Tissue Oximetry Changes during Postoperative Dangling in Lower Extremity Free Flap Reconstruction: A Pilot Study.

Background: Lower extremity free flap dangling protocols are still widely practiced, despite a paucity of evidence for their use. This pilot study investigates the use of tissue oximetry to provide further insight into the physiological effect of postoperative dangling in lower limb free flap transfer. Methods: Ten patients undergoing lower extremity free flap reconstruction were included in this study. Free flap tissue oxygen saturation (StO2) was continuously measured using non-invasive near-infrared spectroscopy. Measurements were performed on the free flap and contralateral limb during dangling from postoperative day (POD) 7 until 11, according to the local dangling protocol. Results: StO2 values measured in the free flap diminished to 70 ± 13.7% during dangling. This minimum StO2 was reached significantly later, and correspondingly the area under the curve (AUC) was significantly larger on POD 11 compared to the start of the dangling protocol on POD 7, reflecting an improving free flap microvascular reactivity. The dangling slope was equal between the free flap and contralateral leg. The reperfusion slope was significantly flatter on POD 7 compared to the other PODs (p < 0.001). Thereafter, no significant differences between PODs were observed. Patients with a history of smoking had significantly lower tissue oximetry values compared to non-smokers. Conclusions: The application of tissue oximetry during dangling provides further insight into the physiological effect (i.e., changes in microcirculatory function) of the free flap of the reconstructed lower extremity. This information could potentially be useful to either revise or disrupt the use of such dangling protocols.

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.).

Clinical evaluation of the novel Capiox NX19 adult oxygenator-a multicenter study.

INTRODUCTION: The novel Capiox NX19 adult oxygenator is, compared to its predecessors, improved with enhanced air removal technology, a polymer heat exchanger and smaller, innovative hollow fibers resulting in a surface area reduction and a lower priming volume. The aim of this study was to evaluate the NX19 oxygenator performance in a clinical setting. METHODS: A prospective multicenter study was performed involving three large European university hospitals. The Capiox NX19 (n = 150) performance was assessed during adult cardiopulmonary bypass and involved gaseous microemboli handling and gas transfer efficiency. The heat exchanger performance was evaluated separately in vitro. RESULTS: The heat exchanger performance factors were 0.80 ± 0.03 and 0.58 ± 0.04 at pump flow rates of 3 L/min and 6 L/min, respectively. After priming, residual post-oxygenator gaseous microemboli count and volume were decreased by 91% and 93.7%, respectively. The gas compartment pressure was 6.0 ± 2.5 mmHg, while the O2 transfer was 69 ± 30 mL/min/m2 and the CO2 transfer 73 ± 34 mL/min/m2. The O2 gradient was 44 ± 19 mmHg/LPM and the O2 diffusing capacity 0.38 ± 0.14 mL/min/mmHg. The shunt fraction was 0.19 ± 0.13, whereas oxygenator resistance and shear stress were 10.5 ± 3.7 mmHg/LPM and 5.1 ± 3.1 dyn/cm2, respectively. CONCLUSION: This multicenter study displayed good clinical safety and performance of the NX19 oxygenator.

Patterns of oxygen debt repayment in cardiogenic shock patients sustained with extracorporeal life support: A retrospective study.

Cardiogenic shock is the most frequent kind of shock in cardiac intensive care, and cardiac dysfunction and hypoxia are often seen in critically ill patients. Inadequate organ and tissue perfusion and hypoxia result in anaerobic metabolism with hyperlactatemia and oxygen debt accumulation. However, the role of accumulated oxygen debt in the course of cardiogenic shock and hypoxia has not been clearly described. Here, we first described the existence of several patterns of oxygen debt repayment in cardiogenic shock patients maintained by an extracorporeal life support system. Oxygen debt was computed from the lactate concentration at five time points, covering the first 26 h of ECLS. Patterns representing basic pathophysiological processes were independent of the cause of the primary insult. Groups of patients classified into specific patterns differed in terms of survival rate from 51.5% to only 4.6%. It is very important that the initial group not predetermine the fate of the patient and may change in the course of treatment due to 'between-cluster migration'. We believe that our finding of different patterns of oxygen debt repayment in cardiogenic shock patients may offer new insights for a more rational, goal-directed treatment of highly morbid conditions such as hypoxia and cardiogenic shock.

Dynamic oxygenator blood volume during prolonged extracorporeal life support.

Current methods for identification of oxygenator clotting during prolonged extracorporeal life support include visual inspection, evaluation of oxygenator resistance and oxygen exchange performance, and assessment of clotting-related laboratory parameters. However, these observations do not provide a quantitative assessment of oxygenator clot formation. By measuring changes in the dynamic oxygenator blood volume this study aimed to evaluate the relation to oxygenator resistance and oxygen transfer performance. Sixty-seven oxygenators were studied during adult extracorporeal life support. Oxygenator blood volume, oxygenator resistance, and oxygen transfer efficiency were monitored. Oxygenator blood volume decreased with increasing runtime (r = -0.462; p <0.001). There was a statistically significant, fair negative correlation between oxygenator blood volume and oxygenator resistance (r = -0.476; p<0.001) in all oxygenators, which became stronger analyzing only exchanged oxygenators (r = -0.680; p<0.001) and oxygenators with an oxygenator blood volume <187 mL (r = 0.831; p<0.001). No relevant correlation between oxygenator blood volume and O2 transfer was found. Oxygenator blood volume declined over time and was clearly associated with an increasing oxygenator resistance during prolonged extracorporeal life support, though O2 transfer was less affected.

Ethics of ECPR research.

The design of emergency medicine trials can raise several ethical concerns - risks may be greater, and randomisation may have to occur before consent. Research in emergency medicine is thus an illuminating context to explore the interplay between risk and randomisation, and the consequences for consent. Using a currently running trial, we describe possible concerns, considerations, and solutions to reconcile the conflicting interests of scientific inquiry, ethical principles, and clinical reality in emergency medicine research.

Point-of-Care Measurement of Kaolin Activated Clotting Time during Cardiopulmonary Bypass: A Single Sample Comparison between ACT Plus and i-STAT.

Heparin anticoagulation monitoring by point-of-care activated clotting time (ACT) is essential for cardiopulmonary bypass (CPB) initiation, maintenance, and anticoagulant reversal. Concerns exist regarding the comparability of kaolin activated ACT devices. The current study, therefore, evaluated the agreement of ACT assays using parallel measurements performed on two commonly used devices. Measurements were conducted in a split-sample fashion on both the ACT Plus (Medtronic, Minneapolis, MN) and i-STAT (Abbott Point of Care, Princeton, NJ) analyzers. Blood samples from 100 adult patients undergoing elective cardiac surgery with CPB were assayed at specified time points: before heparinization, following systemic heparinization, after CPB initiation, every 30 minutes during CPB, and following protamine administration. A cutoff value of 400 seconds (s) was used as part of the local protocol. Measurements were compared using t tests or Wilcoxon signed-rank tests, linear regression, and Bland-Altman analyses. Parallel ACT measurements demonstrated a good linear correlation (r = .831, p < .001). The overall median difference between both measurements was significantly different from zero, amounting to 87 (14-189) (p < .001), with limits of agreement of -124 and 333s. The i-STAT-derived ACT values were systematically lower than the ACT Plus values, which was more pronounced during CPB. Fourteen patients received additional heparin during CPB at a median ACT Plus value of 414s, with a concomitant median i-STAT value of 316s. Assuming 308s as the theoretical i-STAT cutoff value based on the linear regression equation and an ACT Plus threshold of 400s, 29 patients would have received additional heparin. Based on these results, kaolin point-of-care ACT devices cannot be used interchangeably. Device-specific predefined target values are warranted to avert heparin overdosing during CPB.

Economic Analysis of Noninvasive Tissue Oximetry for Postoperative Monitoring of Deep Inferior Epigastric Perforator Flap Breast Reconstruction: A Review.

Background. Postoperative monitoring of deep inferior epigastric perforator (DIEP) flaps for breast reconstruction using noninvasive tissue oximetry enables timely recognition of vascular compromise. This may limit ischemic tissue damage, minimizing postoperative morbidity and healthcare costs. The aim of this review was to provide an economic analysis of tissue oximetry for postoperative monitoring of DIEP flap breast reconstruction. Methods. A systematic literature search was conducted utilizing PubMed and Embase. Articles reporting costs related to tissue oximetry following DIEP flap breast reconstruction, costs directly related to DIEP flap surgical procedure, and costs associated with postoperative complications were included. Risk of bias was assessed using different tools depending on study type. Results. Six articles were included. Four studies provided an overview of total costs associated with DIEP flap breast reconstruction; two studies focused on whether tissue oximetry could facilitate a decrease in hospital costs. Average overall costs for DIEP flap procedure were estimated at $28 000, with additional costs up to $37 530 in case of total flap failure. Tissue oximetry to monitor DIEP flaps could potentially save up to $1667 per procedure. Moreover, it might eliminate the need for specialized postoperative care. Conclusion. Tissue oximetry following DIEP flap breast reconstruction can potentially facilitate a decrease in hospital costs since its readings enable physicians to intervene in an early stage of tissue malperfusion, contributing to minimizing complications. Tissue oximetry may eliminate the need for specialized postoperative care. However, based on the current literature, no firm conclusions can yet be drawn regarding cost-effectiveness of standard implementation.

To Purge or Not to Purge.

To remove gaseous microemboli (GME) using an oxygenator with an integrated arterial filter, it is recommended by some manufacturers to purge the oxygenator as an additional safety feature while on bypass. In this in vitro study, we evaluated whether purging of oxygenators with an integrated arterial filter is efficient in reducing GME. Five different types of commercially available contemporary oxygenators with an integrated arterial filter based on progressive filter filtration (1), cascade filtration (1), screen filtration (2), or self-venting (1) were tested for their efficiency in removing GME while keeping the purge line open or closed. A bubble counter was used for pre- and post-oxygenator GME signaling, from which the filter efficiency was computed. Freshly drawn heparinized porcine blood was used at blood flow rates of 3 and 5 L/min. Three units of each oxygenator were tested with its specific reservoir at a fixed volume level of 1,500 mL. GME load was introduced into the venous line at 1,000 mL air/min. Measurements started as soon as GME were detected by the pre-oxygenator probe and then continued for 1 minute. There was no statistically significant difference in filter efficiency between the purged and non-purged groups for specific oxygenators. At a blood flow of 3 L/min, the average filter efficiency stayed approximately invariable when comparing the non-purged and purged groups, where 89.1-88.2% indicated the largest difference between the groups. At a blood flow rate of 5 L/min, the filter efficiency changed in one screen filter group from an average of 55.7% in the non-purged group to 42.4% in the purged group. Other filter efficiencies at the blood flow rate of 5 L/min for non-purged compared with purged groups were, respectively, 98.0 vs. 98.0% (screen filtration), 88.6 vs. 85.8% (self-venting filtration), 82.8 vs. 75.5% (progressive filter filtration), and 65.4 vs. 65.1% (cascade filtration). Based on these results, purging while confronted with continuous GME challenge did not result in an increased filter efficiency.

Neurophysiological and paraspinal oximetry monitoring to detect spinal cord ischemia in patients during and after descending aortic repair: An international multicenter explorative study.

BACKGROUND: During descending aortic repair, critically decreased blood flow to the myelum can result in ischemic spinal cord injury and transient or permanent paraplegia. Assessment of motor evoked potentials (MEPs) has been shown to be a valuable tool which allows to detect spinal cord ischemia (SCI) intraoperatively within a therapeutic window suitable to prevent progression to paraparesis or paraplegia. MEP monitoring is not feasible during postoperative care in the awakening patient. Therefore, ancillary techniques to monitor integrity of spinal cord function are needed to detect delayed spinal cord ischemia. OBJECTIVE: The purpose of this study is to evaluate whether assessment of long loop reflexes (LLR; F-waves) and paraspinal muscle oximetry using Near-Infrared Spectroscopy (NIRS) are feasible and valid in detecting delayed SCI. METHODS: We aim to include patients from three tertiary referral centers undergoing aortic repair with MEP monitoring in this study.F-wave measurements and paraspinal NIRS oximetry will be operated intra- and postoperatively. Measurement characteristics and feasibility will be assessed in the first 25 patients. Subsequently, a second cohort of 75 patients will be investigated to determine the sensitivity and specificity of F-waves and NIRS in detecting perioperative SCI. In this context for the MEP group SCI is defined intraoperatively as significant MEP changes and postoperatively as newly developed paraplegia. CONCLUSIONS: A clinical study design and protocol is proposed to assess if F-waves and/or NIRS-based paraspinal oximetry are feasible and valid in detecting and monitoring for occurrences of delayed SCI.

Retrograde autologous priming to reduce allogeneic blood transfusion requirements: a systematic review.

BACKGROUND: Efforts have been made to minimize transfusion of packed red blood cells in patients undergoing cardiac surgery with cardiopulmonary bypass. One method concerns retrograde autologous priming. Although the technique has been used for decades, results remain contradictory in terms of transfusion requirements. OBJECTIVE: This systematic literature review aimed to summarize the evidence for the efficacy of retrograde autologous priming in terms of decreasing perioperative packed red blood cell requirements in adults. METHODS: Two researchers independently searched PubMed for articles published in the past 10 years. The modified Cochrane collaboration Risk of Bias Tool and the Research Triangle Institute Item Bank were used to assess bias. RESULTS: Eight studies were included, of which two randomized and six observational studies. Five studies, including one randomized study, report a significant decrease in packed red blood cell use in the retrograde autologous priming group compared to no retrograde autologous priming used. All studies are flawed by at least a high risk bias of bias score on one item of the bias assessment. CONCLUSION: Although most studies reported significantly fewer packed red blood cell transfusions in the retrograde autologous priming group, it is important to note that relatively few articles are available which are flawed by several types of bias. Prospective, randomized multi-center trials are warranted to conclude decisively on the benefits of retrograde autologous priming.

The effect of flow and pressure on the intraoxygenator flow path of different contemporary oxygenators: an in vitro trial.

INTRODUCTION: This study analyzed the effect of different flows and pressures on the intraoxygenator flow path in three contemporary oxygenators and its consequences for oxygen transfer efficiency. METHODS: In an experimental setup, intraoxygenator flow path parameters were analyzed at post-oxygenator pressures of 150, 200, and 250 mm Hg and at flows ranging from 2 L/min to the oxygenators' maximum permitted flow, with and without pulsatility. The oxygen gradient and the oxygen transfer per minute and per 100 mL blood were calculated using previously collected clinical data and compared with the flow path parameters. RESULTS: Increasing pressure did not affect the flow path parameters, whereas pulsatile flow led to significantly increased dynamic oxygenator blood volumes. Increased flow resulted in decreased values of the flow path parameters in all oxygenators, indicating increased flow through short pathways in the oxygenator. In parallel, oxygen transfer/100 mL blood decreased in all oxygenators (average 2.5 ± 0.4 to 2.4 ± 0.3 mL/dL, p > 0.001) and the oxygen gradient increased from 229 ± 45 to 287 ± 29 mm Hg, p > 0.001, indicating decreased oxygen transfer efficiency. Oxygen transfer/min increased (101 ± 15 to 143 ± 20 mL/min/m2, p > 0.001), however, due to the increased flow through the oxygenator. CONCLUSION: Varying trans-membrane oxygenator pressures did not lead to changes in the intraoxygenator flow path, while an increased flow exhibited lower flow path parameters resulting in less efficient use of the gas exchange compartment. The latter was confirmed by a decrease in O2 transfer efficiency during higher blood flows.

Cerebral and Limb Tissue Oxygenation During Peripheral Venoarterial Extracorporeal Life Support.

Femoral access in extracorporeal life support (ECLS) has been associated with regional variations in arterial oxygen saturation, potentially predisposing the patient to ischemic tissue damage. Current monitoring techniques, however, are limited to intermittent bedside evaluation of capillary refill among other factors. The aim of this study was to assess whether cerebral and limb regional tissue oxygen saturation (rSO2) values reflect changes in various patient-related parameters during venoarterial ECLS (VA-ECLS). This retrospective observational study included adults assisted by femorofemoral VA-ECLS. Bifrontal cerebral and bilateral limb tissue oximetry was performed for the entire duration of support. Hemodynamic data were analyzed parallel to cerebral and limb rSO2. A total of 23 patients were included with a median ECLS duration of 5 [1-20] days. Cardiac arrhythmias were observed in 12 patients, which was associated with a decreased mean rSO2 from 61%±11% to 51%±10% during atrial fibrillation and 67%±9% to 58%±10% during ventricular fibrillation (P<0.001 for both). A presumably sudden increase in cardiac output due to myocardial recovery (n=8) resulted in a significant decrease in mean cerebral rSO2 from 73%±7% to 54%±6% and from 69%±9% to 53%±8% for the left and right cerebral hemisphere, respectively (P=0.012 for both hemispheres). Also, right radial artery partial gas pressure for oxygen decreased from 15.6±2.8 to 8.3±1.9 kPa (P=0.028). No differences were found in cerebral desaturation episodes between patients with and without neurologic complications. In six patients, limb rSO2 increased from on average 29.3±2.7 to 64.0±5.1 following insertion of a distal cannula in the femoral artery (P=0.027). Likewise, restoration of flow in a clotted distal cannula inserted in the femoral artery was necessary in four cases and resulted in increased limb rSO2 from 31.3±0.8 to 79.5±9.0; P=0.068. Non-invasive tissue oximetry adequately reflects events influencing cerebral and limb perfusion and can aid in monitoring tissue perfusion in patients assisted by ECLS.

Peripheral cannulae selection for veno-arterial extracorporeal life support: a paradox.

Explosive penetration of veno-arterial extracorporeal life support in everyday practice has drawn awareness to complications of peripheral cannulation, resulting in recommendations to use smaller size cannulae. However, using smaller cannulae may limit the effectiveness of extracorporeal support and thereby the specific needs of the patient. Selection of proper size cannulae may therefore pose a dilemma, especially since pressure-flow characteristics at different hematocrits are lacking. This study evaluates the precision of cannula pressure drop prediction with increase of fluid viscosity from water flow-pressure charts by M-number, dynamic similarity law, and via fitted parabolic equation. Thirteen commercially available peripheral cannulae were used in this in vitro study. Pressure drop and flow were recorded using water and a water-glycerol solution as a surrogate for blood, at ambient temperature. Subsequently, pressure-flow curves were modeled with increased fluid viscosity (0.0031 N s m-2), and then compared by M-number, dynamic similarity law, and fitted parabolic equation. The agreement of predicted and measured values were significantly higher when the M-number (concordance correlation = 0.948), and the dynamic similarity law method (concordance correlation = 0.947) was used in comparison to the fitted parabolic equation (concordance correlation = 0.898, p < 0.01). The M-number and dynamic similarity based model allow for reliable prediction of peripheral cannula pressure drop with changes of fluid viscosity and could therefore aid in well-thought-out selection of cannulae for extracorporeal life support.

Oxygen delivery, oxygen consumption and decreased kidney function after cardiopulmonary bypass.

INTRODUCTION: Low oxygen delivery during cardiopulmonary bypass is related to a range of adverse outcomes. Previous research specified certain critical oxygen delivery levels associated with acute kidney injury. However, a single universal critical oxygen delivery value is not sensible, as oxygen consumption has to be considered when determining critical delivery values. This study examined the associations between oxygen delivery and oxygen consumption and between oxygen delivery and kidney function in patients undergoing cardiopulmonary bypass. METHODS: Oxygen delivery, oxygen consumption and kidney function decrease were retrospectively studied in 65 adult patients. RESULTS: Mean oxygen consumption was 56 ± 8 ml/min/m2, mean oxygen delivery was 281 ± 39 ml/min/m2. Twenty-seven patients (42%) had an oxygen delivery lower than the previously mentioned critical value of 272 ml/min/m2. None of the patients developed acute kidney injury according to RIFLE criteria. However, in 10 patients (15%) a decrease in the estimated glomerular filtration rate of more than 10% was noted, which was not associated with oxygen delivery lower than 272 ml/min/m2. Eighteen patients had a strong correlation (r >0.500) between DO2 and VO2, but this was not related to low oxygen delivery. Central venous oxygen saturation (77 ± 3%), oxygen extraction ratio (21 ± 3%) and blood lactate levels at the end of surgery (1.2 ± 0.3 mmol/l) showed not to be indicative of insufficient oxygen delivery either. CONCLUSIONS: This study could not confirm an evident correlation between O2 delivery and O2 consumption or kidney function decrease, even at values below previously specified critical levels. The variability in O2 consumption however, is an indication that every patient has individual O2 needs, advocating for an individualized O2 delivery goal.

Extracorporeal Life Support in Adult Patients: A Global Perspective of the Last Decade.

Extracorporeal life support (ECLS) is an external medical device to treat critically ill patients with cardiovascular and respiratory failure. In a nutshell, ECLS is only a "bridging" mechanism that provides life support while the heart and/or the lungs is recovering either by therapeutic medical interventions, transplantation, or spontaneously. Extracorporeal life support has been developed since 1950s, and many studies were conducted to improve ECLS techniques, but unfortunately, the survival rate was not improved. Because of Dr Bartlett's success in using ECLS to treat neonates with severe respiratory distress in 1975, ECLS is made as a standard lifesaving therapy for neonates with severe respiratory distress. However, its use for adult patients remains debatable. The objectives of this study are to outline and provide a general overview of the use of ECLS especially for adult patients for the past 10 years and to elaborate on the challenges encountered by each stakeholder involved in ECLS. The data used for this study were extracted from the ELSO Registry Report of January 2018. Results of this study revealed that the number of ECLS centers and the use of ECLS are increasing over the year for the past decade. There was also a shift of the patient's age category from neonatal to adult patients. However, the survival rates for adult patients are relatively low especially for cardiac and extracorporeal cardiopulmonary resuscitation cases. To date, the complications are still the major challenge of ECLS. Other challenges encountered by the stakeholders in ECLS are the limited amount of well-trained and experienced ECLS teams and centers, the limited government expenditure on health, and the lack of improvement and development of ECLS techniques and devices. Further studies are needed to evaluate the value of ECLS for adult patients.

Non-Invasive Tissue Oximetry-An Integral Puzzle Piece.

Non-invasive tissue oximetry is a monitoring method for continuous assessment of tissue oxygenation, which may aid in detection of hemodynamic instability and otherwise unnoticed hypoxia. Numerous studies focused on using non-invasive tissue oximetry intraoperatively, proposing its predictive value in relation to clinical outcome. Tissue oximetry may be part of standard monitoring practice for brain monitoring during cardiac surgery in many clinical centers; however, the monitoring method can be deployed in numerous clinical settings. This succinct overview aims to determine the role of non-invasive tissue oximetry in current clinical practice.

Early initiation of extracorporeal life support in refractory out-of-hospital cardiac arrest: Design and rationale of the INCEPTION trial.

Return of spontaneous circulation occurs in less than 10% of patients with cardiac arrest undergoing cardiopulmonary resuscitation (CPR) for more than 15 minutes. Studies suggest that extracorporeal life support during cardiopulmonary resuscitation (ECPR) improves survival rate in these patients. These studies, however, are hampered by their non-randomized, observational design and are mostly single-center. A multicenter, randomized controlled trial is urgently warranted to evaluate the effectiveness of ECPR. HYPOTHESIS: We hypothesize that early initiation of ECPR in refractory out-of-hospital cardiac arrest (OHCA) improves the survival rate with favorable neurological status. STUDY DESIGN: The INCEPTION trial is an investigator-initiated, prospective, multicenter trial that will randomly allocate 110 patients to either continued CPR or ECPR in a 1:1 ratio. Patients eligible for inclusion are adults (≤ 70 years) with witnessed OHCA presenting with an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT), who received bystander basic life support and who fail to achieve sustained return of spontaneous circulation within 15 minutes of cardiopulmonary resuscitation by emergency medical services. The primary endpoint of the study is 30-day survival rate with favorable neurological status, defined as 1 or 2 on the Cerebral Performance Category score. The secondary endpoints include 3, 6 and 12-month survival rate with favorable neurological status and the cost-effectiveness of ECPR compared to CCPR. SUMMARY: The INCEPTION trial aims to determine the clinical benefit for the use of ECPR in patients with refractory OHCA presenting with VF/VT. Additionally, the feasibility and cost-effectiveness of ECPR will be evaluated.