Therapeutic Hypothermia (Different Depths, Durations, and Rewarming Speeds) for Acute Ischemic Stroke: A Meta-analysis

Wan, Yue-Hong; Chen, Nie; Wang, Huiling; Huang, C

doi:10.1016/j.jstrokecerebrovasdis.2014.06.017

Cited by 25 publications

(12 citation statements)

References 26 publications

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“…Thus, the Nielsen study appears inconclusive and more clinical research is needed. Another recent trial reported no significant benefits for mortality rate or neurological functions in stroke patients received TH of physical cooling (Wan et al, 2014). It is commonly agreed that early treatment after acute stroke is critical for brain protection and functional recovery.…”

Section: Discussionmentioning

confidence: 99%

Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice

Lee

Wei

Cao

et al. 2016

Neurobiology of Disease

121

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Stroke is a leading threat to human life and health in the US and around the globe, while very few effective treatments are available for stroke patients. Preclinical and clinical studies have shown that therapeutic hypothermia (TH) is a potential treatment for stroke. Using novel neurotensin receptor 1 (NTR1) agonists, we have demonstrated pharmacologically induced hypothermia and protective effects against brain damages after ischemic stroke, hemorrhage stroke, and traumatic brain injury (TBI) in rodent models. To further characterize the mechanism of TH-induced brain protection, we examined the effect of TH (at ±33°C for 6 hrs) induced by the NTR1 agonist HPI-201 or physical (ice/cold air) cooling on inflammatory responses after ischemic stroke in mice and oxygen glucose deprivation (OGD) in cortical neuronal cultures. Seven days after focal cortical ischemia, microglia activation in the penumbra reached a peak level, which was significantly attenuated by TH treatments commenced 30 min after stroke. The TH treatment decreased the expression of M1 type reactive factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-12, IL-23, and inducible nitric oxide synthase (iNOS) measured by RT-PCR and Western blot analyses. Meanwhile, TH treatments increased the expression of M2 type reactive factors including IL-10, Fizz1, Ym1, and arginase-1. In the ischemic brain and in cortical neuronal/BV2 microglia cultures subjected to OGD, TH attenuated the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α), two key chemokines in the regulation of microglia activation and infiltration. Consistently, physical cooling during OGD significantly decreased microglia migration 16 hrs after OGD. Finally, TH improved functional recovery at 1, 3, and 7 days after stroke. This study reveals the first evidence for hypothermia mediated regulation on inflammatory factor expression, microglia polarization, migration and indicates that the anti-inflammatory effect is an important mechanism underlying the brain protective effects of a TH therapy.

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Section: Discussionmentioning

confidence: 99%

Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice

Lee

Wei

Cao

et al. 2016

Neurobiology of Disease

121

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“…Clinical trials confirmed powerful protection with TH after accidental neonatal hypoxic-ischemic injury 3, 4 and global cerebral ischemia after cardiac arrest 5, 6 and national and international guidelines recommend TH for these patients 7 . Clinical trials of TH for acute ischemic stroke are less well developed, but pilot studies have suggested benefit 8 . Early pilot trials used surface cooling technology in stroke patients who were intubated due to severe strokes, and therefore pharmacologically paralyzed, facilitating shivering control 9–11 .…”

mentioning

confidence: 99%

Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2)

Lyden

Hemmen

Grotta

et al. 2016

Stroke

141

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Background and Purpose Therapeutic hypothermia (TH) is a potent neuroprotectant approved for cerebral protection after neonatal hypoxia-ischemia and cardiac arrest. TH for acute ischemic stroke is safe and feasible in pilot trials. We designed a study protocol to provide safer, faster TH in stroke patients. Methods Safety procedures and 4°C saline infusions for faster cooling were added to the Intravascular Cooling Treatment in Acute Stroke (ICTuS) trial protocol. A femoral venous intravascular cooling catheter following intravenous rt-PA in eligible patients provided 24 hours cooling followed by a 12 hour re-warm. Serial safety assessments and imaging were performed. The primary endpoint was 3-month modified Rankin score 0,1. Results Of the intended 1600 subjects, 120 were enrolled before the study was stopped. Randomly, 63 were to receive hypothermia (HY) plus anti-shivering treatment and 57 normothermia (NT). Compared to prior studies, cooling rates were improved with a cold saline bolus, without fluid overload. The intention-to-treat primary outcome of 90-day mRS 0,1 occurred in 33% HY and 38% NT subjects, OR (95% CL) of 0.81 (0.36, 1.85). Serious adverse events occurred equally. Mortality was 15.9% HY and 8.8% NT subjects, OR (95% CL) of 1.95 (0.56, 7.79). Pneumonia occurred in 19% HY vs. 10.5% in NT subjects, OR (95% CL) of 1.99 (0.63, 6.98). Conclusion Intravascular TH was confirmed to be safe and feasible in rt-PA treated acute ischemic stroke patients. Protocol changes designed to reduce pneumonia risk appeared to fail, although the sample is small. Clinical trial registration clinicaltrials.gov NCT 01123161.

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“…Definitive data regarding optimal duration of cooling, degree of hypothermia, induction, and rewarming speeds on neurological outcomes in AIS is still lacking. A recent meta-analysis could not answer those questions and remarkably showed no difference in rates of good neurological outcomes between treated and nontreated groups [72]. The incidence of pneumonia, however, was higher in treated group but without translation into a higher mortality [72].…”

Section: Neurocritical Care Of MMImentioning

confidence: 98%

“…Therapeutic hypothermia (TH) has shown promising effects in preclinical data and in small studies by reducing cerebral metabolism, interrupting programed cell death pathways, inhibition of excitotoxicity and free radical formation, reducing infarct size, edema formation, and improving outcomes [71][72][73][74]. Definitive data regarding optimal duration of cooling, degree of hypothermia, induction, and rewarming speeds on neurological outcomes in AIS is still lacking.…”

Section: Neurocritical Care Of MMImentioning

confidence: 99%

“…A recent meta-analysis could not answer those questions and remarkably showed no difference in rates of good neurological outcomes between treated and nontreated groups [72]. The incidence of pneumonia, however, was higher in treated group but without translation into a higher mortality [72]. Ongoing studies are being conducted to assess efficacy, feasibility, and safety, in particular, in the setting of malignant cerebral edema and hemicraniectomy [75].…”

Section: Neurocritical Care Of MMImentioning

confidence: 99%

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Malignant MCA Stroke: an Update on Surgical Decompression and Future Directions

Maciel

Sheth

2015

Curr Atheroscler Rep

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Despite a decline over the past decade in overall stroke mortality, hemispheric strokes retain a strikingly high mortality due to their potential for malignant edema and herniation. The pathogenesis of ischemic cerebral edema is steered by disruption of ionic homeostasis in the neurogliovascular unit. Significant effort has been made to identify potential medical therapies targeting edema formation with promising results. To date, decompressive craniectomy remains the therapy with the most robust impact on mortality. Historically, patient selection for surgical treatment of malignant supratentorial strokes has focused on a strict age cutoff and hemispheric dominance. Recent evidence supports a significant mortality benefit in elderly population, although the impact in morbidity is modest. Careful patient selection for surgical treatment in conjunction with comprehensive neurocritical care and inclusion of family in the educated decision making process remain the mainstay of care for such shattering disease.

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Therapeutic Hypothermia (Different Depths, Durations, and Rewarming Speeds) for Acute Ischemic Stroke: A Meta-analysis

Cited by 25 publications

References 26 publications

Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice

Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice

Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2)

Malignant MCA Stroke: an Update on Surgical Decompression and Future Directions

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