Economic and Humanistic Burden of Cerebral Vasospasm and Its Related Complications after Aneurysmal Subarachnoid Hemorrhage: A Systematic Literature Review

Plain Language Summary Aneurysmal subarachnoid hemorrhage is a sudden, life-threatening emergency caused by bleeding in the subarachnoid space between the brain and skull. Vasospasm of the arteries surrounding the hemorrhage occurs in most patients and may lead to permanent brain damage. This study summarizes the published literature to describe the burden that patients may experience due to vasospasm and its related complications after aneurysmal subarachnoid hemorrhage, focusing on financial and life quality aspects. We show that the burden of vasospasm, and its related complications, is huge. Patients often experience reduced quality of life due to their poor health and are more likely to suffer from depression and intellectual impairment. There is also a substantial financial burden linked to vasospasm and its related complications, driven by the need for more intensive care, hospitalization, and higher investigative costs associated with the treatment and management of these patients. In addition, days off work and unemployment can cause a substantial indirect financial burden. Our study highlights the need for additional research to understand further the "burden of illness" of vasospasm and its related complications after aneurysmal subarachnoid hemorrhage. Introduction Cerebral vasospasm (VSP) is the leading risk factor of neurological deterioration (i.e., delayed cerebral ischemia [DCI] and cerebral infarction) after aneurysmal subarachnoid hemorrhage (aSAH) and a cause of morbidity and mortality. The objective of this systematic literature review is to summarize the economic and humanistic burden of VSP and its related complications after aSAH. Methods A predefined protocol was designed, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Systematic searches were conducted in MEDLINE, Embase, and Cochrane (in January 2021) to identify studies reporting economic and/or humanistic (i.e., health-related quality of life [HRQoL]) outcomes for patients with asymptomatic and symptomatic VSP after aSAH. Related conferences and additional sources were searched manually. Dual screening, data extraction, and qualitative analysis were conducted. Results Of 3818 abstracts identified for review, 43 full-text articles representing 42 single studies met the inclusion criteria and were included. Most studies (33) were observational; nine were randomized clinical trials (RCTs). Economic outcomes were reported in 31 studies, and alongside HRQoL outcomes in 4 studies; 7 studies reported HRQoL outcomes only. Forty studies were conducted in single countries, while only 2 RCTs were conducted in multiple countries. Patients diagnosed with VSP or DCI spent between 2.1 and 7.4 days longer in intensive care and between 4.7 and 17 days longer in hospital (total) compared with patients without VSP or DCI. A significantly higher cost burden of US$33,945 (2021 26,712) pound was identified for patients with VSP and 9370 pound (2021 13,733) pound for patients with DCI compared with patients without. Patients with DCI were also disadvantaged by being employed for 62 fewer days (during 24-month follow-up), with an estimated mean cost of 3821 pound (2021 5600) pound for days off work. Poor HRQoL was associated with >= 1 days with VSP symptoms (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.4-5.3), symptomatic VSP (OR: 1.9, 95% CI: 1.0-3.6), and DCI (OR: 2.3, 95% CI: 1.3-4.2), although this was not consistent across all studies. Symptomatic VSP and DCI were identified as significant risk factors for depressed mood (OR: 2.2, 95% CI: 1.0-4.9) and global cognitive impairment (OR: 2.3) at 12 months, respectively. The severity of VSP was a critical predictor of post-aSAH economic and humanistic burden. Similar trends in economic and humanistic burden were identified in the general aSAH patient population. Study design and patient heterogeneity precluded direct metaanalysis of the results. Conclusion A substantial direct and indirect economic burden is linked to VSP and its related complications after aSAH. Although limited evidence was identified for humanistic burden, these patients seem to suffer from poor HRQoL with long-lasting burden. Overall, there is an urgent need to understand better the concept of "burden of illness" of VSP and its related complications after aSAH.