Blood flow and emboli transport patterns during venoarterial extracorporeal membrane oxygenation: A computational fluid dynamics study.

PROBLEM: Despite advances in Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO), a significant mortality rate persists due to complications. The non-physiological blood flow dynamics of VA-ECMO may lead to neurological complications and organ ischemia. Continuous retrograde high-flow oxygenated blood enters through a return cannula placed in the femoral artery which opposes the pulsatile deoxygenated blood ejected by the left ventricle (LV), which impacts upper body oxygenation and subsequent hyperoxemia. The complications underscore the critical need to comprehend the impact of VA-ECMO support level and return cannula size, as mortality remains a significant concern. AIM: The aim of this study is to predict and provide insights into the complications associated with VA-ECMO using computational fluid dynamics (CFD) simulations. These complications will be assessed by characterising blood flow and emboli transport patterns through a comprehensive analysis of the influence of VA-ECMO support levels and arterial return cannula sizes. METHODS: Patient-specific 3D aortic and major branch models, derived from a male patient's CT scan during VA-ECMO undergoing respiratory dysfunction, were analyzed using CFD. The investigation employed species transport and discrete particle tracking models to study ECMO blood (oxygenated) mixing with LV blood (deoxygenated) and to trace emboli transport patterns from potential sources (circuit, LV, and aorta wall). Two cannula sizes (15 Fr and 19 Fr) were tested alongside varying ECMO pump flow rates (50%, 70%, and 90% of the total cardiac output). RESULTS: Cannula size did not significantly affect oxygen transport. At 90% VA-ECMO support, all arteries distal to the aortic arch achieved 100% oxygen saturation. As support level decreased, oxygen transport to the upper body also decreased to a minimum saturation of 73%. Emboli transport varied substantially between emboli origin and VAECMO support level, with the highest risk of cerebral emboli coming from the LV with a 15 Fr cannula at 90% support. CONCLUSION: Arterial return cannula sizing minimally impacted blood oxygen distribution; however, it did influence the distribution of emboli released from the circuit and aortic wall. Notably, it was the support level alone that significantly affected the mixing zone of VA-ECMO and cardiac blood, subsequently influencing the risk of embolization of the cardiogenic source and oxygenation levels across various arterial branches.

Impact of postoperative hyperlactatemia in orthotopic heart transplantation.

BACKGROUND: Hyperlactatemia (HL) is a common phenomenon after cardiac surgery which is related to tissue hypoperfusion and hypoxia and associated with poor outcomes. It is also often seen in the postoperative period after orthotopic heart transplantation (OHTx), but the association between HL and outcomes after OHTx is not well known. We evaluated the incidence and outcome of HL after OHTx. METHODS: This was a retrospective study of 209 patients who underwent OHTx between January 2011 and December 2020. Patients were classified into 3 groups according to their peak lactate levels within the first 72 h postoperatively: group 1, normal to mild hyperlactatemia (<5 mmol/L, n = 42); group 2, moderate hyperlactatemia (5-10 mmol/L, n = 110); and group 3, severe hyperlactatemia (>10 mmol/L, n = 57). The primary composite endpoint was all-cause mortality or postoperative initiation of veno-arterial extracorporeal membrane oxygenation (VA ECMO) within 30 days. Secondary endpoints included duration of mechanical ventilation, intensive care unit length of stay, and hospital length of stay. RESULTS: Patients with higher postoperative peak lactate levels were more commonly transplanted from left ventricular assist device support (33.3 % vs 50.9 % vs 64.9, p < 0.01) and had longer cardiopulmonary bypass time [127 min (109-148) vs 141 min (116-186) vs 153 min (127-182), p = 0.02]. Composite primary endpoint was met in 18 patients (8.6 %) and was significantly more common in patients with higher postoperative peak lactate levels (0.0 % vs 6.4 % vs 19.3 %, p < 0.01). CONCLUSIONS: Severe hyperlactatemia following orthotopic heart transplant was associated with an increased risk of post-transplant VA ECMO initiation and mortality at 30 days.

Flow characterization of Maquet and Bio-Medicus multi-stage drainage cannulae during venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Drainage cannulae extract blood from a patient during venoarterial extracorporeal membrane oxygenation (VA ECMO), a treatment that temporarily supports patients undergoing severe heart and/or lung dysfunction. Currently, the two most commonly used multi-stage drainage cannulae are manufactured by Maquet and Bio-Medicus, but their designs vary in many aspects which impacts the generated flow dynamics. Therefore, this study aimed to use computational fluid dynamics (CFD) to explore the flow characteristics of the aforementioned cannulae and their impact on complications such as thrombosis. METHODS: The Maquet and Bio-Medicus cannulae were 3D modelled within a patient-specific geometry of the venous vasculature taken from a computed tomography scan of a patient undergoing VA ECMO. A drainage flow rate of 4 L/min was assigned to each cannula. Lastly, a stress blended eddy simulation turbulence model was employed to resolve bulk flow turbulence. RESULTS: The proximal row of side holes in both cannulae generated high intensity counter-rotating vortices, thus generating supraphysiological shear. These proximal rows were also responsible for the majority of flow extraction in both cannulae (>1.6 L/min). Despite identical simulation settings, each cannulae had differing impacts on global flow dynamics. For instance, the Bio-Medicus model produced a total stagnant blood volume of 25.6 ml, compared to 17.8 ml the Maquet cannula, thereby increasing the risk of thrombosis. CONCLUSIONS: Overall, our results demonstrate that differences in design clearly impact flow dynamics and risk of complications. Therefore, further work in optimizing cannula design may be beneficial to prevent harmful flow characteristics.

Extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest in Australia: a narrative review.

Extracorporeal cardiopulmonary resuscitation (ECPR) in patients with prolonged or refractory out-of-hospital cardiac arrest (OHCA) is likely to be beneficial when used as part of a well developed emergency service system. ECPR is technically challenging to initiate and resource-intensive, but it has been found to be cost-effective in hospital-based ECPR programs. ECPR expansion within Australia has thus far been reactive and does not provide broad coverage or equity of access for patients. Newer delivery strategies that improve access to ECPR for patients with OHCA are being trialled, including networked hospital-based ECPR and pre-hospital ECPR programs. The efficacy, scalability, sustainability and cost-effectiveness of these programs need to be assessed. There is a need for national collaboration to determine the most cost-effective delivery strategies for ECPR provision along with its place in the OHCA survival chain.

Oxygenation During Venoarterial Extracorporeal Membrane Oxygenation: Physiology, Current Evidence, and a Pragmatic Approach to Oxygen Titration.

OBJECTIVES: This review aims to: 1) identify the key circuit and patient factors affecting systemic oxygenation, 2) summarize the literature reporting the association between hyperoxia and patient outcomes, and 3) provide a pragmatic approach to oxygen titration, in patients undergoing peripheral venoarterial extracorporeal membrane oxygenation (ECMO). DATA SOURCES: Searches were performed using PubMed, SCOPUS, Medline, and Google Scholar. STUDY SELECTION: All observational and interventional studies investigating the association between hyperoxia, and clinical outcomes were included, as well as guidelines from the Extracorporeal Life Support Organization. DATA EXTRACTION: Data from relevant literature was extracted, summarized, and integrated into a concise narrative review. For ease of reference a summary of relevant studies was also produced. DATA SYNTHESIS: The extracorporeal circuit and the native cardiorespiratory circuit both contribute to systemic oxygenation during venoarterial ECMO. The ECMO circuit's contribution to systemic oxygenation is, in practice, largely determined by the ECMO blood flow, whereas the native component of systemic oxygenation derives from native cardiac output and residual respiratory function. Interactions between ECMO outflow and native cardiac output (as in differential hypoxia), the presence of respiratory support, and physiologic parameters affecting blood oxygen carriage also modulate overall oxygen exposure during venoarterial ECMO. Physiologically those requiring venoarterial ECMO are prone to hyperoxia. Hyperoxia has a variety of definitions, most commonly Pao2 greater than 150 mm Hg. Severe hypoxia (Pao2 > 300 mm Hg) is common, seen in 20%. Early severe hyperoxia, as well as cumulative hyperoxia exposure was associated with in-hospital mortality, even after adjustment for disease severity in both venoarterial ECMO and extracorporeal cardiopulmonary resuscitation. A pragmatic approach to oxygenation during peripheral venoarterial ECMO involves targeting a right radial oxygen saturation target of 94-98%, and in selected patients, titration of the fraction of oxygen in the mixture via the air-oxygen blender to target postoxygenator Pao2 of 150-300 mm Hg. CONCLUSIONS: Hyperoxia results from a range of ECMO circuit and patient-related factors. It is common during peripheral venoarterial ECMO, and its presence is associated with poor outcome. A pragmatic approach that avoids hyperoxia, while also preventing hypoxia has been described for patients receiving peripheral venoarterial ECMO.

The effect of restrictive versus liberal selection criteria on survival in ECPR: a retrospective analysis of a multi-regional dataset.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an established rescue therapy for both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). However, there remains significant heterogeneity in populations and outcomes across different studies. The primary aim of this study was to compare commonly used selection criteria and their effect on survival and utilisation in an Australian ECPR cohort. METHODS: We performed a retrospective, observational study of three established ECPR centres in Australia, including cases from 1 January 2013 to 31 December 2020 to establish the baseline cohort. We applied five commonly used ECPR selection criteria, ranging from restrictive to liberal. RESULTS: The baseline cohort included 199 ECPR cases: 95 OHCA and 104 IHCA patients. Survival to hospital discharge was 20% for OHCA and 41.4% for IHCA. For OHCA patients, strictly applying the most restrictive criteria would have resulted in the highest survival rate 7/16 (43.8%) compared to the most liberal criteria 16/73 (21.9%). However, only 16/95 (16.8%) in our cohort strictly met the most restrictive criteria versus 73/95 (76.8%) with the most liberal criteria. Similarly, in IHCA, the most restrictive criteria would have resulted in a higher survival rate in eligible patients 10/15 (66.7%) compared to 27/59 (45.8%) with the most liberal criteria. With all criteria a large portion of survivors in IHCA would not have been eligible for ECMO if strictly applying criteria, 33/43 (77%) with restrictive and 16/43 (37%) with the most liberal criteria. CONCLUSIONS: Adherence to different selection criteria impacts both the ECPR survival rate and the total number of survivors. Commonly used selection criteria may be unsuitable to select IHCA ECPR patients.

Implementation of Recommendations on the Use of Corticosteroids in Severe COVID-19.

Importance: Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. Objectives: To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary objectives were to evaluate the association between the timing of publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (June 2020) and the WHO guidelines for corticosteroids (September 2020) and the temporal trends observed in corticosteroid use by region and to describe the geographic distribution of the recruitment in clinical trials that informed the WHO recommendation. Design, Setting, and Participants: This prospective cohort study of 434 851 patients was conducted between January 31, 2020, and September 2, 2022, in 63 countries worldwide. The data were collected under the auspices of the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC)-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Analyses were restricted to patients hospitalized for severe COVID-19 (a subset of the ISARIC data set). Exposure: Corticosteroid use as reported to the ISARIC-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Main Outcomes and Measures: Number and percentage of patients hospitalized with severe COVID-19 who received corticosteroids by time period and by WHO geographic region. Results: Among 434 851 patients with confirmed severe or critical COVID-19 for whom receipt of corticosteroids could be ascertained (median [IQR] age, 61.0 [48.0-74.0] years; 53.0% male), 174 307 (40.1%) received corticosteroids during the study period. Of the participants in clinical trials that informed the guideline, 91.6% were recruited from the United Kingdom. In all regions, corticosteroid use for severe COVID-19 increased, but this increase corresponded to the timing of the RECOVERY trial (time-interruption coefficient 1.0 [95% CI, 0.9-1.2]) and WHO guideline (time-interruption coefficient 1.9 [95% CI, 1.7-2.0]) publications only in Europe. At the end of the study period, corticosteroid use for treatment of severe COVID-19 was highest in the Americas (5421 of 6095 [88.9%]; 95% CI, 87.7-90.2) and lowest in Africa (31 588 of 185 191 [17.1%]; 95% CI, 16.8-17.3). Conclusions and Relevance: The results of this cohort study showed that implementation of the guidelines for use of corticosteroids in the treatment of severe COVID-19 varied geographically. Uptake of corticosteroid treatment was lower in regions with limited clinical trial involvement. Improving research diversity and representativeness may facilitate timely knowledge uptake and guideline implementation.

Expert consensus on training and accreditation for extracorporeal cardiopulmonary resuscitation an international, multidisciplinary modified Delphi Study.

BACKGROUND: A multidisciplinary group of stakeholders were used to identify: (1) the core competencies of a training program required to perform in-hospital ECPR initiation (2) additional competencies required to perform pre-hospital ECPR initiation and; (3) the optimal training method and maintenance protocol for delivering an ECPR program. METHODS: A modified Delphi process was undertaken utilising two web based survey rounds and one virtual meeting. Experts rated the importance of different aspects of ECPR training, competency and governance on a 9-point Likert scale. A diverse, representative group was targeted. Consensus was achieved when greater than 70% respondents rated a domain as critical (> or = 7 on the 9 point Likert scale). RESULTS: 35 international ECPR experts from 9 countries formed the expert panel, with a median number of 14 years of ECMO practice (interquartile range 11-38). Participant response rates were 97% (survey round one), 63% (virtual meeting) and 100% (survey round two). After the second round of the survey, 47 consensus statements were formed outlining a core set of competencies required for ECPR provision. We identified key elements required to safely train and perform ECPR including skill pre-requisites, surrogate skill identification, the importance of competency-based assessment over volume of practice and competency requirements for successful ECPR practice and skill maintenance. CONCLUSIONS: We present a series of core competencies, training requirements and ongoing governance protocols to guide safe ECPR implementation. These findings can be used to develop training syllabus and guide minimum standards for competency as the growth of ECPR practitioners continues.

Simvastatin in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2). RESULTS: Enrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control. CONCLUSIONS: Although recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial: Study Protocol and Statistical Analysis Plan.

Introduction: Critically ill patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) are at risk of developing severe arterial hyperoxia, which has been associated with increased mortality. Lower saturation targets in this population may lead to deleterious episodes of severe hypoxia. This manuscript describes the protocol and statistical analysis plan for the Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial. Design: The BLENDER trial is a pragmatic, multicentre, registry-embedded, randomised clinical trial., registered at ClinicalTrials.gov (NCT03841084) and approved by The Alfred Hospital Ethics Committee project ID HREC/50486/Alfred-2019. Participants and setting: Patients supported by VA ECMO for cardiogenic shock or cardiac arrest who are enrolled in the Australian national ECMO registry. Intervention: The study compares a conservative oxygenation strategy (target arterial saturations 92-96%) with a liberal oxygenation strategy (target 97-100%). Main Outcome Measures: The primary outcome is the number of intensive care unit (ICU)-free days for patients alive at day 60. Secondary outcomes include duration of mechanical ventilation, ICU and hospital mortality, the number of hypoxic episodes, neurocognitive outcomes, and health economic analyses. The 300-patient sample size enables us to detect a 3-day difference in ICU-free days at day 60, assuming a mean ICU-free days of 11 days, with a risk of type 1 error of 5% and power of 80%. Data will be analysed according to a predefined analysis plan. Findings will be disseminated in peer-reviewed publications. Conclusions: This paper details the protocol and statistical analysis plan for the BLENDER trial, a registry-embedded, multicentre interventional trial comparing liberal and conservative oxygenation strategies in VA ECMO.

Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials.

Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain. Objective: To determine whether vitamin C improves outcomes for patients with COVID-19. Design, Setting, and Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents. Interventions: Patients were randomized to receive vitamin C administered intravenously or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses). Main Outcomes and Measures: The primary outcome was a composite of organ support-free days defined as days alive and free of respiratory and cardiovascular organ support in the intensive care unit up to day 21 and survival to hospital discharge. Values ranged from -1 organ support-free days for patients experiencing in-hospital death to 22 organ support-free days for those who survived without needing organ support. The primary analysis used a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented efficacy (improved survival, more organ support-free days, or both), an OR less than 1 represented harm, and an OR less than 1.2 represented futility. Results: Enrollment was terminated after statistical triggers for harm and futility were met. The trials had primary outcome data for 1568 critically ill patients (1037 in the vitamin C group and 531 in the control group; median age, 60 years [IQR, 50-70 years]; 35.9% were female) and 1022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years [IQR, 51-72 years]; 39.6% were female). Among critically ill patients, the median number of organ support-free days was 7 (IQR, -1 to 17 days) for the vitamin C group vs 10 (IQR, -1 to 17 days) for the control group (adjusted proportional OR, 0.88 [95% credible interval {CrI}, 0.73 to 1.06]) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support-free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 [95% CrI, 0.60 to 1.01]) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 [95% CrI, 0.73 to 1.17]) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 [95% CrI, 0.61 to 1.17]) and the posterior probability was 17.8% for efficacy. Conclusions and Relevance: In hospitalized patients with COVID-19, vitamin C had low probability of improving the primary composite outcome of organ support-free days and hospital survival. Trial Registration: ClinicalTrials.gov Identifiers: NCT04401150 (LOVIT-COVID) and NCT02735707 (REMAP-CAP).

Surviving Sepsis After Burn Campaign.

INTRODUCTION: The Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns have always been excluded from the Surviving Sepsis efforts. To improve sepsis outcomes in burn patients, an international group of burn experts developed the Surviving Sepsis After Burn Campaign (SSABC) as a testable guideline to improve burn sepsis outcomes. METHODS: The International Society for Burn Injuries (ISBI) reached out to regional or national burn organizations to recommend members to participate in the program. Two members of the ISBI developed specific "patient/population, intervention, comparison and outcome" (PICO) questions that paralleled the 2021 Surviving Sepsis Campaign [1]. SSABC participants were asked to search the current literature and rate its quality for each topic. At the Congress of the ISBI, in Guadalajara, Mexico, August 28, 2022, a majority of the participants met to create "statements" based on the literature. The "summary statements" were then sent to all members for comment with the hope of developing an 80% consensus. After four reviews, a consensus statement for each topic was created or "no consensus" was reported. RESULTS: The committee developed sixty statements within fourteen topics that provide guidance for the early treatment of sepsis in burn patients. These statements should be used to improve the care of sepsis in burn patients. The statements should not be considered as "static" comments but should rather be used as guidelines for future testing of the best treatments for sepsis in burn patients. They should be updated on a regular basis. CONCLUSION: Members of the burn community from the around the world have developed the Surviving Sepsis After Burn Campaign guidelines with the goal of improving the outcome of sepsis in burn patients.

Extracorporeal membrane oxygenation for critically ill adults.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) may provide benefit in certain populations of adults, including those with severe cardiac failure, severe respiratory failure, and cardiac arrest. However, it is also associated with serious short- and long-term complications, and there remains a lack of high-quality evidence to guide practice. Recently several large randomized controlled trials (RCTs) have been published, therefore, we undertook an update of our previous systematic review published in 2014. OBJECTIVES: To evaluate whether venovenous (VV), venoarterial (VA), or ECMO cardiopulmonary resuscitation (ECPR) improve mortality compared to conventional cardiopulmonary support in critically ill adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was March 2022. The search was limited to English language only. SELECTION CRITERIA: We included RCTs, quasi-RCTs, and cluster-RCTs that compared VV ECMO, VA ECMO or ECPR to conventional support in critically ill adults. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome was 1. all-cause mortality at day 90 to one year. Our secondary outcomes were 2. length of hospital stay, 3. survival to discharge, 4. disability, 5. adverse outcomes/safety events, 6. health-related quality of life, 7. longer-term health status, and 8. cost-effectiveness. We used GRADE to assess certainty of evidence. MAIN RESULTS: Five RCTs met our inclusion criteria, with four new studies being added to the original review (total 757 participants). Two studies were of VV ECMO (429 participants), one VA ECMO (41 participants), and two ECPR (285 participants). Four RCTs had a low risk of bias and one was unclear, and the overall certainty of the results (GRADE score) was moderate, reduced primarily due to indirectness of the study populations and interventions. ECMO was associated with a reduction in 90-day to one-year mortality compared to conventional treatment (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.70 to 0.92; P = 0.002, I2 = 11%). This finding remained stable after performing a sensitivity analysis by removing the single trial with an uncertain risk of bias. Subgroup analyses did not reveal a significant subgroup effect across VV, VA, or ECPR modes (P = 0.73). Four studies reported an increased risk of major hemorrhage with ECMO (RR 3.32, 95% CI 1.90 to 5.82; P < 0.001), while two studies reported no difference in favorable neurologic outcome (RR 2.83, 95% CI 0.36 to 22.42; P = 0.32). Other secondary outcomes were not consistently reported across the studies. AUTHORS' CONCLUSIONS: In this updated systematic review, which included four additional RCTs, we found that ECMO was associated with a reduction in day-90 to one-year all-cause mortality, as well as three times increased risk of bleeding. However, the certainty of this result was only low to moderate, limited by a low number of small trials, clinical heterogeneity, and indirectness across studies.

Smaller Return Cannula in Venoarterial Extracorporeal Membrane Oxygenation Does Not Increase Hemolysis: A Single-Center, Cohort Study.

The aim of this study was to explore the association between arterial return cannula diameter and hemolysis during peripheral VA ECMO. We identified 158 adult patients who received peripheral VA ECMO at our institution from the national ECMO database (EXCEL) between January 2019 and July 2021. We classified patients into a small cannula group (15 Fr diameter, n = 45) and a large cannula group (≥17 Fr diameter, n = 113), comparing incidences of clinical hemolysis and plasma free hemoglobin ( pf Hb). Moderate hemolysis is defined as having pf Hb 0.05-0.10 g/L and severe hemolysis as having pf Hb >0.10 g/L sustained for at least two consecutive readings or leading to a circuit change. There were no significant differences in rates of moderate hemolysis between small and large cannula groups (1 vs . 6; p = 0.39) and severe hemolysis (0 vs . 3; p = 0.27), nor was the pf Hb level significantly different at 4 hours (0.086 ± 0.096 vs . 0.112 ± 0.145 g/L; p = 0.58) and at 24 hours (0.042 ± 0.033 vs . 0.051 ± 0.069 g/L; p = 0.99). There were no increased rates of hemolysis when comparing small versus large arterial return cannula diameter in peripheral VA ECMO.

Therapeutic Hypothermia for Refractory Hypoxemia on Venovenous Extracorporeal Membrane Oxygenation: An In Silico Study.

Patients with respiratory failure may remain hypoxemic despite treatment with venovenous extracorporeal membrane oxygenation (VV-ECMO). Therapeutic hypothermia is a potential treatment for such hypoxia as it reduces cardiac output ( ) and oxygen consumption. We modified a previously published mathematical model of gas exchange to investigate the effects of hypothermia during VV-ECMO. Partial pressures were expressed as measured at 37°C (α-stat). The effect of hypothermia on gas exchange was examined in four clinical scenarios of hypoxemia on VV-ECMO, each with different physiological derangements. All scenarios had arterial partial pressure of oxygen (PaO 2 ) ≤ 46 mm Hg and arterial oxygen saturation of hemoglobin (SaO 2 ) ≤ 81%. Three had high with low extracorporeal blood flow to ratio ( ). The problem in the fourth scenario was recirculation, with normal . Cooling to 33°C increased SaO 2 to > 89% and PaO 2 to > 50 mm Hg in all scenarios. Mixed venous oxygen saturation of hemoglobin as % ( ) increased to > 70% and mixed venous partial pressure of oxygen in mm Hg ( ) increased to > 34 mm Hg in scenarios with low . In the scenario with high recirculation, and increased, but to < 50% and < 27 mm Hg, respectively. This in silico study predicted cooling to 33°C will improve oxygenation in refractory hypoxemia on VV-ECMO, but the improvement will be less when the problem is recirculation.

Extracorporeal membrane oxygenation for the treatment of massive pulmonary embolism. An analysis of the ELSO database.

AIM: Extracorporeal membrane oxygenation (ECMO) may be beneficial in treatment of massive pulmonary embolus (PE), however the current evidence to guide its use is limited. We aimed to compare the incidence, characteristics, treatments, and outcomes of patients with massive PE by mode of ECMO from a large international registry. METHODS: Retrospective observational study of the Extracorporeal Life Support Organization (ELSO) database. RESULTS: A total of 821 patients underwent 833 ECMO episodes for PE. Mean age was 49 (±15) years, 408 (50.1%) were female, and 450 (54.7%) had a cardiac arrest prior to ECMO initiation. Venoarterial (VA) ECMO was the most common mode in 489 (58.7%), followed by extracorporeal cardiopulmonary resuscitation (ECPR) in 229 (27.4%) and venovenous (VV) ECMO in 85 (10.2%). The number of episodes per year increased over the study period, predominantly driven by an increase in ECPR. In-hospital mortality was the highest for ECPR 156/229 (68.1%), followed by VA ECMO 209/498 (42.7%) and VV ECMO 24/85 (28.2%) P < 0.001. After controlling for univariate and clinically significant variables at the time of ECMO initiation, increasing age (OR 1.02 (1.00-1.03), lower pH (OR 0.18 (0.03-0.44), lower diastolic blood pressure (OR 0.99 (0.97-1.00) and ECPR mode (OR 3.67 (1.46-9.230) were independently associated with in-hospital mortality. CONCLUSION: ECMO use for massive PE is increasing globally, and overall mortality rates compare favorably with other indications of ECMO. The use of ECPR and worsening metabolic status at initiation were associated with higher in-hospital mortality, suggesting delays in initiating ECMO should be avoided.

Observed differences in nutrition management at two time points spanning a decade in critically ill trauma patients with and without head injury.

BACKGROUND: Nutritional needs of trauma patients admitted to the intensive care unit may differ from general critically ill patients, but most current evidence is based on large clinical trials recruiting mixed populations. OBJECTIVE: The aim of the study was to investigate nutrition practices at two time points that span a decade in trauma patients with and without head injury. METHODS: This observational study recruited adult trauma patients receiving mechanical ventilation and artificial nutrition from a single-centre intensive care unit between February 2005 to December 2006 (cohort 1), and December 2018 to September 2020 (cohort 2). Patients were categorised into head injury and non-head injury subgroups. Data regarding energy and protein prescription and delivery were collected. Data are presented as median [interquartile range]. Wilcoxon rank-sum test assessed the differences between cohorts and subgroups, with a P value ≤ 0.05. The protocol was registered with the Australian and New Zealand Clinical Trials Registry (Trial ID: ACTRN12618001816246). RESULTS: Cohort 1 included 109 patients, and 112 patients were included in cohort 2 (age: 46 ± 19 vs 50 ± 19 y; 80 vs 79% M). Overall, nutrition practice did not differ between head-injured and non-head-injured subgroups (all P > 0.05). Energy prescription and delivery decreased from time point one to time point two, regardless of subgroup (Prescription: 9824 [8820-10 581] vs 8318 [7694-9071] kJ; Delivery: 6138 [5130-7188] vs 4715 [3059-5996] kJ; all P < 0.05). Protein prescription did not change from time point one to time point two. Although protein delivery remained constant from time point one to time point two in the head injury group, protein delivery reduced in the non-head injury subgroup (70 [56-82] vs 45 [26-64] g/d, P < 0.05). CONCLUSION: In this single-centre study, energy prescription and delivery in critically ill trauma patients reduced from time point one to time point two. Protein prescription did not change, but protein delivery reduced from time point one to time point two in non-head injury patients. Reasons for these differing trajectories require exploration. STUDY REGISTRATION: Trial registered at www.anzctr.org.au. TRIAL ID: ACTRN12618001816246.

Nutrition delivery across hospitalisation in critically ill patients with COVID-19: An observational study of the Australian experience.

BACKGROUND: Data on nutrition delivery over the whole hospital admission in critically ill patients with COVID-19 are scarce, particularly in the Australian setting. OBJECTIVES: The objective of this study was to describe nutrition delivery in critically ill patients admitted to Australian intensive care units (ICUs) with coronavirus disease 2019 (COVID-19), with a focus on post-ICU nutrition practices. METHODS: A multicentre observational study conducted at nine sites included adult patients with a positive COVID-19 diagnosis admitted to the ICU for >24 h and discharged to an acute ward over a 12-month recruitment period from 1 March 2020. Data were extracted on baseline characteristics and clinical outcomes. Nutrition practice data from the ICU and weekly in the post-ICU ward (up to week four) included route of feeding, presence of nutrition-impacting symptoms, and nutrition support received. RESULTS: A total of 103 patients were included (71% male, age: 58 ± 14 years, body mass index: 30±7 kg/m2), of whom 41.7% (n = 43) received mechanical ventilation within 14 days of ICU admission. While oral nutrition was received by more patients at any time point in the ICU (n = 93, 91.2% of patients) than enteral nutrition (EN) (n = 43, 42.2%) or parenteral nutrition (PN) (n = 2, 2.0%), EN was delivered for a greater duration of time (69.6% feeding days) than oral and PN (29.7% and 0.7%, respectively). More patients received oral intake than the other modes in the post-ICU ward (n = 95, 95.0%), and 40.0% (n = 38/95) of patients were receiving oral nutrition supplements. In the week after ICU discharge, 51.0% of patients (n = 51) had at least one nutrition-impacting symptom, most commonly a reduced appetite (n = 25; 24.5%) or dysphagia (n = 16; 15.7%). CONCLUSION: Critically ill patients during the COVID-19 pandemic in Australia were more likely to receive oral nutrition than artificial nutrition support at any time point both in the ICU and in the post-ICU ward, whereas EN was provided for a greater duration when it was prescribed. Nutrition-impacting symptoms were common.