title: Prognostic significance of perihematomal edema in acute intracerebral hemorrhage: pooled analysis from the intensive blood pressure reduction in acute cerebral hemorrhage trial studies.
abstract: OBJECTIVE
  Controversy exists over the prognostic significance of perihematomal edema (PHE) in intracerebral hemorrhage. We aimed to determine the association of early PHE and clinical outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies.
  
  
  METHODS
  Pooled analyses of computed tomographic substudies in the pilot phase (INTERACT1) and main phase (INTERACT2), both international, prospective, open, blinded end point, randomized controlled trials, of patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure, randomly assigned to intensive (target systolic blood pressure, <140 mm Hg) or guideline-based (systolic blood pressure, <180 mm Hg) blood-pressure management. Substudy participants (n=1310; 346 INTERACT1, 964 INTERACT2) had blinded central analyses of digital images from standardized baseline and 24-hour computed tomography. Predictors of death or dependency (modified Rankin scale scores, ≥3) at 90 days were assessed in logistic regression models and reported with odds ratios and 95% confidence intervals. INTERACT studies are registered at ClinicalTrials.gov (NCT00226096 and NCT00716079).
  
  
  RESULTS
  Of 1138 (87%) patients with 2 CTs available for edema analysis and outcome information, time from intracerebral hemorrhage onset to baseline computed tomography, baseline hematoma volume, 24-hour hematoma growth, and intraventricular extension were independent predictors of 24-hour PHE growth. Absolute growth in PHE volume was significantly associated with death or dependency (adjusted odds ratio, 1.17; 95% confidence interval, 1.02-1.33 per 5 mL increase from baseline; P=0.025) at 90 days after adjustment for demographic, clinical, and hematoma parameter prognostic factors. Associations were consistent across various sensitivity analyses.
  
  
  CONCLUSIONS
  PHE growth is an independent prognostic factor in intracerebral hemorrhage.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Hisatomi
authors.initials: H
authors.lastname: Arima
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Emma
authors.initials: E
authors.lastname: Heeley
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Candice
authors.initials: C
authors.lastname: Delcourt
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Junshan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Guofang
authors.initials: G
authors.lastname: Chen
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Shihong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: Sungwook
authors.initials: S
authors.lastname: Yu
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.).
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
authors.affiliation: From the Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China (J.Y., J.Z.); The George Institute for Global Health, Central Clinical School, University of Sydney and Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia (J.Y., H.A., G.W., E.H., C.D., G.C., X.W., S.Z., S.Y., J.C., C.S.A.); Department of Neurology, Hebei Yutian Hospital, Tangshan, China (G.W.); Department of Neurology, Xuzhou Central Hospital, Xuzhou, China (G.C.); Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (S.Z.); and Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea (S.Y.). canderson@georgeinstitute.org.au.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Anderson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001929:Brain Edema / Q000000981:diagnostic imaging* / Q000401:mortality; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D046648:Hematoma, Subdural, Intracranial / Q000000981:diagnostic imaging / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011859:Radiography; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents
keywords: cerebral hemorrhage; clinical trial; hypertension