Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Neurocritical Care
Published in: Neurocritical Care 1/2022

16-05-2022 | Edema | Review Article

Perihematomal Edema and Clinical Outcome After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis

Authors: Sarah Marchina, Jorge A. Trevino-Calderon, Sara Hassani, Joseph M. Massaro, Vasileios-Arsenios Lioutas, Filipa Carvalho, Magdy Selim

Published in: Neurocritical Care | Issue 1/2022

Login to get access

Abstract

Background

Perihematomal edema (PHE) has been proposed as a radiological marker of secondary injury and therapeutic target in intracerebral hemorrhage (ICH). We conducted a systematic review and meta-analysis to assess the prognostic impact of PHE on functional outcome and mortality in patients with ICH.

Methods

We searched major databases through December 2020 using predefined keywords. Any study using logistic regression to examine the association between PHE or its growth and functional outcome was included. We examined the overall pooled effect and conducted secondary analyses to explore the impact of individual PHE measures on various outcomes separately. Study quality was assessed by three independent raters using the Newcastle–Ottawa Scale. Odds ratios (per 1-unit increase in PHE) and their confidence intervals (CIs) were log transformed and entered into a DerSimonian-Laird random-effects meta-analysis to obtain pooled estimates of the effect.

Results

Twenty studies (n = 6633 patients) were included in the analysis. The pooled effect size for overall outcome was 1.05 (95% CI 1.02–1.08; p < 0.00). For the following secondary analyses, the effect size was weak: mortality (1.01; 95% CI 0.90–1.14), functional outcome (1.04; 95% CI 1.02–1.07), both 90-day (1.06; 95% CI 1.02–1.11), and in-hospital assessments (1.04; 95% CI 1.00–1.08). The effect sizes for PHE volume and PHE growth were 1.04 (95% CI 1.01–1.07) and 1.14 (95% CI 1.04–1.25), respectively. Heterogeneity across studies was substantial except for PHE growth.

Conclusions

This meta-analysis demonstrates that PHE volume within the first 72 h after ictus has a weak effect on functional outcome and mortality after ICH, whereas PHE growth might have a slightly larger impact during this time frame. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.
Appendix
Available only for authorised users
Literature
1.
van Asch CJ, Luitse MJ, Rinkel GJ, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9(2):167–76.CrossRefPubMed
2.
Gonzalez-Perez A, Gaist D, Wallander MA, McFeat G, Garcia-Rodriguez LA. Mortality after hemorrhagic stroke: data from general practice (the Health Improvement Network). Neurology. 2013;81(6):559–65.CrossRefPubMed
3.
4.
Qureshi AI, Tuhrim S, Broderick JP, et al. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001;344(19):1450–60.CrossRefPubMed
5.
Shoamanesh A, Katsanos AH. Combatting secondary injury from intracerebral hemorrhage with supplemental antioxidant therapy. Stroke. 2021;52(4):1182–4.CrossRefPubMed
6.
Chen W, Guo C, Feng H, Chen Y. Mitochondria: novel mechanisms and therapeutic targets for secondary brain injury after intracerebral hemorrhage. Front Aging Neurosci. 2020;12:615451.CrossRefPubMed
7.
Urday S, Kimberly WT, Beslow LA, et al. Targeting secondary injury in intracerebral haemorrhage–perihaematomal edema. Nat Rev Neurol. 2015;11(2):111–22.CrossRefPubMed
8.
Kim M, Byun J, Chung Y, et al. Reactive oxygen species scavenger in acute intracerebral hemorrhage patients: a multicenter, randomized controlled trial. Stroke. 2021;52(4):1172–81.CrossRefPubMed
9.
Yu J, Yuan Q, Sun YR, et al. Effects of deferoxamine mesylate on hematoma and perihematoma edema after traumatic intracerebral hemorrhage. J Neurotrauma. 2017;34(19):2753–9.CrossRefPubMed
10.
Fu Y, Hao J, Zhang N, et al. Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of-concept study. JAMA Neurol. 2014;71(9):1092–101.CrossRefPubMed
11.
Wu TY, Sharma G, Strbian D, et al. Natural history of perihematomal edema and impact on outcome after intracerebral hemorrhage. Stroke. 2017;48(4):873–9.CrossRefPubMed
12.
Gebel JM Jr, Jauch EC, Brott TG, et al. Natural history of perihematomal edema in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002;33(11):2631–5.CrossRefPubMed
13.
Urday S, Beslow LA, Dai F, et al. Rate of perihematomal edema expansion predicts outcome after intracerebral hemorrhage. Crit Care Med. 2016;44(4):790–7.CrossRefPubMedPubMedCentral
14.
Huan R, Li Y, Tan J, et al. The hounsfield unit of perihematomal edema is associated with poor clinical outcomes in intracerebral hemorrhage. World Neurosurg. 2020;146:e829–36.CrossRefPubMed
15.
Appelboom G, Bruce SS, Hickman ZL, et al. Volume-dependent effect of perihaematomal edema on outcome for spontaneous intracerebral haemorrhages. J Neurol Neurosurg Psychiatry. 2013;84(5):488–93.CrossRefPubMed
16.
17.
18.
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, eds. Cochrane handbook for systematic reviews of interventions version 6.2. The Cochrane Collaboration. 2021. www.​training.​cochrane.​org/​handbook. Accessed 2 Feb 2021.
19.
Godoy DA, Nunez-Patino RA, Zorrilla-Vaca A, Ziai WC, Hemphill JC 3rd. Intracranial hypertension after spontaneous intracerebral hemorrhage: a systematic review and meta-analysis of prevalence and mortality rate. Neurocrit Care. 2019;31(1):176–87.CrossRefPubMed
20.
StataCorp, Stata Statistical Software: Release 16, 2019, StataCorp LLC: College Station, TX. www.​stata.​com. Accessed 30 May 2021.
21.
Chen TA. Fixed or random testlet effects: a comparison of two multilevel testlet models. J Appl Meas. 2012;13(3):231–47.PubMed
22.
Bakhshayesh B, Hosseininezhad M, Saadat SNS, et al. Iron overload is associated with perihematoma edema growth following intracerebral hemorrhage that may contribute to in-hospital mortality and long-term functional outcome. Curr Neurovasc Res. 2014;11(3):248–53.CrossRefPubMed
23.
Bakhshayesh B, Hosseininezhad M, Saadat SMS, et al. Predicting in-hospital mortality in Iranian patients with spontaneous intracerebral hemorrhage. Iran J Neurol. 2014;13(4):231–6.PubMedPubMedCentral
24.
Levine JM, Snider R, Finkelstein D, et al. Early edema in warfarin-related intracerebral hemorrhage. Neurocrit Care. 2007;7(1):58–63.CrossRefPubMed
25.
26.
27.
28.
Tsai YH, Hsu LM, Weng HH, et al. Voxel-based analysis of apparent diffusion coefficient in perihaematomal edema: associated factors and outcome predictive value for intracerebral haemorrhage. BMJ Open. 2011;1(1):e000230.CrossRefPubMedPubMedCentral
29.
Grunwald Z, Beslow LA, Urday S, et al. Perihematomal edema expansion rates and patient outcomes in deep and lobar intracerebral hemorrhage. Neurocrit Care. 2017;26(2):205–12.CrossRefPubMedPubMedCentral
30.
Murthy SB, Urday S, Beslow LA, et al. Rate of perihaematomal edema expansion is associated with poor clinical outcomes in intracerebral haemorrhage. J Neurol Neurosurg Psychiatry. 2016;87(11):1169–73.CrossRefPubMed
31.
Zubkov AY, Mandrekar JN, Claassen DO, et al. Predictors of outcome in warfarin-related intracerebral hemorrhage. Arch Neurol. 2008;65(10):1320–5.CrossRefPubMed
32.
Gupta M, Verma R, Parihar A, et al. Perihematomal edema as predictor of outcome in spontaneous intracerebral hemorrhage. J Neurosci Rural Pract. 2014;5(1):48–54.CrossRefPubMedPubMedCentral
33.
Hurford R, Vail A, Heal C, et al. Edema extension distance in intracerebral haemorrhage: association with baseline characteristics and long-term outcome. Eur Stroke J. 2019;4(3):263–70.CrossRefPubMedPubMedCentral
34.
Murthy SB, Moradiya Y, Dawson J, et al. Perihematomal edema and functional outcomes in intracerebral hemorrhage: influence of hematoma volume and location. Stroke. 2015;46(11):3088–92.CrossRefPubMed
35.
Yang J, Arima H, Wu G, et al. Prognostic significance of perihematomal edema in acute intracerebral hemorrhage: pooled analysis from the intensive blood pressure reduction in acute cerebral hemorrhage trial studies. Stroke. 2015;46(4):1009–13.CrossRefPubMed
36.
Sansing LH, Messe SR, Cucchiara BL, Lyden PD, Kasner SE. Anti-adrenergic medications and edema development after intracerebral hemorrhage. Neurocrit Care. 2011;14(3):395–400.CrossRefPubMed
37.
Leasure AC, Qureshi AI, Murthy SB, et al. Intensive blood pressure reduction and perihematomal edema expansion in deep intracerebral hemorrhage. Stroke. 2019;50(8):2016–22.CrossRefPubMedPubMedCentral
38.
Arima H, Wang JG, Huang Y, et al. Significance of perihematomal edema in acute intracerebral hemorrhage: the INTERACT trial. Neurology. 2009;73(23):1963–8.CrossRefPubMedPubMedCentral
39.
Sansing LH, Kaznatcheeva EA, Perkins CJ, et al. Edema after intracerebral hemorrhage: correlations with coagulation parameters and treatment. J Neurosurg. 2003;98(5):985–92.CrossRefPubMed
40.
Gebel JM, Jauch EC, Brott TG, et al. Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral Hemorrhage. Stroke. 2002;33(11):2636–41.CrossRefPubMed
41.
Staykov D, Wagner I, Volbers B, et al. Natural course of perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2011;42(9):2625–9.CrossRefPubMed
42.
Volbers B, Willfarth W, Kuramatsu JB, et al. Impact of perihemorrhagic edema on short-term outcome after intracerebral hemorrhage. Neurocrit Care. 2016;24(3):404–12.CrossRefPubMed
43.
Volbers B, Giede-Jeppe A, Gerner ST, et al. Peak perihemorrhagic edema correlates with functional outcome in intracerebral hemorrhage. Neurology. 2018;90(12):E1005–12.CrossRefPubMed
44.
Peng WJ, Li Q, Tang JH, et al. The risk factors and prognosis of delayed perihematomal edema in patients with spontaneous intracerebral hemorrhage. CNS Neurosci Ther. 2019;25(10):1189–94.CrossRefPubMedPubMedCentral
45.
Ozdinc S, Unlu E, Karakaya Z, et al. Prognostic value of perihematomal edema area at the initial ED presentation in patients with intracranial hematoma. Am J Emerg Med. 2016;34(7):1241–6.
46.
Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018;27(6):1785–805.CrossRefPubMed
47.
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.CrossRefPubMedPubMedCentral
48.
49.
50.
Ironside N, Chen CJ, Ding D, Mayer SA, Connolly ES Jr. Perihematomal edema after spontaneous intracerebral hemorrhage. Stroke. 2019;50(6):1626–33.CrossRefPubMed
51.
Zheng H, Chen C, Zhang J, Hu Z. Mechanism and therapy of brain edema after intracerebral hemorrhage. Cerebrovasc Dis. 2016;42(3–4):155–69.CrossRefPubMed
52.
Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53–63.CrossRefPubMed
53.
Bhasin RR, Xi G, Hua Y, Keep RF, Hoff JT. Experimental intracerebral hemorrhage: effect of lysed erythrocytes on brain edema and blood-brain barrier permeability. Acta Neurochir Suppl. 2002;81:249–51.PubMed
54.
55.
56.
Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720–31.CrossRefPubMed
57.
Venkatasubramanian C, Mlynash M, Finley-Caulfield A, et al. Natural history of perihematomal edema after intracerebral hemorrhage measured by serial magnetic resonance imaging. Stroke. 2011;42(1):73–80.CrossRefPubMed
58.
Inaji M, Tomita H, Tone O, et al. Chronological changes of perihematomal edema of human intracerebral hematoma. Acta Neurochir Suppl. 2003;86:445–8.PubMed
59.
Selim M, Norton C. Perihematomal edema: implications for intracerebral hemorrhage research and therapeutic advances. J Neurosci Res. 2020;98(1):212–8.CrossRefPubMed
60.
Divani AA, Majidi S, Luo X, et al. The ABCs of accurate volumetric measurement of cerebral hematoma. Stroke. 2011;42(6):1569–74.CrossRefPubMed
61.
Shulman JG, Jara H, Qureshi MM, et al. Perihematomal edema surrounding spontaneous intracerebral hemorrhage by CT: ellipsoidal versus morphometric volumetry. Medicine (Baltimore). 2020;99(28):e20951.CrossRef
62.
Volbers B, Staykov D, Wagner I, et al. Semi-automatic volumetric assessment of perihemorrhagic edema with computed tomography. Eur J Neurol. 2011;18(11):1323–8.CrossRefPubMed
63.
Parry-Jones AR, Wang X, Sato S, et al. Edema extension distance: outcome measure for phase II clinical trials targeting edema after intracerebral hemorrhage. Stroke. 2015;46(6):e137–40.CrossRefPubMed
64.
Metadata
Title
Perihematomal Edema and Clinical Outcome After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis
Authors
Sarah Marchina
Jorge A. Trevino-Calderon
Sara Hassani
Joseph M. Massaro
Vasileios-Arsenios Lioutas
Filipa Carvalho
Magdy Selim
Publication date
16-05-2022
Publisher
Springer US
Keyword
Edema
Published in
Neurocritical Care / Issue 1/2022
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-022-01512-4

Other articles of this Issue 1/2022

Neurocritical Care 1/2022 Go to the issue

Original work

Sex-Related Differences in Patients’ Characteristics, Provided Care, and Outcomes Following Spontaneous Intracerebral Hemorrhage

Original work

Blood Pressure and Spot Sign in Spontaneous Supratentorial Subcortical Intracerebral Hemorrhage

Original work

Effect of Obstructive Sleep Apnea on Outcomes After Traumatic Brain Injury: A Retrospective Cohort Analysis

Original work

Safety and Efficacy of Vinpocetine as a Neuroprotective Agent in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Original work

Prognostication of ICU Patients by Providers with and without Neurocritical Care Training

Original work

Neurological Prognostication After Hypoglycemic Coma: Role of Clinical and EEG Findings