Effect of different therapeutic time windows of mild hypothermia on neurological protection from ventricular fibrillation in rabbit models北大核心CSCD

Objective To investigate the effects of mild hypothermia on post-resuscitation neurological outcome after ventricular fibrillation (VF) in rabbits. Methods Forty-five adult New Zealand rabbits were induced VF by direct current of electricity. The rabbits were randomly(random number) divided into following groups: normothermic resuscitation group (NR), mild hypothermia pre-arrest group (HP), mild hypothermia resuscitation 30 min group (HRe30), mild hypothermia resuscitation 90 min group (HRe90), normothermic sham group (NS), and hypothermia sham group (HS). The rabbits of NR group were observed for 600 min in room temperature after restoration of spontaneous circulation (ROSC). The mild hypothermia was induced by surface cooling, and maintained for 600 min after the aimed low temperature reached. The arterial blood samples were collected for determining neuron-specific enolase (NSE) and thioredoxin (Trx) and the mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP) and left ventricular pressure raise and fall rate (dp/dtmax) were observed at 15 min before CA, and 30 min, 60 min, 120 min, 360 min and 600 min after ROSC. After the animals were sacrificed at 600 min after ROSC, the whole brain of animals was harvested and observed under light microscope to calculate the apoptotic index of the hippocampal CA1 neurons by using TUNEL method. One-way ANOVA was used to determine the statistical significance between two groups, a two-tailed value of P<0.05 was considered statistically significant. Results (1) Hemodynamically compared with normal temperature groups, HR was lower in hypothermia groups. Compared with NR, HRe30, and HRe90 group, LVEDP was higher in HP group at 30 min after ROSC(3.40.8 vs. 4.61.0, 4.10.5, 4.30.2, F=9.85, P=0.019).In HP group, the level of+dp/dtmax was higher than that in NR, HRe30 and HRe90 groups at 30 min and 120 min after ROSC. In HP group, the level of -dp/dtmax was higher than that of NR group at 30 min, 60 min, 120 min, 360 min and 600 min after ROSC. (2) Serologically compared with HP, HRe30 and HRe90 group, NSE levels were higher in NR group at 60 min, 120 min and 360 min after ROSC. Compared with NR, HRe30, and HRe90 group, Trx levels in NR group were lower at 60 min,120 min, 360 min and 600 min after ROSC. Compared with HP group, Trx levels in HRe30 and HRe90 groups were higher at 60 min, 120 min, 360 min and 600 min after ROSC. (3) Pathologically compared with NR group, histopathological changes in hippocampus CA1 area were milder found in HP, HRe30 and HRe90 groups. AI (%) was lower in HP, HRe30 and HRe90 groups than that in NR group[(62.2510.43)% vs. (20.615.02)%, (25.083.92)%, (30.337.15)%, P=0.001]. Concusions This study shows that hypothermia should be initiated as soon as possible, and especially early intra-arrest cooling appears to be significantly better than post-ROSC cooling and normothermia. © 2018 Chinese Medical Association. All Rights Reserved.     

Liquid ventilation with perfluorocarbons facilitates resumption of spontaneous circulation in a swine cardiac arrest model

BACKGROUND: Induced external hypothermia during ventricular fibrillation (VF) improves resuscitation outcomes. Our objectives were twofold (1) to determine if very rapid hypothermia could be achieved by intrapulmonary administration of cold perfluorocarbons (PFC), thereby using the lungs as a vehicle for targeted cardiopulmonary hypothermia, and (2) to determine if this improved resuscitation success. METHODS: Part 1: Nine female swine underwent static intrapulmonary instillation of cold perfluorocarbons (PFC) during electrically induced VF. Part 2: Thirty-three female swine in VF were immediately ventilated via total liquid ventilation (TLV) with pre-oxygenated cold PFC (-15 degrees C) or warm PFC (33 degrees C), while control swine received no ventilation during VF. All swine in both Parts 1 and 2 underwent VF arrest for 11 min, then defibrillation, ventilation and closed chest massage until resumption of spontaneous circulation (ROSC). The endpoint was continued spontaneous circulation for 1h without pharmacologic support. RESULTS: Static intrapulmonary instillation of cold PFC achieved rapid cardiopulmonary hypothermia; pulmonary artery (PA) temperature of 33.5+/-0.2 degrees C was achieved by 10 min. Nine of 9 achieved ROSC. Hypothermia was achieved faster using TLV: at 6 min VF, cold TLV temperature was 32.9+/-0.4 degrees C vs. cold static instillation temperature 34.3+/-0.2 degrees C. Nine of 11 cold TLV swine achieved ROSC for 1h vs. 3 of 11 control swine (p=0.03). Warm PFC also appeared to be beneficial, with a trend toward greater achievement of ROSC than control (ROSC; warm PFC 8 of 11 vs. control 3 of 11, p=0.09). CONCLUSION: Targeted cardiopulmonary intra-arrest moderate hypothermia was achieved rapidly by static intrapulmonary administration of cold PFC and more rapidly by total liquid ventilation with cold PFC; resumption of spontaneous circulation was facilitated. Warm PFC showed a trend toward facilitating ROSC.     

The association between intra-arrest therapeutic hypothermia and return of spontaneous circulation among individuals experiencing out of hospital cardiac arrest

Introduction

Therapeutic hypothermia has been shown to improve both mortality and neurologic outcomes following pulseless ventricular tachycardia and fibrillation. Animal data suggest intra-arrest induction of therapeutic hypothermia (IATH) improves frequency of return of spontaneous circulation (ROSC). Our objective was to evaluate the association between IATH and ROSC.

Methods

This was a retrospective analysis of individuals experiencing non-traumatic cardiac arrest in a large metropolitan area during a 12-month period. Six months into the study a prehospital IATH protocol was instituted whereby patients received 2000 ml of 4 °C normal saline directly after obtaining IV/IO access. The main outcome variables were prehospital ROSC, survival to admission, and to discharge. A secondary analysis was conducted to assess the relationship between the quantity of cold saline infused and the likelihood of prehospital ROSC.

Results

551 patients met inclusion criteria with all the elements available for data analysis. Rates of prehospital ROSC were 36.5% versus 26.9% (OR 1.83; 95% CI 1.19-2.81) in patients who received IATH versus normothermic resuscitation respectively. While the frequency of survival to hospital admission and discharge were increased among those receiving IATH, the differences did not reach statistical significance. The secondary analysis found a linear association between the amount of cold saline infused and the likelihood of prehospital ROSC.

Conclusion

The infusion of 4 °C normal saline during the intra-arrest period may improve rate of ROSC even at low fluid volumes. Further study is required to determine if intra-arrest cooling has a beneficial effect on rates of ROSC, mortality, and neurologic function.     

Intra-arrest selective brain cooling improves success of resuscitation in a porcine model of prolonged cardiac arrest

Aims of study

We have previously demonstrated that early intra-nasal cooling improved post-resuscitation neurological outcomes. The present study utilizing a porcine model of prolonged cardiac arrest investigated the effects of intra-nasal cooling initiated at the start of cardiopulmonary resuscitation (CPR) on resuscitation success. Our hypothesis was that rapid nasal cooling initiated during “low-flow” improves return of spontaneous resuscitation (ROSC).

Methods

In 16 domestic male pigs weighing 40 ± 3 kg, VF was electrically induced and untreated for 15 min. Animals were randomized to either head cooling or control. CPR was initiated and continued for 5 min before defibrillation was attempted. Coincident with starting CPR, the hypothermic group was cooled with a RhinoChill™ device which produces evaporative cooling in the nasal cavity of pigs. No cooling was administrated to control animals. If ROSC was not achieved after defibrillation, CPR was resumed for 1 min prior to the next defibrillation attempt until either successful resuscitation or for a total of 15 min.

Main results

Seven of eight animals in the hypothermic group (87.5%) and two of eight animals in control group (25%) (p = 0.04) were successfully resuscitated. At ROSC, brain temperature was increased from baseline by 0.3 °C in the control group, and decreased by 0.1 °C in the hypothermic animals. Pulmonary artery temperature was above baseline in both groups.

Conclusion

Intra-nasal cooling initiated at the start of CPR significantly improves the success of resuscitation in a porcine model of prolonged cardiac arrest. This may have occurred by preventing brain hyperthermia.     

Intra-arrest hypothermia during cardiac arrest: a systematic review

ABSTRACT: INTRODUCTION: Therapeutic hypothermia is largely used to protect the brain following return of spontaneous circulation (ROSC) after cardiac arrest (CA), but it is unclear whether we should start therapeutic hypothermia earlier, that is, before ROSC. METHODS: We performed a systematic search of PubMed, EMBASE, CINAHL, the Cochrane Library and Ovid/Medline databases using "arrest" OR "cardiac arrest" OR "heart arrest" AND "hypothermia" OR "therapeutic hypothermia" OR "cooling" as keywords. Only studies using intra-arrest therapeutic hypothermia (IATH) were selected for this review. Three authors independently assessed the validity of included studies and extracted data regarding characteristics of the studied cohort (animal or human) and the main outcomes related to the use of IATH: Mortality, neurological status and cardiac function (particularly, rate of ROSC). RESULTS: A total of 23 animal studies (level of evidence (LOE) 5) and five human studies, including one randomized controlled trial (LOE 1), one retrospective and one prospective controlled study (LOE 3), and two prospective studies without a control group (LOE 4), were identified. IATH improved survival and neurological outcomes when compared to normothermia and/or hypothermia after ROSC. IATH was also associated with improved ROSC rates and with improved cardiac function, including better left ventricular function, and reduced myocardial infarct size, when compared to normothermia. CONCLUSIONS: IATH improves survival and neurological outcome when compared to normothermia and/or conventional hypothermia in experimental models of CA. Clinical data on the efficacy of IATH remain limited.     

Emergency Department inter-hospital transfer for post-cardiac arrest care: Initial experience with implementation of a regional cardiac resuscitation center in the United States

Objective

The American Heart Association recently recommended regional cardiac resuscitation centers (CRCs) for post-resuscitation care following out-of-hospital cardiac arrest (OHCA). Our objective was to describe initial experience with CRC implementation.

Methods

Prospective observational study of consecutive post-resuscitation patients transferred from community Emergency Departments (EDs) to a CRC over 9 months. Transfer criteria were: OHCA, return of spontaneous circulation (ROSC), and comatose after ROSC. Incoming patients were received and stabilized in the ED of the CRC where advanced therapeutic hypothermia (TH) modalities were applied. Standardized post-resuscitation care included: ED evaluation for cardiac catheterization, TH (33–34 °C) for 24 h, 24 h/day critical care physician support, and evidence-based neurological prognostication. Prospective data collection utilized the Utstein template. The primary outcome was survival to hospital discharge with good neurological function [Cerebral Performance Category 1 or 2].

Results

Twenty-seven patients transferred from 11 different hospitals were included. The majority (21/27 [78%]) had arrest characteristics suggesting poor prognosis for survival (i.e. asystole/pulseless electrical activity initial rhythm, absence of bystander cardiopulmonary resuscitation, or an unwitnessed cardiac arrest). The median (IQR) time from transfer initiation to reaching TH target temperature was 7 (5–13) h. Ten (37%) patients survived to hospital discharge, and of these 9/10 (90% of survivors, 33% of all patients) had good neurological function.

Conclusions

Despite a high proportion of patients with cardiac arrest characteristics suggesting poor prognosis for survival, we found that one-third of CRC transfers survived with good neurological function. Further research to determine if regional CRCs improve outcomes after cardiac arrest is warranted.     

Therapeutic hypothermia post out-of-hospital cardiac arrest - more questions than answers?

Nearly a decade since the introduction of therapeutic hypothermia to the ICU for cooling out-of-hospital cardiac arrest patients, key questions remain unanswered: when should cooling be initiated, how rapidly should the patient be cooled and using which device? The Time to Target Temperature study group provides important baseline data on the striking direct relationship between body temperature and survival from out-of-hospital cardiac arrest.Patients post out-of-hospital cardiac arrest (OHCA) are common admissions to the ICU. Therapeutic hypothermia has been shown to improve both survival and neurological outcome for OHCA patients surviving to reach the ICU and now forms part of routine post-resuscitation care. The Time to Target Temperature (TTTT) study group presents key observations on the relationship between body temperature and outcome following OHCA [1], yet ultimately are we left with more questions than answers on therapeutic hypothermia?Nearly a decade ago two landmark papers fundamentally changed the practice of post-resuscitation care. The Hypothermia after Cardiac Arrest study group [2] and Bernard and colleagues [3] not only demonstrated the benefit of cooling OHCA patients but also highlighted how hugely effective the therapy was, with a number needed to treat of seven patients and six patients, respectively, for survival. Such impressive therapeutic benefit is rarely seen in medical practice, let alone in critical care medicine. A key difference between these two studies was the time from return of spontaneous circulation (ROSC) to the onset of cooling. The time to reach the target temperature (<34°C) varied greatly from immediately post ROSC to over 16 hours post ROSC and yet the therapeutic benefit of cooling was still evident. The TTTT group demonstrated that the change in body temperature during the period from ROSC to cooling initiation has a direct relationship on survival [1].Since 2002 few studies have examined the optimum method, rate of cooling and timing of initiation. Little is known about the mechanism of action of therapeutic hypothermia. Whilst animal evidence strongly suggests that early cooling, especially intra-arrest, is beneficial, few human studies have demonstrated a benefit from early cooling. Early cooling, in the prehospital or emergency department setting, has significant technical challenges and may distract from the basic principles of resuscitation. Yet emerging evidence suggests that cold reperfusion at the time of ROSC may confer greater benefit in limiting ischaemic-reperfusion injury. For cold reperfusion to occur, very rapid intra-arrest cooling would be required and some novel intranasal cooling devices have shown promising initial results [4]. Previous studies have demonstrated that most OHCA patients are relatively hypothermic in the prehospital phase, and whether initiating cooling, maintaining hypothermia or even normothermia would confer survival benefit remains unknown [5]. Although OHCA patients are naturally hypothermic in the immediate phase following collapse, they may still benefit from early therapeutic cooling.The TTTT group elegantly demonstrate that OHCA patients destined for a favourable outcome re-warm rapidly post OHCA, are warmer at cooling initiation and take longer to reach the target therapeutic temperature than OHCA patients destined for an unfavourable out-come. This observation appears contradictory to the notion that earlier, faster cooling favours a positive outcome post OHCA. No definitive explanation can yet be offered for the TTTT group finding. Unfavourable OHCA patients would appear to lack the homeostatic mechanism to regulate body temperature and appear to cool faster than favourable patients. Underlying mechanisms are postulated to include ischaemic hypothalamic damage and the inability of hypoxic mitochondria to generate heat.Clearly, the underlying cardiovascular and neurological processes involved with regulating body temperature post OHCA need further research and explanation. A better understanding of the mechanisms through which therapeutic hypothermia confers neuroprotection and survival would allow the therapy to be optimised, potentially saving many more lives. Despite nearly a decade of research since the routine introduction of therapeutic hypothermia to the ICU, a key question remains: what is the optimum time point to initiate therapeutic hypothermia post OHCA?Further prospective trials are urgently required to provide answers to the key questions surrounding cooling post OHCA, particularly to determine the optimum means, timing and rate of cooling. The TTTT group study provides a platform with important baseline data for planning this vital future research.     

Dynamic evaluation of myocardial dysfunction in rats after cardiopulmonary resuscitation Zhao Shen北大核心CSCD

Objective: To observe the dynamic changes of myocardial structure and dysfunction during post-resuscitation period in order to establish a rat mode of post-resuscitation myocardial dysfunction after cardiac arrest resulted from electric stimulation-induced ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR). Methods: A total of 40 male Sprague-Dawley (SD) rats were randomly (random number) assigned into post-resuscitation (PR) 4 h, PR 12 h, PR 24 h, PR 72 h and sham groups. VF was induced by an alternating electric current delivered to the right ventricular endocardium and untreated for 8 min. Biphasic waveform defibrillation was attempted and mechanical ventilation was synchronized after 6 min of CPR. Myocardial function was assessed with serum myocardial enzyme activity, echocardiography, mitochondrial respiratory function and histopathologic findings at different intervals. Results: Thirty-two animals were successfully resuscitated with restoration of spontaneous circulation (ROSC) in 86% (32/37) rats. Compared with sham group, severe systolic and diastolic heart failure were found at 4 h after ROSC and then gradually improved without significant difference (P > 0. 05) in ejection fraction at PR 72 h after ROSC was found, whereas thickened ventricular wall and increased myocardial performance index as well as interstitial proliferation were observed at 72 h after ROSC. Conclusions: A rat model of post-resuscitation myocardial dysfunction after cardiac arrest resulted from electric stimulation-induced VF and CPR was successfully established.     

Induction of mild hypothermia with infusion of cold (4 degrees C) fluid during ongoing experimental CPR

INTRODUCTION: Therapeutic hypothermia after resuscitation has been shown to improve the outcome regarding neurological state and to reduce mortality. The earlier hypothermia therapy is induced probably the better. We studied the induction of hypothermia with a large volume of intravenous ice-cold fluid after cardiac arrest during ongoing cardiopulmonary resuscitation (CPR). METHODS: Twenty anaesthetised piglets were subjected to 8 min of ventricular fibrillation, followed by CPR. They were randomized into two groups. The hypothermic group was given an infusion of 4 degrees C acetated Ringer's solution 30 ml/kg at an infusion rate of 1.33 ml/kg/min, starting after 1 min of CPR. The control group received the same infusion at room temperature. All pigs received a bolus dose of vasopressin after 3 min of CPR. After 9 min, defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). Core temperature and haemodynamic variables were measured at baseline and repeatedly until 180 min after ROSC. Cortical cerebral blood flow was measured, using Laser-Doppler flowmetry. RESULTS: All pigs had ROSC, except one animal in the hypothermic group. Only one animal in the hypothermic group died during the observation period. The calculated mean temperature reduction was 1.6+/-0.35 degrees C (S.D.) in the hypothermic group and 1.1+/-0.37 degrees C in the control group (p=0.009). There was no difference in cortical cerebral blood flow and haemodynamic variables. CONCLUSION: Inducing hypothermia with a cold infusion seems to be an effective method that can be started even during ongoing CPR. This method might warrant consideration for induction of early therapeutic hypothermia in cardiac arrest victims.     

Long-term mild hypothermia with extracorporeal lung and heart assist improves survival from prolonged cardiac arrest in dogs.

BACKGROUND AND PURPOSE: although normothermic extracorporeal lung and heart assist (ECLHA) improves cardiac outcomes, patients can not benefit from hypothermia-mediated brain protection. The present study evaluated the effects of long-term ECLHA with mild to moderate hypothermia (33 degrees C) in a canine model of prolonged cardiac arrest. METHODS: 15 dogs were assigned to either the hypothermic (seven dogs, 33 degrees C) or normothermic group (eight dogs, 37.5 degrees C). All dogs were induced to normothermic ventricular fibrillation (VF) for 15 min, followed by 24 h of ECLHA and 72 h of intensive care. The hypothermia group maintained core (pulmonary artery) temperature at 33 degrees C for 20 h starting from resuscitation, then were rewarmed by 28 h. Outcome evaluations included: (1) mortality; (2) catecholamine dose; (3) time to extubation; (4) necrotic myocardial mass (g); and (5) neurological deficits score (NDS). RESULTS: in the normothermic group five dogs died of cardiogenic shock and one dog succumbed to poor oxygenation. The two surviving dogs remained comatose (NDS 60.5 +/- 4.9%) with necrotic myocardial mass of 14.5 +/- 3.5 g. In the hypothermic group, one dog died from pulmonary dysfunction, the other six dogs survived. The surviving dogs showed brain damage (29.8 +/- 2.5%), but there was evidence of some brain-protective effect. The mass of necrotic myocardium was 4.2 +/- 1.3 g in the hypothermic group or 3.4 times smaller than in the normothermic group. The survival rate was significantly higher in the hypothermic than in the normothermic group (P < 0.05). The catecholamine requirement was also lower in the hypothermic than in the normothermic dogs (P < 0.05). CONCLUSIONS: Long-term mild to moderate hypothermia with ECLHA induced immediately after cardiac arrest improved survival as well as cerebral and cardiac outcomes.     

Near-infrared spectroscopy: a tool to monitor cerebral hemodynamic and metabolic changes after cardiac arrest in rats

INTRODUCTION: Cardiac arrest (CA) is associated with poor neurological outcome and is associated with a poor understanding of the cerebral hemodynamic and metabolic changes. The objective of this study was to determine the applicability of near-infrared spectroscopy (NIRS), to observe the changes in cerebral total hemoglobin (T-Hb) reflecting cerebral blood volume, oxygenation state of Hb, oxidized cytochrome oxidase (Cyto-C), and brain water content following CA. METHODS: Fourteen rats were subjected to normothermic (37.5 degrees C) or hypothermic (34 degrees C) CA induced by 8 min of asphyxiation. Animals were resuscitated with ventilation, cardiopulmonary resuscitation (CPR), and epinephrine (adrenaline). Hypothermia was induced before CA. NIRS was applied to the animal head to measure T-Hb with a wavelength of 808 nm (n = 10) and oxygenated/deoxygenated Hb, Cyto-C, and brain water content with wavelengths of 620-1120 nm (n = 4). RESULTS: There were no technical difficulties in applying NIRS to the animal, and the signals were strong and consistent. Normothermic CA caused post-resuscitation hyperemia followed by hypoperfusion determined by the level of T-Hb. Hypothermic CA blunted post-resuscitation hyperemia and resulted in more prominent post-resuscitation hypoperfusion. Both, normothermic and hypothermic CA resulted in a sharp decrease in oxygenated Hb and Cyto-C, and the level of oxygenated Hb was higher in hypothermic CA after resuscitation. There was a rapid increase in brain water signals following CA. Hypothermic CA attenuated increased water signals in normothermic CA following resuscitation. CONCLUSION: NIRS can be applied to monitor cerebral blood volume, oxygenation state of Hb, Cyto-C, and water content following CA in rats.     

The effect of mild hypothermia and induced hypertension on long term survival rate and neurological outcome after asphyxial cardiac arrest in rats

STUDY OBJECTIVE: we studied the long-term effect of a combined treatment with resuscitative mild hypothermia and induced hypertension on survival rate and neurological outcome after asphyxial cardiac arrest (CA) in rats. METHODS: 36 male Wistar rats, were randomised into three groups: Group I (n=10): anaesthetised with halothane and N(2)O/O(2) (70/30%) had vessel cannulation but no asphyxial CA; mechanical ventilation was continued to 1 h. Group II (n=13): under the same anaesthetic conditions and vessel cannulation, was subjected to asphyxial CA of 8 min, reversed by brief external heart massage and followed by mechanical ventilation to 1 h post restoration of spontaneous circulation (ROSC). Group III (n=13): received the same insult and resuscitation as described in group II, but in contrast to the previous group, a combination treatment of hypothermia (34 degrees C) and induced hypertension was started immediately after ROSC and maintained for 60 min ROSC. Survival rate and neurological deficit (ND) scores were determined before arrest, at 2 and 24 h, and each 24-h up to 4 weeks after ROSC. RESULTS: Baseline variables were the same in the three groups. Comparison of the asphyxial CA groups (groups II and III), showed an increased, although not statistically significant, survival rate at 72 h after ROSC in group III, and it became highly significant at 4 weeks after ROSC. The ND scores were the same in both asphyxial CA groups (groups II and III). CONCLUSIONS: Resuscitative mild hypothermia and induced hypertension after asphyxial CA in rats is associated with a better survival rate. This beneficial effect persisted for 4 weeks after ROSC.     

Post-cardiac arrest temperature manipulation alters early EEG bursting in rats

OBJECTIVES: Hypothermia improves outcomes after cardiac arrest (CA), while hyperthermia worsens injury. EEG recovers through periodic bursting from isoelectricity after CA, the duration of which is associated with outcome in normothermia. We quantified burst frequency to study the effect of temperature on early EEG recovery after CA. METHODS: Twenty-four rats were divided into three groups, based on 6h of hypothermia (T=33 degrees C), normothermia (T=37 degrees C), or hyperthermia (T=39 degrees C) immediately post-resuscitation from 7-min asphyxial CA. Temperature was maintained using surface cooling and re-warming. Neurological recovery was defined by 72-h neurological deficit score (NDS). RESULTS: Burst frequency was higher during the first 90min in rats treated with hypothermia (25.6+/-12.2min(-1)) and hyperthermia (22.6+/-8.3min(-1)) compared to normothermia (16.9+/-8.5min(-1)) (p<0.001). Burst frequency correlated strongly with 72-h NDS in normothermic rats (p<0.05) but not in hypothermic or hyperthermic rats. The 72-h NDS of the hypothermia group (74, 61-74; median, 25-75th percentile) was significantly higher than the normothermia (49, 47-61) and hyperthermia (43, 0-50) groups (p<0.001). CONCLUSIONS: In normothermic rats resuscitated from CA, early EEG burst frequency is strongly associated with neurological recovery. Increased bursting followed by earlier restitution of continuous EEG activity with hypothermia may represent enhanced recovery, while heightened metabolic rate and worsening secondary injury is likely in the hyperthermia group. These factors may confound use of early burst frequency for outcome prediction.     

A comparison of electrically induced cardiac arrest with cardiac arrest produced by coronary occlusion

OBJECTIVE: The present study was undertaken to compare an animal model of electrically induced VF with ischemically induced VF. In a preponderance of models of cardiac arrest and resuscitation in intact animals, ventricular fibrillation (VF) is induced by an alternating current delivered directly to the epicardium or endocardium. Yet, the applicability of such animal models has been challenged for it is not an electrical current alone but rather a current generated in the ischemic myocardium that triggers VF. Accordingly, a potentially more clinically relevant model was investigated in which spontaneous VF followed acute myocardial ischemia. METHODS: Twenty anesthetized pigs were randomized to either electrical fibrillation or myocardial ischemia following transient occlusion of the left anterior descending (LAD) coronary artery. RESULTS: VF was untreated for 7 min in both models after which mechanical ventilation and precordial compression were begun. Defibrillation was attempted after 5 min of CPR in both groups. VF appeared within 5.7+/-2.0 min of LAD occlusion. CONCLUSIONS: A significant increase in the number of post-resuscitation premature ventricular beats and recurrent VF followed ROSC and a significantly greater number of shocks was required for restoration of spontaneous circulation (ROSC) after LAD occlusion. Nevertheless, early post-resuscitation myocardial dysfunction, neurological recovery and 72 h survival were indistinguishable between the two models.     

Towards new models of cardiopulmonary resuscitation teaching: the role of practical scenario training on surf lifesavers' perceptions of resuscitation efficacy

Hypothermia during brain ischemia can improve neurological outcome. This study tested whether local cranial cooling during the low-flow state of cardiopulmonary resuscitation (CPR) could produce clinically significant cerebral cooling. Ice was applied to the heads and necks of subjects (hypothermia group) with out-of-hospital cardiac arrest (OOHCA) during CPR. Nasopharyngeal and tympanic temperatures were measured as surrogates for cerebral temperature. The rate of cranial cooling in the hypothermia group (-0.06 +/- 0.06 degrees C/min) was not significantly increased compared with a control group without ice (-0.04 +/- 0.07 degrees C/min), although older age was associated with more rapid cranial cooling. Of note, many subjects with OOHCA are already mildly hypothermic (mean cranial temperature= 35.0 +/- 1.2 degrees C) when they are first encountered in the field. This study suggests that brief cranial cooling is ineffective for rapidly lowering brain temperature. However, most cardiac arrest victims are spontaneously mildly hypothermic and preventing rewarming may provide some of the desired benefits of cerebral hypothermia.     

Application of normothermic cardiac arrest algorithms to hypothermic cardiac arrest in a canine model

BACKGROUND: International guidelines (2000) do not recommend vasopressor and antiarrhythmic medications during ventricular fibrillation (VF) with a core temperature below 30 degrees C. The efficacy of normothermic AHA algorithms using standard doses of epinephrine (EPI) (adrenaline) followed by amiodarone (AMIO) in hypothermic VF is uncertain. OBJECTIVES: To determine the effects of EPI followed by the combination of EPI/AMIO in the treatment of VF in a canine model of severe hypothermia. METHODS: An un-blinded, placebo controlled experiment using 21 mechanically ventilated dogs. Coronary perfusion pressure (CPP), temperature, and electrocardiogram (ECG) were monitored. Animals were cooled to 22 degrees C or the onset of spontaneous VF. VF was induced if necessary. Animals in the treatment group received EPI (0.01 mg/kg IV) and defibrillation. This was followed by EPI (0.01 mg/kg IV), AMIO (10 mg/kg IV) and defibrillation if there was no sustained return of spontaneous circulation (ROSC) for 15 min. RESULTS: Mean CPP in the treatment group increased after the administration of EPI/AMIO (24.7+/-13.3 mmHg to 46.6+/-7.7 mmHg, p<0.004). Cumulatively, the administration of EPI followed by EPI/AMIO achieved ROSC after defibrillation in 10 of 11 animals compared to 3 of 10 in the control group (91% versus 30%, n=21, p=0.0075). CONCLUSIONS: In this model of severe hypothermia, the use of standard 2000 protocols for VF resulted in a significant increase of CPP, and, a higher ROSC rate compared to placebo controls. This study suggests that AHA normothermic algorithms may be beneficial in severe hypothermia.     

Mild hypothermia during prolonged cardiopulmonary cerebral resuscitation increases conscious survival in dogs

OBJECTIVE: Therapeutic hypothermia during cardiac arrest and after restoration of spontaneous circulation enables intact survival after prolonged cardiopulmonary cerebral resuscitation (CPCR). The effect of cooling during CPCR is not known. We hypothesized that mild to moderate hypothermia during CPCR would increase the rate of neurologically intact survival after prolonged cardiac arrest in dogs. DESIGN: Randomized, controlled study using a clinically relevant cardiac arrest outcome model in dogs. SETTING: University research laboratory. SUBJECTS: Twenty-seven custom-bred hunting dogs (19-29 kg; three were excluded from outcome evaluation). INTERVENTIONS: Dogs were subjected to cardiac arrest no-flow of 3 mins, followed by 7 mins of basic life support and 10 mins of simulated unsuccessful advanced life support attempts. Another 20 mins of advanced life support continued with four treatments: In control group 1 (n = 7), CPCR was with normothermia; in group 2 (n = 6, 1 of 7 excluded), with moderate hypothermia via venovenous extracorporeal shunt cooling to tympanic temperature 27 degrees C; in group 3 (n = 6, 2 of 8 excluded), the same as group 2 but with mild hypothermia, that is, tympanic temperature 34 degrees C; and in group 4 (n = 5), with normothermic venovenous shunt. After 40 mins of ventricular fibrillation, reperfusion was with cardiopulmonary bypass for 4 hrs, including defibrillation to achieve spontaneous circulation. All dogs were maintained at mild hypothermia (tympanic temperature 34 degrees C) to 12 hrs. Intensive care was to 96 hrs. MEASUREMENTS AND MAIN RESULTS: Overall performance categories and neurologic deficit scores were assessed from 24 to 96 hrs. Regional and total brain histologic damage scores and extracerebral organ damage were assessed at 96 hrs.In normothermic groups 1 and 4, all 12 dogs achieved spontaneous circulation but remained comatose and (except one) died within 58 hrs with multiple organ failure. In hypothermia groups 2 and 3, all 12 dogs survived to 96 hrs without gross extracerebral organ damage (p < .0001). In group 2, all but one dog achieved overall performance category 1 (normal); four of six dogs had no neurologic deficit and normal brain histology. In group 3, all dogs achieved good functional outcome with normal or near-normal brain histology. Myocardial damage scores were worse in the normothermic groups compared with both hypothermic groups (p < .01). CONCLUSION: Mild or moderate hypothermia during prolonged CPCR in dogs preserves viability of extracerebral organs and improves outcome.     

Mild hypothermia prolongs the survival time during uncontrolled hemorrhagic shock in rats

OBJECTIVE: To test our hypothesis that during lethal uncontrolled hemorrhagic shock (UHS) in rats, mild hypothermia of either 36 or 34 degrees C would prolong the survival time in comparison with normotherma of 38 degrees C. METHODS: Twenty-four rats were lightly anesthetized with halothane and maintained spontaneous breathing. UHS was induced by blood withdrawal of 2.5 ml/100 g over 15 min, followed by 75% tail amputation. Immediately after the tail cut, the rats were randomly divided into three groups (eight rats for each); normothermic Group 1 (control, rectal temperature 38 degrees C), and mild hypothermic Groups 2 (36 degrees C) and 3 (34 degrees C). Hypothermia was induced and maintained by body surface cooling. The rats were then observed without fluid resuscitation until their death (apnea and no pulse) or for a period of 240 min maximum. RESULTS: The rectal temperature was cooled down to 36 and 34 degrees C in 5 and 10 min, respectively. The mean survival time, which was 76+/-26 min in the control group (38 degrees C), was nearly doubled by mild hypothermia, 178+/-65 min for Group 2 (36 degrees C) (P<0.01 vs. control) and 144+/-54 min for Group 3 (34 degrees C) (P<0.05 vs. control) (no significant difference between Group 2 and 3). Additional blood losses from tail stumps were not significantly different among the three groups. CONCLUSION: Mild hypothermia of either 36 or 34 degrees C prolongs the survival time during lethal UHS in rats.     

Nasopharyngeal cooling selectively and rapidly decreases brain temperature and attenuates neuronal damage, even if initiated at the onset of cardiopulmonary resuscitation in rats

OBJECTIVE: To determine the effectiveness of nasopharyngeal cooling for selective brain cooling and neuroprotection from ischemia. DESIGN: Prospective animal study. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Male Wistar rats (n = 28). INTERVENTIONS: In study 1, hippocampal temperature was decreased to 31 degrees C under spontaneous circulation. In the nasopharyngeal cooling group, physiologic saline (5 degrees C) was infused to the bilateral nasal cavities at the rate of 100 mL.min-1.kg weight-1. In the whole body cooling group, a fan and a water blanket (5 degrees C) were used. In study 2, ischemia and resuscitation were performed in normothermic and nasopharyngeal cooling (initiated with resuscitation after 5 mins of ischemia and continued for 20 mins) groups. MEASUREMENTS AND MAIN RESULTS: The hippocampal temperature was decreased to 31 degrees C in 7 +/- 2 mins without any change in the rectal temperature in the nasopharyngeal cooling group, whereas a decrease in hippocampal temperature to 31 degrees C took 33 +/- 1 mins in the whole body cooling group. Although skull base region was cooled by nasopharyngeal cooling, the epidural temperature of the parietal region was lower than the hippocampal temperature, indicating that brain temperature was hematogenously lowered. There was no difference between changes in cerebral blood flow or between the ratios of oxygen extraction from arterial blood in the head region in the nasopharyngeal cooling and whole body cooling groups. In the second study, all animals were successfully resuscitated, and the times required for recovery of mean arterial blood pressure (60 mm Hg) after resuscitation in the nasopharyngeal cooling and normothermic groups were the same. The histologic damage was significantly attenuated in the nasopharyngeal cooling group (33 +/- 21% cell death in the hippocampus) compared with that in the normothermic group (73 +/- 11%). CONCLUSIONS: Nasopharyngeal cooling enables rapid and selective reductions in cortical and subcortical temperatures without disturbing the recovery of systemic circulation after resuscitation.     

Mild hypothermia induced by a helmet device: a clinical feasibility study.

STUDY OBJECTIVE: To test the feasibility and the speed of a helmet device to achieve the target temperature of 34 degrees C in unconscious after out of hospital cardiac arrest (CA). METHODS: Patients with cardiac arrest due to asystole or pulseless electrical activity (PEA) who remained unconscious after restoration of spontaneous circulation (ROSC) were enrolled in the study and randomised into two groups: a normothermic group (NG) and a hypothermic group (HG). Bladder and tympanic temperature were monitored every 15 min. A helmet device was used to induce mild hypothermia in the HG. Later on, the effect of mild hypothermia on the haemodynamics, electrolytes, lactate, arterial pH, CaO2, CvO2 and O2 extraction ratio were analysed and compared to the values obtained from the NG. RESULTS: Thirty patients were eligible for the study, 16 were randomised into the HG and 14 were randomised into the NG. The median tympanic temperature at admission in both groups was 35.5 degrees C (range: 33.3-38.5 degrees C) and the median tympanic temperature after haemodynamic stabilisation was 35.7 degrees C (range: 33.6-38.2 degrees C). In the HG, the core and the central target temperature of 34 degrees C were achieved after a median time of 180 and 60 min, respectively after ROSC. At the start of the study, no significant differences between the NG and HG were seen. At the end of the study, lactate concentration and O2 extraction ratio were significantly lower in the HG; however the CvO2 was significantly lower in the NG. CONCLUSIONS: Mild hypothermia induced by a helmet device was feasible, easy to perform, inexpensive and effective, with no increase in complications.