Subarachnoid hemorrhage (SAH) remains an important cause of mortality and long-term morbidity. This article uses a case-based approach to guide readers through the fundamental epidemiology and pathogenesis of SAH, the approach to diagnosis and management, the results of clinical trials and evidence to date, prognostic considerations, controversies, recent developments, and future directions in SAH.
Historically, management of SAH focused on prevention and treatment of subsequent cerebral vasospasm, which was thought to be the primary cause of delayed cerebral ischemia. Clinical and translational studies over the past decade, including several therapeutic phase 3 randomized clinical trials, suggest that the pathophysiology of SAH-associated brain injury is multiphasic and multifactorial beyond large vessel cerebral vasospasm. The quest to reduce SAH-associated brain injury and improve outcomes is shifting away from large vessel cerebral vasospasm to a new paradigm targeting multiple brain injury mechanisms, including early brain injury, delayed cerebral ischemia, microcirculatory dysfunction, spreading cortical depolarization, inflammation, and the brain-body interaction in vascular brain injury with critical illness.
Despite multiple negative randomized clinical trials in search of potential therapeutic agents ameliorating the downstream effects after SAH, the overall outcome of SAH has improved over recent decades, likely related to improvements in interventional options for ruptured cerebral aneurysms and in critical care management. Emerging clinical evidence also suggests potential harmful impact of historic empiric treatments for SAH-associated vasospasm, such as prophylactic induction of hypertension, hypervolemia, and hemodilution (triple H therapy).
With decreasing mortality, long-term SAH survivorship and efforts to reduce chronic morbidity and to improve quality of life and patient-centered outcome are growing areas of unmet need. Despite existing guidelines, significant variabilities in local and regional practices and in scientific terminologies have historically limited advancement in SAH care and therapeutic development. Large global collaborative efforts developed harmonized SAH common data elements in 2019, and studies are under way to examine how existing variabilities in SAH care impact long-term SAH outcomes.
Although the overall incidence and mortality of SAH is decreasing with advances in preventive and acute care, SAH remains a major cause of long-term morbidity in survivors. Significant variabilities in care settings and empiric treatment protocols and inconsistent scientific terminologies have limited advancement in patient care and therapeutic clinical studies. Large consensus efforts are under way to introduce clinical guidelines and common data elements to advance therapeutic approaches and improve patient outcome.