Risk Factors for Acute Kidney Injury and In-Hospital Mortality in Patients Receiving Extracorporeal Membrane Oxygenation

Background and Objectives

Although acute kidney injury (AKI) is the most frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), few studies have been conducted on the risk factors of AKI. We performed this study to identify the risk factors of AKI associated with in-hospital mortality.

Methods

Data from 322 adult patients receiving ECMO were analyzed. AKI and its stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) classifications. Variables within 24 h before ECMO insertion were collected and analyzed for the associations with AKI and in-hospital mortality.

Results

Stage 3 AKI was associated with in-hospital mortality, with a hazard ratio (HR) (95% CI) of 2.690 (1.472–4.915) compared to non-AKI (p = 0.001). The simplified acute physiology score 2 (SAPS2) and serum sodium level were also associated with in-hospital mortality, with HRs of 1.02 (1.004–1.035) per 1 score increase (p = 0.01) and 1.042 (1.014–1.070) per 1 mmol/L increase (p = 0.003). The initial pump speed of ECMO was significantly related to in-hospital mortality with a HR of 1.333 (1.020–1.742) per 1,000 rpm increase (p = 0.04). The pump speed was also associated with AKI (p = 0.02) and stage 3 AKI (p = 0.03) with ORs (95% CI) of 2.018 (1.129–3.609) and 1.576 (1.058–2.348), respectively. We also found that the red cell distribution width (RDW) above 14.1% was significantly related to stage 3 AKI.

Conclusion

The initial pump speed of ECMO was a significant risk factor of in-hospital mortality and AKI in patients receiving ECMO. The RDW was a risk factor of stage 3 AKI.     

Plasma Free Hemoglobin Is an Independent Predictor of Mortality among Patients on Extracorporeal Membrane Oxygenation Support

Background

Hemolysis is common in all extracorporeal circuits as evident by the elevated plasma free hemoglobin (PFHb) level. We investigated whether increased hemolysis during extracorporeal membrane oxygenation (ECMO) is an independent mortality predictor.

Methods

We performed a retrospective observational study of consecutive subjects who received ECMO at a tertiary care facility from 2007-2013 to investigate independent predictors of in-hospital mortality. We examined variables related to patient demographics, comorbidities, markers of hemolysis, ECMO characteristics, transfusion requirements, and complications. 24-hour PFHb> 50 mg/dL was used as a marker of severe hemolysis.

Results

154 patients received ECMO for cardiac (n= 115) or pulmonary (n=39) indications. Patients’ mean age was 51 years and 75.3% were males. Compared to nonsurvivors, survivors had lower pre-ECMO lactic acid (p=0.026), lower 24-hour lactic acid (p=0.023), shorter ECMO duration (P=0.01), fewer RBC transfusions on ECMO (p=0.008) and lower level of PFHb 24-hours post ECMO implantation (p=0.029). 24-hour PFHb> 50 mg/dL occurred in 3.9 % versus 15.5% of survivors and nonsurvivors, respectively, p=0.002. A Cox proportional hazard analysis identified PFHb> 50 mg/dL 24-hours post ECMO as an independent predictor of mortality (OR= 3.4, 95% confidence interval: 1.3 – 8.8, p= 0.011).

Conclusion

PFHb> 50 mg/dL checked 24-hour post ECMO implantation is a useful tool to predict mortality. We propose the routine checking of PFHb 24-hours after ECMO initiation for early identification and treatment of the cause of hemolysis.     

Plasma Concentrations of Oseltamivir and Oseltamivir Carboxylate in Critically Ill Children on Extracorporeal Membrane Oxygenation Support

Introduction

To evaluate the effect of extracorporeal membrane oxygenation (ECMO) support on pharmacokinetics of oseltamivir and oseltamivir carboxylate (OC) in children.

Methodology

Steady state 0–12 hour pharmacokinetic sampling was performed in new influenza A (H1N1) infected children treated with oseltamivir while on ECMO support. Cmax, Cmin and AUC_{0–12 h} were calculated. The age-specific oseltamivir dosage was doubled to counter expected decreased plasma drug concentrations due to increased volume of distribution on ECMO support.

Principal Findings

Three patients were enrolled aged 15, 6 and 14 years in this pharmacokinetic case series. For two children the OC plasma concentrations were higher than those found in children and adults not on ECMO. These increased plasma concentrations related to the increased oseltamivir dosage and decreased kidney function. In one patient suboptimal plasma concentrations coincided with a decreased gastric motility.

Conclusion

Oseltamivir pharmacokinetics do not appear to be significantly influenced by ECMO support. Caution is required in case of nasogastric administration and decreased gastric motility. Due to the limited number of (paediatric) patients available further multicenter studies are warranted.     

Technical-Induced Hemolysis in Patients with Respiratory Failure Supported with Veno-Venous ECMO – Prevalence and Risk Factors

The aim of the study was to explore the prevalence and risk factors for technical-induced hemolysis in adults supported with veno-venous extracorporeal membrane oxygenation (vvECMO) and to analyze the effect of hemolytic episodes on outcome. This was a retrospective, single-center study that included 318 adult patients (Regensburg ECMO Registry, 2009–2014) with acute respiratory failure treated with different modern miniaturized ECMO systems. Free plasma hemoglobin (fHb) was used as indicator for hemolysis. Throughout a cumulative support duration of 4,142 days on ECMO only 1.7% of the fHb levels were above a critical value of 500 mg/l. A grave rise in fHb indicated pumphead thrombosis (n = 8), while acute oxygenator thrombosis (n = 15) did not affect fHb. Replacement of the pumphead normalized fHb within two days. Neither pump or cannula type nor duration on the first system was associated with hemolysis. Multiple trauma, need for kidney replacement therapy, increased daily red blood cell transfusion requirements, and high blood flow (3.0–4.5 L/min) through small-sized cannulas significantly resulted in augmented blood cell trauma. Survivors were characterized by lower peak levels of fHb [90 (60, 142) mg/l] in comparison to non-survivors [148 (91, 256) mg/l, p≤0.001]. In conclusion, marked hemolysis is not common in vvECMO with modern devices. Clinically obvious hemolysis often is caused by pumphead thrombosis. High flow velocity through small cannulas may also cause technical-induced hemolysis. In patients who developed lung failure due to trauma, fHb was elevated independantly of ECMO. In our cohort, the occurance of hemolysis was associated with increased mortality.     

Geographic Access to High Capability Severe Acute Respiratory Failure Centers in the United States

Objective

Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States.

Design

Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008–2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims.

Setting

Nonfederal acute care hospitals in the United States.

Measurements and Main Results

We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air.

Conclusions

Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate referral center access in the case of disasters and pandemics will depend highly on local and regional care coordination across political boundaries.     

Technical Complications during Veno-Venous Extracorporeal Membrane Oxygenation and Their Relevance Predicting a System-Exchange – Retrospective Analysis of 265 Cases

Objectives

Technical complications are a known hazard in veno-venous extracorporeal membrane oxygenation (vvECMO). Identifying these complications and predictive factors indicating a developing system-exchange was the goal of the study.

Methods

Retrospective study on prospectively collected data of technical complications including 265 adult patients (Regensburg ECMO Registry, 2009-2013) with acute respiratory failure treated with vvECMO. Alterations in blood flow resistance, gas transfer capability, hemolysis, coagulation and hemostasis parameters were evaluated in conjunction with a system-exchange in all patients with at least one exchange (n = 83).

Results

Values presented as median (interquartile range). Patient age was 50(36–60) years, the SOFA score 11(8–14.3) and the Murray lung injury Score 3.33(3.3–3.7). Cumulative ECMO support time 3411 days, 9(6–15) days per patient. Mechanical failure of the blood pump (n = 5), MO (n = 2) or cannula (n = 1) accounted for 10% of the exchanges. Acute clot formation within the pump head (visible clots, increase in plasma free hemoglobin (frHb), serum lactate dehydrogenase (LDH), n = 13) and MO (increase in pressure drop across the MO, n = 16) required an urgent system-exchange, of which nearly 50% could be foreseen by measuring the parameters mentioned below. Reasons for an elective system-exchange were worsening of gas transfer capability (n = 10) and device-related coagulation disorders (n = 32), either local fibrinolysis in the MO due to clot formation (increased D-dimers [DD]), decreased platelet count; n = 24), or device-induced hyperfibrinolysis (increased DD, decreased fibrinogen [FG], decreased platelet count, diffuse bleeding tendency; n = 8), which could be reversed after system-exchange. Four MOs were exchanged due to suspicion of infection.

Conclusions

The majority of ECMO system-exchanges could be predicted by regular inspection of the complete ECMO circuit, evaluation of gas exchange, pressure drop across the MO and laboratory parameters (DD, FG, platelets, LDH, frHb). These parameters should be monitored in the daily routine to reduce the risk of unexpected ECMO failure.     

ECMO et SDRA : Canulation

Initially, extra corporeal membrane oxygenation (ECMO) was a respiratory assistance technique that used a membrane gas exchanger. By extension, ECMO is now a respiratory and cardiorespiratory assistance technique, used in case of respiratory and/or cardiac weakness. The hemodynamic support can be partial or total. ECMO is easily implanted thanks to peripheral vascular approaches. This kind of assistance uses the concept of “blood extracorporeal circulation”. The basic circuit is simple and includes a pump, an oxygenator (allowing CO₂ removal) and peripheral vascular approaches (one for drainage and one for reinjection). It is easy and fast to set up and can be done bedside. Despite recent technological progress, few centers use temporary respiratory assistance. However, some thoracic surgical units use ECMO in the framework of therapeutic interventions (lung transplantation in particular); in addition, some intensive care units use ECMO in the management and treatment of ARDS. In this chapter, we will first present the techniques of ECMO that can be used in the framework of ARDS, then we will describe the material, and finally we will study the area of implantation.In adult pulmonary pathologies, the key point is to develop the notion of “minimal strategy” with the use of an adjuvant partial extracorporeal circulation, allowing ad integrum recovering of patients. In the near future, technological improvement and a better knowledge of indications should improve the prognostic of patients under ECMO.     

Extrakorporale Membranoxygenierung in der Intensivmedizin

Extracorporeal membrane oxygenation (ECMO) represents a valuable tool in the armamentarium of life and organ support measures in intensive care medicine. ECMO is used in fulminant pulmonary failure to prevent acute hypoxia and to allow CO₂ removal (veno-venous ECMO) or, in highly selected cases of acute cardiovascular failure, to maintain organ perfusion and gas exchange and to prevent imminent death (veno-arterial ECMO). The purpose of ECMO is to allow time for intrinsic recovery of the lungs and heart. Alternatively, ECMO can be used as bridging device until a suitable organ for transplantation is available or the implantation of an artificial heart is feasible. ECMO carries a high complication rate and its use should be limited to highly specialized centers. In rare cases, mobile ECMO systems can be used by dedicated teams which allow transportation of critically ill patients over longer distances to specialized institutions. There is no unequivocal evidence from controlled studies that the use of ECMO in adults improves survival in larger cohorts, but its use in selected cases can be life saving. Long-term survivors of ECMO therapy report significant impairments in health-related quality of life (HRQL) when compared to healthy controls. There is, however, a gradual recovery and improvement in HRQL over a prolonged period after discharge from the intensive care unit and severe limitations in cognitive or physical function are rare. The incidence of chronic post-traumatic stress disorder (PTSD) in patients after ECMO can reach up to 30%. PTSD has a major negative impact on HRQL outcomes of ECMO therapy. PTSD or other stress-related disorders need to be diagnosed and adequately treated to allow adequate recovery from the extreme illness these patients have survived.     

Chinese society of cardiology expert consensus statement on the diagnosis and treatment of adult fulminant myocarditis

Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock, with mortality rates as high as 50%–70%. Most importantly, there are no treatment options, guidelines or an expert consensus statement. Here, we provide the first expert consensus, the Chinese Society of Cardiology Expert Consensus Statement on the Diagnosis and Treatment of Fulminant Myocarditis, based on data from our recent clinical trial (NCT03268642). In this statement, we describe the clinical features and diagnostic criteria of fulminant myocarditis, and importantly, for the first time, we describe a new treatment regimen termed life support-based comprehensive treatment regimen. The core content of this treatment regimen includes (i) mechanical life support (applications of mechanical respirators and circulatory support systems, including intraaortic balloon pump and extracorporeal membrane oxygenation, (ii) immunological modulation by using sufficient doses of glucocorticoid, immunoglobulin and (iii) antiviral reagents using neuraminidase inhibitor. The proper application of this treatment regimen may and has helped to save the lives of many patients with fulminant myocarditis.

     

Short-term,medium-term,and long-term risks of nonvariceal upper gastrointestinal bleeding after dengue virus infection

Dengue patients have an increased risk of acute gastrointestinal (GI) bleeding. However, whether dengue virus (DENV) infection can cause an increased long-term risk of GI bleeding remains unknown, especially among elderly individuals who commonly take antithrombotic drugs. A retrospective population-based cohort study was conducted by analyzing the National Health Insurance Research Databases. Laboratory-confirmed dengue patients from 2002 to 2012 and four matched nondengue controls were identified. Multivariate Cox proportional hazard regression was used to evaluate the acute (<30 days), medium-term (31–365 days), and long-term (>365 days) risks of nonvariceal upper GI bleeding after DENV infection. Stratified analyses by age group (≤50, 51–64, ≥65 years old) were also performed. In total, 13267 confirmed dengue patients and 53068 nondengue matched controls were included. After adjusting for sex, age, area of residence, comorbidities, and medications, dengue patients had a significantly increased risk of nonvariceal upper GI bleeding within 30 days of disease onset (adjusted HR 55.40; 95% CI: 32.17–95.42). However, DENV infection was not associated with increased medium-term and long-term risks of upper GI bleeding overall or in each age group. Even dengue patients who developed acute GI bleeding did not have increased medium-term (adjusted HR; 0.55, 95% CI 0.05–6.18) and long-term risks of upper GI bleeding (adjusted HR; 1.78, 95% CI 0.89–3.55). DENV infection was associated with a significantly increased risk of nonvariceal upper GI bleeding within 30 days but not thereafter. Recovered dengue patients with acute GI bleeding can resume antithrombotic treatments to minimize the risk of thrombosis.     

Étude CESAR : justification de l’assistance respiratoire extra corporelle pour les graves syndromes de détresse respiratoire de l’adulte

BackgroundSevere acute respiratory failure in adults still has a high mortality in adults despite improvements in ventilation techniques and other treatments. The evidence about the effectiveness of extracorporeal membrane oxygenation (ECMO) was equivocal.MethodNational multi-center pragmatic randomized controlled trial. 180 adults (18-65 years) with severe (Murray score > 3.0 or pH < 7.2) but potentially reversible respiratory failure were randomized to receive either continued conventional management (CM) or to be transferred to Glenfield Hospital, Leicester, UK for consideration of ECMO. Patients were excluded if they had been on high pressure (> 30 cm H₂O of peak inspiratory pressure) and/or high FiO₂ (> 0.8) ventilation for > 7 days; had signs of intra-cranial bleeding ; had any other contra-indication to limited heparinisation ; or had any contra-indication to continuation of active treatment. The primary outcome measure was death or severe disability at six months. Analysis was by intention to treat.Results766 patients were screened. 180 were randomised; 90 to the ECMO arm of whom 68 received ECMO. No cm patients received ECMO. Fewer patients in the ECMO arm than the cm arm had died or were severely disabled 6 months after randomisation, (33/90 (36.7%) vs 46/87 (52.9%) ; RR=0.69 (95%CI 0.50 to 0.97) ; p=0.030). Only one patient (in the cm arm) was known to be severely disabled at 6 months.Randomised controlled trial and economic evaluationControlled Trial of Conventional Ventilatory Support vs Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) [ISRCTN47279827].     

Trough Concentrations of Vancomycin in Patients Undergoing Extracorporeal Membrane Oxygenation

To investigate the appropriateness of the current vancomycin dosing strategy in adult patients with extracorporeal membrane oxygenation (ECMO), between March 2013 and November 2013, patients who were treated with vancomycin while on ECMO were enrolled. Control group consisted of 60 patients on vancomycin without ECMO, stayed in medical intensive care unit during the same study period and with the same exclusion criteria. Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state. A total of 20 patients were included in the analysis in ECMO group. Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours. The non-steady state trough level of vancomycin after starting administration was subtherapeutic in 19 patients (95.00%) in ECMO group as compared with 40 patients (66.67%) in the control group (p = 0.013). Vancomycin clearance was 1.27±0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 ± 0.37, and elimination rate constant was 0.12 ± 0.04 h^-1. Vancomycin dosingfrequency and total daily dose were significantly increased after clinical pharmacokinetic services of the pharmacist based on calculated pharmacokinetic parameters (from 2.10 ± 0.72 to 2.90 ± 0.97times/day, p = 0.002 and from 32.54 ± 8.43 to 42.24 ± 14.62mg/kg, p = 0.014) in ECMO group in contrast with those (from 2.11 ± 0.69 to 2.37 ± 0.86 times/day, p = 0.071 and from 33.91 ± 11.85 to 31.61 ± 17.50 mg/kg, p = 0.350) in the control group.Although the elimination rate for vancomycin was similar with population parameter of non ECMO patients, the current dosing strategy of our institution for vancomycinin our ICU was not sufficient to achieve the target trough in the initial period in most patients receiving ECMO.     

A Case of Vivax Malaria Complicated by Adult Respiratory Distress Syndrome and Successful Management with Extracorporeal Membrane Oxygenation

Complicated malaria is mainly caused by Plasmodium falciparum, but, increasingly, Plasmodium vivax is also being reported as a cause. Since the reemergence of indigenous vivax malaria in 1993, cases of severe malaria have been steadily reported in Korea. Herein, we report a case of vivax malaria complicated by adult respiratory distress syndrome (ARDS) that was successfully managed with extracorporeal membrane oxygenation (ECMO). A 59-year-old man presented at our hospital with fever and abdominal pain, which had persisted for 10 days. On admission, the patient had impaired consciousness, shock, hypoxia and haziness in both lungs, jaundice, thrombocytopenia and disseminated intravascular coagulation, metabolic acidosis, and acute kidney injury. A peripheral blood smear and a rapid diagnostic test verified P. vivax mono-infection. Ten hours after admission, hypoxia became more severe, despite providing maximal ventilatory support. The administration of antimalarial agents, ECMO, and continuous venovenous hemofiltration resulted in an improvement of his vital signs and laboratory findings. He was discharged from the hospital 7 weeks later, without any sequelae.     

Anticoagulation Management Practices and Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Clinical Research Study

Whether anticoagulation management practices are associated with improved outcomes in elderly patients with acute venous thromboembolism (VTE) is uncertain. Thus, we aimed to examine whether practices recommended by the American College of Chest Physicians guidelines are associated with outcomes in elderly patients with VTE. We studied 991 patients aged ≥65 years with acute VTE in a Swiss prospective multicenter cohort study and assessed the adherence to four management practices: parenteral anticoagulation ≥5 days, INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulation, early start with vitamin K antagonists (VKA) ≤24 hours of VTE diagnosis, and the use of low-molecular-weight heparin (LMWH) or fondaparinux. The outcomes were all-cause mortality, VTE recurrence, and major bleeding at 6 months, and the length of hospital stay (LOS). We used Cox regression and lognormal survival models, adjusting for patient characteristics. Overall, 9% of patients died, 3% had VTE recurrence, and 7% major bleeding. Early start with VKA was associated with a lower risk of major bleeding (adjusted hazard ratio 0.37, 95% CI 0.20–0.71). Early start with VKA (adjusted time ratio [TR] 0.77, 95% CI 0.69–0.86) and use of LMWH/fondaparinux (adjusted TR 0.87, 95% CI 0.78–0.97) were associated with a shorter LOS. An INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulants was associated with a longer LOS (adjusted TR 1.2, 95% CI 1.08–1.33). In elderly patients with VTE, the adherence to recommended anticoagulation management practices showed mixed results. In conclusion, only early start with VKA and use of parenteral LMWH/fondaparinux were associated with better outcomes.     

A pathologist's prognosis for ‘redox reaction’ profiles

Summary

The acute respiratory distress syndrome continues to be a major medical problem. Despite recent advances in treatment, such as the use of nitrogen monoxide (NO), extracorporeal membrane oxygenation (ECMO) and specialized ventilatory techniques in maintaining adequate oxygenation, mortality still remains high. The presence of activated neutrophils coupled with high inspired oxygen concentrations provide conditions that favour increased oxidative stress and this has focused attention on the possible role of free radical species in both the initiation and propagation of ARDS. Although there is evidence implicating increased free radical activity in ARDS, much of this is from animal models and the role of intervention in such processes has not been established. Although antioxidant therapy has been suggested as a possible treatment for ARDS the current literature is less than convincing. We examine the available data from human studies and suggest possible further studies and future therapeutic goals.     

Assessing the Quality of Tuberculosis Evaluation for Children with Prolonged Cough Presenting to Routine Community Health Care Settings in Rural Uganda

Background

Improving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse.

Objective

To describe the current practices and quality of TB evaluation for children with cough ≥2 weeks'' duration presenting to community health centers in Uganda.

Methods

Cross-sectional analysis of children (<15 years) receiving care at five Level IV community health centers in rural Uganda for any reason between 2009–2012. Quality of TB care was assessed using indicators derived from the International Standards of Tuberculosis Care (ISTC).

Results

From 2009–2012, 1713 of 187,601 (0.9%, 95% CI: 0.4–1.4%) children presenting to community health centers had cough ≥ 2 weeks'' duration. Of those children, only 299 (17.5%, 95% CI: 15.7–19.3%) were referred for sputum microscopy, but 251 (84%, 95% CI: 79.8–88.1%) completed sputum examination if referred. The yield of sputum microscopy was only 3.6% (95% CI: 1.3–5.9%), and only 55.6% (95% CI: 21.2–86.3%) of children with acid-fast bacilli positive sputum were started on treatment. Children under age 5 were less likely to be referred for sputum examination and to receive care in accordance with ISTC. The proportion of children evaluated in accordance with ISTC increased over time (4.6% in 2009 to 27.9% in 2012, p = 0.03), though this did not result in increased case-detection.

Conclusion

The quality of TB evaluation was poor for children with cough ≥2 weeks'' duration presenting for health care. Referrals for sputum smear microscopy and linkage to TB treatment were key gaps in the TB evaluation process, especially for children under the age of five.     

Increased Systemic Th17 Cytokines Are Associated with Diastolic Dysfunction in Children and Adolescents with Diabetic Ketoacidosis

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA.     

Complement activation by in vivo neonatal and in vitro extracorporeal membrane oxygenation

Complment activation during extracorporeal membrane oxygenation (ECMO) in newborns can be caused by both the underlying disease processes and by blood contact with the ECMO circuit. We investigated the relative importance of these mechanisms by measuring C3a, C5a and sC5b-9 before, during and after neonatal ECMO in six consecutive newborn patients using enzyme-linked immunoassay. In addition complement activation during in vitro ECMO with repeated flow of the same blood volume was measured using blood from healthy adult donors. C3a increased significantly in vivo after 1 h (from 1035+/-193 to 1865+/-419 microg/l) and in vitro ECMO (from 314+/-75 to 1962+/-1062 microg/l). C5a increased during ECMO without significant differences between in vivo and in vitro activation. In neonatal patients, sC5b-9 rose faster than in vitro, but the rapid increase was also significant for in vitro experiments (in vivo: from 328+/-63 to 1623+/-387 microg/l after 2 h; and in vitro: from 78+/-32 to 453+/-179 microg/l after 8 h). After this initial peak at 1-2 h, complement activation decreased gradually until 2-3 days after the initiation of ECMO. We conclude that in newborns the rapid activation of the complement system after the start of ECMO is predominantly caused by contact with artificial surfaces rather than the patient's underlying disease.     

Flow mixing during peripheral veno-arterial extra corporeal membrane oxygenation – A simulation study

Peripheral veno-arterial extra-corporeal membrane oxygenation (ECMO) is an artificial circulation that supports patients with severe cardiac and respiratory failure. Differential hypoxia during ECMO support has been reported, and it has been suggested that it is due to the mixing of well-perfused retrograde ECMO flow and poorly-perfused antegrade left ventricle (LV) flow in the aorta. This study aims to quantify the relationship between ECMO support level and location of the mixing zone (MZ) of the ECMO and LV flows. Steady-state and transient computational fluid dynamics (CFD) simulations were performed using a patient-specific geometrical model of the aorta. A range of ECMO support levels (from 5% to 95% of total cardiac output) were evaluated. For ECMO support levels above 70%, the MZ was located in the aortic arch, resulting in perfusion of the arch branches with poorly perfused LV flow. The MZ location was stable over the cardiac cycle for high ECMO flows (>70%), but moved 5 cm between systole and diastole for ECMO support level of 60%. This CFD approach has potential to improve individual patient care and ECMO design.