Reduction In Brain Temperature Research Articles

Phase-difference and spectroscopic imaging for monitoring of human brain temperature during cooling

Decrease of the human brain temperature was induced by intranasal cooling. The main purpose of this study was to compare the two magnetic resonance methods for monitoring brain temperature changes during cooling: phase-difference and magnetic resonance spectroscopic imaging (MRSI) with high spatial resolution. Ten healthy volunteers were measured. Selective brain cooling was performed through nasal cavities using saline-cooled balloon catheters. MRSI was based on a radiofrequency spoiled gradient echo sequence. The spectral information was encoded by incrementing the echo time of the subsequent eight image records. Reconstructed voxel size was 1×1×5 mm3. Relative brain temperature was computed from the positions of water spectral lines. Phase maps were obtained from the first image record of the MRSI sequence. Mild hypothermia was achieved in 15–20 min. Mean brain temperature reduction varied in the interval <−3.0; −0.6>°C and <−2.7; −0.7>°C as measured by the MRSI and phase-difference methods, respectively. Very good correlation was found in all locations between the temperatures measured by both techniques except in the frontal lobe. Measurements in the transversal slices were more robust to the movement artifacts than those in the sagittal planes. Good agreement was found between the MRSI and phase-difference techniques.

Local Brain Temperature Reduction Through Intranasal Cooling With the RhinoChill Device: Preliminary Safety Data in Brain-Injured Patients

Local Brain Temperature Reduction Through Intranasal Cooling With the RhinoChill Device: Preliminary Safety Data in Brain-Injured Patients

Letter by Albin Regarding Article, “Local Brain Temperature Reduction via Intranasal Cooling With the RhinoChill Device: Preliminary Safety Data in Brain-Injured Patients”

To the Editor: Abu-Chebel and coworkers are to be congratulated for reporting on a hypothermic technique that produces selective brain cooling in humans using perfluorocarbon-oxygen suffused through the nasopharyngeal pathway with apparently minimal side effects.1 From a historical perspective, 47 years ago, Brown and colleagues produced a striking brain–body temperature gradient in canines by naso-oral perfusion and head immersion using cold saline as the hypothermic medium.2 Within 20 to 38 minutes (median time, 32 minutes), intracerebral temperatures <20°C were reached with right atrial temperatures stabilizing between 30°C and 33°C. Termination of perfusion allowed for rewarming of the brain from the warmer body core without …

Response to Letter by Albin Regarding Article, “Local Brain Temperature Reduction via Intranasal Cooling With the RhinoChill Device: Preliminary Safety Data in Brain-Injured Patients”

Response: We thank Dr Albin for his interest in our study. Dr Albin took issue with a statement in our article that whole-body (core) cooling must begin before cerebral cooling can begin. He correctly stated that there are ways around this, for example, “differential extracorporeal hypothermia perfusion.” We agree and we would like to clarify that in our article, we made the statement in the context of a discussion on the most widely used techniques/devices for inducing hypothermia, that is, external/surface cooling devices and endovascular devices, all of which cool the core first. Due to its ease of use and portability, the RhinoChill device may be used in the field maximizing hypothermia's potential neuroprotective effects, something that is not possible with extracorporeal perfusion. Dr Albin also commented on the lack of animal safety and efficacy data. We did mention 1 …

Selective brain cooling in the febrile sheep

Selective brain cooling (SBC) occurs in artiodactyls (e.g. sheep, goats, pigs) when arterial blood supplying the brain is cooled as it flows through the carotid rete. In certain physiological conditions, cooled venous blood from the nose can be diverted to the cavernous sinus within which the carotid rete is situated. This enables heat exchange from carotid to venous blood causing subsequent reduction of brain temperature (Tb) below core body temperature (Tc) signifying SBC. Sympathetic nerves play a major role in regulating SBC.

Local Brain Temperature Reduction Through Intranasal Cooling With the RhinoChill Device

Hypothermia is neuroprotectant but currently available cooling methods are laborious, invasive, and require whole-body cooling. There is a need for less invasive cooling of the brain. This study was conducted to assess the safety and efficacy of temperature reduction of the RhinoChill transnasal cooling device. We conducted a prospective single-arm safety and feasibility study of intubated patients for whom temperature reduction was indicated. After rhinoscopy, the device was activated for 1 hour. Brain, tympanic, and core temperatures along with vital signs and laboratory studies were recorded. All general and device-related adverse events were collected for the entire hypothermia treatment. A total of 15 patients (mean age, 50.3 ± 17.1 years) were enrolled. Brain injury was caused by intracerebral hemorrhage, trauma, and ischemic stroke in equal numbers. Hypothermia was induced for fever control in 9 patients and for neuroprotection/intracranial pressure control in 6. Core temperature, brain temperature, and tympanic temperature were reduced an average of 1.1 ± 0.6°C (range, 0.3 to 2.1°C), 1.4 ± 0.4°C (range, 0.8 to 5.1°C), and 2.2 ± 2°C (range, 0.5 to 6.5°C), respectively. Only 2 patients did not achieve the goal of ≥1°C decrease in temperature. Brain temperature, tympanic temperature, and core temperature reductions were similar between the afebrile and febrile patients. There were no unanticipated adverse events and only 1 anticipated adverse event: hypertension in 1 subject that led to discontinuation of cooling after 30 minutes. There were no nasal complications. Intranasal cooling with the RhinoChill device appears safe and effectively lowers brain and core temperatures. Further study is warranted to assess the efficacy of hypothermia through intranasal cooling for brain-injured patients.

Novel intracranial brain cooling catheter to mitigate brain injuries

BackgroundThe neuroprotective effects of cooling the spinal cord in a sheep model by a self-contained intrathecal catheter was reported recently by the authors. The present study was designed to determine...

Counterpoint: Humans do not demonstrate selective brain cooling during hyperthermia

Selective brain cooling is an attractive idea for protection of the central nervous system against fatigue ([17][1]) and potentially cellular damage. Several factors influence fatigue, but brain temperature appears to be of utmost importance for hyperthermia-induced fatigue during prolonged exercise

Post‐traumatic seizure susceptibility is attenuated by hypothermia therapy

Traumatic brain injury (TBI) is a major risk factor for the subsequent development of epilepsy. Currently, chronic seizures after brain injury are often poorly controlled by available antiepileptic drugs. Hypothermia treatment, a modest reduction in brain temperature, reduces inflammation, activates pro-survival signaling pathways, and improves cognitive outcome after TBI. Given the well-known effect of therapeutic hypothermia to ameliorate pathological changes in the brain after TBI, we hypothesized that hypothermia therapy may attenuate the development of post-traumatic epilepsy and some of the pathomechanisms that underlie seizure formation. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury, and were then maintained at normothermic or moderate hypothermic temperatures for 4 h. At 12 weeks after recovery, seizure susceptibility was assessed by challenging the animals with pentylenetetrazole, a GABA(A) receptor antagonist. Pentylenetetrazole elicited a significant increase in seizure frequency in TBI normothermic animals as compared with sham surgery animals and this was significantly reduced in TBI hypothermic animals. Early hypothermia treatment did not rescue chronic dentate hilar neuronal loss nor did it improve loss of doublecortin-labeled cells in the dentate gyrus post-seizures. However, mossy fiber sprouting was significantly attenuated by hypothermia therapy. These findings demonstrate that reductions in seizure susceptibility after TBI are improved with post-traumatic hypothermia and provide a new therapeutic avenue for the treatment of post-traumatic epilepsy.

Therapeutic hypothermia for newborn infants with hypoxic–ischaemic encephalopathy

Peripartum asphyxia complicated by moderate or severe hypoxic-ischaemic encephalopathy is a devastating global health issue. A therapeutic 'window of opportunity' exists after resuscitation of the asphyxiated newborn and before the delayed phase of neuronal loss. Animal studies demonstrated that neuronal injury following hypoxia-ischaemia can be prevented or reduced by a mild reduction in brain temperature. Human infant pilot studies confirmed feasibility, without major adverse effects. Randomised trials and systematic reviews comprising term infants with moderate or severe encephalopathy and peripartum asphyxia have established the neuroprotective benefit of therapeutic hypothermia. Hypothermia reduces mortality or major disability to 18 months of age, as well as cerebral palsy, and neuromotor and cognitive delay. Importantly, mortality is reduced without any increase in major neurodevelopmental disability in survivors, and with only minor adverse effects. The evidence supports therapeutic hypothermia when used within strict protocols in tertiary centres to improve the outcome for term and near-term newborns with moderate or severe hypoxic-ischaemic encephalopathy. Equally strict protocols in non-tertiary nurseries will enable earlier initiation of hypothermia under guidance of the regional neonatal intensive care unit and transport team.

Comparison of neuroprotective effects in ischemic rats with different hypothermia procedures

Objective: The neuroprotective effect of hypothermia has long been recognized. The aim of this work was to compare the neuroprotective effect of systemic, head and local vascular cooling hypothermia procedures in ischemic rats.Methods: Stroke in Sprague–Dawley rats (n=64) was induced by a 3 hour right middle cerebral artery occlusion using an intraluminal filament. Before reperfusion, ischemic animals (n=16 in each group) received hypothermia (systemic, head or local vascular) or no treatment. Brain temperature, infarction volume (n=8 in each group) and functional outcome (n=8 in each group) were compared.Results: Regarding brain temperature, vascular cooling significantly reduced the temperature of ischemic territory in cortex from 37·2 ± 0·1 to 33·4 ± 0·4°C and in striatum from 37·5 ± 0·2 to 33·9 ± 0·4°C within 5 minutes. This hypothermic condition remained for up to 60 minutes after reperfusion. However, systemic cooling reduced brain temperature at a similar level for six times longer. In the head cooling group, the target temperature was reached in 15 minutes, but returned to normal within 5 minutes. Although all hypothermia procedures induced neuroprotection, ischemic rats with vascular cooling showed significantly (p<0·001) better neuroprotection with 10·7 ± 2·6% infarction, compared to 54·2 ± 1·9% (no treatment), 37·1 ± 1·0% (head cooling) and 29·1 ± 3·4% (systemic cooling). Significantly (p<0·001) better effects on motor function were also detected in vascular cooling groups at 14 and 28 days.Conclusion: Vascular cooling appears to be the most effective in reducing infarct volume and improving functional outcome than the other two hypothermia methods in a rat ischemia/reperfusion model.

Regional cooling for reducing brain temperature and intracranial pressure

To evaluate the effectiveness of regional cooling for reducing brain temperature (BrTe) and intracranial pressure (ICP) in patients where conventional clinical treatment has failed. Regional cooling was carried out using ice bags covering the area of the craniectomy (regional method) in 23 patients. The BrTe and ICP were determined using a fiber optic sensor. Thirteen patients (56.52%) were female. The ages ranged from 16 to 83 years (mean of 48.9). The mean APACHE II score was 25 points (11-35). The patients were submitted, on mean, to 61.7 hours (20-96) of regional cooling. There was a significant reduction in mean BrTe (p<0.0001--from 37.1 degrees C to 35.2 degrees C) and mean ICP (p=0.0001--from 28 mmHg to 13 mmHg). Our results suggest that mild brain hypothermia induced by regional cooling was effective in the control of ICP in patients who had previously undergone decompressive craniectomy.

Hipotermia intravascular inducida en el manejo de la hipertensión intracraneana en insuficiencia hepática aguda: Caso clínico

Acute liver failure has a mortality rate in excess of 80%. Most deaths are attributed to brain edema with intracranial hypertension and herniation of structures, where ammonium plays a major role in its generation. We report an 18 year-old female with a fulminant hepatic failure caused by virus A infection. The patient developed a profound sopor and required mechanical ventilation. A CT scan showed the presence of brain edema and intracranial hypertension. A Raudemic catheter was inserted to measure intracranial pressure and brain temperature. Intracranial hypertension became refractory and intravascular hypothermia was started, reducing brain temperature to 33 degrees C. Seventy two hours later, a liver transplantation was performed. After testing graft perfusion, rewarming was started, completing 122 hours of hypothermia at 33 degrees C. The patient was discharged in good conditions after 69 days of hospitalization.

Forced convective head cooling device reduces human cross-sectional brain temperature measured by magnetic resonance: a non-randomized healthy volunteer pilot study

This pilot study in five healthy adult humans forms the pre-clinical assessment of the effect of a forced convective head cooling device on intracranial temperature, measured non-invasively by magnetic resonance spectroscopy (MRS). After a 10 min baseline with no cooling, subjects received 30 min of head cooling followed by 30 min of head and neck cooling via a hood and neck collar delivering 14.5 degrees C air at 42.5 litre s(-1). Over baseline and at the end of both cooling periods, MRS was performed, using chemical shift imaging, to measure brain temperature simultaneously across a single slice of brain at the level of the basal ganglia. Oesophageal temperature was measured continuously using a fluoroptic thermometer. MRS brain temperature was calculated for baseline and the last 10 min of each cooling period. The net brain temperature reduction with head cooling was 0.45 degrees C (SD 0.23 degrees C, P=0.01, 95% CI 0.17-0.74 degrees C) and with head and neck cooling was 0.37 degrees C (SD 0.30 degrees C, P=0.049, 95% CI 0.00-0.74 degrees C). The equivalent net reductions in oesophageal temperature were 0.16 degrees C (SD 0.04 degrees C) and 0.36 degrees C (SD 0.12 degrees C). Baseline-corrected brain temperature gradients from outer through intermediate to core voxels were not significant for either head cooling (P=0.43) or head and neck cooling (P=0.07), indicating that there was not a significant reduction in cooling with progressive depth into the brain. Convective head cooling reduced MRS brain temperature and core brain was cooled.

Reduction of magnetic resonance spectroscopy brain temperature by convective head cooling in healthy humans

This pilot study assessed the effect of forced convective head and neck cooling on brain temperature, measured by magnetic resonance spectroscopy (MRS), in five healthy adult humans (three males). Following a 10-minute baseline, subjects received 30 minutes head cooling followed by 30 minutes head and neck cooling. The cooling device delivered air at 11°C and 15 m/s through a hood and separate neck collar made of a double layer of nylon sheeting, the inner layer pierced with holes. Subjects wore a windproof waistcoat taped round the base of their neck and were wrapped in blankets from the base of the neck down. Bilateral foot warming with chemical hot packs was used to encourage heat loss in the presence of normothermia. MRS temperature data were collected at the level of the basal ganglia over the baseline and the last 10 minutes of each cooling intervention. MRS detects naturally occurring brain metabolites and interpretation of the relative frequencies of N-acetyl aspartate and water allows estimation of tissue temperature in 1 cm3 voxels. For assessment of regional cooling, voxels lying within the region formed by joining the tips of the lateral ventricles were defined as 'core', voxels within approximately one voxel of the brain surface were defined as 'outer', and all other voxels were defined as 'intermediate'. The oesophageal temperature was measured continuously with a fluoroptic thermometer. The mean baseline-corrected MRS brain temperature over all voxels reduced by -0.45°C (SD 0.23°C, P = 0.01, 5% CI -0.74 to -0.17°C) with head cooling and -0.37°C (SD 0.30°C, P = 0.049, 95% CI -0.74 to 0.00°C) with head and neck cooling. Head cooling reduced the mean baseline-corrected MRS brain temperature in core voxels in all subjects. The formal test for gradient was not significant (P = 0.43; 95% CI -0.15 to 0.29°C). Head and neck cooling reduced the temperature in core voxels in three subjects; the test for gradient was not significant (P = 0.07; 95% CI -0.03 to 0.58°C). The mean baseline-corrected oesophageal temperature reductions for the last 10 minutes of each intervention were -0.16°C (SD 0.04°C) with head cooling and -0.36°C (SD 0.12°C) with head and neck cooling. Forced convective head cooling reduced the MRS brain temperature at an equivalent of 1.35°C per hour in healthy subjects, and the reduction was apparent across the brain.

Enhanced upper respiratory tract airflow and head fanning reduce brain temperature in brain-injured, mechanically ventilated patients: a randomized, crossover, factorial trial

Heat loss from the upper airways and through the skull are physiological mechanisms of brain cooling which have not been fully explored clinically. This randomized, crossover, factorial trial in 12 brain-injured, orally intubated patients investigated the effect of enhanced nasal airflow (high flow unhumidified air with 20 p.p.m. nitric oxide gas) and bilateral head fanning on frontal lobe brain temperature and selective brain cooling. After a 30 min baseline, each patient received the four possible combinations of the interventions--airflow, fanning, both together, no intervention--in randomized order. Each combination was delivered for 30 min and followed by a 30 min washout, the last 5 min of which provided the baseline for the next intervention. The difference in mean brain temperature over the last 5 min of the preceding washout minus the mean over the last 5 min of intervention, was 0.15 degrees C with nasal airflow (P=0.001, 95% CI 0.06-0.23 degrees C) and 0.26 degrees C with head fanning (P<0.001, 95% CI 0.17-0.34 degrees C). The estimate of the combined effect of airflow and fanning on brain temperature was 0.41 degrees C. Selective brain cooling did not occur. Physiologically, this study demonstrates that heat loss through the upper airways and through the skull can reduce parenchymal brain temperature in brain-injured humans and the onset of temperature reduction is rapid. Clinically, in ischaemic stroke, a temperature decrease of 0.27 degrees C may reduce the relative risk of poor outcome by 10-20%. Head fanning may have the potential to achieve a temperature decrease of this order.

Extracorporeal venovenous cooling for induction of mild hypothermia in human-sized swine*

Several cooling methods have been investigated for inducing mild hypothermia (33-36 degrees C) after cardiac arrest, brain trauma, or stroke. To achieve its best effect, therapeutic hypothermia has to be applied very early after the ischemic insult; otherwise, the beneficial effect would be diminished or even abrogated. The aim of this study was to investigate the effectiveness and safety of extracorporeal venovenous cooling as compared with endovascular cooling. Swine were cooled in a randomized crossover design from 38 degrees C to 33 degrees C brain temperature, either with extracorporeal venovenous cooling or with endovascular cooling. Laboratory investigation. Six swine of human size (85 to 101 kg). Swine were randomly cooled with the first device, and after achieving the target brain temperature, re-warmed via the same technique and with heating lamps to baseline temperature. Then the other catheter was inserted and cooling was performed with the second device. Brain, pulmonary artery and tympanic temperature, blood pressure, and heart rate were recorded continuously. Laboratory samples, including free hemoglobin, were taken at predefined temperature points during cooling. Comparisons between and within (baseline vs. 33 degrees C) the treatment groups were performed with the paired Student's t-test. The time needed to reduce brain temperature from 38.0 degrees C to 33.0 degrees C was 41 +/- 17 mins with venovenous cooling and 126 +/- 37 mins with endovascular cooling (p = .001). Heart rate and mean arterial pressure decreased moderately during cooling and were significantly lower at 33 degrees C than at baseline in both groups, without differences between groups. None of the swine developed significant hemolysis, arrhythmias, or bleeding. Extracorporeal venovenous cooling was an effective and safe method to rapidly induce therapeutic mild hypothermia in human-sized swine. It seems to be promising for further application and investigation in patients.

BRAIN TEMPERATURE CALCULATIONS FOR SWINE USING EXPERIMENTAL MEASUREMENTS OF CEREBRAL BLOOD FLOW

In this study, numerical simulations are performed to analyze the brain temperature reduction in swine during selective head cooling, whole body cooling or while the animals experience ischemia. Brain temperature is calculated using a time dependent thermal model that incorporates available experimental measurements of the rectal temperature, the cerebral blood flow and the cerebral metabolic rate of oxygen consumption.The calculated temperature distribution is validated against the in vivo temperature measurements recorded during the different experiments. These comparisons help to better understand the relations between brain temperature, blood flow and metabolic activity, which are essential to successfully apply hypothermia in the treatment of brain injury.The calculations presented here reproduce the temperature behavior observed in all the experiments considered. It is observed that the arterial temperature and the cerebral metabolic rate are important parameters that affect the deep tissue temperature. It is also concluded that the accurate knowledge of parameters such as the skin and bone thermal conductivity are necessary for effective modeling.

Dauer epileptischer Anfälle während selektiver pharyngealer Hirnkühlung / Duration of induced seizures during selective pharyngeal brain cooling

Whole body hypothermia can be used to treat the injured brain (e.g. after hypoxic events). Side effects include hemodynamic instability, coagulopathy and infection. Because of these side effects it appears reasonable to cool the brain selectively (selective brain cooling, SBC) without changing the core temperature. A new animal model was used to demonstrate SBC from the pharynx and to examine effects of SBC on the duration of pharmacologically induced seizure activity. Sprague-Dawley rats (n=18, 12 successful experiments) were sedated and mechanically ventilated. Invasive blood pressure monitoring was instituted and blood gases were drawn to evaluate the arterial blood gas status. Electrical brain activity was recorded using a microneedle in the extracellular compartment of the rat brain cortex. Cooled water was circulated through a small tubing into and out of the pharynx of the animals. The cortical as well as the rectal temperature were recorded. After the injection of a single dose of bicuculline (1 mg/kg i.v.) per animal the duration of the induced seizure activity was measured and compared with the temperature prior to the induction of seizure activity. The cortical blood flow (CBF) was detected using intra tissue Doppler signals in the rat cortex in the same location as the EP-study. The influence of a brain temperature reduction between 36.5 degrees to 31.5 degrees C on the seizure duration was examined. There was a positive correlation between the seizure duration and the cortical temperature (r=0.64). Also the CBF was increased during seizure activity (p=0.02) and the increase correlated weakly with cortical temperature (r=0.18). The core temperature remained in the normothermic range (36.9+/-0.7 degrees C) Conclusion: The duration of induced seizures correlates with local brain temperature. In the future further studies should examine the efficiency of induced (selective) brain cooling to treat prolonged seizure activity.

Resuscitative hypothermia after cardiac arrest in adults

Resuscitative hypothermia after cardiac arrest in adults