Extracorporeal Versus Conventional Cardiopulmonary Resuscitation For In-hospital Cardiac Arrest: A Propensity Score Matching Study

BackgroundIn-hospital cardiac arrest(IHCA)is a major medical burden worldwide.With the development of science and technology,the treatment of IHCA has been gradually increased,but the discharge survival rate is still low,only 6%to 26%of IHCA patients can survive discharge.Conventional cardiopulmonary resuscitation(CCPR)is a standard treatment for cardiac arrest,which may improve the survival rate of patients.However,CCPR can only provide a hypoperfusion state,producing approximately 25%to 33%cardiac output with limited duration.Previous studies have shown a rapid decline in the likelihood of return of spontaneous circulation(ROSC)and favorable neurological outcomes after 30 minutes of CCPR.The extracorporeal cardiopulmonary resuscitation(ECPR)is a combination of extracorporeal membrane oxygenation(ECMO)and CCPR.It is considered a viable treatment for refractory cardiac arrest.Previous studies have shown that the implementation of ECPR can improve the prognosis of patients with IHCA and can improve the survival rate of patients with reversible cardiac arrest.However,the overall certainty of the evidence for the results of all studies using ECPR in the hospital setting was rated very low(Class Ⅱb).The 2020 American Heart Association(AHA)Guidelines for Cardiopulmonary resuscitation and Cardiovascular Emergency state that there is insufficient evidence to recommend the routine use of ECPR in patients with cardiac arrest,but that ECPR may be considered to provide limited mechanical cardiopulmonary support to patients with reversible cardiac arrest.In addition,most relevant studies are from hospitals with rich experience in ECPR implementation,and their universality may be limited by regional and medical level differences.The AHA guidelines recommend that ECPR be performed only by a trained physician in a specialized resuscitation center,and that indications be strictly applied,discouraging routine ECPR.There are few high-quality studies on the use of ECPR in the treatment of IHCA patients,and whether ECPR treatment can effectively improve the prognosis of patients with IHCA remains unclear.Therefore,the purpose of this study was to compare the survival rate and neurological function prognosis of ECPR and CCPR,to explore the effectiveness of ECPR,and to explore the advantages and limitations of ECPR in China.Aims1.To explore whether ECPR can effectively improve the survival outcome and neurological function prognosis of patients with IHCA compared with CCPR.2.To explore the advantages and limitations of ECPR implementation in China,and then put forward improvement measures to improve the treatment effect of ECPR.MethodsThe data of a prospective observational cohort enrolled in the BASeline Investigation of Cardiac arrest(BASIC)project in China from July 1,2019 to December 31,2020 were analyzed.To determine the current status of ECPR implementation in BAISC-IHCA units,ECPR experts and an independent statistical team developed an electronic questionnaire at the same time as the BASIC-IHCA study was being conducted.Inclusion criteria:age≤75 years,witnessed cardiac arrest and duration of cardiopulmonary resuscitation(CPR)>10 minutes.Exclusion criteria:malignancy;severe trauma;previous severe neurological damage;not receive CPR;abnormal or missing relevant data.Primary outcome:survival at 30 days or discharge;secondary outcomes:ROSC,good neurological prognosis at 30 days(cerebral performance category 1-2),survival at 6 months,survival at 1 year,good neurological prognosis at 6 months and good neurological prognosis at 1 year.Statistical analysis:A propensity score matching(PSM)study method was used to develop a balanced 1:4 matched cohort to reduce the influence of potential confounders.Matching variables included:age,sex,cause of cardiac arrest,location of cardiac arrest,initial rhythm,defibrillation,epinephrine dose during cardiac arrest and CPR duration.Categorical variables were compared using the χ2 test(or Fisher exact test)and expressed as counts and percentages;continuous variables that conformed to a normal distribution were expressed as mean± standard deviation and compared using the t-test,and continuous variables that did not conform to a normal distribution were expressed as median(quadratic spacing)using the Wilcoxon nonparametric test.Kaplan-Meier survival curves at day 30,6 months and 1 year were plotted to demonstrate survival trends inpatients with IHCA.ECPR and associated covariates were added to the Cox regression model to report the Hazard Ratio(HR),95%confidence interval(95%CI)and P-value.To verify the robustness of the model,sensitivity analyses were conducted in this study.Statistical significance was defined as two-sided P<0.05.Results1.Baseline characteristics:Before PSM,a total of 4726 patients who met the inclusion criteria were enrolled in the study.A total of 4693 patients(99.3%)received CCPR,including 3023 males(64.4%),with an average age of 53.5 years.33 patients(0.7%)underwent ECPR,including 21 males(63.6%),with an average age of 47.6 years.Compared with the CCPR group,the ECPR group had a higher proportion of cardiogenic cardiac arrest(75.8%vs.44.9%,P<0.001)and a higher proportion of cardiac arrest in the intensive care unit(48.5%vs.38.4%,P<0.05).The proportion of initial defibrillation rhythm was low in the two groups,including 663 cases(14.1%)in the CCPR group and 6 cases(18.2%)in the ECPR group,and the difference was not statistically significant(P=0.46).There were also no significant differences between the two groups in the presence or absence of defibrillation(25.0%vs 36.4%,P=0.13)and the dose of epinephrine used during cardiac arrest.After PSM,a total of 165 patients were included in further studies.There were 132 patients in the CCPR group,including 77 males(58.3%),with an average age of 48.9 years.A total of 33 patients underwent ECPR,including 21 males(63.6%),with an average age of 47.6 years.After PSM,the baseline characteristics of the two groups were balanced,and the covariate differences were balanced.2.Primary outcome:In the CCPR group,5.7%(266 patients)survived or were discharged at 30 days,and in the ECPR group,18.2%(6 patients)survived or were discharged at 30 days.A total of 165 patients were included for further statistical analysis after 1:4 PSM,including 132 patients in the CCPR group and 33 patients in the ECPR group.Six patients in each group survived or were discharged at 30 days,but the survival rate of patients in the ECPR group was significantly higher than that in the CCPR group(18.2%vs 4.5%,P=0.02).Kaplan-Meier survival analysis showed that at day 30 after cardiac arrest,patients in the ECPR group had a trend toward better survival than patients in the CCPR group.3.Secondary outcome:Among 165 matched patients,the ROSC rate was significantly higher in the ECPR group than in the CCPR group(60.6%vs 22.0%,P<0.001).The 6-month survival rate(18.2%vs 3.8%,P=0.009)and 1-year survival rate(18.2%vs 3.8%,P=0.009)were significantly higher in the ECPR group than in the CCPR group.Patients in the ECPR group had a better prognosis of good neurological function than those in the CCPR group,whether at 30 days after cardiac arrest(12.1%vs 4.5%,P=0.11),6 months(12.1%vs 3.8%,P=0.08),or 1 year(12.1%vs 3.0%,P=0.05).But there was no significant statistical difference.Kaplan-Meier survival analysis showed that ECPR had a better survival trend than CCPR at both 6 months and 1 year after cardiac arrest.4.Factors influencing prognosis:Multivariate Cox regression analysis showed that ECPR([HR]:0.42,95%CI:0.28-0.61,P<0.001)and initial rhythm were shockable rhythm(HR:0.58,95%CI:0.53-0.64,P=0.003)was a protective factor for survival after cardiac arrest,and noncardiogenic cardiac arrest increased the risk of death in patients with IHCA(HR:1.08,95%CI:1.02-1.15,P=0.003).When the site of arrest was a general ward,the 30-day risk of death was 9%lower(HR:0.91,95%CI:0.84-0.99,P=0.03).5.Questionnaire survey:Results showed that less than half of the participants were aware of the indications(45%)and contraindications(47%)of ECPR.ECPR took a long time to install,and 75%of the teams spent more than 20 minutes on catheterization.Conclusion1.Compared with CCPR,patients receiving ECPR after IHCA have better survival outcomes,both in the short and long term.2.Shockable rhythm and general ward location of cardiac arrest are protective factors for survival of patients with IHCA.3.Relevant departments in hospitals should increase ECPR training,improve the knowledge and technical proficiency of medical staff on ECPR,and shorten the low-flow time as much as possible to improve the prognosis.