JOURNAL WATCH Journal Watch By Susanne Muehlschlegel, MD, MPH and Chad Miller, MD Long-term outcome after warfarin-associated in patients fulfi lling all three criteria vs. 44.2%) and in-hospital ICH and timing, degree of INR reversal, mortality (all three criteria 13.5% vs. 20.7%). blood pressure and resumption of warfarin in a large German multi-center cohort OAC were resumed in 23.9% of patients, with the highest rate Kuramatsu JB, Gerner ST, Schellinger PD, et al. among patients with mechanical valves (68%) and rates in atrial JAMA 2015;313:824-836 fi brillation being 19.4%, with a median time to resumption of 31 days (IQR 18-65). Ischemic complications occurred more often In this large retrospective cohort study of without OAC resumption (15% vs. 5.2%, p<0.01), while rates warfarin-associated intracerebral hemorrhage of hemorrhagic complications were not signifi cantly different Susan (wICH) from 19 university-affi liated hospitals (OAC 8.1% vs. no OAC 6.6%, p=0.48). The authors chose to Muehlschlegel, MD, in Germany, the authors sought to study restrict further analyses to the largest subgroup (atrial fi brillation). MPH the relationship between anticoagulation Within this subgroup, OAC resumption had signifi cantly reversal and systolic blood pressure (SBP) decreased mortality (8.2% vs. 37.5%, p<0.01) and less ischemic with hematoma enlargement. In addition, complications (5.5% vs. 14.9%, p=0.008), without a statistically the association of oral anticoagulant (OAC) signifi cant difference in recurrent ICH. Cox-regression analysis resumption with incidence of hemorrhagic revealed a signifi cantly decreased hazard ratio for long-term and ischemic complications with functional mortality of 0.26 (95% CI 0.125-0.534; p<0.001). outcomes one year later was examined. Between 2006 and 2010, 1176 patients were This very large retrospective study provides several very included in a three-tiered analysis: hematoma important insights despite the limitations from its retrospective enlargement analysis (n=853 who underwent nature. For the fi rst time, “optimal” INR, SBP, and timing cut- INR reversal and had follow-up CT), long- offs for wICH were determined in a powerful cohort. Rates Chad Miller, MD term outcome analysis (n=1083 with one-year of hematoma enlargement were smallest in patients with INR follow-up data) and OAC resumption analysis (n=719 with one- reversed to <1.3 within 4 hours of admission and SBP <160 at 4 year follow-up, of which n=566 had atrial fi brillation). hours. OAC resumption decreases ischemic complications and mortality, without increasing hemorrhagic complications. While Data were obtained through retrospective abstraction of the confi rmation of these fi ndings should be ideally confi rmed in a medical records. Long-term follow-up was performed using trial, it is unlikely that any trial is going to be suffi ciently powered mailed questionnaires, as well as telephone interviews as to show such effects. necessary. In cases of missing contact information, a local registry offi ce inquiry was conducted to complete outcome assessments. Despite the study being retrospective, the authors applied rigorous Cross-checking of centralized data with local stroke registries and data extraction rules, and, most importantly, long-term follow- rehab facility reports was performed to improve data integrity. up. In turn, however, because follow-up was obtained mostly by Functional outcome using the modifi ed Rankin Scale (mRS) was self-reported questionnaires, follow-up data may be erroneous. dichotomized to favorable (mRS 0-3) and unfavorable (mRS Furthermore, “optimal” timing refl ects time since admission, but 4-6) and analyzed at discharge, 3- and 12-months. Hematoma not time from symptom onset, which was not collected. This, enlargement was defi ned as >33% increase from initial to however, would have most likely biased the data towards the follow-up CT. INR reversal consisted of prothrombin complex null. SBP was not collected or analyzed continuously, but only concentrates (PCCs), FFP, antithrombin, and IV vitamin K, alone in 4-hour increments, which did not allow the analysis of BP or in combination, but without a specifi c protocol. fl uctuations between observations. OAC included exclusively vitamin K antagonists, as the newer The most interesting data presented relate to the effects of OAC anticoagulants had not been approved yet in Germany. Any resumption on hemorrhagic and ischemic complications, as it is new ischemic and hemorrhagic (intra- and extracranial) the fi rst rigorous study to provide data to support resumption of complications within one year requiring hospitalization were OAC in patients with atrial fi brillation. The authors unfortunately recorded. Statistical analyses were rigid, including controlling do not clearly state why they chose to restrict the mortality for confounders in multivariable models or propensity score analysis to patients with atrial fi brillation alone. One may argue matching, ROC analysis to determine optimal cut-off points for that the authors desired a “clean” dataset with similar risk factors INR values, timing of INR reversal, and SBP values, and Bonferroni for ischemic complications. It would be important to understand correction for multiple comparisons. Hematoma enlargement hemorrhagic risks and mortality with the newer anticoagulants occurred in 36% with a median increase of 14 cc (from a median now available on the market. volume of 13 cc), and secondary IVH in 24.8%. Normothermia Improves Cerebral Adjusted models revealed three modifi able predictors of Metabolism after TBI hematoma enlargement: longer time until initiation of INR reversal (RR 1.56, 95% CI 1.14-2.13), extent of INR reversal (RR Chmayssani M, Stein NR, McArthur DL, et al. Neurocrit Care 2.29, 95% CI 1.28-4.1), and SBP at 4 hours (RR 1.01, 95% CI 2015;22:265-272 1.002-1.014). Additional predictors included deep ICH location and history of coronary artery disease. Analyses for “optimal” This single center retrospective study of severe traumatic brain timing and extent of INR reversal revealed that INR<1.3 within injury (TBI) patients sought to explore the impact of standard 4 hours of admission was associated with the lowest rate of vs. aggressive targeted temperature management (TTM) upon hematoma enlargement. Multivariable analyses of SBP revealed metabolic crisis, as measured by cerebral microdialysis (cMD). that SBP <160 at 4 hours after admission signifi cantly decreased Patients were considered for study analysis if they presented to hematoma enlargement rates. Adding SBP <160 at 4 hours to INR UCLA Reagan Medical Center within 96 hours of trauma and possessed a Glasgow Coma Scale (GCS) ≤8 or 9-12 with evidence reduction in the frequency of hematoma enlargement (18.1% of traumatic intracranial hemorrhage. Subjects were also required to be viable with adequate systemic resuscitation and intracranial 26
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