Nai-Hsin Chi

Cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis

BACKGROUND Extracorporeal life-support as an adjunct to cardiac resuscitation has shown encouraging outcomes in patients with cardiac arrest. However, there is little evidence about the benefit of the procedure compared with conventional cardiopulmonary resuscitation (CPR), especially when continued for more than 10 min. We aimed to assess whether extracorporeal CPR was better than conventional CPR for patients with in-hospital cardiac arrest of cardiac origin. METHODS We did a 3-year prospective observational study on the use of extracorporeal life-support for patients aged 18-75 years with witnessed in-hospital cardiac arrest of cardiac origin undergoing CPR of more than 10 min compared with patients receiving conventional CPR. A matching process based on propensity-score was done to equalise potential prognostic factors in both groups, and to formulate a balanced 1:1 matched cohort study. The primary endpoint was survival to hospital discharge, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00173615. FINDINGS Of the 975 patients with in-hospital cardiac arrest events who underwent CPR for longer than 10 min, 113 were enrolled in the conventional CPR group and 59 were enrolled in the extracorporeal CPR group. Unmatched patients who underwent extracorporeal CPR had a higher survival rate to discharge (log-rank p<0.0001) and a better 1-year survival than those who received conventional CPR (log rank p=0.007). Between the propensity-score matched groups, there was still a significant difference in survival to discharge (hazard ratio [HR] 0.51, 95% CI 0.35-0.74, p<0.0001), 30-day survival (HR 0.47, 95% CI 0.28-0.77, p=0.003), and 1-year survival (HR 0.53, 95% CI 0.33-0.83, p=0.006) favouring extracorporeal CPR over conventional CPR. INTERPRETATION Extracorporeal CPR had a short-term and long-term survival benefit over conventional CPR in patients with in-hospital cardiac arrest of cardiac origin.

Analysis of the outcome for patients experiencing myocardial infarction and cardiopulmonary resuscitation refractory to conventional therapies necessitating extracorporeal life support rescue.

Objective:To analyze the results of acute myocardial infarction (AMI) complicated with refractory shock necessitating extracorporeal life support (ECLS) rescue and to search for associated risk factors. Design:Retrospective review of our 9-yr experience with patients initially presenting with AMI with shock necessitating ECLS rescue; analysis of patient outcomes. Setting:A university-affiliated tertiary referral medical center. Patients:Between 1994 and 2003 inclusively, 36 consecutive patients (age [mean ± sd], 57 ± 10 yrs) with AMI complicated by refractory shock and undergoing cardiopulmonary resuscitation (CPR) necessitating emergent ECLS rescue were enrolled in this study. Intervention:All patients underwent CPR before ECLS, although 30 patients (83.3%) received ECLS during CPR because spontaneous circulation failed to return. All patients underwent intraaortic counterpulsation either before or following rescue. Seven patients underwent angioplasty only, and one underwent heart transplantation without any intervention. Twenty-eight patients underwent coronary artery bypass grafting (CABG), in which the beating-heart technique was used for 20 patients. Measurements and Main Results:The pre-ECLS blood lactate level was high (13.4 ± 8.5 mmol/L), as was the inotropic score (121.4 ± 117.3 &mgr;g/kg/min). Twenty-five patients (69.4%) were successfully weaned off ECLS, and 12 (48%) survived to discharge (one had a neurologic deficit). The overall mortality rate was 66.7%. A lower inotropic score, reduced blood lactate level, shorter CPR duration, surgical revascularization, and a reduced total maximal Sepsis-related Organ Failure Assessment (SOFA) score were noted among survivors. Liver failure, central nervous system failure, and renal failure mainly occurred in nonsurvivors after ECLS. The technique used for surgical revascularization (beating heart or arrested heart) did not influence the outcome. ECLS is associated with a lower mortality rate than that expected (>90%) from the resultant total maximal SOFA score (16.6 ± 3.0). Conclusions:AMI complicated with refractory shock remains associated with a high mortality rate, even following ECLS rescue, although ECLS might afford a better chance of survival. The SOFA score can be applied to ECLS condition as a reference point for predicting outcome.

Extracorporeal membrane oxygenation support can extend the duration of cardiopulmonary resuscitation.

Objectives:To evaluate the use of extracorporeal membrane oxygenation in prolonged cardiopulmonary resuscitation and to estimate how long cardiopulmonary resuscitation can be extended with acceptable results. Design:Review of consecutive adult in-hospital cardiopulmonary resuscitation patients without return of spontaneous circulation in 10 mins and with extracorporeal membrane oxygenation rescue, and analysis of the relationship between outcome and cardiopulmonary resuscitation duration and possible etiologies. The data were collected following the Utstein style guidelines on in-hospital cardiopulmonary resuscitation. Two organ dysfunction scores were incorporated into the analysis for outcome prediction. Setting:A university-affiliated tertiary referral medical center and extracorporeal membrane oxygenation center. Patients:An observational cohort study in 135 consecutive adult in-hospital cardiopulmonary resuscitation patients without return of spontaneous circulation who received extracorporeal membrane oxygenation during cardiopulmonary resuscitation. Main Results:The average cardiopulmonary resuscitation duration was 55.7 ± 27.0 mins and 56.3% of patients received subsequent interventions to treat underlying etiologies. The successful weaning rate was 58.5% and the survival-to-discharge rate was 34.1%. The majority of survivors (89%) had an acceptable neurologic status on discharge. Risk factors for hospital mortality included longer cardiopulmonary resuscitation duration, etiology of acute coronary syndrome, and a higher organ dysfunction score in the first 24 hrs. Logistic regression analysis revealed the probability of survival was approximately 0.5, 0.3, or 0.1 when the duration of cardiopulmonary resuscitation was 30, 60, or 90 mins, respectively. Conclusion:Assisted circulation might extend the presently accepted duration of cardiopulmonary resuscitation in adult in-hospital cardiopulmonary resuscitation patients.

The cardiomyogenic differentiation of rat mesenchymal stem cells on silk fibroin-polysaccharide cardiac patches in vitro.

Polysaccharides and proteins profoundly impact the development and growth of tissues in the natural extra-cellular matrix (ECM). To mimic a natural ECM, polysaccharides were incorporated to/or co-sprayed with silk fibroin (SF) to produce SF/chitosan (CS) or SF/CS-hyaluronic acid (SF/CS-HA) microparticles that were further processed by mechanical pressing and genipin cross-linking to produce hybrid cardiac patches. The ATR-FTIR spectra confirm the co-existence of CS or CS-HA and SF in microparticles and patches. For evaluating the cellular responses of rMSCs to the SF/CS and SF/CS-HA cardiac patches, the growth of rMSCs and cardiomyogenic differentiation of 5-aza inducing rMSCs cultured on patches was examined. First, the isolated rMSCs were identified with various positive and negative surface markers such as CD 44 and CD 31 by a flow cytometric technique, respectively. For examining the growth of rMSCs on the patches, MTT viability assay was performed, and the results demonstrated that the growth of rMSCs on SF and SF-hybrid patches significantly exceeded (P<0.001) that on culture wells after seven days of cultivation. Additionally, the relative growth rates of rMSCs on SF/CS and SF/CS-HA hybrid patches were significantly better (P<0.01) than that on SF patches that were also observed by using vimentin stain to the cells. For instance, the relative cell growth rates (%) in cell culture wells, SF, SF/CS and SF/CS-HA patches were 100%, 282.9+/-6.5%, 337.0+/-8.0% and 332.6+/-6.6% (n=6, for all), respectively. For investigating the effects of the hybrid patches on cardiomyogenic differentiation of 5-aza inducing rMSCs, the expressions of specific cardiac genes of cells such as Gata4 and Nkx2.5 were examined by real-time quantitative polymerase chain reaction (real-time PCR) analysis. The results of cardiomyogenic differentiation of induced rMSCs on SF/CS and SF/CS-HA hybrid patches significantly improved the expressions of cardiac genes of Gata4, Nkx2.5, Tnnt2 and Actc1 genes (all, P<0.01 or better, n=3) than those on SF patches and culture wells. Interestingly, the results of cardiac gene expressions of the cells on the SF/CS-HA hybrid patches were the most pronounced in promoting cardiomyogenic differentiations in this investigation. Furthermore, immunofluorescence staining of cardiac proteins such as cardiotin and connexin 43 for induced rMSCs cultured on SF/CS and SF/CS-HA hybrid patches were much pronounced compared with SF patches, indicating the improvements of cardiomyogenic differentiation on the hybrid patches. The results of this study demonstrate that the SF/CS and SF/CS-HA hybrid patches may be promising biomaterials for regenerating infarcted cardiac tissues.

Improved outcome of extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest--a comparison with that for extracorporeal rescue for in-hospital cardiac arrest.

PURPOSE The aim was to investigate the effects of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) and compare the results with those of in-hospital cardiac arrest (IHCA). METHODS We analyzed our extracorporeal membrane oxygenation (ECMO) results for patients who received ECPR for OHCA or IHCA in the last 5 years. Pre-arrest, resuscitation, and post-resuscitative data were evaluated. RESULTS In the last 5 years, ECPR was used 230 times for OHCA (n=31) and IHCA (n=199). The basic demographic data showed significant differences in age, cardiomyopathy, and location of the initial CPR. Duration of ischemia was shorter in the IHCA group (44.4±24.7 min vs. 67.5±30.6 min, p<0.05). About 50% of each group underwent a further intervention to treat the underlying etiology. ECMO was maintained for a shorter duration in the OHCA patients (61±48 h vs. 94±122 h, p<0.05). Survival to discharge was similar in the two groups (38.7% for OHCA vs. 31.2% for IHCA, p>0.05), as was the favorable outcome rate (25.5% for OHCA vs. 25.1% for IHCA, p>0.05). Survival was acceptable (about 33%) in both groups when the duration of ischemia was no longer than 75 min. CONCLUSIONS In addition to having a beneficial effect in IHCA, ECPR can lead to survival and a positive neurological outcome in selected OHCA patients after prolonged resuscitation. Our results suggest that further investigation of the use of ECMO in OHCA is warranted.

Comparing the survival between extracorporeal rescue and conventional resuscitation in adult in-hospital cardiac arrests: Propensity analysis of three-year data

AIM Extracorporeal cardiopulmonary resuscitation (ECPR) has been shown to have survival benefit over conventional CPR (CCPR) in patients with in-hospital cardiac arrest of cardiac origin. We compared the survival of patients who had return of spontaneous beating (ROSB) after ECPR with the survival of those who had return of spontaneous circulation (ROSC) after conventional CPR. METHODS Propensity score-matched cohort of adults with in-hospital prolonged CPR (>10min) of cardiac origin in a university-affiliated tertiary extracorporeal resuscitation center were included in this study. Fifty-nine patients with ROSB after ECPR and 63 patients with sustained ROSC by CCPR were analyzed. Main outcome measures were survival at hospital discharge, 30 days, 6 months, and one year, and neurological outcome. RESULTS There was no statistical difference in survival to discharge (29.1% of ECPR responders vs. 22.2% of CCPR responders, p=0.394) and neurological outcome at discharge and one year later. In the propensity score-matched groups, 9 out of 27 ECPR patients survived to one month (33.3%) and 7 out of 27 CCPR patients survived (25.9%). Survival analysis showed no survival difference (HR: 0.856, p=0.634, 95% CI: 0.453-1.620) between the groups, either at 30 days or at the end of one year (HR: 0.602, p=0.093, 95% CI: 0.333-1.088). CONCLUSIONS This study failed to demonstrate a survival difference between patients who had ROSB after institution of ECMO and those who had ROSC after conventional CPR. Further studies evaluating the role of ECMO in conventional CPR rescued patients are warranted.

Cardiac repair achieved by bone marrow mesenchymal stem cells/silk fibroin/hyaluronic acid patches in a rat of myocardial infarction model.

Bone marrow mesenchymal stem cells/silk fibroin/hyaluronic acid (BMSC/SH) patches were implanted into myocardial infarction (MI) rat hearts to investigate the efficacies of them on enhancing left ventricular (LV) remodeling and cardiac repair. 45 rats were divided into four groups: Sham, MI (MI hearts, induced by a cryo-injury technique), SH and BMSC/SH (MI hearts with implantations of SH and BMSC/SH patches, respectively). After eight weeks of post-implantation, the patches for the SH and BMSC/SH groups were intact and well adhered on the MI zones with no and minor immunological responses, respectively, examined by a CD68 marker, while severe inflammation on the zones was observed for the MI group. The SH group showed the efficacy of cardiac repair on MI zones. Moreover, BMSC/SH group significantly improved the wall thickness of LV, assessed by echocardiography, and had high viability of delivery BMSC, largely reduced apoptosis, significantly promoted neo-vascularization and stimulated the secretions of various paracrine factors such as VEGF, examined by real-time PCR, in MI zones compared with those of the SH and MI groups. In conclusion, the therapeutic efficacies of using BMSC/SH patches for repairing MI hearts were demonstrated by showing the advantages of both bioactive SH patches and BMSC-based therapy.

Extracorporeal membranous oxygenation support for acute fulminant myocarditis: analysis of a single center's experience.

OBJECTIVES Acute fulminant myocarditis (AFM) is a disease category that is easily neglected. Circulatory mechanical support is sometimes required for this devastating condition. We analyzed our experience in managing AFM with mechanical circulatory support. METHODS We applied extracorporeal membrane oxygenation (ECMO) as a first-line rescue for AFM. The diagnosis was mainly derived from clinical results and biopsy. RESULTS Seventy-five patients were enrolled in the age range of 29.6 ± 18.6 years and the pediatric group (< 18 years) comprised 32% (n = 24) of our patient group. Thirty-five patients (47%) underwent cardiopulmonary resuscitation (CPR) before ECMO. The indication for ECMO included high inotropic support 69% (n = 54) and continuous CPR at ECMO setup 31% (n = 23). The ECMO duration was 171 ± 121 h. Survival to discharge was 64% (n = 48), 61% in adult group, and 70.8% in pediatric group. Six patients were later bridged to ventricular assist device use (5 left ventricular assist device (LVAD) and 1 bi-ventricular assist device (BVAD)) but three died of multiple-organ failure. Three patients (4%) underwent heart transplantation and all of them survived to discharge. Resuscitation did not have a significant factor for survival. Only two patients (3%) developed late mortality due to a cardiac event. CONCLUSIONS AFM still carries high mortality rates in spite of advanced mechanical support. Most of the survivors did not require transplantation and could return to good lifestyle. Due to its simplicity and effectiveness, ECMO can be a first-line tool to rescue this group of patients.

The influence of rat mesenchymal stem cell CD44 surface markers on cell growth, fibronectin expression, and cardiomyogenic differentiation on silk fibroin – Hyaluronic acid cardiac patches

Since MSCs contain an abundant of CD44 surface markers, it is of interesting to investigate whether CD44 on rat MSC (rMSCs) influenced cell growth, fibronectin expression and cardiomyogenic differentiation on new SF/HA cardiac patches. For this investigation, we examined the influences of rMSCs with or without a CD44-blockage treatment on the aforementioned issues after they were cultivated, and further induced by 5-aza on SF and SF/HA patches. The results showed that the relative growth rates of rMSCs cultured on cultural wells, SF/HA patches without or with a CD44-blockage treatment were 100%, 208.9+/-7.1 (%) or 48.4+/-6.0 (%) (n=3, for all), respectively, after five days of cultivations. Moreover, rMSCs cultivated on SF/HA patches highly promoted fibronectin expressions (e.g., 1.8x10(5)/cell, in fluorescent intensity) while cells with a CD44-blockage treatment markedly diminished the expressions (e.g., 1.1x10(4)/cell, in fluorescent intensity) on same patches. For investigating possible influences of CD44 surface markers of rMSCs on their cardiomyogenic differentiation, the expressions of specific cardiac genes of cells were examined by using real-time PCR analysis. The results indicated that 5-aza inducing rMSCs significantly promoted the expressions of Gata4, Nkx2.5, Tnnt2 and Actc1 genes (all, P<0.01 or better, n=3) on SF/HA patches compared with those expressions on SF patches and for cells with a CD44-blockage treatment on SF/HA patches. Furthermore, the intensity of the expressions of cardiotin and connexin 43 of 5-aza inducing rMSCs were markedly higher than those of cells with a CD44-blockage treatment after they were cultured on SF/HA patches. Through this study, we reported that CD44 surface markers of rMSCs highly influenced the proliferations, fibronectin expressions and cardiomyogenic differentiation of rMSCs cultivated on cardiac SF/HA patches.

Extracorporeal membrane oxygenation for perioperative cardiac allograft failure

The utility of mechanical support in pretransplant stabilization and postcardiotomy shock is well established, but its use in perioperative cardiac allograft failure (PCAGF) rescue has not been well documented. Ventricular assist devices (VADs) have been applied to PCAGF rescue with acceptable results. However, studies have not described the results of using extracorporeal membrane oxygenation (ECMO) in PCAGF. We evaluated the outcome of PCAGF rescue with ECMO. A retrospective review of 204 consecutive heart transplants revealed 19 cases of PCAGF requiring ECMO rescue. Donor-, surgery- and ECMO-related variables were evaluated for association with operative mortality, success of weaning, and survival rate. Transplant recipients included 14 males and 5 females with median age of 44.2 years. Weaning rate was 84.2% and survival rate was 52.6%, with duration of ECMO support 157 ± 129 hours. Long ischemic time is a PCAGF risk factor (206.8 ± 96.1 minutes vs. 158.3 ± 60.8 minutes in non-PCAGF, p < 0.05). PCAGF etiology included primary graft failure (n = 7); right heart failure secondary to pulmonary hypertension, coagulopathy/intraoperative hemorrhage (n = 7); and sepsis (n = 2). Compared with data from VAD-supported PCAGF, ECMO had a better weaning and graft survival rates (p < 0.05). ECMO is another choice for PCAGF rescue. It has an acceptable survival rate and may be considered instead of VADs as a first-line rescue for PCAGF.