Utilizing retrograde autologous priming for blood conservation in cardiac surgery.

BACKGROUND: The use of crystalloid priming for extracorporeal circuit in adult cardiac surgery causes inevitable haemodilution. The haemodilution can be reduced by using methods such as retrograde autologous priming (RAP) with the patient's blood. This study compares the RAP technique with standard priming with regards to safety and the impact on haemodilution. METHODS: This was a retrospective cohort study between a control group (n = 100) consisting of consecutive patients undergoing first time isolated coronary artery bypass surgery (CABG) with crystalloid priming solution in the circuit, and the RAP group (n = 100) consisting of patients undergoing isolated first time CABG with the RAP method. All demographics, procedure and perfusion data were gathered from the local surgical and perfusion database. RESULTS: Despite starting with comparable mean pre-operative haemoglobin (Hb) levels (control 127 mg/dL versus RAP 129 mg/dL), the RAP group had significantly higher mean post-op Hb level (109 mg/dL versus 92 mg/dL, P < 0.01). Crystalloid use was also significantly lower in RAP group (3.15 L versus 4.17 L P < 0.02). Freedom from red blood cell transfusion (86% versus 76% P = 0.038) and freedom from blood products (78% versus 66%, P = 0.032) was also significantly better in the RAP group. CONCLUSIONS: This study demonstrates that retrograde autologous priming is a safe and effective method for priming the cardiopulmonary bypass circuit in adult cardiac surgery, with significantly beneficial effects on transfusion rates and intra operative fluid requirements. Given these results the RAP method should be considered as a routine step in priming an extracorporeal circuit for adult cardiac operations.

Evaluation of Thromboelastography 6s prognostication of fibrinogen supplementation in pediatric cardiac surgery.

BACKGROUND: Implementation of point-of-care tests is recommended to provide tailored substitution during cardiac surgery. The measurement and substitution of fibrinogen have gained particular interest since it is the first coagulation factor to become depleted during cardiac surgery. However, the prognostic ability of thromboelastography (TEG) 6s has not been evaluated in pediatric patients. The aim of the present study was to describe patient characteristics of infants receiving fibrinogen substitution during cardiac surgery and evaluate the prognostic ability of TEG6s after weaning off cardiopulmonary bypass (CPB). METHODS: Infants undergoing congenital cardiac surgery with CPB were retrospectively included (n = 279) between January 2017 to July 2019. Patient and perioperative data were collected on the day of surgery until 6:00 AM the next morning. Hemostatic capacity was assessed with TEG6s. The efficacy of TEG-functional fibrinogen-maximal amplitude (TEG-FF-MA) measurements for the prediction of intraoperative bleeding, and thereby cryoprecipitate need, was evaluated by a sensitivity and specificity analysis. RESULTS: Among 174 children with TEG-FF-MA data, 147 (84%) received cryoprecipitate intraoperatively. Cryoprecipitate administration was associated with younger age 66 (10-132) versus 98 (45-204) days (p = .044), higher RACHS-1 classification, and intraoperative bleeding 21 (11-47) versus 5 (3-13) ml/kg (p < .001, mean difference 29 ml/kg [CI: 8-50]). Median TEG-FF-MA values were lower in transfused children 7.6 (5.3-11.0) versus 10.5 (7.3-13.4) mm (p = .004, mean difference - 2.4 mm [CI: -4.1 to - 0.73]). The volume of cryoprecipitate was associated with bypass time, TEG-FF-MA values, and in particular intraoperative bleeding volumes. A TEG-FF-MA threshold of 10.0 mm, resulted in sensitivity: 74%, specificity: 56%, positive predictive value: 80%, and a negative predictive value of 47% for the prediction of intraoperative bleeding (>10 ml/kg) and consequently a need of cryoprecipitate transfusion. CONCLUSION: Fibrinogen substitution in infants was associated with younger age and higher RACHS-1 category. The prognostic value of TEG6s was evaluated, and cryoprecipitate transfusion was related to TEG-FF-MA values, but also CPB-time, surgical complexity, and in particular excessive intraoperative bleeding. A clear-cut threshold for TEG-FF-MA is difficult to establish in infants undertaken congenital heart surgery.

Intraoperative collection of autologous platelet-rich plasma from the cardiopulmonary bypass circuit upon initiation of extracorporeal circulation.

OBJECTIVES: The aim of this study is to evaluate the possibility of the autologous platelet-rich plasma (PRP) collection from the cardiopulmonary bypass (CPB) circuit and to evaluate its effect on the aggregative function. METHODS: For seventy-two patients undergoing cardiac surgery with CPB, an autologous PRP was prepared using the Haemonetics Component Collection System® by drawing blood from the CPB circuit immediately after CPB was established. The blood samples were taken at three points for examination, A: beginning of surgery, B: immediately after heparin reversal with protamine following discontinuation of CPB, C: after the collected autologous PRP was returned to the patient. Platelet count and platelet aggregation ability were analyzed. RESULTS: The mean platelet count in autologous PRP was 5.5 (range: 3-14) units. Platelet count decreased by 115.0 (±27.3) × 1000/µl from A to B and increased by 27.3 ± 17.2 (× 1000/µl) from B to C. When platelet aggregation was measured by Adenosine Diphosphate (ADP) 3.0 µM, it decreased by 42.6% ± 12.1% from A to B and increased by 8.7% ± 7.4% from B to C. CONCLUSIONS: Autologous PRP can be safely collected by drawing blood from the CPB circuit, platelet count and aggregation ability significantly decreased after CPB including autologous PRP collection. Some improvement was detected in the number of the platelets count and platelet aggregation ability by administrating an autologous PRP even if autologous PRP is collected from CPB circuit. TRIAL REGISTRATION: UMI-CTR, UMIN000023776 . Registered 1 October 2016.

Effects of cardiopulmonary bypass with low-priming volume on clinical outcomes in children undergoing congenital heart disease surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) with high-priming volume can significantly activate the inflammatory response and increse the usage of packed red blood cells (PRBCs). As risks and complications related to transfusions are increasing, many cardiac centers are focusing on reducing the priming volume of CPB. In our center, efforts have also been made to reduce the priming volume, and the effects of CPB with low-priming volume on clinical outcomes in children undergoing congenital heart disease (CHD) surgery were investigated in this study to provide referential experiences for pediatric CPB. METHODS: The clinical case data of 158 children undergoing CHD surgery with CPB were collected. The children were divided into the low-priming-volume group (group A, n = 79) and the traditional group (group B, n = 79) according to the priming volume. The amount of PRBCs transfused, the postoperative hematological test results and the clinical outcomes of the two groups were compared by the independent sample t-test or the chi-square test. RESULTS: The amount of PRBCs transfused during CPB and during the whole operation were significantly lower in group A than in group B (p < 0.01), but the hemoglobin (Hb) concentration was higher in group A on the first day after surgery (p < 0.01) and before hospital discharge. However, the latter showed no statistical significant difference. The lowest postoperative platelet count was higher in group A than in group B (p < 0.05). There was no statistical difference in the postoperative inflammatory markers and the main clinical outcomes between the two groups. CONCLUSIONS: The usage of PRBCs in CPB with low-priming volume decreased significantly, but the postoperative Hb concentration and platelet count could still be maintained at a high level, improving the use efficiency of PRBCs. CPB with low-priming volume did not affect the postoperative recovery of patients, so it is worthy of continuous promotion and optimization.

The effect of hypothermia during cardiopulmonary bypass on three electro-encephalographic indices assessing analgesia and hypnosis during anesthesia: consciousness index, nociception index, and bispectral index.

The depth of anesthesia is commonly assessed in clinical practice by the patient's clinical signs. However, during cardiopulmonary bypass and hypothermia, common symptoms of nociception such as tachycardia, hypertension, sweating, or movement have low sensitivity and specificity in the description of the patient nociception and hypnosis, in particular, detecting nociceptive stimuli. Better monitoring of the depth of analgesia during hypothermia under cardiopulmonary bypass will avoid underdosage or overdosage of analgesia, especially opioids. Induced hypothermia has a multifactorial effect on the level of analgesia and hypnosis. Thermoregulatory processes appear essential for the activation of analgesic mechanisms, ranging from a physiological strong negative affiliation between nerve conduction velocity and temperature, until significant repercussions on the pharmacological dynamics of the analgesic drugs, the latter decreasing the clearance rate with a subsequent increase in the effect-site concentrations. Under the hypothesis that deep hypothermia induces massive effects on the analgesia and hypnosis levels of the patient, we studied whether hypothermia effects were mirrored by several neuromonitoring indices: two hypnosis indices, consciousness index and bispectral index, and a novel nociception index designed to evaluate the analgesic depth. In this clinical trial, 39 patients were monitored during general anesthesia with coronary atherosclerosis cardiopathy who were elective for on-pump coronary artery bypass graft surgery under hypothermia. The changes and correlation between the consciousness index, bispectral index, and nociception index with respect to the temperature were compared in different timepoints at basic state, during cardiopulmonary bypass and after cardiopulmonary bypass. While the three neuromonitoring indices showed significant correlations with respect to the temperature, the nociception index and consciousness index showed the strongest sensitivities, indicating that these two indices could be an important means of intraoperative neuromonitoring during induced hypothermia under cardiopulmonary bypass.

Cardioprotective effect of electroacupuncture in cardiopulmonary bypass through apelin/APJ signaling.

Aim Acupuncture, particularly electroacupuncture (EA), can improve the clinical outcomes of cardiopulmonary bypass (CPB) patients; however, the mechanisms remain unclear. This study aimed to examine the effects of EA pre-treatment on myocardial injury after CPB and investigate its potential mechanisms. MAIN METHODS: Male Sprague-Dawley rats were subjected to CPB and divided into Control (sham-operated), CPB, and EA (CPB + EA) groups. In the EA group, rats were treated with EA at the "PC6" acupoint for 30 min before being subjected to CPB. At 0.5, 1, and 2 h after CPB, the expression levels of plasma cardiac troponin I (cTnI) and lactate dehydrogenase (LDH), and myeloperoxidase (MPO) activity, TNFα, IL-1ß, reduced glutathione (GSH), oxidized glutathione (GSSH), and the ratio of GSH/GSSH in the myocardial tissue were measured. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining. The expression of cleaved caspase-3 was detected by immunofluorescence. The expression of apelin, APJ, AKT, p-Akt, ERK1/2, and p-ERK1/2 was determined using western blotting. KEY FINDINGS: Decreased myocardial injury marker levels, myocardial apoptosis, oxidative stress, and the inflammatory response were found in the EA group compared with the CPB group. The expression levels of apelin, APJ, and p-Akt/AKT were increased in the EA group, and the p-ERK1/2/ERK1/2 level was decreased. SIGNIFICANCE: This study showed that EA pre-treatment can protect the heart from damage following CPB, which might be mainly mediated by restoring the apelin/APJ signaling pathway.

A survey of practices during cardiopulmonary bypass in India: An Indian association of cardiovascular and thoracic anesthesiologist endeavor.

Context: Cardiac anesthesiologists play a key role during the conduct of cardiopulmonary bypass (CPB). There are variations in the practice of CPB among extracorporeal technologists in India. Aims: The aim of this survey is to gather information on variations during the conduct of CPB in India. Settings and Design: This was an online conducted survey by Indian College of Cardiac Anaesthesia, which is the research and academic wing of the Indian Association of Cardiovascular Thoracic Anaesthesiologists. Subjects and Methods: Senior consultants heading cardiac anesthesia departments in both teaching and nonteaching centers (performing at least 15 cases a month) were contacted using an online questionnaire fielded using SurveyMonkey™ software. There were 33 questions focusing on institute information, perfusion practices, blood conservation on CPB; monitoring and anesthesia practices. Results: The response rate was 74.2% (187/252). Fifty-one (26%) centers were teaching centers; 18% centers performed more than 1000 cases annually. Crystalloid solution was the most common priming solution used. Twenty-three percent centers used corticosteroids routinely; methylprednisone was the most commonly used agent. The cardioplegia solution used by most responders was the one available commercially containing high potassium St. Thomas solution (55%), followed by Del Nido cardioplegia (33%). Majority of the responders used nasopharyngeal site to monitor intraoperative patient temperature. Antifibrinolytics were commonly used only in patients who were at high risk for bleeding by 51% of responders, while yet, another 39% used them routinely, and 11% never did. About 59% of the centers insist on only fresh blood (<7 days old) when blood transfusion was indicated. The facility to use vaporizer on CPB was available in 62% of the centers. All the teaching centers or high volume centers in India had access to transesophageal echocardiography probe and echo machine, with 51% using them routinely and 38% using them at least sometimes. Conclusions: There is a wide heterogeneity in CPB management protocols among various Indian cardiac surgery centers. The survey suggests that adherence to evidence-based and internationally accepted practices appears to be more prevalent in centers that have ongoing teaching programs and/or have high volumes, strengthening the need to devise guidelines by appropriate body to help bring in uniformity in CPB management to ensure patient safety and high quality of clinical care for best outcomes.

Ultrafiltration and reinfusion of residual cardiopulmonary bypass pump blood: A prospective non-randomized controlled study.

The aim of the study was to investigate whether processing residual pump blood with ultrafiltration could increase the increment of hemoglobin after residual pump blood reinfusion and evaluate its influence on plasma-free hemoglobin (pFHb) level and postoperative renal function. Sixty adult patients undergoing elective cardiac surgery with cardiopulmonary bypass were assigned to 2 groups, based on pump blood processing strategy: ultrafiltration plus reinfusion (n = 30) or reinfusion (control; n = 30). Increment in hemoglobin and pFHb after reinfusion (ΔHgb, ΔpFHb), reinfusion volume, postoperative chest drainage volume (first 24 h), duration of mechanical ventilation, changes in serum creatinine, and prevalence of AKI were compared between the 2 groups. Higher levels of both ΔHgb and ΔpFHb were observed after reinfusion in the ultrafiltration group [ΔHgb 1.8 ± 1.1 g/dL vs. 1.2 ± 0.6 g/dL, P = 0.03, ΔpFHb 100 (0, 200) mg/L vs. 0 (-100, 0) mg/L, P = 0.03]. The reinfusion volume was lower in the ultrafiltration group [550 (325, 615) mL vs. 1000 (900, 1180) mL, P < 0.001]. No differences were found in postoperative chest drainage volume (first 24 h), duration of mechanical ventilation, changes in serum creatinine, and prevalence of AKI. Compared to the unprocessed group, ultrafiltration before reinfusion of residual pump blood improved the hemoglobin level and reduced volume loading. Despite an increase in pFHb, the processing procedure was not related to postoperative kidney injury.

A comparison of haemostatic biomarkers during low-risk patients undergoing cardiopulmonary bypass using either conventional centrifugal cell salvage or the HemoSep device.

BACKGROUND: Cardiac surgery using cardiopulmonary bypass (CPB) is associated with a coagulopathy due to haemodilution, thrombocytopenia and platelet dysfunction and the activation of coagulation and fibrinolysis, despite the use of large doses of unfractionated heparin. Conventional red cell salvage may exacerbate post-operative bleeding as plasma containing haemostatic factors is discarded. We hypothesized that a novel cell salvage device (HemoSep) may attenuate haemostatic changes associated with red cell salvage. We studied haemostatic markers following autologous transfusion from conventional cell salvage or the HemoSep device. METHODS: This randomised, controlled trial compared haemostatic markers in patients undergoing coronary artery bypass grafting or aortic valve replacement who received autologous blood returned from cell salvage (control) or HemoSep (study). Blood samples were taken pre-operatively, end of CPB, post-transfusion of salvaged blood and 3 hours post-operatively and analysed for full blood count (FBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer and endogenous thrombin potential (ETP). RESULTS: Fifty-four patients were recruited (n=28 control, n=26 study). Processed blood volume for transfusion was significantly (p<0.001) higher in the HemoSep group. In the HemoSep group, the PT was shorter (18.7±0.3 vs 19.9±0.3 sec; p<0.05) post-operatively and the aPTT was longer (48.6±3.8 vs 37.3±1.0 sec; p<0.01) following autologous transfusion. In the control group, D-dimer and ETP levels were higher (1903±424 vs.1088±151; p<0.05 and 739±46 vs. 394±60; p<0.001, respectively) following autologous transfusion. CONCLUSIONS: Although centrifuged cell salvage is known to adequately haemoconcentrate and remove unwanted substrates and bacteriological contamination, the process can exacerbate coagulopathy. The HemoSep device demonstrated some increase in haemostatic markers when used in low-risk cardiac surgery patients.

Low-level light therapy reduces platelet destruction during extracorporeal circulation.

Extracorporeal circulation causes many deleterious effects on blood cells. Low-level light therapy (LLLT) in the red/near-infrared spectral range is known for its cytoprotective properties but its use during cardiopulmonary bypass (CPB) has not yet been studied. We aimed to assess whether LLLT protects platelets during CPB. 24 pigs were connected to 1-hour-CPB and observed for the next 23 hours. In 12 animals, blood circulating through the oxygenator was treated with LLLT. Platelet count and function were monitored throughout the experiment. The decrease in platelet count was greater in the control group, especially during CPB and after 24 hours. In LLLT group CD62P expression remained quite stable up to the 12th hour of the experiment, whereas in the control group it continuously decreased till the end of observation. Platelets in the control group were more prone to aggregation in the postoperative period than at the beginning of the experiment, whereas platelets in the LLLT group aggregated similarly or less intense. Limitation of platelet loss, pattern of aggregation and CD62P expression suggest that LLLT may stabilize platelet function during CPB and diminish the negative effects associated with the interaction of cells with an artificial surface.

Effect of Shenmai injection on cognitive function after cardiopulmonary bypass in cardiac surgical patients: a randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac surgery that influences the clinical outcomes and quality of life of patients. This study aimed to evaluate the effects of Shenmai injection (SMI) on POCD of patients who underwent cardiac valve replacement under cardiopulmonary bypass (CPB). METHODS: This prospective, randomized, controlled trial was conducted from September 2014 to January 2017. Eighty-eight patients receiving cardiac valve replacement under CPB were randomized into the control (C) or the SMI (S) group. SMI (0.6 mL/kg) was administered intravenously from the time of anesthesia induction to the beginning of CPB. Cognitive function was assessed at 3 days before surgery and 3 days, 7 days, and 1 month after surgery using the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) score. The serum levels of neuroglobin (Ngb), hypoxia-inducible factor-1α (HIF-1α), and neuron-specific enolase (NSE) were measured at 30 min after induction (T0), immediately after the endonasal temperature rewarmed to 36 °C (T1), and 1 h (T2), 6 h (T3), 24 h (T4), 48 h (T5), and 72 h (T6) after CPB. RESULTS: Compared with the baseline values at T0, the serum Ngb levels in group C were significantly decreased at T1-2 and then increased at T3-6, while the levels in group S were decreased at T1-2 and increased at T4-6, compared to group C (p < 0.05). The serum HIF-1α levels at T1-4 and the serum NSE levels at T1-6 were significantly increased in both groups (p < 0.05). The serum levels of Ngb at T3, HIF-1α at T1-3, and NSE at T3-4,6 were lower in group S, compared to group C (p < 0.01). The MoCA-BJ scores were decreased at 3 and 7 days after surgery in both groups, and the MoCA-BJ scores in group S were higher than those in group C at 3 and 7 days after surgery (p < 0.01). CONCLUSION: Cognitive function is impaired postoperatively in patients who have undergone cardiac valve replacement under CPB. In addition, treatment with the traditional Chinese medicine SMI decreases the serum levels of Ngb, HIF-1α, and NSE as well as attenuates cognitive dysfunction. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov as ChiCTR-TRC-14004373 on March 11, 2014.

Feasibility of autologous intraoperative blood collection and retransfusion in small children with complex congenital heart defects undergoing cardiopulmonary bypass.

INTRODUCTION: Allogeneic blood product transfusion is common in pediatric patients undergoing cardiopulmonary bypass although it is associated with an increased risk for adverse events. Furthermore, numerous donor exposures may affect future blood transfusion needs and human leukocyte antigen matching for patients who may ultimately require cardiac transplantation. Autologous intraoperative blood collection and retransfusion is a known method of blood preservation, but has not been extensively practiced in pediatric patients. In this study we assess the feasibility of this blood conservation technique in small children with complex congenital heart defects undergoing cardiopulmonary bypass. METHODS: After Institutional Review Board approval, we retrospectively reviewed the medical records of children weighing <10 kg who underwent cardiopulmonary bypass over a 2-year period. Eighteen patients underwent autologous intraoperative blood collection and retransfusion and comprised the study group. Eighteen control patients were chosen by a 1:1 matched design using preoperative hematocrit, surgical procedure, and body weight. Multiple corresponding demographic and surgical variables, transfusion data, and clinical outcomes were compared. RESULTS: Patient demographics, operative parameters and preoperative laboratory, and coagulation values were similar between the two groups. Despite the removal of autologous blood, study patients did not require more inotropic support prior to cardiopulmonary bypass. They also did not experience a significant increase in bleeding as measured by 24-hour postoperative chest tube output. Study patients were exposed to significantly fewer donor units intraoperatively and within the first 24 hours postoperatively. DISCUSSION: The use of autologous intraoperative blood collection and retransfusion is a feasible option for small children with complex congenital heart defects undergoing cardiopulmonary bypass. Study patients received significantly fewer donor exposures without an increase in postoperative bleeding. Children who require multiple cardiac surgeries or eventually transplantation could benefit from this blood conservation technique.

The Impact of Three Different Wash Solutions on Autotransfusion Products.

Many blood conservation techniques and strategies have been implemented to aid in decreasing the use of allogenic blood utilization during pediatric cardiothoracic surgery. Use of techniques, such as acute normovolemic hemodilution, retrograde autologous prime, venous autologous prime, and autotransfuion, may lead to a decrease in the need for allogenic blood products. Autotransfusion has become a standard of care for all cardiothoracic surgical procedures requiring cardiopulmonary bypass (CPB). Although widely used, there is still debate over which wash solution will produce the most physiologically normal autotransfusion product. Pediatric patients can be at a higher risk for electrolyte imbalance intraoperatively and postoperatively. In an attempt to minimize this, we sought out to evaluate three different wash solutions and how they would affect the final autotransfusion product. This comparison consisted of three wash solutions; .9% sodium chloride, Normosol-R™, and Plasma-Lyte A. Based on the evaluation of all wash solutions, Plasma-Lyte A produced the most physiological normal final autotransfusion product in regards to electrolytes.

Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass during cardiac surgery leads to impaired microcirculatory perfusion. We hypothesized that vascular leakage is an important contributor to microcirculatory dysfunction. Imatinib, a tyrosine kinase inhibitor, has been shown to reduce vascular leakage in septic mice. We investigated whether prevention of vascular leakage using imatinib preserves microcirculatory perfusion and reduces organ injury markers in a rat model of cardiopulmonary bypass. METHODS: Male Wistar rats underwent cardiopulmonary bypass after treatment with imatinib or vehicle (n=8 per group). Cremaster muscle microcirculatory perfusion and quadriceps microvascular oxygen saturation were measured using intravital microscopy and reflectance spectroscopy. Evans Blue extravasation was determined in separate experiments. Organ injury markers were determined in plasma, intestine, kidney, and lungs. RESULTS: The onset of cardiopulmonary bypass decreased the number of perfused microvessels by 40% in the control group [9.4 (8.6-10.6) to 5.7 (4.8-6.2) per microscope field; P<0.001 vs baseline], whereas this reduction was not seen in the imatinib group. In the control group, the number of perfused capillaries remained low throughout the experiment, whilst perfusion remained normal after imatinib administration. Microvascular oxygen saturation was less impaired after imatinib treatment compared with controls. Imatinib reduced vascular leakage and decreased fluid resuscitation compared with control [3 (3-6) vs 12 ml (7-16); P=0.024]. Plasma neutrophil-gelatinase-associated-lipocalin concentrations were reduced by imatinib. CONCLUSIONS: Prevention of endothelial barrier dysfunction using imatinib preserved microcirculatory perfusion and oxygenation during and after cardiopulmonary bypass. Moreover, imatinib-induced protection of endothelial barrier integrity reduced fluid-resuscitation requirements and attenuated renal and pulmonary injury markers.

Positive impact of retrograde autologous priming in adult patients undergoing cardiac surgery: a randomized clinical trial.

BACKGROUND: Adult cardiac surgery with extracorporeal circulation is known to be associated with increased risk of blood transfusion leading to adverse outcomes. Procedures like retrograde autologous priming (RAP) may reduce these negative side effects. This randomized prospective study was initiated to assess whether RAP using specifically designed RAP bag (Terumo) has immediate effects on patient outcome. METHODS: One hundred eighteen adults undergoing elective CABG or elective aortic valve replacement were randomly assigned by a computer program into two groups: the RAP group (n = 54) in which the retrograde autologous priming was applied and the non-RAP (n = 64) group in which the same setting was used without the possibility to save priming volume. Patient demographics, preoperative characteristics and postoperative outcomes were analyzed for both groups. RESULTS: The primary endpoint defined as rate of intraoperative blood transfusion was significantly reduced in the RAP-group (p = 0.04). The absolute risk reduction for RAP managed patients was 13.5 percent points. There were no significant differences in operation time and blood loss. No deaths and no myocardial infarctions were observed. The number of patients needed to treat to prevent at least one red blood cell transfusion was around 8 (NNT = 7.42). CONCLUSIONS: Retrograde autologous priming is a safe and less invasive procedure which achieves clear benefits for adult cardiac surgery patients. In the light of increasing red blood cell transfusion risks and costs and the wish of patients to avoid a transfusion implementation of retrograde autologous priming is an interesting option. TRIAL REGISTRATION: German Clinical Trials Register ID: DRKS00013512 , registered 04 December 2017.

A red cell preservation strategy reduces postoperative transfusions in pediatric heart surgery patients.

BACKGROUND: Blood transfusion has well-documented adverse effects. As part of a blood conservation initiative at our center, we began routine use of cell saver for all congenital heart surgery performed on cardiopulmonary bypass since 2014. AIMS: This study aimed to compare transfusion rates prior to, and in the first and second year after this initiative. We hypothesized that cell saver use would decrease transfusion requirements in second year after use of the cell saver compared to the pre cell saver group. METHODS: Consecutive patients under 18 years undergoing congenital heart surgery on cardiopulmonary bypass were retrospectively analyzed as 3 one-year cohorts defined above. We excluded patients who required mechanical support or reoperation at index admission. Baseline characteristics, and use of blood intraoperatively and postoperatively were compared between groups. RESULTS: The 3 groups had similar baseline characteristics. Blood use was significantly lower in year 2 after cell saver initiation as compared to the pre cell saver group both intra- and postoperatively. The median difference in volume of intraoperative blood transfusion was lower by 138 mL/m2 (-266, -10 mL/m2 ) in year 2 when compared to the pre cell saver group. Similarly, the proportion of subjects requiring red blood cell transfusion postoperatively on day of surgery was lower by 10% (-15%, -6%). CONCLUSION: Standardized use of cell saver significantly decreased perioperative blood use in children undergoing cardiac surgery at our center. A risk-adjusted transfusion threshold for children undergoing heart surgery needs to be developed to further decrease exposure to blood products and associated costs.

Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass.

The purpose of this study was to investigate the population pharmacokinetics (PK) of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples from 78 patients were analyzed. The PK for cefuroxime were best described by a two-compartment model with between-subject variability on clearance, the volume of distribution of the central compartment, and the volume of distribution of the peripheral compartment. The clearance of cefuroxime was related to creatinine clearance (CLCR). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of the percentage of the time that the free concentration is maintained above the MIC during a dosing interval (fTMIC) of 65% for an MIC of 8 mg/liter in patients with a CLCR of 30, 60, or 90 ml/min, whereas this dosing regimen failed to achieve the PK-PD target in patients with a CLCR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CLCR values required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CLCR values (≤30 ml/min).

Neutralizing IL-6 reduces heart injury by decreasing nerve growth factor precursor in the heart and hypothalamus during rat cardiopulmonary bypass.

AIMS: To investigate whether the expression of nerve growth factor precursor (proNGF) changes during cardiopulmonary bypass (CPB) and whether neutralizing interleukin-6 (IL-6) during CPB has cardiac benefits. MAIN METHODS: Thirty patients undergoing CPB were recruited and their serum proNGF and troponin-I (TNI) were detected. In addition, rats were divided into three groups: CPB group, CPB with cardiac ischemia-reperfusion (IR) group, and a control group. The pre-CPB standard deviation of N-N intervals (SDNN) and post-CPB SDNN were compared. At the end of CPB, nerve peptide Y (NPY), acetylcholinesterase, cell apoptosis, and proNGF protein expression were measured in the heart and hypothalamus. Another rat cohort undergoing CPB was divided into two groups: an anti-IL-6 group with IL-6 antibody and a control group with phosphate buffer solution. At the end of CPB, serum hs-troponin-T and cardiac caspases 3 and 9 were detected. NPY and proNGF in the heart and hypothalamus were detected. KEY FINDINGS: In patients, serum proNGF increased during CPB, and the concentration was positively correlated with TNI. In rats, cardiac autonomic nervous function was disturbed during CPB. More apoptotic cells and higher levels of proNGF were found in the heart and hypothalamus in the CPB groups than in the control groups. Neutralizing IL-6 was beneficial to lower cardiac injury by decreasing proNGF and apoptosis. SIGNIFICANCE: CPB induced changes in proNGF in the heart and hypothalamus. Suppressing inflammation attenuated myocardial apoptosis and autonomic nerve function disturbance in CPB rats, likely due in part to regulation of proNGF in the heart and hypothalamus.

A BMI >35 does not protect patients undergoing cardiac bypass surgery from red blood cell transfusion.

The effect of obesity on allogeneic intraoperative blood product transfusion in patients undergoing coronary artery bypass graft surgery (CABG) is poorly understood. We analyzed the influence of obesity on the risk of intraoperative red blood cell (RBC) transfusion among 45,200 consecutive non-reoperative CABG procedures from a multi-institutional perfusion database. A body mass index (BMI) in obese I category was associated with a 9.9% decrease in transfusion risk (p<0.05). Compared to patients with a normal BMI, obese I and obese III patients do not have any change in the relative risk of RBC transfusion. Overweight and mild obesity have a protective role in reducing intraoperative blood transfusion during cardiopulmonary bypass (CPB) surgery. However, logistic regression analysis showed that much of the observed reduction in transfusion rates for obese patients can be accounted for by other known confounds. The lack of a linear effect of increasing BMI on blood transfusion risk is a novel finding and warrants further investigation.

Carvedilol-Enriched Cold Oxygenated Blood Cardioplegia Improves Left Ventricular Diastolic Function After Weaning From Cardiopulmonary Bypass.

OBJECTIVES: To investigate whether adding carvedilol, a nonselective ß- and selective α1-receptor blocking agent with antioxidant properties, to oxygenated blood cardioplegia improves myocardial function after weaning from bypass. DESIGN: A randomized controlled study. SETTING: A university laboratory. PARTICIPANTS: Twenty anesthetized pigs, Norwegian Landrace. INTERVENTIONS: On cardiopulmonary bypass, cardiac arrest was induced with cold (12°C), oxygenated blood cardioplegia, enriched with carvedilol or vehicle, and repeated every 20 minutes. After 100 minutes, the heart was reperfused and weaned. MEASUREMENTS AND MAIN RESULTS: Left ventricular function was evaluated with pressure-volume loops, local myocardial systolic strain, and strain rate from Speckle tracking analysis and multilayer short-axis tissue Doppler Imaging. In the carvedilol group, the load-independent logarithmic end-diastolic pressure volume relationship, ß, decreased from 1 to 3 hours of reperfusion and was low, 0.028±0.004 v 0.042±0.007 (p<0.05) in controls at 3 hours, demonstrating improved left ventricular compliance. The diastolic relaxation constant τ was decreased, 28.9±0.6 ms v 34.6±1.3 ms (pg<0.035), and dP/dtmin was more negative,-1,462±145 mmHg/s v-1,105±105 mmHg/s (pg = 0.024), for carvedilol v control group. The systolic variables, preload recruitable stroke work and end-systolic pressure-volume relationship, did not differ between groups, neither did left ventricular systolic strain and strain rate. Myocardial oxidative stress, measured as tissue levels of malondialdehyde, was reduced by carvedilol, 0.19±0.01 compared to 0.24±0.01 nmol/mg (p = 0.004) in controls. CONCLUSIONS: Carvedilol added to blood cardioplegia improved diastolic cardiac function and reduced oxidative stress during the first 3 hours after reperfusion in a porcine model, with 100 minutes of cardioplegic arrest.