Perfusion

Gaseous microemboli that originate from the cardiopulmonary bypass circuit may contribute to adverse outcome after cardiac surgery. We prospectively evaluated the influence of gaseous microemboli on the release of various biomarkers after use of a minimally invasive extracorporeal technology system.

In 70 patients undergoing coronary artery bypass grafting with minimized cardiopulmonary bypass, gaseous microemboli were measured intraoperatively with a bubble counter. Intra- and postoperative biomarker levels for inflammatory response (interleukin-6, C5b-9), endothelial damage (von Willebrand factor, soluble vascular cell adhesion molecule-1), oxidative stress (malondialdehyde, 8-isoprostane, neuroketal), and neurological injury (neuron-specific enolase, brain-type fatty acid-binding protein) were analyzed using immune assay techniques. The relationship between gaseous microemboli number or volume and the incremental area under the curve (iAUC_24h) or peak change for the biomarkers was calculated.

All biomarkers except for malondialdehyde increased at least temporarily after coronary artery bypass grafting with a minimally invasive extracorporeal technology system. The median total gaseous microemboli number was 6,174 (interquartile range: 3,507-10,531) and the median total gaseous microemboli volume was 4.31 µL (interquartile range: 2.71-8.50). There were no significant correlations between total gaseous microemboli number or volume and iAUC_24h or peak change for any of the biomarkers. After controlling for the variance of possible other predictor variables, multiple linear regression analysis showed no association between gaseous microemboli parameters and release of biomarkers.

This study showed no evidence that gaseous microemboli contribute to increased biomarker levels after coronary artery bypass grafting with cardiopulmonary bypass. A reason for the absence of damage by gaseous microemboli may be the relative and considerably small amount of gaseous microemboli entering the patients in this study.

Dexmedetomidine is a sedative administered to minimize distress and decrease the risk of life threatening complications in children supported with extracorporeal membrane oxygenation. The extracorporeal membrane oxygenation circuit can extract drug and decrease drug exposure, placing the patient at risk of therapeutic failure.

To determine the extraction of dexmedetomidine by the extracorporeal membrane oxygenation circuit.

Dexmedetomidine was studied in three closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing on circuit extraction. Each circuit was primed with human blood according to standard practice for Duke Children’s Hospital, and flow was set to 1 L/min. Dexmedetomidine was dosed to achieve a therapeutic concentration of ~600 pg/mL. Dexmedetomidine was added to a separate tube of blood to serve as a control and evaluate for natural drug degradation. Serial blood samples were collected over 24 hours and concentrations were quantified with a validated assay. Drug recovery was calculated at each time point.

Dexmedetomidine was highly extracted by the oxygenator evidenced by a mean recovery of 62-67% at 4 hours and 23-34% at 24 hours in circuits with an oxygenator in-line. In contrast, mean recovery with the oxygenator removed was 96% at 4 hours and 93% at 24 hours. Dexmedetomidine was stable over time with a mean recovery in the control samples of 102% at 24 hours.

These results suggest dexmedetomidine is extracted by the oxygenator in the extracorporeal membrane oxygenation circuit which may result in decreased drug exposure in vivo.

Extracorporeal gas exchange requires the passage of oxygen and carbon dioxide (CO₂) across an artificial membrane. Current European Union regulations do not require the transfer to be assessed in models using clinically relevant haemoglobin, making it difficult for clinicians to understand the CO₂ clearance of a membrane, and how it changes in relation to sweep gas flow through the membrane. The characteristics of membrane CO₂ clearance are described using a single membrane at different sweep gas flows in an in vitro model with clinically relevant haemoglobin concentrations using three separate methods of calculating CO₂ clearance.

To define the CO₂ removal characteristics of the extra-corporeal CO₂ removal (ECCO₂R) device, we devised an in-vitro gas exchange circuit formed by a dedicated ECCO₂R circuit (ALung, Pittsburgh, USA) in series with two membrane oxygenators. The system was primed with donated expired human red cells provided by the local blood bank. The experimental set-up allowed constant CO₂ input (via one membrane oxygenator) with variable removal from a portion of the blood in a manner which was analogous to that seen in vivo. Blood gases were measured from different ports in the circuit in order to measure the experimental membrane CO₂ clearance (VCO₂).

Results demonstrate that the relationship between VCO₂ and gas flow at a constant blood flow of 0.4 L/minute with a haemoglobin of 7 g/dL increases sharply from a gas flow of 0 to 2 L/min but plateaus at gas flows >4 L/minute. VCO₂, calculated using three different methods, showed a strong linear correlation with minimal bias.

The CO₂ clearance of the membrane used in this bench test is non-linear. This has implications for clinical practice, especially during the weaning phase of the device.

Patients with preoperative dual antiplatelet therapy prior to coronary artery bypass surgery are at risk of bleeding and blood component transfusion. We hypothesise that an optimised cardiopulmonary bypass strategy reduces postoperative blood loss and transfusions.

In total, 60 patients admitted for coronary artery bypass grafting with ticagrelor and aspirin medication withdrawn <96 hours before surgery were prospectively randomised into two equal sized groups. Cardiopulmonary bypass combined a closed Cortiva^® heparin-coated circuit with low systemic heparinisation (activated clotting time < 250 seconds) and intraoperative cell salvage in the study group, whereas the control group used a Balance^® coated open circuit, full systemic heparinisation (activated clotting time > 480 seconds) and conventional cardiotomy suction. This perfusion strategy was evaluated by the chest drain volume after 24 hours, perioperative haemoglobin and platelet loss accompanied by global coagulation assessments.

Patients in the study group demonstrated significantly better outcomes signified by lower blood loss 554 ± 224 versus 1,100 ± 989 mL (p < 0.001), reduced packed red cell transfusion 7% versus 53% (p < 0.001), reduced haemoglobin −28 ± 15 versus −40 ± 14 g/L (p = 0.004) and platelet loss −35 ± 36 versus −82 ± 67 × 10⁹/L (p = 0.001). Indices of rotational thromboelastometry indicated shorter clotting times within the internal and external pathways. Adenosine diphosphate activated platelet function was within normal range based on Multiplate^® aggregometry, while ROTEM^® platelet analyses indicated inhibited function both preoperatively and post-bypass. Platelet inhibition by aspirin was verified throughout the perioperative period. Platelet function showed no intergroup differences.

A stringent perfusion strategy reduced blood loss and transfusions in dual antiplatelet therapy patients requiring urgent surgery.

While reported mortality rates on post-cardiotomy extracorporeal membrane oxygenation vary from center to center, impact of baseline surgical status (elective/urgent/emergency/salvage) on mortality is still unknown.

A systematic search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using PubMed/Medline databases until March 2018 using the keywords “postcardiotomy,” “cardiogenic shock,” “extracorporeal membrane oxygenation,” and “extracorporeal life support.” Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and baseline surgical status. The correlations between mortality and percentage of elective/urgent/emergency cases were investigated. Inference analysis of baseline status and extracorporeal membrane oxygenation complications was conducted as well.

Twenty-two studies (conducted between 1993 and 2017) enrolling N = 2,235 post-cardiotomy extracorporeal membrane oxygenation patients were found. Patients were mostly of non-emergency status (65.2%). Overall in-hospital/30-day mortality event rate (95% confidence intervals) was 66.7% (63.3-69.9%). There were no differences in in-hospital/30-day mortality with respect to baseline surgical status in the subgroup analysis (test for subgroup differences; p = 0.406). Similarly, no differences between mortality in studies enrolling <50 versus ⩾50% of emergency/salvage cases was found: respective event rates were 66.9% (63.1-70.4%) versus 64.4% (57.3-70.8%); p = 0.525. Yet, there was a significant positive association between increasing percentage of emergency/salvage cases and rates of neurological complications (p < 0.001), limb complications (p < 0.001), and bleeding (p = 0.051). Incidence of brain death (p = 0.099) and sepsis (p = 0.134) was increased as well.

Other factors than baseline surgical status may, to a higher degree, influence the mortality in patients treated with extracorporeal membrane oxygenation for post-cardiotomy cardiogenic shock. Baseline status, however, strongly influences the complication occurrence while on extracorporeal membrane oxygenation.

MicroRNAs (miRNAs) are involved in myocardial ischemia-reperfusion injury. miRNA-421 (miR-421) plays a significant role in the initiation of apoptosis and myocardial infarction. However, the molecular regulation of miR-421 in myocardial ischemia-reperfusion injury requires further elucidation.

An in vitro hypoxia/reoxygenation model was established, and the expression levels of miR-421 and Sirtuin-3 (Sirt3) in H9c2 cells were quantified using quantitative real-time polymerase chain reaction. Flow cytometry was employed to measure the effects of miR-421 on myocardial apoptosis induced by hypoxia/reoxygenation. The activity of lactate dehydrogenase and superoxide dismutase and levels of malondialdehyde were measured. The binding sites of miR-421 on Sirt3 were predicted using TargetScan software. A luciferase reporter assay was used to validate the direct targeting of Sirt3 with miR-421. Protein expression levels of Sirt3 and its downstream proteins were evaluated using Western blot analysis.

Exposure of H9c2 cells to hypoxia/reoxygenation led to increased apoptosis, levels of malondialdehyde and lactate dehydrogenase, and decreased levels of superoxide dismutase. miR-421 knockdown resulted in decreased apoptosis, levels of lactate dehydrogenase and malondialdehyde, and increased superoxide dismutase levels in H9c2 cells. Hypoxia/reoxygenation significantly decreased the relative expression levels of Sirt3. Down-regulation of Sirt3 resulted from overexpression of miR-421, which directly targeted Sirt3. Knockdown of miR-421 up-regulated Sirt3 expression, inhibited activation of the Jun N-terminal kinase/activator protein 1 pathway and caspase 9/3-dependent cell death.

The miR-421-Sirt3-Jun N-terminal kinase/activator protein 1 axis is a novel molecular mechanism that accommodates hypoxia/reoxygenation-induced oxidative stress and apoptosis and provides a new direction for the study and treatment of hypoxia/reoxygenation.

New antibiotics with bactericidal activity against multi-drug-resistant bacteria are increasingly used in the intensive care units. Here, we aimed to evaluate the influence of the extracorporeal membrane oxygenation on plasma levels of ceftolozane.

A 34-year-old female was admitted to the intensive care unit after bilateral lung transplantation, complicated by primary graft dysfunction and cardiogenic shock needing venoarterial extracorporeal membrane oxygenation. Ceftolozane/tazobactam was started. Plasma ceftolozane levels were monitored on the first and third days of antibiotic treatment. A non-compartment pharmacokinetic analysis was performed and the extraction rate through the oxygenator was calculated.

The extracorporeal circuit of extracorporeal membrane oxygenation may alter the pharmacokinetics of antibiotics, to varying degrees due to drug sequestration and increased distribution volume. In this case, the extracorporeal membrane oxygenation circuit had little impact on the ceftolozane plasma concentration.

Plasma levels of ceftolozane are stable in the extracorporeal membrane oxygenation circuit, suggesting that adjustment of standard doses of ceftolozane in patients with extracorporeal membrane oxygenation support may not be needed.