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Risk Factors Related to Aneurysmal Rebleeding
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Risk Factors Related to Aneurysmal Rebleeding Lie-mei Guo, Hong-yu Zhou, Ji-wen Xu, Yong Wang, Yong-ming Qiu, Ji-yao Jiang
Key words 䡲 Aneurysm 䡲 Binary logistic regression 䡲 Rebleeding 䡲 Risk factors 䡲 Subarachnoid hemorrhage Abbreviations and Acronyms CT: Computed tomography EVD: External ventricular drain OR: Odds ratio SAH: Subarachnoid hemorrhage SBP: Systolic arterial blood pressure Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China To whom correspondence should be addressed: Hong-yu Zhou, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2011) 76, 3/4:292-298. DOI: 10.1016/j.wneu.2011.03.025 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2011 Elsevier Inc. All rights reserved.
INTRODUCTION Aneurysmal rebleeding has long been recognized as a catastrophic complication of subarachnoid hemorrhage (SAH) that was associated with high mortality and morbidity (3, 5, 23, 30, 31). Unfortunately, the incidence of aneurysmal rebleeding is considerably high within hours after the initial SAH (1, 8, 12-14, 23, 30). However, even in many neurosurgical centers that aim for early aneurysm repair (aneurysm neck clipping or endovascular coiling), rebleeding cannot be completely eliminated. Undoubtedly, knowledge about the risk factors that predict rebleeding is essential for prioritizing the surgical management policies and optimizing the outcome. However, there is controversy regarding the risk factors that contribute to aneurysmal rebleeding (2, 4, 8, 9, 17-23, 25, 26). Several investigators have reported that rebleeding occurred more often in patients with advanced age, larger aneurysms, poor clinical
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䡲 OBJECTIVE: Rebleeding from ruptured intracranial aneurysms is a major cause of death and disability. The aim of this study was to investigate the incidence of rebleeding and the risk factors related to rebleeding before early aneurysm repair. 䡲 METHODS: The incidence of rebleeding, demographic data, and clinical data from 326 patients with aneurysmal subarachnoid hemorrhage (SAH) were retrospectively collected. All clinical variables were examined by univariate analysis, and a binary logistic regression analysis was performed to identify the risk factors related to rebleeding. 䡲 RESULTS: Rebleeding occurred in 70 (21.5%) of the 326 aneurysm patients during transfer or during the in-hospital stay (within 72 hours); 24 episodes (34.3%) occurred within 3 hours, and 44 episodes (62.9%) occurred within 6 hours after the initial SAH. Univariate analysis showed that there were significant differences between the rebleeding and nonrebleeding patients in terms of age, aneurysm size, systolic arterial blood pressure (SBP), Hunt– Hess grade and outcome at discharge. The binary logistic regression analysis revealed that age (odds ratio [OR] ⴝ 1.167), aneurysm size (OR ⴝ 1.624), SBP (OR ⴝ 3.338), and Hunt–Hess grade (OR ⴝ 2.512) were independent risk factors for aneurysmal rebleeding (for each P < 0.05). 䡲 CONCLUSIONS: The incidence of early aneurysmal rebleeding within hours after the initial SAH is high during transfer or during the in-hospital stay. Advanced age, an aneurysm size larger than 10 mm, SBP higher than 160 mmHg, and poor Hunt–Hess grade were independent risk factors for aneurysmal rebleeding. The importance of early aneurysm repair should be emphasized because aneurysmal rebleeding contributes to a poor outcome.
condition, or increased systolic arterial blood pressure (SBP) on admission, but these findings were not confirmed by other studies (2, 4, 8, 9, 17-23, 25, 26). Therefore, it is necessary to systematically validate these factors in a separate population of patients. In this study, the incidence of rebleeding, demographic data and clinical data were retrospectively collected, and all variables were examined by univariate analysis. Furthermore, possible risk factors related to aneurysmal rebleeding were investigated by a binary logistic regression analysis.
METHODS This study represented a retrospective review of aneurysmal SAH patients who presented between December 2002 and March 2010 to the Neurosurgery Department of Renji Hospital, which is affiliated to Shanghai Jiao Tong University. The predefined inclusion criteria for this study were as follows: 1) SAH demonstrated by computed tomography (CT) or lumbar puncture; 2) the presence of an aneurysm confirmed by cerebral digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography; and 3) rebleeding that originated from
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the ruptured aneurysm before aneurysm repair. Aneurysm neck clipping or endovascular coiling was performed in patients within 72 hours after the initial SAH. In addition, an external ventricular drain (EVD) was placed in patients with symptomatic hydrocephalus or intraventricular hemorrhage with depressed level of consciousness before aneurysm clipping or endovascular coiling. Antifibrinolytics were routinely administered in all of the aneurysm patients to decrease the incidence of rebleeding. Based on our treatment policies, nimodipine was not recommended before aneurysm clipping or endovascular coiling except when serious cerebral vasospasm was identified on digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography. For the assessment of rebleeding, all patients were followed up until the episode of rebleeding, surgery, discharge, or death. Rebleeding was defined as a sudden deterioration in the level of consciousness or a sudden increase in headache, combined with an increase of blood on CT compared with the previous scan. The clinical condition was assessed by Hunt–Hess grade (11), and CT scan SAH findings were assessed by Fisher’s grade (6). The location of the aneurysm was classified as follows: 1) the anterior communicating artery or the anterior cerebral artery; 2) the middle cerebral artery; 3) the internal carotid artery, including the posterior communicating artery; and 4) the vertebrobasilar arteries. In addition, aneurysm size was divided into five categories on the basis of maximal aneurysm diameter: ⱕ5 mm, ⬎5 to ⱕ10 mm, ⬎10 to ⱕ15 mm, ⬎15 to ⱕ20 mm, and ⬎20 mm. In cases with multiple aneurysms, only the ruptured aneurysm was considered. Generally, SBP was not aggressively lowered to avoid ischemic problems except when the blood pressure exceeded 160 mmHg. To evaluate the possible role of SBP as a factor that contributes to rebleeding, the SBP measured during transfer or during the in-hospital stay within 15 minutes before rebleeding was used for comparison in the rebleeding group; whereas in the nonrebleeding group, the values of SBP measured during transfer or during the in-hospital stay and the maximum SBP for each patient were selected for comparison. For a
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more convenient and easy analysis, the SBP was divided into two categories (ⱕ160 mmHg and ⬎160 mmHg) in the univariate and multivariate analysis. In addition, the functional outcome of patients at discharge was evaluated according to the Glasgow Outcome Scale (15). The following data were collected: the incidence of rebleeding, demographic data (gender, age, the time interval between the initial SAH and admission, the time interval between rebleeding and the initial SAH, and the time interval between aneurysm repair and the initial SAH), clinical condition during the transfer or during the in-hospital stay (SBP, Hunt–Hess grade), radiologic findings (the location and size of the aneurysm and Fisher’s grade on the CT scan), aneurysm treatment (aneurysm neck clipping, endovascular coiling or conservative treatment), and the functional outcome of patients at discharge (Glasgow Outcome Scale scores). SPSS 13.0 (SPSS, Inc.; Chicago, USA) for Windows was used for the statistical analysis. Statistical significance was defined as P ⬍ 0.05. Independent t-tests and chisquare tests were used to compare the mean for continuous data and categorical data, respectively. Furthermore, a binary logistic regression analysis was performed to investigate the possible risk factors for aneurysmal rebleeding.
RESULTS Study Population and Features of Rebleeding In the study period, 326 patients fulfilled the inclusion criteria. Comparative analysis of the demographic and clinical data between the rebleeding group and the nonrebleeding group is shown in Table 1. Rebleeding before aneurysm repair occurred in 70 patients (21.5%); 17 rebleeds occurred during transfer and 53 occurred during the in-hospital stays. In terms of the time interval between the initial SAH and admission, 182 patients (71.1%) were admitted within 6 hours in the non-rebleeding group, whereas 53 (75.7%) were admitted within 6 hours in the rebleeding group, which represents no significant difference between the two groups (P ⫽ 0.445). The time intervals between the initial SAH and admission in the 70 rebleeding patients are shown in Figure 1.
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After the initial SAH, rebleeding occurred in 24 patients (34.3%) within 3 hours and in 44 patients (62.9%) within 6 hours. Rebleeding occurred in the remaining 26 patients (37.1%) more than 6 hours after the initial SAH. The distribution of patients based on the interval between the initial SAH and rebleeding is shown in Figure 2, and a statistical description of the rate of rebleeding versus the time after the initial SAH is shown in Figure 3. Interventions and Outcome Interventions after rebleeding consisted of aneurysm neck clipping in 45 patients (64.3%), endovascular coiling in 15 patients (21.4%), and nonsurgical conservative treatment in 10 patients (14.3%). In the nonrebleeding group, surgical clipping was performed in 172 patients (67.2%), endovascular coiling in 76 patients (29.7%), and nonsurgical conservative treatment in 8 patients (3.1%). As a result, there were significant differences in the choice of post-rebleeding treatment compared to the treatment choices in the non-rebleeding group (P ⫽ 0.001). In addition, 31 patients received an EVD before aneurysm clipping (20 patients) or endovascular coiling (11 patients). No rebleeding was observed in any of those 31 patients. Moreover, the median time interval between the initial SAH and aneurysm repair was 9.5 hours, whereas the median time interval between the initial SAH and rebleeding was 4.5 hours. Contributing to the date above, we could find that these time intervals were too long to prevent rebleeding in this study. In terms of the functional outcome for the rebleeding patients, the Glasgow Outcome Scale scores at hospital discharge showed good recovery in 15 patients (21.4%), moderate disability in 9 patients (12.9%), and severe disability in 8 patients (11.4%); 33 patients (47.1%) died before discharge, and 5 patients (7.1%) demonstrated a persistent vegetative state. In comparison, the outcome of the nonrebleeding group was much better. In this group, 96 patients (37.5%) had good recovery, 67 patients (26.2%) had moderate disability, and 42 patients (16.4%) had severe disability; 28 patients (10.9%) remained in a persistent vegetative state and 23 patients (9.0%) died. Significant differences were found between the rebleeding and non-re-
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bleeding groups (P ⬍ 0.001), and rebleeding in this group would have likely resulted in a much poorer outcome.
Table 1. Univariate Analysis of Demographic and Clinical Data in 326 Aneurysm Patients No. of Patients Variables
Rebleeding
Non-rebleeding
31 (44.3%)
99 (38.7%)
Patient sex
0.395
Male Female
39 (55.7%)
157 (61.3%)
58.20 ⫾ 8.99
52.07 ⫾ 10.15
ⱕ6
53 (75.7%)
182 (71.1%)
⬎6
17 (24.3%)
74 (28.9%)
Age (mean ⫾ SD)
P Value
Admission and initial SAH (hours)
0.445
Aneurysm location
0.575
ACoA/ACA
20 (28.6%)
82 (32.0%)
MCA
17 (24.3%)
53 (20.7%)
ICA
29 (41.4%)
95 (37.1%)
VBA
4 (5.7%)
26 (10.2%)
4 (5.7%)
60 (23.4%)
⬎5 to ⱕ10
14 (20.0%)
91 (35.5%)
⬎10 to ⱕ15
27 (38.6%)
57 (22.3%)
⬎15 to ⱕ20
17 (24.3%)
36 (14.1%)
8 (11.4%)
12 (4.7%)
ⱕ160
26 (37.1%)
191 (74.6%)
⬎160
44 (62.9%)
65 (25.4%)
⬍0.001
Aneurysm size (mm) ⱕ5
⬎20 SBP on admission (mmHg)
0.002
Hunt–Hess grade
0.001
I
7 (10.0%)
44 (17.2%)
II
11 (15.7%)
89 (34.8%)
III
21 (30.0%)
58 (22.7%)
IV
28 (40.0%)
53 (20.7%)
V
3 (4.3%)
12 (4.7%)
Fisher’s grade
0.295
I
3 (4.3%)
20 (7.8%)
II
20 (28.6%)
96 (37.5%)
III
32 (45.7%)
94 (36.7%)
IV
15 (21.4%)
46 (18.0%)
45 (64.3%)
172 (67.2%)
Endovascular coiling
15 (21.4%)
76 (29.7%)
Conservative treatment
10 (14.3%)
8 (3.1%)
I
15 (21.4%)
96 (37.5%)
II
9 (12.9%)
67 (26.2%)
Treatments Aneurysm neck clipping
⬍0.001
0.001
⬍0.001
GOS score
Continues
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Factors Related to Aneurysmal Rebleeding Among the 70 rebleeding patients, 39 were female (55.7%), and in the non-rebleeding group, 157 patients were female (61.3%). Statistical analysis revealed no significant differences in the number of rebleeds based on gender (P ⫽ 0.395). However, a statistically significant difference was observed for age, with a mean age of 58.20 ⫾ 8.99 in the rebleeding group and 52.07 ⫾ 10.15 in the non-rebleeding group (P ⬍ 0.001). A significant difference was also found in terms of aneurysm size between the two groups (P ⬍ 0.001). In the rebleeding group, 74.3% of the aneurysms were ⬎10 mm, whereas only 41.1% of the aneurysms in the non-rebleeding group were ⬎10 mm. In terms of the SBP during transfer or on admission, 44 patients (62.9%) had an SBP ⬎160 mmHg in the rebleeding group, whereas 65 patients (25.4%) in the non-rebleeding group had an SBP ⬎160 mmHg; statistical analysis revealed that there was a significant difference between the two groups (P ⫽ 0.002). After the initial SAH, a significant difference existed between the two groups in terms of the clinical condition (Hunt–Hess grade); 44.3% patients in the rebleeding group and 25.4% patients in the non-rebleeding group presented with a poor Hunt–Hess grade (IV–V) (P ⫽ 0.001). In addition, no statistically significant differences were found in the location of the aneurysm and Fisher’s grade between the two groups (P ⫽ 0.575 and P ⫽ 0.295, respectively). Furthermore, a binary logistic regression model was used to adjust for potential confounding factors, such as age, aneurysm size, SBP, and Hunt–Hess grade. For the purpose of the analysis, the categories of aneurysm size were compressed into two categories (ⱕ10 mm and ⬎10 mm), and the clinical condition on admission was also classified into two groups (Hunt–Hess grades I–III and IV–V). The significance of the binary logistic regression was tested by chi-square analysis, which generated a probability value of ⬍0.05. Using this model, we were able to predict rebleeding among the 326 aneu-
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Table 1. Continued No. of Patients Variables
Rebleeding
Non-rebleeding
8 (11.4%)
42 (16.4%)
IV
5 (7.1%)
28 (10.9%)
V
33 (47.1%)
23 (9.0%)
III
P Value
Data are presented as number of patients (%) or mean ⫾ standard deviation. ACA, anterior cerebral artery; ACoA, anterior communicating artery; GOS, Glasgow Outcome Scale; ICA, internal carotid artery; MCA, middle cerebral artery; SAH, subarachnoid hemorrhage; SBP, systolic blood pressure; VBA, vertebrobasilar artery
rysm patients with a positive predictive value of 76.9% and a negative predictive value of 89.1%. The results of the binary logistic regression analysis indicated that age (OR ⫽ 1.167), aneurysm size (OR ⫽ 1.624), SBP (OR ⫽ 3.338), and Hunt–Hess grade (OR ⫽ 2.512) were independent risk factors for rebleeding (each with P ⬍ 0.05) (Table 2).
DISCUSSION Aneurysmal rebleeding is a serious and devastating complication of SAH with high mortality and morbidity (3, 5, 23, 30, 31). The results of this study indicated the following: 1) the incidence of early aneurysmal
rebleeding within hours after the initial SAH is high during transfer or during the in-hospital stay; and 2) advanced age, aneurysm size larger than 10 mm, SBP ⬎160 mmHg, and poor Hunt–Hess grade were independent risk factors for aneurysmal rebleeding.
Features of Rebleeding Previous reports stated that rebleeding occurred more often during the latter part of the first week or at the beginning of the second week after the initial SAH (16, 20, 26). More recent studies have focused on the hourly changes after the SAH; these studies found that the peak incidence of re-
Figure 1. Time interval between the initial subarachnoid hemorrhage (SAH) and admission in 70 patients with aneurysm rebleeds. Overall, 10 patients (14.3%) were admitted within 1 hour, 40 (57.1%) within 3 hours, and 53 (75.7%) within 6 hours after the initial SAH.
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bleeding was within the first 2– 6 hours (1, 14, 30). These findings suggested that aneurysmal rebleeding occurs more frequently in the earlier period after the initial SAH than previously believed. Therefore, Aoyagi et al. (1) proposed that within a short time period after the first rupture, the fibrin net covering the site of rupture could not tolerate a slight internal pressure increase in the aneurysmal dome. In this study, rebleeding occurred in 24 patients (34.3%) within 3 hours and in 44 patients (62.9%) within 6 hours. Thus, the results indicated that the early aneurysmal rebleeding within hours after the initial SAH was very common during transfer or during the in-hospital stay. In recent years, because of the quick evaluation of the clinical situation and the skilled efforts of the emergency medical transport personnel, patients have been admitted to hospitals much sooner after the onset of symptoms. In fact, 72.1% of the patients in the present study were admitted within 6 hours after the initial SAH, which is consistent with other recent reports (1, 8, 14, 30). Several previous reports have mentioned the prevalent rebleeding circumstances. Sasaki et al. (27) reported that 19.9% of aneurysmal rebleeding occurred during transfer in a series of 559 patients. In 2001, Ohkuma et al. (23) reported that 13.6% of patients with SAH experienced rebleeding in the ambulance or at the referring hospital before admission. Cha et al. (4) found that the incidence of prehospitalization rebleeding was 37.1%. Our results showed that 24.3% of rebleeding occurred during transfer. This discrepancy may be caused by the differences in emergency medical delivery systems. Interventions and Outcome At present, increasing numbers of neurosurgical centers aim for early aneurysm repair (aneurysm neck clipping or endovascular coiling). In this study, early repair for ruptured aneurysms was performed within 72 hours after the initial SAH. However, because the median time interval between the initial SAH and the aneurysm repair was 9.5 hours and the median time interval between the initial SAH and rebleeding was 4.5 hours, we found that these time intervals before repair were too long to prevent rebleeding in this study.
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uted to that finding. Therefore, similar to other studies (7, 10), there was no evidence in this study to suggest that EVDs cause rebleeding in aneurysmal patients. Rebleeding contributes to a poor outcome. The mortality due to rebleeding has been reported to be as high as 50%– 80% (3, 5, 23, 31). In this study, there were significant differences in the outcome at discharge between the rebleeding group and the nonrebleeding group; the rebleeding group showed a mortality of 47.1%, whereas the non-rebleeding group showed only 9.0%. Although many advances have been made in surgical techniques and medical management, early repair still seems to be the most effective method of preventing rebleeding and reducing the probability of serious sequelae.
Figure 2. Time interval between the initial subarachnoid hemorrhage and rebleeding. Rebleeding occurred in 3 (4.3%) patients within 1 hour, and in 21 (30.0%) it occurred between 1 and 3 hours. Overall, rebleeding occurred in 24 (34.3%) patients within 3 hours and in 44 (62.9%) within 6 hours.
In addition, in this study, EVDs were placed before aneurysm clipping or endovascular coiling in 31 aneurysmal patients to relieve acute hydrocephalus. However,
no rebleeding was found in any of those 31 patients, and the short time interval between EVD placement and surgical clipping or endovascular coiling might have contrib-
Figure 3. A statistical description of the rate of rebleeding versus time after the initial subarachnoid hemorrhage. It shows that there was a peak in the incidence of rebleeding at 2–3 hours, which then decreased with time.
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Factors Related to Aneurysmal Rebleeding The risk factors for aneurysmal rebleeding have been defined in various studies, but no consensus has been reached (2, 4, 8, 9, 1723, 25, 26). In this study, we found that age, aneurysm size, SBP, and Hunt–Hess grade were independent risk factors for aneurysmal rebleeding. No significant differences were found in terms of gender, the location of the aneurysms, and Fisher’s grade between the rebleeding and non-rebleeding groups. Advanced age was recognized as a prognostic indicator of poor outcome after SAH (19). Nevertheless, whether it could be used to predict rebleeding and its relationship to other prognostic factors needs to be evaluated. Several prior studies have reported that rebleeding occurred in patients who were significantly older than the control subjects (20, 29). Lanzino et al. (19) found that the rate of rebleeding increased from 4.5% in the youngest age group to 16.4% in patients who were older than age 70 years. However, Naidech (22) recently studied the univariate analysis of the predictors of rebleeding and suggested that age was not associated with rebleeding. However, in this study, age was determined to be an independent risk factor for rebleeding. Aneurysm size was a major risk factor for initial rupture (24, 28, 32), and was also directly linked to the risk of rebleeding (17, 21, 22, 25). In 2006, Machiel et al. (21) found that patients with larger aneurysms (⬎10 mm) had a higher risk of rebleeding,
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Table 2. Risk Factors Related to Aneurysmal Rebleeding Revealed by the Binary Logistic Regression Analysis Rebleeding Yes/no
Variables
Categories
Age Aneurysm size (mm) SBP (mmHg) Hunt–Hess grade
ⱕ10 or ⬎10 ⱕ160 or ⬎160 I–III or IV–V
P Value
Odds Ratios
95% CI
⬍0.001
1.167
1.116–1.220
0.002
1.624
1.188–2.221
⬍0.001
3.338
1.734–7.737
0.001
2.512
1.734–3.639
CI, confidence interval; SBP, systolic arterial blood pressure.
particularly within the first 3 days after the initial SAH. Similarly, aneurysm size was found to be an independent risk factor in predicting aneurysmal rebleeding in this study. We found that the probability of rebleeding in patients with aneurysms larger than 10 mm was 1.624-fold greater than in those with aneurysms of 10 mm or less. To date, no well-controlled studies exist that determine whether blood pressure control in acute SAH influences rebleeding (3). A large retrospective study reported a rebleeding rate of 6.9% after admission, but no relationship to blood pressure was found (17). In contrast, many other studies found that persistently elevated blood pressure after the first SAH led to a higher risk of rebleeding (3, 5, 8, 23, 30). In a retrospective review of 179 patients who were admitted within 24 hours of SAH, 17% experienced rebleeding, which was associated with SBP ⬎150 mmHg (8). In addition, Ohkuma et al. found that rebleeding was more common in patients with SBP ⬎160 mmHg in the ambulance or at the referring hospital (23). Similarly, this study revealed that the frequency of rebleeding in SAH patients with SBP ⬎160 mmHg was nearly 3.4 times greater than in those with SBP ⱕ160 mmHg. Consequently, efforts should be focused on lowering the blood pressure moderately (not aggressively) to prevent both rebleeding and ischemic problems. The patient’s clinical status on admission was assessed using the Hunt–Hess scale, which describes the patient’s condition immediately after SAH and is often used as a predictor of clinical outcome. Several investigators have reported that poor Hunt–Hess grade was significantly related to aneurysmal rebleeding (22, 23, 25, 26). This relationship was supported by our results, which showed that initial SAH patients with poor Hunt–Hess grades (IV–V)
had a higher incidence of rebleeding than those with good Hunt–Hess grades (I–III). In addition, in contrast with previous studies that showed the location of the aneurysm was implicated in aneurysmal rebleeding (4, 30), the present study revealed that the aneurysm location was not a risk factor for rebleeding. The amount of SAH on CT scans (Fisher’s grade), which was regularly used to predict cerebral vasospasm after aneurysmal SAH, also appeared to have no relationship to rebleeding. The limitations of this study should also be mentioned. One of the major limitations is that the sample size was relatively small. In addition, a possible bias might have been introduced using the binary logistic regression model. To better predict aneurysmal rebleeding, more clinical factors should be introduced into the analysis and further investigations are necessary in the future. In conclusion, the incidence of early rebleeding within hours after the initial SAH is high in aneurysm patients during transfer or during the in-hospital stay. Advanced age, larger aneurysm size, SBP ⬎160 mmHg, and poor Hunt–Hess grade were independent risk factors for aneurysmal rebleeding. Because aneurysmal rebleeding contributes to a poor outcome, the importance of early aneurysm repair must be emphasized in patients with risk factors for rebleeding.
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25. Roganovic Z, Pavlicevic G, Tadic R, Djirkovic S: [Risk factors for the onset of vasospasm and rebleeding after spontaneous subarachnoid hemorrhage]. Vojnosanit Pregl 58:17-23, 2001 [in Serbian].
20. Locksley HB: Natural history of subarachnoid hemorrhage, intracranial aneurysms and arteriovenous malformations. Based on 6368 cases in the cooperative study. J Neurosurg 25:219-239, 1966.
26. Rosenorn J, Eskesen V, Schmidt K, Ronde F: The risk of rebleeding from ruptured intracranial aneurysms. J Neurosurg 67:329-332, 1987.
21. Machiel Pleizier C, Algra A, Velthuis BK, Rinkel GJ: Relation between size of aneurysms and risk of rebleeding in patients with subarachnoid haemorrhage. Acta Neurochir (Wien) 148:1277-1279, 2006. 22. Naidech AM, Janjua N, Kreiter KT, Ostapkovich ND, Fitzsimmons BF, Parra A, Commichau C, Connolly ES, Mayer SA: Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage. Arch Neurol 62:410-416, 2005.
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27. Sakaki T, Morimoto T, Hoshida T, Kawaguchi S, Nakase H, Fukuzumi A: Rebleeding during transport of patients with a ruptured intracranial aneurysm. J Stroke Cerebrovasc Dis 8:38-41, 1999. 28. Salary M, Quigley MR, Wilberger JE Jr: Relation among aneurysm size, amount of subarachnoid blood, and clinical outcome. J Neurosurg 107:13-17, 2007. 29. Steiger HJ, Fritschi J, Seiler RW: Current pattern of inhospital aneurysmal rebleeds. Analysis of a series treated
with individually timed surgery and intravenous nimodipine. Acta Neurochir (Wien) 127:21-26, 1994. 30. Tanno Y, Homma M, Oinuma M, Kodama N, Ymamoto T: Rebleeding from ruptured intracranial aneurysms in North Eastern Province of Japan. A cooperative study. J Neurol Sci 258:11-16, 2007. 31. van Gijn J, Kerr RS, Rinkel GJ: Subarachnoid haemorrhage. Lancet 369:306-318, 2007. 32. Wiebers DO, Whisnant JP, Huston J 3rd, Meissner I, Brown RD Jr, Piepgras DG, Forbes GS, Thielen K, Nichols D, O’Fallon WM, Peacock J, Jaeger L, Kassell NF, Kongable-Beckman GL, Torner JC: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:103-110, 2003.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. received 23 September 2010; accepted 22 March, 2011 Citation: World Neurosurg. (2011) 76, 3/4:292-298. DOI: 10.1016/j.wneu.2011.03.025 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2011 Elsevier Inc. All rights reserved.
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Risk Factors Related to Aneurysmal Rebleeding Lie-mei Guo, Hong-yu Zhou, Ji-wen Xu, Yong Wang, Yong-ming Qiu, Ji-yao Jiang
Key words 䡲 Aneurysm 䡲 Binary logistic regression 䡲 Rebleeding 䡲 Risk factors 䡲 Subarachnoid hemorrhage Abbreviations and Acronyms CT: Computed tomography EVD: External ventricular drain OR: Odds ratio SAH: Subarachnoid hemorrhage SBP: Systolic arterial blood pressure Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China To whom correspondence should be addressed: Hong-yu Zhou, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2011) 76, 3/4:292-298. DOI: 10.1016/j.wneu.2011.03.025 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2011 Elsevier Inc. All rights reserved.
INTRODUCTION Aneurysmal rebleeding has long been recognized as a catastrophic complication of subarachnoid hemorrhage (SAH) that was associated with high mortality and morbidity (3, 5, 23, 30, 31). Unfortunately, the incidence of aneurysmal rebleeding is considerably high within hours after the initial SAH (1, 8, 12-14, 23, 30). However, even in many neurosurgical centers that aim for early aneurysm repair (aneurysm neck clipping or endovascular coiling), rebleeding cannot be completely eliminated. Undoubtedly, knowledge about the risk factors that predict rebleeding is essential for prioritizing the surgical management policies and optimizing the outcome. However, there is controversy regarding the risk factors that contribute to aneurysmal rebleeding (2, 4, 8, 9, 17-23, 25, 26). Several investigators have reported that rebleeding occurred more often in patients with advanced age, larger aneurysms, poor clinical
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䡲 OBJECTIVE: Rebleeding from ruptured intracranial aneurysms is a major cause of death and disability. The aim of this study was to investigate the incidence of rebleeding and the risk factors related to rebleeding before early aneurysm repair. 䡲 METHODS: The incidence of rebleeding, demographic data, and clinical data from 326 patients with aneurysmal subarachnoid hemorrhage (SAH) were retrospectively collected. All clinical variables were examined by univariate analysis, and a binary logistic regression analysis was performed to identify the risk factors related to rebleeding. 䡲 RESULTS: Rebleeding occurred in 70 (21.5%) of the 326 aneurysm patients during transfer or during the in-hospital stay (within 72 hours); 24 episodes (34.3%) occurred within 3 hours, and 44 episodes (62.9%) occurred within 6 hours after the initial SAH. Univariate analysis showed that there were significant differences between the rebleeding and nonrebleeding patients in terms of age, aneurysm size, systolic arterial blood pressure (SBP), Hunt– Hess grade and outcome at discharge. The binary logistic regression analysis revealed that age (odds ratio [OR] ⴝ 1.167), aneurysm size (OR ⴝ 1.624), SBP (OR ⴝ 3.338), and Hunt–Hess grade (OR ⴝ 2.512) were independent risk factors for aneurysmal rebleeding (for each P < 0.05). 䡲 CONCLUSIONS: The incidence of early aneurysmal rebleeding within hours after the initial SAH is high during transfer or during the in-hospital stay. Advanced age, an aneurysm size larger than 10 mm, SBP higher than 160 mmHg, and poor Hunt–Hess grade were independent risk factors for aneurysmal rebleeding. The importance of early aneurysm repair should be emphasized because aneurysmal rebleeding contributes to a poor outcome.
condition, or increased systolic arterial blood pressure (SBP) on admission, but these findings were not confirmed by other studies (2, 4, 8, 9, 17-23, 25, 26). Therefore, it is necessary to systematically validate these factors in a separate population of patients. In this study, the incidence of rebleeding, demographic data and clinical data were retrospectively collected, and all variables were examined by univariate analysis. Furthermore, possible risk factors related to aneurysmal rebleeding were investigated by a binary logistic regression analysis.
METHODS This study represented a retrospective review of aneurysmal SAH patients who presented between December 2002 and March 2010 to the Neurosurgery Department of Renji Hospital, which is affiliated to Shanghai Jiao Tong University. The predefined inclusion criteria for this study were as follows: 1) SAH demonstrated by computed tomography (CT) or lumbar puncture; 2) the presence of an aneurysm confirmed by cerebral digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography; and 3) rebleeding that originated from
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the ruptured aneurysm before aneurysm repair. Aneurysm neck clipping or endovascular coiling was performed in patients within 72 hours after the initial SAH. In addition, an external ventricular drain (EVD) was placed in patients with symptomatic hydrocephalus or intraventricular hemorrhage with depressed level of consciousness before aneurysm clipping or endovascular coiling. Antifibrinolytics were routinely administered in all of the aneurysm patients to decrease the incidence of rebleeding. Based on our treatment policies, nimodipine was not recommended before aneurysm clipping or endovascular coiling except when serious cerebral vasospasm was identified on digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography. For the assessment of rebleeding, all patients were followed up until the episode of rebleeding, surgery, discharge, or death. Rebleeding was defined as a sudden deterioration in the level of consciousness or a sudden increase in headache, combined with an increase of blood on CT compared with the previous scan. The clinical condition was assessed by Hunt–Hess grade (11), and CT scan SAH findings were assessed by Fisher’s grade (6). The location of the aneurysm was classified as follows: 1) the anterior communicating artery or the anterior cerebral artery; 2) the middle cerebral artery; 3) the internal carotid artery, including the posterior communicating artery; and 4) the vertebrobasilar arteries. In addition, aneurysm size was divided into five categories on the basis of maximal aneurysm diameter: ⱕ5 mm, ⬎5 to ⱕ10 mm, ⬎10 to ⱕ15 mm, ⬎15 to ⱕ20 mm, and ⬎20 mm. In cases with multiple aneurysms, only the ruptured aneurysm was considered. Generally, SBP was not aggressively lowered to avoid ischemic problems except when the blood pressure exceeded 160 mmHg. To evaluate the possible role of SBP as a factor that contributes to rebleeding, the SBP measured during transfer or during the in-hospital stay within 15 minutes before rebleeding was used for comparison in the rebleeding group; whereas in the nonrebleeding group, the values of SBP measured during transfer or during the in-hospital stay and the maximum SBP for each patient were selected for comparison. For a
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more convenient and easy analysis, the SBP was divided into two categories (ⱕ160 mmHg and ⬎160 mmHg) in the univariate and multivariate analysis. In addition, the functional outcome of patients at discharge was evaluated according to the Glasgow Outcome Scale (15). The following data were collected: the incidence of rebleeding, demographic data (gender, age, the time interval between the initial SAH and admission, the time interval between rebleeding and the initial SAH, and the time interval between aneurysm repair and the initial SAH), clinical condition during the transfer or during the in-hospital stay (SBP, Hunt–Hess grade), radiologic findings (the location and size of the aneurysm and Fisher’s grade on the CT scan), aneurysm treatment (aneurysm neck clipping, endovascular coiling or conservative treatment), and the functional outcome of patients at discharge (Glasgow Outcome Scale scores). SPSS 13.0 (SPSS, Inc.; Chicago, USA) for Windows was used for the statistical analysis. Statistical significance was defined as P ⬍ 0.05. Independent t-tests and chisquare tests were used to compare the mean for continuous data and categorical data, respectively. Furthermore, a binary logistic regression analysis was performed to investigate the possible risk factors for aneurysmal rebleeding.
RESULTS Study Population and Features of Rebleeding In the study period, 326 patients fulfilled the inclusion criteria. Comparative analysis of the demographic and clinical data between the rebleeding group and the nonrebleeding group is shown in Table 1. Rebleeding before aneurysm repair occurred in 70 patients (21.5%); 17 rebleeds occurred during transfer and 53 occurred during the in-hospital stays. In terms of the time interval between the initial SAH and admission, 182 patients (71.1%) were admitted within 6 hours in the non-rebleeding group, whereas 53 (75.7%) were admitted within 6 hours in the rebleeding group, which represents no significant difference between the two groups (P ⫽ 0.445). The time intervals between the initial SAH and admission in the 70 rebleeding patients are shown in Figure 1.
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After the initial SAH, rebleeding occurred in 24 patients (34.3%) within 3 hours and in 44 patients (62.9%) within 6 hours. Rebleeding occurred in the remaining 26 patients (37.1%) more than 6 hours after the initial SAH. The distribution of patients based on the interval between the initial SAH and rebleeding is shown in Figure 2, and a statistical description of the rate of rebleeding versus the time after the initial SAH is shown in Figure 3. Interventions and Outcome Interventions after rebleeding consisted of aneurysm neck clipping in 45 patients (64.3%), endovascular coiling in 15 patients (21.4%), and nonsurgical conservative treatment in 10 patients (14.3%). In the nonrebleeding group, surgical clipping was performed in 172 patients (67.2%), endovascular coiling in 76 patients (29.7%), and nonsurgical conservative treatment in 8 patients (3.1%). As a result, there were significant differences in the choice of post-rebleeding treatment compared to the treatment choices in the non-rebleeding group (P ⫽ 0.001). In addition, 31 patients received an EVD before aneurysm clipping (20 patients) or endovascular coiling (11 patients). No rebleeding was observed in any of those 31 patients. Moreover, the median time interval between the initial SAH and aneurysm repair was 9.5 hours, whereas the median time interval between the initial SAH and rebleeding was 4.5 hours. Contributing to the date above, we could find that these time intervals were too long to prevent rebleeding in this study. In terms of the functional outcome for the rebleeding patients, the Glasgow Outcome Scale scores at hospital discharge showed good recovery in 15 patients (21.4%), moderate disability in 9 patients (12.9%), and severe disability in 8 patients (11.4%); 33 patients (47.1%) died before discharge, and 5 patients (7.1%) demonstrated a persistent vegetative state. In comparison, the outcome of the nonrebleeding group was much better. In this group, 96 patients (37.5%) had good recovery, 67 patients (26.2%) had moderate disability, and 42 patients (16.4%) had severe disability; 28 patients (10.9%) remained in a persistent vegetative state and 23 patients (9.0%) died. Significant differences were found between the rebleeding and non-re-
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bleeding groups (P ⬍ 0.001), and rebleeding in this group would have likely resulted in a much poorer outcome.
Table 1. Univariate Analysis of Demographic and Clinical Data in 326 Aneurysm Patients No. of Patients Variables
Rebleeding
Non-rebleeding
31 (44.3%)
99 (38.7%)
Patient sex
0.395
Male Female
39 (55.7%)
157 (61.3%)
58.20 ⫾ 8.99
52.07 ⫾ 10.15
ⱕ6
53 (75.7%)
182 (71.1%)
⬎6
17 (24.3%)
74 (28.9%)
Age (mean ⫾ SD)
P Value
Admission and initial SAH (hours)
0.445
Aneurysm location
0.575
ACoA/ACA
20 (28.6%)
82 (32.0%)
MCA
17 (24.3%)
53 (20.7%)
ICA
29 (41.4%)
95 (37.1%)
VBA
4 (5.7%)
26 (10.2%)
4 (5.7%)
60 (23.4%)
⬎5 to ⱕ10
14 (20.0%)
91 (35.5%)
⬎10 to ⱕ15
27 (38.6%)
57 (22.3%)
⬎15 to ⱕ20
17 (24.3%)
36 (14.1%)
8 (11.4%)
12 (4.7%)
ⱕ160
26 (37.1%)
191 (74.6%)
⬎160
44 (62.9%)
65 (25.4%)
⬍0.001
Aneurysm size (mm) ⱕ5
⬎20 SBP on admission (mmHg)
0.002
Hunt–Hess grade
0.001
I
7 (10.0%)
44 (17.2%)
II
11 (15.7%)
89 (34.8%)
III
21 (30.0%)
58 (22.7%)
IV
28 (40.0%)
53 (20.7%)
V
3 (4.3%)
12 (4.7%)
Fisher’s grade
0.295
I
3 (4.3%)
20 (7.8%)
II
20 (28.6%)
96 (37.5%)
III
32 (45.7%)
94 (36.7%)
IV
15 (21.4%)
46 (18.0%)
45 (64.3%)
172 (67.2%)
Endovascular coiling
15 (21.4%)
76 (29.7%)
Conservative treatment
10 (14.3%)
8 (3.1%)
I
15 (21.4%)
96 (37.5%)
II
9 (12.9%)
67 (26.2%)
Treatments Aneurysm neck clipping
⬍0.001
0.001
⬍0.001
GOS score
Continues
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Factors Related to Aneurysmal Rebleeding Among the 70 rebleeding patients, 39 were female (55.7%), and in the non-rebleeding group, 157 patients were female (61.3%). Statistical analysis revealed no significant differences in the number of rebleeds based on gender (P ⫽ 0.395). However, a statistically significant difference was observed for age, with a mean age of 58.20 ⫾ 8.99 in the rebleeding group and 52.07 ⫾ 10.15 in the non-rebleeding group (P ⬍ 0.001). A significant difference was also found in terms of aneurysm size between the two groups (P ⬍ 0.001). In the rebleeding group, 74.3% of the aneurysms were ⬎10 mm, whereas only 41.1% of the aneurysms in the non-rebleeding group were ⬎10 mm. In terms of the SBP during transfer or on admission, 44 patients (62.9%) had an SBP ⬎160 mmHg in the rebleeding group, whereas 65 patients (25.4%) in the non-rebleeding group had an SBP ⬎160 mmHg; statistical analysis revealed that there was a significant difference between the two groups (P ⫽ 0.002). After the initial SAH, a significant difference existed between the two groups in terms of the clinical condition (Hunt–Hess grade); 44.3% patients in the rebleeding group and 25.4% patients in the non-rebleeding group presented with a poor Hunt–Hess grade (IV–V) (P ⫽ 0.001). In addition, no statistically significant differences were found in the location of the aneurysm and Fisher’s grade between the two groups (P ⫽ 0.575 and P ⫽ 0.295, respectively). Furthermore, a binary logistic regression model was used to adjust for potential confounding factors, such as age, aneurysm size, SBP, and Hunt–Hess grade. For the purpose of the analysis, the categories of aneurysm size were compressed into two categories (ⱕ10 mm and ⬎10 mm), and the clinical condition on admission was also classified into two groups (Hunt–Hess grades I–III and IV–V). The significance of the binary logistic regression was tested by chi-square analysis, which generated a probability value of ⬍0.05. Using this model, we were able to predict rebleeding among the 326 aneu-
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Table 1. Continued No. of Patients Variables
Rebleeding
Non-rebleeding
8 (11.4%)
42 (16.4%)
IV
5 (7.1%)
28 (10.9%)
V
33 (47.1%)
23 (9.0%)
III
P Value
Data are presented as number of patients (%) or mean ⫾ standard deviation. ACA, anterior cerebral artery; ACoA, anterior communicating artery; GOS, Glasgow Outcome Scale; ICA, internal carotid artery; MCA, middle cerebral artery; SAH, subarachnoid hemorrhage; SBP, systolic blood pressure; VBA, vertebrobasilar artery
rysm patients with a positive predictive value of 76.9% and a negative predictive value of 89.1%. The results of the binary logistic regression analysis indicated that age (OR ⫽ 1.167), aneurysm size (OR ⫽ 1.624), SBP (OR ⫽ 3.338), and Hunt–Hess grade (OR ⫽ 2.512) were independent risk factors for rebleeding (each with P ⬍ 0.05) (Table 2).
DISCUSSION Aneurysmal rebleeding is a serious and devastating complication of SAH with high mortality and morbidity (3, 5, 23, 30, 31). The results of this study indicated the following: 1) the incidence of early aneurysmal
rebleeding within hours after the initial SAH is high during transfer or during the in-hospital stay; and 2) advanced age, aneurysm size larger than 10 mm, SBP ⬎160 mmHg, and poor Hunt–Hess grade were independent risk factors for aneurysmal rebleeding.
Features of Rebleeding Previous reports stated that rebleeding occurred more often during the latter part of the first week or at the beginning of the second week after the initial SAH (16, 20, 26). More recent studies have focused on the hourly changes after the SAH; these studies found that the peak incidence of re-
Figure 1. Time interval between the initial subarachnoid hemorrhage (SAH) and admission in 70 patients with aneurysm rebleeds. Overall, 10 patients (14.3%) were admitted within 1 hour, 40 (57.1%) within 3 hours, and 53 (75.7%) within 6 hours after the initial SAH.
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bleeding was within the first 2– 6 hours (1, 14, 30). These findings suggested that aneurysmal rebleeding occurs more frequently in the earlier period after the initial SAH than previously believed. Therefore, Aoyagi et al. (1) proposed that within a short time period after the first rupture, the fibrin net covering the site of rupture could not tolerate a slight internal pressure increase in the aneurysmal dome. In this study, rebleeding occurred in 24 patients (34.3%) within 3 hours and in 44 patients (62.9%) within 6 hours. Thus, the results indicated that the early aneurysmal rebleeding within hours after the initial SAH was very common during transfer or during the in-hospital stay. In recent years, because of the quick evaluation of the clinical situation and the skilled efforts of the emergency medical transport personnel, patients have been admitted to hospitals much sooner after the onset of symptoms. In fact, 72.1% of the patients in the present study were admitted within 6 hours after the initial SAH, which is consistent with other recent reports (1, 8, 14, 30). Several previous reports have mentioned the prevalent rebleeding circumstances. Sasaki et al. (27) reported that 19.9% of aneurysmal rebleeding occurred during transfer in a series of 559 patients. In 2001, Ohkuma et al. (23) reported that 13.6% of patients with SAH experienced rebleeding in the ambulance or at the referring hospital before admission. Cha et al. (4) found that the incidence of prehospitalization rebleeding was 37.1%. Our results showed that 24.3% of rebleeding occurred during transfer. This discrepancy may be caused by the differences in emergency medical delivery systems. Interventions and Outcome At present, increasing numbers of neurosurgical centers aim for early aneurysm repair (aneurysm neck clipping or endovascular coiling). In this study, early repair for ruptured aneurysms was performed within 72 hours after the initial SAH. However, because the median time interval between the initial SAH and the aneurysm repair was 9.5 hours and the median time interval between the initial SAH and rebleeding was 4.5 hours, we found that these time intervals before repair were too long to prevent rebleeding in this study.
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uted to that finding. Therefore, similar to other studies (7, 10), there was no evidence in this study to suggest that EVDs cause rebleeding in aneurysmal patients. Rebleeding contributes to a poor outcome. The mortality due to rebleeding has been reported to be as high as 50%– 80% (3, 5, 23, 31). In this study, there were significant differences in the outcome at discharge between the rebleeding group and the nonrebleeding group; the rebleeding group showed a mortality of 47.1%, whereas the non-rebleeding group showed only 9.0%. Although many advances have been made in surgical techniques and medical management, early repair still seems to be the most effective method of preventing rebleeding and reducing the probability of serious sequelae.
Figure 2. Time interval between the initial subarachnoid hemorrhage and rebleeding. Rebleeding occurred in 3 (4.3%) patients within 1 hour, and in 21 (30.0%) it occurred between 1 and 3 hours. Overall, rebleeding occurred in 24 (34.3%) patients within 3 hours and in 44 (62.9%) within 6 hours.
In addition, in this study, EVDs were placed before aneurysm clipping or endovascular coiling in 31 aneurysmal patients to relieve acute hydrocephalus. However,
no rebleeding was found in any of those 31 patients, and the short time interval between EVD placement and surgical clipping or endovascular coiling might have contrib-
Figure 3. A statistical description of the rate of rebleeding versus time after the initial subarachnoid hemorrhage. It shows that there was a peak in the incidence of rebleeding at 2–3 hours, which then decreased with time.
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Factors Related to Aneurysmal Rebleeding The risk factors for aneurysmal rebleeding have been defined in various studies, but no consensus has been reached (2, 4, 8, 9, 1723, 25, 26). In this study, we found that age, aneurysm size, SBP, and Hunt–Hess grade were independent risk factors for aneurysmal rebleeding. No significant differences were found in terms of gender, the location of the aneurysms, and Fisher’s grade between the rebleeding and non-rebleeding groups. Advanced age was recognized as a prognostic indicator of poor outcome after SAH (19). Nevertheless, whether it could be used to predict rebleeding and its relationship to other prognostic factors needs to be evaluated. Several prior studies have reported that rebleeding occurred in patients who were significantly older than the control subjects (20, 29). Lanzino et al. (19) found that the rate of rebleeding increased from 4.5% in the youngest age group to 16.4% in patients who were older than age 70 years. However, Naidech (22) recently studied the univariate analysis of the predictors of rebleeding and suggested that age was not associated with rebleeding. However, in this study, age was determined to be an independent risk factor for rebleeding. Aneurysm size was a major risk factor for initial rupture (24, 28, 32), and was also directly linked to the risk of rebleeding (17, 21, 22, 25). In 2006, Machiel et al. (21) found that patients with larger aneurysms (⬎10 mm) had a higher risk of rebleeding,
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Table 2. Risk Factors Related to Aneurysmal Rebleeding Revealed by the Binary Logistic Regression Analysis Rebleeding Yes/no
Variables
Categories
Age Aneurysm size (mm) SBP (mmHg) Hunt–Hess grade
ⱕ10 or ⬎10 ⱕ160 or ⬎160 I–III or IV–V
P Value
Odds Ratios
95% CI
⬍0.001
1.167
1.116–1.220
0.002
1.624
1.188–2.221
⬍0.001
3.338
1.734–7.737
0.001
2.512
1.734–3.639
CI, confidence interval; SBP, systolic arterial blood pressure.
particularly within the first 3 days after the initial SAH. Similarly, aneurysm size was found to be an independent risk factor in predicting aneurysmal rebleeding in this study. We found that the probability of rebleeding in patients with aneurysms larger than 10 mm was 1.624-fold greater than in those with aneurysms of 10 mm or less. To date, no well-controlled studies exist that determine whether blood pressure control in acute SAH influences rebleeding (3). A large retrospective study reported a rebleeding rate of 6.9% after admission, but no relationship to blood pressure was found (17). In contrast, many other studies found that persistently elevated blood pressure after the first SAH led to a higher risk of rebleeding (3, 5, 8, 23, 30). In a retrospective review of 179 patients who were admitted within 24 hours of SAH, 17% experienced rebleeding, which was associated with SBP ⬎150 mmHg (8). In addition, Ohkuma et al. found that rebleeding was more common in patients with SBP ⬎160 mmHg in the ambulance or at the referring hospital (23). Similarly, this study revealed that the frequency of rebleeding in SAH patients with SBP ⬎160 mmHg was nearly 3.4 times greater than in those with SBP ⱕ160 mmHg. Consequently, efforts should be focused on lowering the blood pressure moderately (not aggressively) to prevent both rebleeding and ischemic problems. The patient’s clinical status on admission was assessed using the Hunt–Hess scale, which describes the patient’s condition immediately after SAH and is often used as a predictor of clinical outcome. Several investigators have reported that poor Hunt–Hess grade was significantly related to aneurysmal rebleeding (22, 23, 25, 26). This relationship was supported by our results, which showed that initial SAH patients with poor Hunt–Hess grades (IV–V)
had a higher incidence of rebleeding than those with good Hunt–Hess grades (I–III). In addition, in contrast with previous studies that showed the location of the aneurysm was implicated in aneurysmal rebleeding (4, 30), the present study revealed that the aneurysm location was not a risk factor for rebleeding. The amount of SAH on CT scans (Fisher’s grade), which was regularly used to predict cerebral vasospasm after aneurysmal SAH, also appeared to have no relationship to rebleeding. The limitations of this study should also be mentioned. One of the major limitations is that the sample size was relatively small. In addition, a possible bias might have been introduced using the binary logistic regression model. To better predict aneurysmal rebleeding, more clinical factors should be introduced into the analysis and further investigations are necessary in the future. In conclusion, the incidence of early rebleeding within hours after the initial SAH is high in aneurysm patients during transfer or during the in-hospital stay. Advanced age, larger aneurysm size, SBP ⬎160 mmHg, and poor Hunt–Hess grade were independent risk factors for aneurysmal rebleeding. Because aneurysmal rebleeding contributes to a poor outcome, the importance of early aneurysm repair must be emphasized in patients with risk factors for rebleeding.
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. received 23 September 2010; accepted 22 March, 2011 Citation: World Neurosurg. (2011) 76, 3/4:292-298. DOI: 10.1016/j.wneu.2011.03.025 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2011 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2011.03.025