The Effect of Cytokine Adsorption on Leukocyte and Platelet Activation after Extracorporeal Cardiopulmonary Resuscitation.

BACKGROUND: Post-cardiac arrest syndrome (PCAS) is a frequent complication following successful cardiopulmonary resuscitation and correlates with poor outcome. PCAS is characterized by an excessive inflammatory response to whole-body ischemia and reperfusion. Cytokine adsorption was suggested as an adjunctive treatment option for the removal of cytokines from the patients' blood to restore the physiological equilibrium of pro- and anti-inflammatory activity and thus mitigate hemodynamic instability and end-organ complications. MATERIAL AND METHODS: To better understand the cellular effects of cytokine adsorption in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR) after in- and out-of-hospital cardiac arrest, we compared the activation status of neutrophils, monocytes, and platelets as well as the formation of platelet-leukocyte complexes in intravenous whole blood samples from an exploratory subgroup (n = 24) from the randomized CYTER study. RESULT: At 48 hours after initiation of ECPR, flow cytometry analyses did neither reveal significant differences in neutrophil (CD11b, CD66b, L-selectin, and PSGL-1) and monocyte (CD11b, L-selectin, and PSGL-1) surface molecule expression nor in circulating platelet-monocyte complexes between patients receiving cytokine adsorption and those without. CONCLUSION: Data did not show a relevant effect of cytokine adsorption on neutrophil and monocyte activation during the first 48 hours after initiation of ECPR.

The Impact of Head Position on Neurological and Histopathological Outcome Following Controlled Automated Reperfusion of the Whole Body (CARL) in a Pig Model.

Introduction: Based on extracorporeal circulation, targeted reperfusion strategies have been developed to improve survival and neurologic recovery in refractory cardiac arrest: Controlled Automated Reperfusion of the whoLe Body (CARL). Furthermore, animal and human cadaver studies have shown beneficial effects on cerebral pressure due to head elevation during conventional cardiopulmonary resuscitation. Our aim was to evaluate the impact of head elevation on survival, neurologic recovery and histopathologic outcome in addition to CARL in an animal model. Methods: After 20 min of ventricular fibrillation, 46 domestic pigs underwent CARL, including high, pulsatile extracorporeal blood flow, pH-stat acid-base management, priming with a colloid, mannitol and citrate, targeted oxygen, carbon dioxide and blood pressure management, rapid cooling and slow rewarming. N = 25 were head-up (HUP) during CARL, and N = 21 were supine (SUP). After weaning from ECC, the pigs were extubated and followed up in the animal care facility for up to seven days. Neuronal density was evaluated in neurohistopathology. Results: More animals in the HUP group survived and achieved a favorable neurological recovery, 21/25 (84%) versus 6/21 (29%) in the SUP group. Head positioning was an independent factor in neurologically favorable survival (p < 0.00012). Neurohistopathology showed no significant structural differences between HUP and SUP. Distinct, partly transient clinical neurologic deficits were blindness and ataxia. Conclusions: Head elevation during CARL after 20 min of cardiac arrest independently improved survival and neurologic outcome in pigs. Clinical follow-up revealed transient neurologic deficits potentially attributable to functions localized in the posterior perfusion area, whereas histopathologic findings did not show corresponding differences between the groups. A possible explanation of our findings may be venous congestion and edema as modifiable contributing factors of neurologic injury following prolonged cardiac arrest.

Effects of Prolonged Serum Calcium Suppression during Extracorporeal Cardiopulmonary Resuscitation in Pigs.

Controlled reperfusion by monitoring the blood pressure, blood flow, and specific blood parameters during extracorporeal reperfusion after cardiac arrest has the potential to limit ischemia-reperfusion injury. The intracellular calcium overload as part of the ischemia-reperfusion injury provides the possibility for the injury to be counteracted by the early suppression of serum calcium with the aim of improving survival and the neurological outcome. We investigated the effects of prolonged serum calcium suppression via sodium citrate during extracorporeal resuscitation using the CARL protocol (CARL-controlled automated reperfusion of the whole body) compared to a single-dose approach in a porcine model after prolonged cardiac arrest. A control group (N = 10) was resuscitated after a 20 min cardiac arrest, initially lowering the intravascular calcium with the help of a single dose of sodium citrate as part of the priming solution. Animals in the intervention group (N = 13) received additional sodium citrate for the first 15 min of reperfusion. In the control group, 9/10 (90.0%) animals survived until day 7 and 7/13 (53.8%) survived in the intervention group (p = 0.09). A favorable neurological outcome on day 7 after the cardiac arrest was observed in all the surviving animals using a species-specific neurological deficit score. The coronary perfusion pressure was significantly lower with a tendency towards more cardiac arrhythmias in the intervention group. In conclusion, a prolonged reduction in serum calcium levels over the first 15 min of reperfusion after prolonged cardiac arrest tended to be unfavorable regarding survival and hemodynamic variables compared to a single-dose approach in this animal model.

Development of an in-vitro model for extracorporeal blood pumps to study the effects of artificial pulsatility on human blood.

Introduction: The application of extracorporeal circulation (ECC) systems is known to be associated with several implications regarding hemolysis, inflammation, and coagulation. In the last years, systems with pulsatile blood flow are increasingly used with the intention to improve hemodynamics in reperfusion. However, their implications on the aforementioned aspects remain largely unknown. To investigate the effects of pulsatility, this ex-vivo study was initiated. Methods: Test circuits (primed with human whole blood) were set up in accordance with the recommendations of international standards for in-vitro evaluation of new components and systems of ECC. Diagonal pumps were either set up with non-pulsatile (n = 5, NPG) or pulsatile (n = 5, PG) pump settings and evaluated for 6 h. All analyses were conducted with human whole blood. Blood samples were repeatedly drawn from the test circuits and analyzed regarding free hemoglobin, interleukin 8 (IL-8), platelet aggregation and acquired von Willebrand syndrome (AVWS). Results: After 1 h of circulation, a significant coagulation impairment (impaired platelet function and AVWS) was observed in both groups. After 6 h of circulation, increased IL-8 concentrations were measured in both groups (NPG: 0.05 ± 0.03 pg./mL, PG: 0.03 ± 0.01 pg./mL, p = 0.48). Pulsatile pump flow resulted in significantly increased hemolysis after 6 h of circulation (NPG: 37.3 ± 12.4 mg/100 L; PG: 59.6 ± 14.5 mg/100 L; p < 0.05). Conclusion: Our results indicate that the coagulative impairment takes place in the early phase of ECC. Pulsatility did not affect the occurrence of AVWS ex-vivo. Prolonged durations of pulsatile pump flow led to increased hemolysis and therefore, its prolonged use should be employed cautiously in clinical practice with appropriate monitoring.

Extracorporeal Membrane Oxygenation in Intoxication and Overdoses: A Systematic Review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been increasingly applied over recent decades to treat severe cardiogenic shock and acute lung failure and cardiac arrest of various causes. Acute intoxication with therapeutic substances or other chemical substances can cause severe cardiogenic shock or even cardiac arrest. The purpose of this study was to conduct a qualitative systematic review of ECMO use in intoxication and poisoning. METHODS: We searched the PubMed, Medline, and Web of Science databases from January 1971 to December 2021 and selected appropriate studies according to our inclusion and exclusion criteria to evaluate the role of ECMO in intoxication and poisoning systematically. Survival at hospital discharge was examined to describe the outcome. RESULTS: The search resulted in 365 publications after removing duplicates. In total, 190 full-text articles were assessed for eligibility. A total of 145 articles from 1985 to 2021 were examined in our final qualitative analysis. A total of 539 (100%) patients were included (mean age: 30.9 ± 16.6 years), with a distribution of n = 64 (11.9%) cases with venovenous (vv) ECMO, n = 218 (40.4%) cases with venoarterial (va) ECMO, and n = 257 (47.7%) cases with cardiac arrest and extracorporeal cardiopulmonary resuscitation. Survival at hospital discharge was 61.0% for all patients, 68.8% for vaECMO, 75% for vvECMO, and 50.9% for extracorporeal cardiopulmonary resuscitation. CONCLUSION: When used and reported, ECMO seems to be a valid tool for adult and pediatric patients suffering intoxication from various pharmaceutical and nonpharmaceutical substances due to a high survival rate at hospital discharge.

Enabling the control of reperfusion parameters in out-of-hospital cardiac arrest: First applications of the CARL system.

INTRODUCTION: There is increasing evidence for extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue therapy for selected patients in refractory cardiac arrest (CA). Besides patient selection, the control of reperfusion parameters is of eminent importance. Especially in out-of-hospital CA, monitoring and individualized, targeted reperfusion remains a great challenge for emergency personnel. The CARL® system is designed to enable an early control of a variety of reperfusion parameters and to pursue a targeted reperfusion strategy in ECPR. CASE PRESENTATION: We report the first 10 ECPR applications of the CARL® system in Regensburg, Germany. Early blood gas analysis, oxygen titration and pressure monitoring were feasible and enabled an individualized and targeted reperfusion strategy in all patients. After suffering from refractory CA and prolonged resuscitation attempts, five out of the first 10 patients survived and were successfully discharged from the hospital (CPC one on hospital discharge). CONCLUSION: Application of the CARL® system contributed to early monitoring and control of reperfusion parameters. Whether targeted ECPR may have the potential to improve outcomes in refractory OHCA remains the subject of future investigations.

Limiting calcium overload after cardiac arrest: The role of human albumin in controlled automated reperfusion of the whole body.

BACKGROUND: Regarding the overall inadequate results after cardiopulmonary resuscitation, the development of new treatment concepts is urgently needed. Controlled Automated Reperfusion of the whoLe body (CARL) represents a therapy bundle to control the conditions of reperfusion and the composition of the reperfusate after cardiac arrest (CA). The aim of this study was to investigate the plasma expander's role in the CARL priming solution and examine its mechanism of action. METHODS: Viscosity, osmolality, colloid osmotic pressure (COP), pH and calcium binding of different priming solutions were measured in vitro and compared to in vivo data. N = 16 pigs were allocated to receive CARL following 20 min of untreated CA with either human albumin 20% (HA, N = 8) or gelatin polysuccinate 4% (GP, N = 8). Blood gas analyses were performed during the first hour of reperfusion and catecholamine and fluid requirements were recorded. Neurological outcome was assessed by neurological deficit scoring (NDS) on the seventh day. RESULTS: In vitro, addition of HA to the CARL priming solution resulted in higher COP and higher calcium-binding than GP. In vivo, treatment with HA led to greater reduction of ionized calcium and higher extracorporeal flows within the first 30 min of reperfusion with no difference in catecholamine support and fluid requirement. Seven-day survival of 75% with no difference in NDS was observed in both groups. CONCLUSIONS: Our data show that the plasma expander in the CARL priming solution has a significant effect on the initial reperfusate and can potentially influence the course of resuscitation. However, seven-day survival and NDS did not differ between groups.

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.

Carboxyhemoglobin (CO-Hb) Correlates with Hemolysis and Hospital Mortality in Extracorporeal Membrane Oxygenation: A Retrospective Registry.

Background: Patients supported with extracorporeal membrane oxygenation (ECMO) may develop elevated carboxyhemoglobin (CO-Hb), a finding described in the context of hemolysis. Clinical relevance of elevated CO-Hb in ECMO is unclear. We therefore investigated the prognostic relevance of CO-Hb during ECMO support. Methods: Data derives from a retrospective single-center registry study. All ECMO patients in a medical ICU from October 2010 through December 2019 were considered. Peak arterial CO-Hb value during ECMO support and median CO-Hb values determined by point-of-care testing for distinct time intervals were determined. Groups were divided by CO-Hb (<2% or ≥2%). The primary endpoint was hospital survival. Results: A total of 729 patients with 59,694 CO-Hb values met the inclusion criteria. Median age (IQR) was 59 (48−68) years, 221/729 (30.3%) were female, and 278/729 (38.1%) survived until hospital discharge. Initial ECMO configuration was veno-arterial in 431/729 (59.1%) patients and veno-venous in 298/729 (40.9%) patients. Markers for hemolysis (lactate dehydrogenase, bilirubin, hemolysis index, and haptoglobin) all correlated significantly with higher CO-Hb (p < 0.001, respectively). Hospital survival was significantly higher in patients with CO-Hb < 2% compared to CO-Hb ≥ 2%, evaluating time periods 24−48 h (48.6% vs. 35.2%, p = 0.003), 48−72 h (51.5% vs. 36.8%, p = 0.003), or >72 h (56.9% vs. 31.1%, p < 0.001) after ECMO cannulation. Peak CO-Hb was independently associated with lower hospital survival after adjustment for confounders. Conclusions: In ECMO, CO-Hb correlates with hemolysis and hospital survival. If high CO-Hb measured should trigger a therapeutic intervention in order to reduce hemolysis has to be investigated in prospective trials.

Serum proteome alterations during conventional and extracorporeal resuscitation in pigs.

BACKGROUND: Only a small number of patients survive an out-of-hospital cardiac arrest (CA) and can be discharged from hospital alive with a large percentage of these patients retaining neurological impairments. In recent years, extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a beneficial strategy to optimize cardiac arrest treatment. However, ECPR is still associated with various complications. To reduce these problems, a profound understanding of the underlying mechanisms is required. This study aims to investigate the effects of CA, conventional cardiopulmonary resuscitation (CPR) and ECPR using a whole-body reperfusion protocol (controlled and automated reperfusion of the whole body-CARL) on the serum proteome profiles in a pig model of refractory CA. METHODS: N = 7 pigs underwent 5 min of untreated CA followed by 30 min CPR and 120 min perfusion with CARL. Blood samples for proteomic analysis were drawn at baseline, after CPR and at the end of the CARL period. Following albumin-depletion, proteomic analysis was performed using liquid chromatography-tandem mass spectrometry. RESULTS: N = 21 serum samples were measured resulting in the identification and quantification of 308-360 proteins per sample and 388 unique proteins in total. The three serum proteome profiles at the investigated time points clustered individually and segregated almost completely when considering a 90% confidence interval. Differential expression analysis showed significant abundance changes in 27 proteins between baseline and after CPR and in 9 proteins after CARL compared to CPR. Significant findings were further validated through a co-abundance cluster analysis corroborating the observed abundance changes. CONCLUSIONS: The presented data highlight the impact of systemic ischemia and reperfusion on the entire serum proteome during resuscitation with a special focus on changes regarding haemolysis, coagulation, inflammation, and cell-death processes. Generally, the observed changes contribute to post-ischemic complications. Better understanding of the underlying mechanisms during CA and resuscitation may help to limit these complications and improve therapeutic options.

Extracorporeal membrane oxygenation during the first three waves of the coronavirus disease 2019 pandemic: A retrospective single-center registry study.

BACKGROUND: Despite increasing knowledge about the optimal treatment for patients with severe COVID-19, data from different cohorts suggested that survival of patients treated with ECMO seemed to decline over the course of the pandemic. METHODS: In this non-interventional retrospective single-center registry study we analyzed all consecutive patients tested positive for SARS-CoV-2 infection and supported with VV ECMO in our center during the first three waves of the pandemic. From March 2020 through June 2021, 59 patients have been included. RESULTS: Overall 90-day survival was 32%. Besides changes in drug treatment for COVID-19 and a lower PaO2 /FiO2 ratio before ECMO initiation during the third wave, all other patient baseline characteristics were similar during the three waves. Survival rate was highest during the first wave and lowest during the third wave, yet this difference was not statistically significant. CONCLUSIONS: VV ECMO has shown to be a feasible and safe support option for patients with severe respiratory failure due to COVID-19. The results from this single-center study confirm findings from other cohorts showing declining survival rates of patients treated with VV ECMO during the COVID-19 pandemic, however, the specific reasons for this finding remain unclear.

Beneficial Effects of Adjusted Perfusion and Defibrillation Strategies on Rhythm Control within Controlled Automated Reperfusion of the Whole Body (CARL) for Refractory Out-of-Hospital Cardiac Arrest.

Survival and neurological outcomes after out-of-hospital cardiac arrest (OHCA) remain low. The further development of prehospital extracorporeal resuscitation (ECPR) towards Controlled Automated Reperfusion of the Whole Body (CARL) has the potential to improve survival and outcome in these patients. In CARL therapy, pulsatile, high blood-flow reperfusion is performed combined with several modified reperfusion parameters and adjusted defibrillation strategies. We aimed to investigate whether pulsatile, high-flow reperfusion is feasible in refractory OHCA and whether the CARL approach improves heart-rhythm control during ECPR. In a reality-based porcine model of refractory OHCA, 20 pigs underwent prehospital CARL or conventional ECPR. Significantly higher pulsatile blood-flow proved to be feasible, and critical hypotension was consistently prevented via CARL. In the CARL group, spontaneous rhythm conversions were observed using a modified priming solution. Applying potassium-induced secondary cardioplegia proved to be a safe and effective method for sustained rhythm conversion. Moreover, significantly fewer defibrillation attempts were needed, and cardiac arrhythmias were reduced during reperfusion via CARL. Prehospital CARL therapy thus not only proved to be feasible after prolonged OHCA, but it turned out to be superior to conventional ECPR regarding rhythm control.

Development of a Novel Adapter to Enable Less-Invasive Left Ventricular Assist Device Implantation via the Left Ventricular Apex.

The first prototype of an adapter to enable left ventricular assist device (LVAD) implantation solely via the left ventricular (LV) apex and without requiring cardiopulmonary bypass (CPB) was tested in healthy and acutely failing pig hearts. The adapter consists of a fixation, blood guiding, and connecting module fitting to a HeartMate 3 (HM3; Abbott, Chicago, IL) pump. Implantation was performed via a left thoracotomy in five pigs (96 ± 18 kg). Invasive blood pressure was measured before (CTRL), 30 minutes after HM3 initiation (HM3_CTRL), during acute heart failure (HF) induced by rapid pacing (CTRL_HF), and 5 minutes after initiating HM3 support (HM3_HF). To further estimate the LVAD performance, blood pressure amplitudes were calculated in the healthy heart without (CTRL) and with HM3 support (HM3_CTRL) as: systolic-diastolic blood pressure. Our adapter implantation and connection to the HM3 pump succeeded in all animals. Compared to the normal beating healthy heart, blood pressure amplitudes were significantly smaller during HM3 support (CTRL: 41 ± 5 mm Hg vs. HM3_CTRL: 20 ± 4 mm Hg; p < 0.05). Under HF conditions, mean blood pressure returned to normal values after pump initiation (CTRL_HF: 29 ± 6 mm Hg, HM3_HF: 83 ± 24 mm Hg). The adapter prototype allowed safe, straightforward, and less-invasive LVAD implantation solely via the LV apex without using CPB and support of the LV during acute HF in the pig heart.

Ex-Vivo Preservation with the Organ Care System in High Risk Heart Transplantation.

OBJECTIVE: Ex vivo organ perfusion is an advanced preservation technique that allows graft assessment and extended ex situ intervals. We hypothesized that its properties might be especially beneficial for high-risk recipients and/or donors with extended criteria. METHODS: We reviewed the outcomes of 119 consecutive heart transplant patients, which were divided into two groups: A (OCS) vs. B (conventional). Ex vivo organ perfusion was performed using the Organ Care System (OCS). Indications for OCS-usage were expected ischemic time of >4 h or >2 h plus given extended donor criteria. RESULTS: Both groups included mostly redo cases (A: 89.7% vs. B: 78.4%; p = 0.121). Incidences of donors with previous cardiac arrest (%) (A: 32.4 vs. B: 22.2; p < 0.05) or LV-hypertrophy (%) (A: 19.1 vs. B: 8.3; p = 0.119) were also increased in Group A. Ex situ time (min) was significantly longer in Group A (A: 381 (74) vs. B: 228 (43); p < 0.05). Ventilation time (days) (A: 10.0 (19.9) vs. B: 24.3 (43.2); p = 0.057), postoperative need for ECLS (%) (A: 25.0 vs. B: 39.2; p = 0.112) and postoperative dialysis (chronic) (%) (A: 4.4 vs. B: 27.5; p < 0.001) were numerically better in the OCS group, without any difference in the occurrence of early graft rejection. The 30-d-survival (A: 92.4% vs. B: 90.2%; p = 0.745) and mid-term survival were statistically not different between both groups. CONCLUSIONS: OCS heart allowed safe transplantation of surgically complex recipients with excellent one-year outcomes, despite long preservation times and unfavourable donor characteristics. Furthermore, we observed trends towards decreased ventilation times and fewer ECLS treatments. In times of reduced organ availability and increasing recipient complexity, OCS heart is a valuable instrument that enables otherwise infeasible allocations and contributes to increase surgical safety.

Cytokine adsorption in patients with post-cardiac arrest syndrome after extracorporeal cardiopulmonary resuscitation (CYTER) - A single-centre, open-label, randomised, controlled trial.

AIM: To investigate the effect of cytokine adsorption in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR) after cardiac arrest. METHODS: CYTER was a single-centre, open-label, randomised, controlled trial. Patients selected for ECPR at the University Medical Center Freiburg (Freiburg, Germany) were assigned to extracorporeal membrane oxygenation (ECMO) support with or without cytokine adsorption (1:1) using the CytoSorb adsorber, incorporated into the ECMO, replaced every 24 hours, and removed after 72 hours. The primary endpoint was serum interleukin (IL)-6 concentration at 72 hours (intention-to-treat analysis). Secondary endpoints included 30-day survival, vasopressor support and biomarkers of end-organ injury. RESULTS: Of 50 patients enrolled in the trial, 26 (52%) were treated with cytokine adsorption and 24 (48%) without. Nine patients were excluded (informed consent could not be obtained); 41 patients were therefore included in the primary analysis. Median IL-6 levels (IQR) decreased from 408.0(93.4-906.5) to 324.0 (134.3-4617.3) pg/mL and increased from 133.0 (56.2-528.5) to 241.0 (132.8-718.0) pg/mL in the cytokine adsorption and control group, respectively (linear regression for treatment [cytokine adsorption vs control]: p = 0.48). Three (14%) of 22 patients treated with cytokine adsorption and 8 (42%) of 19 patients treated without cytokine adsorption survived to day 30 (HR = 1.85, 95% CI 0.86-4.01; p = 0.10). Vasopressor support and NSE, S100b, troponin T, CRP and PCT levels were similar between groups. CONCLUSION: Cytokine adsorption in patients receiving ECPR did not reduce serum IL-6 and had no significant effect on survival, vasopressor support, or biomarkers of injury. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03685383.

Effect of Cytokine Adsorption on Survival and Circulatory Stabilization in Patients Receiving Extracorporeal Cardiopulmonary Resuscitation.

Even after the introduction of extracorporeal cardiopulmonary resuscitation (ECPR), survival after cardiac arrest remains poor. Excess release of vasoactive cytokines may be a reason for cardiovascular instability and death after ECPR. Recently, an extracorporeal cytokine adsorption device (CytoSorb) to reduce elevated levels of circulating cytokines has been introduced. So far, it remains unclear if this device may improve survival and cardiovascular stabilization after ECPR. We report data from our investigator-initiated, single-center ECPR registry. We compared 23 ECPR patients treated with cytokine adsorption with a propensity-matched cohort of ECPR patients without cytokine adsorption. We analyzed survival, lactate clearance, vasopressor need, and fluid demand in both groups and performed between-group comparisons. Survival to discharge from intensive care unit (ICU) was 17.4% (4/23) in the cytokine adsorption group and 21.7% in the control group (5/23, P > 0.99). In both groups, we observed a decrease of serum-lactate, need for vasopressors, and fluid demand during the first 72 hours after ECPR. However, in direct comparison, we did not find significant between-group differences. In this retrospective registry study employing propensity score matching, cytokine adsorption in severely ill patients after ECPR was not associated with improved ICU survival nor a decrease of lactate, fluid, or vasopressor levels. Due to small case numbers and the retrospective design of the study, our results neither disprove nor confirm a clinically relevant treatment effect of cytokine adsorption. Results from larger trials, preferably randomized-controlled trials are required to better understand the clinical benefit of cytokine adsorption after ECPR.

Postcardiotomy mechanical support in patients with mitral valve prostheses is associated with poor survival.

AIMS: To elaborate on early survival in patients with mitral valve replacement requiring temporary extracorporeal life support system (ECLS). METHODS: We analyzed survival, significant bleeding, wound infection, and ECLS duration in 421 from 14,400 patients with postoperative need for ECLS from January 2008 to December 2017 at our institution. Finally, patients were stratified according to the type of surgery performed: the mitral group (mitral valve replacement) n = 63 and the control group (any cardiac surgery excluding the mitral valve) n = 358. In order to adjust for preoperative patient characteristics, a propensity matching analysis was performed. Differences in in-hospital mortality were analyzed accordingly. RESULTS: In-hospital mortality was significantly higher in the mitral group as compared to the control group before and after adjustment (p < 0.001). Median duration of ECLS was 4 days in both groups. Perioperative bleeding (p < 0.001) and wound infection (p < 0.001) also showed significant worse outcome parameters in the mitral group. The main causes of death in the mitral group were multiorgan failure, n = 48 (76%), stroke, n = 7 (12%), and intracardiac thrombus formation, n = 5 (10%). CONCLUSIONS: ECLS is associated with a high in-hospital mortality rate in patients after mitral valve replacement.

A Systematic Review with Meta-Analysis Investigating the Impact of Targeted Perfusion Parameters during Extracorporeal Cardiopulmonary Resuscitation in Out-of-Hospital and Inhospital Cardiac Arrest.

Evidence regarding perfusion conditions during extracorporeal cardiopulmonary resuscitation (ECPR) is rare. Therefore, we investigated the impact of perfusion parameters on neurologic outcome and survival in patients with in- or out-of-hospital cardiac arrest (IHCA; OHCA) treated with ECPR. We performed a systematic review with meta-analysis. The focus was set on perfusion parameters and their impact on survival and a goal neurological outcome using the cerebral performance category score of 1-2. We conducted random- and mixed-effects meta-analyses and computed pooled estimates and 95% confidence intervals (CI). We included a total of n = 1,282 ECPR (100%) patients from 20 ECPR studies. The target values of flow and mean arterial pressure (MAP) were frequently available. We transferred flow and MAP target values to high, medium, and low categories. The meta-analysis could not demonstrate a single effect of flow or MAP on outcome variables. In a second mixed-effects model, the combined occurrence of targeted flow and MAP as medium and high showed a significant effect on survival (OHCA: 52%, 95% CI: 29%, 74%; IHCA: 60%, 95% CI: 35%, 85%) and on neurological outcomes (OHCA: 53%, 95% CI: 27%, 78%; IHCA: 62%, 95% CI: 38%, 86%). Random-effects analysis showed also that IHCA led to a significant 11% (p = 0.006; 95% CI: 3%, 18%) improvement in survival and 12% (p = .005; 95% CI: 4%, 21%) improvement in neurological outcomes compared to OHCA. A combination of medium flow and high MAP showed advantages in survival and for neurological outcomes. We also identified improved outcomes for IHCA.

Brain vulnerability and viability after ischaemia.

The susceptibility of the brain to ischaemic injury dramatically limits its viability following interruptions in blood flow. However, data from studies of dissociated cells, tissue specimens, isolated organs and whole bodies have brought into question the temporal limits within which the brain is capable of tolerating prolonged circulatory arrest. This Review assesses cell type-specific mechanisms of global cerebral ischaemia, and examines the circumstances in which the brain exhibits heightened resilience to injury. We suggest strategies for expanding such discoveries to fuel translational research into novel cytoprotective therapies, and describe emerging technologies and experimental concepts. By doing so, we propose a new multimodal framework to investigate brain resuscitation following extended periods of circulatory arrest.