Hypothermia for severe traumatic brain injury in adults: Recent lessons from randomized controlled trials

Shaefi, Shahzad; Mittel, Aaron; Hyam, Jonathan A.; Boone, M. Dustin; Chen, Clark C.; Kasper, Ekkehard M.

doi:10.4103/2152-7806.194816

Cited by 14 publications

(6 citation statements)

References 31 publications

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“…Although therapeutic hypothermia remains one of the most potent neuroprotective strategies investigated to date, it is clear from the current literature that there remain many challenges for successfully utilizing therapeutic hypothermia in severe TBI patients. [ 65 ] Only through the continued translation of supportive preclinical data to the clinic will important advancements be made in this exciting field. Controlled, hypothesis-driven approaches are required to treat TBI patients with specialized targeted temperature management protocols that have a chance of improving outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Although the current literature including systematic reviews and meta-analyses does not support the routine use of hypothermia for the management of severe TBI in pediatric and adult patients, more recent studies suggest that specific patient populations may benefit from this experimental treatment. [ 59 60 61 62 63 64 65 66 67 ] Over the last several years, there have been reports suggesting various explanations for the lack of efficacy of therapeutic hypothermia with severe TBI. [ 68 ] Furthermore, considerable work has continued using preclinical TBI models to more clearly define the most critical factors that may be important when designing clinical trials for the use of therapeutic hypothermia.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic hypothermia and targeted temperature management for traumatic brain injury: Experimental and clinical experience

Dietrich

Bramlett

2017

Brain Circ

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Traumatic brain injury (TBI) is a worldwide medical problem, and currently, there are few therapeutic interventions that can protect the brain and improve functional outcomes in patients. Over the last several decades, experimental studies have investigated the pathophysiology of TBI and tested various pharmacological treatment interventions targeting specific mechanisms of secondary damage. Although many preclinical treatment studies have been encouraging, there remains a lack of successful translation to the clinic and no therapeutic treatments have shown benefit in phase 3 multicenter trials. Therapeutic hypothermia and targeted temperature management protocols over the last several decades have demonstrated successful reduction of secondary injury mechanisms and, in some selective cases, improved outcomes in specific TBI patient populations. However, the benefits of therapeutic hypothermia have not been demonstrated in multicenter randomized trials to significantly improve neurological outcomes. Although the exact reasons underlying the inability to translate therapeutic hypothermia into a larger clinical population are unknown, this failure may reflect the suboptimal use of this potentially powerful therapeutic in potentially treatable severe trauma patients. It is known that multiple factors including patient recruitment, clinical treatment variables, and cooling methodologies are all important in yielding beneficial effects. High-quality multicenter randomized controlled trials that incorporate these factors are required to maximize the benefits of this experimental therapy. This article therefore summarizes several factors that are important in enhancing the beneficial effects of therapeutic hypothermia in TBI. The current failures of hypothermic TBI clinical trials in terms of clinical protocol design, patient section, and other considerations are discussed and future directions are emphasized.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Therapeutic hypothermia and targeted temperature management for traumatic brain injury: Experimental and clinical experience

Dietrich

Bramlett

2017

Brain Circ

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“… 10) In brain trauma foundation TBI guideline, hypothermal treatment for TBI patients trend to non-improving outcomes when was used early (within 2.5 hour after trauma), short term (48 hours) and prophylactic. 17) Shaefi et al 81) analyzed recent 8 randomized controlled trials (RCTs) of hypothermia therapy for TBI published since 2007. The majority of these trials did not identify improvement with the use of hypothermia, though there were subgroups of patients that may have benefited from hypothermia.…”

Section: Critical Care Of Asdhmentioning

confidence: 99%

“…They recommended that empiric hypothermia should be avoided and hypothermia may use in very limiting conditions as for keeping body temperature control at their focus with the intend to avoid hyperthermia. 81) Mild hypothermia may try to be applied in TBI patients who may get some benefits.…”

Section: Critical Care Of Asdhmentioning

confidence: 99%

Neurocritical Management of Traumatic Acute Subdural Hematomas

Shin

Hwang

2020

Korean J Neurotrauma

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Acute subdural hematoma (ASDH) has been a major part of traumatic brain injury. Intracranial hypertension may be followed by ASDH and brain edema. Regardless of the complicated pathophysiology of ASDH, the extent of primary brain injury underlying the ASDH is the most important factor affecting outcome. Ongoing intracranial pressure (ICP) increasing lead to cerebral perfusion pressure (CPP) decrease and cerebral blood flow (CBF) decreasing occurred by CPP decrease. In additionally, disruption of cerebral autoregulation, vasospasm, decreasing of metabolic demand may lead to CBF decreasing. Various protocols for ICP lowering were introduced in neuro-trauma field. Usage of anti-epileptic drugs (AEDs) for ASDH patients have controversy. AEDs may reduce the risk of early seizure (<7 days), but, does not for late-onset epilepsy. Usage of anticoagulants/antiplatelets is increasing due to life-long medical disease conditions in aging populations. It makes a difficulty to decide the proper management. Tranexamic acid may use to reducing bleeding and reduce ASDH related death rate. Decompressive craniectomy for ASDH can reduce patient's death rate. However, it may be accompanied with surgical risks due to big operation and additional cranioplasty afterwards. If the craniotomy is a sufficient management for the ASDH, endoscopic surgery will be good alternative to a conventional larger craniotomy to evacuate the hematoma. The management plan for the ASDH should be individualized based on age, neurologic status, radiologic findings, and the patient's conditions.

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“…11 Studies have been conducted to determine the utility of hypothermia in severe TBI patients, but they possess conflicting results. 12 However, this question has not been formally studied in any of the groups at high risk for recurrent TBI (rTBI), which can lead to CTE.…”

Section: Introductionmentioning

confidence: 99%

Can Therapeutic Hypothermia Diminish the Impact of Traumatic Brain Injury in Drosophila melanogaster?

Lateef¹,

Holman²,

Carpenter

et al. 2019

J Exp Neurosci

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Background/main objectives:No effective strategy exists to treat the well-recognized, devastating impact of traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE), which is the brain degeneration likely caused by repeated head trauma. The goals of this project were (1) to study the effects of single and recurrent TBI (rTBI) on Drosophila melanogaster’s (a) life span, (b) response to sedatives, and (c) behavioral responses to light and gravity and (2) to determine whether therapeutic hypothermia can mitigate the deleterious effects of TBI.Methods:Five experimental groups were created: (1) control, (2) single TBI or concussion; (3) concussion + hypothermia, (4) rTBI, and (5) rTBI + hypothermia. A “high-impact trauma” (HIT) device was built, which used a spring-based mechanism to propel flies against the wall of a vial, causing mechanical damage to the brain. Hypothermia groups were cooled to 15°C for 3 minutes. Group differences were analyzed with chi-square tests for the categorical variables and with ANOVA tests for the continuous variables.Results:Survival curve analysis showed that rTBI can decrease Drosophila lifespan and hypothermia diminished this impact. Average sedation time for control vs concussion vs concussion + hypothermia was 78 vs 52 vs 61 seconds (P < .0001). Similarly, rTBI vs rTBI/hypothermia groups took 43 vs 59 seconds (P < .0001). Concussed flies preferred dark environments compared with control flies (risk ratio 3.3, P < .01) while flies who were concussed and cooled had a risk ratio of 2.7 (P < .01). Flies with rTBI were almost 4 times likely to prefer the dark environment but only 3 times as likely if they were cooled, compared with controls. Geotaxis was significantly affected by rTBI only and yet less so if rTBI flies were cooled.Conclusions:Hypothermia successfully mitigated many deleterious effects of single TBI and rTBI in Drosophila and may represent a promising breakthrough in the treatment of human TBI.

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Hypothermia for severe traumatic brain injury in adults: Recent lessons from randomized controlled trials

Cited by 14 publications

References 31 publications

Therapeutic hypothermia and targeted temperature management for traumatic brain injury: Experimental and clinical experience

Therapeutic hypothermia and targeted temperature management for traumatic brain injury: Experimental and clinical experience

Neurocritical Management of Traumatic Acute Subdural Hematomas

Can Therapeutic Hypothermia Diminish the Impact of Traumatic Brain Injury in Drosophila melanogaster?

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