Cerebral Vasospasm after Subarachnoid Hemorrhage: Holding on to Old Beliefs
Aneurysmal SAH affects approximately 30,000 patients a year in the United States, and while accounting for only 5% of strokes, accounts for a disproportionately large amount of the death and disability attributed to stroke. No small part of this is from cerebral vasospasm (cVS) and delayed cerebral ischemia (DCI). One of the first kernels of neurosurgical knowledge imparted to the new resident is the algorithm for initial management of the patient with subarachnoid hemorrhage. However, our basic understanding and approach to treating cVS/DCI has remained largely the same for the over 30 years. We continue to teach and implement treatment plans that have failed to hold up under scrutiny. We have failed to introduce new therapies which capitalize on an improved understanding of the pathophysiology of cVS/DCI. Old habits truly die hard.
Early Models of Vasospasm – As Primitive as a Flat Earth?
Classic approaches to prophylaxis and treatment are rooted in the idea that the pathophysiological process results from mechanical limitations of blood flow. This is visualized radiographically as luminal narrowing- whether it be large proximal vessels or smaller distal (3rd and 4th order) branches of the cerebral arteries. “Triple H Therapy” (hypertension, hypervolemia and hemodilution) and oral nimodipine have been mainstays of cVS prevention and treatment for years contrary to evidence that they have limited effect on outcome and in some cases detrimental effects on other organ systems. Rescue endovascular therapies such as balloon angioplasty and intra-arterial vasodilator theory are likewise based on the premise of DCI driven by angiographic vessel narrowing. A better understanding of cVS and the mechanisms of DCI are needed, and as such several novel therapies based on a broader pathophysiological understanding are currently undergoing study as will be described in Part II of this article.
Triple H Therapy has been a mainstay of cVS prophylaxis and treatment for decades, and despite no clear patient benefit and potentially harmful effects, remains in use today. Originally proposed in the early 1980s by Dr. Neil Kassell, it is based on the premise that cVS and DCI are all driven purely by fluid mechanical effects of radiographic spasm. The intent was to maintain cerebral perfusion with hypertension by increasing the pressure gradient across the spasmodic segment(s), counteract the diuresis seen after SAH by increasing the circulating volume, and reducing the resistance to laminar flow by hemodilution to the intersection of curves of the rheostatic properties and oxygen carrying capacity of human serum.
However, vasopressor induced hypertension is accompanied by several deleterious systemic side effects such as distal limb ischemia, renal damage and cardiac dysfunction. Similarly, hypervolemia is associated with pulmonary edema/adult respiratory distress syndrome, increased incidence of pneumonia, and cardiac failure. Finally, hemodilution has shown no positive effects on patient outcomes, and results in decreased cerebral oxygen delivery secondary to decreased serum hematocrits, thereby propagating the effects of DCI.
AHA Guidelines now recommend euvolemia and the use of hypertension only in the most extreme cases for refractory, angiographically documented vasospasm with neurological deficits.
An Ounce of Prevention…
The use of calcium-channel blockers to prevent vasospasm was likewise born of a primitive understanding of the mechanisms of cVS and DCI. Based on their use for prevention of cardiac ischemia, the original concept was to blunt the smooth muscle contractility of large resistance vessels in the cerebral vasculature. Despite the fact that use of prophylactic oral nimodipine has held up to scrutiny of a randomized double blind placebo controlled trial, nimodipine administration has never demonstrated a reduction in radiographic vasospasm, suggesting it effect has nothing to do with smooth muscle contractility.
Moving out of the Dark Ages
The lack of evidence surrounding “Triple H Therapy” and poor understanding of the true mechanism of calcium channel blockade in the setting of subarachnoid hemorrhage suggest that the pathophysiology of cVS and DCI are far more complex than we appreciate. Vasospasm probably occurs at several levels of the vascular tree including distal arteries, arterioles, and the microcirculation that are not visualized on conventional angiography. DCI appears to be driven by multiple mechanisms beyond just luminal narrowing. Research has focused on other potential mechanisms such as microvascular thrombosis, cortical spreading depression, dysfunctional autoregulation of the microcirculation, and induction of delayed neuronal cell death. Until we have a better understanding of these mechanisms, continued implementation of time-honored therapies such as Triple H are more likely to have a positive effect on the neurosurgeon than the patient. In Part II of this article, we will discuss novel therapeutic strategies that take advantage of more robust models of the pathophysiology of cVS and DCI.
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