TIMECARD score: An easily operated prediction model of unfavorable neurological outcomes in out-of-hospital cardiac arrest patients with targeted temperature management.

BACKGROUND: Targeted temperature management (TTM) is recommended for comatose out-of-hospital cardiac arrest (OHCA) survivors. Several prediction models have been proposed; however, most of these tools require data conversion and complex calculations. Early and easy predictive model of neurological prognosis in OHCA survivors with TTM warrant investigation. MATERIALS AND METHODS: This multicenter retrospective cohort study enrolled 408 non-traumatic adult OHCA survivors with TTM from the TaIwan network of targeted temperature ManagEment for CARDiac arrest (TIMECARD) registry during January 2014 to June 2019. The primary outcome was unfavorable neurological outcome at discharge. The clinical variables associated with unfavorable neurological outcomes were identified and a risk prediction score-TIMECARD score was developed. The model was validated with data from National Taiwan University Hospital. RESULTS: There were 319 (78.2%) patients presented unfavorable neurological outcomes at hospital discharge. Eight independent variables, including malignancy, no bystander cardiopulmonary resuscitation (CPR), non-shockable rhythm, call-to-start CPR duration >5 min, CPR duration >20 min, sodium bicarbonate use during resuscitation, Glasgow Coma Scale motor score of 1 at return of spontaneous circulation, and no emergent coronary angiography, revealed a significant correlation with unfavorable neurological prognosis in TTM-treated OHCA survivors. The TIMECARD score was established and demonstrated good discriminatory performance in the development cohort (area under the receiver operating characteristic curve [AUC] = 0.855) and validation cohorts (AUC = 0.918 and 0.877, respectively). CONCLUSION: In emergency settings, the TIMECARD score is a practical and simple-to-calculate tool for predicting neurological prognosis in OHCA survivors, and may help determine whether to initiate TTM in indicated patients.

Factors affecting outcomes in patients with cardiac arrest who receive target temperature management: The multi-center TIMECARD registry.

BACKGROUND: Target temperature management (TTM) is a recommended therapy for patients after cardiac arrest (PCA). The TaIwan Network of Targeted Temperature ManagEment for CARDiac Arrest (TIMECARD) registry was established for PCA who receive TTM therapy in Taiwan. We aim to determine the variables that may affect neurologic outcomes in PCA who undergo TTM. METHODS: We retrieved demographic variables, resuscitation variables, and cerebral performance category (CPC) scale score at hospital discharge from the TIMECARD registry. The primary outcome was a favorable neurologic outcome, defined as a CPC scale of 1 or 2 at discharge. A total of 540 PCA treated between January 2014 and September 2019 were identified from the registry. Univariate and multivariate analyses were performed to identify significant variables. RESULTS: The mortality rate was 58.1% (314/540). Favorable neurologic outcomes were noted in 117 patients (21.7%). The factors significantly influencing the neurologic outcome (p < 0.05) were the presence of an initial shockable rhythm or pulseless electric activity, a witnessed cardiac-arrest event, bystander cardiopulmonary resuscitation, a smaller total dose of epinephrine, the diastolic blood pressure value at return of spontaneous circulation, a pre-arrest CPC score of 1, coronary angiography, new-onset seizure, and new-onset serious infection. Older patients and those with premorbid diabetes mellitus, chronic kidney disease, malignancy, obstructive lung disease, or cerebrovascular accident were more likely to have an unfavorable neurologic outcome. CONCLUSION: In the TIMECARD registry, some PCA baseline characteristics, cardiac arrest events, cardiopulmonary resuscitation characteristics, and post-arrest management characteristics were significantly associated with neurologic outcomes.

Blood gas phenotyping and tracheal intubation timing in adult in-hospital cardiac arrest: a retrospective cohort study.

To investigate whether the optimal time to tracheal intubation (TTI) during cardiopulmonary resuscitation would differ by different blood gas phenotypes. Adult patients experiencing in-hospital cardiac arrest (IHCA) from 2006 to 2015 were retrospectively screened. Early intra-arrest blood gas analysis, performed within 10 min of resuscitation, was used to define different phenotypes. In total, 567 patients were included. Non-severe acidosis (pH≧7.15) was associated with favourable neurological outcome (odds ratio [OR]: 4.60, 95% confidence interval [CI] 1.63-12.95; p value = 0.004) and survival (OR: 3.25, 95% CI 1.72-6.15; p value < 0.001) in the multivariable logistic regression analyses. In the interaction analysis, normal blood gas phenotype (pH: 7.35-7.45, PCO2: 35-45 mm Hg, HCO3- level: 22-26 mmol/L) × TTI ≦ 6.3 min (OR: 20.40, 95% CI 2.53-164.75; p value = 0.005) and non-severe acidosis × TTI ≦ 6.3 min (OR: 3.35, 95% CI 1.00-11.23; p value = 0.05) were associated with neurological recovery while metabolic acidosis × TTI ≦ 5.7 min (OR: 3.63, 95% CI 1.36-9.67; p value = 0.01) and hypercapnic acidosis × TTI ≦ 10.4 min (OR: 2.27, 95% CI 1.20-4.28; p value = 0.01) were associated with survival. Intra-arrest blood gas analysis may help guide TTI during for patients with IHCA.

The Use of Gray-White-Matter Ratios May Help Predict Survival and Neurological Outcomes in Patients Resuscitated From Out-of-Hospital Cardiac Arrest.

BACKGROUND: The gray-white-matter ratio (GWR) measured on brain computed tomography (CT) following return of spontaneous circulation (ROSC) has been reported to be helpful in the prognostication of mortality or comatose status of cardiac arrest victims. However, whether the use of GWR in predicting the outcomes in out-of-hospital cardiac arrest (OHCA) survivors in Taiwan population remains uninvestigated. METHODS: This retrospective observational study conducted in a single tertiary medical center in Taiwan enrolled all the non-traumatic OHCA adults (> 18 years old) with sustained ROSC (≥ 20 minutes) during the period from 2006 to 2014. Patients with following exclusion criteria were further excluded: no brain CT within 24 hours following ROSC; the presence of intracranial hemorrhage, severe old insult, brain tumor, ventriculoperitoneal shunt, and severe image artifact. The GWR values were obtained from the density measurement of bilateral putamen, caudate nuclei, posterior limbs of internal capsule, corpus callosum, medial cortex and medial white matter of cerebrum in Hounsfield unit with region of interest of 0.11 cm2, and further compared between the patients who survived to hospital discharge or not and the patients with and without good neurological outcome (good: cerebral performance category [CPC] of 1-2, poor: CPC of 3-5), respectively. RESULTS: A total of 228 patients were included in the final analysis with 59.2% in male gender and mean age of 65.8-year-old. There were 106 patients (46.5%) survived to hospital discharge and 40 patients (17.5%) discharged with good neurological outcomes. The GWR values of patients who survived to hospital discharge was significantly higher than ones of those who failed (e.g. basal ganglion: 1.239 vs. 1.199, p < 0.001). Patients with good neurological outcome also had higher GWR values than those with poor outcome (e.g. basal ganglion: 1.243 vs. 1.208, p = 0.010). The Area Under Curve of Receiver of Characteristic curve demonstrated fair predicting ability of GWR for survival and neurological outcomes. CONCLUSION: The use of GWR measured on bran CT within 24 hours following ROSC can help in predicting survival-to-hospital discharge and neurological outcome in OHCA survivors.

Synergistic Effects of Moderate Therapeutic Hypothermia and Levosimendan on Cardiac Function and Survival After Asphyxia-Induced Cardiac Arrest in Rats.

Background This study investigated whether levosimendan, an inotropic calcium sensitizer, when combined with moderate therapeutic hypothermia, may exert synergistic benefits on post-cardiac arrest myocardial dysfunction and improve outcomes. Methods and Results After 9.5-minute asphyxia-induced cardiac arrest and resuscitation, 48 rats were randomized equally into 4 groups following return of spontaneous circulation (ROSC), including normothermia, hypothermia, normothermia-levosimendan, and hypothermia-levosimendan groups. For the normothermia group, the target temperature was 37°C while for the hypothermia group, the target temperature was 32°C, both of which were to be maintained for 4 hours after ROSC. Levosimendan was administered after ROSC with a loading dose of 10 µg/kg and then infused at 0.1 µg/kg per min for 4 hours. In the hypothermia-levosimendan group, left ventricular systolic function and cardiac output increased significantly, whereas the heart rate and systemic vascular resistance decreased significantly compared with the normothermia group. Also, the concentrations of interleukin 1ß at 4 hours post-ROSC and the production of NO between 1 hour and 4 hours post-ROSC were reduced significantly in the hypothermia-levosimendan group compared with the normothermia group. The 72-hour post-ROSC survival and neurological recovery were also significantly better in the hypothermia-levosimendan group compared with the normothermia group (survival, 100% versus 50%, χ2 test, P=0.006). Conclusions Compared with normothermia, only combined moderate therapeutic hypothermia and levosimendan treatment could consistently improve post-cardiac arrest myocardial dysfunction and decrease the release of pro-inflammatory molecules, thereby improving survival and neurological outcomes. These findings suggest synergistic benefits between moderate therapeutic hypothermia and levosimendan.

Validation of the Cardiac Arrest Survival Postresuscitation In-hospital (CASPRI) score in an East Asian population.

BACKGROUND: The Cardiac Arrest Survival Postresuscitation In-hospital (CASPRI) score is a useful tool for predicting neurological outcome following in-hospital cardiac arrest (IHCA), and was derived from a cohort selected from the Get With The Guidelines-Resuscitation registry between 2000 and 2009 in the United States. In an East Asian population, we aimed to identify the factors associated with outcomes of resuscitated IHCA patients and assess the validity of the CASPRI score. METHODS: A retrospective study was conducted in a single centre in Taiwan. Patients with IHCA between 2006 and 2014 were screened. RESULTS: Among the 796 included patients, 94 (11.8%) patients achieved neurologically intact survival. Multivariable logistic regression analyses identified factors significantly associated with neurological outcome. Six of these factors were also components of the CASPRI score, including duration of resuscitation, neurological status before IHCA, malignant disease, initial arrest rhythms, renal insufficiency and age. In univariate logistic regression analysis, the CASPRI score was significantly associated with neurological outcome (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.80-0.87); the area under the receiver operating characteristics curve was 0.79 (95% CI: 0.74-0.84). CONCLUSION: In this retrospective study conducted in a single centre at Taiwan, we identified the common prognosticators of IHCA shared by both East Asian and Western societies. As a composite prognosticator, CASPRI score predicts outcomes with excellent accuracy among successfully resuscitated IHCA patients in an East Asian population. This tool allows accurate IHCA prognostication in an East Asian population.

Association between early arterial blood gas tensions and neurological outcome in adult patients following in-hospital cardiac arrest.

OBJECTIVE: The early partial pressures of arterial O2 (PaO2) and CO2 (PaCO2) have been found in animal studies to be correlated with neurological outcome after brain injury. However, the relationship of early PaO2 and PaCO2 to the neurological outcomes of resuscitated patients after cardiac arrest was still not clear. METHODS: This was a retrospective observational cohort study in a single medical center. Adult patients who had in-hospital cardiac arrest between 2006 and 2012 and achieved sustained return of spontaneous circulation (ROSC) (ROSC>20min without resumption of chest compression) were included. Multivariable logistic regression analysis was used to identify factors associated with favorable neurological outcome at hospital discharge. The first PaO2 and PaCO2 values measured after first sustained ROSC were used for analysis. RESULTS: Of the 550 included patients, 154 (28%) survived to hospital discharge and 74 (13.5%) achieved favorable neurological outcome. The mean time from sustained ROSC to the measurement of PaO2 and PaCO2 was 136.8min. The mean PaO2 and PaCO2 were 167.4mmHg and 40.3mmHg, respectively. PaO2 between 70 and 240mmHg (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.08-3.64) and PaCO2 levels (OR 0.98, 95% CI 0.95-0.99) were positively and inversely associated with favorable neurological outcome, respectively. CONCLUSIONS: The early PaO2 and PaCO2 levels obtained after ROSC might be correlated with neurological outcome of patients with in-hospital cardiac arrest. However, because of the inherent limitations of the retrospective design, these results should be further validated in future studies.

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.

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.

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 degrees C to 31 degrees 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 degrees C and 37.5 degrees 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.