Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive. METHODS: In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis. RESULTS: Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups. CONCLUSIONS: In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).

Higher mean cerebral oxygen saturation shortly after extracorporeal cardiopulmonary resuscitation in patients who regain consciousness.

INTRODUCTION: In cardiac arrest, cerebral ischemia and reperfusion injury mainly determine the neurological outcome. The aim of this study was to investigate the relation between the course of cerebral oxygenation and regain of consciousness in patients treated with extracorporeal cardiopulmonary resuscitation (ECPR). We hypothesized that rapid cerebral oxygenation increase causes unfavorable outcomes. METHODS: This prospective observational study was conducted in three European hospitals. We included adult ECPR patients between October 2018 and March 2020, in whom cerebral regional oxygen saturation (rSO2 ) measurements were started minutes before ECPR initiation until 3 h after. The primary outcome was regain of consciousness, defined as following commands, analyzed using binary logistic regression. RESULTS: The sample consisted of 26 ECPR patients (23% women, Agemean 46 years). We found no significant differences in rSO2 values at baseline (49.1% versus 49.3% for regain versus no regain of consciousness). Mean cerebral rSO2 values in the first 30 min after ECPR initiation were higher in patients who regained consciousness (38%) than in patients who did not regain consciousness (62%, odds ratio 1.23, 95% confidence interval 1.01-1.50). CONCLUSION: Higher mean cerebral rSO2 values in the first 30 min after initiation of ECPR were found in patients who regained consciousness.

Functional evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO in cardiogenic shock.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly adopted for the treatment of cardiogenic shock (CS). However, a marker of successful weaning remains largely unknown. Our hypothesis was that successful weaning is associated with sustained microcirculatory function during ECMO flow reduction. Therefore, we sought to test the usefulness of microcirculatory imaging in the same sublingual spot, using incident dark field (IDF) imaging in assessing successful weaning from VA-ECMO and compare IDF imaging with echocardiographic parameters. METHODS: Weaning was performed by decreasing the VA-ECMO flow to 50% (F50) from the baseline. The endpoint of the study was successful VA-ECMO explantation within 48 hours after weaning. The response of sublingual microcirculation to a weaning attempt (WA) was evaluated. Microcirculation was measured in one sublingual area (single spot (ss)) using CytoCam IDF imaging during WA. Total vessel density (TVDss) and perfused vessel density (PVDss) of the sublingual area were evaluated before and during 50% flow reduction (TVDssF50, PVDssF50) after a WA and compared to conventional echocardiographic parameters as indicators of the success or failure of the WA. RESULTS: Patients (n = 13) aged 49 ± 18 years, who received VA-ECMO for the treatment of refractory CS due to pulmonary embolism (n = 5), post cardiotomy (n = 3), acute coronary syndrome (n = 2), myocarditis (n = 2) and drug intoxication (n = 1), were included. TVDssF50 (21.9 vs 12.9 mm/mm2, p = 0.001), PVDssF50 (19.7 vs 12.4 mm/mm2, p = 0.01) and aortic velocity-time integral (VTI) at 50% flow reduction (VTIF50) were higher in patients successfully weaned vs not successfully weaned. The area under the curve (AUC) was 0.99 vs 0.93 vs 0.85 for TVDssF50 (small vessels) >12.2 mm/mm2, left ventricular ejection fraction (LVEF) >15% and aortic VTI >11 cm. Likewise, the AUC was 0.91 vs 0.93 vs 0.85 for the PVDssF50 (all vessels) >14.8 mm/mm2, LVEF >15% and aortic VTI >11 cm. CONCLUSION: This study identified sublingual microcirculation as a novel potential marker for identifying successful weaning from VA-ECMO. Sustained values of TVDssF50 and PVDssF50 were found to be specific and sensitive indicators of successful weaning from VA-ECMO as compared to echocardiographic parameters.

Microcirculatory assessment of patients under VA-ECMO.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective technique for providing emergency mechanical circulatory support for patients with cardiogenic shock. VA-ECMO enables a rapid restoration of global systemic organ perfusion, but it has not been found to always show a parallel improvement in the microcirculation. We hypothesized in this study that the response of the microcirculation to the initiation of VA-ECMO might identify patients with increased chances of intensive care unit (ICU) survival. METHODS: Twenty-four patients were included in this study. Sublingual microcirculation measurements were performed using the CytoCam-IDF (incident dark field) imaging device. Microcirculatory measurements were performed at baseline, after VA-ECMO insertion (T1), 48-72 h after initiation of VA-ECMO (T2), 5-6 days after (T3), 9-10 days after (T4), and within 24 h of VA-ECMO removal. RESULTS: Of the 24 patients included in the study population, 15 survived and 9 died while on VA-ECMO. There was no significant difference between the systemic global hemodynamic variables at initiation of VA-ECMO between the survivors and non-survivors. There was, however, a significant difference in the microcirculatory parameters of both small and large vessels at all time points between the survivors and non-survivors. Perfused vessel density (PVD) at baseline (survivor versus non-survivor, 19.21 versus 13.78 mm/mm2, p = 0.001) was able to predict ICU survival on initiation of VA-ECMO; the area under the receiver operating characteristic curve (ROC) was 0.908 (95 % confidence interval 0.772-1.0). CONCLUSION: PVD of the sublingual microcirculation at initiation of VA-ECMO can be used to predict ICU mortality in patients with cardiogenic shock.

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body: A Multicenter, Prospective Observational Study.

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6-26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.

Disturbance of glucose homeostasis after pediatric cardiac surgery.

This study aimed to evaluate the time course of perioperative blood glucose levels of children undergoing cardiac surgery for congenital heart disease in relation to endogenous stress hormones, inflammatory mediators, and exogenous factors such as caloric intake and glucocorticoid use. The study prospectively included 49 children undergoing cardiac surgery. Blood glucose levels, hormonal alterations, and inflammatory responses were investigated before and at the end of surgery, then 12 and 24 h afterward. In general, blood glucose levels were highest at the end of surgery. Hyperglycemia, defined as a glucose level higher than 8.3 mmol/l (>150 mg/dl) was present in 52% of the children at the end of surgery. Spontaneous normalization of blood glucose occurred in 94% of the children within 24 h. During surgery, glucocorticoids were administered to 65% of the children, and this was the main factor associated with hyperglycemia at the end of surgery (determined by univariate analysis of variance). Hyperglycemia disappeared spontaneously without insulin therapy after 12-24 h for the majority of the children. Postoperative morbidity was low in the study group, so the presumed positive effects of glucocorticoids seemed to outweigh the adverse effects of iatrogenic hyperglycemia.

Recovery of long-axis left ventricular function after aortic valve replacement in patients with severe aortic stenosis.

BACKGROUND: Patients with aortic stenosis (AS) should undergo aortic valve replacement (AVR) before irreversible LV dysfunction has developed. Assessment of long-axis left ventricular (LV) function may assist in proper timing of AVR. OBJECTIVES: To assess serial changes in long-axis LV function before and after AVR in patients with severe AS and preserved LV ejection fraction. METHODS: The study comprised 27 consecutive patients (mean age 64.9 ± 11.7 years, 15 males) with symptomatic severe AS, scheduled for AVR. Seventeen subjects without known cardiac disease, matched for age, gender, LV ejection fraction and cardiovascular risk factors, served as a control group. Long-axis LV function assessment was done with tissue Doppler imaging at 3 weeks, 6 months, and 12 months after AVR. RESULTS: Mean aortic valve area in the AS group was 0.70 ± 0.24 cm². Pre-AVR peak systolic mitral annular velocities were significantly lower compared to controls (6.7 ± 1.5 vs. 8.9 ± 2.0 cm/s, P < 0.05). Post-AVR peak systolic mitral annular velocities improved to 9.1 ± 2.9 at 3 weeks, 8.6 ± 2.7 at 6 months, and 8.1 ± 1.7 cm/s at 12 months (P < 0.05). Improvements were seen over the whole range of pre-AVR peak systolic mitral annular velocities. Patients with improved Sm after AVR (defined as ≥ 10% compared to baseline values) did not differ in baseline characteristics as compared to those who did not improve. CONCLUSIONS: In patients with severe AS and preserved LV ejection fraction, abnormal systolic mitral annular velocities improve after AVR, independent of the pre-AVR value.

A novel mortality risk score predicting intensive care mortality in cardiogenic shock patients treated with veno-arterial extracorporeal membrane oxygenation.

PURPOSE: Mortality after veno-arterial extracorporeal membrane oxygenation (VA-ECMO) implantation remains a major problem in patients with cardiogenic shock. Our objective was to assess the utility of the SOFA score in combination with markers of right ventricular (RV) dysfunction in predicting mortality in the ICU. MATERIALS AND METHODS: Data were retrospectively obtained from all adult patients (n=103) who were treated with VA-ECMO between November 2004 and January 2016. The primary outcome of this study was ICU mortality after VA-ECMO implantation. Using the clinical, demographic and echocardiographic data, we developed a novel mortality risk score, the SOFA-RV score, which combine RV-function to the SOFA score at the time of VA-ECMO implantation. RESULTS: Out of 103 patients, 37 (36%) died in the ICU. The median duration of VA-ECMO support was 7 days [IQR 4-11], mean age 49 ± 16 years, and 54% were male. SOFA-RV score has an AUC of 0.70, and was significantly better than SOFA alone (AUC of 0.57) in predicting ICU mortality. In addition, SAVE and MELD scores were not able to predict ICU mortality. CONCLUSION: Adding RV-function to the existing SOFA score improves significantly the prediction of ICU mortality in patients on VA-ECMO. Dedicated evaluation of RV function in patients with VA-ECMO is therefore recommended.

Survival and neurological outcome with extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest caused by massive pulmonary embolism: A two center observational study.

BACKGROUND: Cardiac arrest (CA) due to pulmonary embolism (PE) is associated with low survival rates and poor neurological outcomes. We examined whether Extracorporeal Cardiopulmonary Resuscitation (ECPR) improves the outcomes of patients who suffer from CA due to massive PE. METHODS: We retrospectively included 39 CA patients with proven or strongly suspected PE in two hospitals in the Netherlands, in a 'before/after'-design. 20 of these patients were treated with Conventional Cardiopulmonary Resuscitation (CCPR) and 19 patients with ECPR. RESULTS: The main outcomes of this study were ICU survival and favourable neurological outcome, defined as Cerebral Performance Category (CPC) score 1-2. The ICU survival rate in CCPR patients was 5% compared to 26% in ECPR patients (p<0.01). Survival with favourable neurological outcome was present in 0/20 (0%) CCPR patients compared to 4/19 (21%) of the ECPR patients (p<0.05). CONCLUSION: ECPR seems a promising treatment for cardiac arrest patients due to (suspected) massive pulmonary embolism compared to conventional CPR, though outcomes remain poor.

[Infections during glucocorticoid use]. / Infecties bij gebruik van glucocorticoïden.

Glucocorticoid treatment increases the risk of opportunistic infection. Infections that can arise during glucocorticoid use, and for which preventative measures can be taken, include reactivation of latent tuberculosis and hepatitis B, pneumococcal and Pneumocystis jiroveci pneumonia, influenza, herpes zoster and Strongyloides stercoralis hyperinfection syndrome. The risk of such infections depends upon the duration of glucocorticoid use and dosage, as well as comorbidity and comedication. It is important to enquire about vaccinations, travel, exposure and previous infections when taking a case history. Possible infectious complications should be considered in patients who are receiving high-dose glucocorticoids treatment amounting to more than 420 mg PED per 4 weeks. Preventative measures are not usually required in patients who receive a short high-dosed treatment (30 mg PED in 7 days) or prednisolone at a dosage of < 15 mg/day.

Metabolic alkalosis after pediatric cardiac surgery.

OBJECTIVE: To determine occurrence, causes and associated mortality of postoperative metabolic alkalosis in pediatric cardiac surgery. METHODS: We retrospectively analyzed clinical and biochemical variables of 186 consecutive cardiac operations other than ductal ligations on children less than 2 years old during the years 1999 and 2000. Metabolic alkalosis was defined as a pH>7.48 corrected for PCO2, with a base excess > or =5 on two or more consecutive measurements during an 8h period. RESULTS: Median age was 15 weeks [range 2 days-95 weeks] and median weight 4.5 kg [range 2.1-15.7 kg]. In 157 cases, cardiopulmonary bypass was used. In 92 [49%] procedures, metabolic alkalosis occurred with the highest corrected pH 24.3h after operation. Multivariate regression analysis associated age [P<0.001], cardiopulmonary bypass [P<0.001] and preoperative ductal dependency [P=0.04] with postoperative metabolic alkalosis. Of the surgical procedures the arterial switch for transposition of the great arteries [n=19] was strongly associated with metabolic alkalosis [100%, P<0.001]. Hemodilution appeared to enhance the development of alkalosis: those who experienced alkalosis had been hemodiluted to a greater extent [P=0.007]. Nearly 95% of patients experienced some increase in bicarbonate, but patients with metabolic alkalosis experienced more than those without [5.9 versus 3.5 mmol/l, P<0.001]. There were four postoperative deaths, only one coincidental with metabolic alkalosis. CONCLUSIONS: Metabolic alkalosis has a high incidence after pediatric cardiac surgery, strongly associated with younger age, cardiopulmonary bypass, preoperative ductal dependency and perioperative hemodilution. Early recognition allows for timely therapeutic intervention.

[Heart transplantation in the 21st century in Netherlands: improved survival in the last decade]. / Harttransplantatie in de 21e eeuw: de overleving wordt beter.

OBJECTIVE: Over the past decades donor and recipient characteristics and medical management of heart transplantations patients have changed markedly. We studied the impact of these changes on long-term clinical outcome. DESIGN AND METHODS: Data of all consecutive heart transplant recipients in our center have been collected prospectively. Cohort A (n = 353 patients) was defined as the patients transplanted between 1984 and 1999, and was compared with cohort B (n = 227 patients) transplanted between 2000 and 2013. RESULTS: Compared to cohort A, recipients in cohort B had older donors (mean age 29 vs. 43 years, donors aged > 50 year: 2% vs. 33%, respectively). One-year survival in cohort A vs. B was 89% vs. 86% and at 10 years 53% vs. 68%, respectively (p = 0.02). Cohort B patients were treated more often with tacrolimus based immunosuppression (77% vs. 22%; p < 0.001), and early statins post-heart transplantation (88% vs. 18%; p = 0.001), while renal function was better conserved at 5 and 10 years (p = 0.001 and 0.02). Multivariate analysis showed significant reduction in 10 years mortality with tacrolimus-based immunosuppression (HR: 0.27 and 95% CI 0.17-0.42), treatment of hypertension (HR: 0.5, 95% CI 0.36-0.72) and revascularization (HR: 0.28, 95% CI 0.15-0.52). CONCLUSION: In spite of the use of much older donors, the long-term outcome after heart transplantation has improved considerably in the last decade, probably due to the introduction of newer treatment modalities.

Mechanical circulatory support devices improve tissue perfusion in patients with end-stage heart failure or cardiogenic shock.

OBJECTIVES: This study evaluated the effects of mechanical circulatory support (MCS) on sub-lingual microcirculation as a surrogate for splanchnic microvascular perfusion. METHODS: Between May 2008 and April 2009, 10 consecutive patients received an MCS device or extracorporeal membrane oxygenation for end-stage chronic heart failure (n = 6) or cardiogenic shock (n = 4). Microcirculation was investigated using a hand-held Sidestream Dark Field imaging device. Perfused capillary density (PCD) and capillary red blood cell velocity (cRBCv) were assessed before device implantation (T0), immediately after implantation (T1), and 1 day after implantation (T2). RESULTS: Median patient age was 45 years (interquartile range [IQR] 38-52 years) and 70% were men. MCS significantly decreased pulmonary capillary wedge pressure (p = 0.04). Median cardiac power index increased (0.29 [IQR, 0.21-0.34] W/m(2) at T0 vs 0.48 [IQR, 0.39-0.54] W/m(2) at T1, p = 0.005) as well as median central venous oxygen saturation (54% [IQR, 46%-61%] at T0 vs 78% [IQR, 67%-85%] at T1, p = 0.007). There was a 3-fold increase in tissue perfusion index (sub-lingual PCD x cRBCv) during mechanical circulatory support (573 [IQR, 407-693] at T0 vs 1909 [IQR, 1771-2835] at T1, p = 0.005). Microcirculatory parameters remained improved at T2. CONCLUSION: Mechanical circulatory support for severe heart failure is associated with a consistent, significant, and sustained improvement in tissue perfusion, as measured at the bedside by a 2-dimensional microcirculation imaging technique.

Connecting the Centrimag Levitronix pump to Berlin Heart Excor cannulae; a new approach to bridge to bridge.

BACKGROUND: An increasing number of children are requiring circulatory support. Hospitals offering pediatric Ventricular Assist Device (VAD) should have devices of different sizes available to cover the full range of patient sizes incurring considerable expense. As in adults, post-operative bleeding often complicates VAD implantation. The use of a Levitronix Centrimag centrifugal pump, connected to Berlin Heart Excor cannulae, seems an attractive and logic combination, both in terms of patient safety and of hospital economics. METHODS: We describe 3 children with therapy resistant cardiac failure who underwent extracorporeal membrane oxygenation (ECMO) as a rescue before proceeding to placement of the Berlin Heart Excor paracorporeal assist device. The Levitronix Centrimag pump was used as an intermediate device to allow the patients to be stabilised. Therefore, only Berlin Heart cannulae of different sizes have to be readily available; if successful stabilization can be achieved, the Berlin Heart Excor ventricles and the drive unit can then be ordered to replace the Levitronix pump. RESULTS: Two patients were successfully stabilised with the Levitronix pump and were switched to the definitive Berlin Heart Excor ventricles after 6 days of support. The third child succumbed due to intractable pulmonary hemorrhage in severely damaged lungs. No device related complications, especially no thrombo-embolic events, occurred during Levitronix support. CONCLUSION: The Levitronix Centrimag pump was easy to handle and gave effective circulatory support, the patients were only switched to the Berlin Heart Excor system after stabilization. In patients with a high risk of failure, it is a relatively cheap but safe and effective support system.

Early detection of left ventricular dysfunction by Doppler tissue imaging and N-terminal pro-B-type natriuretic peptide in patients with symptomatic severe aortic stenosis.

BACKGROUND: Patients with severe aortic stenosis (AS) require valve replacement before development of irreversible left ventricular (LV) dysfunction. It has been postulated that Doppler tissue imaging (DTI) parameters are more sensitive to detect subtle LV dysfunction compared with conventional echocardiographic parameters. OBJECTIVE: We sought to assess early LV dysfunction with DTI-derived echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with severe AS and normal LV ejection fraction. METHODS: A total of 29 patients (mean age 65 +/- 12 years, 15 male) with symptomatic severe AS and 17 control subjects were included in the study. DTI was performed at the level of the mitral lateral (m(lat)) and septal (m(sep)) annulus. Systolic (Sm), early (Em), and late (Am) diastolic velocities were measured, and E/Em ratio was calculated. NT-proBNP was determined by an electrochemiluminescence immunoassay. RESULTS: Baseline characteristics between patients and control subjects were similar regarding LV ejection fraction and mitral inflow E/A ratio. However, patients with AS had significantly lower DTI values (Sm, Em, Am) compared with control subjects. Moreover, LV filling pressures, expressed by the E/Em ratio, were significantly higher in patients. Correlation analysis showed a relationship between the natural logarithm of NT-proBNP and aortic valve area, Sm(lat), and E/Em((sep)) ratio. Using stepwise multiple linear regression, Sm(lat) was found to be independently related to NT-proBNP. CONCLUSIONS: In patients with severe AS and normal LV ejection fraction, DTI showed LV systolic and diastolic dysfunction compared with control subjects. DTI-derived variables, and especially Sm(lat), were correlated with NT-proBNP levels.