Min-Shan Tsai

The effect of hyperoxia on survival following adult cardiac arrest: A systematic review and meta-analysis of observational studies

OBJECTIVE Studies have shown the detrimental effect of hyperoxia in animals with return of spontaneous circulation (ROSC) after cardiac arrest. To maximize the value of existing clinical studies, we performed the systemic review and meta-analysis of human observational studies to examine the effect of hyperoxia on outcomes of post-ROSC patients. METHODS We searched PubMed and Embase from the inception to October 2013. We selected adult observational studies that compared different levels of partial pressure of arterial oxygen (PaO2) in post-ROSC patients with mortality or neurological status at hospital discharge as outcome. Studies comparing hypoxia with normoxia only were excluded. RESULTS Fourteen studies were identified from 2982 references. Odds ratio (OR) was used as effect estimate. OR was reconstructed if not provided in original articles. Hyperoxia was defined as a PaO2>300 mmHg. Meta-analysis indicated that hyperoxia appeared to be correlated with increased in-hospital mortality (OR, 1.40; 95% CI, 1.02-1.93; I2, 69.27%; 8 studies) but not worsened neurological outcome (OR, 1.62; 95% CI, 0.87-3.02; I2, 55.61%; 2 studies). However, the results were inconsistent in subgroup and sensitivity analyses. CONCLUSIONS Hyperoxia appears to be correlated with increased in-hospital mortality of post-ROSC patients. This result should be interpreted cautiously because of the significant heterogeneity and limited number of studies analyzed. However, because exposure to hyperoxia had no obvious benefits, clinicians should monitor PaO2 closely and titrate oxygen administration cautiously.

Rapid Head Cooling Initiated Coincident With Cardiopulmonary Resuscitation Improves Success of Defibrillation and Post-Resuscitation Myocardial Function in a Porcine Model of Prolonged Cardiac Arrest

To the Editor: In cardiac arrest, systemic hypothermia initiated after resuscitation has been shown to improve survival and long-term neurologic outcome ([1,2][1]). Systemic hypothermia established before cardiac arrest improved the defibrillation success and resuscitation outcome in a porcine model

Cardioprotective effect of therapeutic hypothermia for postresuscitation myocardial dysfunction.

Mild-to-moderate therapeutic hypothermia after resuscitation from cardiac arrest is neuroprotective, but its effect on postresuscitation myocardial dysfunction is not clear. We hypothesized that therapeutic hypothermia is cardioprotective in postresuscitation. Male adult Wistar rats underwent asphyxia-induced cardiac arrest and manual resuscitation with epinephrine. Therapeutic hypothermia is induced immediately after successful resuscitation and the return of spontaneous circulation (ROSC). One hour after ROSC, the rats achieved a target temperature of 30°C to 31°C, which was maintained for 1.5 h and then transitioned to the passive rewarming process in the hypothermia group. A temperature between 36.5°C and 37.5°C was maintained in the normothermia group. Echocardiography revealed that hypothermia resulted in significantly better systolic function of fractional shortening in 60 and 120 min after ROSC (both P < 0.05). The benefit of cardioprotection was also confirmed by the general linear mixed-models analysis of dP/dt, which revealed significantly better systolic function in positive dP/dtR(40) and diastolic function in maximal negative dP/dt (both P < 0.001). The 4-h and 3-day survival analyses both revealed better outcomes in the hypothermia groups in the log-rank test (P < 0.001 for the 4-h analysis, and P < 0.05 for the 3-day analysis). Serum level of heart-type, fatty acid-binding protein at 4 h after resuscitation as the myocardium damage marker was also significantly lower in the hypothermia group (52.4 ng/mL vs 186.5 ng/mL in the normothermia group; P < 0.05). Western blotting of myocardium showed that myocardial Akt and ERK1/2 were more activated in the hypothermia group 2 h after spontaneous circulation returned. In conclusion, postresuscitation mild-to-moderate therapeutic hypothermic is cardioprotective in the asphyxia-induced cardiac arrest animal model. It stabilizes hemodynamics, improves short-term survival, and decreases myocardial damage. The cardioprotective effect is associated with Akt and ERK1/2 activation in signal transduction.

Effects of pre-arrest comorbidities on 90-day survival of patients resuscitated from out-of-hospital cardiac arrest

Background Factors that affect prognosis in successfully resuscitated out-of-hospital cardiopulmonary arrest (OHCA) patients in the intensive care unit (ICU) who survived the initial 24 h period of post-resuscitation have not been established. This study was conducted to evaluate the clinical prognostic factors associated with 90-day survival in patients who were successfully resuscitated from OHCA. Methods This study was conducted at a tertiary large university hospital. Clinical data were obtained from the medical records of 224 adult non-traumatic patients who were successfully resuscitated from OHCA and who survived the initial 24 h post-resuscitation phase. Univariate and multivariate analyses were performed to identify independent predictors associated with 90-day survival. Results Significant adverse prognosticators included liver cirrhosis (HR 4.36, 95% CI 1.76 to 10.79), prolonged cardiopulmonary resuscitation (CPR) duration >20 min (HR 1.95, 95% CI 1.27 to 3.00) and underlying malignancy (HR 1.64, 95% CI 1.06 to 2.54). Favourable prognostic factors included the best Glasgow Coma Scale within 24–48 h after return of spontaneous circulation >5 (HR 0.16, 95% CI 0.04 to 0.68), mean arterial pressure on ICU admission >100 mmHg (HR 0.81, 95% CI 0.43 to 0.94) and the presenting rhythm of pulseless electrical activity (HR 0.44, 95% CI 0.1 to 0.63). A high burden of comorbidities (by Charlson score >5) was associated with significantly poorer 90-day survival (HR 1.60, 95% CI 1.03 to 2.49). Conclusions Underlying comorbidities have a significant influence on survival. CPR duration, post-resuscitative blood pressure and early neurological recovery may serve as practical clinical predictors of short-term survival.

Erythropoietin improves the postresuscitation myocardial dysfunction and survival in the asphyxia-induced cardiac arrest model.

To investigate the effect of erythropoietin for the management of postresuscitation myocardial dysfunction following asphyxia-induced cardiac arrest. Male adult Wistar rats were used for the prospective controlled animal study. Asphyxia-induced cardiac arrest was performed by turning-off the ventilator and clamping the endotracheal tube. Cardiopulmonary resuscitation with an intravenous injection of 0.01 mg/kg epinephrine and mechanical ventilation were started after 6.5 minutes of asphyxia. The resuscitated animals received either erythropoietin (5000 U/kg) or equivalent volume of 0.9% saline as placebo intravenously 3 minutes after return of spontaneous circulation. The erythropoietin treatment produced better left ventricular dP/dt40 and −dP/dt in the invasive hemodynamic measurements, and left ventricular fraction shortening by echocardiography. Administration of erythropoietin also improved three days survival among those successfully resuscitated. The molecular effects of erythropoietin were shown by activation of its down streaming Akt and ERK 42/44 signaling pathways. EPO has the potential to improve postresuscitation myocardial dysfunction and short term survival in rats after asphyxia-induced cardiac arrest.

Circulating cell-free DNA levels correlate with postresuscitation survival rates in out-of-hospital cardiac arrest patients ☆ ☆☆

Early prediction of prognosis is helpful in cardiac arrest patients. Plasma cell-free DNA, which increases rapidly after cell death, is a novel biomarker for the prognosis of critical ill patients. Changes in the plasma cell-free DNA level and its role for the early prognosis of cardiac arrest patients remain unclear. We prospectively enrolled adult out-of-hospital cardiac arrest (OHCA) patients with sustained return of spontaneous circulation. The resuscitation variables were recorded following the Utstein recommendation. The plasma cell-free DNA concentration was determined by quantitative real-time polymerase chain reaction assay of β-globin gene. A total of 42 patients were enrolled for the study. The plasma cell-free DNA level within 2h after cardiac arrest was higher in the non-survival group than the survival-to-discharge group (median level 1659.9 g.e./mL vs. 1121.6g.e./mL, p=0.003 by non-parametric test). The plasma cell-free DNA level at 72 h became no difference between these two groups. The optimal cutoff value of plasma cell-free DNA for predicting survival-to-discharge was 1,170 g.e./mL by ROC curve analysis (area under curve 0.752, p=0.010). A plasma cell-free DNA level higher than 1,170 g.e./mL and was an independent predictor for in-hospital mortality by multiple logistic regression analysis (adjusted odds ratio of 12.35, p=0.023) and was also associated with higher 90 day mortality (p=0.021 by log-rank test). In conclusion, the plasma cell-free DNA level increases during the early post-cardiac arrest phase and can be an early prognostic factor for OHCA patients.

Acute cardiac dysfunction after short-term diesel exhaust particles exposure.

Epidemiological studies show an association between particulate matter exposure and acute heart failure. However, underlying mechanisms remain unclear. In this study, we investigated acute cardiac hemodynamic effects and related mechanisms after 1 day exposure to diesel exhaust particles (DEPs). Male Sprague-Dawley rats were randomized and instilled with 250 microg (low dose) or 500 microg (high dose) of DEP or saline placebo intra-tracheally. The cardiac systolic function by dP/dt(40) and diastolic functions by maximal negative dP/dt were both worse in DEP low dose and DEP high dose groups than the control group, respectively. In the heart rate variability analysis, SDNN in DEP low dose and DEP high dose groups were both lower than the control group. The low frequency heart rate variability was higher in the DEP groups compared to the control group. The cardiac IL-1beta expression and circulating cardiac troponin I level were higher in the DEP group than the control group. Plasma IL-1beta and IL-6 protein were significantly higher in the DEP groups than the control group. In conclusion, DEP exposure causes acute cardiac systolic and diastolic dysfunction. The changes may be related to decreased heart rate variability, increased cardiac inflammatory reaction and myocardial damage.

Antiapoptotic Cardioprotective Effect of Hypothermia Treatment Against Oxidative Stress Injuries

OBJECTIVES The effect of hypothermia on cardiomyocyte injury induced by oxidative stress remains unclear. The authors investigated the effects of hypothermia on apoptosis and mitochondrial dysfunction in cardiomyocytes exposed to oxidative stress. METHODS Cardiomyocytes (H9c2) derived from embryonic rat heart cell culture were exposed to either normothermic (37 degrees C) or hypothermic (31 degrees C) environments before undergoing oxidative stress via treatment with hydrogen peroxide (H(2)O(2)). The degree of apoptosis was determined by annexin V and terminal deoxynucleotidyl transferase (TUNEL) staining. The amount of reactive oxygen species (ROS) was compared after H(2)O(2) exposure between normo- and hypothermic-pretreated groups. Mitochondrial dysfunction in both groups was measured by differential reductase activity and transmembrane potential (DeltaPsim). RESULTS Hydrogen peroxide induced significant apoptosis in both normothermic and hypothermic cardiomyocytes. Hypothermia ameliorated apoptosis as demonstrated by decreased annexin V staining (33 +/- 1% vs. 49 +/- 4%; p < 0.05) and TUNEL staining (27 +/- 17% vs. 80 +/-25%; p < 0.01). The amount of intracellular ROS increased after H(2)O(2) treatment and was higher in the hypothermic group than that in the normothermic group (237.9 +/- 31.0% vs. 146.6 +/- 20.6%; p < 0.05). In the hypothermic group, compared with the normothermic group, after H(2)O(2) treatment mitochondrial reductase activity was greater (72.0 +/- 17.9% vs. 27.0 +/- 13.3%; p < 0.01) and the mitochondria DeltaPsim was higher (101.0 +/- 22.6% vs. 69.7 +/- 12.9%; p < 0.05). Pretreatment of cardiomyocytes with the antioxidant ascorbic acid diminished the hypothermia-induced increase in intracellular ROS and prevented the beneficial effects of hypothermia on apoptosis and mitochondrial function. CONCLUSIONS Hypothermia at 31 degrees C can protect cardiomyocytes against oxidative stress-induced injury by decreasing apoptosis and mitochondrial dysfunction through intracellular ROS-dependent pathways.

Diagnostic accuracy of tissue Doppler echocardiography for patients with acute heart failure

Background: Acute heart failure leads to high mortality and morbidity rates. The symptom of acute dyspnoea is non-specific and the diagnostic tools of acute heart failure are still not satisfactory. Tissue Doppler echocardiography is accurate in evaluating cardiac function; however, its efficacy in diagnosing patients with acute dyspnoea in emergency departments remains unclear. Methods: Patients with acute dyspnoea were included prospectively while visiting the emergency department. Tissue Doppler echocardiography was carried out and the ratios of peak early diastolic transmitral blood flow velocity (E) to the peak early diastolic tissue velocity over mitral annulus (Ea) were recorded. The sensitivity, specificity and accuracy of tissue Doppler parameters and the receiver-operating characteristic curves for diagnosing acute heart failure were also evaluated. Results: A total of 92 patients were enrolled. The ratio E:Ea was found to be a good diagnostic test to estimate the diagnostic performances of tissue Doppler echocardiography using receiver-operating characteristic curves in cases of acute heart failure in patients with preserved left ventricular systolic function (mean (SD) area under the curve = 0.875 (0.049); p<0.001; cut-off value = 11) and with left ventricular systolic dysfunction (mean (SD) area under the curve = 0.903 (0.061); p = 0.003; cut-off value = 16). E:Ea was an independent predictor of acute heart failure in multiple logistic regressions. For patients with a B-type natriuretic peptide level between 100 and 500 pg/ml, E:Ea provided an accuracy of 90.9% (p = 0.015) for diagnosing acute heart failure. Conclusions: Tissue Doppler echocardiography is accurate in diagnosing patients with acute heart failure in emergency departments. It can be a useful supplementary diagnostic tool for patients with inconclusive blood B-type natriuretic peptide level.

Post-cardiac arrest myocardial dysfunction is improved with cyclosporine treatment at onset of resuscitation but not in the reperfusion phase

AIM OF STUDY Significant myocardial dysfunction and high mortality occur after whole-body ischaemia-eperfusion injuries in the post-cardiac arrest status. The inhibition of mitochondrial permeability transition pore (mPTP) opening during ischaemia-reperfusion can ameliorate injuries in the specific organs. We investigated the effect and therapeutic window of pharmacological inhibition of mPTP opening in cardiac arrest. METHODS Forty male Wistar rats were resuscitated after cardiac arrest induced by 8.5 min of asphyxia. Cyclosporine (10 mg/kg) was administered intravenously at onset of resuscitation in protocol 1 study and administered 3 min after ROSC in protocol 2 with placebo control in both. RESULTS Left ventricular systolic (dP/dt 40), diastolic (maximal negative dP/dt) functions and cardiac output were improved in the group with cyclosporine treatment at onset of resuscitation compared to control group (p < 0.01, respectively). Seventy-two hour survival was better in the group with cyclosporine treatment at onset of resuscitation compared to control (p = 0.046). Left ventricular systolic and diastolic function, cardiac output and 72 h survival were not improved in the group with cyclosporine treatment 3 min after ROSC. The severity of mitochondrial damage under electronic microscopy, mPTP opening, mitochondrial respiratory control ratio and ADP:O ratio were ameliorated in the group with cyclosporine treatment at onset of resuscitation (p< 0.05, respectively) but not in the group with cyclosporine treatment at 3 min after ROSC. CONCLUSIONS Post-cardiac arrest myocardial dysfunction and survival can be improved by cyclosporine treatment at onset of resuscitation, but not by the cyclosporine treatment at 3 min after ROSC.