A novel predictor of unsustained return of spontaneous circulation in cardiac arrest patients through a combination of capnography and pulse oximetry: a multicenter observational study

BACKGROUND:Unsustained return of spontaneous circulation(ROSC)is a critical barrier to survival in cardiac arrest patients.This study examined whether end-tidal carbon dioxide(ETCO_(2))and pulse oximetry photoplethysmogram(POP)parameters can be used to identify unsustained ROSC.METHODS:We conducted a multicenter observational prospective cohort study of consecutive patients with cardiac arrest from 2013 to 2014.Patients’general information,ETCO_(2),and POP parameters were collected and statistically analyzed.RESULTS:The included 105 ROSC episodes(from 80 cardiac arrest patients)comprised 51 sustained ROSC episodes and 54 unsustained ROSC episodes.The 24-hour survival rate was significantly higher in the sustained ROSC group than in the unsustained ROSC group(29.2%vs.9.4%,P<0.05).The logistic regression analysis showed that the difference between after and before ROSC in ETCO_(2)(ΔETCO_(2))and the difference between after and before ROCS in area under the curve of POP(ΔAUCp)were independently associated with sustained ROSC(odds ratio[OR]=0.931,95%confi dence interval[95%CI]0.881-0.984,P=0.011 and OR=0.998,95%CI 0.997-0.999,P<0.001).The area under the receiver operating characteristic curve ofΔETCO_(2),ΔAUCp,and the combination of both to predict unsustained ROSC were 0.752(95%CI 0.660-0.844),0.883(95%CI 0.818-0.948),and 0.902(95%CI 0.842-0.962),respectively.CONCLUSION:Patients with unsustained ROSC have a poor prognosis.The combination ofΔETCO_(2) andΔAUCp showed signifi cant predictive value for unsustained ROSC.

Correction:Establishment of a prediction model for prehospital return of spontaneous circulation in out-of-hospital patients with cardiac arrest

This is an erratum to an already published paper named“Establishment of a prediction model for prehospital return of spontaneous circulation in out-ofhospital patients with cardiac arrest”.We found errors in the affiliated institution of the authors.We apologize for our unintentional mistake.Please note,these changes do not affect our results.

Establishment of a prediction model for prehospital return of spontaneous circulation in out-of-hospital patients with cardiac arrest

BACKGROUND Out-of-hospital cardiac arrest(OHCA)is a leading cause of death worldwide.AIM To explore factors influencing prehospital return of spontaneous circulation(P-ROSC)in patients with OHCA and develop a nomogram prediction model.METHODS Clinical data of patients with OHCA in Shenzhen,China,from January 2012 to December 2019 were retrospectively analyzed.Least absolute shrinkage and selection operator(LASSO)regression and multivariate logistic regression were applied to select the optimal factors predicting P-ROSC in patients with OHCA.A nomogram prediction model was established based on these influencing factors.Discrimination and calibration were assessed using receiver operating charac-teristic(ROC)and calibration curves.Decision curve analysis(DCA)was used to evaluate the model’s clinical utility.RESULTS Among the included 2685 patients with OHCA,the P-ROSC incidence was 5.8%.LASSO and multivariate logistic regression analyses showed that age,bystander cardiopulmonary resuscitation(CPR),initial rhythm,CPR duration,ventilation mode,and pathogenesis were independent factors influencing P-ROSC in these patients.The area under the ROC was 0.963.The calibration plot demonstrated that the predicted P-ROSC model was concordant with the actual P-ROSC.The good clinical usability of the prediction model was confirmed using DCA.CONCLUSION The nomogram prediction model could effectively predict the probability of P-ROSC in patients with OHCA.

Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway

Bradykinin(BK)is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects.We previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spontaneous circulation(ROSC)after cardiac arrest.However,the precise mechanism underlying this process remains poorly understood.In this study,we treated a rat model of ROSC after cardiac arrest(induced by asphyxiation)with 150μg/kg BK via intraperitoneal injection 48 hours after ROSC following cardiac arrest.We found that BK postconditioning effectively promoted the recovery of rat neurological function after ROSC following cardiac arrest,increased the amount of autophagosomes in the hippocampal tissue,inhibited neuronal cell apoptosis,up-regulated the expression of autophagy-related proteins LC3 and NBR1 and down-regulated p62,inhibited the expression of the brain injury marker S100βand apoptosis-related protein caspase-3,and affected the expression of adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway-related proteins.Adenosine monophosphate-activated protein kinase inhibitor compound C clearly inhibited BK-mediated activation of autophagy in rats after ROSC following cardiac arrest,which aggravated the injury caused by ROSC.The mechanistic target of rapamycin inhibitor rapamycin enhanced the protective effects of BK by stimulating autophagy.Our findings suggest that BK postconditioning protects against injury caused by ROSC through activating the adenosine monophosphate-activated protein kinase/mechanistic target of the rapamycin pathway.

β-receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation

Objective:We investigated the influence of β-receptor blocker metoprolol on return of spontaneous circulation(ROSC) during cardiopulmonary resuscitation(CPR) in rats with induced myocardial infarction(MI).Methods:Male Sprague-Dawley rats were randomly divided into three groups:the sham-operated group,the MI group without metoprolol,which was fed the vehicle,and the MI+metoprolol group receiving intragastric metoprolol.Each group was further divided randomly into three subgroups,depending on the dosage of epinephrine administered during subsequent CPR applied after the induction of asphyxial cardiac arrest.Results:The ROSC rate was significantly decreased in the low dose subgroup of MI group,unchanged in the medium dose subgroup of MI group,and significantly decreased in the high dose subgroup of MI group,compared with the same dose subgroup of sham-operated group.MI+metoprolol group had a lower ROSC rate than MI group in the medium dose subgroup,and a higher ROSC rate than MI group in the high dose subgroup.There was no difference in blood K+ values of successful rats between MI group and MI+metoprolol group.The rats with successful CPR had lower blood K+ values than rats with unsuccessful CPR in each of the three treatment groups.Conclusions:Metoprolol administered to MI rats over a long period significantly improved ROSC rates under an appropriate dose of epinephrine during CPR.An increasing high blood K+ value would attenuate the rate of a successful CPR.

Risk Factor Analyses for the Return of Spontaneous Circulation in the Asphyxiation Cardiac Arrest Porcine Model

Background： Animal models of asphyxiation cardiac arrest （ACA） are frequently used in basic research to mirror the clinical course of cardiac arrest （CA）. The rates of the return of spontaneous circulation （ROSC） inACA animal models are lower than those from studies that have utilized ventricular fibrillation （VF） animal models. The purpose of this study was to characterize the factors associated with the ROSC in the ACA porcine model. Methods： Forty-eight healthy miniature pigs underwent endotracheal tube clamping to induce CA. Once induced, CA was maintained untreated for a period of 8 min. Two minutes following the initiation of cardiopulmonary resuscitation （CPR）, defibrillation was attempted until ROSC was achieved or the animal died. To assess the factors associated with ROSC in this CA model, logistic regression analyses were performed to analyze gender, the time of preparation, the amplitude spectrum area （AMSA） from the beginning of CPR and the pH at the beginning of CPR. A receiver-operating characteristic （ROC） curve was used to evaluate the predictive value ofAMSA for ROSC. Results： ROSC was only 52.1% successful in this ACA porcine model. The multivariate logistic regression analyses revealed that ROSC significantly depended on the time of preparation, AMSA at the beginning of CPR and pH at the beginning of CPR. The area under the ROC curve in for AMSA at the beginning of CPR was 0.878 successful in predicting ROSC （95% confidence intervals： 0.773-0.983）, and the optimum cut-offvalue was 15.62 （specificity 95.7% and sensitivity 80.0%）. Conclusions： The time of preparation, AMSA and the pH at the beginning of CPR were associated with ROSC in this ACA porcine model. AMSA also predicted the likelihood of ROSC in this ACA animal model.

Association between duration of return of spontaneous circulation and outcomes after out-of-hospital cardiac arrest

Background:Return of spontaneous circulation(ROSC)is a core outcome element of cardiopulmonary resuscitation(CPR);however,the definition or criterion of ROSC is disputed and varies in resuscitation for out-of-hospital cardiac arrest(OHCA).Methods:This was a retrospective study of 126 patients with OHCA who achieved ROSC between January and December 2020.The probability of survival after OHCA related to CPR and ROSC duration was analyzed using the probability density function and empirical cumulative density functions.Results:There were no significant differences between ROSC sustained until emergency department arrival and that sustained for at least 20 minutes in terms of the 24-hour survival rate(31.3%[31/99]vs.35.7%[10/30];P=0.84),30-day survival rate(23.2%[23/99]vs.25.0%[7/30];P=0.99),or survival at 30 days with cerebral performance category(CPC)1 and 2(18.2%[18/99]vs.10.7%[3/30];P=0.44).The Kolmogorov-Smirnov test values from the empirical cumulative density functions with ROSC sustained until hospital arrival and that sustained for at least 20 minutes were 0.44,0.20,and 0.24 for CPC 1 or 2,CPC 3 or 4,and CPC 5,respectively.Conclusion:Return of spontaneous circulation is a core outcome element of CPR.It should be defined as sustained for at least 20 minutes or until arrival at the emergency department and as a basic standard for evaluating resuscitation success after OHCA.

Modified Glucose-insulin-potassium Therapy for Hemorrhage-induced Traumatic Cardiac Arrest in Rabbits

Objective Resuscitation with whole blood is known to be better than that with saline in attaining the return of spontaneous circulation(ROSC)and improving the short-term survival rate for hemorrhage-induced traumatic cardiac arrest(HiTCA).However,the resuscitation with whole blood alone fails to address the pathophysiological abnormalities,including hyperglycemia,hyperkalemia and coagulopathy,after HiTCA.The present study aimed to determine whether the modified glucose-insulin-potassium(GIK)therapy can ameliorate the above-mentioned pathophysiological abnormalities,enhance the ROSC,improve the function of key organs,and reduce the mortality after HiTCA.Methods HiTCA was induced in rabbits(n=36)by controlled hemorrhage.Following arrest,the rabbits were randomly divided into three groups(n=12 each):group A(no resuscitation),group B(resuscitation with whole blood),and group C(resuscitation with whole blood plus GIK).The GIK therapy was administered based on the actual concentration of glucose and potassium.The ROSC rate and survival rate were obtained.Hemodynamical and biochemical changes were detected.Thromboelastography(TEG)was used to measure coagulation parameters,and enzyme-linked immunosorbent assay to detect parameters related to inflammation,coagulation and the function of brain.Results All animals in groups B and C attained ROSC.Two rabbits died 24–48 h after HiTCA in group B,while no rabbits died in group C.The GIK therapy significantly reduced the levels of blood glucose,potassium,and biological markers for inflammatory reaction,and improved the heart,kidney,liver and brain function in group C when compared to group B.Furthermore,the R values of TEG were significantly lower in group C than in group B,and the maximum amplitude of TEG was slightly lower in group B than in group C,with no significant difference found.Conclusion Resuscitation with whole blood and modified GIK therapy combined can ameliorate the pathophysiological disorders,including hyperglycemia,hyperkalemia and coagulopathy,and may improve the function of key organs after HiTCA.

Do cardiopulmonary resuscitation real-time audiovisual feedback devices improve patient outcomes? A systematic review and metaanalysis

BACKGROUND Cardiac arrest is a leading cause of mortality in America and has increased in the incidence of cases over the last several years.Cardiopulmonary resuscitation(CPR)increases survival outcomes in cases of cardiac arrest;however,healthcare workers often do not perform CPR within recommended guidelines.Real-time audiovisual feedback(RTAVF)devices improve the quality of CPR performed.This systematic review and meta-analysis aims to compare the effect of RTAVF-assisted CPR with conventional CPR and to evaluate whether the use of these devices improved outcomes in both in-hospital cardiac arrest(IHCA)and out-of-hospital cardiac arrest(OHCA)patients.AIM To identify the effect of RTAVF-assisted CPR on patient outcomes and CPR quality with in-and OHCA.METHODS We searched PubMed,SCOPUS,the Cochrane Library,and EMBASE from inception to July 27,2020,for studies comparing patient outcomes and/or CPR quality metrics between RTAVF-assisted CPR and conventional CPR in cases of IHCA or OHCA.The primary outcomes of interest were return of spontaneous circulation(ROSC)and survival to hospital discharge(SHD),with secondary outcomes of chest compression rate and chest compression depth.The methodo-logical quality of the included studies was assessed using the Newcastle-Ottawa scale and Cochrane Collaboration’s“risk of bias”tool.Data was analyzed using R statistical software 4.2.0.results were statistically significant if P<0.05.RESULTS Thirteen studies(n=17600)were included.Patients were on average 69±17.5 years old,with 7022(39.8%)female patients.Overall pooled ROSC in patients in this study was 37%(95%confidence interval=23%-54%).RTAVF-assisted CPR significantly improved ROSC,both overall[risk ratio(RR)1.17(1.001-1.362);P=0.048]and in cases of IHCA[RR 1.36(1.06-1.80);P=0.002].There was no significant improvement in ROSC for OHCA(RR 1.04;0.91-1.19;P=0.47).No significant effect was seen in SHD[RR 1.04(0.91-1.19);P=0.47]or chest compression rate[standardized mean difference(SMD)-2.1;(-4.6-0.5);P=0.09].A significant improvement was seen in chest compression depth[SMD 1.6;(0.02-3.1);P=0.047].CONCLUSION RTAVF-assisted CPR increases ROSC in cases of IHCA and chest compression depth but has no significant effect on ROSC in cases of OHCA,SHD,or chest compression rate.

Application of Positron Emission Tomography in the Detection of Myocardial Metabolism in Pig Ventricular Fibrillation and Asphyxiation Cardiac Arrest Models after Resuscitation

Objective To study the application of positron emission tomography （PET） in detection of myocardia metabolism in pig ventricular fibrillation and asphyxiation cardiac arrest models after resuscitation. Methods Thirty-two healthy miniature pigs were randomized into a ventricular fibrillation cardiac arrest （VFCA） group （n=16） and an asphyxiation cardiac arrest （ACA） group （n=16）. Cardiac arrest （CA） was induced by programmed electric stimulation or endotracheal tube clamping followed by cardiopulmonary resuscitation （CPR） and defibrillation. At four hours and 24 h after spontaneous circulation was achieved, myocardial metabolism was assessed by PET. 18F-FDG myocardial uptake in PET was analyzed and the maximum standardized uptake value （SUVmax） was measured. Results Spontaneous circulation was 200% and 62.5% in VFCA group and ACA group, respectively. PET demonstrated that the myocardial metabolism injuries was more severe and widespread after ACA than after VFCA. The SUVrnax was higher in VFCA group than in ACA group （P〈0.01）. In VFCA group, SUVmax at 24 h after spontaneous circulation increased to the level of baseline. Conclusion ACA causes more severe cardiac metabol associated with less successful resuscitation. Myocardial sm injuries than VFCA. Myocardial dysfunction is stunning does occur with VFCA but not with ACA.

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.

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

BACKGROUND: Partial pressure of end-tidal carbon dioxide(PETCO2) 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 PETCO2 during CPR in rats with ventricular fi brillation(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). PETCO2 was measured during CPR from a 6-minute period of VF or asphyxial cardiac arrest.RESULTS: The initial values of PETCO2 immediately after PC in the VF group were signifi cantly 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 PETCO2 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 PETCO2 after 2 minutes of PC in rats with ROSC were signifi cantly 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 PETCO2 showed signifi cant sensitivity and specifi city for predicting ROSC in VF versus asphyxial cardiac arrest.CONCLUSIONS: The initial values of PETCO2 immediately after CPR may be helpful in differentiating the causes of cardiac arrest. Changes of PETCO2 during CPR can predict outcomes of CPR.

Epinephrine in Out-of-hospital Cardiac Arrest： Helpful or Harmful？

Objective：Epinephrine is the primary drug administered during cardiopulmonary resuscitation （CPR） to reverse cardiac arrest.The evidence for the use of adrenaline in out-of-hospital cardiac arrest （OHCA） and in-hospital resuscitation is inconclusive.We conducted a systematic review on the clinical efficacy of adrenaline in adult OHCA patients to evaluate whether epinephrine provides any overall benefit for patients.Data Sources：The EMBASE and PubMed databases were searched with the key words ＆quot;epinephrine,＆quot; ＆quot;cardiac arrest,＆quot; and variations of these terms.Study Selection：Data from clinical randomized trials,meta-analyses,guidelines,and recent reviews were selected for review.Results：Sudden cardiac arrest causes 544,000 deaths in China each year,with survival occurring in 〈1% of cases （compared with 12% in the United States）.The American Heart Association recommends the use of epinephrine in patients with cardiac arrest,as part of advanced cardiac life support.There is a clear evidence of an association between epinephrine and increased return of spontaneous circulation （ROSC）.However,there are conflicting results regarding long-term survival and functional recovery,particularly neurological outcome,after CPR.There is currently insufficient evidence to support or reject epinephrine administration during resuscitation.We believe that epinephrine may have a role in resuscitation,as administration of epinephrine during CPR increases the probability of restoring cardiac activity with pulses,which is an essential intermediate step toward long-term survival.Conclusions：The administration of adrenaline was associated with improved short-term survival （ROSC）.However,it appears that the use of adrenaline is associated with no benefit on survival to hospital discharge or survival with favorable neurological outcome after OHCA,and it may have a harmful effect.Larger placebo-controlled,double-blind,randomized control trials are required to definitively establish the effect of epinephrine.