Vasospasm after SAH due to aneurysm rupture of the anterior circle of Willis: value of TCD monitoring

OBJECTIVE: The aim of this study was to verify the presence of angiographic vasospasm in patients with transcranial Doppler (TCD) of high velocities after subarachnoid hemorrhage (SAH). METHODS: Seven hundred and eighty-six cases admitted within 48 hours after SAH due to the rupture of anterior circulation aneurysm, were prospectively studied with TCD. In cases of TCD velocities higher than 120 cm/s (TCD vasospasm), the patient underwent a control angiography. Hunt-Hess and Fisher's grade on admission CT and location of the aneurysm were related to occurrence of TCD vasospasm. The increase in TCD velocities within 24 hours was calculated and related to the presence of cerebral ischemia on discharge CT, considering three groups of patients: Group A with an increase in velocities higher than 60%, Group B with an increase in velocities between 30 and 60%, and Group C with an increase in velocities lower than 30%. RESULTS: TCD vasospasm was observed in 216 patients (27%). In 97% of patients with TCD vasospasm on middle cerebral artery (MCA) and in 71% with TCD vasospasm on anterior cerebral artery (ACA), control angiography confirmed the vasospasm, with a significant lower diagnostic TCD predictivity of ACA spasm (chi2=28.204, p=0.000). The overall positive predictive value of TCD was 89%. There was no significant correlation of TCD vasospasm with clinical status on admission and location of the aneurysm, but a significant correlation between occurrence of TCD vasospasm and Fisher's grade (chi2=15.470, p=0.002) and between the increase rate in TCD velocities and cerebral ischemia (chi2=56.564, p=0.000). CONCLUSION: Our study shows a good correlation between TCD and angiography to detect vasospasm on MCA, but the correlation is low for ACA. TCD alone cannot discriminate different hemodynamic pathways after SAH.     

The Value of CT Angiography and Transcranial Doppler Sonography in Triaging Suspected Cerebral Vasospasm in SAH Prior to Endovascular Therapy

Background  Transcranial Doppler sonography (TCD) is a noninvasive method for detecting arterial cerebral vasospasm (CVS) in aneurysmal subarachnoid hemorrhage (SAH). Computed tomographic angiography (CTA) has been increasingly used for CVS diagnosis. The purpose of this study was to evaluate the degree of agreement between TCD and CTA in diagnosing clinical CVS following SAH, and to define the role of CTA in triaging patients prior to digital subtraction angiography (DSA) and endovascular intervention. Methods  Fifty-five consecutive patients with aneurysmal SAH who underwent sequential TCD and CTA were analyzed. TCD CVS was defined as anterior circulation peak mean velocity (PMV) >160 cm/s, basilar artery (BA) PMV >90 cm/s, and Lindegaard ratio (LR) >6. CTA CVS was defined as >50% luminal narrowing in the affected vessel. Clinical CVS was defined as the onset of new focal neurological deficit attributed to delayed ischemic injury. Results  Thirteen patients (24%) had clinical CVS and 42 patients (76%) were asymptomatic. All patients with clinical CVS had also radiological evidence of CVS (agreement 100%). In 35 patients without clinical CVS, both tests agreed for absence of CVS in 28 cases (agreement 83%). The remaining 7 asymptomatic patients had radiological CVS only, in disagreement with clinical absence of CVS (17%). Conclusions  Clinical evaluation and TCD can reliably diagnose CVS in symptomatic patients and PMV >180 cm/s, or can rule out CVS in asymptomatic patients with PMV <140 cm/s. In this category of patients, adding a CTA to clinical evaluation and TCD may not be warranted.     

Vasospasm followed by diastolic flow reversal in the intracranial arteries after subarachnoid haemorrhage.

Vasospasm and raised intracranial pressure (ICP) are common complications in subarachnoid haemorrhage (SAH) due to ruptured intracranial aneurysm. Vasospasm can be reliably monitored by repeated transcranial Doppler (TCD) examinations. The changes in flow velocities due to vasospasm are useful for early diagnosis, monitoring effectiveness of treatment and determining prognosis. Intracranial pressure can also increase to dangerous levels and affect blood flow in the intracranial circulation. These changes in ICP may be evaluated by the spectral waveform patterns obtained during TCD examination. We describe the dynamic TCD spectral changes in a patient with SAH that progressed from vasospasm to diastolic flow reversal. These temporal changes observed during serial TCD examinations were well correlated with the ICP. Transcranial Doppler is a reliable, beat-to-beat, non-invasive and reproducible bedside test that can be used to monitor vasospasm and ICP in SAH. The use of TCD can be extended to other intracranial diseases that can potentially lead to an abnormally high ICP.     

Sensitivity and specificity of transcranial Doppler ultrasonography in the diagnosis of vasospasm following subarachnoid hemorrhage

Vasospasm is the leading cause of death and disability in patients with aneurysmal subarachnoid hemorrhage (SAH). Transcranial Doppler ultrasonography (TCD) can detect the arterial narrowing noninvasively, but the sensitivity and specificity of this technique have not been reported in a population of patients with a high frequency of angiographic vasospasm. In this study, 34 consecutive patients with SAH undergoing angiography during the period of risk for vasospasm had technically adequate TCD examinations within 24 hours of the angiogram. Using a mean flow velocity of 120 cm/sec and above as indicative of vasospasm, TCD correctly detected angiographic vasospasm in 17 patients; there were no false positives. It correctly determined that 5 patients did not have vasospasm, whereas there were 12 false negatives. False negatives were frequently due to angiographic vasospasm involving vessels not assessable by TCD. The correlation between mean flow velocity and the angiographic residual lumen diameter of the middle cerebral artery was statistically significant. These data suggest that TCD is a highly specific (100%), but less sensitive (58.6%) test for the detection of angiographic vasospasm following SAH. Confirmatory angiography may be avoided if the TCD study is positive, but additional studies may be necessary if the clinical picture is suspicious and the TCD study is negative.     

Statins may not protect against vasospasm in subarachnoid haemorrhage

Statins have been shown in two recent small phase I/II trials to be associated with a marked reduction in clinical and transcranial Doppler (TCD) evidence of vasospasm after aneurysmal subarachnoid haemorrhage (SAH). The purpose of this study was to assess the clinical impact of this treatment in a larger number of patients. Fifty-eight individuals were treated in the year before, and 72 patients treated in the year after, the introduction of a 2 week course of 40 mg/day pravastatin therapy for SAH. Statins did not result in reduced TCD velocities, clinical or angiographic vasospasm, or improvements in global outcome at the time of hospital discharge. A measurable reduction in the rates of vasospasm was expected, based on the size of the effect of statin therapy in the previous small studies. There remains significant uncertainty as to the role of statins in preventing vasospasm after SAH.     

Arteriovenous differences of oxygen and transcranial Doppler sonography in the management of aneurysmatic subarachnoid hemorrhage.

After subarachnoid hemorrhage (SAH) the detection of hemodynamically significant vasospasm is frequently difficult, especially in comatose patients. Most clinicians use transcranial Doppler sonography (TCD) to detect increasing mean blood flow velocities in the basal arteries as markers of cerebral vasospasm, without accounting for the effects of sedation and variations in blood pressure or pCO(2). This study was conducted to test the hypothesis that the arteriovenous difference of oxygen (avDO(2); in terms of % volume) could also be useful for the evaluation of vasospasm. A total of 22 SAH patients (M : F = 1 : 1.75, age 58+/-10 years, median Hunt and Hess grade 4) were prospectively enrolled. All patients were sedated with continuous doses of midazolam/fentanyl and/or propofol. TCD studies and avDO(2) measurements were conducted at the same time or in close succession. The blood flow velocity of the middle cerebral artery was recorded. A cranial CT scan was conducted if the avDO(2) increased by at least 0.8%. Overall, 82 measurements were recorded in 22 patients between days 1 and 13 after SAH. TCD mean flow velocities increased as expected. In contrast, avDO(2) decreased until post-hemorrhage day 4 before it increased again. Overall, after SAH, avDO(2) was significantly lower than in normal individuals. Cerebral infarction occurred primarily in patients with a maximal change of avDO(2) of more than 1%. TCD velocities alone are poor indicators of the severity of vasospasm. In contrast, daily avDO(2) seems to be a more robust parameter. However, collection of additional metabolic information is warranted.     

Intra-arterial papaverine used to treat cerebral vasospasm reduces brain oxygen

Introduction  

Intra-arterial papaverine (IAP) is used to treat symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). IAP, however, can increase intracranial pressure (ICP). In this study we examined whether IAP alters brain oxygen (BtO₂).     

Microembolic signals in subarachnoid hemorrhage

Microembolic signals (MES) detected by transcranial Doppler (TCD) have been reported in subarachnoid hemorrhage (SAH), although their origin and contribution to brain ischemia remain uncertain. We conducted a prospective study to evaluate the frequency of MES among patients with SAH and to determine their origin. Twenty-seven patients with SAH, comprising 15 aneurysmal and 12 non-aneurysmal patients, participated in the study. TCD evaluation was performed using a 2 MHz probe. Patients were studied three times per week during their in-patient stay to detect vasospasm, and then each middle cerebral artery (MCA) was monitored for 30 min using the Monolateral Multigate mode to detect MES. Using this method, MES were detected in 7 out of 15 patients (47%) with aneurysmal SAH and were not seen in non-aneurysmal patients (p = 0.007). Vasospasm occurred in 52% (14/27) of cases. However, clinical signs and symptoms of vasospasm were identified in only 18.5% (5/27). There was no significant relationship between MES and vasospasm (p = 0.224). Also, no relationship was found between MES and the location of the aneurysm (p = 0.685). Thus, in this study MES were only detected in aneurysmal SAH. However, we did not find a relationship between the location of the aneurysm and MES, or the presence of vasospasm and MES. Therefore, MES in patients with SAH may also originate from vascular pathology other than the aneurysm sac or vascular spasm.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛的脑血流动力学改变

目的探讨动脉瘤性蛛网膜下腔出血（aSAH）后脑血管痉挛（CVS）的血流动力学改变。方法对337例（382枚动脉瘤）aSAH患者临床资料进行回顾性分析,均经数字减影血管造影（DSA）和／或CT血管造影（CTA）检查证实为动脉瘤（An）,其中动脉瘤颈夹闭术297例,瘤颈夹闭及载瘤动脉塑形术29例,动脉瘤孤立术8例及包裹术3例。术后给予尼莫地平持续泵入扩血管、脑脊液引流、3H疗法等治疗,并于SAH1—3d．4～7d,8～14d、15～20d进行床边经颅超声多普勒（TCD）检测,主要观察MCA平均血流速度（VmMcA）、计算Lindegaard指数,即同侧MCA与颅外段ICAVm之比（LI）,观察CVS及颅内压（ICP）等脑血流动力学变化。结果SAH患者不同程度的存在CVS,25％的患者1—3d就出现CVS,8～14d达高峰;Hunt-Hess分级与CVS的变化成正相关;102例患者（102／337,30．3％）出现不同程度的颅内压增高;17例（17／337,5％）出现延迟性缺血性神经功能障碍（DIND）,颅内压增高且有CVS者预后较差。结论TCD可以床边、动态监测aSAH患者的脑血流动力学改变,具有无创、简单易行的特点。TCD检测的脑血流速度、Lindegaard指数和频谱形态相结合对临床和血管造影诊断CVS有价值。     

经颅多普勒监测蛛网膜下腔出血后脑血管痉挛的临床观察

目的总结应用经颅多普勒(TCD)监测蛛网膜下腔出血(SAH)后脑血管痉挛的临床价值。方法对2015-06—2016-05本院收治的78例SAH患者进行回顾性分析,均进行TCD监测,同时对患者进行数字减影血管造影(DSA)检查,观察各个时间段患者颅内血管血流速度变化,并以DSA检查结果作为标准判断TCD诊断颅内血管痉挛的价值。结果在7~10d时间段,患者的MCA、ACA、VA、BA血流速度达到峰值,后逐渐下降,颅内血管痉挛现象逐渐缓解;SAH患者MCA、ACA、VA、BA血流速度在7d、7~10d、10~14d三个时间段比较差异均具有统计学意义(P0.05);78例SAH患者,TCD诊断发生颅内血管痉挛59例,DSA诊断发生率颅内血管痉挛62例,TCD诊断SAH患者发生颅内血管痉挛的灵敏度为93.55%、特异度为93.75%、漏诊率为6.45%、误诊率为6.25%,TCD诊断颅内血管痉挛与DSA的一致性Kappa=0.816,P0.05。结论 TCD检查诊断SAH后出现颅内血管痉挛具有准确性高、无创等优点,值得临床推广应用。     

Intraventricular sodium nitroprusside therapy: a future promise for refractory subarachnoid hemorrhage-induced vasospasm

A prospective study was carried out to evaluate the efficacy of intraventricular sodium nitroprousside (SNP) in the reversal of refractory vasospasm secondary to aneurysmal subarachnoid hemorrhage (SAH). Ten patients of aneurysmal SAH with symptomatic vasospasm, corroborated on Transcranial Doppler (TCD) and/or angiography, were included in the study. The mean age distribution of the patients was 50.8 years (range 33-65 years) with an equal number of males and females. Once vasospasm was refractory even after 12 hours of SAH therapy, intraventricular SNP was instilled in an escalating dose and the reversal of vasospasm was monitored on TCD and/or angiography. All patients showed improvement in TCD velocity on day 0 through day 3. Partial to complete reversal of vasospasm was demonstrated on angiography in all the patients, though not in all the vessels. Two patients who had weakness of limbs due to vasospasm improved following intraventricular SNP therapy. Vomiting was the commonest adverse effect (7/10). Three patients had mild fluctuation in blood pressure. The overall outcome was good in 6 out of 10 patients. The study suggests that intraventricular SNP therapy is effective in reversing the changes even in established cases of SAH-induced vasospasm.     

The safety and feasibility of continuous intravenous magnesium sulfate for prevention of cerebral vasospasm in aneurysmal subarachnoid hemorrhage

Introduction: Cerebral vasospasm in aneurysmal subarachnoid hemorrhage (SAH) is associated with poor outcome. The safety and feasibility of continuous high-dose intravenous magnesium sulfate (MgSO₄) for the prevention of cerebral vasospasm and ischemic cerebral injury has not been well studied. Methods: Patients presenting to our center within 72 hours of aneurysmal SAH (confirmed by computed tomography [CT] scanning and cerebral angiography) between June 2001 and October 2002 were enrolled in a prospective pilot study in which they received MgSO₄ as an adjunct to standard SAH management. Study patients received an intravenous infusion of 12 g of MgSO₄ in a 500-mL solution of 0.9% NaCl administered at a rate of 4.06 mM (or 0.5 g) every hour over a 24-hour period for 10 days to achieve a target predetermined serum Mg range of more than 1.5 to less than 4.0 mM/L. The effect of MgSO₄ on clinical examination, heart rate, and blood pressure was measured every 2 hours; serum glucose and phenytoin levels were monitored daily. Outcome measures included evidence of vasospasm on clinical examination, transcranial Doppler study ((TCD); velocity ≥100 cm/s), or repeat cerebral angiogram obtained within 10 days of SAH; and Glasgow Outcome Scale (GOS) score assessment and CT scan evidence of ischemic infarction at 30 days. Results: Nineteen patients (mean age: 55 years; range: 39–84 years; 11 males, 8 females) were enrolled in the study. Presenting Hunt & Hess grade was II or higher; mean Fisher grade was 3. Vasospasm was observed in nine patients (by clinical examination in two, TCD in five, and angiogram in nine). The mean serum Mg level was 2.7 mM/L (standard deviation: ±0.37) and was maintained during the infusion period. No clinical adverse effects, hemodynamic changes, or fluctuations in serum glucose or phenytoin levels were observed. None of the patients died; no CT evidence of ischemic infarction was present; and most had good outcomes (GOS 5 in 10 patients; GOS 4 in 8 patients). Conclusion: Our study confirmed the safety and feasibility of a continuous infusion of high-dose intravenous MgSO₄ in patients with aneurysmal SAH. Randomized controlled trials are required to confirm the promising results.     

Metaanalysis of Tirilazad Mesylate in Patients with Aneurysmal Subarachnoid Hemorrhage

Background  Tirilazad is a non-glucocorticoid, 21-aminosteriod that inhibits lipid peroxidation. It had neuroprotective effects in experimental ischemic stroke and reduced angiographic vasospasm after experimental subarachnoid hemorrhage (SAH). Five randomized clinical trials of tirilazad were conducted in patients with SAH. We performed a meta-analysis of these trials to assess the effect of tirilazad on unfavorable outcome, symptomatic vasospasm, and cerebral infarction after SAH. Methods  Data from 3,797 patients were analyzed and modeled using random effect and Mantel-Haenszel meta-analyses and multivariable logistic regression to determine the effect of tirilazad on clinical outcome, symptomatic vasospasm, and cerebral infarction. Clinical outcome was assessed 3 months after SAH using the Glasgow outcome scale, and symptomatic vasospasm was defined by clinical criteria with laboratory and radiological exclusion of other causes of neurological deterioration. Results  The five trials were randomized, double-blind, and placebo-controlled. Tirilazad did not significantly decrease unfavorable clinical outcome on the GOS (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89–1.20) or cerebral infarction (OR 1.04, 95% CI 0.89–1.22). There was a significant reduction in symptomatic vasospasm in patients treated with tirilazad (OR 0.80, 95% CI 0.69–0.93). There was no heterogeneity across the five trials. Conclusion  Tirilazad had no effect on clinical outcome but did decrease symptomatic vasospasm in five trials of aneurysmal SAH. The dissociation between clinical outcome and symptomatic vasospasm deserves further investigation.     

蛛网膜下腔出血后脑血管痉挛实验研究

目的　在兔蛛网膜下腔出血 (SAH)模型上 ,尝试建立经颅多普勒超声 (TCD)及血管造影 ,监测椎基动脉脑血管痉挛 (CVS)的新方法。方法　兔枕大池一次性注血 ,同时行逆行颈总动脉插管椎基动脉造影及开骨窗TCD监测。结果　逆行性脑血管造影能清晰显示椎基底动脉系统 ,注血前后血管直径差异明显 (P <0 .0 5 ) ,平均血流速度注血后明显增快 ,但中、重度痉挛之间基底动脉血流速度变化无明显差异。结论　一侧颈总动脉逆行插管椎基动脉造影 ,操作简便 ,结果可靠。采取开骨窗以提高TCD超声频率的方法 ,可获得兔基底动脉稳定的频谱图并易于重复。     

Transdermal nitroglycerin in patients with subarachnoid hemorrhage

Delayed ischemic neurological deficit (DIND) following cerebral vasospasm remains a cause for high morbidity and mortality in patients with subarachnoid hemorrhage (SAH). There is experimental and clinical evidence of positive effects of nitric oxide (NO) donors on cerebral vasospasm. We therefore analysed the effect of transdermal nitroglycerin in patients with SAH measuring transcranial Doppler velocities (TCD), cerebral blood flow (CBF) and DIND. Nitroglycerin was used in a target dose of 14 microg/kg/h. TCD assessment was performed daily. CBF measurements were done using the perfusion CT-technique. Blood pressure, volume intake and vasopressor administration, were registered. Nine patients were randomly assigned either to the nitroglycerin group (N-group) and eight patients in the control group (C-group). Mean TCD values in the extracranial portion of the internal carotid artery (ICA) were lower in the N-group (p<0.005). Mean TCD in the middle cerebral arteries (MCA) showed no difference. The Lindegaard ratio was higher in the N-group (p<0.04). CBF in the N-group was higher than in the C-group (p<0.03). Even though nitroglycerin reduces blood pressure and lowers ICA TCD-values and increases the Lindegaard ratio, a higher CBF was measured in the N-group. Thus, nitroglycerin influences the cerebral vascular tone and increases CBF. SAH therapy with nitroglycerin is possible without increasing the risk of DIND. The exact timing of onset, duration and reduction of nitroglycerin administration in respect to the appearance of vasospasm may have a strong impact on the success of such a therapy.     

Packed Red Blood Cell Transfusion Causes Greater Hemoglobin Rise at a Lower Starting Hemoglobin in Patients with Subarachnoid Hemorrhage

Introduction  Each unit of packed red blood cells (PRBCs) is expected to raise circulating hemoglobin (HGB) by ∼1 g/dL. There are few data on modifiers of this relationship other than gender and body mass index (BMI). Methods  We recorded HGB before and after PRBC transfusion in a retrospective cohort of 103 patients and a prospective cohort of 93 patients with subarachnoid hemorrhage (SAH). Results  In the retrospective cohort, 48 of 103 patients were transfused, and in the prospective cohort, 56 of 93 patients were transfused. In both groups, lower pre-transfusion HGB was associated with a larger increase in HGB (P < 0.001) after correction for the number of units of PRBCs given. In the prospective cohort, lower pre-transfusion HGB was associated with a greater rise in HGB (P < 0.001) after correction for number of units of PRBCs given, gender, and BMI in repeated measures analysis. Pre-transfusion HGB explained an additional 12% of variance in the data (P < 0.001). In both cohorts, the magnitude of the effect was similar. Conclusion  In patients with SAH, transfusion at lower HGB leads to a greater increase in HGB. Transfusion at lower HGB may be relatively more cost-effective, and this should be balanced against any potential benefit from higher HGB in SAH. One rather than 2 units of PRBCs are likely to be sufficient for most HGB targets after SAH, especially in patients with more severe anemia.     

Calcitonin-gene related peptide and cerebral vasospasm

The pathophysiology of arterial vasospasm following subarachnoid hemorrhage (SAH) is poorly understood and the contribution of endogenous neuropeptides has not been sufficiently elucidated. Recently, we detected an excessive release of vasoconstrictive neuropeptide Y (NPY) in SAH patients and identified a significant correlation of NPY cerebrospinal fluid (CSF) levels with vasospasm-related ischemia. Here, we present the results of an experimental study on the possible role of the potent endogenous vasodilator calcitonin-gene related peptide (CGRP) in the acute stage of SAH. Twelve consecutive patients with SAH were included. Seven patients had severe arterial vasospasm, confirmed by transcranial doppler-sonography (TCD). Prospectively, CSF was collected from day 1 to day 10 after onset of the SAH. The levels of CGRP were determined in a competitive enzyme immunoassay and were correlated with the clinical course and hemodynamic changes. A cohort of 29 patients without CNS disease served as a control. CGRP was significantly higher in SAH patients compared with the control group (p < 0.05). From day 1 to day 4, the CGRP levels in patients without vasospasm were significantly higher than the levels of CGRP in patients with vasospasm (p < 0.05). These patients did not develop cerebral ischemia. The significantly increased levels of the CGRP during the first days after onset of the SAH in the non-vasospasm group indicate a potential protective role of CGRP. CGRP may alleviate arterial vasoconstriction and thus protect the brain from vasospasm and subsequent ischemia.     

Transcranial Doppler sonography in subarachnoid hemorrhage

Ten patients presenting a subarachnoid hemorrhage (SAH) due to rupture of a middle cerebral or an anterior communicating aneurysm are presented. Transcranial Doppler (TCD) values are obtained at different time intervals after SAH. The correlation of TCD values, vasospasm and clinical course is discussed.     

Noninvasive assessment of the intracranial pressure in non-traumatic intracranial hemorrhage

The article describes the modified technique of measuring the diameters of the optic nerve sheath (ONSD) for assessment of the intracranial pressure (ICP) in patients with intracerebral or subarachnoid hemorrhage (SAH). The CT scans of 443 patients were analyzed retrospectively. The ONSDs were measured at 3 mm behind the globe and at the point where the ophthalmic artery crosses the optic nerve. The ONSD/eyeball transverse diameter (ETD) ratio was calculated. The correlation analysis was performed with the Glasgow Coma Scale score, Hemispheric Stroke Scale score, Glasgow Outcome Score, and invasive ICP readings. ONSD was enlarged in 95% of patients with intracerebral hemorrhage or SAH. Pathological ONSDs were 6.6 ± 0.8 mm (cut-off value >5.5 mm; p < 0.05). ONSD/ETD ratio was 0.29 ± 0.05 against normative 0.19 ± 0.02 (p < 0.01) with no correlation with initial Glasgow Coma Scale score or Hemispheric Stroke Scale score. There was an inverse correlation between ONSD/ETD ratio and Glasgow Outcome Score (r = −0.7) and direct correlation with invasive ICP readings. This study provides further evidence that in patients with intracranial hemorrhage and SAH, the presence of ONSD greater than a threshold of 5.5 mm is significantly predictive of invasively measured elevated ICP. The prediction of raised ICP can be further refined by measuring ONSD at the point where the optic nerve and the ophthalmic artery cross, and by determining the ratio between the ONSD and ETD.     

The Burden of the Systemic Inflammatory Response Predicts Vasospasm and Outcome after Subarachnoid Hemorrhage

Introduction  Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce the systemic inflammatory response syndrome (SIRS). This may promote both extra-cerebral organ dysfunction and delayed cerebral ischemia, contributing to worse outcome. We ascertained the frequency and predictors of SIRS after spontaneous SAH, and determined whether degree of early systemic inflammation predicted the occurrence of vasospasm and clinical outcome. Methods  Retrospective analysis of prospectively collected data on 276 consecutive patients admitted to a neurosciences intensive care unit with acute, non-traumatic SAH between 2002 and 2005. A daily SIRS score was derived by summing the number of variables meeting standard criteria (HR >90, RR >20, Temperature >38°C, or <36°C, WBC count <4,000 or >12,000). SIRS was considered present if two or more criteria were met, while SIRS burden over the first four days was calculated by averaging daily scores. Regression modeling was used to determine the relationship among SIRS burden (after controlling for confounders including infection, surgery, and corticosteroid use), symptomatic vasospasm, and outcome, determined by hospital disposition. Results  SIRS was present in over half the patients on admission and developed in 85% within the first four days. Factors associated with SIRS included poor clinical grade, thick cisternal blood, larger aneurysm size, higher admission blood pressure, and surgery for aneurysm clipping. Higher SIRS burden was independently associated with death or discharge to nursing home (OR 2.20/point, 95% CI 1.27–3.81). All of those developing clinical vasospasm had evidence of SIRS, with greater SIRS burden predicting increased risk for delayed ischemic neurological deficits (OR 1.77/point, 95% CI 1.12–2.80). Conclusions  Systemic inflammatory activation is common after SAH even in the absence of infection; it is more frequent in those with more severe hemorrhage and in those who undergo surgical clipping. Higher burden of SIRS in the initial four days independently predicts symptomatic vasospasm and is associated with worse outcome. Financial support: Supported by NIH-N535906 (MND).