Perioperative measures to improve outcome after subarachnoid hemorrhage-revisiting the concept of secondary brain injury.

ABSTRACT

Progress in the management of aneurysmal subarachnoid hemorrhage (SAH) is reflected most clearly in a continuously decreasing case fatality rate over the last decades. The purpose of the present review is to identify the relevant factors responsible for this progress and to outline future possibilities of improvement. Although data on intracerebral hemorrhage and ischemic stroke are less homogeneous, the respective data suggest that reduction of case fatalities could also be achieved with these types of stroke. Therefore, advances of general neurocritical care may be the common denominator responsible for the decreasing case fatality rates. Additionally, a change in practice with regard to treatment of elderly patients that is more active may also be a factor. Regarding SAH, the majority of unfavorable outcomes is still related to early or delayed cerebral injury. Therefore, efforts to pharmacologically prevent secondary neuronal damage are likely to play a certain role in achieving improvement in overall outcome. However, the data from previous randomized clinical trials conducted during the last three decades does not strongly support this. A clear benefit has only been proven for oral nimodipine, whereas other calcium antagonists and the rho-kinase inhibitors were not conclusively shown to have a significant effect on functional outcome, and all other tested substances disappointed in clinical trials. Regarding ischemic stroke and traumatic brain injury, intensive clinical research has also been conducted during the last 30 years to improve outcome and to minimize secondary neuronal injury. For ischemic stroke, treatment focusing on reversal of the primary pathomechanism, such as thrombolysis, proved effective, but none of the pharmacological neuroprotective concepts resulted in any benefit. To date, decompressive hemicraniectomy has been the only effective effort focused at reducing secondary damage that resulted in a clear reduction of mortality. In the case of traumatic brain injury, none of the pharmacological or other efforts to limit secondary damage met our hopes. In summary, although limited, pharmacotherapy to limit delayed neuronal injury is more effective for SAH than for ischemic stroke and traumatic brain injury. The disappointing results of most trials addressing secondary damage force one to question the general concept of mechanisms of secondary damage that do not also have a positive side in the natural course of the disease. For example, in the case of SAH, the data from the Cooperative Study from the 1960s showed that vasospasm to some degree protects against rerupture of unsecured aneurysms. Thus, one could argue from an evolutionary standpoint that the purpose of vasospasm was not exclusively a detrimental or suicide pathomechanism, but an attempt to protect against life-threating aneurysm rerupture. Because of the above-discussed arguments, SAH may indeed differ from ischemic stroke and traumatic brain injury with regard to the usefulness of blocking secondary mechanisms pharmacologically. Further efforts to limit vasospasm should therefore be made, and the most promising drugs, calcium antagonists, deserve further development. Because, with various drugs, systemic side effects counteracted the local beneficial effect, future efforts should focus on topical administration of drugs instead of systemic administration. Furthermore, efforts for a better understanding of the variations of the calcium channels and the interplay between the different types of calcium channels should be made.