Association between pediatric intensive care mortality and mechanical ventilation settings during extracorporeal membrane oxygenation for pediatric acute respiratory distress syndrome.

The main objective of this study was to describe the current mechanical ventilation (MV) settings during extracorporeal membrane oxygenation (ECMO) for pediatric acute respiratory distress syndrome (P-ARDS) in six European centers. This is a retrospective observational cohort study performed in six European centers from January 2009 to December 2019. Children > 1 month to 18 years supported with ECMO for refractory P-ARDS were included. Collected data were as follows: patients' pre-ECMO medical condition, pre-ECMO adjunctive therapies for P-ARDS, pre-ECMO and during ECMO MV settings on day (D) 1, D3, D7, and D14 of ECMO, use of adjunctive therapies during ECMO, duration of ECMO, pediatric intensive care unit length of stay, and survival. A total of 255 patients with P-ARDS were included. The multivariate analysis showed that PEEP on D1 (OR = 1.13, 95% CI [1.03-1.24], p = 0.01); D3 (OR = 1.17, 95% CI [1.06-1.29], p = 0.001); and D14 (OR = 1.21, 95% CI [1.05-1.43], p = 0.02) and DP on D7 were significantly associated with higher odds of mortality (OR = 0.82, 95% CI [0.71-0.92], p = 0.001). Moreover, DP on D1 above 15 cmH2O (OR 2.23, 95% CI (1.09-4.71), p = 0.03) and native lung FiO2 above 60% on D14 (OR 10.36, 95% CI (1.51-116.15), p = 0.03) were significantly associated with higher odds of mortality.   Conclusion: MV settings during ECMO for P-ARDS varied among centers; however, use of high PEEP levels during ECMO was associated with higher odds of mortality as well as a DP above 15 cmH2O and a native lung FiO2 above 60% on D14 of ECMO. What is Known: • Invasive ventilation settings are well defined for pediatric acute respiratory distress syndrome; however, once the children required an extracorporeal respiratory support, there is no recommendation how to set the mechanical ventilator. • Impact of invasive ventilator during extracorporeal respiratory support ad only been during the first days of this support but the effects of these settings later in the assistance are not described. What is New: • It seems to be essential to early decrease FiO2 on native lung once the ECMO flow allows an efficient oxygenation. • Tight control to limit the driving pressure at 15 cmH20 during ECMO run seems to be associated with better survival rate.

Differential hypoxemia and the clinical significance of venous drainage position during extracorporeal membrane oxygenation.

Differential hypoxemia (DH) has been recognized as a clinical problem during veno-arterial extracorporeal membrane oxygenation (VA ECMO) although its features and consequences have not been fully elucidated.This single center retrospective study aimed to investigate the clinical characteristics of patients manifesting DH as well as the impact of repositioning the drainage point from the inferior vena cava (IVC) to the superior vena cava to alleviate DH.All patients (>15 years) commenced on VA ECMO at our center between 2009 and 2020 were screened. Of 472 eligible patients seven were identified with severe DH. All patients had the drainage cannula tip in the IVC or at the junction between the IVC and right atrium.The mean peripheral capillary saturation increased from 54 (±6.6) to 86 (±6.6) %, (p = <0.001) after repositioning of the cannula. Pre-oxygenator saturation increased from 62 (±8.9) % prior to adjustment to 74 (±3.7) %, (p = 0.016) after repositioning. Plasma lactate tended to decrease within 24 h after adjustment. Five patients (71%) survived ECMO treatment, to discharge from hospital, and were alive at 1-year follow-up.Although DH has been described in several studies, the condition has not been investigated in a clinical setting comparing the effect on upper body saturation before and after repositioning of the drainage cannula. This study shows that moving the drainage zone into the upper part of the body has a marked positive effect on upper body saturation in patients with DH.

Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study.

BACKGROUND: In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. METHODS: PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. FINDINGS: Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). INTERPRETATION: During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. FUNDING: Extracorporeal Life Support Organization.

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

Extracorporeal Membrane Oxygenation in Patients With COVID-19: An International Multicenter Cohort Study.

BACKGROUND: To report and compare the characteristics and outcomes of COVID-19 patients on extracorporeal membrane oxygenation (ECMO) to non-COVID-19 acute respiratory distress syndrome (ARDS) patients on ECMO. METHODS: We performed an international retrospective study of COVID-19 patients on ECMO from 13 intensive care units from March 1 to April 30, 2020. Demographic data, ECMO characteristics and clinical outcomes were collected. The primary outcome was to assess the complication rate and 28-day mortality; the secondary outcome was to compare patient and ECMO characteristics between COVID-19 patients on ECMO and non-COVID-19 related ARDS patients on ECMO (non-COVID-19; January 1, 2018 until July 31, 2019). RESULTS: During the study period 71 COVID-19 patients received ECMO, mostly veno-venous, for a median duration of 13 days (IQR 7-20). ECMO was initiated at 5 days (IQR 3-10) following invasive mechanical ventilation. Median PaO2/FiO2 ratio prior to initiation of ECMO was similar in COVID-19 patients (58 mmHg [IQR 46-76]) and non-COVID-19 patients (53 mmHg [IQR 44-66]), the latter consisting of 48 patients. 28-day mortality was 37% in COVID-19 patients and 27% in non-COVID-19 patients. However, Kaplan-Meier curves showed that after a 100-day follow-up this non-significant difference resolves. Non-surviving COVID-19 patients were more acidotic prior to initiation ECMO, had a shorter ECMO run and fewer received muscle paralysis compared to survivors. CONCLUSIONS: No significant differences in outcomes were found between COVID-19 patients on ECMO and non-COVID-19 ARDS patients on ECMO. This suggests that ECMO could be considered as a supportive therapy in case of refractory respiratory failure in COVID-19.

Extracorporeal Membrane Oxygenation Support in Children With Hematologic Malignancies in Sweden.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used in severe respiratory and/or circulatory failure when conventional critical care fails. Studies on patients with hematologic malignancies on ECMO have shown contradictory results; immunosuppression and coagulopathy are relative contraindications to ECMO. OBSERVATIONS: This nationwide Swedish retrospective chart review identified 958 children with hematologic malignancies of whom 12 (1.3%) required ECMO support. Eight patients survived ECMO, 7 the total intensive care period, and 6 survived the underlying malignancy. CONCLUSIONS: ECMO may be considered in children with hematologic malignancy. Short-term and long-term survival, in this limited group, was similar to that of children on ECMO at large.

Carbon Dioxide Elimination During Veno-Venous Extracorporeal Membrane Oxygenation Weaning: A Pilot Study.

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) represents a component of the treatment strategy for severe respiratory failure. Clinical evidence on the management of the lung during V-V ECMO are limited just as the consensus regarding timing of weaning. The monitoring of the carbon dioxide (CO2) removal (V'CO2TOT) is subdivided into two components: the membrane lung (ML) and the native lung (NL) are both taken into consideration to evaluate the improvement of the function of the lung and to predict the time to wean off ECMO. We enrolled patients with acute respiratory distress syndrome (ARDS). The V'CO2NL ratio (V'CO2NL/V'CO2TOT) value was calculated based on the distribution of CO2 between the NL and the ML. Of 18 patients, 15 were successfully weaned off of V-V ECMO. In this subgroup, we observed a significant increase in the V'CO2NL ratio comparing the median values of the first and last quartiles (0.32 vs. 0.53, p = 0.0045), without observing any modifications in the ventilation parameters. An increase in the V'CO2NL ratio, independently from any change in ventilation could, despite the limitations of the study, indicate an improvement in pulmonary function and may be used as a weaning index for ECMO.

An experimental model of veno-venous arterial extracorporeal membrane oxygenation.

INTRODUCTION: Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure. AIM: To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump-driven circuit. METHODS: We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels. RESULTS: In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min. CONCLUSION: Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings.

Weaning from veno-venous extracorporeal membrane oxygenation: how I do it.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is a rescue treatment for acute respiratory distress syndrome (ARDS) failing protective mechanical ventilation. It temporarily provides proper gas exchange: hypoxia is treated by adjusting the blood flow rate and fraction in spired oxygen over the ventilator (FiO2) on the extracorporeal membrane oxygenation (ECMO) circuit while CO2 removal is regulated by the ECMO fresh gas flow. Therefore, ventilator settings can be gradually reduced allowing the lungs to rest and recover. Nowadays, indications for ECMO referral and implantation are clearly formulated; on the contrary, little evidence currently exists to guide the process of weaning from ECMO support, especially concerning the timing during the course of lung healing. Therefore, indications to stop ECMO are less well standardized so that in clinical trials extracorporeal assistance is generally continued until lung recovery, with neither specific nor homogenous criteria for withdrawal. Notably, in almost all papers dealing with data on VV ECMO support, the management of weaning and the weaning procedure itself are not described. The aim of this paper is to make a picture of VV ECMO weaning, as it is performed in three European large volume intensive care units (ICUs) which represent referral centers for VV ECMO treatment. We focused on data concerning the timing of VV ECMO weaning and parameters at the time of weaning, in order to assess adequacy and safety of VV ECMO removal.

A narrative review of the technical standards for extracorporeal life support devices (pumps and oxygenators) in Europe.

This review summarizes the European rules to control the market when introducing new products. In particular, it shows all the steps to achieve the European Conformity (CE Mark), a certification that all new medical products must achieve before being used in Europe. Extracorporeal membrane oxygenation (ECMO) devices are exposed to the same procedures. Hereby, we present some regulatory issues regarding pumps and oxygenators, providing technical details as released by the manufacturers on their websites and information charts.

Extracorporeal CO2 removal in critically ill patients: a systematic review.

INTRODUCTION: The use of extracorporeal CO2 removal (ECCO2R) is increasingly employed in critically ill patients. However, the clinical evidence supporting its efficacy remains currently poor. EVIDENCE ACQUISITION: A systematic review using MEDLINE via PubMed was performed to identify eligible studies (until 30th September 2016). The amount of CO2 reduction, the effect on the duration of mechanical ventilation and weaning, the impact on patients' outcome and the occurrence of complications were evaluated. The quality of evidence was evaluated according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. EVIDENCE SYNTHESIS: Six studies were included (three evaluating patients with chronic obstructive pulmonary disease [COPD]; three evaluating patients with acute respiratory distress syndrome [ARDS]), involving 279 adult patients; 142 treated with ECCO2R and 137 controls. No study on pediatric population met the inclusion criteria for analysis. The overall quality of evidence of the two randomized trials and four case-control studies varied from moderate to very low. PaCO2 was generally reduced by 25-33% within a few hours following ECCO2R initiation. One ARDS study showed a significant decrease in the duration of mechanical ventilation, although this result was only found by post-hoc analysis. The three studies on COPD demonstrated that some patients supported by ECCO2R devices could avoid endotracheal intubation, however the ICU-LOS and survival was not influenced by ECCO2R when compared to controls. CONCLUSIONS: In COPD patients, a significantly reduced need for endotracheal intubation was reported. However, the use of ECCO2R has not shown significant improvement on the outcome of critically ill patients in the reviewed studies. Therefore appropriately powered, randomized, controlled studies are urgently needed.