Elsevier

World Neurosurgery

Volume 77, Issues 5–6, May–June 2012, Pages 686-697
World Neurosurgery

Peer-Review Report
How Large Is the Typical Subarachnoid Hemorrhage? A Review of Current Neurosurgical Knowledge

https://doi.org/10.1016/j.wneu.2011.02.032Get rights and content

Background

Despite the morbidity and mortality of subarachnoid hemorrhage (SAH), the average volume of a typical hemorrhage is not well defined. Animal models of SAH often do not accurately mimic the human disease process.

Objective

The purpose of this study is to estimate the average SAH volume, allowing standardization of animal models of the disease.

Methods

We performed a MEDLINE search of SAH volume and erythrocyte counts in human cerebrospinal fluid as well as for volumes of blood used in animal injection models of SAH, from 1956 to 2010. We polled members of the American Association of Neurological Surgeons (AANS) for estimates of typical SAH volume. Using quantitative data from the literature, we calculated the total volume of SAH as equal to the volume of blood clotted in basal cisterns plus the volume of dispersed blood in cerebrospinal fluid. The results of the AANS poll confirmed our estimates.

Results

The human literature yielded 322 publications and animal literature, 237 studies. Four quantitative human studies reported blood clot volumes ranging from 0.2 to 170 mL, with a mean of ∼20 mL. There was only one quantitative study reporting cerebrospinal fluid red blood cell counts from serial lumbar puncture after SAH. Dispersed blood volume ranged from 2.9 to 45.9 mL, and we used the mean of 15 mL for our calculation. Therefore, total volume of SAH equals 35 mL. The AANS poll yielded 176 responses, ranging from 2 to 350 mL, with a mean of 33.9 ± 4.4 mL.

Conclusions

Based on our estimate of total SAH volume of 35 mL, animal injection models may now become standardized for more accurate portrayal of the human disease process.

Introduction

Subarachnoid hemorrhage (SAH) commonly occurs spontaneously, usually from a ruptured cerebral aneurysm, and subsequently precipitates widespread brain dysfunction. The estimated annual incidence of aneurysmal SAH in the Western world is 6–8 per 100,000 (19), accounting for 1%–7% of all strokes (65). Up to 50% of cases result in fatality and 10%–15% of patients die before reaching a hospital (275). For those that survive, preventing further morbidity revolves around minimizing the risk of rebleeding, as well as preventing delayed ischemic neurologic deficits secondary to cerebral vasospasm. Symptomatic cerebral ischemia peaks between 7 and 10 days post-SAH (123) and remains the most significant cause of death and disability following an SAH. Therefore, to devise sound treatment strategies for SAH, accurate and representative animal models are necessary.

The amount of hemorrhage is thought to be important for the mechanism by which bleeding stops and possibly restarts, as the initial flow rate of SAH has a positive linear correlation with the volume of hemorrhage volume, regardless of cerebral perfusion pressure (21, 168). The amount of hemorrhage in the subarachnoid space is also directly correlated with cerebral vasospasm (70). Animal models have corroborated this, demonstrating that oxyhemoglobin from extravasated erythrocytes, as well as other molecular mechanisms, can cause vasospasm (51).

The kinetics of SAH are complicated (Figure 1), with red blood cells not incorporated in the subarachnoid clot circulating throughout the cerebrospinal subarachnoid space, where they ultimately undergo lysis (94) and phagocytosis (111). Although intact erythrocytes have been shown to return from cerebrospinal fluid (CSF) to the circulation in animals (243), this is not the case in humans (268). Therefore, the total hemorrhage is composed of blood in the subarachnoid clot, plus erythrocytes dispersed in the CSF at any one time (Figure 2). Red blood cells in the CSF spread with CSF flow (114) and usually appear in the lumbar theca within hours of SAH. The red cell count peaks rapidly and fades more slowly, with the exact rates being quite variable (268).

There is a need for accurate representation of SAH in animal models, so that brain physiology, erythrocyte kinetics, and the development of vasospasm can be further studied. Unfortunately, quantifying the amount of SAH in humans is rarely addressed, with only a few comparisons in the animal literature, and virtually none in the human literature (21, 70). To delineate the current state of neurosurgical knowledge in terms of quantifying SAH, we performed a review of clinical and experimental literature and conducted a survey of AANS members.

Section snippets

Materials and Methods

Clinical and experimental studies on SAH volume and erythrocyte counts in human cerebrospinal fluid, published between 1956 and 2010, were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. We probed the current state of neurosurgical knowledge in terms of size of SAH by using a strategy that involved three independent lines of inquiry. First, we performed a structured literature search for information on subarachnoid clot volume

Results

The human literature search yielded 4817 English-language publications. After removing the abstracts that referred to diagnostic imaging (n = 3059), case reports (n = 786), and opinion articles (n = 650), we were left with 322 case series and reviews. The literature searches yielded almost no information on the total volume of an aneurysmal hemorrhage. Burnett et al. (21) mention that most hemorrhages total less than 150 mL, but cite no references. Most articles (7, 16, 38, 70, 75, 89, 106, 172

Discussion

Despite the morbidity and mortality associated with SAH from a ruptured aneurysm, very little is known about the exact volume of blood required to elicit neurologic symptoms or vasospasm. From the studies of Fisher et al. (70) and others, a larger quantity of SAH is strongly correlated with worsened clinical outcome. However, our ability to accurately measure the quantity of SAH through advanced imaging is limited by resolution. In addition, prediction of SAH volume from the RBC count in the

Conclusion

This is the first effort to combine multiple sources of data to estimate the average SAH volume of 35 mL. The amount of SAH is an important consideration for studying clinical outcome and evaluating the utility of animal models. It is possible that with advanced imaging techniques available today, a more accurate estimate of SAH may be obtained. However, SAH remains one of the deadliest diseases that neurosurgeons treat, and all efforts should be made to accurately study and treat this disorder.

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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.

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