TY - JOUR
T1 - Spreading depolarization-modulating drugs and delayed cerebral ischemia after subarachnoid hemorrhage
T2 - A hypothesis-generating retrospective clinical study
AU - Hamming, Arend M.
AU - Mulder, Inge A.
AU - Gathier, Celine S.
AU - van den Bergh, Walter M.
AU - Dankbaar, Jan Willem
AU - Hoff, Reinier G.
AU - Vandertop, W. Peter
AU - Verbaan, Dagmar
AU - Ferrari, Michel D.
AU - Rinkel, Gabriel J. E.
AU - Algra, Ale
AU - Wermer, Marieke J. H.
PY - 2016/7/15
Y1 - 2016/7/15
N2 - Background: Delayed cerebral ischemia (DCI) occurs in approximately one-third of patients with aneurysmal subarachnoid hemorrhage (aSAH). A proposed underlying mechanism for DCI is spreading depolarization (SD). Our aim was to, retrospectively, investigate the influence of the use of SD-modulating drugs on the occurrence of DCI.Methods: We, retrospectively, combined data from four cohorts of aSAH patients with data on the use of home medication prior to hospital admission, occurrence of DCI, and clinical outcome. Home medication was classified as "SD-inhibiting", "SD-facilitating", or "SD-neutral based" on a comprehensive literature review. We defined subgroups "likely", "possibly" and "weak" concerning the amount of evidence in literature. We performed Cox and Poisson regression analysis and calculated hazard ratios (HR) and risk ratios (RR) for the influence of "SD-modulating" drugs on primary outcome measure DCI and secondary outcome measure poor clinical outcome (modified Rankin Scale >= 3) three months after aSAH. We adjusted for age, sex and clinical condition on admission (aHR/aRR).Results: DCI occurred in 343 (29%) of 1194 patients. Patients using SD-inhibiting home medication had an aHR for DCI of 0.66 (95% CI: 0.42-1.06) and an aRR for poor outcome of 1.13 (95% CI: 0.90-1.41). Patients using SD- facilitating drugs had an aHR for DCI of 1.24 (95% CI: 0.83-1.87) and an aRR for poor outcome of 1.19 (95% CI: 0.95-1.50). When comparing patients using SD-inhibiting drugs with patients using SD-facilitating drugs, the aHR was 0.54 (95% CI: 029-0.99) for DCI and the aRR 0.97 (95% CI: 0.71-1.32) for outcome.Conclusions: In this exploratory study chronic use of SD-inhibiting drugs tended to reduce DCI but did not result in a better clinical outcome. Additional research is needed to investigate the specific effects of SD-modulation on DCI and outcome and to further explore its effectiveness in preventing DCI after aSAH. (C) 2016 Elsevier B.V. All rights reserved.
AB - Background: Delayed cerebral ischemia (DCI) occurs in approximately one-third of patients with aneurysmal subarachnoid hemorrhage (aSAH). A proposed underlying mechanism for DCI is spreading depolarization (SD). Our aim was to, retrospectively, investigate the influence of the use of SD-modulating drugs on the occurrence of DCI.Methods: We, retrospectively, combined data from four cohorts of aSAH patients with data on the use of home medication prior to hospital admission, occurrence of DCI, and clinical outcome. Home medication was classified as "SD-inhibiting", "SD-facilitating", or "SD-neutral based" on a comprehensive literature review. We defined subgroups "likely", "possibly" and "weak" concerning the amount of evidence in literature. We performed Cox and Poisson regression analysis and calculated hazard ratios (HR) and risk ratios (RR) for the influence of "SD-modulating" drugs on primary outcome measure DCI and secondary outcome measure poor clinical outcome (modified Rankin Scale >= 3) three months after aSAH. We adjusted for age, sex and clinical condition on admission (aHR/aRR).Results: DCI occurred in 343 (29%) of 1194 patients. Patients using SD-inhibiting home medication had an aHR for DCI of 0.66 (95% CI: 0.42-1.06) and an aRR for poor outcome of 1.13 (95% CI: 0.90-1.41). Patients using SD- facilitating drugs had an aHR for DCI of 1.24 (95% CI: 0.83-1.87) and an aRR for poor outcome of 1.19 (95% CI: 0.95-1.50). When comparing patients using SD-inhibiting drugs with patients using SD-facilitating drugs, the aHR was 0.54 (95% CI: 029-0.99) for DCI and the aRR 0.97 (95% CI: 0.71-1.32) for outcome.Conclusions: In this exploratory study chronic use of SD-inhibiting drugs tended to reduce DCI but did not result in a better clinical outcome. Additional research is needed to investigate the specific effects of SD-modulation on DCI and outcome and to further explore its effectiveness in preventing DCI after aSAH. (C) 2016 Elsevier B.V. All rights reserved.
KW - Subarachnoid hemorrhage
KW - Spreading depolarizations
KW - Cortical spreading depression
KW - Secondary ischemia
KW - Delayed cerebral ischemia
KW - Drugs
KW - MIGRAINE PROPHYLAXIS
KW - CONTROLLED-TRIAL
KW - DEPRESSION
KW - VASOSPASM
KW - MAGNESIUM
KW - PERFUSION
KW - THERAPY
KW - STROKE
U2 - 10.1016/j.jns.2016.04.056
DO - 10.1016/j.jns.2016.04.056
M3 - Article
SN - 0022-510X
VL - 366
SP - 224
EP - 228
JO - JOURNAL OF THE NEUROLOGICAL SCIENCES
JF - JOURNAL OF THE NEUROLOGICAL SCIENCES
ER -