Adverse renal effects associated with cardiopulmonary bypass.

Cardiac surgery on cardiopulmonary bypass (CPB) is associated with postoperative renal dysfunction, one of the most common complications of this surgical cohort. Acute kidney injury (AKI) is associated with increased short-term morbidity and mortality and has been the focus of much research. There is increasing recognition of the role of AKI as the key pathophysiological state leading to the disease entities acute and chronic kidney disease (AKD and CKD). In this narrative review, we will consider the epidemiology of renal dysfunction after cardiac surgery on CPB and the clinical manifestations across the spectrum of disease. We will discuss the transition between different states of injury and dysfunction, and, importantly, the relevance to clinicians. The specific facets of kidney injury on extracorporeal circulation will be described and the current evidence evaluated for the use of perfusion-based techniques to reduce the incidence and mitigate the complications of renal dysfunction after cardiac surgery.

Neurologic complications after cardiopulmonary bypass - A narrative review.

Neurologic complications, associated with cardiac surgery and cardiopulmonary bypass (CPB) in adults, are common and can be devastating in some cases. This comprehensive review will not only consider the broad categories of stroke and neurocognitive dysfunction, but it also summarises other neurological complications associated with CPB, and it provides an update about risks, prevention and treatment. Where appropriate, we consider the impact of off-pump techniques upon our understanding of the contribution of CPB to adverse outcomes.

Cardiac surgery-Associated acute kidney injury - A narrative review.

Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) is a serious complication seen in approximately 20-30% of cardiac surgery patients. The underlying pathophysiology is complex, often involving both patient- and procedure related risk factors. In contrast to AKI occurring after other types of major surgery, the use of cardiopulmonary bypass comprises both additional advantages and challenges, including non-pulsatile flow, targeted blood flow and pressure as well as the ability to manipulate central venous pressure (congestion). With an increasing focus on the impact of CSA-AKI on both short and long-term mortality, early identification and management of high-risk patients for CSA-AKI has evolved. The present narrative review gives an up-to-date summary on definition, diagnosis, underlying pathophysiology, monitoring and implications of CSA-AKI, including potential preventive interventions. The review will provide the reader with an in-depth understanding of how to identify, support and provide a more personalized and tailored perioperative management to avoid development of CSA-AKI.

2021 MiECTiS focused update on the 2016 position paper for the use of minimal invasive extracorporeal circulation in cardiac surgery.

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.

Enzymatic Deglycation of Damaged Skin by Means of Combined Treatment of Fructosamine-3-Kinase and Fructosyl-Amino Acid Oxidase.

The consensus in aging is that inflammation, cellular senescence, free radicals, and epigenetics are contributing factors. Skin glycation through advanced glycation end products (AGEs) has a crucial role in aging. Additionally, it has been suggested that their presence in scars leads to elasticity loss. This manuscript reports fructosamine-3-kinase (FN3K) and fructosyl-amino acid oxidase (FAOD) in counteracting skin glycation by AGEs. Skin specimens were obtained (n = 19) and incubated with glycolaldehyde (GA) for AGE induction. FN3K and FAOD were used as monotherapy or combination therapy. Negative and positive controls were treated with phosphate-buffered saline and aminoguanidine, respectively. Autofluorescence (AF) was used to measure deglycation. An excised hypertrophic scar tissue (HTS) (n = 1) was treated. Changes in chemical bonds and elasticity were evaluated using mid-infrared spectroscopy (MIR) and skin elongation, respectively. Specimens treated with FN3K and FAOD in monotherapy achieved an average decrease of 31% and 33% in AF values, respectively. When treatments were combined, a decrease of 43% was achieved. The positive control decreased by 28%, whilst the negative control showed no difference. Elongation testing of HTS showed a significant elasticity improvement after FN3K treatment. ATR-IR spectra demonstrated differences in chemical bounds pre- versus post-treatment. FN3K and FAOD can achieve deglycation and the effects are most optimal when combined in one treatment.

Adult essential extracorporeal membrane oxygenation (ECMO) skills for use in an e-learning program for ICU physicians, nurses and perfusionists: a consensus by a modified Delphi questionnaire.

BACKGROUND: Education in ECMO starts with basic theory and physiology. For this type of training, self-assessment e-learning modules may be beneficial. The aim of this study was to generate consensus on essential ECMO skills involving various professional groups involved in caring for ECMO patients. These skills can be used for educational purposes: development of an e-learning program and fine-tuning of ECMO-simulation programs. METHODS: Experts worldwide received an e-mail inviting them to participate in the modified Delphi questionnaire. A mixture of ECMO experts was contacted. The expert list was formed based on their scientific track record mainly in adult ECMO (research, publications, and invited presentations). This survey consisted of carefully designed questionnaires, organized into three categories, namely knowledge skills, technical skills, and attitudes. Each statement considered a skill and was rated on a 5-point Likert-scale and qualitative comments were made if needed. Based on the summarized information and feedback, the next round Delphi questionnaire was developed. A statement was considered as a key competency when at least 80% of the experts agreed or strongly agreed (rating 4/5 and 5/5) with the statement. Cronbach's Alpha score tested internal consistency. Intraclass correlation coefficient was used as reliability index for interrater consistency and agreement. RESULTS: Consensus was achieved in two rounds. Response rate in the first round was 45.3% (48/106) and 60.4% (29/48) completed the second round. Experts had respectively for the first and second round: a mean age of 43.7 years (8.2) and 43.4 (8.8), a median level of experience of 11.0 years [7.0-15.0] and 12.0 years [8.3-14.8]. Consensus was achieved with 29 experts from Australia (2), Belgium (16), France (1), Germany (1), Italy (1), Russia (2), Spain (1), Sweden, (1), The Netherlands (4). The consensus achieved in the first round was 90.9% for the statements about knowledge, 54.5% about technical skills and 75.0% about attitudes. Consensus increased in the second round: 94.6% about knowledge skills, 90.9% about technical skills and 75.0% about attitudes. CONCLUSION: An expert consensus was accomplished about the content of "adult essential ECMO skills". This consensus was mainly created with participation of physicians, as the response rate for nurses and perfusion decreased in the second round.

Opportunities, controversies, and challenges of extracorporeal hemoadsorption with CytoSorb during ECMO.

Extracorporeal membrane oxygenation (ECMO) is frequently used in many centers around the globe for various indications. However, prognosis is often poor even with all supportive therapies, and in many cases, clinical deterioration is associated with inflammation. Hemoadsorption with CytoSorb is a novel approach to limit the inflammatory response, and the device can be safely and easily installed into ECMO circuits. CytoSorb has been used more than 130.000 times to date, but because randomized controlled trials are largely lacking, there is substantial debate on its use. Here, experts from critical care medicine, cardiology, cardiac surgery, and perfusion technology discuss the pros and cons of this novel therapy and outline the future aspects for its clinical application and research.

The evolving role of the modern perfusionist: insights from transesophageal echocardiography.

Transesophageal echocardiography is a relatively non-invasive, mobile, safe imaging technique that is ideal for providing real-time information on cardiac anatomy and function during heart surgery. The technology has evolved from two-dimensional to real-time three-dimensional imaging during cardiac procedures, which has significantly benefited preoperative planning, intraoperative guidance, evaluation, and postoperative follow-up. Transesophageal echocardiography may serve the clinical perfusionist by providing imaging guidance for identifying potential problems before cardiopulmonary bypass, guiding the proper placement of cannulas, monitoring cardiac performance on cardiopulmonary bypass, and providing useful feedback during weaning from cardiopulmonary bypass. Although the perfusionist should be able to understand all echocardiographic images and measurements in depth, perfusion-related echocardiographic information can or should be used to optimize the clinical practice of the modern perfusionist. Vice versa, whenever the perfusionist suspects a problem, the surgical team including the sonographer should verify this "clinical treat" by echocardiography whenever possible.

A Potential Role for Fructosamine-3-Kinase in Cataract Treatment.

Cataracts are the major cause of blindness worldwide, largely resulting from aging and diabetes mellitus. Advanced glycation end products (AGEs) have been identified as major contributors in cataract formation because they alter lens protein structure and stability and induce covalent cross-linking, aggregation, and insolubilization of lens crystallins. We investigated the potential of the deglycating enzyme fructosamine-3-kinase (FN3K) in the disruption of AGEs in cataractous lenses. Macroscopic changes of equine lenses were evaluated after ex vivo intravitreal FN3K injection. The mechanical properties of an equine lens pair were evaluated after treatment with saline and FN3K. AGE-type autofluorescence (AF) was measured to assess the time-dependent effects of FN3K on glycolaldehyde-induced AGE-modified porcine lens fragments and to evaluate its actions on intact lenses after in vivo intravitreal FN3K injection of murine eyes. A potential immune response after injection was evaluated by analysis of IL-2, TNFα, and IFNγ using an ELISA kit. Dose- and time-dependent AF kinetics were analyzed on pooled human lens fragments. Furthermore, AF measurements and a time-lapse of macroscopic changes were performed on intact cataractous human eye lenses after incubation with an FN3K solution. At last, AF measurements were performed on cataractous human eyes after crossover topical treatment with either saline- or FN3K-containing drops. While the lenses of the equine FN3K-treated eyes appeared to be clear, the saline-treated lenses had a yellowish-brown color. Following FN3K treatment, color restoration could be observed within 30 min. The extension rate of the equine FN3K-treated lens was more than twice the extension rate of the saline-treated lens. FN3K treatment induced significant time-dependent decreases in AGE-related AF values in the AGE-modified porcine lens fragments. Furthermore, in vivo intravitreal FN3K injection of murine eyes significantly reduced AF values of the lenses. Treatment did not provoke a systemic immune response in mice. AF kinetics of FN3K-treated cataractous human lens suspensions revealed dose- and time-dependent decreases. Incubation of cataractous human eye lenses with FN3K resulted in a macroscopic lighter color of the cortex and a decrease in AF values. At last, crossover topical treatment of intact human eyes revealed a decrease in AF values during FN3K treatment, while showing no notable changes with saline. Our study suggests, for the first time, a potential additional role of FN3K as an alternative treatment for AGE-related cataracts.

Lower limit of adequate oxygen delivery for the maintenance of aerobic metabolism during cardiopulmonary bypass in neonates.

BACKGROUND: The objective of cardiopulmonary bypass (CPB) is to maintain an adequate balance between oxygen delivery (Do2) and consumption. The critical Do2 is that at which consumption becomes supply dependent. This study aimed to identify the critical Do2 in neonates, who have higher metabolic rates than adults. METHODS: In a retrospective cohort of neonates, Do2 was calculated from CPB parameters recorded during aortic cross-clamping. High lactate concentration measured after aortic unclamping (lactOFF) was used to identify anaerobic metabolism. Data were analysed using mixed linear and proportional odds regression models. The relationship between Do2 and temperature was analysed in a subgroup of patients with lactOFF <2.5 mM, thought to have had balanced oxygen delivery and consumption. The estimated regression coefficient was further used to adjust hypothetical Do2 thresholds, and Do2 excursions below the threshold were quantified as magnitude-durations. The lowest threshold that provided magnitude-durations and linked with an increase in lactOFF was used as the lowest suitable (critical) Do2 at 37°C. RESULTS: Overall, 22 896 time points were analysed in 180 neonates. In 40 patients with lactOFF <2.5 mM, Do2 varied by 22.87 (0.70) ml min-1 m-2 °C-1. When varying the Do2 threshold between 340 and 380 ml min-1 m-2, excursions below the threshold were linked with incremental lactOFF. A 100 ml m-2 excursion below the 340 ml min-1 m-2Do2 threshold increased the risk of a 1 mM increment in lactOFF by 22% (odds ratio: 1.22; 95% confidence interval: 1.02-1.45). CONCLUSIONS: It was found that 340 ml min-1 m-2 is likely to represent the lowest suitable Do2 required in neonates to maintain aerobic metabolism during normothermic CPB.

Evaluation with micro-CT of different anticoagulation strategies during hemodialysis in patients with thrombocytopenia: A randomized crossover study.

In patients with enhanced risk for bleeding, heparin-free hemodialysis (HD) with conventional dialyzers is routinely used. To explore the potential benefit of using heparin-coated dialyzers, we used a reference CT-scanning technique and registered different clotting parameters to quantify coagulation with heparin-coated versus non-coated dialyzers. Six HD patients with thrombocytopenia were dialyzed 240 min in a randomized crossover study with Evodial 1.3 or FX600 Cordiax, each without anticoagulation. Blood samples were taken from the vascular access predialysis, and from the dialyzer inlet and outlet at 5 and 240 min after dialysis start. Predialysis blood samples were analyzed for hemoglobin, hematocrit, thrombocytes, fibrinogen, and activated partial thromboplastin time. On dialyzer inlet and outlet blood samples, a viscoelastic measurement of blood coagulation was performed using a Sonoclot analyzer. After dialysis, dialyzers were visually scored, subsequently dried for 24 h, weighed, and scanned with micro-CT at a resolution of 25 µm. After image reconstruction, the open, non-coagulated fibers were counted in a representative cross-section at the dialyzer outlet. No sessions were terminated prematurely for circuit clotting. Heparin-coated dialyzers had more patent fibers on micro-CT versus non-coated dialyzers and also had a better score of subjective visual assessment of fiber clotting. There was no difference in subjective assessment of clotting at the venous drip chamber. With both dialyzers, all ACT values remained in the normal range, and were lower at the dialyzer outlet versus inlet. In conclusion, dialysis with a heparin-coated versus non heparin-coated membrane results in substantially less coagulated fibers during 4 h hemodialysis without systemic anticoagulation. Eventual leaching of heparin, immobilized on the fiber membrane, does not result in measurable systemic anticoagulation.

Quality evaluation of the emergency program of three contemporary cell-washing machines.

This study evaluates the efficiency of emergency programs used by three contemporary cell washers. Both time necessary to process a given amount of blood and quality of the processed blood are investigated. The Fresenius Kabi Smart, Haemonetics Elite and LivaNova Xtra were validated using bovine blood, with a starting hematocrit of 13% or 21%. For all devices, the pre-programmed emergency program was used. The total volume processed in the 13% hematocrit group was 358 ± 68 mL for Fresenius, 375 ± 308 mL for Haemonetics and 497 ± 87 mL for LivaNova. In the 21% hematocrit group, the volumes were 533 ± 60 mL, 713 ± 142 mL and 798 ± 96 mL, respectively, showing a statistical difference between the Fresenius and LivaNova (p = 0.02). In the 13% hematocrit group, the Fresenius processed 45 ± 15 mL blood/min, the Haemonetics 62 ± 8 mL blood/min and the LivaNova 66 ± 1.5 mL blood/min. The difference between the Fresenius and LivaNova was statistically significant (p = 0.04). In the 21% hematocrit group, the processing speed was 69 ± 4 mL blood/min, 62 ± 8 mL blood/min and 77 ± 5 mL blood/min for the Fresenius, LivaNova and Haemonetics, respectively (p = 0.25). No major differences in the elimination of potassium, albumin and total protein or in hemolytic index were observed. No major differences were observed between discontinuous and continuous systems with respect to processing speed and wash quality with a starting hematocrit of 21%. Minor differences in processing speed were observed with a starting hematocrit of 13%.

Optical verification and in-vitro characterization of two commercially available acoustic bubble counters for cardiopulmonary bypass systems.

INTRODUCTION: Gaseous microemboli (GME) introduced during cardiac surgery are considered as a potential source of morbidity, which has driven the development of the first bubble counters. Two new generation bubble counters, introduced in the early 2000s, claim correct sizing and counting of GME. This in-vitro study aims to validate the accuracy of two bubble counters using monodisperse bubbles in a highly controlled setting at low GME concentrations. METHODS: Monodisperse GME with a radius of 43 µm were produced in a microfluidic chip. Directly after their formation, they were injected one-by-one into the BCC200 and the EDAC sensors. GME size and count, measured with the bubble counters, were optically verified using high-speed imaging. RESULTS: During best-case scenarios or low GME concentrations of GME with a size of 43 µm in radius in an in-vitro setup, the BCC200 overestimates GME size by a factor of 2 to 3 while the EDAC underestimates the average GME size by at least a factor of two. The BCC200 overestimates the GME concentration by approximately 20% while the EDAC overestimates the concentration by nearly one order of magnitude. Nevertheless, the calculated total GME volume is only over-predicted by a factor 2 since the EDAC underestimates the actual GME size. For the BCC200, the total GME volume was over-predicted by 25 times due to the over-estimation of GME size. CONCLUSIONS: The measured errors in the absolute sizing/counting of GME do not imply that all results obtained using the bubble counters are insignificant or invalid. A relative change in bubble size or bubble concentration can accurately be measured. However, care must be taken in the interpretation of the results and their absolute values. Moreover, the devices cannot be used interchangeably when reporting GME activity. Nevertheless, both devices can be used to study the relative air removal characteristics of CPB components or for the quantitative monitoring of GME production during CPB interventions.

Population pharmacokinetics of cefazolin before, during and after cardiopulmonary bypass to optimize dosing regimens for children undergoing cardiac surgery.

Objectives: The objective of this study was to characterize cefazolin serum pharmacokinetics in children before, during and after cardiopulmonary bypass (CPB), in order to derive an evidence-based dosing regimen. Patients and methods: This study included children who received cefazolin before surgical incision, before cessation of CPB and after surgery. Blood samples of total and unbound cefazolin concentrations were collected before, during and after CPB. The cefazolin concentration-time profiles were analysed using population pharmacokinetic modelling and predictors for interindividual variability in pharmacokinetic parameters were investigated. Subsequently, optimized dosing regimens were developed using stochastic simulations. Clinicaltrials.gov: NCT02749981. Results: A total of 494 total and unbound cefazolin concentrations obtained from 56 children (aged 6 days to 15 years) were included. A two-compartment model with first-order elimination plus an additional compartment for the effect of CPB best described the data. Clearance (1.56 L/h), central volume (1.93 L) and peripheral volume (2.39 L) were allometrically scaled by body weight. The estimated glomerular filtration rate (eGFR) was identified as a covariate on clearance and the serum albumin concentration was associated with maximum protein binding capacity. Our simulations showed that an additional bolus dose at the start of CPB improves the PTA in typical patients from 59% to >94%. Prolonged surgery and preserved renal function (i.e. drop in eGFR <25%) had a negative impact on PTA. Conclusions: We propose an optimized dosing regimen for cefazolin during cardiac surgery in paediatric patients to avoid treatment failure due to inadequate antibiotic prophylaxis.

Low flow extracorporeal CO2 removal in ARDS patients: a prospective short-term crossover pilot study.

BACKGROUND: Lung protective mechanical ventilation (MV) is the corner stone of therapy for ARDS. However, its use may be limited by respiratory acidosis. This study explored feasibility of, effectiveness and safety of low flow extracorporeal CO2 removal (ECCO2R). METHODS: This was a prospective pilot study, using the Abylcap® (Bellco) ECCO2R, with crossover off-on-off design (2-h blocks) under stable MV settings, and follow up till end of ECCO2R. Primary endpoint for effectiveness was a 20% reduction of PaCO2 after the first 2-h. Adverse events (AE) were recorded prospectively. We included 10 ARDS patients on MV, with PaO2/FiO2 < 150 mmHg, tidal volume ≤ 8 mL/kg with positive end-expiratory pressure ≥ 5 cmH2O, FiO2 titrated to SaO2 88-95%, plateau pressure ≥ 28 cmH2O, and respiratory acidosis (pH <7.25). RESULTS: After 2-h of ECCO2R, 6 patients had a ≥ 20% decrease in PaCO2 (60%); PaCO2 decreased 28.4% (from 58.4 to 48.7 mmHg, p = 0.005), and pH increased (1.59%, p = 0.005). ECCO2R was hemodynamically well tolerated. During the whole period of ECCO2R, 6 patients had an AE (60%); bleeding occurred in 5 patients (50%) and circuit thrombosis in 3 patients (30%), these were judged not to be life threatening. CONCLUSIONS: In ARDS patients, low flow ECCO2R significantly reduced PaCO2 after 2 h, Follow up during the entire ECCO2R period revealed a high incidence of bleeding and circuit thrombosis. TRIAL REGISTRATION: https://clinicaltrials.gov identifier: NCT01911533 , registered 23 July 2013.