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 2/2022

01-04-2022 | Subdural Hematoma | Original work

Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial

Authors: Georgene W. Hergenroeder, Shoji Yokobori, Huimahn Alex Choi, Karl Schmitt, Michelle A. Detry, Lisa H. Schmitt, Anna McGlothlin, Ava M. Puccio, Jonathan Jagid, Yasuhiro Kuroda, Yukihiko Nakamura, Eiichi Suehiro, Faiz Ahmad, Kert Viele, Elisabeth A. Wilde, Stephen R. McCauley, Ryan S. Kitagawa, Nancy R. Temkin, Shelly D. Timmons, Michael N. Diringer, Pramod K. Dash, Ross Bullock, David O. Okonkwo, Donald A. Berry, Dong H. Kim

Published in: Neurocritical Care | Issue 2/2022

Login to get access

Abstract

Background

Hypothermia is neuroprotective in some ischemia–reperfusion injuries. Ischemia–reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia–reperfusion injury and improve global neurologic outcome.

Methods

This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels.

Results

Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups.

Conclusions

This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups.
Appendix
Available only for authorised users
Literature
1.
Taylor CA, Bell JM, Breiding MJ, Xu L. Traumatic brain injury-related emergency department visits, hospitalizations, and deaths—United States, 2007 and 2013. MMWR Surveill Summ. 2017;66(9):1–16.PubMedPubMedCentral
2.
Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. TBI-related emergency department visits, hospitalizations, and deaths (EDHDs). Healthcare cost and utilization project's (HCUP) nationwide emergency department sample for emergency department visits; HCUP's Nationwide Inpatient Sample for hospitalizations; CDC's National Vital Statistics System for deaths. 3–29–0019. Accessed 11–23–2020.
3.
Povlishock JT, Katz DI. Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehabil. 2005;20(1):76–94.PubMed
4.
Dixon CE, Markgraf CG, Angileri F, et al. Protective effects of moderate hypothermia on behavioral deficits but not necrotic cavitation following cortical impact injury in the rat. J Neurotrauma. 1998;15(2):95–103.PubMed
5.
Markgraf CG, Clifton GL, Moody MR. Treatment window for hypothermia in brain injury. J Neurosurg. 2001;95(6):979–83.PubMed
6.
Callaway CW, Donnino MW, Fink EL, et al. Part 8: post-cardiac arrest care: 2015 American heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 Suppl 2):S465–82.PubMedPubMedCentral
7.
Lascarrou JB, Merdji H, Le GA, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med. 2019;381(24):2327–37.PubMed
8.
Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369(23):2197–206.PubMed
9.
Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischaemic encephalopathy. N Engl J Med. 2005;353(15):1574–84.PubMed
10.
Laptook AR, Shankaran S, Tyson JE, et al. Effect of therapeutic hypothermia initiated after 6 hours of age on death or disability among newborns with hypoxic-ischaemic encephalopathy: a randomized clinical trial. JAMA. 2017;318(16):1550–60.PubMedPubMedCentral
11.
Polderman KH, Ely EW, Badr AE, Girbes AR. Induced hypothermia in traumatic brain injury: considering the conflicting results of meta-analyses and moving forward. Intensive Care Med. 2004;30(10):1860–4.PubMed
12.
Andrews PJ, Sinclair HL, Battison CG, et al. European society of intensive care medicine study of therapeutic hypothermia (32–35 degrees C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial). Trials. 2011;12:8.PubMedPubMedCentral
13.
Andrews PJ, Sinclair HL, Rodriguez A, et al. Therapeutic hypothermia to reduce intracranial pressure after traumatic brain injury: the Eurotherm3235 RCT. Health Technol Assess. 2018;22(45):1–134.PubMedPubMedCentral
14.
Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med. 2001;344(8):556–63.PubMed
15.
Clifton GL, Valadka A, Zygun D, et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol. 2011;10(2):131–9.PubMed
16.
Clifton GL, Coffey CS, Fourwinds S, et al. Early induction of hypothermia for evacuated intracranial hematomas: a post hoc analysis of two clinical trials. J Neurosurg. 2012;117(4):714–20.PubMed
17.
Dash PK, Zhao J, Hergenroeder G, Moore AN. Biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy for traumatic brain injury. Neurotherapeutics. 2010;7(1):100–14.PubMedPubMedCentral
18.
Yokobori S, Gajavelli S, Mondello S, et al. Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model. J Neurosurg. 2013;118(2):370–80.PubMed
19.
Papa L, Brophy GM, Welch RD, et al. Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA Neurol. 2016;73(5):551–60.PubMedPubMedCentral
20.
Vos PE, Lamers KJ, Hendriks JC, et al. Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology. 2004;62(8):1303–10.PubMed
21.
Welch RD, Ayaz SI, Lewis LM, et al. Ability of serum glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, and S100B to differentiate normal and abnormal head computed tomography findings in patients with suspected mild or moderate traumatic brain injury. J Neurotrauma. 2016;33(2):203–14.PubMedPubMedCentral
22.
Marion DW, Penrod LE, Kelsey SF, et al. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med. 1997;336(8):540–6.PubMed
23.
Kilpatrick MM, Lowry DW, Firlik AD, Yonas H, Marion DW. Hyperthermia in the neurosurgical intensive care unit. Neurosurgery. 2000;47(4):850–5.PubMed
24.
Marion DW. Therapeutic moderate hypothermia and fever. Curr Pharm Des. 2001;7(15):1533–6.PubMed
25.
Puccio AM, Fischer MR, Jankowitz BT, Yonas H, Darby JM, Okonkwo DO. Induced normothermia attenuates intracranial hypertension and reduces fever burden after severe traumatic brain injury. Neurocrit Care. 2009;11(1):82–7.PubMedPubMedCentral
26.
Broessner G, Beer R, Lackner P, et al. Prophylactic, endovascularly based, long-term normothermia in ICU patients with severe cerebrovascular disease: bicenter prospective, randomized trial. Stroke. 2009;40(12):e657–65.PubMed
27.
Fischer M, Lackner P, Beer R, et al. Keep the brain cool–endovascular cooling in patients with severe traumatic brain injury: a case series study. Neurosurgery. 2011;68(4):867–73.PubMed
28.
Schmutzhard E, Engelhardt K, Beer R, et al. Safety and efficacy of a novel intravascular cooling device to control body temperature in neurologic intensive care patients: a prospective pilot study. Crit Care Med. 2002;30(11):2481–8.PubMed
29.
Choi HA, Ko SB, Presciutti M, et al. Prevention of shivering during therapeutic temperature modulation: the Columbia anti-shivering protocol. Neurocrit Care. 2011;14(3):389–94.PubMed
30.
Carney N, Totten AM, O’Reilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury. Fourth Edition Neurosurg. 2017;80(1):6–15.
31.
Teasdale G, Jennett B. Assessment of coma and impaired consciousness A practical scale. Lancet. 1974;2(7872):81–4.PubMed
32.
33.
Olah E, Poto L, Hegyi P, et al. Therapeutic whole-body hypothermia reduces death in severe traumatic brain injury if the cooling index is sufficiently high: meta-analyses of the effect of single cooling parameters and their integrated measure. J Neurotrauma. 2018;35(20):2407–17.PubMed
34.
Cooper DJ, Nichol AD, Bailey M, et al. Effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury: the POLAR randomized clinical trial. JAMA. 2018;320(21):2211–20.PubMedPubMedCentral
35.
Hol EM, Pekny M. Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Curr Opin Cell Biol. 2015;32:121–30.PubMed
36.
Liu H, Povysheva N, Rose ME, et al. Role of UCHL1 in axonal injury and functional recovery after cerebral ischemia. Proc Natl Acad Sci USA. 2019;116(10):4643–50.PubMedPubMedCentral
37.
Frankel M, Fan L, Yeatts SD, et al. Association of very early serum levels of S100B, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, and spectrin breakdown product with outcome in ProTECT III. J Neurotrauma. 2019;36(20):2863–71.PubMedPubMedCentral
38.
Papa L, Zonfrillo MR, Welch RD, et al. Evaluating glial and neuronal blood biomarkers GFAP and UCH-L1 as gradients of brain injury in concussive, subconcussive and non-concussive trauma: a prospective cohort study. BMJ Paediatr Open. 2019;3(1):e000473.PubMedPubMedCentral
39.
Anderson TN, Hwang J, Munar M, et al. Blood-based biomarkers for prediction of intracranial hemorrhage and outcome in patients with moderate or severe traumatic brain injury. J Trauma Acute Care Surg. 2020;89(1):80–6.PubMedPubMedCentral
40.
Bazarian JJ, Biberthaler P, Welch RD, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17(9):782–9.PubMed
41.
Yokobori S, Spurlock MS, Lee SW, Gajavelli S, Bullock RM. Microdialysis as clinical evaluation of therapeutic hypothermia in rat subdural hematoma model. Methods Mol Biol. 2016;1462:413–31.PubMed
42.
Yokobori S, Bullock R, Gajavelli S, et al. Preoperative-induced mild hypothermia attenuates neuronal damage in a rat subdural hematoma model. Acta Neurochir Suppl. 2013;118:77–81.PubMed
43.
Ebner F, Moseby-Knappe M, Mattsson-Carlgren N, et al. Serum GFAP and UCH-L1 for the prediction of neurological outcome in comatose cardiac arrest patients. Resuscitation. 2020;154:61–8.PubMed
44.
Mondello S, Papa L, Buki A, et al. Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study. Crit Care. 2011;15(3):R156.PubMedPubMedCentral
45.
Wilberger JE Jr, Harris M, Diamond DL. Acute subdural hematoma: morbidity, mortality, and operative timing. J Neurosurg. 1991;74(2):212–8.PubMed
46.
Bullock MR, Chesnut R, Ghajar J, et al. Surgical management of acute subdural hematomas. Neurosurgery. 2006;58(3 Suppl):S16-24.PubMed
47.
Bajsarowicz P, Prakash I, Lamoureux J, et al. Nonsurgical acute traumatic subdural hematoma: what is the risk? J Neurosurg. 2015;123(5):1176–83.PubMed
48.
49.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.
Metadata
Title
Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial
Authors
Georgene W. Hergenroeder
Shoji Yokobori
Huimahn Alex Choi
Karl Schmitt
Michelle A. Detry
Lisa H. Schmitt
Anna McGlothlin
Ava M. Puccio
Jonathan Jagid
Yasuhiro Kuroda
Yukihiko Nakamura
Eiichi Suehiro
Faiz Ahmad
Kert Viele
Elisabeth A. Wilde
Stephen R. McCauley
Ryan S. Kitagawa
Nancy R. Temkin
Shelly D. Timmons
Michael N. Diringer
Pramod K. Dash
Ross Bullock
David O. Okonkwo
Donald A. Berry
Dong H. Kim
Publication date
01-04-2022
Publisher
Springer US
Published in
Neurocritical Care / Issue 2/2022
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-021-01334-w

Other articles of this Issue 2/2022

Neurocritical Care 2/2022 Go to the issue

Correction

Correction to: Cortical Spreading Depolarizations in a Mouse Model of Subarachnoid Hemorrhage

Review Article

Acute Kidney Injury at the Neurocritical Care Unit

Original work

Size-Related Differences in Computed Tomography Markers of Hematoma Expansion in Acute Intracerebral Hemorrhage

Original work

Accelerating Prediction of Malignant Cerebral Edema After Ischemic Stroke with Automated Image Analysis and Explainable Neural Networks

Invited Commentary

Cerebral Oxygenation: An Additional Target for the Management of Patients with Traumatic Brain Injury

Original work

Diffuse Axonal Injury Grade on Early MRI is Associated with Worse Outcome in Children with Moderate-Severe Traumatic Brain Injury