Induction Of Therapeutic Hypothermia Research Articles

Droperidol lowers the shivering threshold in rabbits.

Perioperative shivering is common and can occur as a result of hypothermia or changes in the threshold of thermoregulation. Droperidol usage for anesthesia is currently limited to its sedative and antiemetic effects. We investigated the effects of high and low doses of droperidol on the shivering threshold in rabbits. Forty-two male Japanese white rabbits were anesthetized with isoflurane and randomly assigned to the control, high-dose, or low-dose group. Rabbits in the high-dose group received a 5mg/kg droperidol bolus followed by continuous infusion at 5mg/kg/h, those in the low-dose group received a 0.5mg/kg droperidol bolus, and those in the control group received the same volume of saline as the high-dose group. Body temperature was reduced at a rate of 2-3°C/h, and the shivering threshold was defined as the subject's core temperature (°C) at the onset of shivering. The shivering thresholds in the control, high-dose, and low-dose groups were 38.1°C ± 1.1°C, 36.7°C ± 1.2°C, and 36.9°C ± 1.0°C, respectively. The shivering thresholds were significantly lower in the high-dose and low-dose groups than in the control group (P < 0.01). The thresholds were comparable between the high-dose and low-dose groups. Droperidol in high and low doses effectively reduced the shivering threshold in rabbits. Droperidol has been used in low doses as an antiemetic. Low doses of droperidol can reduce the incidence of shivering perioperatively and during the induction of therapeutic hypothermia.

Targeting focal ischemic and hemorrhagic stroke neuroprotection: Current prospects for local hypothermia.

Therapeutic hypothermia (TH) has applications dating back millennia. In modern history, however, TH saw its importation into medical practice where investigations have demonstrated that TH is efficacious in ischemic insults, notably cardiac arrest and hypoxic-ischemic encephalopathy. As well, studies have been undertaken to investigate whether TH can provide benefit in focal stroke (i.e., focal ischemia and intracerebral hemorrhage). However, clinical studies have encountered various challenges with induction and maintenance of post-stroke TH. Most clinical studies have attempted to use body-wide cooling protocols, commonly hindered by side effects that can worsen post-stroke outcomes. Some of the complications and difficulties with systemic TH can be circumvented by using local hypothermia (LH) methods. Additional advantages include the potential for lower target temperatures to be achieved and faster TH induction rates with LH. This systematic review summarizes the body of clinical and preclinical LH focal stroke studies and raises key points to consider for future LH research. We conclude with an overview of LH neuroprotective mechanisms and a comparison of LH mechanisms with those observed with systemic TH. Overall, whereas many LH studies have been conducted preclinically in the context of focal ischemia, insufficient work has been done in intracerebral hemorrhage. Furthermore, key translational studies have yet to be done in either stroke subtype (e.g., varied models and time-to-treat, studies considering aged animals or animals with co-morbidities). Few clinical LH investigations have been performed and the optimal LH parameters to achieve neuroprotection are unknown.

THERAPEUTIC HYPOTERMIA IN THE COMPLEX TREATMENT OF POST-RESUSCITATION DISEASE

This article is about of two cases of successful cardiopulmonary resuscitation (CPR) and using therapeutic hypothermia as a important part of treatment of post-resuscitation disease. Current evidence supports that induction of therapeutic hypothermia in selected patients after cardiac arrest can improve neurological outcome. It is hoped that by summarizing the current state of knowledge on the subject and highlighting issues on clinical management will enable more patients to benefit from the therapy.

A Comprehensive Update of Current Anesthesia Perspectives on Therapeutic Hypothermia.

Normal thermal regulation is a result of the integration of afferent sensory, central control, and efferent responses to temperature change. Therapeutic hypothermia (TH) is a technique utilized during surgery to protect vital organs from ischemia; however, in doing so leads to other physiological changes. Indications for inducing hypothermia have been described for neuroprotection, coronary artery bypass graft (CABG) surgery, surgical repair of thoracoabdominal and intracranial aneurysms, pulmonary thromboendarterectomy, and arterial switch operations in neonates. Initially it was thought that induced hypothermia worked exclusively by a temperature-dependent reduction in metabolism causing a decreased demand for oxygen and glucose. Induced hypothermia exerts its neuroprotective effects through multiple underlying mechanisms including preservation of the integrity and survival of neurons through a reduction of extracellular levels of excitatory neurotransmitters dopamine and glutamate, therefore reducing central nervous system hyperexcitability. Risks of hypothermia include increased infection risk, altered drug pharmacokinetics, and systemic cardiovascular changes. Indications for TH include ischemia-inducing surgeries and diseases. Two commonly used methods are used to induce TH, surface cooling and endovascular cooling. Core body temperature monitoring is essential during induction of TH and rewarming, with central venous temperature as the gold standard. The aim of this review is to highlight current literature discussing perioperative considerations of TH including risks, benefits, indications, methods, and monitoring.

Significant Cytokine mRNA Expression Changes Immediately after Initiation of Cardiopulmonary Resuscitation.

Introduction The purpose of this study was to evaluate immediate immunological changes following cardiopulmonary resuscitation (CPR). mRNA expression levels of selected immunomodulatory cytokines in out-of-hospital cardiac arrest (OHCA) survivors were detected and correlated to clinical parameter. Methods OHCA survivors with sustained unconsciousness after return of spontaneous circulation (ROSC) were included. PAXgene whole blood samples were drawn immediately after initiation of CPR and subsequently after 6 h, 12 h, 24 h, 48 h, and 72 h. TNF-alpha, IL-8, IL-10, and IL-1ra mRNA levels were quantified by RT-qPCR and compared to multiple organ failure, 30-day survival, and the induction of therapeutic hypothermia (TH). Results 25 patients (63 ± 15 years) were enrolled presenting a characteristic time-dependent cytokine profile in the early postresuscitation period. High initial TNF-alpha and IL-8 mRNA levels were followed by a significant decrease. IL-1ra mRNA levels significantly increased beginning after 6 h. Nonsurvivors showed significantly higher IL-8 mRNA levels immediately after CPR. TH induced significantly higher IL-1ra mRNA levels compared to normothermia. Conclusion Significant mRNA cytokine expression changes are already detectable immediately after initiation of CPR. These expressional changes are significantly different depending on 30-day survival. TH seems to attenuate proinflammatory immune reaction by a significant increase of IL-1ra mRNA levels. This trial is registered with DRKS00012940.

Therapeutic hypothermia during CPR did not improve survival to discharge in out-of-hospital cardiac arrest.

Source Citation Bernard SA, Smith K, Finn J, et al. Induction of therapeutic hypothermia during out-of-hospital cardiac arrest using a rapid infusion of cold saline: the RINSE trial (Rapid Infusion...

Morphological characteristics of heart after induction of therapeutic hypothermia and the introduction of mesenchymal stromal cells in therapy of experimental myocardial infarction.

Background. Diseases of cardiovascular system still occupy the first place among the causes of death and disability of population. Currently the new methods for stimulating the regeneration of damaged myocardium are actively developing. It is assumed that the transplantation of mesenchymal stromal cells (MSCs) can promote the replacement of necrotic areas by newly formed cardiomyocytes and stimulate angiogenesis in the ischemic area. In the last decade the method of application of therapeutic hypothermia in order to protect heart and brain cells from oxygen starvation in acute coronary and cerebral insufficiency has become widespread. Objective. The purpose of this work was to study the morphological features of necrosis development and cardiac remodeling in myocardial infarction in rats after the induction of therapeutic hypothermia and injection of MSCs. Methods. The experiment was carried out in 60 white outbred male rats. All the animals were divided into 4 groups after modeling of infarction by ligation of a. coronaries sinistra: 1 – control (myocardial infarction), 2 – myocardial infarction and induction of hypothermia for 60 min, 3 – myocardial infarction and once intravenous injection of allogeneic placental MSCs (concentration 1.2×106cells/ml), 4 – myocardial infarction and combined use of hypothermia and injection of MSCs. Heart tissue for morphological studies was taken on 7th, 14th and 30th days of experiment. Morphometric studies of myocardial infarction area was performed using BioVision 4,0 program. The relative area of connective tissue, the vessel relative area and the number of vessels were assessed. Results. In group 4, in contrast to other groups with myocardial infarction, on 7th day of the experiment the reparative processes in myocardium prevailed over destructive ones. Reparation of myocardium was manifested in the stimulation of angiogenesis, the development of collateral circulation and also in the recovery of contractile elements of cardiomyocytes of the peri-infarction zone. The data of morphometric study in group 4 showed the smallest area of connective-tissue scar on the 30th day of the experiment. Conclusion. Transplantation of MSCs, and especially, combination of therapeutic hypothermia and MSC transplantation lead to a significant improvement in vascularization in the infarcted zone and reduces the connective tissue scar square surface.

Induction of therapeutic hypothermia during out-of-hospital cardiac arrest

Induction of therapeutic hypothermia during out-of-hospital cardiac arrest

Repeated diffusion weighted imaging in comatose cardiac arrest patients with therapeutic hypothermia

BackgroundThe aim of this study was to evaluate the changing pattern and prognostic values of diffusion-weighted imaging (DWI) at two time points in cardiac arrest patients treated with therapeutic hypothermia. MethodsTwenty two patients with cardiac arrest who underwent two DWI studies were enrolled in the retrospective study. The first DWI was performed after the induction of therapeutic hypothermia (median 6.0h) and was repeated between 48h and 168h (second DWI, median 74h). Apparent diffusion coefficient (ADC) values were measured in the predefined brain regions, and qualitative analysis was also performed. Good neurologic outcomes were defined as Cerebral Performance Category (CPC) scores of 1 and 2. ResultsThe ADC value tended to increase over time except the cortical regions of the poor outcome group (N=10). In the comparisons of receiver operating characteristic (ROC) curve to predict poor outcome using ADC value, postcentral cortex in the second DWI has a better association with neurological outcome (p=0.001, area under the curve (AUC)=0.996 for second DWI, AUC=0.571 for first DWI). In the same analysis using qualitative score, precentral cortex, postcentral cortex, parietal lobe, occipital lobe, caudate and putamen in the second DWI have a better association with neurological outcome. ConclusionsThe changing pattern of ADC values after cardiac arrest is different according to anatomic region and neurologic status. The DWI after 48h has a better association with neurological outcome of cardiac arrest patients in both quantitative and qualitative analysis.

Abstract 317: Effect of Intra-arrest Induction of Therapeutic Hypothermia on Out-of-Hospital Cardiac Arrest

Introduction: The resuscitation literature has recently suggested that the prehospital initiation of therapeutic hypothermia following successful resuscitation does not alter outcomes among patients who suffer sudden out-of-hospital cardiac arrest (OOHCA). We sought to assess the impact of earlier, intra-arrest induction of therapeutic hypothermia on OOHCA survival. Methodology: Out-of-hospital cardiac arrest data from two consecutive twelve-month periods was analyzed: August 1, 2009 - July 31, 2010 (Phase I), August 1, 2010 - July 31, 2011 (Phase II). In Phase I, paramedics in this urban system transported OOHCA patient to participating Cardiac Arrest Centers where the use of therapeutic hypothermia had been incorporated to the standard post-resuscitation care pathway. In Phase II, paramedics initiated hypothermia during the initial resuscitation effort through the rapid infusion of large-volume, ice-cold saline. Consistent with the Utstein definitions, analyses utilized only those cases which were bystander witnessed and of cardiac etiology. Results: There were 1,487 and 850 bystander witnessed arrests of cardiac etiology in the two phases. Patient and arrest characteristics for the two groups did not differ with respect to age, gender, race, response time, bystander witnessed status, or the frequency of bystander CPR. Return of spontaneous circulation (ROSC), sustained ROSC, survival to hospital admission and survival to hospital discharge did not differ significantly from Phase I to Phase II: 40.82% vs 39.59% (p=.54), 31.10% vs 31.17% (p=0.58), 27.15% vs 24.88% (p=0.27), and 6.62% vs 6.19% (p=0.41). In addition, among those survivors for whom neurologic status is known, the intra-arrest initiation of therapeutic hypothermia did not significantly change the proportion of survivors considered neurologically intact (76.47% vs 70.37%, all p=0.59). Conclusions: The intra-arrest initiation of therapeutic hypothermia did not alter outcomes among OOHCA patients, demonstrating neither harm nor benefit. Whether this is due to a lack of continuation of hypothermia following hospital admission or a true lack of benefit requires further collaborative work between the prehospital and hospital communities.

Nefopam and meperidine are infra-additive on the shivering threshold in humans.

Induction of therapeutic hypothermia is often complicated by shivering. Nefopam, a nonsedative benzoxazocine analgesic, reduces the shivering threshold (triggering core temperature) with minimal side effects. Consequently, nefopam is an attractive drug for inducing therapeutic hypothermia. However, nefopam alone is insufficient and thus needs to be combined with another drug. Meperidine also reduces the shivering threshold. We therefore determined whether the combination of nefopam and meperidine is additive, infra-additive, or synergistic on the shivering threshold. Ten volunteers were each studied on 4 randomly assigned days. In random order, they were given the following treatments: (1) control, no drug; (2) nefopam to a target concentration of 0.1 μg/mL; (3) meperidine to a target concentration of 0.1 μg/mL; and (4) both nefopam and meperidine at target concentrations of 0.1 μg/mL each. Lactated Ringer's solution at 4°C was infused to decrease core temperature while mean skin temperature was kept near 30.5°C. The core temperature that increased oxygen consumption >25% defined the shivering threshold. Nefopam reduced the shivering thresholds by 0.7°C ± 0.3°C compared with no drug. Meperidine reduced the shivering thresholds by 0.4°C ± 0.3°C compared with no drug. When combined, the shivering threshold decreased by only 0.6°C ± 0.4°C, which was about half what would have been expected based on the individual effects of each drug (P < 0.001). The effect of combined nefopam and meperidine on the shivering threshold was thus infra-additive. The combination of nefopam and meperidine should be avoided for induction of therapeutic hypothermia. Better options would be combinations of drugs that are at least additive or even synergistic.

Effects of adenosine monophosphate on induction of therapeutic hypothermia and neuronal damage after cardiopulmonary resuscitation in rats

BackgroundAnimal studies and pathophysiological considerations suggest that therapeutic hypothermia after cardiopulmonary resuscitation is the more effective the earlier it is induced. Therefore this study is sought to examine whether pharmacological facilitated hypothermia by administration of 5′-adenosine monophosphate (AMP) is neuroprotective in a rat model of cardiac arrest (CA) and resuscitation. MethodsSixty-one rats were subjected to CA. After 6min of ventricular fibrillation advanced cardiac life support was started. After successful return of spontaneous circulation (ROSC, n=40), animals were randomized either to placebo group (n=14) or AMP group (800mg/kg body weight, n=14). Animals were kept at an ambient temperature of 18°C for 12h after ROSC and core body temperature was measured using a telemetry temperature probe. Neuronal damage was analyzed by counting Nissl-positive (i.e. viable) neurons and TUNEL-positive (i.e. apoptotic) cells in coronal brain sections 7 days after ROSC. Functional status evaluated on days 1, 3 and 7 after ROSC by a tape removal test. ResultsTime until core body temperature dropped to <34.0°C was 31min [28; 45] in AMP-treated animals and 125min [90; 180] in the control group (p=0.003). Survival until 7 days after ROSC was comparable in both groups. Also number of Nissl-positive cells (AMP: 1 [1; 7] vs. placebo: 2 [1; 3] per 100 pixel; p=0.66) and TUNEL-positive cells (AMP: 56 [44; 72] vs. placebo: 53 [41; 67] per 100 pixel; p=0.70) did not differ. Neither did AMP affect functional neurological outcome up to 7 days after ROSC. Mean arterial pressure 20min after ROSC was 49 [45; 55] mmHg in the AMP group in comparison to 91 [83; 95] mmHg in the control group (p<0.001). ConclusionAlthough application of AMP reduced the time to reach a core body temperature of <34°C neither survival was improved nor neuronal damage attenuated. Reason for this is probably induction of marked hypotension as an adverse reaction to AMP treatment.

Utilization of rapid infusion system with cold saline in the induction of therapeutic hypothermia

To examine the cooling effectiveness of a rapid infusion system (RIS) during induction of therapeutic hypothermia. This laboratory study simulated the effect of three fluid delivery methods: rapid dripping without any other equipment (control); RIS; pressure bag. Cold energy loss (℃ × min) was calculated as: (temperature of the proximal thermoprobe--temperature of the distal thermoprobe) × (total infusion time). Infusion time was significantly shorter and cold energy loss significantly lower in the RIS group than in the two other groups. RIS preserves the cold energy of fluid more effectively than pressure bag or control. RIS allows for rapid infusion at a constant pressure and can be easily applied in an emergency setting.

Hypothermie thérapeutique en traumatologie crânienne grave

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients.

Pharmacologically Induced Hypothermia with WIN55,212-2 and Extracorporeal Life Support after Cardiac Arrest as a Preservation Strategy for Heart Transplantation

Purpose To investigate the hypothesis that induction of therapeutic hypothermia with cannabinoid receptor agonist WIN55,212-2 and extracorporeal life support (ECLS) after cardiac arrest is an effective heart preservation strategy. Methods and Materials Ventricular fibrillation (VF) was induced in male Wistar rats. After 10 min of untreated VF, venoarterial ECLS was instituted and rats were randomized to three groups of ten: normothermia, therapeutic hypothermia (32°C) and pharmacological hypothermia by WIN55,212 intravenous infusion (1 mg/kg/h). After 120 minutes heterotopic heart transplantation was performed in syngeneic donors using a working heart model. After 24 hours left ventricular (LV) systolic and diastolic functions were evaluated at different preloads using a conductance catheter. Results WIN55,212-2 led to a significantly better recovery of the slope of the LV end-systolic pressure volume relationship (Ees) and Preload recruitable stroke work (PRSW) than hypothermia and normothermia: as percent of baseline 87+12 vs 54+9 vs 39+11 and 88+11 vs 59+10 vs 33+8 respectively (p.01). LV stiffness expressed by end-diastolic pressure volume relationship (EDPVR) was significantly lower after WIN55,212-2 administration (p Conclusions Pharmacologically induced hypohermia with WIN55,212-2 during ECLS improve myocardial protection through activation of the pro-survival kinase Akt and ERK and could be an organ preservation strategy after cardiac arrest.

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Introduction: Therapeutic hypothermia (TH) is now widely used worldwide in the management of post-cardiac arrest encephalopathy. Due to the use of limited ICU resources, there has also been a search for predictors with the required specificity as early as possible after cardiac arrest so futile treatment can be terminated; however, the reliability of predictors that can identify TH candidates remains unknown. Hypothesis: We can develop a prediction rule to predict the neurological outcome of TH patients; clinical predictors are obtained before patients underwent TH. Methods: We performed a single-center retrospective cohort study over 12 years (2001-2012). Inclusion criteria were out-of-hospital cardiac arrest of cardiac origin, successful return of spontaneous circulation and induction of therapeutic hypothermia. Data were abstracted from the charts included demographics, characteristics of cardiac arrest, clinical variables on hospital arrival and subsequent interventions. Outcome measure was neurological status at hospital discharge (cerebral-performance category [CPC]). Backward elimination of non-significant variables was used to identify the important predictors in a stepwise logistic regression model. The beta-coefficient of each of the predictors was used to build a score. We tested the discriminative power of prediction scores using receiver-operator characteristic (ROC) curve analysis with the area under the curve (AUC). Results: Of 72 eligible patients, 44 (61.1%) had favorable outcome (CPC1-2) and 28 (38.9%) had poor outcome (CPC3-5). Four variables were identified as important predictors of poor outcome (age >= 60 yrs, cardiac arrest in the home, absence of pupillary reflex on hospital arrival and CPR duration >= 20 min). The integer score of 2 was assigned for age >= 60 yrs and absence of pupillary reflex, and the integer score of 1 assigned for cardiac arrest in the home and CPR duration >= 20 min, weighted by beta-coefficient values. ROC analysis showed an AUC was 0.92 (95% confidence interval [CI], 0.87-0.98) and identified a prediction score >= 5 as an optimal cut-off point, with a sensitivity of 0.61 (95% CI, 0.50-0.64), specificity of 0.98 (95% CI, 0.91-1.00) and positive predictive value of 0.94 (95% CI, 0.78-0.99), negative predictive value of 0.80 (95% CI, 0.74-0.81) for predicting poor outcome. Conclusions: Our prediction rule was valid to identify futility of TH in patients after cardiac arrest. This tool requires external validation study.

Abstract 19470: Presence of Anemia at Induction of Therapeutic Hypothermia as a Predictor of Neurological Outcome in Cardiac Arrest Survivors

Introduction: Therapeutic hypothermia (TH) has become an accepted practice to improve neurological outcome in survivors of cardiac arrest. Co-morbid factors that may impact neurological outcome in such patients are not well understood. Anemia has been shown to have a prognostic value in a wide variety of diseases. We investigated the effect of hematocrit on neurological outcome in cardiac arrest survivors undergoing TH. Methods: A retrospective analysis was performed on 196 consecutive cardiac arrest survivors who underwent TH with endovascular cooling in the cardiac intensive care unit at a tertiary care center between January 2007 and April 2012. Patients were divided into two groups based on anemia as per their hematocrit (Hct) value at induction of TH (Hct≤36 and Hct&gt;36). The primary endpoint was measured using the Pittsburgh cerebral performance category (CPC) scale and patients were assessed for a good (CPC 1 and 2) or poor (CPC 3-5) neurological outcome prior to discharge from hospital. Results: Of the 196 patients, 130 patients (66 %) had a Hct ≤ 36 and 66 patients (34 %) had a Hct &gt; 36. Forty two (32%) patients with Hct ≤ 36 and 25 patients (38%) with Hct&gt;36 had a good neurologic outcome (P=0.50) (Figure 1) . On multivariable analysis, initial/presenting rhythm (OR: 8.752; 95 % CI 2.60-29.40, P&lt; 0.001) and time to return of spontaneous circulation (OR: 0.942; 95 % CI 0.90-0.99, P=0.02) were independent predictors of neurologic outcome. Conclusion: Presence of anemia at induction of TH is not associated with neurological outcome in cardiac arrest survivors.

Abstract 235: The Glasgow Motor Score Before Induction of Therapeutic Hypothermia Is an Independent Predictor of Good Outcome in Cardiac Arrest

Background: With the recent introduction of therapeutic hypothermia, the application of sedation becomes necessary in cardiac arrest patients. Therefore early prediction of neurologic outcome in these patients is challenging problem. Nevertheless neurologic examination including the Glasgow coma scale should be basis for decision making. So, we investigated the usefulness of the Glasgow motor score before induction of therapeutic hypothermia for outcome prediction in survivors of cardiac arrest treated with therapeutic hypothermia. Methods: Between March 2009 and July 2011, patients who successfully resuscitated from cardiac arrest and treated with mild therapeutic hypothermia were included in this study. Data were collected by local post-cardiac arrest care registry. Neurologic outcome was assessed with Cerebral Performance Category (CPC) at hospital discharge and good neurologic outcome was defined CPC score of 1 and 2. Results: Total 89 patients were treated with therapeutic hypothermia during study period. Among these patients, 39 were good neurologic outcome and 50 were poor neurologic outcome. The value for prediction of good outcome was as follows: sensitivity 53.8%, specificity 96.0%, PPV 91.3%, NPV 72.7% and AUC 0.749. Conclusions: The results of this study show that the Glasgow motor score &gt; 1 before induction of therapeutic hypothermia is an independent predictor of good outcome in patients treated with therapeutic hypothermia. Thus, the patients with the Glasgow motor score &gt; 1 soon after ROSC should be treated aggressively including therapeutic hypothermia.

Abstract 92: Prehospital Activation of an Emergency Department Cardiac Arrest Response Team Improves ROSC and Hypothermia Utilization

BACKGROUND: The induction of therapeutic hypothermia (TH) in comatose survivors of out-of-hospital cardiac arrest (OOHCA) improves survival and neurologic recovery outcomes. Despite results from high-quality randomized control trials and international consensus statements, TH utilization rates remain low. Pre-hospital activation of specialized care teams improves outcomes at trauma, ST-segment elevation myocardial infarction, and stroke receiving centers. We hypothesized that pre-hospital activation of a cardiac arrest response team would augment Emergency Department resuscitation resources and thus improve TH utilization and outcomes for out-of-hospital cardiac arrest patients. METHODS: An emergency department cardiac arrest response team (eCART) comprised of a cardiology fellow, pharmacist, respiratory therapist, hospital chaplain, and a therapeutic hypothermia expert (“Dr. COOL”) was created at an urban academic hospital. The eCART team was immediately activated by emergency department staff after receiving EMS radio notification of an arrest transport. We compared outcomes in consecutive adult OOHCA patients during the 8 month period before (PRE) and after (POST) instantiation of the eCART activation system. RESULTS: Clinical characteristics of patients in the PRE (n = 46) and POST (n = 63) intervention periods were similar. The CART activation system was utilized for 97% of OOCHA cases presenting to the emergency department. Rate or return of spontaneous circulation (ROSC) was significantly higher during the POST vs. PRE period (37% vs. 17%, p &lt; 0.05). Initiation of TH in eligible patients was also significantly higher during the POST vs. PRE period (100% vs. 80%, p &lt; 0.05). No difference in the time from ROSC to TH goal temperature &lt; 34 degrees Celsius (201 min +/- 125 vs. 212 min +/- 81, p &gt;0.05) or cardiac catheterization laboratory utilization (43% vs. 50%, p &gt; 0.05) was noted between POST and PRE periods respectively. CONCLUSION: Pre-hospital activation of an eCART team is associated with improvements in ROSC rate and tended to increase TH utilization. These results suggest that rapid deployment of a specialized cardiac arrest response team to the emergency department may be an effective strategy for improving OOHCA resuscitation.

Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated. Hypoxic-ischemic brain injury and traumatic brain injury both trigger a series of biochemical and molecular events that cause additional brain insult. Induction of therapeutic hypothermia seems to ameliorate the molecular cascade that culminates in neuronal damage. Hypothermia attenuates the toxicity produced by the initial injury that would normally produce reactive oxygen species, neurotransmitters, inflammatory mediators, and apoptosis. Experiments have been performed on various depths and levels of hypothermia to explore neuroprotection. This review summarizes what is currently known about the beneficial effects of therapeutic hypothermia in experimental models of neonatal hypoxic-ischemic brain injury and traumatic brain injury, and explores the molecular mechanisms that could become the targets of novel therapies. In addition, this review summarizes the clinical implications of therapeutic hypothermia in newborn hypoxic-ischemic encephalopathy and adult traumatic brain injury.