Effects of Hemin on neuroglobin expression after cardiopulmonary resuscitation in rats

BACKGROUND:

Despite a large amount of resuscitation research, the survival rate after cardiac arrest remains low, and brain injury is the key issue. Neuroglobin (NGB) is an oxygen-binding heme protein found in the brain with a protection role against ischemic-hypoxic brain injury. Hemin is an effective activator of neuroglobin. This study was undertaken to assess the effect of hemin on expression of neuroglobin (NGB) in the cerebral cortex, neuro-deficit score (NDS) and pathological changes after cardiopulmonary resuscitation (CPR) in rats.

METHODS:

A total of 120 male Sprague-Dawley (SD) rats were randomly divided into a control group (A), a CPR group (B) and a Hemin group (C). The animal model of cardiac arrest (CA) induced by asphyxia and CPR was established. NGB expression in the cerebral cortex with immunohistochemistry, NDS and pathological changes in the cerebral cortex were examined at 3, 6, 12, 24 hours after recovery of spontaneous circulation (ROSC) in each group. Experimental data were treated as one-factor analysis of variance and the Tukey test.

RESULTS:

In comparison with group A, NGB expression was increased significantly at 12 and 24 hours after ROSC (P<0.05 or P<0.01), NDS was decreased significantly at each time point after ROSC (P<0.01), and pathological changes were severe at each time point after ROSC in group B. In comparison with group A, NGB expression was increased significantly at 6, 12, 24 hours after ROSC (P<0.05 or P<0.01), NDS was decreased significantly at 3, 6, 12 hours after ROSC (P<0.01) in group C. In comparison with group B, NGB expression was increased significantly at 12 and 24 hours after ROSC, NDS was increased significantly at 12 and 24 hours after ROSC, and pathological changes were milder in group C.

CONCLUSION:

There were increased NGB expression in the cerebral cortex, decreased NDS, and severe pathological changes after CPR in rats. Hemin treatment up-regulated expression of NGB, improved NDS, mitigated pathological changes, and alleviated cerebral injury after CPR.KEY WORDS: Cardiopulmonary resuscitation, Neuroglobin, Neurodeficit score, Hemin, Cerebral injury, Rats     

Therapeutic benefits of mild hypothermia in patients successfully resuscitated from cardiac arrest: A meta-analysis

BACKGROUND:

Good neurological outcome after cardiac arrest (CA) is hard to achieve for clinicians. Experimental and clinical evidence suggests that therapeutic mild hypothermia is beneficial. This study aimed to assess the effectiveness and safety of therapeutic mild hypothermia in patients successfully resuscitated from CA using a meta-analysis.

METHODS:

We searched the MEDLINE (1966 to April 2012), OVID (1980 to April 2012), EMBASE (1980 to April 2012), Chinese bio-medical literature & retrieval system (CBM) (1978 to April 2012), Chinese medical current contents (CMCC) (1995 to April 2012), and Chinese medical academic conference (CMAC) (1994 to April 2012). Studies were included if 1) the study design was a randomized controlled trial (RCT); 2) the study population included patients successfully resuscitated from CA, and received either standard post-resuscitation care with normothermia or mild hypothermia; 3) the study provided data on good neurologic outcome and survival to hospital discharge. Relative risk (RR) and 95% confidence interval (CI) were used to pool the effect.

RESULTS:

The study included four RCTs with a total of 417 patients successfully resuscitated from CA. Compared to standard post-resuscitation care with normothermia, patients in the hypothermia group were more likely to have good neurologic outcome (RR=1.43, 95% CI 1.14–1.80, P=0.002) and were more likely to survive to hospital discharge (RR=1.32, 95% CI 1.08–1.63, P=0.008). There was no significant difference in adverse events between the normothermia and hypothermia groups (P>0.05), nor heterogeneity and publication bias.

CONCLUSION:

Therapeutic mild hypothermia improves neurologic outcome and survival in patients successfully resuscitated from CA.KEY WORDS: Cardiac arrest, Cardiopulmonary resuscitation, Return of spontaneous circulation, Mild hypothermia, Meta-analysis     

Comparison of early sequential hypothermia and delayed hypothermia on neurological function after resuscitation in a swine model

Background

We utilized a porcine cardiac arrest model to compare early sequential hypothermia (ESH) with delayed hypothermia (DH) and no hypothermia (NH) to investigate the different effects on cerebral function after resuscitation.

Parenchymal lung injuries related to standard cardiopulmonary resuscitation

Objectives

We analyzed chest computed tomographic scan to evaluate parenchymal lung injury and its clinical significance in patients who received standard cardiopulmonary resuscitation and were resuscitated from cardiac arrest.

Effects of hypothermia on brain injury assessed by magnetic resonance imaging after cardiopulmonary resuscitation in a porcine model of cardiac arrest

Objective

To evaluate the effects of hypothermia on cerebral edema and metabolism, a porcine model of cardiac arrest was assessed by magnetic resonance imaging during the first 72 hours after restoration of spontaneous circulation (ROSC).

Methods

Ventricular fibrillation was induced in 33 pigs. After 8 minutes of untreated ventricular fibrillation, 30:2 cardiopulmonary resuscitation was performed. After ROSC, 30 survival animals were randomly divided into normothermia group (n = 15) and hypothermia group (n = 15). The hypothermia group immediately received endovascular cooling to regulate temperature to 33°C, which was maintained for 12 hours, followed by passive rewarming at 0.5°C/h to 37°C. Diffusion-weighted imaging and ¹hydrogen proton magnetic resonance spectroscopy were acquired for each group at 6, 12, 24, and 72 hours after ROSC.

Results

Compared with the normothermia group, the hypothermia group exhibited a higher 72-hour survival (73.3% vs. 33.3%, P = .028) and a superior neurological deficit score (P = .031). Cerebral injury was found in both groups, but a lesser decrease in the apparent diffusion coefficient and N-acetyl aspartate/creatinine (P < .05) and a greater increase in choline/creatinine (P < .05) were found in the hypothermia group.

Conclusions

Magnetic resonance imaging could effectively detect the dynamic trend of cerebral injury in a porcine model of cardiac arrest within the first 72 hours after ROSC. Hypothermia produced a protective effect on neurological function by reducing brain edema and formation of adverse metabolites.     

Factors influencing outcomes after cardiopulmonary resuscitation in emergency department

BACKGROUND:

The outcome of cardiopulmonary resuscitation (CPR) may depend on a variety of factors related to patient status or resuscitation management. To evaluate the factors influencing the outcome of CPR after cardiac arrest (CA) will be conducive to improve the effectiveness of resuscitation. Therefore, a study was designed to assess these factors in the emergency department (ED) of a city hospital.

METHODS:

A CPR registry conforming to the Utstein-style template was conducted in the ED of the First Affiliated Hospital of Wenzhou Medical College from January 2005 to December 2011. The outcomes of CPR were compared in various factors groups. The primary outcomes were rated to return of spontaneous circulation (ROSC), 24-hour survival, survival to discharge and discharge with favorable neurological outcomes. Univariate analysis and multivariable logistic regression analysis were performed to evaluate factors associated with survival.

RESULTS:

A total of 725 patients were analyzed in the study. Of these patients, 187 (25.8%) had ROSC, 100 (13.8%) survived for 24 hours, 48 (6.6%) survived to discharge, and 23 (3.2%) survived to discharge with favorable neurologic outcomes. A logistic regression analysis demonstrated that the independent predictors of ROSC included traumatic etiology, first monitored rhythms, CPR duration, and total adrenaline dose. The independent predictors of 24-hour survival included traumatic etiology, cardiac etiology, first monitored rhythm and CPR duration. Previous status, cardiac etiology, first monitored rhythms and CPR duration were included in independent predictors of survival to discharge and neurologically favorable survival to discharge.

CONCLUSIONS:

Shockable rhythms, CPR duration ≤15 minutes and total adrenaline dose ≤5 mg were favorable predictors of ROSC, whereas traumatic etiology was unfavorable. Cardiac etiology, shockable rhythms and CPR duration ≤15 minutes were favorable predictors of 24-hour survival, whereas traumatic etiology was unfavorable. Cardiac etiology, shockable rhythms, CPR duration ≤15 minutes were favorable predictors of survival to discharge and neurologically favorable survival to discharge, but previous terminal illness or multiple organ failure (MOF) was unfavorable.KEY WORDS: Cardiac arrest, Cardiopulmonary resuscitation, Utstein-style, Logistical regression analysis, Outcome     

Effect of β-sodium aescinate on hypoxia-inducible factor-1α expression in rat brain cortex after cardiopulmonary resuscitation

BACKGROUND:

This study was undertaken to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in rat cerebral cortex and the effects of β-sodium aescinate (SA) administration after return of spontaneous circulation (ROSC).

METHODS:

Sixty rats were divided into three groups: SA group, injected intraperitoneally with SA instantly after ROSC; control group, injected intraperitoneally with normal saline; and sham-operated group, without cardiac arrest or SA. The cardiac arrest model was established using asphyxiation and intravenous potassium chloride. Blood was sampled 1, 6, 12, and 24 hours after ROSC. Protein and mRNA levels of HIF-1α, VEGF and EPO were detected in the cerebral cortex by immunohistochemistry and real-time RT-PCR; serum levels of NSE and S100β were determined by enzyme-linked immunosorbent assays.

RESULTS:

Serum S100β and NSE were significantly increased in the control group versus the sham-operated group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1α, VEGF and EPO were significantly increased in the control rats (P<0.05). Serum NSE and S100β were significantly decreased in the SA group versus the control group 1, 6, 12 and 24 hours after ROSC (P<0.05). Protein and mRNA levels of HIF-1α, VEGF and EPO were significantly increased in the SA group (P<0.05).

CONCLUSIONS:

The expression of HIF-1α is increased in rat cerebral cortex after ROSC, and SA up-regulates the expression of HIF-1α. The up-regulation of HIF-1α improves the resistance of the cortex to ischemia and hypoxia and contributes to neuroprotection, possibly because of up-regulation of EPO and VEGF expression.KEY WORDS: Cardiopulmonary resuscitation, HIF-1α, Erythropoietin, Vascular endothelial growth factor, β-sodium aescinate, Neuroprotection     

Active compression-decompression cardiopulmonary resuscitation (CPR) versus standard CPR for cardiac arrest patients: a meta-analysis

BACKGROUND:

Active compression-decompression cardiopulmonary resuscitation (ACDCPR) has been popular in the treatment of patients with cardiac arrest (CA). However, the effect of ACD-CPR versus conventional standard CPR (S-CRP) is contriversial. This study was to analyze the efficacy and safety of ACD-CPR versus S-CRP in treating CA patients.

METHODS:

Randomized or quasi-randomized controlled trials published from January 1990 to March 2011 were searched with the phrase “active compression-decompression cardiopulmonary resuscitation and cardiac arrest” in PubMed, EmBASE, and China Biomedical Document Databases. The Cochrane Library was searched for papers of meta-analysis. Restoration of spontaneous circulation (ROSC) rate, survival rate to hospital admission, survival rate at 24 hours, and survival rate to hospital discharge were considered primary outcomes, and complications after CPR were viewed as secondary outcomes. Included studies were critically appraised and estimates of effects were calculated according to the model of fixed or random effects. Inconsistency across the studies was evaluated using the I2 statistic method. Sensitivity analysis was made to determine statistical heterogeneity.

RESULTS:

Thirteen studies met the criteria for this meta-analysis. The studies included 396 adult CA patients treated by ACD-CPR and 391 patients by S-CRP. Totally 234 CA patients were found out hospitals, while the other 333 CA patients were in hospitals. Two studies were evaluated with high-quality methodology and the rest 11 studies were of poor quality. ROSC rate, survival rate at 24 hours and survival rate to hospital discharge with favorable neurological function indicated that ACD-CPR is superior to S-CRP, with relative risk (RR) values of 1.39 (95% CI 0.99–1.97), 1.94 (95% CI 1.45–2.59) and 2.80 (95% CI 1.60–5.24). No significant differences were found in survival rate to hospital admission and survival rate to hospital discharge for ACD-CPR versus S-CRP with RR values of 1.06 (95% CI 0.76–1.60) and 1.00 (95% CI 0.73–1.38).

CONCLUSION:

Quality controlled studies confirmed the superiority of ACD-CPR to S-CRP in terms of ROSC rate and survival rate at 24 hours. Compared with S-CRP, ACD-CPR could not improve survival rate to hospital admission or survival rate to hospital discharge.KEY WORDS: Active compression-decompression, Cardiopulmonary resuscitation, Cardiac arrest, Meta-analysis     

S-100B is superior to NSE, BDNF and GFAP in predicting outcome of resuscitation from cardiac arrest with hypothermia treatment

Objective

To conduct a pilot study to evaluate the blood levels of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE) and S-100B as prognostic markers for neurological outcome 6 months after hypothermia treatment following resuscitation from cardiac arrest.

Design

Prospective observational study.

Setting

One intensive care unit at Uppsala University Hospital.

Patients

Thirty-one unconscious patients resuscitated after cardiac arrest.

Interventions

None.

Measurements and main results

Unconscious patients after cardiac arrest with restoration of spontaneous circulation (ROSC) were treated with mild hypothermia to 32-34 °C for 26 h. Time from cardiac arrest to target temperature was measured. Blood samples were collected at intervals of 1-108 h after ROSC. Neurological outcome was assessed with Glasgow-Pittsburgh cerebral performance category (CPC) scale at discharge from intensive care and again 6 months later, when 15/31 patients were alive, of whom 14 had a good outcome (CPC 1-2). Among the predictive biomarkers, S-100B at 24 h after ROSC was the best, predicting poor outcome (CPC 3-5) with a sensitivity of 87% and a specificity of 100%. NSE at 96 h after ROSC predicted poor outcome, with sensitivity of 57% and specificity of 93%. BDNF and GFAP levels did not predict outcome. The time from cardiac arrest to target temperature was shorter for those with poor outcome.

Conclusions

The blood concentration of S-100B at 24 h after ROSC is highly predictive of outcome in patients treated with mild hypothermia after cardiac arrest.     

Effect of hypertransfusion on the gastrointestinal tract after cardiac arrest in a porcine model

BACKGROUND:

This study aimed to determine the potential protective effect of inducing hypertransfusion to the gastrointestinal tract following a porcine model of cardiac arrest and cardiopulmonary resuscitation (CPR) by evaluating the influence of gastrointestinal ultrastructure, ATPase and serum diamine oxidase.

METHODS:

Ventricular fibrillation was induced by programmed electrical stimulation in 16 male domestic pigs (n=8/group). Four minutes after ventricular fibrillation, CPR was performed. The pigs that successfully restored spontaneous circulation received intravenous infusion of either norepinephrine to maintain the mean arterial pressure at 130% of the baseline before ventricular fibrillation or normal saline. Serum diamine oxidase and gastrointestinal ATPase activity were determined, and histopathological examination of the gastrointestinal tract was performed by light and electron microscopy.

RESULTS:

CPR caused significant injury to the gastrointestinal tract, elevating serum diamine oxidase and causing destruction of intestinal microvillus in control animals. Na⁺-K⁺ ATPase and Ca²⁺ ATPase activity in gastric tissue were significantly elevated in animals receiving hypertransfusion treatment compared with the control animals. Hypertransfusion also significantly reduced serum diamine oxidase to below control levels after CPR. Moreover, severe injury sustained by the gastrointestinal tissue was markedly ameliorated under hypertransfusion conditions compared with the control animals.

CONCLUSIONS:

Gastrointestinal injury and abnormal energy metabolism were strikingly evident following CPR. Hypertransfusion inducing hypertension can improve energy metabolism and ameliorate gastrointestinal mucosal injury, indicating that hypothermia significantly ameliorates gastrointestinal injury sustained following cardiac arrest.KEY WORDS: Cardiopulmonary resuscitation, Cardiac arrest, Gastrointestinal tract, Diamine oxidase, Ultra structure     

Induction of therapeutic hypothermia via the esophagus: a proof of concept study

BACKGROUND:

Induction of hypothermia (a 4 °C decrease from baseline) improves outcomes in adult cardiac arrest and neonatal hypoxic ischemic encephalopathy, and may benefit other conditions as well. Methods used to implement or prevent hypothermia typically require skin contact with blankets or pads or intravascular access with catheter devices. The study was to evaluate the potential to induce mild therapeutic hypothermia via an esophageal route in a porcine model.

METHODS:

Single-animal proof-of-concept study of a prototype esophageal device in a 70 kg Yorkshire swine. We measured the rate of temperature change after placement of a prototype device to induce hypothermia via the esophagus, and compared this rate to known temperature changes that occur under similar laboratory conditions without a hypothermic device.

RESULTS:

Swine temperature decreased from a starting temperature of 37.8 °C to 33.8 °C (achieving the goal of a 4 °C decrease) in 175 minutes, resulting in a cooling rate of 1.37 °C/h. Histopathology of the esophagus showed normal tissue without evidence of injury.

CONCLUSION:

A prototype of an esophageal cooling device induced hypothermia effectively in a large single-swine model.KEY WORDS: Mild therapeutic hypothermia, Esophagus, Swine, Cardiac arrest     

Cerebrospinal fluid biochemistry reflects effects of therapeutic hypothermia after cardiac arrest in a porcine model

Background

Mild induced hypothermia (MIH) is recommended to treat neurologic injury after cardiac arrest (CA). However, clinical trials to assess MIH benefit after CA have been largely inconclusive. We investigated the subsequent changes in cerebrospinal fluid (CSF) biochemistry after MIH (33°C-34°C for 12 hours) and evaluated the importance of ongoing fever control.

Methods

Thirty-two male Wuzhishan inbred mini pigs (n = 16/group) underwent ventricular fibrillation followed by cardiopulmonary resuscitation and were randomized into 2 groups: hypothermic and control. Upon resumption of spontaneous circulation (ROSC) from CA, the hypothermic group was treated with MIH by endovascular cooling. The control group received no temperature intervention. Core temperatures were continually monitored. At various points throughout the procedure, CSF samples were obtained to measure glutamate, lactate, and pyruvate levels.

Results

The core temperature of the hypothermic group was found to have increased postrewarming and reached levels comparable with those of the control group at ROSC 72 hours. In both groups, glutamate increased significantly after ROSC, but the glutamate levels in the hypothermic group were lower than those in the control group, except at ROSC 1 hour. The lactate-pyruvate ratio increased in the control group at ROSC 1 hour and was significantly lower in the hypothermic group (P < .05).

Conclusions

Mild induced hypothermia mitigated and delayed the CA-induced increase of CSF glutamate. Therefore, our results suggest that clinically inducing hypothermia as soon as possible after CA, or prolonging the time of MIH in combination with controlling ongoing fever, may enhance hypothermic protective effects.     

The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest

Introduction

Early prognostication after successful cardiopulmonary resuscitation is difficult, and there is a need for novel methods to estimate the extent of brain injury and predict outcome. In this study, we evaluated the impact of the cardiac arrest syndrome on the plasma levels of selected tissue-specific microRNAs (miRNAs) and assessed their ability to prognosticate death and neurological disability.

Methods

We included 65 patients treated with hypothermia after cardiac arrest in the study. Blood samples were obtained at 24 hours and at 48 hours. For miRNA-screening purposes, custom quantitative polymerase chain reaction (qPCR) panels were first used. Thereafter individual miRNAs were assessed at 48 hours with qPCR. miRNAs that successfully predicted prognosis at 48 hours were further analysed at 24 hours. Outcomes were measured according to the Cerebral Performance Category (CPC) score at 6 months after cardiac arrest and stratified into good (CPC score 1 or 2) or poor (CPC scores 3 to 5).

Results

At 48 hours, miR-146a, miR-122, miR-208b, miR-21, miR-9 and miR-128 did not differ between the good and poor neurological outcome groups. In contrast, miR-124 was significantly elevated in patients with poor outcomes compared with those with favourable outcomes (P < 0.0001) at 24 hours and 48 hours after cardiac arrest. Analysis of receiver operating characteristic curves at 24 and 48 hours after cardiac arrest showed areas under the curve of 0.87 (95% confidence interval (CI) = 0.79 to 0.96) and 0.89 (95% CI = 0.80 to 0.97), respectively.

Conclusions

The brain-enriched miRNA miR-124 is a promising novel biomarker for prediction of neurological prognosis following cardiac arrest.     

Protective effects of therapeutic hypothermia in post-resuscitation myocardium

Aim of the study

Post-resuscitation therapeutic hypothermia has been recommended because of its neuroprotective effects. However, a few studies have reported the effects of therapeutic hypothermia on the heart, especially in ventricular fibrillation cardiac arrest. The aim of this study was to determine whether therapeutic hypothermia attenuates post-resuscitation myocardial injury in a swine cardiac arrest model.

Methods

A prospective animal study was performed in the university hospital animal research laboratory. Ventricular fibrillation cardiac arrest was induced in domestic pigs weighing 35–40 kg. After 6 min of no flow time, cardiopulmonary resuscitation was provided to pigs, and the restoration of spontaneous circulation (ROSC) was achieved. The subjects were randomly allocated to a normothermic (NT group, n = 5) or hypothermic (HT group, n = 5) group. In the HT group, therapeutic hypothermia (core temperature 32–34 °C) was maintained for 24 h, and rewarming was performed over a period of 8 h. In the NT group, core temperature was maintained at 37 °C throughout the experiments. Sixty hours after ROSC, blood and myocardial tissues were harvested.

Results

Serum troponin I was not significantly different between the groups. However, myocardial histological damage was attenuated in the HT group. Myocardial ATP contents were higher in the HT group than in the NT group. Immunohistochemistry for apoptosis-related protein showed that survivin expression was higher in the HT group, and XAF1 and cleaved caspase-3 expressions were lower in the HT group than in the NT group.

Conclusions

Therapeutic hypothermia attenuated histological myocardial injury in ventricular fibrillation cardiac arrest model of pigs while preserving more ATP and decreased apoptosis.     

Changes of end-tidal carbon dioxide during cardiopulmonary resuscitation from ventricular fibrillation versus asphyxial cardiac arrest

BACKGROUND:

Partial pressure of end-tidal carbon dioxide (P_ETCO₂) has been used to monitor the effectiveness of precordial compression (PC) and regarded as a prognostic value of outcomes in cardiopulmonary resuscitation (CPR). This study was to investigate changes of P_ETCO₂ during CPR in rats with ventricular fibrillation (VF) versus asphyxial cardiac arrest.

METHODS:

Sixty-two male Sprague-Dawley (SD) rats were randomly divided into an asphyxial group (n=32) and a VF group (n=30). P_ETCO₂ was measured during CPR from a 6-minute period of VF or asphyxial cardiac arrest.

RESULTS:

The initial values of P_ETCO₂ immediately after PC in the VF group were significantly lower than those in the asphyxial group (12.8±4.87 mmHg vs. 49.2±8.13 mmHg, P=0.000). In the VF group, the values of P_ETCO₂ after 6 minutes of PC were significantly higher in rats with return of spontaneous circulation (ROSC), compared with those in rats without ROSC (16.5±3.07 mmHg vs. 13.2±2.62 mmHg, P=0.004). In the asphyxial group, the values of P_ETCO₂ after 2 minutes of PC in rats with ROSC were significantly higher than those in rats without ROSC (20.8±3.24 mmHg vs. 13.9±1.50 mmHg, P=0.000). Receiver operator characteristic (ROC) curves of P_ETCO₂ showed significant sensitivity and specificity for predicting ROSC in VF versus asphyxial cardiac arrest.

CONCLUSIONS:

The initial values of P_ETCO₂ immediately after CPR may be helpful in differentiating the causes of cardiac arrest. Changes of P_ETCO₂ during CPR can predict outcomes of CPR.KEY WORDS: Partial pressure of end-tidal carbon dioxide, Cardiac arrest, Cardiopulmonary resuscitation, Return of spontaneous circulation, Rats     

Epinephrine in out-of-hospital cardiac arrest: A critical review

BACKGROUND:

Epinephrine is recommended in advanced cardiac life support guidelines for use in adult cardiac arrest, and has been used in cardiopulmonary resuscitation since 1896. Yet, despite its long time use and incorporation into guidelines, epinephrine suffers from a paucity of evidence regarding its influence on survival. This critical review was conducted to address the knowledge deficit regarding epinephrine in out-of-hospital cardiac arrest and its effect on return of spontaneous circulation, survival to hospital discharge, and neurological performance.

METHODS:

The EMBASE and MEDLINE (through the Pubmed interface) databases, and the Cochrane library were searched with the key words “epinephrine”, “cardiac arrest” and variations of these terms. Original research studies concerning epinephrine use in adult, out-of-hospital cardiac arrest were selected for further review.

RESULTS:

The search yielded nine eligible studies based on inclusion criteria. This includes five prospective cohort studies, one retrospective cohort study, one survival analysis, one case control study, and one RCT. The evidence clearly establishes an association between epinephrine and increased return of spontaneous circulation, the data were conflicting concerning survival to hospital discharge and neurological outcome.

CONCLUSIONS:

The results of this review exhibit the paucity of evidence regarding the use of epinephrine in out of hospital cardiac arrest. There is currently insufficient evidence to support or reject its administration during resuscitation. Larger sample, placebo controlled, double blind, randomized control trials need to be performed to definitively establish the effect of epinephrine on both survival to hospital discharge and the neurological outcomes of treated patients.KEY WORDS: Emergency medicine, Epinephrine, Cardiac arrest, Prehospital, Out-of-hospital, Resuscitation     

Outcomes from low versus high-flow cardiopulmonary resuscitation in a swine model of cardiac arrest

Background

Return of spontaneous circulation (ROSC) is improved by greater vital organ blood flow during cardiopulmonary resuscitation (CPR). We tested the hypothesis that myocardial flow above the threshold needed for ROSC may be associated with greater vital organ injury and worse outcome.

Methods

Aortic and right atrial pressures were measured with micromanometers in 27 swine. After 10 minutes of untreated ventricular fibrillation, chest compression was performed with an automatic, load-distributing band. Animals were randomly assigned to receive flows just sufficient for ROSC (low flow: target coronary perfusion pressure = 12 mm Hg) or well above the minimally effective level (high flow: coronary perfusion pressure = 30 mm Hg). Myocardial flow was measured with microspheres, defibrillation was performed after 3.5 minutes of CPR, and ejection fraction was measured with echocardiography.

Results

Return of spontaneous circulation was achieved by 9 of 9 animals in the high-flow group and 15 of 18 in the low-flow group. All animals in the high-flow group defibrillated initially into a perfusing rhythm, whereas 12 of 15 animals achieving ROSC in the low-flow group defibrillated initially into pulseless electrical activity (P < .05, Fisher exact test). Compared with animals in the low-flow group, animals in the high-flow group had shorter resuscitation times, higher mean aortic pressures at ROSC, and higher ejection fractions at 2 hours post-ROSC (all P < .05).

Conclusion

High-flow CPR significantly improved arrest hemodynamics, rates of ROSC, and post-ROSC indicators of myocardial status, all indicating less injury with higher flows. No evidence of organ injury from vital organ blood flow substantially above the threshold for ROSC was found.     

Effect of exogenous phosphocreatine on cardiomycytic apoptosis and expression of Bcl-2 and Bax after cardiopulmonary resuscitation in rats

BACKGROUND:

Ischemia-reperfusion injury in the myocardium after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is an important pathologic basis of post-cardiac arrest of syndrome (PCAS), and apoptosis is one of the major mechanisms in myocardial ischemia-reperfusion injury. To lessen myocardial ischemia-reperfusion injury after cardiac arrest and CPR, it is important to reduce energy consumption and to increase energy supply in the myocardium. This study aimed to observe changes of cell apoptosis and expression of Bcl-2 and Bax protein on the myocardium after CPR in rats, and the protective effects of different doses of exogenous phosphocreatine (creatine phosphate, CP) on them.

METHODS:

A total of 32 male adult Sprague-Dawley rats were randomly divided into 4 groups: control group (group A), CPR group (group B), low-dose CP group (group C, CP 0.5 g/kg at beginning of CPR and 1.0 g/kg at 2 hours after CPR) and high-dose CP group (group D, CP 1.0 g/kg at beginning of CPR and 2.0 g/kg at 2 hours after CPR). Cardiac arrest was induced by asphyxiation and CPR started at 7 minutes after asphyxiation in groups B, C and D. Myocardium samples were taken at 24 hours after CPR. Cardiomycytic apoptosis was detected by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. The expression of Bcl-2 and Bax protein was measured by immunohistochemistry.

RESULTS:

Cardiomyocytic apoptosis index (AI) and expression of Bcl-2 and Bax protein increased more significantly in groups B, C and D than in group A (P<0.01), but Bcl-2/Bax ratio significantly decreased (P<0.01). Cardiomyocytic AI and expression of Bcl-2 and Bax protein decreased more significantly in groups C and D than in group B (P<0.01), but Bcl-2/Bax ratio increased more significantly (P<0.01). Cardiomyocytic AI and expression of Bcl-2 and Bax protein decreased more significantly in group D than in group C (P<0.05), but Bcl-2/Bax ratio increased more significantly (P<0.05).

CONCLUSION:

Exogenous phosphocreatine, especially at a large dose, could inhibit cardiomyocytic apoptosis and alleviate myocardial injury after CPR in rats.KEY WORDS: Cardiopulmonary resuscitation, Phosphocreatine, Apoptosis, Bcl-2, Bax, TUNEL     

Cardiac arrest patients have an impaired immune response,which is not influenced by induced hypothermia

Introduction

Induced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest.

Methods

A prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at three time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined.

Results

In total, 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C.

Conclusions

Patients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01020916","term_id":"NCT01020916"}}NCT01020916, registered 25 November 2009     

Erythropoietin improved initial resuscitation and increased survival after cardiac arrest in rats

Introduction

Recent data have demonstrated potent cardioprotective and neuroprotective effects of the application of growth hormones like erythropoietin (EPO) after focal cardiac or cerebral ischemia. In order to assess possible benefits regarding survival and resuscitation conditions, EPO was tested against placebo in a model of cardiac arrest in the rat.

Methods

Thirty-four male Wistar rats were randomized into two groups (EPO versus control; n = 17 per group). Under anesthesia, cardiac arrest was induced by asphyxia after neuromuscular blockade. After 6 min of global ischemia, animals were resuscitated by external chest compression combined with epinephrine administration. An intravenous bolus of recombinant human EPO (rhEPO, 3000 UI kg⁻¹ body weight, i.v.) or saline (in control group) was performed 15 min before cardiac arrest, by a blinded investigator. Restoration of spontaneous circulation (ROSC), survival at 1, 24, 48 and 72 h and hemodynamic changes after cardiac arrest were studied.

Results

Survival to 72 h was significantly improved in the EPO group (n = 15/17) compared to the control group (n = 7/17). All the EPO-treated rats were successfully resuscitated whereas only 13 of 17 control animals resuscitated. EPO-treated animals required a significantly smaller dose of epinephrine before resuscitation, compared to control rats. Time course of systolic arterial blood pressure after resuscitation revealed no significant differences between both groups.

Conclusion

EPO, when administrated before cardiac arrest, improved initial resuscitation and increased the duration of post-resuscitation survival.