This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Charpentier, C. Articles by Laxenaire, M. C. Search for Related Content PubMed PubMed Citation Articles by Charpentier, C. Articles by Laxenaire, M. C. Related Collections Aneurysm, AVM, hematoma Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage Risk Factors for Stroke

(Stroke. 1999;30:1402-1408.)
© 1999 American Heart Association, Inc.

Original Contributions

Multivariate Analysis of Predictors of Cerebral Vasospasm Occurrence After Aneurysmal Subarachnoid Hemorrhage

Claire Charpentier, MD; Gerard Audibert, MD, PhD; Francis Guillemin, MD, PhD; Thierry Civit, MD; Xavier Ducrocq, MD; Serge Bracard, MD; Henri Hepner, MD; Luc Picard, MD Marie Claire Laxenaire, MD

From the Departments of Anesthesiology (C.C., G.A., M.C.L.), Clinical Epidemiology UPRES EA 1124 (F.G.), Neurosurgery (T.C., H.H.), Neurology (X.D.), and Neuroradiology (S.B., L.P.), Nancy University Hospital, University Henri Poincaré, Nancy, France.

Correspondence to Dr Gérard Audibert, Département d'Anesthésie, Hôpital Central, 29 Avenue de Lattre de Tassigny, 54 000 Nancy, France. E-mail audibert{at}spieao.u-nancy.fr

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose—The role of type of treatment on cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage (SAH) has not been studied. Through multivariate analysis we determined the independent prognostic factors of the occurrence of symptomatic vasospasm following aneurysmal SAH in a study cohort of 244 patients undergoing either surgical or endovascular treatment. The prognostic factors of sequelae after aneurysmal SAH were studied as well.

Methods—Symptomatic vasospasm was defined as the association of deterioration in a patient's neurological condition between 3 and 14 days after SAH with no other explanation and an increase in mean transcranial Doppler velocities of >120 cm/s. The prognostic factors were registered on admission and during the intensive care stay.

Results—Symptomatic vasospasm occurred in 22.2% surgical patients compared with 17.2% endovascular treatment patients (P=0.37). Multivariate analysis revealed that the probability of occurrence of symptomatic vasospasm decreased with age >50 years (relative risk [RR], 0.47 [0.25 to 0.88]) and severe World Federation of Neurological Surgeons (WFNS) grade measured on admission (RR, 0.43 [0.20 to 0.90]) and increased with hyperglycemia occurring during the intensive care stay (RR, 1.94 [1.04 to 3.63]). No difference in risk of symptomatic vasospasm could be identified between surgical and endovascular treatment. Symptomatic vasospasm (OR, 4.73 [CI, 1.77 to 12.6]) as well as WFNS grade of >2 (OR, 8.95 [3.46 to 23.2]), treatment complications (OR, 8.39 [3.16 to 22.3]), and secondary brain insults were associated with an increased risk of 6-month sequelae.

Conclusions—Age <50 years, good neurological grade, and hyperglycemia were all associated with an increased risk of cerebral vasospasm whereas treatment was not. This provides a basis for future clinical prospective randomized trials comparing both treatments.

Key Words: cerebral vasospasm • endovascular therapy • prognosis • subarachnoid hemorrhage • surgical treatment

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Cerebral arterial vasospasm with delayed ischemic neurological deficit occurs in 17% to 40% of patients with aneurysmal subarachnoid hemorrhage (SAH)^{1 2 3 4 5} and worsens their clinical outcome.^{1 6 7} Several studies have evaluated the potential risk factors for the development of symptomatic vasospasm. The role of the amount of extravascular blood and that of clinical grade were initially reported with use of univariate analysis^{3 8 9 10} and further confirmed as independent prognostic factors of symptomatic vasospasm occurrence with multivariate analysis.^{1 4 11} Moreover, Rabb et al⁴ identified younger age as a predictor of symptomatic vasospasm. Nevertheless, the etiology of vasospasm has not been fully established. Many experimental studies have proved that the presence of erythrocytes in cerebrospinal fluid is essential in causing vasospasm,^{12 13} perhaps through the release of superoxide anions.¹⁴ As a result, it has been suggested in clinical studies that early surgical evacuation of the cisternal blood clot may reduce the incidence of vasospasm.^{15 16}

Endovascular treatment with Guglielmi detachable coils (GDCs) is an alternative treatment for acutely ruptured aneurysms that is now well established.^{17 18} In contrast to surgical clipping, the endovascular procedure does not allow removal of the subarachnoid clot. Murayama et al¹⁹ measured the incidence of symptomatic vasospasm after early endovascular treatment of acutely ruptured aneurysms in 69 patients with Hunt and Hess clinical grades between I and III. The 23% incidence of symptomatic vasospasm was comparable with that found in surgical series. In a series of 37 patients,²⁰ preliminary data have suggested that the frequency of cerebral vasospasm may be reduced in those treated by endovascular therapy compared with those treated by direct surgical clipping. Recently, it has been shown in a univariate analysis²¹ that the vasospasm-related ischemic infarction rate was higher with endovascular treatment versus surgery.

The purpose of this study was to assess, through use of multivariate analysis, the prognostic factors of the occurrence of symptomatic vasospasm after aneurysmal SAH in a cohort of patients undergoing either surgical or endovascular treatment and to determine whether the type of treatment was an independent prognostic factor of symptomatic vasospasm. A secondary outcome was to study the prognostic factors of sequelae after aneurysmal SAH.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patient Population
Patients admitted for SAH in a university hospital were eligible for the study. Prestudy calculation showed that a sample of 250 patients with an expected vasospasm incidence of 20% would allow for the detection of a factor associated with a 1.4 increased risk of vasospasm at a significance level of 0.05 and a power of 0. To reach this number, it was necessary to review the charts of 432 patients from October 1992 to December 1997. Among these, patients were excluded if (1) cerebral angiography failed to demonstrate any underlying vascular abnormality (n=60) (14%); (2) treatment was performed after day 8 following SAH (n=59, 13%); (3) death occurred before angiography (n=13, 3%) or before treatment (n=22, 5%) or before day 4, minimal delay for vasospasm occurrence (n=12, 3%); (4) symptomatic acute cerebral vasoconstriction,²² angiographically proved, was present on admission (n=21, 5%), which could make the diagnosis of cerebral vasospasm inaccurate; and (5) both surgical and endovascular treatment were performed (n=1). In the remaining 244 patients the medical records, radiographic studies, transcranial Doppler records, and intensive care parameters were available for all patients and were reviewed.

The condition at the initial medical consultation was graded according to the Hunt and Hess²³ and the World Federation of Neurological Surgeons²⁴ classifications. The severity of SAH was radiologically classified from the initial CT appearance according to Fisher et al.⁸ When patients had multiple aneurysms, only the ruptured aneurysm was considered.

Patients were classified as having a history of hypertension or cardiac failure if they were receiving antihypertensive or cardiotonic medications. Hypertension on admission was defined as a systolic blood pressure of 160 mm Hg or a diastolic blood pressure of 100 mm Hg or both. Secondary brain insults occurring during the first 14 days after the SAH and at least 48 hours before the appearance of symptomatic cerebral vasospasm were defined as follows: hypoxemia (arterial oxygen saturation <90%), hypercapnia (arterial CO₂ pressure >45 mm Hg), hyperglycemia (blood glucose >12 mmol/L), hypoglycemia (blood glucose <3.5 mmol/L), systemic hypotension (systolic blood pressure <90 mm Hg), and pyrexia (body temperature >38.5°C). Such insults lasting for at least 6 consecutive hours were taken into account. Concerning glucose level measurements, they were obtained using a blood glucose meter (Glucometer, Baxter) every 4 hours during the intensive care stay and at least 3 times a day during the following days. Furthermore, laboratory values were obtained once or twice a day. The values of the first day were excluded.

Treatment of Aneurysmal SAH
Diagnostic cerebral angiography was performed during the first 24 hours after admission. The ruptured aneurysm was treated immediately after the diagnostic cerebral angiography was achieved. The decision about using surgery or endovascular treatment was made after a short meeting between the surgical and endovascular teams. The most important factors influencing the decision were the location of the aneurysm and its accessibility. The presence of an intracranial hematoma could indicate surgery. During the study period there were 2 seniors and 1 junior in the surgical team and 2 seniors and 1 junior in the endovascular team. Surgical treatment consisted of standard craniotomy for clipping of the aneurysm. The endovascular procedure used GDCs. In all cases treatment was performed under general anesthesia. Technical complications included aneurysm perforation, incomplete treatment, and ischemic complication by unintentional parent artery occlusion or cerebral embolism. Ischemic complications diagnosed concomitantly with the endovascular procedure were noted on the procedure report. Ischemic complications attributable to surgery were due to cerebral attrition with CT evidence of cerebral infarction. When ischemia occurred after aneurysm perforation, we considered perforation to be the main complication. Patients underwent ventricular drainage when hydrocephalus was detected on the cerebral CT. After surgery or embolization, most of the patients were admitted to the neurosurgical intensive care unit. They received nimodipine as a continuous intravenous infusion (2 mg/h) for at least 7 days and then orally (30 mgx6) for at least an additional 7 days. Induced hypervolemia was not used systematically for vasospasm prevention, but a systolic blood pressure was maintained above 120 mm Hg with use of hydroxyethyl starch or dopamine if necessary.

Outcomes
The main outcome was the occurrence of symptomatic cerebral vasospasm. Transcranial Doppler (TCD) velocities were recorded at least once a week after admission in all the patients by 1 senior neurologist. More frequent monitoring of TCD velocities was used in patients who exhibited dramatic increases in velocities or changes in neurological status. The transtemporal approach was used to measure flow velocities in the middle cerebral artery, the anterior cerebral artery, the posterior cerebral artery and the intracranial internal carotid artery. Sometimes the ophthalmic approach through the orbit allowed better identification of the carotid siphon. Detection of vertebrobasilar artery vasospasm was performed using the transforamenal approach. Symptomatic vasospasm was diagnosed on the basis of a combination of (1) the development of focal neurological signs or deterioration of the level of consciousness, or both, occurring between 3 and 14 days after SAH and (2) an increase in mean TCD velocities of >120 cm/s in the investigated territories. We considered a 1-point Glasgow Coma Scale decrease as a meaningful deterioration. Ischemia secondary to vasospasm was assumed to be the cause of delayed neurological deficits when other obvious causes had been ruled out. Metabolic disorders were searched by reviewing biological results, blood gases, and fever. Structural causes (ie, hydrocephalus, rebleeding, or intracerebral hematoma), were eliminated by cerebral CT scan These patients were treated with aggressive hypervolemic therapy and induced arterial hypertension by use of dopamine or norepinephrine to maintain the systolic blood pressure above 150 mm Hg. For hypervolemic therapy, hydroxyethyl starch was administered as often as required to maintain the central venous pressure at 10 cm H₂O.

To confirm the severity of symptomatic vasospasm consequences, we defined 2 secondary outcomes obtained at 6 months from the report of the treating physician, from questionnaire mailed to the referring physician or from telephone conversation with the patient or patient's relatives. Clinical outcome was measured with the Glasgow Outcome Scale (GOS).²⁵ Patients with moderate or severe disability or vegetative condition (GOS scores of 4, 3, and 2, respectively) were defined as having an unfavorable outcome or 6-month sequelae, whereas full recovery (GOS 5) was considered a favorable outcome.^{6 26} Death occurrence was studied separately.⁶

Statistical Analysis
Descriptive continuous data were reported as mean±SD and compared with the Student t test. Categorical data were reported in percentage and tested by the Pearson ² or Fisher exact test.

Time to vasospasm occurrence from first SAH symptom was considered censored data under the potential influence of covariates, ie, prognostic factors. Univariate analysis was performed with the log-rank test. Thereafter, the Cox proportional hazards regression model was used to identify covariates that predicted the time until vasospasm occurred.²⁷ All these variables were treated as fixed covariates. The assumption that the hazard for exposed individuals was proportional to the baseline hazard was checked by plotting the log minus log of the survivor function against time.²⁸ The results are expressed as relative risks (RRs) that relate the effect of each covariate on the probability of vasospasm occurrence.

Determinants of 6-month sequelae versus full recovery were analyzed with use of a multivariate logistic regression model.²⁹ The ORs were calculated to approximate relative risk and are presented with 95% CIs. Probability of death occurrence was also analyzed with the Cox proportional hazards model. In addition to other prognostic factors, symptomatic vasospasm was incorporated into this model and treated as a time-dependent covariate.

The age was dichotomized at its median value. Clinical and scanographic grades were grouped into grades I and II (asymptomatic or minor signs) versus other grades. All variables with probability values of <0.20 in the univariate analysis were then candidate in the multivariate analysis with stepwise forward selection of the variables. In the final models, variables with probability values of <0.05 were deemed significant. The risk estimates were adjusted for age and sex, and the analysis was stratified by 2-year study periods. There were no missing values. Data analysis was performed with use of BMDP statistical software (BMDP version 7.0, BMDP Statistical Software Inc).

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Population Characteristics
The demographic and clinical characteristics of the 244 patients are reported in Table 1. Eighty-one percent of the patients were treated within the first 72 hours after onset of SAH and 13% between days 3 and 5. Less than 15% of the patients were referred from outside the health district. The clinical and scanographic grades on admission are shown in Table 2. Among the 142 patients scored as Fisher grade IV, 108 patients had intraventricular hemorrhage without or with small hematoma. Thirty-four patients had significant hematoma and were treated surgically.

View this table: [in this window] [in a new window]   Table 1. Demographic and Clinical Characteristics at Admission

View this table: [in this window] [in a new window]   Table 2. Distribution of Fisher, Hunt and Hess, and WFNS Grades at Admission

Characteristics of Endovascular and Surgical Treatment Groups
Endovascular treatment was performed in 145 patients (59.4%) and surgical treatment in the remaining 99 (40.6%). The distribution between the 2 treatments varied over time, with a significant increase in endovascular treatment from 31% in 1992 to 1993, 58% in 1994 to 1995 and 77% in 1996 to 1997 (P<0.0001). Neither age, sex, delay to treatment, experience of the operator, nor Fisher CT scan grades and both Hunt and Hess and WFNS clinical grades differed between the treatment groups. Endovascular treatment was performed preferentially in posterior circulation (P<0.0001) and in the anterior communicating artery within anterior circulation, whereas surgical treatment was more frequent for aneurysms of the middle cerebral artery (P=0.002). Large aneurysms (>25 mm in diameter) were treated endovascularly in 11 cases and surgically in 9. Multiple aneurysms were observed in 55 patients, among whom the ruptured aneurysm was treated radiologically in 30 cases. Fifty-four patients received ventricular drainage because of significant ventricular enlargement, mainly in the endovascular group (42 versus 12 patients, P=0.002). The procedure-related complications did not differ between surgical and endovascular group (25.2% versus 19.3%, P=0.27). Aneurysm perforation occurred during 15 surgical and 4 endovascular treatments, ischemic complications during 8 surgical and 15 endovascular treatments, and incomplete aneurysm occlusion after 2 surgical and 9 endovascular procedures. One patient never had >1 complication. The mortality and sequelae after treatment complications did not differ, either, between the surgical and endovascular groups (mortality, 28.0% versus 32.1%; sequelae, 52.0% versus 39.3%; and good recovery, 20.0% versus 28.6%; P=0.62).

Factors Associated With Cerebral Symptomatic Vasospasm
Symptomatic vasospasm occurred in 47 patients (19.3%; 22.2% surgical patients compared with 17.2% endovascular treatment patients [P=0.37]). Among the factors associated with the occurrence of cerebral symptomatic vasospasm (Table 3), the risk of symptomatic vasospasm was significantly greater for patients aged 50 years, whereas operator experience, hyperglycemia, hypotension, and pyrexia had a nonsignificant level (<0.20). Clinical grades, CT scan grades, and treatment were nonsignificant but were retained for the multivariate analysis because of their potential role.^{1 3 4 8 11 19 30}

View this table: [in this window] [in a new window]   Table 3. Relationship Between Symptomatic Vasospasm Occurrence and Parameters Measured at Admission and During the Intensive Care Unit Period (Log-Rank Test)

After adjusting for sex in a Cox model stratified by the study periods, 3 variables remained significantly and independently associated with the occurrence of cerebral symptomatic vasospasm (Table 4). The RR was 1.94 for patients with hyperglycemia during intensive care unit stay (P=0.03). The risk of symptomatic vasospasm was roughly halved for patients with a WFNS clinical grade -of >2 (P=0.01) and for those aged >50 years (P=0.01). A nonsignificant increased risk of vasospasm was observed in high Fisher grades. No difference in risk of symptomatic vasospasm could be identified between surgical and endovascular treatment groups (RR=0.97, P=0.93; Figure). We explored possible first-order interactions between treatment and clinical grade or aneurysm location, between operator experience and clinical grade, between study period and clinical grade, scanographic grade or age, and between clinical grade and hyperglycemia, with respect to vasospasm occurrence, but none was found to be significant.

View this table: [in this window] [in a new window]   Table 4. Independent Prognostic Factors of Cerebral Vasospasm Occurrence Over Time

View larger version (14K): [in this window] [in a new window]   Figure 1. Comparison of the risk of symptomatic vasospasm between the surgical treatment and endovascular treatment groups.

Consequences of Cerebral Vasospasm
Patients with cerebral symptomatic vasospasm had a longer intensive care unit stay (14.8±13.9 versus 10.4±12.0 days, P=0.05), and a longer hospital stay (33.9±22.5 versus 23.3±18.9 days, P=0.004) than the others. Death was directly attributable to vasospasm in only 4 patients. Six months after SAH, mortality was similar (19%), whether patients had suffered from cerebral vasospasm or not. In contrast, sequelae were 2 times more frequent after symptomatic vasospasm (43 versus 21%, P=0.007).

With use of multiple logistic regression analysis, 5 factors were found independently associated with 6-month sequelae (Table 5). Whereas the treatment itself did not influence sequelae, the treatment complications coming either from surgical or endovascular strategies were strongly significant.

View this table: [in this window] [in a new window]   Table 5. Independent Prognostic Factors of Sequelae (Glasgow Outcome Scale 2 to 4) at 6 Months After Aneurysmal SAH

Symptomatic cerebral vasospasm was not associated with death occurrence (RR=1.20; 95% CI, 0.52 to 2.78; P=0.66). The independent factors significantly associated with death occurrence were the following: WFNS clinical grades of >2 (RR=3.21; 95% CI, 1.64 to 6.29; P=0.0005), time to treatment from first SAH symptom of >72 hours (RR=0.29; 95% CI, 0.08 to 1.01; P=0.03), treatment complications (RR=2.46; 95% CI, 1.23 to 4.95; P=0.01), hypoxemia (RR=3.35; 95% CI, 1.70 to 6.60; P=0.0009), hyperglycemia (RR=2.30; 95% CI, 1.08 to 4.87; P=0.02), and hypotension (RR=1.97; 95% CI, 1.03 to 3.75; P=0.04).

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
This study analyzed the prognostic factors of cerebral vasospasm occurrence after SAH in a singular population of 244 patients treated either by an endovascular technique using GDCs or by conventional surgical treatment. An age of 50 years, WFNS clinical grades 2, and hyperglycemia were independently and significantly associated with the occurrence of cerebral vasospasm. In contrast, no relationship was found with the type of treatment. The risk of 6-month sequelae was quadrupled when cerebral vasospasm occurred after SAH and strongly increased with treatment complications and secondary brain insults.

Methodological Considerations
This study was a preliminary analysis of the relationship between the type of treatment and cerebral vasospasm. We ensured that the severity of the SAH did not influence the choice of treatment. Although the study was not randomized, the evolution of the practices over time was taken into account by stratifying analysis according to the study period. The times to vasospasm occurrence, ie, censored data, were taken into consideration using the Cox proportional hazards regression, which allowed the selection of independent variables associated with the occurrence of cerebral vasospasm. As no previous multivariate analysis has compared the incidence of cerebral vasospasm between surgical and endovascular treatments, these data should provide a basis for further studies.

Incidence of Symptomatic Vasospasm
The incidence of symptomatic vasospasm in the literature was recently discussed by Murayama et al¹⁹ who first reported a series of GDC-treated cases. They included 69 patients with Hunt and Hess grades I to III and found a 23% incidence of symptomatic vasospasm that compared favorably with conventional surgical series.^{1 2 5 15 31} The 19% incidence of symptomatic vasospasm found in our study tends to be lower than that reported in previous studies, but we included a large proportion of patients with clinical grades IV and V, in whom it is difficult to diagnose accurately neurological deterioration caused by vasospasm. Thus, comparisons between different studies require care. We have used the definition of symptomatic cerebral vasospasm retained by the Canadian Neurological Society³² and excluded acute cerebral vasoconstriction considered as a specific entity.²²

Prognostic Factors of Cerebral Vasospasm
By using multivariate analysis we found that the following 3 factors—age, WFNS clinical grade, and hyperglycemia—were independently associated with symptomatic vasospasm occurrence.

Some of the factors are well-known predictors. Thus, younger patients are more likely to experience vasospasm than the others.^{4 33} In this study, WFNS clinically low grades (I and II) were predictors of symptomatic vasospasm. Using the Hunt and Hess grades, Rabb et al⁴ reported similar results, while in another study the Hunt and Hess clinical grades³⁰ were not found to be predictors of vasospasm. It should be kept in mind that our results are likely to have been influenced by the inclusion of patients with clinical grades IV or V. As previously mentioned, it is difficult to accurately diagnose neurological deterioration caused by vasospasm in such patients, and the relationship between clinical grades and vasospasm occurrence may be underestimated.

By contrast, hyperglycemia was found to be a new and independent predictor of symptomatic vasospasm occurrence. Yoshimoto and Kwak³⁴ suggested that electrolyte imbalance may contribute to neurological deterioration after SAH, especially in elderly patients. In our study, the glucose level was recorded at least 48 hours before vasospasm occurred and not at the time of aggravation in order to avoid the confusion with a catecholaminergic response to stress. For the same reason, the values of the first day were excluded. The date of the first hyperglycemia was not recorded, but it may be interesting to study whether the delay between hyperglycemia and vasospasm occurrence influences the severity of the latter. Although hyperglycemia is an independent predictor of vasospasm occurrence, it would appear premature to state that it is a risk factor for vasospasm occurrence. Nevertheless, several studies have emphasized the importance of avoiding secondary insults in patients with head injury, both those occurring during the initial management and later during intensive care.^{35 36} Although the impact on clinical outcome of secondary brain insults during the intensive care stay of patients with SAH has recently been reported,³⁷ their influence on cerebral vasospasm has not been described. It can be hypothesized that the initial hemorrhage may expose the brain to secondary insults. There is no available experimental data concerning hyperglycemia. A study in rats³⁸ has shown that the priming of the brain with a transient rise in intracranial pressure before a subsequent middle cerebral artery occlusion causes both increased infarct size and perifocal edema. Whether they are confirmed, these findings would be of great importance in clinical practice for early management care.

Relationship Between Treatment and Cerebral Vasospasm Occurrence
Studying such a relationship appears crucial, because the technique of aneurysm occlusion with GDC coils has known an accelerated development in ruptured aneurysm treatment for the past 8 years.^{17 18 39 40} In our practice, it has been taking on an ever-increasing role since 1992, whereas surgical indications have been decreasing. In contrast to the first reports,^{17 18 41} no difference was found in neurological status or in age, according to treatment. The lack of a relationship between the type of treatment and cerebral vasospasm occurrence would suggest that the early evacuation of the cisternal blood clot is not determinant of the occurrence of cerebral vasospasm. Ventricular drainage was more frequent after endovascular treatment. The role of ventricular drainage in attenuating the difference between the 2 treatments should be further investigated. The difficulty in removing subarachnoid clots has been already emphasized and may explain the failure of early surgery to reduce the incidence of vasospasm.^{6 16} Another possible explanation of the occurrence of vasospasm may be the role of surgical mechanical manipulations.^{19 31} Finally, rather than the presence of erythrocytes, both clinical⁴² and experimental¹⁴ studies have argued in favor of vascular and systemic reactions to the rupture of an artery.

Prognostic Factors of Death and Sequelae
Although the overall mortality was comparable with that reported in previous reports,⁷ we did not confirm that symptomatic vasospasm occurrence was associated with increased mortality. However, those studies that described a high death rate attributable to vasospasm occurrence used univariate analysis.^{7 43} Taking into account the multiple prognostic factors of mortality, multivariate analysis would appear to be the best method of analyzing the relationship between vasospasm and mortality, allowing to control for confounding.

We chose to separate the cases of death from unfavorable clinical outcome, as already proposed,⁶ to evaluate the sequelae attributable to symptomatic cerebral vasospasm. Symptomatic vasospasm has already been associated with unfavorable outcome.⁴ In a review of >1000 reports appearing in the literature, a common OR of 3.05 (95% CI, 2.73 to 3.40) has been calculated, indicating much better odds for a full recovery for a patient without vasospasm.²⁶ Using multivariate analysis we were able to assess the other prognostic factors independently associated with 6-month sequelae. Patients who experienced secondary brain insults were found to be at higher risk of unfavorable outcome than the others.³⁷ In our study, both hyperglycemia and pyrexia increased the risk of 6-month sequelae. Thus, potentially preventable complications after ruptured cerebral aneurysm may increase the 6-month sequelae rate of patients. Finally, the occurrence of treatment-related complications was strongly associated with the risk of 6-month sequelae. The rate and the severity of those complications did not differ between the treatment procedures.

Conclusion
In this study of 244 patients receiving either endovascular or surgical treatment after aneurysmal SAH, we have demonstrated that age, WFNS clinical grade, and hyperglycemia are independently associated with an increased risk of symptomatic vasospasm, whereas no relationship has been found between the type of treatment and the occurrence of symptomatic vasospasm. Apart from WFNS clinical grade, treatment complications, and vasospasm, both hyperglycemia and pyrexia are independent prognostic factors of 6-month sequelae.

The lack of a relationship between type of treatment and cerebral vasospasm needs to be confirmed. Instead of being oriented toward detecting a significant difference between the 2 treatments, the future trials should be directed toward demonstrating that endovascular treatment is equivalent to surgical treatment in terms of cerebral vasospasm occurrence. The design of a clinical trial to establish the equivalence of 2 treatments differs from that of an efficacy trial, and appropriate statistics should be used.⁴⁴ Prospective studies should also be initiated to define the impact of secondary brain insults on both symptomatic vasospasm occurrence and 6-month sequelae after SAH.

	Acknowledgments

 
We express our sincere gratitude to Prof Patrick Ravussin, Department of Anesthesiology, Sion, for reviewing the manuscript.

Received January 5, 1999; revision received April 23, 1999; accepted April 23, 1999.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Adams HP, Kassel NF, Torner JC, Haley EC. Predicting outcome ischemia after aneurysmal subarachnoid hemorrhage: influences of clinical condition, CT results and antifibrinolytic therapy: a report of the Cooperative Aneurysm Study. Neurology. 1987;37:1586–1591.[Abstract/Free Full Text]
2. Haley EC Jr, Kassel NF, Torner JC, Truskowski LL, Germanson TP, and the participants. A randomized trial of two doses of nicardipine in aneurysmal subarachnoid hemorrhage: a report of the Cooperative Aneurysm Study. J Neurosurg. 1994;80:788–796.[Medline] [Order article via Infotrieve]
3. Inagawa T. Cerebral vasospasm in elderly patients treated by early operation for ruptured intracranial aneurysms. Acta Neurochir (Wien). 1992;115:79–85.[Medline] [Order article via Infotrieve]
4. Rabb CH, Tang G, Chin LS. A statistical analysis of factors related to symptomatic cerebral vasospasm. Acta Neurochir (Wien). 1994;127:27–31.[Medline] [Order article via Infotrieve]
5. Solomon RA, Onesti ST, Klebanoff L. Relationship between the timing of aneurysm surgery and the development of delayed cerebral ischemia. J Neurosurg. 1991;75:56–61.[Medline] [Order article via Infotrieve]
6. Kassel NF, Torner JC, Haley EC, Jane JA, Adams HP, Kongable GL. The International Cooperative Study on the Timing of Aneurysm Surgery, part 1: overall management results. J Neurosurg. 1990;73:18–36.[Medline] [Order article via Infotrieve]
7. Solenski NJ, Haley EC, Kassel NF, Kongable G, Germanson T, Trukowski L, Torner JC, and the Participants of the Multicenter Cooperative Aneurysm Study. Medical complications of aneurysmal subarachnoid hemorrhage: a report of the multicenter, cooperative aneurysm study. Crit Care Med. 1995;23:1007–1017.[Medline] [Order article via Infotrieve]
8. Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualised by computerised tomographic scanning. Neurosurgery. 1980;6:1–9.[Medline] [Order article via Infotrieve]
9. Inagawa T, Ohbayahi N, Hada H. Rapid spontaneous diminution of cisternal blood on computed tomography in patients with subarachnoid hemorrhage. Surg Neurol. 1995;44:356–364.[Medline] [Order article via Infotrieve]
10. Kistler JP, Crowell RM, Davis KR, Heros R, Ojemann RG, Zervas T, Fisher CM. The relation of cerebral vasospasm to the extent and location of subarachnoid blood visualised by CT scan: a prospective study. Neurology. 1983;33:424–436.[Abstract/Free Full Text]
11. Lasner TM, Weil RJ, Riina HA, King JT, Zager EL, Raps EC, Flamm ES. Cigarette smoking-induced increase in the risk of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg. 1997;87:381–384.[Medline] [Order article via Infotrieve]
12. Duff TA, Louie J, Feilbach, Scott G. Erythrocytes are essential for development of cerebral vasculopathy resulting from subarachnoid hemorrhage in cats. Stroke. 1988;19:68–72.[Abstract/Free Full Text]
13. Mac Donald RL, Weir BKA, Runzer TD, Grace MGA, Findlay JM, Saito K, Cook DA, Mielke BW, Kanamaru K. Etiology of cerebral vasospasm in primate. J Neurosurg. 1991;75:415–424.[Medline] [Order article via Infotrieve]
14. Shishido T, Suzuki R, Qian L, Hirakawa K. The role of superoxide anions in the pathogenesis of cerebral vasospasm. Stroke. 1994;25:864–868.[Abstract]
15. Inagawa T, Kamika K, Matsuda Y. Effect of continuous cisternal drainage on cerebral vasospasm. Acta Neurochir. 1991;112:28–36.[Medline] [Order article via Infotrieve]
16. Taneda E. Effect of early operation for ruptured aneurysms on prevention of delayed ischemic symptoms. J Neurosurg. 1982;57:622–628.[Medline] [Order article via Infotrieve]
17. Guglielmi G, Viñuela F, Dion J, Duckwiler G. Electrothrombosis of saccular aneurysms via endovascular approach, part 2: preliminary clinical experience. J Neurosurg. 1991;75:8–14.[Medline] [Order article via Infotrieve]
18. Viñuela F, Duckwiler G, Mawad M. Guglielmi detachable coil embolization of acute intracranial aneurysm: perioperative anatomical and clinical outcome in 403 patients. J Neurosurg. 1997;86:475–482.[Medline] [Order article via Infotrieve]
19. Murayama Y, Malisch T, Guglielmi G, Mawad ME, Viñuela F, Duckwiler GR, Gobin YP, Klucznick RP, Martin NA, Frazee J. Incidence of cerebral vasospasm after endovascular treatment of acutely ruptured aneurysms: report on 69 cases. J Neurosurg. 1997;87:830–835.[Medline] [Order article via Infotrieve]
20. Yalamanchili K, Rosenwasser RH, Thomas JE, Liebman K, Mc Morrow C, Gannon P. Frequency of cerebral vasospasm in patients treated with endovascular occlusion of intracranial aneurysms. AJNR Am J Neuroradiol. 1998;19:553–558.[Abstract]
21. Gruber A, Ungersböck K, Reinprecht A, Czech t, Gross C, Bednar M, Richling B. Evaluation of cerebral vasospasm after early surgical and endovascular treatment of ruptured intracranial aneurysms. Neurosurgery. 1998;42:258–268.[Medline] [Order article via Infotrieve]
22. Bederson JB, Levy AL, Wan Hong Ding, Kahn R, DiPerna CA, Jenkins AL III, Vallabhajosyula P. Acute vasoconstriction after subarachnoid hemorrhage. Neurosurgery. 1998;42:352–362.[Medline] [Order article via Infotrieve]
23. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg. 1968;28:14–20.[Medline] [Order article via Infotrieve]
24. Drake CG. Report of the World Federation of Neurological Surgeons Committee on a Universal Subarachnoid Hemorrhage Grading Scale. J Neurosurg. 1988;68:985–986.[Medline] [Order article via Infotrieve]
25. Jennett B, Bond M. Assessment of outcome after severe brain damage: a practical scale. Lancet. 1975;1:480–484.[Medline] [Order article via Infotrieve]
26. Dorsch NWC, King MT. A review of cerebral vasospasm in aneurysmal subarachnoid hemorrhage, part 1: incidence and effects. J Clin Neurosci. 1994;1:19–26.
27. Cox DR. Regression models and life-tables. J R Stat Soc (B). 1972;34:187–202.
28. Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data. New York, NY: John Wiley & Sons; 1980.
29. Hosmer DW, Lemeshow S. Applied Logistic Regression. New York, NY: John Wiley & Sons; 1989.
30. Hijdra A, Van Gijn J, Nagelkerke NJD, Vermeulen M, Van Crevel H. Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage. Stroke. 1988;19:1250–1256.[Abstract/Free Full Text]
31. Miyaoka M, Sato K, Ishii S. A clinical study of the relationship of timing to outcome of surgery for ruptured cerebral aneurysms: a retrospective analysis of 1622 cases. J Neurosurg. 1993;79:373–378.[Medline] [Order article via Infotrieve]
32. Findlay JM. Current management of aneurysmal subarachnoid hemorrhage: guidelines from the Canadian Neurological Society. Can J Neurol Sci. 1997;24:161–170.[Medline] [Order article via Infotrieve]
33. Mac Donald RL, Wallace MC, Coyne TJ. The effect of surgery on the severity of vasospasm. J Neurosurg. 1994;80:433–439.[Medline] [Order article via Infotrieve]
34. Yoshimoto Y, Kwak S. Age-related multifactorial causes of neurological deterioration after early surgery for aneurysmal subarachnoid hemorrhage. J Neurosurg. 1995;83:984–988.[Medline] [Order article via Infotrieve]
35. Chesnut RM, Marshall LF, Klauber MR, Blunt BA, Baldwin N, Eisenberg HM, Jane JA, Marmarou A, Foulkes MA. The role of secondary brain injury in determining outcome from head injury. J Trauma. 1993;34:216–222.[Medline] [Order article via Infotrieve]
36. Jones PA, Andrews PJD, Midgley S, Anderson SI, Piper IR, Tocher JL, Housley AM, Corrie JA, Slattery J, Dearden NM, Miller D. Measuring the burden of secondary insults in head-injured patients during intensive care. J Neurosurg Anesthesiol. 1994;6:4–14.[Medline] [Order article via Infotrieve]
37. Enblad P, Persson L. Impact on clinical outcome of secondary brain insults during the neurointensive care of patients with subarachnoid hemorrhage: a pilot study. J Neurol Neurosurg Psychiatry. 1997;62:512–516.[Abstract]
38. Valtysson J, Jiang M, Persson L. Transient elevation of the intracranial pressure increases the infarct size and perifocal edema after subsequent middle cerebral artery occlusion in the rat. Neurosurgery. 1992;30:887–890.[Medline] [Order article via Infotrieve]
39. Cognard C, Weill A, Castaings L, Rey A, Moret J. Intracranial berry aneurysms: angiographic and clinical results after endovascular treatment. Radiology. 1998;206:499–510.[Abstract/Free Full Text]
40. Guterman LR, Hopkins LN. Endovascular treatment of cerebral aneurysms. Diagnosis and treatment. Clin Neurosurg. 1993;40:56–83.[Medline] [Order article via Infotrieve]
41. Redekop GJ, Durity FA, Woodhurst WB. Management-related morbidity in unselected aneurysms of the upper basilar artery. J Neurosurg. 1997;87:836–842.[Medline] [Order article via Infotrieve]
42. Brouwers PJAM, Wijdicks EFM, Van Gijn J. Infarction after aneurysm rupture does not depend on distribution or clearance rate of blood. Stroke. 1992;23:374–379.[Abstract/Free Full Text]
43. Shimoda M, Oda S, Tsugane R, Sato O. Prognostic factors in delayed ischaemic deficit with vasospasm in patients undergoing early aneurysm surgery. Br J Neurosurg. 1997;11:210–215.[Medline] [Order article via Infotrieve]
44. Com-Nougué C, Rodary C, Patte C. How to establish equivalence between treatments for censored data: a randomized trial on B non-Hodgkin lymphomas. Stat Med. 1993;12:1354–1364.

This article has been cited by other articles:

				K. Tsuda, J. Frontera, and S. Mayer Hyperglycemia and Hyperinsulinemia in Circulatory Disorder After Subarachnoid Hemorrhage Stroke, April 1, 2006; 37(4): 944 - 945. [Full Text] [PDF]

				J. A. Frontera, A. Fernandez, J. Claassen, M. Schmidt, H. C. Schumacher, K. Wartenberg, R. Temes, A. Parra, N. D. Ostapkovich, and S. A. Mayer Hyperglycemia After SAH: Predictors, Associated Complications, and Impact on Outcome Stroke, January 1, 2006; 37(1): 199 - 203. [Abstract] [Full Text] [PDF]

				A. A. Rabinstein, S. Weigand, J. L.D. Atkinson, and E. F.M. Wijdicks Patterns of Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage Stroke, May 1, 2005; 36(5): 992 - 997. [Abstract] [Full Text] [PDF]

				A. B. Singhal, M. A. Topcuoglu, D. J. Dorer, C. S. Ogilvy, B. S. Carter, and W. J. Koroshetz SSRI and statin use increases the risk for vasospasm after subarachnoid hemorrhage Neurology, March 22, 2005; 64(6): 1008 - 1013. [Abstract] [Full Text] [PDF]

				H.-K. Park, M. Horowitz, C. Jungreis, J. Genevro, C. Koebbe, E. Levy, and A. Kassam Periprocedural Morbidity and Mortality Associated with Endovascular Treatment of Intracranial Aneurysms AJNR Am. J. Neuroradiol., March 1, 2005; 26(3): 506 - 514. [Abstract] [Full Text] [PDF]

				A J P Goddard, P P J Raju, and A Gholkar Does the method of treatment of acutely ruptured intracranial aneurysms influence the incidence and duration of cerebral vasospasm and clinical outcome? J. Neurol. Neurosurg. Psychiatry, June 1, 2004; 75(6): 868 - 872. [Abstract] [Full Text] [PDF]

				T. Vogel, R. Verreault, J.-F. Turcotte, M. Kiesmann, and M. Berthel Review Article. Intracerebral Aneurysms: A Review With Special Attention to Geriatric Aspects J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2003; 58(6): M520 - 524. [Abstract] [Full Text] [PDF]

				S. Bracard, A. Lebedinsky, R. Anxionnat, J. M. Neto, G. Audibert, Y. Long, and L. Picard Endovascular Treatment of Hunt and Hess Grade IV and V Aneuryms AJNR Am. J. Neuroradiol., June 1, 2002; 23(6): 953 - 957. [Abstract] [Full Text] [PDF]

				V. Aiyagari, D. T. Cross III, E. Deibert, R. G. Dacey Jr, and M. N. Diringer Safety of Hemodynamic Augmentation in Patients Treated With Guglielmi Detachable Coils After Acute Aneurysmal Subarachnoid Hemorrhage Stroke, September 1, 2001; 32(9): 1994 - 1997. [Abstract] [Full Text] [PDF]

				J. Claassen, G. L. Bernardini, K. Kreiter, J. Bates, Y. E. Du, D. Copeland, E. S. Connolly, and S. A. Mayer Effect of Cisternal and Ventricular Blood on Risk of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage:: The Fisher Scale Revisited Stroke, September 1, 2001; 32(9): 2012 - 2020. [Abstract] [Full Text] [PDF]

				S. Condette-Auliac, S. Bracard, R. Anxionnat, E. Schmitt, J. C. Lacour, M. Braun, J. Meloneto, A. Cordebar, L. Yin, and L. Picard Vasospasm After Subarachnoid Hemorrhage: Interest in Diffusion-Weighted MR Imaging Stroke, August 1, 2001; 32(8): 1818 - 1824. [Abstract] [Full Text] [PDF]

				M. Fujioka, K. Nishio, T. Sakaki, N. Minamino, and K. Kitamura Adrenomedullin in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage Stroke, December 1, 2000; 31 (12): 3079 - 3083. [Full Text]

				J.-i. Hamada, T. Mizuno, Y. Kai, M. Morioka, and Y. Ushio Microcatheter Intrathecal Urokinase Infusion Into Cisterna Magna for Prevention of Cerebral Vasospasm : Preliminary Report Stroke, September 1, 2000; 31(9): 2141 - 2148. [Abstract] [Full Text] [PDF]

				M. van der Jagt, D. Hasan, H. W. C. Bijvoet, H. Pieterman, P. J. Koudstaal, and C. J. J. Avezaat Interobserver variability of cisternal blood on CT after aneurysmal subarachnoid hemorrhage Neurology, June 13, 2000; 54(11): 2156 - 2158. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar