was significantly lower among tPA patients (17.5% ± 6.0) than controls (42.8% ± 8.6). There were 2 clinically silent tract hemorrhages in the tPA group (4.8%).

CONCLUSION: Intraventricular tPA is a safe and effective treatment for reducing both angioplasty and shunting rates in patients with SAH H&H Grades 3 to 5. A randomized trial is indicated.

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