Cardiopulmonary Bypass Priming Solution Research Articles

A pharmacokinetic framework describing antibiotic adsorption to cardiopulmonary bypass devices.

Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta-lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An exvivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using Bmax (binding capacity), Kd (dissociation constant), and T2off (half-time of dissociation), described cefazolin adsorption. Bmax estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ Kd estimate was 139 mg/L (95% CI 27.0, 283) and the T2off estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with Kd and T2off estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The Bmax was small (< 10%) relative to a typical total patient dose during cardiac surgery supported by CPB. A dose adjustment for cefazolin based solely on drug adsorption is not required. This framework could be extended to other PK studies involving CPB.

Development of new colloid osmotic pressure measurement method using ultrafiltration membrane during cardiopulmonary bypass

Background: Clinical practice of measuring colloid osmotic pressure (COP) was abandoned after correcting hypoosmolarity did not improve overall patient outcomes. However, the use of albumin and colloidal solutions has contributed to maintaining intraoperative and postoperative fluid balance at lower levels. Reduced perioperative fluid balance is consistently reported to have positive effects on clinical outcomes. Priming solutions for cardiopulmonary bypass typically include colloids; however, the optimal type of priming solution has not yet been determined. Stricter COP management may further improve postoperative courses. To achieve this, the widespread adoption of a measurement method suitable for COP monitoring during cardiopulmonary bypass is required. Methods: A test circuit was made which measured COP using an ultrafiltration membrane method based on the changes in hydrostatic pressure that occurs across a semipermeable membrane. We then compared the measurements obtained using this method with colloidal osmometer measurements. Results: COP measurements were obtained for a total of 100 tests (10 times each for 10 test solutions). The evaluation parameters included simultaneous reproducibility, correlation with the colloid osmometer, and measurement time. The results demonstrated high accuracy of the ultrafiltration membrane method, simultaneous reproducibility within 3%, a high positive correlation with the colloid osmometer (correlation coefficient: R2 = 0.99; p &lt; 0.01), and equal time required for measurement. Conclusion: Measuring COP using ultrafiltration membranes solves problems within existing measurement methods. Although further improvements in the method are necessary, it has implications for future research and clinical applications.

Effectiveness of Dexmedetomidine as Myocardial Protector in Children With Classic Tetralogy of Fallot Having Corrective Surgery: A Randomized Controlled Trial

ObjectivesEfficacy of dexmedetomidine as cardioprotective agent in Indonesian children undergoing classic tetralogy of Fallot (TOF) repair with cardiopulmonary bypass (CPB). DesignA prospective, parallel trial utilizing block randomization along with double-blinded preparation of treatment agents by other parties. SettingNational Cardiovascular Center Harapan Kita, Indonesia. Participants66 children with classic TOF scheduled for corrective surgery. No children were excluded. All patients had fulfilled criteria for analysis. Interventions0.5 mcg/kg bolus of dexmedetomidine was added in CPB priming solution, followed by 0.25 mcg/kg/hour maintenance during bypass. Placebo group used normal saline. Follow-ups were up to 30 days. Measurement and Main ResultsTroponin I was lower in the dexmedetomidine (Dex) group at 6 hours (30.48± 19.33 vs. 42.73± 27.16, p = 0.039) and 24 hours after CPB (8.89± 5.42 vs. 14.04± 11.17, p = 0.02). Within similar timeframe, Dexmedetomidine successfully lowered IL-6 (p = 0.03; p = 0.035, respectively). Lactate was lower in the Dex group at 1, 6, and 24 hours after CPB (p = <0.01; p = 0.048; p = 0.035, respectively). Dexmedetomidine increased cardiac output and index from 6 hours after bypass, but vice versa in systemic vascular resistance. Reduction of vasoactive inotropic score was seen during ICU monitoring in the Dex group (p = 0.049). Nevertheless, dexmedetomidine did not significantly affect length of ventilation (p = 0.313), ICU stay (p = 0.087), and mortality (p >0.99). ConclusionsDexmedetomidine during CPB is an effective cardioprotective agent in TOF children having surgery. Postoperative mortality was comparable across groups.

EFFECT OF MANNITOL ON ELECTROLYTES AND ITS RELATION WITH KIDNEY INJURY IN CARDIOPULMONARY BYPASS

The optimal composition of the priming solution used in cardiopulmonary bypass (CPB) during human cardiac surgery is still uncertain. Mannitol is a common component of CPB priming solutions, but its efficacy is debated. To clarify the effect of mannitol on CPB prime solutions, a prospective, randomized, double-blind trial was conducted on 40 patients with sound cardiac and renal functions who were undergoing coronary artery bypass grafting. The trial included two groups: one received Ringer's acetate-based prime (n = 20), and the other received a combination of Ringer's acetate and 200 mL mannitol as prime (n = 20). The study examined changes in renal-related parameters, electrolytes, osmolality, and acid-base balance. Interestingly, no significant differences in osmolality were observed between the Mannitol and Ringer's acetate groups. However, the Mannitol group showed a significant decrease in sodium levels from 138.7±2.8 mmol/L at the start of anesthesia to 133.9±2.6 mmol/L after the initiation of CPB (p &lt;0.001). Renal parameters remained consistent across groups, except for a temporary effect of mannitol on post-surgery urine output (p = 0.003). In conclusion, this study found no significant differences in osmolality between Ringer's acetate-based prime and Mannitol-based prime in individuals with healthy cardiac and renal function. However, the addition of mannitol to the prime resulted in a significant, albeit short-term, reduction in sodium levels. These findings contribute to the ongoing discourse on optimizing CPB prime solutions, especially in cardiac surgical procedures involving mannitol inclusion.

Hemostatic effects of a dextran-based priming solution for cardiopulmonary bypass: A secondary analysis of a randomized clinical trial

IntroductionIntravascular fluids administered to patients may influence hemostasis. In patients undergoing cardiac surgery with cardiopulmonary bypass, the heart-lung machine is primed with 1300 ml of fluid. We assessed postoperative coagulation and platelet function in patients randomized to two different priming solutions, one colloid-based (dextran 40) and one crystalloid-based. Materials and methodsEighty-four elective cardiac surgery patients were randomized to either a dextran-based prime or Ringer's acetate with added mannitol. Blood samples were collected before, and 2 and 24 h after cardiopulmonary bypass. Coagulation was assessed by standard coagulation tests and rotational thromboelastometry. Platelet function was assessed with impedance aggregometry. Bleeding volumes and transfusion requirements were recorded. ResultsComparing the groups 2 h after bypass, the dextran group showed lower hemoglobin concentration, hematocrit, platelet count, and fibrinogen concentration, and higher INR and aPTT, as well as longer clot formation time (+41 ± 21 % vs. +8 ± 18 %, p < 0.001) and a larger reduction in fibrinogen-dependent clot strength (−37 ± 12 % vs. -7 ± 20 %, p < 0.001). Adenosine diphosphate-dependent platelet activation was reduced in the dextran group but not in the crystalloid group 2 h after bypass (−14 ± 29 % vs. -1 ± 41 %, p = 0.041). No significant between-group differences in hemostatic variables remained after 24 h, and no significant differences in perioperative bleeding volumes, re-explorations for bleeding, or transfusion rates were observed. ConclusionsCompared to a crystalloid solution, a dextran-based prime had measurable negative impact on hemostatic variables but no detectable increase in bleeding volume or transfusion requirements in cardiac surgery patients.

Assessment of Clinical and Laboratory Outcomes in Using of Albumin and Fresh Frozen Plasma as Cardiopulmonary Bypass Prime Solutions in Pediatric Arterial Switch Surgery

Background: Cardiopulmonary bypass (CBP) prime solution in pediatric heart surgeries is critical to avoid adverse effects resulting from dilution of coagulation factors, red blood cells, and other plasma protein. This study aimed to evaluate clinical and laboratory outcomes of administration of albumin and fresh frozen plasma (FFP) in CPB prime solution in children candidates for arterial switch surgery.&#x0D; Methods: This cross-sectional study was performed on 30 transposition of the great arteries (TGA) patients, candidates for the arterial switch in Tehran Children's Medical Center, Iran. As CBP prime solution, 15 patients received albumin (1 gr/kg Albumin 20%) and 15 patients received FFP (15 cc/kg). also, clinical and laboratory parameters were measured in different intervals. The statistical analysis were performed by SPSS v.20.&#x0D; Results: The volume platelet infusion in the ICU was higher in FFP-received patients (40.00 ±20.70 ml) than albumin-received patients (26.67 ±25.82 ml; p-value =0.01). Upon entry into ICU, the mean of Hb and Hct in FFP-received patients (11.55 ±0.64 g/l and 34.44 ±2.44 %) was significantly higher than patients who received albumin (11.08 ±0.87 g/l and 31.44 ±3.97 %; p-value =0.04 for both). Upon entry into ICU and also 48 hours after admission into the ICU, the Cr level in the FFP-received group (median: 19 mg/dl) was significantly higher than the albumin-received group (median: 12 mg/dl; p-value =0.03).&#x0D; Conclusion: FFP in CPB prime solution reduces the hemostatic complications and infusion of blood products, as well as to stabilizes Hb and Htc. Therefore, FFP is more suitable as CPB prime solution.

Effect of 4% Albumin Solution vs Ringer Acetate on Major Adverse Events in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass

In cardiac surgery, albumin solution may maintain hemodynamics better than crystalloids and reduce the decrease in platelet count and excessive fluid balance, but randomized trials are needed to compare the effectiveness of these approaches in reducing surgical complications. To assess whether 4% albumin solution compared with Ringer acetate as cardiopulmonary bypass prime and perioperative intravenous volume replacement solution reduces the incidence of major perioperative and postoperative complications in patients undergoing cardiac surgery. A randomized, double-blind, single-center clinical trial in a tertiary university hospital during 2017-2020 with 90-day follow-up postoperatively involving patients undergoing on-pump coronary artery bypass grafting; aortic, mitral, or tricuspid valve surgery; ascending aorta surgery without hypothermic circulatory arrest; and/or the maze procedure were randomly assigned to 2 study groups (last follow-up was April 13, 2020). The patients received in a 1:1 ratio either 4% albumin solution (n = 693) or Ringer acetate solution (n = 693) as cardiopulmonary bypass priming and intravenous volume replacement intraoperatively and up to 24 hours postoperatively. The primary outcome was the number of patients with at least 1 major adverse event: death, myocardial injury, acute heart failure, resternotomy, stroke, arrhythmia, bleeding, infection, or acute kidney injury. Among 1407 patients randomized, 1386 (99%; mean age, 65.4 [SD, 9.9] years; 1091 men [79%]; 295 women [21%]) completed the trial. Patients received a median of 2150 mL (IQR, 1598-2700 mL) of study fluid in the albumin group and 3298 mL (IQR, 2669-3500 mL) in the Ringer group. The number of patients with at least 1 major adverse event was 257 of 693 patients (37.1%) in the albumin group and 234 of 693 patients (33.8%) in the Ringer group (relative risk albumin/Ringer, 1.10; 95% CI, 0.95-1.27; P = .20), an absolute difference of 3.3 percentage points (95% CI, -1.7 to 8.4). The most common serious adverse events were pulmonary embolus (11 [1.6%] in the albumin group vs 8 [1.2%] in the Ringer group), postpericardiotomy syndrome (9 [1.3%] in both groups), and pleural effusion with intensive care unit or hospital readmission (7 [1.0%] in the albumin group vs 9 [1.3%] in the Ringer group). Among patients undergoing cardiac surgery with cardiopulmonary bypass, treatment with 4% albumin solution for priming and perioperative intravenous volume replacement solution compared with Ringer acetate did not significantly reduce the risk of major adverse events over the following 90 days. These findings do not support the use of 4% albumin solution in this setting. ClinicalTrials.gov Identifier: NCT02560519.

Hemostatic Effects of a Dextran-Based Priming Solution for Cardiopulmonary Bypass: A Secondary Analysis of a Randomized Clinical Trial

Hemostatic Effects of a Dextran-Based Priming Solution for Cardiopulmonary Bypass: A Secondary Analysis of a Randomized Clinical Trial

Evaluating the Impact of Cardiopulmonary Bypass Priming Fluids on Bleeding After Pediatric Cardiac Surgery: A Systematic Review and Meta-Analysis

Cardiopulmonary bypass (CPB) predisposes young children to coagulopathy. The authors evaluated possible effects of CPB priming fluids on perioperative bleeding in pediatric cardiac surgery. Meta-analysis and systematic review of previously published studies. Each study was conducted in a surgical center or intensive care unit. Studies investigating patients <18 years without underlying hematologic disorders were included. The authors evaluated randomized controlled trials (RCTs) published between 1980 and 2020 on MEDLINE, EMBASE, PubMed, and CENTRAL databases. The primary outcome was postoperative bleeding; secondary endpoints included blood product transfusion, mortality, and safety. Twenty eligible RCTs were analyzed, with a total of 1,550 patients and a median of 66 patients per study (range 20-200). The most frequently assessed intervention was adding fresh frozen plasma (FFP) to the prime (8/20), followed by albumin (5/20), artificial colloids (5/20), and blood-based priming solutions (3/20). Ten studies with 771 patients evaluated blood loss at 24 hours in mL/kg and were included in a meta-analysis. Most of them investigated the addition of FFP to the priming fluid (7/10). No significant difference was found between intervention and control groups, with a mean difference of -0.13 (-2.61 to 2.34), p=0.92, I2=69%. Further study endpoints were described but their reporting was too heterogeneous to be quantitatively analyzed. This systematic review of current evidence did not show an effect of different CPB priming solutions on 24-hour blood loss. The analysis was limited by heterogeneity within the dataset regarding population, type of intervention, dosing, and the chosen comparator, compromising any conclusions.

Dextran-based priming solution during cardiopulmonary bypass attenuates renal tubular injury-A secondary analysis of randomized controlled trial in adult cardiac surgery patients.

Acute kidney injury (AKI) is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In the present secondary analysis of a blinded randomized controlled trial, we evaluated the effects of a colloid-based versus a conventional crystalloid-based prime on tubular injury and postoperative renal function in patients undergoing cardiac surgery with CPB. Eighty-four adult patients undergoing cardiac surgery with CPB were randomized to receive either a crystalloid- or colloid- (dextran 40) based CPB priming solution. The crystalloid solution was based on Ringer-Acetate plus mannitol. The tubular injury biomarker, N-acetyl-b-D-glucosaminidase (NAG), serum creatinine and diuresis were measured before, during and after CPB. The incidence of AKI was assessed according to the KDIGO criteria. The urinary-NAG/urinary-creatinine ratio rose in both groups during and after CPB, with a more pronounced increase in the crystalloid group (p=.038). One hour after CPB, the urinary-NAG/urinary-creatinine ratio was 88% higher in the crystalloid group (4.7±6.3 vs. 2.5±2.7, p=.045). Patients that received the dextran 40-based priming solution had a significantly lower intraoperative diuresis (p<.001) compared to the crystalloid group. The incidence of AKI was 18% in the colloid and 22% in the crystalloid group (p=.66). Postoperative serum creatinine did not differ between groups. In patients undergoing cardiac surgery with CPB, colloid-based priming solution (dextran 40) induced less renal tubular injury compared to a crystalloid-based priming solution. Whether a colloid-based priming solution will improve renal outcome in high-risk cardiac surgery, or not, needs to be evaluated in future studies on higher risk cardiac surgery patients.

The Choice of Priming Solution for Cardiopulmonary Bypass during Pulmonary Endarterectomy for CTEPH Patients Has Important Impact

<h3>Purpose</h3> Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH). In recent decades, refined surgical PEA technique using cardiopulmonary bypass (CPB) has achieved significant reduction in mortality. Hemodilution generated by crystalloid priming solution in heart surgery causes a number of disadvantages, and no standard for PEA is described. We aim to assess the outcome of CTEPH patients after protocol change for CPB with adding 5% albumin to priming solution during PEA. <h3>Methods</h3> Since changing the CPB protocol in 2018, 28 CTEPH patients were retrospectively compared to a historical control by 1:1 propensity score matching gender, age, PVR (pulmonary vascular resistance) before PEA surgery. The resulting two cohort groups were analysed for intraoperative fluid balance, vasoactive inotropic score (VIS), operative time and their influence on outcome. Regression models of hospitalization, ICU (intensive care unit) and intubation time considered the total blood volume balance as mediator of the effect of the new protocol. <h3>Results</h3> Lower CPB-balance (p<0.001), VIS score (p=0.04), shorter operative time (p=0.03) and hospitalization (p=0.008) were observed in the cohort operated with the new protocol. Postoperative 30 and 90 day mortality and morbidity were similar between groups. Shorter operative time (mean change (mc) 1.4, 95% CI [0.8. 2.0], p< 0.0001) and new protocol (mc -3.68, 95% CI [-5.22, -2.14], p< 0.0001) are independently associated with lower CPB balance, resulting in a beneficial effect on VIS score, ICU, intubation and hospitalization time (mean ratio (mr) 1.12, 1.11, 1.14, 1.05, p<0.0001, p=0.0011, 0.0013, 0.008, respectively). The protocol change shows positive trend with significant impact on hospitalization time (p=0.02). <h3>Conclusion</h3> Priming protocol for CPB with addition of 5% albumin had a beneficial effect on the CPB balance and improved postoperative outcome after PEA for CTEPH patients.

Effect of Albumin Addition to Cardiopulmonary Bypass Prime on Outcomes in Children Undergoing Open-Heart Surgery (EACPO Study)-A Randomized Controlled Trial.

There is a paucity of literature regarding the association of high oncotic priming solutions for pediatric cardiopulmonary bypass (CPB) and outcomes, and no consensus exists regarding the composition of optimal CPB priming solution. This study aimed to examine the impact of high oncotic pressure priming by the addition of 20% human albumin on outcomes. Double-blinded, randomized controlled study was done in the pediatric cardiac intensive care unit of a tertiary care hospital. Consecutive children with congenital heart diseases admitted for open-heart surgery were randomized into two groups, where the study group received an additional 20% albumin to conventional blood prime before CPB initiation. We enrolled 39 children in the high oncotic prime (added albumin) group and 37 children in the conventional prime group. In the first 24-hour postoperative period, children in the albumin group had significantly lower occurrence of hypotension (28.2% vs 54%, P = .02), requirement of fluid boluses (25.6% vs 54%, P = .006), and lactate clearance time (6 vs 9 hours, P < .001). Albumin group also had significantly higher platelet count (×103/µL) at 24 hours (112 vs 91, P = .02). There was no significant difference in intra-CPB hemodynamic parameters and incidence of acute kidney injury. In subgroup analysis based on risk category, significantly decreased intensive care unit stay (4 vs 5 days, P = .04) and hospital stay (5 vs 7 days, P = .002) were found in the albumin group in low-risk category. High oncotic pressure CPB prime using albumin addition might be beneficial over conventional blood prime, and our study does provide a rationale for further studies.

Extracorporeal hemadsorption versus glucocorticoids during cardiopulmonary bypass: a prospective, randomized, controlled trial

Introduction Cardiopulmonary bypass (CPB) surgery initiates systemic inflammatory response syndrome, which in 2-10% of all cases can be considerably severe. This complex chain of events might contribute to the development of postoperative complications. Different therapeutic interventions that can reduce inflammatory reactions during CPB have been used, in hope for improvement of patient outcome after open-heart surgery. Extracorporeal hemadsorption might reduce the inflammatory reaction in CPB surgery. Glucocorticoids, on the other hand, have been used for years during open-heart surgery for alleviation of systemic inflammation after CPB. We compared intraoperative hemadsorption and methylprednisolone, with usual care, during complex cardiac surgery on CPB, for inflammatory responses, hemodynamics, and perioperative course. Methods Seventy-six patients with prolonged CPB were recruited and randomized, with 60 included in the final analysis. The allocation was into three groups: Methylprednisolone group (n=20; 1g of methylprednisolone added in CPB priming solution), Cytosorb group (n=20; CytoSorb® adsorber, Cytosorbents Europe GmbH, Germany, installed in CPB circuit), and Control group (n=20, usual care, neither methylprednisolone nor CytoSorb® during CPB). Pro-inflammatory (TNF-a, IL-1b, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines, complement C5a, CD64 and CD163 expression by immune cells were analyzed within the first five postoperative days, in addition to hemodynamic and clinical outcome parameters. Results Methylprednisolone group, compared to Cytosorb and Control, had significantly lower levels of TNF-a (until end of the surgery, p Discussion In this clinical trial, we have confirmed that intraoperative use of a median dose of methylprednisolone during CPB more effectively ameliorates systemic inflammatory responses after adult cardiac surgery. This is seen by reductions in pro-inflammatory and increases in anti-inflammatory mediators when compared to both uses of CytoSorb® adsorber for hemadsorption and usual treatment (Control). However, methylprednisolone did not provide better short-term clinical outcome. Hemadsorption itself, compared with usual care, caused higher prolonged expression of CD64 on monocytes and higher expression of CD163 on granulocytes, which only lasted until end of surgery. The use of CytoSorb® adsorber seems to be safe and well-tolerated. We haven't observed an association between its application and significant thrombocytopenia or more significant decrease in albumin concentration.

Blood management in a patient with anti-Oka antibody who underwent cardiac surgery using cardiopulmonary bypass: a case report

BackgroundCardiac surgery under cardiopulmonary bypass (CPB) is often associated with massive bleeding and blood transfusion. For patients requiring specific blood products, meticulous blood management is critical to reduce blood loss, as well as the need for transfusion. Here, we have described the intraoperative blood management in a patient with anti-Oka antibody, who underwent cardiac surgery with CPB.Case presentationA 79-year-old woman was scheduled for open aortic valve replacement and tricuspid valve annuloplasty under hypothermic CPB. Her blood type was A RhD(+) Ok(a−), and anti-Oka, an extremely rare antibody against erythrocyte antigen, was detected. Eight units of Ok(a−) frozen thawed red cells (FTRCs), and six units of red blood cells donated by three Ok(a−) individuals were collected just prior to surgery. Although she was anemic, acute normovolemic hemodilution was conducted after anesthesia induction to preserve the autologous whole blood. Four units of FTRCs were loaded in the CPB priming solution, and modified ultrafiltration was adopted during CPB to prevent further hemodilution. After CPB termination, two units of FTRCs, four units of fresh frozen plasma, and ten units of platelet concentrate were intensively transfused, facilitating surgical hemostasis and stable hemodynamics. The autologous whole blood was returned to the patient in the intensive care unit. Since the hemoglobin and hematocrit levels were maintained postoperatively, no additional transfusion was required throughout her hospital stay.ConclusionsMultidisciplinary intraoperative blood management in a patient with anti-Oka antibody facilitated successful cardiac surgery using CPB, along with effective use of limited blood products.

Comparison of plasma-lyte A and trometamol-balanced priming solutions for cardiopulmonary bypass in a swine model: a pilot study

Comparison of plasma-lyte A and trometamol-balanced priming solutions for cardiopulmonary bypass in a swine model: a pilot study

Large volume infusions of hydroxyethyl starch during cardiothoracic surgery may be associated with postoperative kidney injury: propensity-matched analysis

BackgroundThe safety of intraoperative administration of hydroxyethyl starch (HES) has been debated. We hypothesized that intraoperative use of HES is associated with postoperative acute kidney injury (AKI) following cardiopulmonary bypass (CPB).Materials and methodsPatients who underwent cardiothoracic surgery using CPB between 2007 and 2014 were retrospectively reviewed. The incidence of AKI within 7 days after surgery, defined by the Kidney Disease Improving Global Outcome criteria, was compared for patients who did or did not receive 6% (70/0.5) or 6% (130/0.4) HES for anesthesia management before or after CPB. Multivariable logistic regression and propensity matching analysis were performed to examine whether use of HES is associated with postoperative AKI. Outcomes comparing patients receiving HES ≥ 1000 mL and < 1000 mL were also compared.ResultsData from 1976 patients were reviewed. All patients received 70/0.5 HES as a part of the priming solution for CPB. The incidence of postoperative AKI was 28.2% in patients who received HES and 26.0% in patients who did not (p = 0.33). In multivariable analysis, there was no correlation between the use of HES and the incidence of AKI (odds ratio 0.87, 95% CI 0.30–2.58, p = 0.81). Propensity matching showed that the incidence of AKI was not significantly different between 481 patients administered with HES and 962 patients (26.6% vs. 26.9%, p = 0.95) who did not receive HES for anesthesia management. However, peak creatinine levels, needed for renal replacement therapy, and in-hospital mortality were higher, and 28-day hospital-free days were lower in patients receiving HES ≥ 1000 mL than those receiving HES < 1000 mL (p < 0.05).ConclusionsIntraoperative use of HES was not associated with postoperative AKI following CPB. However, administration of large volumes of HES may be associated with kidney-related adverse clinical outcomes.

The use of mannitol in cardiopulmonary bypass prime solution-Prospective randomized double-blind clinical trial.

BackgroundThe optimal prime solution for the cardiopulmonary bypass (CPB) circuit in adult cardiac surgery has not yet been defined. Mannitol is widely used in the priming solution for CPB despite the fact that there is no clear consensus on the role of mannitol in cardiac surgery. The aim of this study was to investigate the effect of mannitol in the CPB prime solution.MethodsThis prospective, randomized, double‐blind study included 40 patients with normal cardiac and renal functions, who underwent coronary artery bypass grafting. One group received a prime based on Ringer's acetate (n = 20), and the other a prime consisting of Ringer's acetate with 200 mL mannitol (n = 20). Changes in osmolality, acid‐base status, electrolytes, and renal‐related parameters were monitored.ResultsNo significant differences were found in osmolality between the Ringer's acetate group and the mannitol group at any time. The mannitol group showed a pronounced decrease in sodium, from 138.7 ± 2.8 mmol/L at anaesthesia onset, to 133.9 ± 2.6 mmol/L after the start of CPB (P < .001). No differences were seen in the renal parameters between the groups, apart from a short‐term effect of mannitol on peroperative urine production (P = .003).ConclusionWe observed no effects on osmolality of a prime solution containing mannitol compared to Ringer's acetate‐based prime in patients with normal cardiac and renal function. The use of mannitol in the prime resulted in a short‐term, significant decrease in sodium level.

Adenosine A2areceptor agonist CGS21680 treatment attenuates cardiopulmonary bypass‑associated inflammatory lung injury in juvenile rats.

The adenosineA2areceptor agonist CGS21680 has been suggested to act as an anti‑inflammatory agent that protects against cardiopulmonary bypass (CPB)‑induced organ injury. However, the therapeutic effects of CGS21680 for CPB‑induced lung injury have not been comprehensively evaluated. Using a juvenile rat model, the present study was designed to evaluated whether CGS21680 attenuates CPB‑induced lung injury. Our juvenile rat CPB model was established by 60min CPB with or without CGS21680 pretreatment (100µg/kg, in the CPB priming solution). Rats in the Sham group only underwent cannulation and heparinization. Serum and pulmonary levels of inflammatory markers and histological features of pulmonary tissues were analyzed. All juvenile rats survived following CPB. Significantly elevated serum levels of tumor necrosis factor‑α (TNF‑α), myeloperoxidase(MPO) and interleukin‑1β(IL‑1β), and decreased glutathione peroxidase (GSH‑PX) levels were observed in the CPB group compared to the Sham group (all P<0.05). TNF‑α, MPO and IL‑1β were significantly decreased, while GSH‑PX was markedly increased in the CGSgroup when compared to the CPBgroup. Consistently, pulmonary tissues from rats in the CPBgroup showed considerable amounts of damaged pneumocytes, severe edema, and increased alveolar macrophages, and significantly higher lung injury scores compared to the controls. Collectively, these changes were all further attenuated by CGS21680. Pretreatment with CGS21680 before CPB attenuated pulmonary injury, which may be related to the anti‑inflammatory effects of CGS21680 downstream of A2areceptor activation.

Pharmacokinetics of cefazolin delivery via the cardiopulmonary bypass circuit priming solution in infants and children

Our aim was to describe the pharmacokinetics of cefazolin in paediatric patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) who received cefazolin for peri-operative surgical prophylaxis in addition to having cefazolin added to the CPB circuit priming solution. Secondary aims were to determine the pharmacodynamic exposure associated with the addition of cefazolin to the CPB priming solution and to assess whether a target cefazolin concentration range for the CPB priming solution could be identified. A multicentre, prospective, open-label pharmacokinetic study was carried out in children from birth to 16 years of age undergoing cardiac surgery. Forty-one patients met the inclusion criteria and accounted for 492 samples for analysis. Cefazolin concentrations were best described by a one-compartment model with weight as a covariate on the volume of distribution (Vd) with allometric scaling. The mean ± standard deviation (SD) total body CL for the birth-6 month cohort was 0.009 ± 0.006 mL/min/kg with a mean ± SD Vd of 0.59 ± 0.26 L/kg, the mean ± SD total body CL for the 7 month-3 year cohort was 0.01 ± 0.005 mL/min/kg with a mean ± SD Vd of 0.79 ± 0.15 L/kg, and the mean ± SD total body CL for the 4-16 year cohort was 0.007 ± 0.004 mL/min/kg with a mean ± SD Vd of 3.4 ± 0.94 L/kg. The median cefazolin loss in the CPB circuit ranged from 78% to 95% and the median patient cefazolin concentration after CPB circuit detachment ranged from 92 to 197 mg/L. These data demonstrate that mixing cefazolin in the CPB circuit priming solution was effective in maintaining cefazolin serum concentrations during surgery. If this practice is utilized, re-dosing of cefazolin during the CPB run and upon CPB circuit detachment is most probably not needed. Larger pharmacokinetic studies are warranted.

Is the use of hydroxyethyl starch as priming solution during cardiac surgery advisable? A randomized, single-center trial.

The use of cardiopulmonary bypass (CPB) leads to increased fluid filtration and edema. The use of artificial colloids to counteract fluid extravasation during cardiac surgery is controversial. Beneficial effects on global fluid loading, leading to better cardiac performance and hemodynamics, have been claimed. However, renal function and coagulation may be adversely affected, with unfavorable impact on outcome following cardiac surgery. Forty patients were randomly allocated to study groups receiving either acetated Ringer's solution (CT group) or hydroxyethyl starch (HES group, Tetraspan®) as CPB priming solution. Fluid balance, bleeding and hemodynamics, including cardiac output, were followed postoperatively. The occurrence of acute kidney injury was closely registered. Two patients were excluded from further analyzes due to surgical complications. Fluid accumulation was attenuated in the HES group (3374 (883) ml) compared with the CT group (4328 (1469) ml) (p=0.024). The reduced perioperative fluid accumulation was accompanied by an increased cardiac index immediately after surgery (2.7 (0.4) L/min/m2 in the HES group and 2.1 (0.3) L/min/m2 in the CT group (p<0.001)). No increase in bleeding could be demonstrated in the HES group. Three patients, all of them in the HES group, experienced acute kidney injury postoperatively. CPB priming with HES solution lowers fluid loading during bypass and improves cardiac function in the early postoperative period. The manifestation of acute kidney injury exclusively in the HES group of patients raises doubts about the use of HES products in conjunction with cardiac surgery. ( https://clinicaltrials.gov/ct2/show/NCT01511120 ).