Hypothermia after acute ischemic stroke (original) (raw)

Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials?

Journal of Cerebral Blood Flow & Metabolism, 2010

Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke.

Therapeutic Hypothermia for Brain Ischemia: Where Have We Come and Where Do We Go?

Stroke, 2010

Mild hypothermia is an established neuroprotectant in the laboratory, showing remarkable and consistent effects across multiple laboratories and models of brain injury. At the clinical level, mild hypothermia has shown benefits in patients who have experienced cardiac arrest and in some pediatric populations experiencing hypoxic brain insults. Its role, however, in stroke therapy has yet to be established. Translating preclinical data to the clinical arena presents unique challenges with regard to cooling in patients who are generally awake and may require additional therapies, such as reperfusion. We review the state of therapeutic hypothermia in ischemic and hemorrhagic stroke and provide an outlook for its role in stroke therapy.

Therapeutic hypothermia for acute stroke

International Journal of Stroke, 2006

Hypothermia is the most potent neuroprotective therapy available. Clinical use of hypothermia is limited by technology and homeostatic mechanisms that maintain core body temperature. Recent advances in intravascular cooling catheters and successful trials of hypothermia for cardiac arrest revivified interest in hypothermia for stroke, resulting in Phase 1 clinical trials and plans for further development. Given the recent spate of neuroprotective therapy failures, we sought to clarify whether clinical trials of therapeutic hypothermia should be mounted in stroke patients. We reviewed the preclinical and early clinical trials of hypothermia for a variety of indications, the putative mechanisms for neuroprotection with hypothermia, and offer several hypotheses that remain to be tested in clinical trials. Therapeutic hypothermia is promising, but further Phase 1 and Phase 2 development efforts are needed to ensure that cooling of stroke patients is safe, before definitive efficacy trials.

The emerging role of induced hypothermia in the management of acute stroke

Journal of Clinical Neuroscience, 2002

Current treatment of acute stroke remains unsatisfactory. This review presents experimental and clinical data which suggest that mild induced hypothermia could be a potent and practicable neuroprotective treatment of acute ischaemic stroke and intracerebral haemorrhage. Hypothermia, if proven to be safe, effective and widely practicable in patients with acute stroke, could have an enormous positive impact on reducing the burden of stroke worldwide. Critical issues that will need to be considered in a well designed randomised controlled trial of induced hypothermia in acute stroke patients are discussed. &

Use of Prolonged Hypothermia to Treat Ischemic and Hemorrhagic Stroke

Journal of Neurotrauma, 2009

Therapeutic (induced) hypothermia (TH) has been extensively studied as a means to reduce brain injury following global and focal cerebral ischemia, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Here, we briefly review the clinical and experimental evidence supporting the use of TH in each condition. We emphasize the importance of systematically evaluating treatment parameters, especially the duration of cooling, in each condition. We contend that TH provides considerable protection after global and focal cerebral ischemia, especially when cooling is prolonged (e.g., >24 h). However, there is presently insufficient evidence to support the clinical use of TH for ICH and SAH. In any case, further animal work is needed to develop optimized protocols for treating cardiac arrest (global ischemia), and to maximize the likelihood of successful clinical translation in focal cerebral ischemia.

Therapeutic Hypothermia in Stroke and Traumatic Brain Injury

Frontiers in Neurology, 2011

Therapeutic hypothermia (TH) is considered to improve survival with favorable neurological outcome in the case of global cerebral ischemia after cardiac arrest and perinatal asphyxia. The efficacy of hypothermia in acute ischemic stroke (AIS) and traumatic brain injury (TBI), however, is not well studied. Induction of TH typically requires a multimodal approach, including the use of both pharmacological agents and physical techniques. To date, clinical outcomes for patients with either AIS or TBI who received TH have yielded conflicting results; thus, no adequate therapeutic consensus has been reached. Nevertheless, it seems that by determining optimal TH parameters and also appropriate applications, cooling therapy still has the potential to become a valuable neuroprotective intervention. Among the various methods for hypothermia induction, intravascular cooling (IVC) may have the most promise in the awake patient in terms of clinical outcomes. Currently, the IVC method has the capability of more rapid target temperature attainment and more precise control of temperature. However, this technique requires expertise in endovascular surgery that can preclude its application in the field and/or in most emergency settings. It is very likely that combining neuroprotective strategies will yield better outcomes than utilizing a single approach.

Feasibility of hypothermia beyond 3weeks in severe ischemic stroke

Journal of the Neurological Sciences, 2012

Hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of very prolonged moderate hypothermia for severe acute ischemic stroke. Moderate hypothermia was induced within 24h after a severe ischemic stroke involving the middle cerebral artery. Hypothermia, with cooling blankets, reduced body-core temperature to 32-33°C, and was prolonged for up to 22 days until cerebral edema had significantly decreased (assessed by serial cerebral computed tomography) before slow rewarming (<1.5°C/day). Patients were mechanically ventilated and sedated with gamma-hydroxybutyrate (GHB), a naturally occurring metabolite of gamma-aminobutyric acid (GABA), which acts on the GABA(B) receptors. Outcomes and side effects at 12 months were recorded. Nineteen patients (mean age: 52.6 years, mean National Institute of Health Stroke Scale (NIHSS) score 21) were enrolled. Cooling was achieved in all patients. The mean time to reach target temperature was 11.4 ± 8.6h and the mean duration of rewarming was 4.0 ± 1.1 days. For the 10 survivors (53%), the mean duration of hypothermia and rewarming was 22.6 ± 4.9 days. Five patients underwent a hemicraniectomy. All patients presented with hypotension, bradycardia, and hematological side effects. Eight patients had pneumonia (42%). At 12 months, the mean NIHSS score was 8.3 ± 2.7, the Barthel Index was 67 ± 18, and the modified Rankin scale was 3.2 ± 0.9. This study shows the feasibility of very prolonged hypothermia beyond 3 weeks using GHB sedation in severe hemispheric infarcts.

Is hypothermia useful in malignant ischemic stroke? Current status and future perspectives

Journal of the Neurological Sciences, 2008

Background and aims: In acute stroke patients, mild and moderate hypothermia with a body temperature (T core) target of 32°C to 34°C is being tested and has shown some promising results. The feasibility of MH to control of ICP increases in patients with malignant ischemic stroke has been proven, but controversy as to its effectiveness and safety still continues. The most recent results of clinical trials and possible future applications of MH in acute stroke patients are analyzed in this review. Design, methods and material: A search in MEDLINE/PubMed was performed. The references of selected articles were investigated and the Cochrane Library searched. Articles including severe, massive, malignant or hemispheric ischemic stroke, induced hypothermia, and animal studies with focal cerebral or brain ischemic models were considered. Results: 196 patients with ischemic stroke treated with hypothermia have been reported in eleven small clinical studies, with a mild benefit of MH over the mortality rate and final outcome. Conclusions: Moderate hypothermia ameliorates ischemic injury by multiple mechanisms. Treatment of acute ischemic stroke patients is feasible, and additional studies, including randomized clinical trials, are warranted.

Hypothermia and stroke: the pathophysiological background

Pathophysiology, 2003

Hypothermia to mitigate ischemic brain tissue damage has a history of about six decades. Both in clinical and experimental studies of hypothermia, two principal arbitrary patterns of core temperature lowering have been defined: mild (32-35 • C) and moderate hypothermia (30-33 • C). The neuroprotective effectiveness of postischemic hypothermia is typically viewed with skepticism because of conflicting experimental data. The questions to be resolved include the: (i) postischemic delay; (ii) depth; and (iii) duration of hypothermia. However, more recent experimental data have revealed that a protected reduction in brain temperature can provide sustained behavioral and histological neuroprotection, especially when thermoregulatory responses are suppressed by sedation or anesthesia. Conversely, brief or very mild hypothermia may only delay neuronal damage. Accordingly, protracted hypothermia of 32-34 • C may be beneficial following acute cerebral ischemia. But the pathophysiological mechanism of this protection remains yet unclear. Although reduction of metabolism could explain protection by deep hypothermia, it does not explain the robust protection connected with mild hypothermia. A thorough understanding of the experimental data of postischemic hypothermia would lead to a more selective and effective clinical therapy. For this reason, we here summarize recent experimental data on the application of hypothermia in cerebral ischemia, discuss problems to be solved in the experimental field, and try to draw parallels to therapeutic potentials and limitations.