Laboratory biomarkers of delayed cerebral ischemia following subarachnoid hemorrhage: A systematic review

Abstract

Delayed cerebral ischemia (DCI) substantially contributes to disability and death in subarachnoid hemorrhage (SAH) patients; however, its pathophysiology is incompletely understood and diagnostic and therapeutic strategies are lacking. Biomarkers may help to elucidate the pathophysiology, optimize early diagnosis, or provide treatment targets. We systematically searched PubMed and Embase on October 13, 2021, for studies that evaluated at least one laboratory biomarker in patients with DCI, using the most up-to-date definition of DCI as proposed by a panel of experts in 2010. Quality of studies was assessed using the Newcastle-Ottawa Scale or Cochrane Collaboration’s risk of bias assessment tool. Biomarkers of clinical and radiological DCI were analyzed separately. Results were meta-analyzed if possible, otherwise narratively reviewed. Biomarkers were classified as significant, inconclusive, or nonsignificant. We defined validated biomarkers as those with significant results in meta-analyses, or in at least two studies using similar methodologies within the same time interval after SAH. The search yielded 209 articles with 724 different biomarkers; 166 studies evaluated 646 biomarkers of clinical DCI, of which 141 were significant and 7 were validated biomarkers (haptoglobulin 2-1 and 2-2, ADAMTS13, vWF, NLR, P-selectin, F2-isoprostane); 78 studies evaluated 165 biomarkers of radiological DCI, of which 63 were significant and 1 was a validated biomarker (LPR). Hence, this review provides a selection of seven biomarkers of clinical DCI and one biomarker of radiological DCI as most promising biomarkers of DCI. Future research should focus on determining the exact predictive, diagnostic, and therapeutic potentials of these biomarkers.

Sodium and Its Impact on Outcome After Aneurysmal Subarachnoid Hemorrhage in Patients With and Without Delayed Cerebral Ischemia

“…In previous reports, sodium and free water disorders were more often observed in patients with a ruptured ACOM aneurysm; however, we did not find differences between these patients ( 68 ). Comparison of different studies is virtually impossible due to heterogeneity in the definition of hyponatremia and sodium fluctuations, methodology, frequency/timing of sampling, without regards to the day of DCI onset and the timing of clinical outcome assessment ( 11 , 68 ). Similarly, there is significant variation in fluid management across hospitals ( 21 , 69 , 70 ).…”

“…To predict DCI, countless biomarkers related to the multifactorial pathophysiology of DCI have been investigated ( 10 , 11 ). Essentially, any event that decreases cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) could contribute to the development of DCI ( 12 – 14 ).…”