A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure

Shiozaki, Tadahiko; Hayakata, Toshiaki; Taneda, Mamoru; Nakajima, Yoshikazu; Hashiguchi, Naoyuki; Fujimi, Satoshi; Nakamori, Yasushi; Tanaka, Hiroshi; Shimazu, Takeshi; Sugimoto, Hisashi

doi:10.3171/jns.2001.94.1.0050

Cited by 203 publications

(115 citation statements)

References 9 publications

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“…83 However, two multicenter studies have failed to show beneficial effects of hypothermia. 85,86 In infants and children, hypothermia treatment has shown preservation of oxidative defenses in the CSF after TBI. 87 A meta-analysis of the clinical trials has shown that hypothermia reduced mortality and improved neurological outcome, although this was offset with an increased risk of pneumonia.…”

Section: Clinical Studies With Hypothermiamentioning

confidence: 99%

Use of Magnesium in Traumatic Brain Injury

Sen¹,

Gulati

2010

Neurotherapeutics

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Summary: Depletion of magnesium is observed in animal brain and in human blood after brain injury. Treatment with magnesium attenuates the pathological and behavioral changes in rats with brain injury; however, the therapeutic effect of magnesium has not been consistently observed in humans with traumatic brain injury (TBI). Secondary brain insults are observed in patients with brain injury, which adversely affect clinical outcome. Systemic administration studies in rats have shown that magnesium enters the brain; however, inducing hypermagnesemia in humans did not concomitantly increase magnesium levels in the CSF. We hypothesize that the neuroprotective effects of magnesium in TBI patients could be observed by increasing its brain bioavailability with mannitol. Here, we review the role of magnesium in brain injury, preclinical studies in brain injury, clinical safety and efficacy studies in TBI patients, brain bioavailability studies in rat, and pharmacokinetic studies in humans with brain injury. Neurodegeneration after brain injury involves multiple biochemical pathways. Treatment with a single agent has often resulted in poor efficacy at a safe dose or toxicity at a therapeutic dose. A successful neuroprotective therapy needs to be aimed at homeostatic control of these pathways with multiple agents. Other pharmacological agents, such as dexanabinol and progesterone, and physiological interventions, with hypothermia and hyperoxia, have been studied for the treatment of brain injury. Treatment with magnesium and hypothermia has shown favorable outcome in rats with cerebral ischemia. We conclude that coadministration of magnesium and mannitol with pharmacological and physiological agents could be an effective neuroprotective regimen for the treatment of TBI.

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Section: Clinical Studies With Hypothermiamentioning

confidence: 99%

Use of Magnesium in Traumatic Brain Injury

Sen¹,

Gulati

2010

Neurotherapeutics

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“…A higher rate of infection and worsening of coagulation have been reported in some clinical studies of hypothermia in neurotrauma [158], [159] and [160]. These complications, however, have not constituted a major problem in the majority of randomized studies [19], [20], [24] and [161], have been absent so far in ALF patients [80], [81], [119] and [120] and, importantly, they can be prevented and managed.…”

Section: Therapeutic Implicationsmentioning

confidence: 98%

Keeping cool in acute liver failure: Rationale for the use of mild hypothermia

Vaquero

Rose

Butterworth

2005

Journal of Hepatology

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Encephalopathy, brain edema and intracranial hypertension are neurological complications responsible for substantial morbidity/mortality in patients with acute liver failure (ALF), where, aside from liver transplantation, there is currently a paucity of effective therapies. Mirroring its cerebro-protective effects in other clinical conditions, the induction of mild hypothermia may provide a potential therapeutic approach to the management of ALF. A solid mechanistic rationale for the use of mild hypothermia is provided by clinical and experimental studies showing its beneficial effects in relation to many of the key factors that determine the development of brain edema and intracranial hypertension in ALF, namely the delivery of ammonia to the brain, the disturbances of brain organic osmolytes and brain extracellular amino acids, cerebro-vascular haemodynamics, brain glucose metabolism, inflammation, subclinical seizure activity and alterations of gene expression. Initial uncontrolled clinical studies of mild hypothermia in patients with ALF suggest that it is an effective, feasible and safe approach. Randomized controlled clinical trials are now needed to adequately assess its efficacy, safety, clinical impact on global outcomes and to provide the guidelines for its use in ALF.

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“…More than 10 randomized controlled trials have not yielded consistent findings at the effects of therapeutic hypothermia in TBI [106,107]. A recent Cochrane metaanalysis evaluated the effect of hypothermia to <35°C for at least 12 consecutive hours on outcome in TBI in a total of 23 trials and 1614 patients, and concluded that there was no beneficial effect of hypothermia [108].…”

Section: Tbimentioning

confidence: 99%

Therapeutic Hypothermia for Acute Neurological Injuries

2012

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Therapeutic hypothermia (TH) is the intentional reduction of core body temperature to 32°C to 35°C, and is increasingly applied by intensivists for a variety of acute neurological injuries to achieve neuroprotection and reduction of elevated intracranial pressure. TH improves outcomes in comatose patients after a cardiac arrest with a shockable rhythm, but other off-label applications exist and are likely to increase in the future. This comprehensive review summarizes the physiology and cellular mechanism of action of TH, as well as different means of TH induction and maintenance with potential side effects. Indications of TH are critically reviewed by disease entity, as reported in the most recent literature, and evidence-based recommendations are provided.

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A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure

Abstract: Mild hypothermia should not be used for the treatment of severely head injured patients with low ICP because this therapy conveys no advantage over normothermia in such patients.

Cited by 203 publications

References 9 publications

Use of Magnesium in Traumatic Brain Injury

Use of Magnesium in Traumatic Brain Injury

Keeping cool in acute liver failure: Rationale for the use of mild hypothermia

Therapeutic Hypothermia for Acute Neurological Injuries

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