Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA, USA.
Department of Neurological Surgery, Columbia University Medical Center, 710 W. 168th St., New York, NY, 10032, USA.
Neurocrit Care. 2021 Apr;34(2):566-580. doi: 10.1007/s12028-020-01022-1.
Preclinical and clinical studies have suggested a potential benefit from COX-2 inhibition on secondary injury activation after spontaneous intracerebral hemorrhage (ICH). The aim of this study was to investigate the effect of pre-admission NSAID use on functional recovery in spontaneous ICH patients.
Consecutive adult ICH patients enrolled in the Intracerebral Hemorrhage Outcomes Project (2009-2018) with available 90-day follow-up data were included. Patients were categorized as NSAID (daily COX inhibitor use ≤ 7 days prior to ICH) and non-NSAID users (no daily COX inhibitor use ≤ 7 days prior to ICH). Primary outcome was the ordinal 90-day modified Rankin Scale (mRS) score. Outcomes were compared between cohorts using multivariable regression and propensity score-matched analyses. A secondary analysis excluding aspirin users was performed.
The NSAID and non-NSAID cohorts comprised 228 and 361 patients, respectively. After 1:1 matching, the matched cohorts each comprised 140 patients. The 90-day mRS were comparable between the NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.914 [0.626-1.336], p = 0.644) and matched (aOR = 0.650 [0.392-1.080], p = 0.097) analyses. The likelihood of recurrent ICH at 90 days was also comparable between the NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.845 [0.359-1.992], p = 0.701) and matched analyses (aOR = 0.732 [0.241-2.220], p = 0.581). In the secondary analysis, the non-aspirin NSAID and non-NSAID cohorts comprised 38 and 361 patients, respectively. After 1:1 matching, the matched cohorts each comprised 38 patients. The 90-day mRS were comparable between the non-aspirin NSAID and non-NSAID cohorts in both the unmatched (aOR = 0.615 [0.343-1.101], p = 0.102) and matched (aOR = 0.525 [0.219-1.254], p = 0.147) analyses. The likelihood of recurrent ICH at 90 days was also comparable between the non-aspirin NSAID and non-NSAID cohorts in both the unmatched (aOR = 2.644 [0.258-27.091], p = 0.413) and matched (aOR = 2.586 [0.228-29.309], p = 0.443) analyses. After the exclusion of patients with DNR or withdrawal of care status, NSAID use was associated with lower mRS at 90 days (aOR = 0.379 [0.212-0.679], p = 0.001), lower mRS at hospital discharge (aOR = 0.505 [0.278-0.919], p = 0.025) and lower 90-day mortality rates (aOR = 0.309 [0.108-0.877], p = 0.027).
History of nonselective COX inhibition may affect functional outcomes in ICH patients. Pre-admission NSAID use did not appear to worsen the severity of presenting ICH or increase the risk of recurrent ICH. Additional clinical studies may be warranted to investigate the effects of pre-admission NSAID use on ICH outcomes.
临床前和临床研究表明,COX-2 抑制剂对自发性脑出血(ICH)后继发性损伤激活可能有益。本研究旨在探讨入院前使用 NSAID 对自发性 ICH 患者功能恢复的影响。
连续纳入参加颅内出血结局项目(2009-2018 年)且有 90 天随访数据的成年 ICH 患者。患者分为 NSAID 组(ICH 前 7 天内每日使用 COX 抑制剂≤7 天)和非 NSAID 组(ICH 前 7 天内无每日 COX 抑制剂使用)。主要结局为 90 天改良 Rankin 量表(mRS)评分。使用多变量回归和倾向评分匹配分析比较队列之间的结果。进行了排除阿司匹林使用者的二次分析。
NSAID 组和非 NSAID 组分别包含 228 例和 361 例患者。经过 1:1 匹配后,每个匹配组各包含 140 例患者。在未匹配(aOR=0.914 [0.626-1.336],p=0.644)和匹配(aOR=0.650 [0.392-1.080],p=0.097)分析中,90 天 mRS 在 NSAID 组和非 NSAID 组之间无差异。在未匹配(aOR=0.845 [0.359-1.992],p=0.701)和匹配(aOR=0.732 [0.241-2.220],p=0.581)分析中,90 天复发性 ICH 的可能性在 NSAID 组和非 NSAID 组之间也无差异。在二次分析中,非阿司匹林 NSAID 组和非 NSAID 组分别包含 38 例和 361 例患者。经过 1:1 匹配后,每个匹配组各包含 38 例患者。在未匹配(aOR=0.615 [0.343-1.101],p=0.102)和匹配(aOR=0.525 [0.219-1.254],p=0.147)分析中,90 天 mRS 在非阿司匹林 NSAID 组和非 NSAID 组之间无差异。在未匹配(aOR=2.644 [0.258-27.091],p=0.413)和匹配(aOR=2.586 [0.228-29.309],p=0.443)分析中,90 天复发性 ICH 的可能性在非阿司匹林 NSAID 组和非 NSAID 组之间也无差异。在排除有 DNR 或放弃治疗状态的患者后,NSAID 使用率与 90 天 mRS 评分较低(aOR=0.379 [0.212-0.679],p=0.001)、出院时 mRS 评分较低(aOR=0.505 [0.278-0.919],p=0.025)和 90 天死亡率较低(aOR=0.309 [0.108-0.877],p=0.027)相关。
非选择性 COX 抑制史可能影响 ICH 患者的功能结局。入院前 NSAID 使用似乎不会加重 ICH 的严重程度或增加复发性 ICH 的风险。可能需要进一步的临床研究来探讨入院前 NSAID 使用对 ICH 结局的影响。