End Of Cardiopulmonary Bypass Research Articles

CytoSorb® hemoadsorption of apixaban during cardio-pulmonary bypass for heart transplantation

IntroductionHeart transplantation is an emergency surgery requiring cardio-pulmonary bypass (CPB) and its timing is unpredictable. Patients on the transplant waiting list often have multiple reasons for being anticoagulated. Direct oral anticoagulants (DOACs) such as apixaban are very popular due to their well-known advantages. Intraoperative removal of apixaban using CytoSorb® (CytoSorbents Inc., Princeton, NJ, USA), seems to be an interesting solution for patients on DOACs requiring an emergency CPB intervention. The aim of this short communication is to describe the perioperative effects of the use of the CytoSorb® hemoadsorption device during emergency CPB for a heart transplant patient Case presentationA 61-year-old male patient (75kg/173cm) wait-listed for heart transplantation was admitted to our hospital (Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France) to benefit from a heart transplantation. This patient, with many comorbidities, has an end-stage heart failure with multiple episodes of decompensation over the previous year. He was anticoagulated with a Vitamin K antagonist (VKA) due to atrial fibrillation and was switched to apixaban (5mg twice daily) 9 days before surgery based on poor clotting control. A NaCl 0.9% primed CytoSorb cartridge was inserted into the CPB circuit. Hemoadsorption was performed during the entire CPB duration. Anti-Factor Xa Activity (AFXaA) levels were taken at multiple time points before, during and after surgery in order to monitor anticoagulation. Results. Preoperatively, activated Clotting Time (ACT) was 146 seconds. The ACT reached 545 seconds after administration of 25,000IU of unfractionated heparin (UFH). Surgery consisted of an orthotopic heart transplantation with bi-caval anastomoses.CPB duration was 133 minutes with 83 minutes of aortic cross clamping. Total graft ischemic time was 249 minutes. At the time of anesthesia induction and after UFH administration, AFXaA levels were 330ng/mL and 317ng/mL, respectively. Thereafter, AFXaA decreased to 137ng/mL during CPB and to 57ng/mL after the end of CPB and 250mg (=25,000IU) of protamine administration.After surgery, AFXaA levels stabilized over 50ng/mL over the next 14 hours. Postoperative anticoagulation was performed with the use of UFH starting 6 hours after surgery.No primary graft dysfunction (PGD) was observed, and during the post-operative period of 72 hours, the patient did not have any bleeding events requiring reintervention or transfusion. ConclusionIn conclusion, we observed that CytoSorb® could be a potential solution to remove apixaban intraoperatively. If this efficacy is confirmed in larger trials, it would allow transplant candidates to be treated with DOACs without requiring a switch to VKAs.

Low Frequency Ventilation During Cardiopulmonary Bypass to Protect Postoperative Lung Function in Cardiac Valvular Surgery: The PROTECTION Phase II Randomized Trial.

Cardiac surgery with cardiopulmonary bypass (CPB) triggers pulmonary injury. In this trial we assessed the feasibility, safety, and efficacy of low frequency ventilation (LFV) during CPB in patients undergoing valvular surgery. Patients with severe mitral or aortic valve disease were randomized to either LFV or usual care. Primary outcomes included release of generic inflammatory and vascular biomarkers and the lung-specific biomarker sRAGE (soluble receptor for advance glycation end products) up to 24 hours postsurgery. Secondary outcomes included pulmonary function tests and 6-minute walking test up to 8 weeks postdischarge. Sixty-three patients were randomized (33 LFV versus 30 usual care). Mean age was 66.8 years and 30% were female. LFV was associated with changes of sRAGE (soluble receptor for advance glycation end products) levels (geometric mean ratio, 3.05; [95% CI, 1.13-8.24] 10 minutes post CPB, and 1.07 [95% CI, 0.64-1.79], 0.84 [95% CI, 0.55-1.27], 0.67 [95% CI, 0.42-1.07], and 0.62 [95% CI, 0.45-0.85] at 2, 6, 12, and 24 hours post CPB respectively). No changes were observed for any of the generic biomarkers. Respiratory index soon after surgery (mean difference, -0.61 [95% CI, -1.24 to 0.015] 10 minutes post end of CPB), forced expiratory volume after 1 second/forced vital capacity ratio (0.050 [95% CI, 0.007-0.093] at 6 to 8 weeks pos-surgery), Forced vital capacity alone (95% CI, -0.191 L [-0.394 to 0.012]) and 6-minute walking test score at discharge (63.2 m [95% CI, 12.9-113.6]) were better preserved in the LFV group. No other differences were noted. The use of LFV during CPB in patients undergoing valvular surgery was feasible and safe and was associated with changes in sRAGE levels along with better preserved lung function and walking performance. These observations warrant further investigation in larger future studies. URL: https://www.isrctn.com; Unique Identifier: ISRCTN75795633.

#624 The impact of hemoadsorption in patients with borderline chronic kidney disease undergoing coronary artery bypass grafting

Abstract Background and Aims With an annual incidence of up to 30%, cardiac surgery–associated acute kidney injury (CSA-AKI) may be one of the most underappreciated yet frequent complications and renal protective adjustments are crucial. We evaluated the impact of hemoadsorption as adjunctive therapy on clinical outcome in Kidney Disease Improving Global Outcomes (KDIGO) G2/A2) patients undergoing coronary artery bypass grafting (CABG). Method During a three-year period, 40 patients undergoing CABG with borderline chronic kidney disease (KDIGO-G2/A2) were treated with adjunctive hemoadsorption therapy and were compared by propensity score-matched 40 patients (KDIGO G2/A2) (Control). Primary endpoints were the need for renal replacement therapy (RRT)/dialysis and/or worsening of KDIGO stage in the perioperative period. Secondary endpoints were the change in inflammatory biomarkers, vasopressor requirement and ICU/hospital stay. In the study group, a 300 mL hemoadsorber (Cytosorbents Inc, NJ) was used for the entire duration of cardiopulmonary bypass (CPB). All patients were prepared via enhanced recovery after surgery (ERAS) protocol and surgical procedures were performed under moderate hypothermia with pulsatile flow and ultrafiltration. Patients with septic shock, limited life expectancy and refused to give consent were excluded. Results After institutional ethics committee approval was obtained, written informed consent was received from each patient. No significant difference was noted between groups in demographic, operative data and preoperative baseline laboratory. At the end of CPB; s-Creatinine (mg/dL) (1.85 ± 0.6 vs 2.751 ± 0.6; p = 0.035), NT-proBNP (pg/L) (130 ± 30 vs 180 ± 40; p = 0.04), IL-6 (pg/mL) (8.2 ± 4 vs 22.2 ± 4; p = 0.012) and myoglobulin (pg/L) (210 ± 75 vs 310 ± 80; p = 0.04) levels were significantly lower in the study group versus control. Clinical outcome is summarized in Figure. Conclusion This pioneering study demonstrated the additional protective effects of hemoadsorption in patients with borderline chronic kidney disease (KDIGO-G2/A2) undergoing CABG. Elimination of inflammatory parameters might be a complementary mechanism resulting in lesser worsening of kidney function/need of RRT and ICU stay. These findings require validation in large, multicenter trials.

The effects of pentoxyphiline on neurocognitive functions and neurobiochemical markers in coronary artery bypass graft surgery

Aim: Neurocognitive dysfunction is a complication of cardiopulmonary bypass (CPB). Neuron-specific enolase (NSE) and S100ß protein are markers of cerebral injury. With its beneficial rheological and anti-inflammatory properties, pentoxyphiline (PTX) is an interesting agent in cardiac surgery patients. The study was designed to evaluate the influence of prophylactic use of PTX on cognitive function and S100ß and NSE in on-pump coronary artery bypass grafting (CABG) patients.Method: In this prospective study, 40 patients undergoing on-pump CABG and received either PTX (bolus of 5 mg kg-1) after induction of anesthesia or saline are included. Neurological examination and neuropsychologic tests, including the mini-mental state examination test (MMSET) and Benton visual retention test (BVRT), were obtained preoperatively and on the seventh postoperative day. Blood samples for analysis of S100ß and NSE were collected before anesthesia, at the end of CPB, at the 3rd hour and 24th hour postoperatively.Results: Demographic and perioperative data were similar for the two groups. Mean cross-clamping times were 67.86±22.22 and 66.32±27.84 min, respectively. In both groups, S100ß and NSE increased significantly (p<0.01) at the end of the CPB and remained slightly increased at T2 (at the CPB exit), and T3 (at the 3rd hour after surgery) than preoperative levels (p>0.05). MMSET and BVRT performances of the two groups were similar and did not change compared to preoperative scores.Conclusions: Coronary artery bypass surgery caused a significant increase in NSE and S100ß serum levels but with no deterioration in neuropsychological outcome assessed in the first postoperative week. Although it was reported that PTX could be a promising agent to prevent post-CPB organ dysfunction in elderly cardiac surgery patients, prophylactic use of PTX appeared to offer no advantage for cerebral protection in the age group involved in this study.

The renal vascular resistive index as a predictor of acute kidney injury in children of the first year of life in congenital heart surgery with cardiopulmonary bypass

The objective was to evaluate the renal vascular resistive index as a predictor of acute kidney injury in children of the first year of life in congenital heart surgery with cardiopulmonary bypass. Materials and methods. A single-center retrospective study included 150 patients with congenital heart disease (CHD), whose renal vascular resistive index (RVRI) was assessed at the stages of surgical interventions (before surgery, 6 hours after the end of cardiopulmonary bypass (CPB) and the 1st day after surgery). Acute kidney injury (AKI) was diagnosed according to the KDIGO criteria. To achieve comparability of the obtained groups, pseudo-randomization was performed. After compensating for the uneven distribution of cofounders, groups of patients comparable in number were obtained (n= 52 in both groups). Results. The renal vascular resistive index at the stages of surgical intervention did not differ among patients with and without acute kidney injury. The baseline of creatinine was higher in the group without AKI, however, starting from the 1st postoperative day, it prevailed in the group with AKI. The chances of developing AKI in male patients were 74% lower. Conclusion. The absence of a predictive ability of the renal vascular resistive index in acute kidney injury in children aged 1 month to 1 year with congenital heart disease operated with cardiopulmonary bypass was demonstrated.

Minimal invasive extracorporeal circulation in comorbid patients

Background: As the severity of comorbid diseases increases, risks of cardiopulmonary bypass (CPB) complications significantly increase. A complex of the procedure’s damaging factors provokes a systemic inflammatory response that in some cases is accompanied by the damage to target organs, transitioning from chronic organ dysfunctions into acute ones. Some studies on the use of minimal invasive extracorporeal circulation (MiECC) systems show their advantage over conventional extracorporeal circulation (CECC); however, the diversity of MiECC systems, patients, and outcomes precludes us from confidently extrapolating these data to older comorbid patients.Objective: To compare the severity of systemic inflammation and treatment outcomes in comorbid patients who underwent cardiac surgery with CECC and MiECC.Methods: We conducted a retrospective cohort study of 760 patients who consecutively underwent elective cardiac operations in 2019-2022. Inclusion criteria: comorbid status (age-adjusted Charlson Comorbidity Index score of ≥6); CPB time ≥90 min. Exclusion criteria: emergency surgery, refusal to participate in the study. A total of 68 patients met the inclusion criteria. We formed 2 study groups based on the extracorporeal circulation method: CECC group (n = 51) and MiECC group (n = 17). Control points: before CPB and 24 hours after the surgery (lactate; creatinine; oxygenation index, hemolysis level). For systemic inflammatory response markers: 1 hour after the CPB start and 24 hours after the CPB end (interleukin 6; interleukin 10; procalcitonin; C-reactive protein; soluble Triggering Receptor Expressed on Myeloid Cells-1 [sTREM-1]). We evaluated respiratory and renal complications, drainage-related hemorrhages, hemostatic disorders, the need for sympathomimetic drugs, and the length of stay in an intensive care unit and inpatient hospital.Results: Between the groups there were no statistically significant differences in gender and anthropometric characteristics, surgery types, and main perfusion parameters. In the CECC group, we observed significantly higher doses of vasoconstrictors (norepinephrine) as well as a decrease in urine output and lung injury and an increase in lactate and hemolysis. The systemic inflammatory response markers were also significantly higher.Conclusion: Compared with CECC, MiECC does not significantly affect the frequency of organ dysfunctions; however, it reduces the severity of the systemic inflammatory response and immune suppression that are trigger mechanisms for multiple organ dysfunction syndrome. It is particularly important for patients with chronic organ dysfunctions. A range of indications for MiECC systems should be defined given its high cost and off-target effect on pleiotropic factors of systemic inflammatory response development. Received 6 April 2023. Revised 17 August 2023. Accepted 18 August 2023. Funding: The study was conducted within the framework of the research project "Development of minimally invasive and hybrid technologies for surgical treatment of heart diseases". Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: A.Sh. Revishvili, G.P. Plotnikov, V.A. PopovData collection and analysis: R.A. Kornelyuk, L.B. Berikashvili, I.P. Komkov, E.S. Malyshenko, V.M. ZemskovStatistical analysis: L.B. BerikashviliDrafting the article: R.A. Kornelyuk, G.P. Plotnikov, L.B. Berikashvili Critical revision of the article: G.P. PlotnikovFinal approval of the version to be published: A.Sh. Revishvili, R.A. Kornelyuk, G.P. Plotnikov, L.B. Berikashvili, I.P. Komkov, E.S. Malyshenko, V.M. Zemskov, V.A. Popov

Early plasma proteomic biomarkers and prediction model of acute respiratory distress syndrome after cardiopulmonary bypass: a prospective nested cohort study.

Early recognition of the risk of acute respiratory distress syndrome (ARDS) after cardiopulmonary bypass (CPB) may improve clinical outcomes. The main objective of this study was to identify proteomic biomarkers and develop an early prediction model for CPB-ARDS. We conducted three prospective nested cohort studies of all consecutive patients undergoing cardiac surgery with CPB at XXX Hospital. Plasma proteomic profiling was performed in ARDS patients and matched controls (Cohort 1, April, 2021 to July, 2021) at multiple timepoints: before CPB (T1), at end of CPB (T2), and 24 h after CPB (T3). Then, for Cohort 2 (August, 2021 to July, 2022), biomarker expression was measured and verified in the plasma. Furthermore, lung ischemia/reperfusion injury (LIRI) models and sham-operation were established in 50 rats to explore the tissue-level expression of biomarkers identified in the aforementioned clinical cohort. Subsequently, a machine learning-based prediction model incorporating protein and clinical predictors from Cohort 2 for CPB-ARDS was developed and internally validated. Model performance was externally validated on Cohort 3 (January, 2023 to March, 2023). A total of 709 proteins were identified, with 9, 29, and 35 altered proteins between ARDS cases and controls at T1, T2, and T3, respectively, in Cohort 1. Following quantitative verification of several predictive proteins in Cohort 2, higher levels of thioredoxin domain containing 5 (TXNDC5), cathepsin L (CTSL), and NPC intracellular cholesterol transporter 2 (NPC2) at T2 were observed in CPB-ARDS patients. A dynamic online predictive nomogram was developed based on three proteins (TXNDC5, CTSL, and NPC2) and two clinical risk factors (CPB time, massive blood transfusion), with excellent performance (precision: 83.33%, sensitivity: 93.33%, specificity: 61.16%, F1 score: 85.05%). Mean area under the receiver operating characteristics curve (AUC) of the model after 10-fold cross-validation was 0.839 (95% confidence interval (CI): 0.824 to 0.855). Model discrimination and calibration were maintained during external validation dataset testing, with AUC of 0.820 (95% CI: 0.685 to 0.955) and Brier Score of 0.177 (95% CI: 0.147 to 0.206). Moreover, the considerably overexpressed TXNDC5 and CTSL proteins identified in the plasma of patients with CPB-ARDS, exhibited a significant upregulation in the lung tissue of LIRI rats. This study identified several novel predictive biomarkers, developed and validated a practical prediction tool using biomarker and clinical factor combinations for individual prediction of CPB-ARDS risk. Assessing the plasma TXNDC5, CTSL, and NPC2 levels might identify patients who warrant closer follow-up and intensified therapy for ARDS prevention following major surgery.

Effect of cardiopulmonary bypass on plasma and erythrocytes oxylipins

BackgroundOxylipins, the oxidative metabolites of polyunsaturated fatty acids (PUFAs), serve as key mediators of oxidative stress, inflammatory responses, and vasoactive reactions in vivo. Our previous work has established that hemodialysis affects both long chain fatty acids (LCFAs) and oxylipins in plasma and erythrocytes to varying degrees, which may be responsible for excess cardiovascular complications in end-stage renal disease. In this study, we aimed to determine changes in blood oxylipins during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery to identify novel biomarkers and potential metabolites of CPB-related complications. We tested the hypothesis that CPB would differentially affect plasma oxylipins and erythrocytes oxylipins.MethodsWe conducted a prospective observational study of 12 patients undergoing elective cardiac surgery with expected CPB procedure. We collected venous and arterial blood samples before CPB, 15 and 45 min after the start of CPB, and 60 min after the end of CPB, respectively. Oxylipins profiling in plasma and erythrocytes was achieved using targeted HPLC‐MS mass spectrometry.ResultsOur results revealed that most venous plasma diols and hydroxy- oxylipins decreased after CPB initiation, with a continuous decline until the termination of CPB. Nevertheless, no statistically significant alterations were detected in erythrocytes oxylipins at all time points.ConclusionsCPB decreases numerous diols and hydroxy oxylipins in blood plasma, whereas no changes in erythrocytes oxylipins are observed during this procedure in patients undergoing cardiac surgery. As lipid mediators primarily responsive to CPB, plasma diols and hydroxy oxylipins may serve as potential key biomarkers for CPB-related complications.

Application of ultrasound microbubble contrast to evaluate the effect of sitaxentan on renal microvascular perfusion in beagles undergoing cardiopulmonary bypass.

We aimed to evaluate the effect of sitaxentan on renal microvascular perfusion via application of ultrasound microbubble contrast. Male beagles were randomly divided into: Sham, cardiopulmonary bypass (CPB) and sitaxentan-infused (Sit) groups (n = 6). The ascending slope rate (ASR), area under the curve (AUC), derived peak intensity, and time to peak (TTP) were obtained via ultrasound microbubble contrast before CPB (T1), after 1 h CPB (T2), at end of CPB (T3), and 2 h after CPB (T4). Compared with the Sham group, the CPB group had lower ASR of the renal cortex and medulla at T2-4, higher AUC and TTP at T3-4, and lower derived peak intensity at T4. The ASR at T2-4 in the Sit group was lower, TTP was higher at T2-4, and AUC was higher at T3-4 (P < 0.05). Compared with the CPB group, the Sit group had higher ASR of the renal cortex and medulla at T3-4 and AUC and TTP at T3-4 (P < 0.05). Compared with that at T1, the ASR of the renal cortex and medulla at T2-4 in the CPB group was lower, and AUC and TTP were higher at T3-4. The ASR of the renal cortex and medulla at T2-4 in the Sit group was lower, TTP was higher at T2-4, and AUC was higher at T4 (P < 0.05). Ultrasound microbubble contrast could be effectively used to evaluate renal microvascular perfusion peri-CPB in beagles, which was prone to decrease and could be improved via pretreatment with sitaxentan.

Loss or Dilution-A New Diagnostic Method to Assess the Impact of Dilution on Standard Laboratory Parameters.

Intraoperative fluid therapy is regularly used in patients undergoing cardiac surgery procedures with cardiopulmonary bypass (CPB). Although fluid administration has several advantages, it unavoidably leads to hemodilution. The hemodilution may further influence the interpretation of concentration-based laboratory parameters like hemoglobin (Hgb), platelet count (PLT) or prothrombin time (PT). These all parameters are commonly used to guide blood product substitution. To assess the impact of dilution on these values, we performed a prospective observational study in 174 patients undergoing elective cardiac surgery. We calculated the total blood volume according to Nadler's formula, and fluid therapy was correlated with a newly developed dilution coefficient formula at the end of CPB. Intravenously applied fluids were measured from the beginning of the anesthesia (baseline, T0) and 15 min after the end of protamine infusion (end of CPB, T1). The amount of the administered volume (crystalloids or colloids) was calculated according to the percentage of the intravascular fluid effect, and intraoperative diuresis was further subtracted. The median blood volume increased by 148% in all patients at T1 compared to the calculated total blood volume at T0. This led to a dilution-dependent decrease of 38% in all three parameters (Hgb 24%, corrCoeff = 0.53; PLT 41%, corrCoeff = 0.68; PT 44%, corrCoeff = 0.54). The dilution-correlated decrease was significant for all parameters (p < 0.001), and the effect was independent from the duration of CPB. We conclude that the presented calculation-based approach could provide important information regarding actual laboratory parameters and may help in the guidance of the blood product substitution and potential transfusion thresholds. Further research on the impact of dilution and related decision-making for blood product substitution, including its impact on morbidity and mortality, is warranted.

Association Between Risk of Stroke and Delirium After Cardiac Surgery and a New Electroencephalogram Index of Interhemispheric Similarity

Neurologic complications after surgery (stroke, delirium) remain a major concern despite advancements in surgical and anesthetic techniques. The authors aimed to evaluate whether a novel index of interhemispheric similarity, the lateral interconnection ratio (LIR), between 2 prefrontal electroencephalogram (EEG) channels could be associated with stroke and delirium following cardiac surgery. Retrospective observational study. Single university hospital. A total of 803 adult patients without documentation of a previous stroke, who underwent cardiac surgery with cardiopulmonary bypass (CPB) between July 2016 and January 2018. The LIR index was calculated retrospectively from the patients' EEG database. LIR was analyzed intraoperatively every 10 seconds and compared among patients with postoperative stroke, patients with delirium, and patients without documented neurologic complications, during 5 key periods, each lasting10 minutes: (1) surgery start, (2) before CPB, (3) on CPB, (4) after CPB, and (5) surgery end. After cardiac surgery, 31 patients suffered from stroke; 48 patients were diagnosed with delirium; and 724 had no documented neurologic complications. Patients with stroke demonstrated a decrease in LIR index between the start of surgery and the postbypass period of 0.08 (0.01, 0.36 [21]; median and [interquartile range {IQR}]; valid EEG samples); whereas there was no similar decrease in the no-dysfunction group (-0.04 [-0.13, 0.04; {551}], p < 0.0001). Patients with delirium showed a decrease in LIR index between the start of surgery and the end of the surgery by 0.15 (0.02, 0.30 [12]), compared with no such decrease in the no-dysfunction group (-0.02 [-0.12, 0.08 {376}], p ≈ 0.001). After improvement of SNR, it might be of value to further study the index decrease as an indication for risk for brain injury after surgery. The timing of decrease (after CPB or end of surgery) may provide hints regarding the injury pathophysiology and its onset.

Intraoperative ticagrelor removal via hemoadsorption during on-pump coronary artery bypass grafting

ObjectivesPatients on ticagrelor undergoing urgent cardiac surgery are at high risk for perioperative bleeding complications. We sought to determine whether intraoperative hemoadsorption could remove ticagrelor and lower circulating drug concentrations. MethodsThe hemoadsorption device was incorporated in the cardiopulmonary bypass (CPB) circuit and remained active for the duration of the pump run. Blood samples were collected before and after CPB. The main objective of the current analysis was to compare mean total plasma ticagrelor levels (ng/mL) at baseline with ticagrelor levels obtained at the end of CPB. Plasma ticagrelor levels were measured at a certified outside laboratory (LabConnect). Data are presented as mean ± standard deviation. ResultsA total of 11 patients undergoing urgent coronary artery bypass grafting at 3 institutions were included (mean age, 67.9 ± 9.9 years; 91% male; mean European System for Cardiac Operative Risk Evaluation II of 3.0 ± 3.3%; range, 0.7%-12.4%). Mean intraoperative hemoadsorption duration was 97.1 ± 43.4 minutes with a mean flow rate through the device of 422.9 ± 40.3 mL/min. Mean ticagrelor levels pre-CPB were 103.5 ± 63.8 ng/mL compared with mean post-CPB levels of 34.0 ± 17.5 ng/mL, representing a significant 67.1% reduction (P < .001). Intraoperative integration of the device was simple and safe without any device-related adverse events reported. ConclusionsThis is the first in vivo report demonstrating that intraoperative hemoadsorption can efficiently remove ticagrelor and significantly reduce circulating drug levels. Whether active ticagrelor removal can reduce serious perioperative bleeding in patients undergoing urgent cardiac surgery is currently being evaluated in the double-blinded, randomized Safe and Timely Antithrombotic Removal–Ticagrelor (STAR-T) trial.

Platelet Function is Preserved After Moderate Cardiopulmonary Bypass Times But Transiently Impaired After Protamine

Previous studies have described impaired platelet function after cardiopulmonary bypass (CPB). Whether this is still valid in contemporary cardiac surgery is unclear. This study aimed to quantify changes in function and number of platelets during CPB in a present-day cardiac surgery cohort. Prospective, controlled clinical study. A single-center university hospital. Thirty-nine patients scheduled for coronary artery bypass graft surgery with CPB. Platelet function and numbers were measured at 6 timepoints in 39 patients during and after coronary artery bypass graft surgery; at baseline before anesthesia, at the end of CPB, after protamine administration, at intensive care unit (ICU) arrival, 3 hours after ICU arrival, and on the morning after surgery. Platelet function was assessed with impedance aggregometry and flow cytometry. Platelet numbers are expressed as actual concentration and as numbers corrected for dilution using hemoglobin as a reference marker. There was no consistent impairment of platelet function during CPB with either impedance aggregometry or flow cytometry. After protamine administration, a decrease in platelet function was seen with impedance aggregometry and for some markers of activation with flow cytometry. Platelet function was restored 3 hours after arrival in the ICU. During CPB (85.0 ± 21 min), the number of circulating platelets corrected for dilution increased from 1.73 ± 0.42×109/g to 1.91 ± 0.51×109/g (p < 0.001). During cardiac surgery with moderate CPB times, platelet function was not impaired, and no consumption of circulating platelets could be detected. Administration of protamine transiently affected platelet function.

Relationships Between Systemic Inflammation, Intestinal Damage and Postoperative Organ Dysfunction in Adults Undergoing Low-Risk Cardiac Surgery.

Approximately half of patients who undergo cardiac surgery develop systemic inflammatory response syndrome. Extracorporeal circulation and intestinal injury may play a role in this inflammatory response, although their relative contributions remain elusive. Moreover, it is largely unknown to what extent these factors contribute to cardiac surgery-induced postoperative organ dysfunction. In this secondary analysis, we measured circulating levels of the intestinal damage marker intestinal fatty acid binding protein (I-FABP) and of the inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-10, IL-1RA, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and MIP-1β in 180 patients undergoing on-pump cardiac surgery. The average Z-score of levels of the different cytokines was used as an integral measure of the cytokine response. Relationships between duration of extracorporeal circulation, extent of intestinal injury, inflammation, and postoperative organ dysfunction were explored. Plasma I-FABP levels increased during surgery, with peak levels observed at the end of cardiopulmonary bypass (CPB). Except for TNF-α, the levels of all cytokines increased during surgery, with peak levels observed either 2 (MCP-1, MIP-1α, and MIP-1β), 4 (IL-6, IL-8, and IL-1RA) or 6 (IL-10) hours after the end of CPB. While the duration of CPB significantly correlated with cytokine Z-score (r=0.544, p<0.05), no relationship with I-FABP levels was found. Furthermore, no significant correlations between I-FABP and cytokine levels were observed. The duration of CPB correlated with a deterioration in postoperative kidney function (estimated glomerular filtration rate [eGFR]) and troponin levels. Cytokine Z-score was associated with postoperative troponin levels, fluid administration, inotropic score, pulmonary alveolar-arterial gradient on the first postoperative morning, and deterioration of kidney function (eGFR). I-FABP levels did not correlate with any of the cardiovascular, pulmonary, or renal parameters. In patients undergoing low-risk cardiac surgery, the duration of CPB represents an important determinant of the systemic cytokine response, whereas both the CPB duration and the systemic inflammatory response contribute to subsequent organ dysfunction. Intestinal damage does not appear to play a relevant role in the postoperative inflammatory response and development of postoperative organ dysfunction in these patients.

Intraoperative transfusion is a risk factor for cerebral injury after cardiac surgery in children: a prospective observational study

INTRODUCTION: Donor blood components are able to initiate a systemic inflammatory response syndrome (SIRS) and potentiate neuroinflammation with subsequent cerebral damage. OBJECTIVE: To study the effect of transfusion on the development of cerebral damage during the surgical correction of congenital heart defects in children. MATERIALS AND METHODS: 78 patients aged from 1 to 78 months, weighing from 3.3 to 21.5 kg, were studied. All patients underwent correction of a septal defect under cardiopulmonary bypass. All patients were divided to group 1 — without the use of transfusion and group 2 — with the use of red blood cell transfusion. Cerebral damage markers (S-100-β protein, neuron-specific enolase (NSE) and glial fibrillar acidic protein (GFAP)) and SIRS (interleukins 1 (ILb-1), 6 (IL-6), 10 (IL-10) and tumor necrosis factor alpha (TNF-α) were studied. Markers ware studied at three control points: 1 — before the start of surgery, 2 — immediately after end of cardiopulmonary bypass, 3 — 16 hours after the end of the operation. RESULTS: The peak concentration of most markers in the blood in both groups of patients was noted at the 2nd control point. The concentration of all markers of cerebral damage was significantly higher in the transfusion group at the 2nd control point: S-100-β protein (ng/ml) — 509.90 [379.30–871.70] and 717.10 [517.90–1195.33] (р = 0.024); NSE (ng/ml) — 17.55 [11.19–26.41] and 34.05 [17.06–44.90] (р = 0,023); GFAP (ng/ml) — 0.1190 [0.1135–0.1245] and 0.1231 [0.1138–0.1493]. Correlations were found between markers of cerebral damage and SIRS, the strongest of which was the relationship between NSE and TNF-α at the 3rd control point — Rho = 0.43 (p = 0.0001). A correlation of S-100-β protein with transfusion volume was observed at the 2nd (Rho = 0.48, p = 0.00065) and 3rd control points (Rho = 0.36, p = 0.01330). CONCLUSIONS: The influence of the fact of transfusion and the dose of red blood cell on the development of cerebral damage during cardiac surgery in children has been proven.

Proenkephalin A and bioactive adrenomedullin are useful for risk prognostication in cardiac surgery.

Various clinical scores have been developed to predict organ dysfunction and mortality in patients undergoing cardiac surgery, but outcome prediction may be inaccurate for some patient groups. Proenkephalin A (penKid) and bioactive adrenomedullin (bio-ADM) have emerged as promising biomarkers correlating with shock and organ dysfunction. This imposes the question of whether they can be used as prognostic biomarkers for risk stratification in the perioperative setting of cardiac surgery. Patients undergoing cardiac surgery were prospectively enrolled in this observational study. PenKid and bio-ADM plasma levels, as well as markers evaluating inflammation and organ dysfunction, were measured at five perioperative time points from before the induction of anesthesia to up to 48 h postoperatively. Clinical data regarding organ dysfunction and patient outcomes were recorded during the intensive care unit (ICU)-stay with a special focus on acute kidney injury (AKI). In 136 patients undergoing cardiac surgery, the bio-ADM levels increased and the penKid levels decreased significantly over time. PenKid was associated with chronic kidney disease (CKD), the incidence of AKI, and renal replacement therapy (RRT). Bio-ADM was associated with lactate and the need for vasopressors. PenKid was useful to predict an ICU-length of stay (LOS)>1 day and added prognostic value to the European System for Cardiac Operative Risk Evaluation Score (EuroSCORE) II when measured after the end of cardiopulmonary bypass and 24 h after cardiac surgery. For bio-ADM, the same was true when measured 24 h after surgery. PenKid also added prognostic value to the EuroSCORE II for the combined outcome "ICU length of stay >1 day and in-hospital mortality." The combination of preoperative EuroSCORE II and intraoperative measurement of penKid may be more useful to predict a prolonged ICU LOS and increased mortality than EuroSCORE II alone. Bio-ADM correlates with markers of shock. More research is encouraged for early risk stratification and validation of penKid and bio-ADM as a tool involved in clinical decisions, which may enable the early initiation of organ protective strategies.

Modification of Vancomycin Dosing in Cardiac Surgery With Cardiopulmonary Bypass.

This study aims to assess the risk factors for insufficient vancomycin concentrations for its prophylactic use in adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and to modify the dosing regimen to achieve appropriate plasma concentrations. A total of 27 patients with vancomycin dosing of 1 to 1.5g based on a weight cutoff of 67kg were included, of which only 13 (48.15%) had vancomycin plasma concentration >15mg/L at surgical closure. Risk factors of vancomycin concentration <15mg/L at surgical-site closure were confirmed by multivariate logistic regression analysis, which showed that CPB duration was an independent predictor. Patients with CPB duration >4hours had significantly lower vancomycin concentrations and lower proportion in achieving target vancomycin concentration at the end of CPB and surgical closure. For patients with CPB >4hours, the modified dosing regimen that a second dose of 0.5 to 0.75g added at 4hours since the onset of CPB improved the target achievement of vancomycin concentration at surgical closure. Taken together, CPB duration >4hours was the risk factor for insufficient vancomycin concentration at surgical closure, while our modified dosing could improve the vancomycin concentrations for its prophylactic use in patients undergoing cardiac surgery with CPB.

Protamine titration to optimize heparin antagonization after cardiopulmonary bypass.

To optimize protamine titration for heparin antagonization after weaning from cardiopulmonary bypass (CPB). A prospective, observational trial. Single-center, non-university teaching hospital. Forty patients presenting for elective on-pump coronary artery bypass grafting with or without single valve surgery. At the end of CPB, the residual amount of heparin in the patient was estimated using a Bull-curve. The total protamine dose was calculated as 1unit of protamine for 1unit of heparin. Protamine was administered as 5 aliquots containing 20% of the total protamine dose each, with 2-min intervals. Activated Clotting Time (ACT) values were measured 2min after administration of each aliquot. ROTEM(®)-analysis was performed after the full dose of protamine had been administered. After 60% of the total protamine dose had been administered, ACT values were normalized in 86.5% of patients. After the complete dose of protamine had been administered, 61.1% of patients displayed signs of protamine overdose on ROTEM(®)-analysis. In patients who present for on-pump coronary artery bypass grafting with or without single valve surgery, a 0.6-to-1 ratio of protamine-to-heparin to antagonize heparin may be sufficient and beneficial for patients.

NUMBERS AND FUNCTION OF PLATELETS ARE NOT REDUCED DURING CARDIOPULMONARY BYPASS, BUT BOTH ARE REDUCED AFTER ADMINISTRATION OF PROTAMINE

<h3>Objective</h3> To assess changes in numbers and function of platelets during cardiopulmonary bypass (CPB) in CABG surgery. <h3>Methods</h3> Platelet concentration and numbers corrected for hemodilution using hemoglobin as a marker were measured before anesthesia induction (Baseline), at the end of CPB (End CPB), after administration of protamine (After protamine), at arrival at the ICU (ICU) and after 3 hours in the ICU (ICU 3h). Platelet function was assessed after activation with thrombin PAR1-receptor activating peptide (TRAP) and adenosine diphosphate (ADP), with both flow cytometry for fibrinogen receptor activation and impedance aggregometry. Flow cytometry data are presented as median fluorescence intensity (MFI), impedance aggregometry data as area under the curve in units (U). Mean ± SD and repeated measures mixed effects model together with Šídák's multiple comparisons test was used. Subsequent time points were compared to baseline. In addition, "After protamine" was compared to "End CPB". <h3>Results</h3> Thirty-nine CABG patients with mean CPB time 85.1 ± 21.3 mins were studied. During CPB platelet concentration decreased from 227 ± 48 *109/L at baseline to 179 ± 38*109/L at end of CPB (p<0.001), remained at 171 ± 41*109/L after protamine, but increased to 204 ± 48*109/L at ICU 3h (p<0.001 vs baseline). Corrected for hemodilution the number of platelets increased during CPB from 1.73 ± 0.41*109/g to 1.91 ± 0.49 *109/g (p<0.001) but decreased to 1.74 ± 0.51*109/g after protamine (p<0.01 vs End CPB), and then increased to 1.82 ± 0.48*109/g at ICU 3h (p<0.01 vs Baseline). Activation of the fibrinogen receptor, after stimulation using TRAP, did not change during CPB, but was reduced after protamine administration and lower than baseline at ICU arrival (see figure). With ADP as agonist the fibrinogen receptor activation increased from baseline 2.15 ± 1.6 to end of CPB 2.55 ± 1.6 (p<0.001) but decreased to 2.01 ± 1.3 after protamine (p<0.001 vs End CPB), returning to baseline levels at ICU 2.17 ± 1.2 and ICU 3h 2.26 ± 1.2. Platelet function measured with impedance aggregometry using TRAP as activator showed a similar pattern from baseline 114 ± 29 U, maintained levels at end of CPB 118 ± 40 U, but decreased after protamine 103 ± 34 U (p<0.05 vs End CPB), and returned to baseline levels at ICU 118 ± 32 U and finally increased at ICU 3h 126 ± 30 (p<0.05 vs Baseline). With ADP as activator the changes were similar; baseline 77.1 ± 26 U, maintained at end of CPB 68.6 ± 28 U, reduced after protamine 58.9 ± 29 U (p<0.001 vs Baseline), with return to baseline levels at ICU 66.5 ± 28 U, and ICU 3h 86.7 ± 26 U. <h3>Conclusions</h3> The number of circulating platelets increased during CPB when corrected for hemodilution. CPB did not impair platelet function. Administration of protamine reduced the function and numbers of platelets with a return to normal values at the arrival or after 3 hours in the ICU.

Serum level of calpains product as a novel biomarker of acute lung injury following cardiopulmonary bypass.

The aim of this study was to test the hypothesis whether serum level of calpains could become a meaningful biomarker for diagnosis of acute lung injury (ALI) in clinical after cardiac surgery using cardiopulmonary bypass (CPB) technology. Seventy consecutive adults underwent cardiac surgery with CPB were included in this prospective study. Based on the American-European Consensus Criteria (AECC), these patients were divided into ALI (n = 20, 28.57%) and non-ALI (n = 50, 71.43%) groups. Serum level of calpains in terms of calpains' activity which was expressed as relative fluorescence unit (RFU) per microliter and measured at beginning of CPB (baseline), 1 h during CPB, end of CPB as well as 1, 12, and 24 h after CPB. Difference of serum level of calpains between two groups first appeared at the end of CPB and remained different at subsequent test points. Univariate and multivariate logistic regression analysis indicated that serum level of calpains 1 h after CPB was an independent predictor for postoperative ALI (OR 1.011, 95% CI 1.001, 1.021, p = 0.033) and correlated with a lower PaO2/FiO2 ratio in the first 2 days (The first day: r = -0.389, p < 0.001 and the second day: r = -0.320, p = 0.007) as well as longer mechanical ventilation time (r = 0.440, p < 0.001), intensive care unit (ICU) length of stay (LOS) (r = 0.419, p < 0.001) and hospital LOS (r = 0.297, p = 0.013). Elevated serum level of calpains correlate with impaired lung function and poor clinical outcomes, indicating serum level of calpains could act as a potential biomarker for postoperative ALI following CPB in adults. [https://clinicaltrials.gov/show/NCT05610475], identifier [NCT05610475].