Evaluating Therapeutic Interventions For Cerebral Vasospasm
Evaluating Therapeutic Interventions For Cerebral Vasospasm
The authors tested the null hypothesis that published literature with a high level of evidence does not support the assertion that subarachnoid hemorrhage (SAH) causes cerebral vasospasm, which in turn causes cerebral infarction and poor outcome after aneurysmal SAH. The medical literature on SAH was searched in MEDLINE. The author's personal files of all published literature on SAH were reviewed. References cited in Cochrane reviews as well as the published papers that were reviewed were also retrieved.
There is no question that SAH causes what the authors have chosen to call "angiographic vasospasm." However, the incidence and severity of vasospasm in recent series of patients is not well defined. There is reasonable evidence that vasospasm causes infarction, but again, accurate data on how severe and how diffuse vasospasm has to be to cause infarction and how often vasospasm is the primary cause of infarction are not available. There are good data on the incidence of cerebral infarction after SAH, and these data indicate that it is highly associated with poor outcome. The link between angiographic vasospasm and poor outcome is particularly poorly described in terms of what would be considered data of a high level of evidence.
The question as to whether there is a clear pathway from SAH to vasospasm to cerebral infarction to poor outcome seems so obvious to neurosurgeons as to make it one not worth asking. Nevertheless, the obvious is not always true or accurate, so it is important to note that published literature only weakly supports the causative association of vasospasm with infarction and poor outcome after SAH. It behooves neurosurgeons to document this seemingly straightforward pathway with high-quality evidence acceptable to the proponents of evidence-based medicine.
Cerebral vasospasm is frequently cited as a leading cause of instances of morbidity and mortality after an eurysmal SAH. Its first description, which was based on angiographic findings, is attributed to Ecker and Riemenschneider in 1951. Although there was some skepticism expressed about the importance of the phenomenon early on, it has come to be accepted as a major contributor to poor outcome after SAH. The presumed path way leading to poor outcome is as follows: SAH causes cerebral vasospasm, which causes cerebral infarction, and cerebral infarction contributes to poor outcome (Fig. 1).
(Enlarge Image)
Figure 1.
The rigor with which information on clinical medicine is assessed is increasing. Students, regulatory agencies, and increasingly, patients and representatives in industry will not rely on evidence based on expert opinion and case series to decide the best diagnostic and treatment methods. In deed, these are now regarded as the least powerful forms of information on which to base medical decision making. Only in the legal profession does such information still trump vigorous science. When, for example, one tells officials at the Food and Drug Administration or a person in a drug company who is deciding whether to pursue a treatment for cerebral vasospasm that this condition causes cerebral infarction and poor outcome, so that preventing vasospasm would be beneficial, they will ask to see the data supporting this contention. They also want quantitative data on every aspect of this pathway. Several such encounters led us to search the world literature to find the evidence. The first purpose of this manuscript is therefore to de termine what evidence exists to support the pathway from SAH to vasospasm to cerebral infarction to poor outcome.
There are additional reasons for doing this. If such a path were strongly supported by data of a high level of evidence, then this would be a first step in developing the use of angiographic vasospasm and possibly cerebral infarction as surrogate markers for outcome in future clinical trials conducted to evaluate interventions for delayed cerebral vasospasm. Other criteria for surrogate end points are required, for instance, that they make sense pathophysiologically and that they respond to treatment in parallel with a patient-based, long-term outcome measure, but the first step is to establish the relationship outlined here.
Abstract and Introduction
Abstract
The authors tested the null hypothesis that published literature with a high level of evidence does not support the assertion that subarachnoid hemorrhage (SAH) causes cerebral vasospasm, which in turn causes cerebral infarction and poor outcome after aneurysmal SAH. The medical literature on SAH was searched in MEDLINE. The author's personal files of all published literature on SAH were reviewed. References cited in Cochrane reviews as well as the published papers that were reviewed were also retrieved.
There is no question that SAH causes what the authors have chosen to call "angiographic vasospasm." However, the incidence and severity of vasospasm in recent series of patients is not well defined. There is reasonable evidence that vasospasm causes infarction, but again, accurate data on how severe and how diffuse vasospasm has to be to cause infarction and how often vasospasm is the primary cause of infarction are not available. There are good data on the incidence of cerebral infarction after SAH, and these data indicate that it is highly associated with poor outcome. The link between angiographic vasospasm and poor outcome is particularly poorly described in terms of what would be considered data of a high level of evidence.
The question as to whether there is a clear pathway from SAH to vasospasm to cerebral infarction to poor outcome seems so obvious to neurosurgeons as to make it one not worth asking. Nevertheless, the obvious is not always true or accurate, so it is important to note that published literature only weakly supports the causative association of vasospasm with infarction and poor outcome after SAH. It behooves neurosurgeons to document this seemingly straightforward pathway with high-quality evidence acceptable to the proponents of evidence-based medicine.
Introduction
Cerebral vasospasm is frequently cited as a leading cause of instances of morbidity and mortality after an eurysmal SAH. Its first description, which was based on angiographic findings, is attributed to Ecker and Riemenschneider in 1951. Although there was some skepticism expressed about the importance of the phenomenon early on, it has come to be accepted as a major contributor to poor outcome after SAH. The presumed path way leading to poor outcome is as follows: SAH causes cerebral vasospasm, which causes cerebral infarction, and cerebral infarction contributes to poor outcome (Fig. 1).
(Enlarge Image)
Figure 1.
The rigor with which information on clinical medicine is assessed is increasing. Students, regulatory agencies, and increasingly, patients and representatives in industry will not rely on evidence based on expert opinion and case series to decide the best diagnostic and treatment methods. In deed, these are now regarded as the least powerful forms of information on which to base medical decision making. Only in the legal profession does such information still trump vigorous science. When, for example, one tells officials at the Food and Drug Administration or a person in a drug company who is deciding whether to pursue a treatment for cerebral vasospasm that this condition causes cerebral infarction and poor outcome, so that preventing vasospasm would be beneficial, they will ask to see the data supporting this contention. They also want quantitative data on every aspect of this pathway. Several such encounters led us to search the world literature to find the evidence. The first purpose of this manuscript is therefore to de termine what evidence exists to support the pathway from SAH to vasospasm to cerebral infarction to poor outcome.
There are additional reasons for doing this. If such a path were strongly supported by data of a high level of evidence, then this would be a first step in developing the use of angiographic vasospasm and possibly cerebral infarction as surrogate markers for outcome in future clinical trials conducted to evaluate interventions for delayed cerebral vasospasm. Other criteria for surrogate end points are required, for instance, that they make sense pathophysiologically and that they respond to treatment in parallel with a patient-based, long-term outcome measure, but the first step is to establish the relationship outlined here.
Source...