Moderate Therapeutic Hypothermia Research Articles

The Effect of Therapeutic Hypothermia on Prognosis in Patients Receiving Continuous Renal Replacement Therapy.

Continuous renal replacement therapy (CRRT) is a commonly used therapeutic modality in the pediatric intensive care unit (PICU) for the treatment of severe acute kidney injury, as well as for addressing metabolic abnormalities, fluid-electrolyte imbalances, and acid-base disorders. According to reports, therapeutic hypothermia treatment has demonstrated the ability to decrease cellular metabolism, oxygen consumption, formation of free radicals, cell death, and inflammatory signals. The study encompassed all individuals who underwent CRRT at both Manisa City Hospital and Manisa Celal Bayar University Hospital throughout the period from February 2021 to November 2022. A total of 14 patients who received CRRT were subjected to a warming procedure utilizing an external blanket and an external heater attached to the CRRT venous return line, resulting in the attainment of a body temperature exceeding 36°C. Therapeutic hypothermia was implemented on 12 patients to maintain their body temperature within the range of 32-35°C. The study population exhibited a median age of 24.5 months, with males comprising 61.5% of the sample. A therapeutic hypothermia treatment was administered to a cohort of 12 patients. The patients who had therapeutic hypothermia exhibited a significantly reduced vasoactive-inotropic score (p = 0.038). Patients who did not receive therapeutic hypothermia exhibited a prolonged need for mechanical ventilation (p = 0.020). The duration of stay in the PICU for patients who underwent therapeutic hypothermia was shown to be considerably shorter compared to those who did not receive therapeutic hypothermia (p = 0.047). The potential efficacy of moderate therapeutic hypothermia appears promising, particularly in the context of patients who are receiving CRRT for severe sepsis and acute respiratory distress syndrome. This is attributed to the anti-inflammatory properties and hypometabolic effects associated with this intervention. To the best of our current understanding, this study represents the initial investigation showcasing the effectiveness of combining therapeutic hypothermia with CRRT in the pediatric population.

The Protective Role and Mechanism of Mild Therapeutic Hypothermia Protection on Brain Cells.

Moderate therapeutic hypothermia is protective against several cellular stressors. However, the mechanisms behind this protection are not entirely known. In the current investigation, we investigated that therapeutic hypothermia at 33°C administered following peroxide-induced oxidative stress might protect human oligodendroglioma cells using an in vitro model. Tert-butyl peroxide treatment for one hour significantly increased cell apoptosis and suppressed cell viability. In the range of 50-1000 M tert-butyl peroxide, this cell death was dose-dependent. MTT assay and cell apoptosis assay were applied to analyze cell viability/death at 24 hours after peroxide-induced stress. Therapeutic hypothermia at 33°C delivered for two hours after peroxide exposure significantly increased cell viability and suppressed cell death. Even 15 minutes after peroxide washout when delayed hypothermia was used, this protection was still apparent. Three FDA-approved antioxidants (Tempol, EUK134, and Edaravone at 100 M) were added immediately after tert-butyl peroxide, followed by hypothermia treatment. These three antioxidants greatly increased cell viability and cell apoptosis. RT-qPCR was applied to determine the effects of hypothermia treatment on the expression of caspase-3 and -8 as well as tumor necrosis factor-alpha (TNF-α). Therapeutic hypothermia significantly downregulated these three factors. Overall, these findings confirmed that hypothermia and antioxidants quenching reactive oxygen species may lower mitochondrial oxidative stress and/or apoptotic pathways. Further investigation are needed to investigate the role of hypothermia in other cell models.

Moderate systemic therapeutic hypothermia is insufficient to protect blood-spinal cord barrier in spinal cord injury.

Blood-spinal cord barrier (BSCB) disruption is a pivotal event in spinal cord injury (SCI) that aggravates secondary injury but has no specific treatment. Previous reports have shown that systemic therapeutic hypothermia (TH) can protect the blood-brain barrier after brain injury. To verify whether a similar effect exists on the BSCB after SCI, moderate systemic TH at 32°C was induced for 4 h on the mice with contusion-SCI. In vivo two-photon microscopy was utilized to dynamically monitor the BSCB leakage 1 h after SCI, combined with immunohistochemistry to detect BSCB leakage at 1 and 4 h after SCI. The BSCB leakage was not different between the normothermia (NT) and TH groups at both the in vivo and postmortem levels. The expression of endothelial tight junctions was not significantly different between the NT and TH groups 4 h after SCI, as detected by capillary western blotting. The structural damage of the BSCB was examined with immunofluorescence, but the occurrence of junctional gaps was not changed by TH 4 h after SCI. Our results have shown that moderate systemic TH induced for 4 h does not have a protective effect on the disrupted BSCB in early SCI. This treatment method has a low value and is not recommended for BSCB disruption therapy in early SCI.

Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest

Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures. To determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest. Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020. Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours. The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit. Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P = .004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively. In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference. ClinicalTrials.gov Identifier: NCT02011568.

Therapeutic Hypothermia Reduces Peritoneal Dialysis Induced Myocardial Blood Flow Heterogeneity and Arrhythmia.

Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH.Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model.Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (−14%, p = 0.03) at rest and after stress (−14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave.Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

Current guidelines from the International Liaison Committee on Resuscitation (ILCOR) recommends that all patients with coma after successful resuscitation from cardiac arrest undergo targeted temperature management with moderate therapeutic hypothermia. However, some studies showed that these interventions had inconclusive effects, especially in patients who are presenting in cardiac arrest with non-shockable rhythms. These patients historically have poorer neurological outcomes compared to patients who present in cardiac arrest with shockable rhythms. With an equal number of studies showing benefit, harm, and no effect, and an increasing number of patients presenting in cardiac arrest with nonshockable rhythms, this study aims to identify whether or not therapeutic hypothermia provides benefit to this patient population. The objective of this study was to assess if therapeutic hypothermia at 33°C versus targeted normothermia improved neurological outcomes at 90 days in coma patients, specifically in those who were successfully resuscitated from nonshockable rhythms.

Abstract WP117: Therapeutic Hypothermia in Patients With Malignant Ischemic Stroke and Hemicraniectomy: A Systematic Review and Meta-Analysis

Introduction: Numerous animal models have demonstrated the efficacy of mild to moderate therapeutic hypothermia (TH) in reducing cerebral edema and conferring protection after ischemic injury. We investigated whether TH had a beneficial effect in stroke patients after hemicraniectomy (HC). Methods: A MEDLINE systematic review was performed. Inclusion criteria included: ≥10 patients with acute malignant ischemic stroke having undergone HC, studies published in full in the English language, and studies reporting on clinical outcome and complications. Results: Thirty-four studies met our search criteria. Six studies with 302 patients with malignant ischemic stroke (TH: n=146, HC alone: n=156) were included. Age, and initial median NIHSS were comparable between the two groups. All studies used systemic TH; four utilized combined TH (venous endovascular and surface cooling), while one study used systemic surface and one used systemic venous endovascular TH. TH was initiated within 37.2 hours (range 24-42 hours) from onset for a median target temperature of TH was 33.6°C (range 33-35°C) and maintained for a median of 72 hours (range 48-96 hours). Target temperature was achieved within 4.5 hours (range 2-36 hours). All studies used rewarming (3 active rewarming). Clinical outcomes at follow-up were not different (follow-up modified Rankin’s 0-2; RR 1.04, 95% CI 0.60-1.80, p=0.9; Figure 1). Cardiac complications were greater in TH (RR 1.79, 95% CI 1.16-2.76, p<0.01). A suggestion of greater mortality was seen with TH (RR 1.43, 95% CI 0.97-2.10, p=0.07), and was significantly greater in studies that did not actively rewarm patients (RR 1.65, 95% CI 1.04-2.60, p<0.05). Conclusions: Clinical and functional outcomes were comparable between patients undergoing systemic TH vs. normothermia following HC despite higher complications associated with TH.

Does therapeutic hypothermia reduce mortality and improve neurological outcome in severe tbi? A systematic review study

Introduction: Traumatic Brain Injury (TBI) is the leading cause of death and permanent disability in young populations in Africa. In Tanzania, 74% of patients with TBI are due to motor traffic accidents with overall mortality of 13% with 80% occurring in ICU. Despite adequate resuscitation, severe TBI patients tend to have poor outcome which is mostly caused by secondary insult leading to neurological damage to brain. Prophylactic Therapeutic Hypothermia (TH) has shown promising outcome in treating Severe Traumatic Brain Injury (STBI). Objectives/Aims: Examine whether TH reduces mortality caused by secondary injury and improves neurological outcome. Methods: Searches involved various data bases in review: CINAHIL, MEDLINE, EMBASE, Cochrane library and Google Scholar. Data were searched using MeSH terms and Boolean operators were used. Results: A meta-analysis conducted Sichuan Hospital shows that patient treated with moderate TH has significantly less mortality in Asian population. Another study involving patients with TBI in adults using TH was associated with 19% reduction in risk of death and 22% reduction in poor neurological outcome. Discussion: It has been shown that TH reduced the risk of mortality and poor neurologic outcome in adults with TBI. 18 trials evaluating mortality as one outcome, showed that TH was associated with mortality reduction p.=0.0004 and significant reduction in poor outcome p.=0.00001. The effectiveness of TH was determined by early application of cooling (within 6hrs of injury) in the Emergency Room and continuation in the ICU. Decreased death and good neurological outcome were determined by duration of cooling, depth (32⁰C-34⁰C) and frequency of re-warming (1⁰C/4hrs). Conclusion: Hypothermia reduces ICP, decrease cerebral metabolic demand, decrease disruption of blood brain barrier and inhibit inflammatory cascades that leads to reperfusion injury.

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

BackgroundModerate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated.MethodsWe performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed.ResultsFrom January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P=0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, −1.9 percentage points; 95% CI, −8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups.ConclusionsAmong patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia. (Funded by the French Ministry of Health and others; HYPERION ClinicalTrials.gov number, NCT01994772.)

Impact of Education on Hypothermia Delivery during Neonatal Transport

Background: Moderate therapeutic hypothermia (TH) initiated within 6 h of life reduces adverse neurodevelopmental outcomes in infants after perinatal hypoxic ischaemic insult. For infants born in non-tertiary centres, TH may be initiated manually en route to a neonatal intensive care unit (NICU). However, both over- and undercooling is reported with this strategy, precluding some infants from the benefits of TH. Objectives: To evaluate the impact of a region-wide educational programme on the safety and efficacy of manual cooling administered by the Wellington Neonatal Transport Service (NeTS). Methods: Clinical records of infants with hypoxic ischaemic encephalopathy (HIE) retrieved by the Wellington NeTS for TH between January 2012 and June 2017 were reviewed retrospectively. Temperature outcomes of infants retrieved before and after the education programme were compared. Results: A total of 101 infants were cooled manually by Wellington NeTS for TH during the study period. Education and training significantly reduced the rate of overcooling to ≤32.0°C (4/43 [9%] vs. 0/58, p = 0.02). However, there was no difference in the proportion of infants who achieved target rectal temperature within 6 h of life (29/43 [65%] vs. 35/58 [60%], p = 0.57). Conclusions: Introduction of a region-wide educational programme may have improved the safety of manual cooling during neonatal transport but it had a negligible impact on its efficacy. The use of servo-controlled cooling during transport should therefore be considered to improve access to the optimal neuroprotective benefits of TH for outborn infants with HIE.

Effect of rewarming in oxygenation and respiratory condition after neonatal exposure to moderate therapeutic hypothermia

BackgroundTo assess changes in clinical condition and oxygenation in neonates after rewarming following moderate therapeutic hypothermia (MTH) for neonatal encephalopathy. MethodsRetrospective study of 28 neonates receiving MTH in a tertiary neonatal intensive care unit in Israel. We compared pre-and 24 h post-rewarming arterial oxygen saturation (SaO2) as measured by the blood gases analyzer, pulse-oximetry saturation (SpO2), and cardio-respiratory condition. ResultsThe SpO2 declined from 96.9% (±2.9) before rewarming to 95.2% (±2.6) after rewarming (p < 0.001). Twelve neonates (42.9%) had clinical respiratory impairment (needing higher respiratory support or had new onset desaturations). In 16 neonates (57.1%) with no change in respiratory support after rewarming, SpO2 decreased from 98.3 ± 1.9% to 95.6 ± 3.0% (p < 0.001) and SaO2 decreased from 97.1 ± 1.7% to 96.0 ± 2.3% (p = 0.002). The mean SpO2 decrease was greater than mean SaO2 decrease (2.63 ± 1.8 and 1.1 ± 1.3 respectively, p = 0.021). ConclusionNeonates who underwent MTH showed reduction in oxygenation after rewarming either by decreasing SpO2 or increasing FiO2 requirements. The SpO2 decline was larger than the SaO2 decline. We suggest careful monitoring of neonates after rewarming.

Benefit Absence of Therapeutic Moderate Hypothermia in the Treatment of Cardiac Arrest: A Systematic Review and Meta-Analysis

Background: Hyperthermia is frequent after cardiac arrest, and is associated with poor vital and neurological prognosis. In the last few years there have been published some studies that show benefits with moderate hypothermia in these patients, and other studies haven´t shown such benefits. Aim: To collect all clinical trials evaluating the utility of moderate therapeutic hypothermia in survivors of a cardiac arrest. Method: A comprehensive search of clinical trials evaluating moderate hypothermia in patients who survive a cardiac arrest was carried out. The mortality and quality of life of the survivors were evaluated. The quality of the included studies, the publication bias and the heterogeneity of the results were evaluated. Results: there is no significant reduction in mortality (RR 0.97, 95% CI 0.93-1.01) or increase in quality of life (RR 1.07, 95% CI 0.94-1.21) of the patients undergoing moderate hypothermia versus those not treated with that. There are no different results in patients with cardiac arrest with defibrillable and non – defibrillable rhythms, with the different used cooling methods, or even with the induction of intra – cardiac arrest hypothermia. The mortality of these patients is high, and there are no significant differences in relation to the age or sex of them. Conclusion: In patients who survive a cardiac arrest, the induction of moderate hypothermia is not recommended.

Complement interaction with cells undergoing immunogenic cell death

Therapeutic hypothermia has been shown to attenuate myocardial cell death due to ischemia/reperfusion injury. However, cellular mechanisms of cooling remain to be elucidated. Especially during reperfusion, mitochondrial dysfunction contributes to cell death by releasing apoptosis inductors. The aim of the present study was to investigate the effects of moderate therapeutic hypothermia (33.5 °C) on mitochondrial mediated apoptosis in ischemia/reperfusion-injured cardiomyocytes.Ischemic injury was simulated by oxygen-glucose deprivation for 6 h in glucose/serum-free medium at 0.2% O2 in mouse atrial HL-1 cardiomyocytes. Simulation of reperfusion was achieved by restoration of nutrients in complete supplemented medium and incubation at 21% O2. Early application of therapeutic hypothermia, cooling during the oxygen-glucose deprivation phase, was initiated after 3 h of oxygen-glucose deprivation and maintained for 24 h. Mitochondrial membrane integrity was assessed by cytochrome c and AIF protein releases. Furthermore, mitochondria were stained with MitoTracker Red and intra-cellular cytochrome c localization was visualized by immunofluorescence staining. Moreover, anti-apoptotic Bcl-2 and Hsp70 as well as phagophore promoting LC3-II protein expressions were analyzed by Western-blot analysis.Therapeutic hypothermia initiated during oxygen-glucose deprivation significantly reduced mitochondrial release of cytochrome c and AIF in cardiomyocytes during reperfusion. Secondly, anti-apoptotic Bcl-2/Bax ratio and Hsp70 protein expressions were significantly upregulated due to hypothermia, indicating an inhibition of both caspase-dependent and -independent apoptosis. Furthermore, cardiomyocytes treated with therapeutic hypothermia showed increased LC3-II protein levels associated with the mitochondria during the first 3 h of reperfusion, indicating the initiation of phagophores formation and sequestration of presumably damaged mitochondrion.Early application of therapeutic hypothermia effectively inhibited cardiomyocyte cell death due to oxygen-glucose deprivation/reperfusion-induced injury via multiple pathways. As hypothermia preserved mitochondrial membrane integrity, which resulted in reduced cytochrome c and AIF releases, induction of both caspase-dependent and -independent apoptosis was minimized. Secondly, cooling attenuated intrinsic apoptosis via Hsp70 upregulation and increasing anti-apoptotic Bcl-2/Bax ratio. Moreover, therapeutic hypothermia promoted mitochondrial associated LC3-II during the early phase of reperfusion, possibly leading to the sequestration and degradation of damaged mitochondrion to attenuate the activation of cell death.

Moderate therapeutic hypothermia induces multimodal protective effects in oxygen-glucose deprivation/reperfusion injured cardiomyocytes

ObjectiveTherapeutic hypothermia has been shown to attenuate myocardial cell death due to ischemia/reperfusion injury. However, cellular mechanisms of cooling remain to be elucidated. Especially during reperfusion, mitochondrial dysfunction contributes to cell death by releasing apoptosis inductors. The aim of the present study was to investigate the effects of moderate therapeutic hypothermia (33.5°C) on mitochondrial mediated apoptosis in ischemia/reperfusion-injured cardiomyocytes. MethodsIschemic injury was simulated by oxygen-glucose deprivation for 6h in glucose/serum-free medium at 0.2% O2 in mouse atrial HL-1 cardiomyocytes. Simulation of reperfusion was achieved by restoration of nutrients in complete supplemented medium and incubation at 21% O2. Early application of therapeutic hypothermia, cooling during the oxygen-glucose deprivation phase, was initiated after 3h of oxygen-glucose deprivation and maintained for 24h. Mitochondrial membrane integrity was assessed by cytochrome c and AIF protein releases. Furthermore, mitochondria were stained with MitoTracker Red and intra-cellular cytochrome c localization was visualized by immunofluorescence staining. Moreover, anti-apoptotic Bcl-2 and Hsp70 as well as phagophore promoting LC3-II protein expressions were analyzed by Western-blot analysis. ResultsTherapeutic hypothermia initiated during oxygen-glucose deprivation significantly reduced mitochondrial release of cytochrome c and AIF in cardiomyocytes during reperfusion. Secondly, anti-apoptotic Bcl-2/Bax ratio and Hsp70 protein expressions were significantly upregulated due to hypothermia, indicating an inhibition of both caspase-dependent and -independent apoptosis. Furthermore, cardiomyocytes treated with therapeutic hypothermia showed increased LC3-II protein levels associated with the mitochondria during the first 3h of reperfusion, indicating the initiation of phagophores formation and sequestration of presumably damaged mitochondrion. ConclusionEarly application of therapeutic hypothermia effectively inhibited cardiomyocyte cell death due to oxygen-glucose deprivation/reperfusion-induced injury via multiple pathways. As hypothermia preserved mitochondrial membrane integrity, which resulted in reduced cytochrome c and AIF releases, induction of both caspase-dependent and -independent apoptosis was minimized. Secondly, cooling attenuated intrinsic apoptosis via Hsp70 upregulation and increasing anti-apoptotic Bcl-2/Bax ratio. Moreover, therapeutic hypothermia promoted mitochondrial associated LC3-II during the early phase of reperfusion, possibly leading to the sequestration and degradation of damaged mitochondrion to attenuate the activation of cell death.

Decompressive Craniectomy in a Patient with Severe Traumatic Brain Injury during Mild Therapeutic Hypothermia

Mild Therapeutic Hypothermia (MTH) and decompressive craniectomy are therapeutic measures used for the treatment of intracranial hypertension (ICHT) refractory to medical treatment and cerebrospinal fluid drainage. One of the side effects of MTH is the increased risk of coagulopathy, thus the performance of neurosurgical procedures in these cases is very controversial.We present the case of a patient with traumatic brain injury and ICHT refractory to medical treatment, in which moderate therapeutic hypothermia was initiated. After a transient improvement, the patient presented ICHT again, requiring a decompressive craniotomy while keeping the patient in moderate hypothermia. Due to the history of traumatic brain injury and the use of MTH, we decided on the use of viscoelastic tests as goal-directed therapy to assess haemostasis prior to surgery.

Insufficient Humidification of Respiratory Gases in Patients Who Are Undergoing Therapeutic Hypothermia at a Paediatric and Adult Intensive Care Unit.

For cooled newborn infants, humidifier settings for normothermic condition provide excessive gas humidity because absolute humidity at saturation is temperature-dependent. To assess humidification of respiratory gases in patients who underwent moderate therapeutic hypothermia at a paediatric/adult intensive care unit, 6 patients were studied over 9 times. Three humidifier settings, 37-default (chamber-outlet, 37°C; Y-piece, 40°C), 33.5-theoretical (chamber-outlet, 33.5°C; Y-piece, 36.5°C), and 33.5-adjusted (optimised setting to achieve saturated vapour at 33.5°C using feedback from a thermohygrometer), were tested. Y-piece gas temperature/humidity and the incidence of high (>40.6 mg/L) and low (<32.9 mg/L) humidity relative to the target level (36.6 mg/L) were assessed. Y-piece gas humidity was 32.0 (26.8–37.3), 22.7 (16.9–28.6), and 36.9 (35.5–38.3) mg/L {mean (95% confidence interval)} for 37-default setting, 33.5-theoretical setting, and 33.5-adjusted setting, respectively. High humidity was observed in 1 patient with 37-default setting, whereas low humidity was seen in 5 patients with 37-default setting and 8 patients with 33.5-theoretical setting. With 33.5-adjusted setting, inadequate Y-piece humidity was not observed. Potential risks of the default humidifier setting for insufficient respiratory gas humidification were highlighted in patients cooled at a paediatric/adult intensive care unit. Y-piece gas conditions can be controlled to the theoretically optimal level by adjusting the setting guided by Y-piece gas temperature/humidity.

Hypothermia for Increased Intracranial Pressure: Is It Dead?

Mild to moderate therapeutic hypothermia (HT) has been used to alleviate intracranial hypertension in traumatic brain injury (TBI). Its main contribution is thought to be via reduction in cerebral metabolic requirement leading both to favorable oxygen/metabolic delivery-demand ratios as well as a reduction of cerebral blood volume resulting in decreased ICP. Nevertheless, HT is a clinically complex, labor-intensive procedure with numerous potential adverse effects. Furthermore, randomized controlled trials suggest either no effect or harm. These facts challenge the role of HT in TBI. We address this challenge by posing three questions that relate to the overarching value of controlling ICP, the effectiveness of HT in reducing ICP, and the benefit-risk ratio of the intervention. We conclude that HT should not be used as an "early" intervention unless as a part of a clinical trial, although it may still have a role in patients with refractory intracranial hypertension.

"Cool" Topic: Feeding During Moderate Hypothermia After Intracranial Hemorrhage.

Therapeutic moderate hypothermia (MH; T core 33°C-34°C) is being studied for treatment of spontaneous intracerebral hemorrhage (ICH). Nutrition assessment begins with accurate basal metabolic rate (BMR) determination. Although early enteral nutrition (EN) is associated with improved outcomes, it is often deferred until rewarming. We sought to determine the accuracy of predictive BMR equations and the safety and tolerance of EN during MH after ICH. Patients were randomized to 72 hours of MH or normothermia (NT; T core 36°C-37°C). Harris-Benedict (BMR-HB) and Penn-State equation (BMR-PS) calculations were compared with indirect calorimetry (IC) at day (D) 0 and D1-3. Patients with MH received trophic semi-elemental gastric EN. Occurrences of feeding intolerance, gastrointestinal (GI)-related adverse events, and ventilator-associated pneumonia (VAP) were analyzed with a double-sided matched pairs t test. Thirteen patients with ICH participated (6 MH, 7 NT). Mean time to initiate EN: 29.9 (MH) vs 18.4 (NT) hours ( P = .046). Average daily EN calories received D0-3: 398 (MH) vs 1006 (NT) ( P < .01). Three patients with MH experienced high gastric residuals prior to prokinetic agents, 1 had mild ileus, and 1 patient with NT vomited. No GI-related adverse events were reported. One patient with MH and 1 patient with NT had VAP. Two patients with MH received IC, and from D0 to D1-3, BMR-HB remained stable (1331 kcal), BMR-PS decreased (1511 vs 1145 kcal, P = .5), and IC decreased (1413 vs 985 kcal, P = .2). In patients with ICH undergoing MH, resting energy expenditure is decreased and predictive equations overestimate BMR. EN is feasible, although delayed EN initiation, high gastric residuals, and less EN provision are common. Future studies should focus on EN initiation within 24 hours, advanced EN rates, and postpyloric feeds during hypothermia.

A cool approach to reducing electrode-induced trauma: Localized therapeutic hypothermia conserves residual hearing in cochlear implantation

ObjectiveThe trauma caused during cochlear implant insertion can lead to cell death and a loss of residual hair cells in the cochlea. Various therapeutic approaches have been studied to prevent cochlear implant-induced residual hearing loss with limited success. In the present study, we show the efficacy of mild to moderate therapeutic hypothermia of 4 to 6 °C applied to the cochlea in reducing residual hearing loss associated with the electrode insertion trauma. ApproachRats were randomly distributed in three groups: control contralateral cochleae, normothermic implanted cochleae and hypothermic implanted cochleae. Localized hypothermia was delivered to the middle turn of the cochlea for 20 min before and after implantation using a custom-designed probe perfused with cooled fluorocarbon. Auditory brainstem responses (ABRs) were recorded to assess the hearing function prior to and post-cochlear implantation at various time points up to 30 days. At the conclusion of the trials, inner ears were harvested for histology and cell count. The approach was extended to cadaver temporal bones to study the potential surgical approach and efficacy of our device. In this case, the hypothermia probe was placed next to the round window niche via the facial recess or a myringotomy. Main resultsA significant loss of residual hearing was observed in the normothermic implant group. Comparatively, the residual hearing in the cochleae receiving therapeutic hypothermia was significantly conserved. Histology confirmed a significant loss of outer hair cells in normothermic cochleae receiving the surgical trauma when compared to the hypothermia treated group. In human temporal bones, a controlled and effective cooling of the cochlea was achieved using our approach. SignificanceCollectively, these results suggest that therapeutic hypothermia during cochlear implantation may reduce traumatic effects of electrode insertion and improve conservation of residual hearing.

Therapeutic Hypothermia in Perinatal Asphyxia

Therapeutic hypothermia for infants with perinatal asphyxia has been studied in several randomised controlled trials. There is convincing evidence that moderate therapeutic hypothermia (33-34°C for 72 h), when initiated within 6 h after birth among term & near-term infants (≥35 weeks) with moderate to severe HIE reduces the risk of death or major disability & increases the rate of disability-free survival at 6-7 years of age.