Early extracorporeal CPR for refractory out-of-hospital cardiac arrest

BACKGROUNDExtracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxy-genation in a patient who does not have spontaneous circulation. The evidencewith regard to the effect of extracorporeal CPR on survival with a favorable neu-rologic outcome in refractory out-of-hospital cardiac arrest is inconclusive.METHODSIn this multicenter, randomized, controlled trial conducted in the Netherlands, weassigned patients with an out-of-hospital cardiac arrest to receive extracorporealCPR or conventional CPR (standard advanced cardiac life support). Eligible patientswere between 18 and 70 years of age, had received bystander CPR, had an initialventricular arrhythmia, and did not have a return of spontaneous circulationwithin 15 minutes after CPR had been initiated. The primary outcome was sur-vival with a favorable neurologic outcome, defined as a Cerebral PerformanceCategory score of 1 or 2 (range, 1 to 5, with higher scores indicating more severedisability) at 30 days. Analyses were performed on an intention-to-treat basis.RESULTSOf the 160 patients who underwent randomization, 70 were assigned to receiveextracorporeal CPR and 64 to receive conventional CPR; 26 patients who did notmeet the inclusion criteria at hospital admission were excluded. At 30 days, 14 pa-tients (20%) in the extracorporeal-CPR group were alive with a favorable neuro-logic 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 seri-ous adverse events per patient was similar in the two groups.CONCLUSIONSIn patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR andconventional CPR had similar effects on survival with a favorable neurologic out-come. (Funded by the Netherlands Organization for Health Research and Develop-ment and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.govnumber, NCT03101787.)Cardiolog

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands: the COVID-OLD study

BackgroundDuring the first wave of the COVID-19 pandemic older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting.ObjectiveThe aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands.MethodsThis was a multi-centre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality.ResultsA total of 1,376 patients were included (median age 78 years (IQR 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 vs. 7 days), lower oxygen demand and lower levels of CRP. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared to patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95%CI 1.3-3.0) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95%CI 1.8-4.3)).ConclusionsThe in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.Pathophysiology, epidemiology and therapy of agein

Towards predicting cardiac function during veno-arterial extracorporeal life support

Severe heart failure patients that do not respond to conventional treatment will certainly die, unless such patients are placed on veno-arterial extracorporeal life support (VA-ELS). The VA-ELS (partially) takes over the cardiac and lung function, hereby reducing the burden on these organs. This support allows the heart and lungs to rest in order for them to recover, or serve as time to decide on next steps (transplantation, long term mechanical support, etc.). Current challenges in the management of these patients includes maintaining a proper filling status and determining when the heart and lungs are recovered sufficiently for the support to be withdrawn.A patient specific mathematical model could help gain insight on the physical and physiological processes that take place during VA-ELS. Additionally this model could serve as a clinical decision support tool to predict the optimal support flow and cardiac function.The project described in this report describes the first steps towards such a model. These steps can be divided in three parts: the design and start of a clinical study on measuring the cardiac function, choosing a mathematical model, and providing input on the pump, the oxygenator and on venous collapse.Previous research showed that the dynamic filling index (DFI) gives a measure of the cardiac function by assessing the drainable volume. A protocol was developed to measure the DFI. Approval to perform this protocol was received in July of 2014 by the central medical ethical comity. Currently 5 patients have been included and a total of 55 measurements have been performed. A major problem occurring in the measured data is the drift present in the pressures measured in the last two included patients.This drift should be investigated and solved before continuation of the measurements.Concerning the mathematical model, a one dimensional pulse wave propagation model was chosen.The pump and oxygenator were characterized to serve as input for this model. Additionally, in vitro measurements on venous collapse were performed as input for the model. The data measured this way raises some questions regarding the theory behind DFI measurements and warrant further investigation

Towards predicting cardiac function during veno-arterial extracorporeal life support

Severe heart failure patients that do not respond to conventional treatment will certainly die, unless such patients are placed on veno-arterial extracorporeal life support (VA-ELS). The VA-ELS (partially) takes over the cardiac and lung function, hereby reducing the burden on these organs. This support allows the heart and lungs to rest in order for them to recover, or serve as time to decide on next steps (transplantation, long term mechanical support, etc.). Current challenges in the management of these patients includes maintaining a proper filling status and determining when the heart and lungs are recovered sufficiently for the support to be withdrawn. A patient specific mathematical model could help gain insight on the physical and physiological processes that take place during VA-ELS. Additionally this model could serve as a clinical decision support tool to predict the optimal support flow and cardiac function. The project described in this report describes the first steps towards such a model. These steps can be divided in three parts: the design and start of a clinical study on measuring the cardiac function, choosing a mathematical model, and providing input on the pump, the oxygenator and on venous collapse. Previous research showed that the dynamic filling index (DFI) gives a measure of the cardiac function by assessing the drainable volume. A protocol was developed to measure the DFI. Approval to perform this protocol was received in July of 2014 by the central medical ethical comity. Currently 5 patients have been included and a total of 55 measurements have been performed. A major problem occurring in the measured data is the drift present in the pressures measured in the last two included patients. This drift should be investigated and solved before continuation of the measurements. Concerning the mathematical model, a one dimensional pulse wave propagation model was chosen. The pump and oxygenator were characterized to serve as input for this model. Additionally, in vitro measurements on venous collapse were performed as input for the model. The data measured this way raises some questions regarding the theory behind DFI measurements and warrant further investigation

Variability of microcirculatory measurements in healthy volunteers

Reliable assessment of the microcirculation is important to investigate microcirculatory properties in various disease states. The GlycoCheck system automatically analyzes sublingual sidestream dark field images to determine the perfused boundary region (PBR; a measure of glycocalyx thickness), red blood cell filling percentage, and microvascular vessel density. Although GlycoCheck has been used to study the microcirculation in patients, little is known about the reproducibility of measurements in healthy volunteers. We assessed intra- and interobserver agreement by having two experienced observers perform three consecutive microcirculation measurements with the GlycoCheck system in 49 healthy volunteers. Intraobserver agreement of single measurements were poor (intraclass correlation coefficients (ICCs)  0.6 (indicating good reproducibility) for all parameters when performing and averaging three consecutive measurements. No systematic differences were observed between observers for any parameter. Interobserver variability was fair for PBR (ICC = 0.53) and red blood cell filling percentage (ICC = 0.58) and poor for perfused vessel density (ICC = 0.20). In conclusion, GlycoCheck software can be used with acceptable reliability and reproducibility for microcirculation measurements on a population level when averaging three consecutive measurements. Repeated measurements are preferably performed by the same observer

National and reporting differences of pre-hospital factors in extracorporeal cardiopulmonary resuscitation studies

Extracorporeal cardiopulmonary resuscitation is the rapid deployment of extracorporeal life support during cardiac arrest and has emerged as a rescue therapy for refractory cardiac arrest. Systemic circulation and oxygenation are temporarily restored, such that medical efforts can be focussed on the diagnosis and treatment of the underlying cause of the arrest. Observational research has shown this may improve survival with good neurological outcome. Crucial in resuscitation is the interval between arrest and return of circulation. Four factors are of influence during this phase: 1) witnessed arrest, 2) no-flow duration, 3) bystander basic life support, and 4) low-flow duration. The purpose of this review is to describe the current level of evidence for these factors in conventional and extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest. Underreporting and national variability of the pre-hospital links in the chain-of-survival is prevalent. Consistent reporting is essential for new trials to enable comparison and generalisation to other regions

National and reporting differences of pre-hospital factors in extracorporeal cardiopulmonary resuscitation studies

Extracorporeal cardiopulmonary resuscitation is the rapid deployment of extracorporeal life support during cardiac arrest and has emerged as a rescue therapy for refractory cardiac arrest. Systemic circulation and oxygenation are temporarily restored, such that medical efforts can be focussed on the diagnosis and treatment of the underlying cause of the arrest. Observational research has shown this may improve survival with good neurological outcome. Crucial in resuscitation is the interval between arrest and return of circulation. Four factors are of influence during this phase: 1) witnessed arrest, 2) no-flow duration, 3) bystander basic life support, and 4) low-flow duration. The purpose of this review is to describe the current level of evidence for these factors in conventional and extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest. Underreporting and national variability of the pre-hospital links in the chain-of-survival is prevalent. Consistent reporting is essential for new trials to enable comparison and generalisation to other regions