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Annals of Indian Academy of Neurology
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ORIGINAL ARTICLE
Year : 2007  |  Volume : 10  |  Issue : 4  |  Page : 247-251
 

Patterns and predictors of in-hospital aneurysmal rebleed: An institutional experience and review of literature


Department of Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India

Correspondence Address:
Girish Ramachandran Menon
Department of Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum - 695 011
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-2327.37817

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   Abstract 

Background: Rebleeding is an important cause for mortality following aneurysmal subarachnoid hemorrhage. Early intervention is believed to reduce the risk of rebleeding. However, in developing countries such as India, early intervention is often difficult due to various reasons. The knowledge about the risks and predictors for rebleeding is essential to prioritize the management policy. Aims: To describe the frequency and impact of rebleeding in the modern era of aneurysm care, to study the clinical profile of patients with rebleed and to review the controversial aspects on aneurysmal rebleed. Materials and Methods: This observational study is based on the retrospective analysis of the case records of all patients admitted with aneurysmal subarachnoid hemorrhage (SAH) since January 1999 in our institute. Twenty patients rebled after admission before surgical clipping, and these patients formed our study group. The findings were compared with all the major series on rebleeding published in literature. Results: Since January 1999, 952 patients underwent treatment for aneurysmal subarachnoid hemorrhage in our institute. Twenty patients rebled while awaiting surgery following the admission with an incidence of 2.14%. The study group included nine males and eleven females. The age of the patients ranged from 31 to 69 years, but the majority were in the sixth decade. Mean bleed to admission days was 7.9 days (range: 1-27 days), the mean admission to rebleed was 1.42 days (Range: 0-4) and the mean first bleed to rebleed was 9.26 days. The history of loss of consciousness at the time of bleeding was observed in 16 patients. Four patients bled before an angiogram could be performed. Two patients had giant aneurysms, while the rest had small aneurysms; two patients had multiple aneurysms. Angiographic spasm was observed in eight patients. In three patients, rebleeding was precipitated by angiogram. Twelve patients rebled while taking rest or in sleep, while one person rebled while defecating. Nine patients were taken up for emergency exploration immediately after rebleeding. From these, six patients died and three survived, but were severely disabled. The remaining eleven patients who were conservatively treated expired after varying periods of intensive care. Conclusions: Our incidence of rebleeding (2.14%) is considerably less than most of the other reported series, probably related to the delayed referral pattern. Probable predisposing factors for rebleed include old age, female sex and an anterior communicating artery location. Known risk factors such as hypertension, poor neurological grade on admission, stressful activity and aneurysm morphology do not appear to be significant in our study. Outcome is extremely poor following the rebleeds, either in immediate surgery or conservative treatment.


Keywords: Aneurysms, rebleeding, subarachnoid hemorrhage


How to cite this article:
Menon GR, Nair S, Rao RM, Abraham M, Easwer H V, Krishnakumar K. Patterns and predictors of in-hospital aneurysmal rebleed: An institutional experience and review of literature. Ann Indian Acad Neurol 2007;10:247-51

How to cite this URL:
Menon GR, Nair S, Rao RM, Abraham M, Easwer H V, Krishnakumar K. Patterns and predictors of in-hospital aneurysmal rebleed: An institutional experience and review of literature. Ann Indian Acad Neurol [serial online] 2007 [cited 2020 Sep 24];10:247-51. Available from: http://www.annalsofian.org/text.asp?2007/10/4/247/37817



   Introduction Top


The genesis of intracranial arterial aneurysms is a matter of debate. Similarly, little is known about the factors that predispose an aneurysm to bleed and the factors that precipitate rebleed in an already bled aneurysm. Rebleeding carries a high risk of poor outcome and early intervention is the rule in developed countries. In developing countries such as India, organizational constraints prohibit the adoption of an aggressive "early intervention" policy. During the last 8 years, 20 patients admitted with aneurysmal subarachnoid hemorrhage (SAH) rebled in our institute while awaiting surgery. This study focuses on the clinical profile of these patients, and an attempt is made to review the controversial aspects on aneurysmal rebleeding.


   Materials and Methods Top


Retrospective analysis of the case records of all patients admitted with aneurysmal subarachnoid hemorrhage (SAH) since January 1999 in our institute. Twenty patients rebled after admission before surgical clipping and these patients formed our study group. Rebleeding was defined as a sudden decrease in consciousness or a sudden increase in headache and an increased amount of blood on computerized tomography (CT scan) compared with previous scans. Clinical grading was done based on the WFNS grading system. Fischer's grading scores were used for CT scan grading of subarachnoid hemorrhage. Outcome was assessed based on the Glasgow outcome score. The findings were compared with all major series on rebleeding published in literature. The influence of following known predisposing factors for rebleed were analysed : age, gender, hypertension, time since first bleed, grade on admission, activity prior to bleed and the aneurysm location and morphology.


   Results Top


Since January 1999, 952 patients underwent treatment for aneurysmal SAH in our institute. Twenty patients rebled while awaiting surgery following admission with an incidence of 2.14%. The study group included nine males and eleven females. The age of the patients ranged from 31 to 69 years; however, the majority were in the sixth decade [Table - 1]. Being a tertiary referral center, admission to our center often gets delayed and the mean bleed to admission days was 7.9 days (range: 1-27 days). One patient had bled twice before admission. The mean period from the first bleed to admission was 7.9 days (Range 1- 27 days). The average period from admission to rebleed was 1.42 days (Range: 0-4) and the average number of days from the first bleed to rebleed was 9.26 days. Majority of the patients rebled in the first week after the initial bleed [Table - 2]. The history of loss of consciousness at the time of bleed was observed in 16 patients. The admission grades of the patients are shown in [Table - 3]. Hydrocephalus was observed in 6 patients. Four patients bled before digital subtraction angiography (DSA) could be performed. DSA could be performed in 15 patients, and one patient underwent CT angiogram. From the 15 angiograms available, two patients had giant aneurysms, while the rest had small aneurysms; two patients had multiple aneurysms. Angiographic spasm was observed in eight patients. The location of the aneurysms is shown in [Table - 4]. In three patients, rebleeding was precipitated by angiogram. Twelve patients were resting in bed at the time of rebleeding, and in four patients, rebleeding occurred in sleep. One person rebled while defecating. Only eight patients gave prior history of hypertension; however, a high blood pressure was recorded in almost all the patients following admission. Nine patients were subjected to emergency surgery immediately after rebleed. Six of these patients died and three survived, but were severely disabled. The remaining eleven patients were conservatively managed following the rebleed. All the patients who were conservatively treated expired after varying periods of intensive care (mean period from bleeding to death: 7.02 days, range: 1-21 days).


   Discussion Top


Along with vasospasm, rebleeding constitutes the two major catastrophic complications of aneurysmal SAH. Opinions differ on the exact incidence of rebleeding. Locksley's [1] report on the Cooperative Aneurysm Study - one of the landmark publications on the natural history and clinical course of aneurysms - states that for aneurysms of the anterior circulation, the incidence of rebleeding is 10% in the first week; 12% in the second week, 6.9% in the third week and 8.2% in the fourth week. Thereafter, the rate falls sharply to 1.8% per week for the period of 5-12 weeks after the initial bleed. The preliminary report of Kassell et al. [2] from the Cooperative Aneurysm Study (1983) report a cumulative 2-week rebleed rate (excluding the first day) of 19%. Carl J Graf's [3] analysis of the cooperative study of intracranial aneurysms and SAH (1971) reports an interesting observation on the day-to-day risk of death from a second hemorrhage. On the first day, it is around 10%, on the second day, it is 5% and by the end of the first week, 27% of the conservatively treated patients died. The mortality progressively dropped from 15% in the 8-14 day interval to 7% in the 22-28 day interval. There was an unexplained rise to 16% in the second month. The risk then dropped off sharply to 2% for the third to twelfth month. The analysis by Steiger et al. [4] (1994) gave a cumulative rebleed rate of 23% by day 14 and of 42% by day 28 after the primary SAH. In a later report on ultra early bleeding refers to bleeding within 6 hrs in spontaneous SAH published by Fuji et al . [5] (1996) quoted that in spite of scheduling of very early surgery, incidence of ultra-early bleeding is quite high (17.3%) and carries a very high mortality of around 64.5%. In spite of adopting a more aggressive policy in the management of SAH, Naidech et al . [6] recently found that rebleeding still occurs in nearly 1 out of every 15 patients. In general, an incidence of 15-25% is accepted within the first 2 weeks, and it is generally agreed that 50% of patients rebleed within 6 months of the first bleed. Six months after SAH, the rebleeding rates decreased to 3% per year, which persists for at least the first decade. [7] In sharp contrast to reported literature, our incidence of rebleeding is rather low (2.14%). One probable explanation could be due to the delayed referral and patients getting admitted after the peak risk of rebleeding. Being a tertiary referral center in a developing country, we seldom get patients within the first 24 h following the bleeding. (mean: 7.2 days). We presume that this low incidence does not reflect the true statistics as most of the rebleeding might be occurring in the primary health centers or might be going unnoticed.

Disagreement exists on the period of greatest risk for rebleeding. Locksley [1] and Graf [3] reported that the peak incidence of rebleeding occurred at the end of the first week after the initial ictus. The risk of rebleeding is greatest from the seventh to tenth day, falling off gradually between the fourteenth and twenty-first day and then dropping sharply at 28 days. Our observation is similar with the mean period for rebleed in our series being 9.2 days after the first bleed. However, Kassel [2] et al. did not observe a late peak of rebleeding at the end of first week and the beginning of the second week after the ictus. They report that the maximal rebleeding rate (4%) occurred on the same day as that of initial hemorrhage and that the rate thereafter decreased rapidly to a relatively constant level (1.5%). Steiger [4] provides a 2% rebleed rate on the day of the original hemorrhage, a very low re-rupture rate on days 1 to 3 followed by a period of higher risk until the end of the second week and a further peak during the fourth week. Their pattern is almost identical with the one observed by Hijdra and coworkers, [8] who observed a 2% rebleed rate on the day of original SAH. They attribute this high incidence on day 0 to the additional stress associated with transportation to a specialized center, shifting the patient for imaging studies and use of other maneuvers such as ventriculostomy in some cases. Consistent bed rest, control of hypertension and elimination of external stress is probably responsible for the low rebleed rate during days 1 to 3. On the other hand, the termination of these preventive measures approximately 3 weeks after SAH may be responsible for a rebound effect that can explain the late peak of rebleeds. The withdrawal of Nimodipine could also contribute to the late peak during the fourth week. With regard to the long-term risks of rebleed, the findings of the Cooperative study [1],[2],[3] suggest that if a patient survives 3 weeks after aneurysmal SAH, the chances of surviving for 6 weeks is 83% and if he survives 6 weeks, the chance for surviving for one year is 82%. Recurrent hemorrhage from an aneurysm is rare after one year and particularly after two years. However, Nishioka [9] states that although repeated bleeding continues to be a significant risk to the patients, primarily during the first decade after aneurysmal rupture after 10 years, patients are more likely to succumb to diseases that are not related to aneurysm or SAH. Our observations are similar and we did not have any patient presenting with a rebleed after 30 days of the initial bleed.

Considerable disagreement exists in literature regarding the effect of age and sex on the risk of re-rupture. In Steiger's [4] series, patients suffering from rebleeding were significantly older and female preponderance was more pronounced - as observed by Dumont [7] and in the Cooperative study. [1],[2],[3] However, Naidech [6] recently studied the univariate analysis of predictors and suggested that sex and age were not associated with rebleeding. In our study group, females and the elderly outnumbered the rest. However, a statistical correlation was difficult to establish as the numbers were small. In general, aneurysms are more common among females, and this could explain the higher risk of rebleeding among females. Similarly, surgery is more likely to be deferred or postponed in the elderly, resulting in a higher incidence of rebleeding.

The size of aneurysm has been directly linked with the risk of rebleeding. The larger the aneurysm, the greater is the risk of rebleeding - this association is a topic of debate. In 2006, Pleizier et al. [10] found that patients with larger aneurysms have a higher risk of rebleeding, particularly within the first three days after initial hemorrhage. This higher risk was not influenced by the age of the patient. Several other authors also reported a similar observation [4],[6],[11] and found that rebleeding aneurysms were found to be somewhat larger than aneurysms without re-rupture. However, they denied any causal relationship stating that the aforementioned differences were primarily a consequence of a management bias as the operation was more often postponed in patients with large aneurysms than those with small aneurysms, thereby leaving these groups of patients exposed to a longer period of risk. The International study of unruptured intracranial aneurysms (ISUIA) study on incidental aneurysms too confirmed the relationship of the size of the unruptured aneurysm to the risk of rebleeding. In our series, we had had only two giant aneurysms, the rest being small aneurysms. This probably could reflect a selection bias as the overall proportion of giant aneurysms treated in our institute is significantly less as compared to small aneurysms.

Although subsequent studies have failed to reinforce it, initial analysis of the Cooperative study on aneurysms conducted by Graf [3] suggest that the risk of rebleeding is highest for anterior communicating artery aneurysms followed by those of the ICA and least for those of the middle cerebral artery aneurysms. Aoyagi reported a higher incidence of re-rupture in complex aneurysms, a factor that was not reported by other authors. Some of the recent studies have failed to establish a link between the risk of rebleeding and the aneurysm location or morphology. [6] Our series shows a definite preference for anterior circulation aneurysms, particulary anterior communicating artery aneurysms.

Patients with a history of systemic hypertension and patients who are found to have persistently high BP recordings after the first bleed are thought to have a higher risk of rebleeding. [5],[6],[7] In a recent review, Juvela [11] stated that increased systolic BP values and long-term definite hypertension (BP 160/95 mm Hg or use of antihypertensive medication), but not borderline hypertension (Hg BP 140/190 mm Hg), before aneurysm rupture seem to predict fatal SAH and risk of rebleeding; this prediction is independent of the aneurysm size or patient age or sex at the time of aneurysm rupture. On the basis of this study, which also includes SAH patients who died soon after the bleeding as a result of the primary bleed or ultra-early rebleeding, systolic BP values and definite hypertension were considered to be significant independent predictors for fatal SAH. Aneurysm size and patient age and alcohol consumption also seem to be important risk factors, but had less predictive effect on the severity of bleeding than the BP values. A part of the deleterious effect of age and alcohol consumption on the outcomes may be due to hypertension because the BP values are directly correlated with age and alcohol use. Heavy alcohol consumption may also impair the outcomes through increased severity of the episodes of rebleeding and symptomatic vasospasm. Similarly, the investigations of the Cooperative Study on antihypertensive therapy presented a clear reduction in the rate of rebleeds in patients who received antihypertensive drugs. This finding is in contrast to the observations made by Steiger [4] and us - although patients suffering re-ruptures had somewhat higher systolic arterial pressures at the time of admission and on an average during the period at risk, no relation between the baseline or average systolic pressure and the daily risk of re-rupture could be identified. The higher arterial pressure in patients suffering a rebleed may be a consequence of the worse neurological condition in these patients. The lack of importance of arterial pressure found in our study does not prove that control of this parameter is not relevant. However, antihypertensive therapy is known to protect against rebleeding and some authors believe that Nimodipine, an antivasospasm agent, also helps to decrease the risk of rebleeding through its blood-pressure-lowering action.

It is generally believed that the occurrence of coma after the initial hemorrhage is significantly related to the rate of re-rupture. The Cooperative Study [1],[2],[3] and some other investigations performed under a policy of delayed surgery report age, female sex and bad neurological condition as the risk factors for early re-rupture. Nadiechs [6] concluded by univariate analysis that the baseline predictors of rebleeding included sentinel bleeding, seizure or loss of consciousness at ictus, higher National Institutes of Health Stroke Scale score, higher Hunt-Hess grade, lower GCS score, higher APACHE II physiologic subscores, larger aneurysm size and presence of intraventricular or intracerebral hemorrhage. In the same series, predictors of rebleeding in a multiple logistic regression model of factors present on admission included only Hunt-Hess grade (odds ratio [OR], 1.92 per grade; 95% confidence interval [CI], 1.33-2.75; P = 0.001) and larger aneurysm size (OR, 1.07/mm; 95% CI, 1.02-1.13; P = 0.005) without interaction. Some authors [4] believe that it is more likely for rebleeding to be associated with the severity of the initial hemorrhage than the clinical grade of the patient. In sharp contrast to other reported series, we found that most of the patients who rebled were in good grades (WFNS grade 1 and 2). This again could be a selection bias as we restricted the admission to patients with good grade. The severity of bleed on CT scan (Fischer's grading) also did not appear to influence the risk of rebleeding as most of the rebleeds occurred in patients with minimal blood on CT scan.

Although it is generally believed that any stressful activity could precipitate a rebleed ironically, majority of our patients bled while taking rest or during sleep. Similarly, diagnostic angiograms proved to be catastrophic in three patients, probably due to the stress involved during the angiogram or during transportation. A similar observation was noted by Fuji et al. , [5] who reported that performing a diagnostic angiogram within 6 h has a two-fold increase in the risk of rebleeding and is an independent risk factor for early rebleeding.

In their analysis on ultra-early bleeding in spontaneous SAH, Fuji et al . [5] suggested that the time elapsed from the last attack until admission is an important independent risk factor for ultra-early rebleeding after admission and the patients admitted within 6 h, particulary those who are admitted within 1 h, are at high risk of rebleeding after admission. Other predictors for ultra-early rebleeding include the history of rebleeding/sentinel bleed before admission and patients who had platelet hypoaggregability and those with a high level of thrombin-antithrombin complex. The continuous drainage of CSF in the acute phase after SAH, before aneurysm repair is generally thought to be associated with an increased risk of aneurysm rebleeding, suggesting that the zealous control of ICP with drainage might reduce the tamponade effect on a recently ruptured aneurysm and lead to rebleeding. Ruijs [12] claimed in their study that the drainage of CSF though a lumbar puncture is safer and preferable and did not observe any increased risk of rebleeding by external lumbar drainage in the acute phase after aneurysmal SAH. However, they warned that if the drainage of CSF is used before the aneurysm is occluded, it needs to be done carefully and excess drainage or drainage of large amounts of CSF should be avoided. Recent trials [11],[13],[14] have shown that the administering tranexaminic acid up to 72 h from time of rupture until the repair decreased rebleeding by 80%. However, the reduction in the rate of rebleeding before delayed surgery by the use of long-term antifibrinolytics can be offset by an increase in poor outcome secondary to cerebral ischemia. The general consensus seems to favor the routine use of antifibrinolytics, particularly in patients with poor grade and large aneurysms or patients who must be transferred to a tertiary care center. All the abovementioned parameters could not be analyzed in our series due to insufficient data because our protocol does not include CSF drainage or antifibrinolytics.

The ideal management protocol for patients who rebleed following hospitalization is doubtful. We prefer to be conservative on patients with severe bleed and patients with absent brain stem reflexes following the bleed. Other patients are offered surgery after obtaining a high-risk consent. We operated nine patients, while the rest were conservatively managed. Outcome was uniformly poor in both the groups. All the eleven patients who were managed conservatively expired. Out of the nine patients operated, six expired, but the three survivors were severely disabled. The rationale for aggressive management in patients who deteriorate following a rebleed is doubtful.


   Conclusion Top


Controversy shrouds the true incidence and timing of rebleed in cases with aneurysmal SAH. Probable predisposing factors include old age, female sex and the location of anterior communicating artery. Known risk factors such as hypertension, poor neurological grade on admission, stressful activity and aneurysm morphology are not the significant predisposing factors in our study. The role of tranexaminic acid in preventing rebleeds requires further study. Outcome was extremely poor following the rebleed in patients undergoing immediate surgery or those who were conservatively managed.

 
   References Top

1.Locksley HB. Report on the Cooperative study of intracranial aneurysms and subarachnoid hemorrhage section V, Part II: Natural history of SAH, Intracranial aneurysms and arteriovenous malformations. J Neurosurg 1966;25:321-68.  Back to cited text no. 1  [PUBMED]  
2.Kassell FN, Torner CJ. Aneurysmal rebleeding: A preliminary report from the cooperative aneurysm study. Neurosurgery 1983;13:479-81.  Back to cited text no. 2    
3.Graf CJ. Prognosis for patients with non surgically treated aneurysms-analysis of the cooperative study of intracranial aneurysms and subarachnoid hemorrhage. J Neurosurg 1971;35:438-43.  Back to cited text no. 3  [PUBMED]  
4.Steiger HJ, Fritschi J, Seiler RW. Current pattern of in-hospital aneurysmal rebleeds Analysis of a series treated with individually timed surgery and intravenous Nimodipine. Acta Neurochir (Wien) 1994;127:21-6.  Back to cited text no. 4  [PUBMED]  
5.Fuji Y, Takeuchi S, Sasaki O, Minakawa T, Koike T, Tanaka R. Ultra-early bleeding in spontaneous subarachnoid hemorrhage. J Neurosurg 1996;84:35-42.  Back to cited text no. 5    
6.Naidech AM, Janjua N, Kreiter KT, Ostapkovich ND, Brian-Fred Fitzsimmons, Parra A, et al. Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage. Arch Neurol 2005;62:410-6.  Back to cited text no. 6    
7.Dumont AS, Lanzino G. Kassel NF. The ruptured aneurysms -timing of occlusion. In: Peter D Le Roux, et al., editors. Management of cerebral aneurysm Saunders, Elsevier: Philadelphia; 2004. p. 335-46.  Back to cited text no. 7    
8.Hijdra A, Vermeulen M, van Gijn J, van Crevel H. Re-rupture of intracranial aneurysms: A clinicoanatomic study. J Neurosurg 1987;67:29-33.  Back to cited text no. 8  [PUBMED]  
9.Nishioka H, Torner JC, Graf CJ, Kassell NF, Sahs AL, Goettler LC. Cooperative study of intracranial aneurysms and subarachnoid hemorrhage: A long term prognostic study. Arch Neurol 1984;41:1142-6.  Back to cited text no. 9  [PUBMED]  
10.Machiel Pleizier C, Algra A, Velthuis BK, Rinkel GJ. Relation between size of aneurysm and risk of rebleeding in patients with subarachnoid hemorrhage. Acta Neurochir (Wien) 2006;148:1277-80.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Juvela S. Prehemorrhage risk factors for fatal intracranial aneurysm rupture. Stroke 2003;34:1852-7.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Ruijs AC, Dirven CM, Algra A, Beijer I, Vandertop WP, Rinkel G. The risk of rebleeding after external lumbar drainage in patients with untreated ruptured cerebral aneurysms. Acta Neurochir (Wien) 2005;147:1157-62.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Rosenorn J, Eskesen V, Schmidt K, Ronde F. The risk of rebleeding from ruptured intracranial aneurysms. J Neurosurg 1987;67:329-32.  Back to cited text no. 13    
14.Feigin VL, Findlay M. Advances in subarachnoid hemorrhage. Stroke 2006;37:305-8.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]



 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3], [Table - 4]


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