Extracorporeal Membrane Oxygenation Blood Flow Research Articles

Physiologic Effects of ECMO in Patients with Severe Acute Respiratory Distress Syndrome.

Blood flow rate affects mixed venous oxygenation (SvO2) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. We aimed at describing the physiologic effects of different levels of SvO2 obtained by changing ECMO blood flow, in patients with severe ARDS receiving ECMO and controlled mechanical ventilation. Low (SvO2 target 70-75%), intermediate (SvO2 target 75-80%) and high (SvO2 target > 80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography (EIT). Cardiac output decreased from low to intermediate and to high blood flow/SvO2 (9.2 [6.2-10.9] vs 8.3 [5.9-9.8] vs 7.9 [6.5-9.1] L/min, p = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs 31 ± 6 vs 30 ± 5 mmHg, p < 0.001), and right ventricle stroke work index (14.2 ± 4.4 vs 12.2 ± 3.6 vs 11.4 ± 3.2 g*m/beat/m2, p = 0.002). Cardiac output was inversely correlated with mixed venous and arterial PO2 values (R2 = 0.257, p = 0.031 and R2 = 0.324, p = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous PO2 (R2 = 0.29, p <0.001) and with increasing cardiac output (R2 = 0.378 p < 0.007). Measures of ventilation/perfusion mismatch did not differ between the three steps. In severe ARDS patients, increased ECMO blood flow rate resulting in higher SvO2 decreases pulmonary artery pressure, cardiac output, and right heart workload.

Effects of adding the second drainage cannula in severely hypoxemic patients supported with VV ECMO due to COVID-19-associated ARDS.

Extracorporeal membrane oxygenation (ECMO) is a recognized method of support in patients with severe and refractory acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection. While veno-venous (VV) ECMO is the most common type, some patients with severe hypoxemia may require modifications to the ECMO circuit. In this study, we aimed to investigate the effects of adding a second drainage cannula to the circuit in patients with refractory hypoxemia, on their gas exchange, mechanical ventilation, ECMO settings, and clinical outcomes. We conducted an observational retrospective study based on a single-center institutional registry including all consecutive cases of COVID-19 patients requiring ECMO admitted to the Centre of Extracorporeal Therapies in Warsaw between March 1, 2020 and March 1, 2022. We selected patients who had an additional drainage cannula inserted. Changes in ECMO and ventilator settings, blood oxygenation, and hemodynamic parameters, as well as clinical outcomes were assessed. Of 138 VV ECMO patients, 12 (9%) patients met the inclusion criteria. Ten patients (83%) were men, and mean age was 42.2 ± 6.8. An addition of drainage cannula resulted in a significant raise in ECMO blood flow (4.77 ± 0.44 to 5.94 ± 0.81 [L/min]; p = 0.001), and the ratio of ECMO blood flow to ECMO pump rotations per minute (RPM), whereas the raise in ECMO RPM alone was not statistically significant (3432 ± 258 to 3673 ± 340 [1/min]; p = 0.064). We observed a significant drop in ventilator FiO2 and a raise in PaO2 to FiO2 ratio, while blood lactates did not change significantly. Nine patients died in hospital, one was referred to lung transplantation center, two were discharged uneventfully. The use of an additional drainage cannula in severe ARDS associated with COVID-19 allows for an increased ECMO blood flow and improved oxygenation. However, we observed no further improvement in lung-protective ventilation and poor survival.

High- versus Low-Flow Extracorporeal Respiratory Support in Experimental Hypoxemic Acute Lung Injury.

Rationale: In the EOLIA (ECMO to Rescue Lung Injury in Severe ARDS) trial, oxygenation was similar between intervention and conventional groups, whereas [Formula: see text]e was reduced in the intervention group. Comparable reductions in ventilation intensity are theoretically possible with low-flow extracorporeal CO2 removal (ECCO2R), provided oxygenation remains acceptable. Objectives: To compare the effects of ECCO2R and extracorporeal membrane oxygenation (ECMO) on gas exchange, respiratory mechanics, and hemodynamics in animal models of pulmonary (intratracheal hydrochloric acid) and extrapulmonary (intravenous oleic acid) lung injury. Methods: Twenty-four pigs with moderate to severe hypoxemia (PaO2:FiO2 ⩽ 150 mm Hg) were randomized to ECMO (blood flow 50-60 ml/kg/min), ECCO2R (0.4 L/min), or mechanical ventilation alone. Measurements and Main Results: [Formula: see text]o2, [Formula: see text]co2, gas exchange, hemodynamics, and respiratory mechanics were measured and are presented as 24-hour averages. Oleic acid versus hydrochloric acid showed higher extravascular lung water (1,424 ± 419 vs. 574 ± 195 ml; P < 0.001), worse oxygenation (PaO2:FiO2 = 125 ± 14 vs. 151 ± 11 mm Hg; P < 0.001), but better respiratory mechanics (plateau pressure 27 ± 4 vs. 30 ± 3 cm H2O; P = 0.017). Both models led to acute severe pulmonary hypertension. In both models, ECMO (3.7 ± 0.5 L/min), compared with ECCO2R (0.4 L/min), increased mixed venous oxygen saturation and oxygenation, and improved hemodynamics (cardiac output = 6.0 ± 1.4 vs. 5.2 ± 1.4 L/min; P = 0.003). [Formula: see text]o2 and [Formula: see text]co2, irrespective of lung injury model, were lower during ECMO, resulting in lower PaCO2 and [Formula: see text]e but worse respiratory elastance compared with ECCO2R (64 ± 27 vs. 40 ± 8 cm H2O/L; P < 0.001). Conclusions: ECMO was associated with better oxygenation, lower [Formula: see text]o2, and better hemodynamics. ECCO2R may offer a potential alternative to ECMO, but there are concerns regarding its effects on hemodynamics and pulmonary hypertension.

Pressure ulcers after prone positioning in patients undergoing extracorporeal membrane oxygenation: A cross-sectional study.

The combination of prone positioning and extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome (ARDS) is recognized as safe but its use has been limited due to potential complications. To report the prevalence of pressure ulcers and other complications due to prone positioning in adult patients receiving veno-venous ECMO. This cross-sectional study was conducted in a tertiary level intensive care unit (ICU) in Milan (Italy), between January 2015 and December 2019. The study population was critically ill adult patients undergoing veno-venous ECMO. Statistical association between pressure ulcers and the type of body positioning (prone versus supine) was explored fitting a logistic model. In the study period, 114 patients were treated with veno-venous ECMO and 62 (54.4%) patients were placed prone for a total of 130 prone position cycles. ECMO cannulation was performed via femoro-femoral configuration in the majority of patients (82.4%, 94/114). Pressure ulcers developed in 57.0% of patients (95%CI: 44.0%-72.6%), most often arising on the face and the chin (37.1%, 23/62), particularly in those placed prone. The main reason of prone positioning interruption was the decrease of ECMO blood flow (8.1%, 5/62). The fitted model showed no association between body position during ECMO and occurrence of pressure ulcers (OR 1.3, 95%CI: 0.5-3.6, p=.532). Facial pressure ulcers were the most frequent complications of prone positioning. Nurses should plan and implement evidence-based care to prevent such pressure injuries in patients undergoing ECMO. The combination of prone positioning and ECMO shows few life-threating complications. This manoeuvre during ECMO is feasible and safe when performed by experienced ICU staff.

Effects of changes in veno-venous extracorporeal membrane oxygenation blood flow on the measurement of intrathoracic blood volume and extravascular lung water index: a prospective interventional study

In severe acute respiratory distress syndrome (ARDS), veno-venous extracorporeal membrane oxygenation (V-V ECMO) has been proposed as a therapeutic strategy to possibly reduce mortality. Transpulmonary thermodilution (TPTD) enables monitoring of the extravascular lung water index (EVLWI) and cardiac preload parameters such as intrathoracic blood volume index (ITBVI) in patients with ARDS, but it is not generally recommended during V-V ECMO. We hypothesized that the amount of extracorporeal blood flow (ECBF) influences the calculation of EVLWI and ITBVI due to recirculation of indicator, which affects the measurement of the mean transit time (MTt), the time between injection and passing of half the indicator, as well as downslope time (DSt), the exponential washout of the indicator. EVLWI and ITBVI were measured in 20 patients with severe ARDS managed with V-V ECMO at ECBF rates from 6 to 4 and 2 l/min with TPTD. MTt and DSt significantly decreased when ECBF was reduced, resulting in a decreased EVLWI (26.1 [22.8–33.8] ml/kg at 6 l/min ECBF vs 22.4 [15.3–31.6] ml/kg at 4 l/min ECBF, p < 0.001; and 13.2 [11.8–18.8] ml/kg at 2 l/min ECBF, p < 0.001) and increased ITBVI (840 [753–1062] ml/m2 at 6 l/min ECBF vs 886 [658–979] ml/m2 at 4 l/min ECBF, p < 0.001; and 955 [817–1140] ml/m2 at 2 l/min ECBF, p < 0.001). In patients with severe ARDS managed with V-V ECMO, increasing ECBF alters the thermodilution curve, resulting in unreliable measurements of EVLWI and ITBVI. German Clinical Trials Register (DRKS00021050). Registered 14/08/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021050

Extracorporeal membrane oxygenation circuits in parallel for refractory hypoxemia in patients with COVID-19

ObjectivesRefractory hypoxemia can occur in patients with acute respiratory distress syndrome from COVID-19 despite support with venovenous (VV) extracorporeal membrane oxygenation (ECMO). Parallel ECMO circuits can be used to increase physiologic support. We report our clinical experience using ECMO circuits in parallel for select patients with persistent severe hypoxemia despite the use of a single ECMO circuit. MethodsWe performed a retrospective cohort study of all patients with COVID–19-related acute respiratory distress syndrome who received VV-ECMO with an additional circuit in parallel at Vanderbilt University Medical Center between March 1, 2020, and March 1, 2022. We report demographic characteristics and clinical characteristics including ECMO settings, mechanical ventilator settings, use of adjunctive therapies, and arterial blood gas results after initial cannulation, before and after receipt of a second ECMO circuit in parallel, and before removal of the circuit in parallel, and outcomes. ResultsOf 84 patients with COVID-19 who received VV-ECMO during the study period, 22 patients (26.2%) received a circuit in parallel. The median duration of ECMO was 40.0 days (interquartile range, 31.6-53.1 days), of which 19.0 days (interquartile range, 13.0-33.0 days) were spent with a circuit in parallel. Of the 22 patients who received a circuit in parallel, 16 (72.7%) survived to hospital discharge and 6 (27.3%) died before discharge. ConclusionsIn select patients, the additional use of an ECMO circuit in parallel can increase ECMO blood flow and improve oxygenation while allowing for lung-protective mechanical ventilation and excellent outcomes.

A Novel Mock Circuit to Test Full-Flow Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) has become an important therapeutic approach in the COVID-19 pandemic. The development and research in this field strongly relies on animal models; however, efforts are being made to find alternatives. In this work, we present a new mock circuit for ECMO that allows measurements of the oxygen transfer rate of a membrane lung at full ECMO blood flow. The mock utilizes a large reservoir of heparinized porcine blood to measure the oxygen transfer rate of the membrane lung in a single passage. The oxygen transfer rate is calculated from blood flow, hemoglobin value, venous saturation, and post-membrane arterial oxygen pressure. Before the next measuring sequence, the blood is regenerated to a venous condition with a sweep gas of nitrogen and carbon dioxide. The presented mock was applied to investigate the effect of a recirculation loop on the oxygen transfer rate of an ECMO setup. The recirculation loop caused a significant increase in post-membrane arterial oxygen pressure (paO2). The effect was strongest for the highest recirculation flow. This was attributed to a smaller boundary layer on gas fibers due to the increased blood velocity. However, the increase in paO2 did not translate to significant increases in the oxygen transfer rate because of the minor significance of physically dissolved oxygen for gas transfer. In conclusion, our results regarding a new ECMO mock setup demonstrate that recirculation loops can improve ECMO performance, but not enough to be clinically relevant.

Effect of different connection schemes of continuous renal replacement therapy and extracorporeal membrane oxygenation on arterial and venous pressure: an in vitro and in vivo study

To investigate the effects of different connection schemes of continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) on arterial pressure (PA), venous pressure (PV), and transmembrane pressure (TMP), and to provide a theoretical basis for choosing a suitable connection scheme. (1) In vitro study: the different connection schemes of CRRT and ECMO were simulated and divided into 6 schemes according to the connection between CRRT and ECMO circuits at different positions. Scheme A: connected to the front and back points of the oxygenator; scheme B: connected to the points behind and in front of the oxygenator; scheme C: connected to the points in front of the oxygenator and in front of the centrifugal pump; scheme D: connected to the points behind the oxygenator and in front of the centrifugal pump; scheme E: connected to the points in front of the oxygenator and the return catheter; scheme F: connected to the points after the oxygenator and the return catheter. Each set of ECMO circuits was measured 5 times under each connection scheme and different flow rates (2, 3, 4, 5, 5.5 L/min). Six ECMO circuits for a total of 30 measurements, and the PA, PV, and TMP of the 6 schemes were compared. (2) In vivo study: the patients who were treated with ECMO combined with CRRT in the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from August 2017 to August 2021 changed the connection scheme due to high PA or PV (from scheme A or B to scheme E or F) were retrospectively analyzed. The changes of PA and PV before and after changing the scheme were compared. (1) In vitro study results: there was no significant difference in PA between schemes A and B, C and D, E and F under different ECMO blood flow (2-5.5 L/min). The PA of schemes C and D was the lowest, followed by schemes E and F. PV of scheme B was higher than that of scheme A under different ECMO blood flow (2-5.5 L/min). There was no significant difference in PV between schemes C and D, E and F under high ECMO blood flow (3-5.5 L/min), and the absolute value of PV was lowest in schemes E and F. Compared with schemes A and B [partial PA > 300 mmHg (1 mmHg ≈ 0.133 kPa) at high flow rate], C and D (partial PV > 350 mmHg at high flow rate), schemes E and F were more reasonable connection schemes. TMP was negative in schemes C and D at ECMO blood flow of 5 L/min and 5.5 L/min (mmHg; 5 L/min: scheme C was -29.14±11.42, scheme D was -42.45±15.70; 5.5 L/min: scheme C was -35.75±13.21, scheme D was -41.58±15.42), which indicated the presence of dialysate reverse filtration. Most of the differences in TMP among schemes A, B, E, and F under different ECMO blood flow (2-5.5 L/min) were statistically significant, and the absolute value of mean fluctuation was 9.89-49.55 mmHg, all within the normal range. (2) In vivo study results: a total of 10 patients who changed the connection scheme (from scheme A or B to E or F) due to high PA or PV were enrolled, including 8 males and 2 females; 7 cases of venous-arterial ECMO (VA-ECMO) and 3 cases of venous-venous ECMO (VV-ECMO), all used continuous veno-venous hemodiafiltration (CVVHDF) mode. After changing the scheme, both PA and PV decreased significantly as compared with those before changing [PA (mmHg): 244.00±22.58 vs. 257.20±21.92, PV (mmHg): 257.20±18.43 vs. 326.40±15.41, both P < 0.01], and PV decreased more significantly than PA [difference (mmHg): 69.20±6.55 vs. 13.20±5.45, P < 0.01]. For patients treated with ECMO in combination with CRRT, the scheme of connecting the access line of CRRT to the pre-oxygenator or post-oxygenator and connecting the return line to the point of the return catheter can significantly reduce PA and PV and maintains normal CRRT operation even running high-flow ECMO.

A retrospective analysis of the hemolysis occurrence during extracorporeal membrane oxygenation in a single center.

Extracorporeal membrane oxygenation (ECMO)-associated hemolysis still represents a serious complication. The present study aimed to investigate those predictive factors, such as flow rates, the use of anticoagulants, and circuit connected dialysis, that might play a pivotal role in hemolysis in adult patients. This is a retrospective single-center case series of 35 consecutive adult patients undergoing veno-venous ECMO support at our center between April 2014 and February 2020. Daily plasma-free hemoglobin (pfHb) and haptoglobin (Hpt) levels were chosen as hemolysis markers and they were analyzed along with patients' characteristics, daily laboratory findings, and corresponding ECMO system variables, as well as continuous renal replacement therapy (CRRT) when administered, looking for factors influencing their trends over time. Among the many settings related to the ECMO support, the presence of CRRT connected to the ECMO circuit has been found associated with both higher daily pfHb levels and lower Hpt levels. After correction for potential confounders, hemolysis was ascribable to circuit-related variables, in particular the membrane oxygenation dead space was associated with an Hpt reduction (B = -215.307, p = 0.004). Moreover, a reduction of ECMO blood flow by 1L/min has been associated with a daily Hpt consumption of 93.371mg/dL (p = 0.001). Technical-induced hemolysis during ECMO should be monitored not only when suspected but also during quotidian management and check-ups. While considering the clinical complexity of patients on ECMO support, clinicians should not only be aware of and anticipate possible circuitry malfunctions or inadequate flow settings, but they should also take into account the effects of an ECMO circuit-connected CRRT, as an equally important key factor triggering hemolysis.

Comparative polymyxin B pharmacokinetics in patients receiving extracorporeal membrane oxygenation.

To describe polymyxin B pharmacokinetics in patients receiving veno-venous extracorporeal membrane oxygenation (ECMO) in comparison with critically ill patients without ECMO support and to explore potential covariates that could affect the pharmacokinetics in this group of patients. In 13 critically ill patients on ECMO and in 21 critically ill patients without ECMO support, 6-8 blood samples were collected during 12 h intervals after reaching steady state. Polymyxin B concentration in serum was determined using a previously developed ELISA. Protein binding was assessed by rapid equilibrium dialysis. In 13 critically ill patients on ECMO who received polymyxin B, the median area under the concentration-time curve over 12 h (AUC0-12h) was 48.38 mg/h/L for the total drug and 14.08 mg/h/L for the free drug. The unbound fraction was 0.35. Total body clearance was 1.16 L/h. In non-ECMO patients, the median AUC0-12h was 34.7 mg/h/L and the median CL was 1.76 L/h. The volume of distribution was significantly lower in ECMO patients (19.7 versus 30.4 L, respectively). We found a moderate negative correlation between the ECMO blood flow rate and AUC0-12h, a strong negative correlation between SOFA score and polymyxin B clearance and a moderate correlation between polymyxin B clearance and renal function in ECMO patients. Currently recommended polymyxin B dosage regimens are sufficient for patients receiving ECMO and no dosage increase is required. In our study, polymyxin B exposure was higher in ECMO patients compared with the control group.

Exploring the association of two oxygenators in parallel or in series during respiratory support using extracorporeal membrane oxygenation.

To characterize the pressures, resistances, oxygenation, and decarboxylation efficacy of two oxygenators associated in series or in parallel during venous-venous extracorporeal membrane oxygenation support. Using the results of a swine severe respiratory failure associated with multiple organ dysfunction venous-venous extracorporeal membrane oxygenation support model and mathematical modeling, we explored the effects on oxygenation, decarboxylation and circuit pressures of in-parallel and in-series associations of oxygenators. Five animals with a median weight of 80kg were tested. Both configurations increased the oxygen partial pressure after the oxygenators. The return cannula oxygen content was also slightly higher, but the impact on systemic oxygenation was minimal using oxygenators with a high rated flow (~ 7L/minute). Both configurations significantly reduced the systemic carbon dioxide partial pressure. As the extracorporeal membrane oxygenation blood flow increased, the oxygenator resistance decreased initially with a further increase with higher blood flows but with a small clinical impact. Association of oxygenators in parallel or in series during venous-venous extracorporeal membrane oxygenation support provides a modest increase in carbon dioxide partial pressure removal with a slight improvement in oxygenation. The effect of oxygenator associations on extracorporeal circuit pressures is minimal.

Transpulmonary thermodilution in patients treated with veno-venous extracorporeal membrane oxygenation

BackgroundWe tested the effect of different blood flow levels in the extracorporeal circuit on the measurements of cardiac stroke volume (SV), global end-diastolic volume index (GEDVI) and extravascular lung water index derived from transpulmonary thermodilution (TPTD) in 20 patients with severe acute respiratory distress syndrome (ARDS) treated with veno-venous extracorporeal membrane oxygenation (ECMO).MethodsComparative SV measurements with transesophageal echocardiography and TPTD were performed at least 5 times during the treatment of the patients. The data were interpreted with a Bland–Altman analysis corrected for repeated measurements. The interchangeability between both measurement modalities was calculated and the effects of extracorporeal blood flow on SV measurements with TPTD was analysed with a linear mixed effect model. GEDVI and EVLWI measurements were performed immediately before the termination of the ECMO therapy at a blood flow of 6 l/min, 4 l/min and 2 l/min and after the disconnection of the circuit in 7 patients.Results170 pairs of comparative SV measurements were analysed. Average difference between the two modalities (bias) was 0.28 ml with an upper level of agreement of 40 ml and a lower level of agreement of -39 ml within a 95% confidence interval and an overall interchangeability rate between TPTD and Echo of 64%. ECMO blood flow did not influence the mean bias between Echo and TPTD (0.03 ml per l/min of ECMO blood flow; p = 0.992; CI − 6.74 to 6.81). GEDVI measurement was not significantly influenced by the blood flow in the ECMO circuit, whereas EVLWI differed at a blood flow of 6 l/min compared to no ECMO flow (25.9 ± 10.1 vs. 11.0 ± 4.2 ml/kg, p = 0.0035).ConclusionsIrrespectively of an established ECMO therapy, comparative SV measurements with Echo and TPTD are not interchangeable.Such caveats also apply to the interpretation of EVLWI, especially with a high blood flow in the extracorporeal circulation. In such situations, the clinician should rely on other methods of evaluation of the amount of lung oedema with the haemodynamic situation, vasopressor support and cumulative fluid balance in mind.Trial registration: German Clinical Trials Register (DRKS00021050). Registered 03/30/2020https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017237

Management of intra-abdominal hypertension during ECMO: Total water-assisted colonoscopy as a step-up minimally invasive treatment, and a literature review.

Background and study aims During extracorporeal membrane oxygenation (ECMO), intra-abdominal hypertension (IAH) can impair ECMO venous drainage, reducing its ability to provide an adequate oxygenated blood flow. When medical therapy is ineffective in managing IAH, guidelines recommend a decompressive laparotomy (DL), though the procedure is associated with several complications and poor outcomes. Patients and methods This was a case series of IAH in patients affected with acute respiratory distress syndrome (ARDS) on veno-venous (V-V) ECMO, in whom we performed total water-assisted colonoscopy (t-WAC) to treat IAH. Results In three patients who underwent t-WAC, we report a real-time intra-procedural reduction of IAH, normalization of ECMO blood flow, and a reduction of vasopressors and lactates. t-WAC was performed in the context of evident abdominal compartment syndrome with multiorgan failure, and in one case was performed because of IAH and ECMO impairment. One patient was discharged alive, while the other two died of multiorgan failure, although the cause of death was apparently not secondary to IAH. Conclusions During ECMO, in select cases,T-WAC may represent a first-line non-invasive approach.

Atelectasis, Shunt, and Worsening Oxygenation Following Reduction of Respiratory Rate in Healthy Pigs Undergoing ECMO: An Experimental Lung Imaging Study

Rationale: Reducing the respiratory rate during extracorporeal membrane oxygenation (ECMO) decreases the mechanical power, but it might induce alveolar de-recruitment. Dissecting de-recruitment due to lung edema vs. the fraction due to hypoventilation may be challenging in injured lungs.Objectives: We characterized changes in lung physiology (primary endpoint: development of atelectasis) associated with progressive reduction of the respiratory rate in healthy animals on ECMO.Methods: Six female pigs underwent general anesthesia and volume control ventilation (Baseline: PEEP 5 cmH2O, Vt 10 ml/kg, I:E = 1:2, FiO2 0.5, rate 24 bpm). Veno-venous ECMO was started and respiratory rate was progressively reduced to 18, 12, and 6 breaths per minute (6-h steps), while all other settings remained unchanged. ECMO blood flow was kept constant while gas flow was increased to maintain stable PaCO2.Measurements and Main Results: At Baseline (without ECMO) and toward the end of each step, data from quantitative CT scan, electrical impedance tomography, and gas exchange were collected. Increasing ECMO gas flow while lowering the respiratory rate was associated with an increase in the fraction of non-aerated tissue (i.e., atelectasis) and with a decrease of tidal ventilation reaching the gravitationally dependent lung regions (p = 0.009 and p = 0.018). Intrapulmonary shunt increased (p < 0.001) and arterial PaO2 decreased (p < 0.001) at lower rates. The fraction of non-aerated lung was correlated with longer expiratory time spent at zero flow (r = 0.555, p = 0.011).Conclusions: Progressive decrease of respiratory rate coupled with increasing CO2 removal in mechanically ventilated healthy pigs is associated with development of lung atelectasis, higher shunt, and poorer oxygenation.

Carboxyhemglobin and Drainage Pressure During Venovenous Extracorporeal Membrane Oxygenation.

To the Editor: We read with interest the article1 recently published by Nisar et al. on ASAIO Journal. The authors describe the frequent development of carboxyhemoglobinemia in patients treated with venovenous (V-V) extracorporeal membrane oxygenation (ECMO). As highlighted in the article, high carboxyhemoglobin levels cause significant discrepancies between pulse oximetry and actual oxyhemoglobin levels. This may lead to erroneous interpretation of patient oxygenation when the latter is assessed noninvasively. Carboxyhemoglobinemia has been described since 19492 as a marker for hemolysis. Hemolysis during V-V ECMO occurs in up to 18% of patients.3 The principal causes of mechanical hemolysis during ECMO support include circuit components (oxygenator, pump,4 cannula size) as well as patient’s characteristics.5 Centrifugal pump could be a major source of hemolysis when rotating in unsuitable conditions. High rotation speed (e.g., >3000 rpm) may result in high negative pressures at the pump head, thus promoting hydrodynamic cavitation and a high level of hemolysis.6 We performed a retrospective analysis of prospectively collected data of our historical cohort of acute respiratory distress syndrome patients treated with V-V ECMO, to compare our findings with Nisar et al. We included adult patients admitted to our ECMO unit (Rianimazione Generale, ASST Monza, Italy) between 2014 and 2020. We excluded patients with veno-venoarterial ECMO and COVID-19 patients, who may present coagulopathy as a part of the underlying disease.7 Arterial blood gas (ABG) analysis was performed with the RAPIDPoint 500e System (Siemens Healthcare, Erlangen, Germany). Elevated carboxyhemoglobin was defined according to the authors’ threshold (i.e., >3%).1 Eighty-four patients (39% females, 53 ± 10 years) were included in our analysis. ECMO configuration was femoro-femoral (86% of patients) or femoro-jugular. Median duration of ECMO support was 20 days, ranging from 3 to 83 days. Average blow flow was 3.5 ± 0.5 (2,520 ± 287 rpm), whereas mean drainage pressure was −42 ± 14 mm Hg. Overall, mean carboxyhemoglobin level was 1.1 ± 0.8%. Carboxyhemoglobin level at ECMO connection was 0.6 ± 0.5%%, and its average increase was 0.011% for each ECMO day. Among 1,653 ABG analyses, carboxyhemoglobin was >3% in only 23 samples (1.4%). A carboxyhemoglobin higher than 3% occurred at least once in eight (9.5%) patients. In our study, we found a lower incidence of hemolysis compared with Nisar et al.1 This finding may have different explanations. First, at our institution, we are used to carefully monitor the drainage pressure and adjusting the ECMO blood flow to avoid drainage pressures lower than −60/−70 mm Hg. This may limit hemolysis due to hydrodynamic cavitation. Moreover, a minor difference due to technical reason (i.e., two different blood gas analyzers) cannot be excluded. In absence of recirculation, a BF of 3–4 L/min usually allows achieving a safe oxygenation in adult patients.8 If adequate drainage cannulae are used (i.e., 21–25 Fr), this blood flow range can be usually achieved with drainage pressure of −30 to −60 mm Hg.9,10 Therefore, we hypothesize that limiting the blood flow rate to maintain “safe” drainage pressures may help in reducing the increase of carboxyhemoglobinemia during the ECMO course.

Early Findings after Implementation of Veno-Arteriovenous ECMO: A Multicenter European Experience.

Extracorporeal membrane oxygenation (ECMO) is increasingly used to treat cardiopulmonary failure in critically ill patients. Peripheral cannulation may be complicated by a persistent low cardiac output in case of veno-venous cannulation (VV-ECMO) or by differential hypoxia (e.g., lower PaO2 in the upper than in the lower body) in case of veno-arterial cannulation (VA-ECMO) and severe impairment of pulmonary function associated with cardiac recovery. The treatment of such complications remains challenging. We report the early effects of the use of veno-arterial-venous (V-AV) ECMO in this setting. Methods: Retrospective analysis including patients from five different European ECMO centers (January 2013 to December 2016) who required V-AV ECMO. We collected demographic data as well as comorbidities and ECMO characteristics, hemodynamics, and arterial blood gas values before and immediately after (i.e., within 2 h) V-AV implementation. Results: A total of 32 patients (age 53 (interquartiles, IQRs: 31–59) years) were identified: 16 were initially supported with VA-ECMO and 16 with VV-ECMO. The median time to V-AV conversion was 2 (1–5) days. After V-AV implantation, heart rate and norepinephrine dose significantly decreased, while PaO2 and SaO2 significantly increased compared to baseline values. Lactate levels significantly decreased from 3.9 (2.3–7.1) to 2.8 (1.4–4.4) mmol/L (p = 0.048). A significant increase in the overall ECMO blood flow (from 4.5 (3.8–5.0) to 4.9 (4.3–5.9) L/min; p < 0.01) was observed, with 3.0 (2.5–3.2) L/min for the arterial and 2.8 (2.1–3.6) L/min for the venous return flows. Conclusions: In ECMO patients with differential hypoxia or persistently low cardiac output syndrome, V-AV conversion was associated with improvement in some hemodynamic and respiratory parameters. A significant increase in the overall ECMO blood flow was also observed, with similar flow distributed into the arterial and venous return cannulas.

Optimization of extracorporeal membrane oxygenation therapy using near-infrared spectroscopy to assess changes in peripheral circulation: A pilot study.

Near-infrared spectroscopy (NIRS) has been proposed as a noninvasive modality for detecting complications in patients undergoing extracorporeal membrane oxygenation (ECMO), and it can simultaneously reveal the global circulatory status of these patients. We optimized ECMO therapy on the basis of real-time peripheral NIRS probing. Three patients underwent venoarterial (VA) ECMO and one patient underwent venovenous (VV) ECMO. All patients received peripheral ECMO cannulation with routine distal perfusion catheter placement. We designed an experimental protocol to adjust ECMO blood flow over 1 hour. Hemodynamic responses were measured using NIRS devices attached to the calf at approximately 60% of the distance from the ankle to the knee. HbO2 levels change substantially with adjustments in ECMO flow, and they are more sensitive than HHb levels and the tissue saturation index (TSI) are. NIRS for optimizing ECMO therapy may be reliable for monitoring global circulatory status.

Assessment of Right Heart Function during Extracorporeal Therapy by Modified Thermodilution in a Porcine Model.

Veno-arterial extracorporeal membrane oxygenation therapy is a growing treatment modality for acute cardiorespiratory failure. Cardiac output monitoring during veno-arterial extracorporeal membrane oxygenation therapy remains challenging. This study aims to validate a new thermodilution technique during veno-arterial extracorporeal membrane oxygenation therapy using a pig model. Sixteen healthy pigs were centrally cannulated for veno-arterial extracorporeal membrane oxygenation, and precision flow probes for blood flow assessment were placed on the pulmonary artery. After chest closure, cold boluses of 0.9% saline solution were injected into the extracorporeal membrane oxygenation circuit, right atrium, and right ventricle at different extracorporeal membrane oxygenation flows (4, 3, 2, 1 l/min). Rapid response thermistors in the extracorporeal membrane oxygenation circuit and pulmonary artery recorded the temperature change. After calculating catheter constants, the distributions of injection volumes passing each circuit were assessed and enabled calculation of pulmonary blood flow. Analysis of the exponential temperature decay allowed assessment of right ventricular function. Calculated blood flow correlated well with measured blood flow (r2 = 0.74, P < 0.001). Bias was -6 ml/min [95% CI ± 48 ml/min] with clinically acceptable limits of agreement (668 ml/min [95% CI ± 166 ml/min]). Percentage error varied with extracorporeal membrane oxygenation blood flow reductions, yielding an overall percentage error of 32.1% and a percentage error of 24.3% at low extracorporeal membrane oxygenation blood flows. Right ventricular ejection fraction was 17 [14 to 20.0]%. Extracorporeal membrane oxygenation flow reductions increased end-diastolic and end-systolic volumes with reductions in pulmonary vascular resistance. Central venous pressure and right ventricular ejection fractions remained unchanged. End-diastolic and end-systolic volumes correlated highly (r2 = 0.98, P < 0.001). Adapted thermodilution allows reliable assessment of cardiac output and right ventricular behavior. During veno-arterial extracorporeal membrane oxygenation weaning, the right ventricle dilates even with stable function, possibly because of increased venous return.

An urgent open surgical approach for left ventricle venting during peripheral veno-arterial extracorporeal membrane oxygenation for refractory cardiac arrest: case report

The objective of the study is to describe an emergency procedure for left ventricle venting during veno-arterial extracorporeal life support for refractory cardiac arrest. Veno-arterial extracorporeal membrane oxygenation is widely used in refractory cardiac arrest but is characterized by an increase in left ventricle afterload, which may impair cardiac contractility improvement. Different left ventricle venting techniques are available. We report the use of a surgical approach with sternotomy for left ventricle venting in a 21-year-old patient who was placed under veno-arterial extracorporeal membrane oxygenation for refractory cardiac arrest with severe pulmonary edema, respiratory failure, and left ventricle stasis. A 21-year-old woman was admitted for laparoscopic sleeve gastrectomy. In the recovery room, she developed a refractory circulatory shock. Transthoracic echocardiography revealed a dilated cardiomyopathy with severe left ventricle systolic dysfunction (left ventricle ejection fraction at 20%). Coronary angiogram was normal. On day 2, she underwent laparotomy for sepsis and she presented cardiac arrest secondary to ventricular tachycardia. We proceeded to peripheral veno-arterial extracorporeal membrane oxygenation as the cardiac arrest was refractory. A miniaturized veno-arterial extracorporeal membrane oxygenation system was implanted into the right femoral vessels onsite .The low flow duration was 40 minutes. Veno-arterial extracorporeal membrane oxygenation blood flow was set to 3 L min-1, resulting in a closed aortic valve and a massive pulmonary edema. Transesophageal echocardiography showed left ventricular ejection fraction at 5% without aortic valve opening. We first implanted an intra-aortic balloon pump without clinical improvement. Transesophageal echocardiography revealed massive thrombus formation into the aortic root. We decided to perform an open surgical approach for left ventricle unload using a transmitral cannula (22 Fr) via the right superior pulmonary vein connected to the inflow tube of the veno-arterial extracorporeal membrane oxygenation with Y connection. Transesophageal echocardiography showed a full opening of aortic valve and elimination of valve aortic thrombus. Chest radiography showed a significant decrease of pulmonary congestion. We were able to withdraw extracorporeal life support organization on day 10 and discharged on day 54. Clinical explorations reveal a fulminant rocuronium-related hypersensitivity myocarditis. This salvage surgical technique using a modified central veno-arterial extracorporeal membrane oxygenation cannulation technique has efficiently decreased blood stasis and permitted rapid recovery.

Management of accidental hypothermia: an established extracorporeal membrane oxygenation centre experience.

Data on management of severe accidental hypothermia published from an established high-volume extracorporeal membrane oxygenation centre are scarce. A total of 28 patients with intravesical temperature lower than 28°C on admission were either treated with veno-arterial extracorporeal membrane oxygenation or rewarmed conservatively. A total of 10 patients rewarmed on veno-arterial extracorporeal membrane oxygenation (age: 37 ± 12.6 years) and 18 conservatively (age: 55.2 ± 11.2 years) were collected over a course of 5 years. The dominant cause was alcohol intoxication with exposure to cold (39%), 12 patients were resuscitated prior to admission. The admission temperature in the extracorporeal membrane oxygenation group (23.8 ± 2.6°C) was lower than in the non-extracorporeal membrane oxygenation group (26.0 ± 1.5°C, p = 0.01). The peripheral percutaneous veno-arterial extracorporeal membrane oxygenation was always cannulated in malignant arrhythmias causing refractory cardiac arrest. The typical extracorporeal membrane oxygenation blood flow was 3-4 L/minute and sweep gas flow 2 L/minute, the median extracorporeal membrane oxygenation duration was 48.3 (28.1-86.7) hours. The median rates of rewarming did not differ (0.41 (0.35-0.7)°C/hour in extracorporeal membrane oxygenation and 0.77 (0.54-0.98)°C/hour in non-extracorporeal membrane oxygenation, p = 0.46) as well as the admission arterial lactate, pH and potassium. Their development was not different between the groups except for higher pH between the third and ninth hour of rewarming in the extracorporeal membrane oxygenation group. The hospital mortality was 10% in the extracorporeal membrane oxygenation group and 11.1% in the non-extracorporeal membrane oxygenation group with the median last Glasgow Coma Scale 15 and Cerebral Performance Score 1. Veno-arterial extracorporeal membrane oxygenation for severe hypothermia shows promising outcome data collected in an extracorporeal membrane oxygenation/extracorporeal cardiopulmonary resuscitation centre located in a European urban area. Except for presence of refractory cardiac arrest, the established hypothermia-related prognostic indicators did not differ between patients in need for extracorporeal membrane oxygenation and those rewarmed without extracorporeal membrane oxygenation.