Plasma hyperosmolality during cardiopulmonary bypass is a risk factor for postoperative acute kidney injury: Results from double blind randomised controlled trial.

INTRODUCTION: The study objective was to investigate whether a Ringer's acetate based priming solution with addition of Mannitol and sodium concentrate increases the risk of cardiac surgery associated kidney injury (CSA-AKI). METHODS: This is a double blind, prospective randomized controlled trial from a single tertiary teaching hospital in Sweden including patients aged ≥65 years (n = 195) admitted for routine cardiac surgery with cardiopulmonary bypass. Patients in the study group received Ringer's acetate 1000 mL + 400 mL Mannitol (60 g) + sodium chloride 40 mL (160 mmol) and heparin 2 mL (10 000 IU) 966 mOsmol (n = 98), while patients in the control group received Ringer's acetate 1400 mL + heparin 2 mL (10 000 IU), 388 mOsmol (n = 97) as pump prime. Acute kidney injury was analysed based on the Kidney Disease Improving Outcomes (KDIGO 1-3) definition. RESULTS: The overall incidence of CSA-AKI (KDIGO stage 1) was 2.6% on day 1 in the ICU and 5.6% on day 3, postoperatively. The serum creatinine level did not show any postoperative intergroup differences, when compared to baseline preoperative values. Six patients in the Ringer and five patients in the Mannitol group developed CSA-AKI (KDIGO 1-3), all with glomerular filtration rates <60 mL/min/1.73 m2. These patients showed significantly higher plasma osmolality levels compared to preoperative values. Hyperosmolality together with patient age and the duration of the surgery were independent risk factors for postoperative acute kidney injury (KDIGO 1-3). CONCLUSIONS: The use of a hyperosmolar prime solution did not increase the incidence of postoperative CSA-AKI in this study, while high plasma osmolality alone increased the associated risk by 30%. The data suggests further examination of plasma hyperosmolality as a relative risk factor of CSA-AKI.

Is a hyperosmolar pump prime for cardiopulmonary bypass a risk factor for postoperative delirium? A double blinded randomised controlled trial.

Objective: Postoperative delirium (POD) is common after cardiac surgery. We have previously identified plasma sodium concentration and the volume of infused fluids during surgery as possible risk factors. Both are linked to the selection and composition of the pump prime used for cardiopulmonary bypass (CPB). Present study aims to examine whether hyperosmolality increases the risk for POD. Design: Patients ≥65 years (n = 195) scheduled for cardiac surgery were prospectively enrolled into this double blinded randomised clinical trial. Study group received a pump prime containing mannitol and ringer-acetate (966 mOsmol) (n = 98) vs. ringer-acetate (388 mOsmol) (n = 97) in the control group. Postoperative delirium was defined according to DSM-5 criteria based on a test-battery pre- and postoperatively (days 1-3). Plasma osmolality was measured on five occasions and coordinated with the POD assessments. The primary outcome was the POD incidence related to hyperosmolality as the secondary outcome. Results: The incidence of POD was 36% in the study group and 34% in the control group, without intergroup difference (p=.59). The plasma osmolality was significantly higher in the study group, both on days 1 and 3 and after CPB (p<.001). Post hoc analysis indicated that high osmolality levels increased the risk for delirium on day 1 by 9% (odds ratio (OR) 1.09, 95% CI 1.03-1.15) and by 10% on day 3 (OR 1.10, 95% CI 1.04-1.16). Conclusions: Use of a prime solution with high osmolality did not increase the incidence of POD. However, the influence of hyperosmolality as a risk factor for POD warrants further investigation.

Our initial experience of monitoring the autoregulation of cerebral blood flow during cardiopulmonary bypass.

BACKGROUND: Cerebral blood flow (CBF) is believed to be relatively constant within an upper and lower blood pressure limit. Different methods are available to monitor CBF autoregulation during surgery. This study aims to critically analyze the application of the cerebral oxygenation index (COx), one of the commonly used techniques, using a reference to data from a series of clinical registrations. METHOD: CBF was monitored using near-infrared spectroscopy, while cerebral blood pressure was estimated by recordings obtained from either the radial or femoral artery in 10 patients undergoing cardiopulmonary bypass. The association between CBF and blood pressure was calculated as a moving continuous correlation coefficient. A COx index > 0.4 was regarded as a sign of abnormal cerebral autoregulation (CA). Recordings were examined to discuss reliability measures and clinical feasibility of the measurements, followed by interpretation of individual results, identification of possible pitfalls, and suggestions of alternative methods. RESULTS AND CONCLUSION: Monitoring of CA during cardiopulmonary bypass is intriguing and complex. A series of challenges and limitations should be considered before introducing this method into clinical practice.

Productivity in relation to organization of a surgical department: a retrospective observational study.

BACKGROUND: Responsible and efficient resource utilization are important factors in healthcare. The aim of this study was to investigate how total case time differs between two differently organized surgical departments. METHODS: This is a retrospective observational study of a cohort of patients undergoing elective surgery for breast cancer or malignant melanoma in a university hospital setting in Sweden. All patients were operated on by the same set of surgeons but in two different surgical departments: a general surgery (GS) and a cardiothoracic (CT) surgery department. Patients were selected to the two departments from a waiting list in the order of referral for surgery. The effect of being operated on at the CT department compared to the GS department was estimated by linear regression. RESULTS: The final study cohort comprised 349 patients in the GS department and 177 patients in the CT department. Both groups were similar regarding surgical procedures, American Society of Anesthesiologists' score, body mass index, age, sex, and the skill level of the operating surgeon. These covariates were included in the linear regression model. The total case time, defined by the Procedural Time Glossary as room set-up start to room clean-up finish, was significantly shorter for the patients who underwent a surgical procedure at the CT department compared to the GS department, even after adjusting for the background characteristics of the patients and surgeon. After adjusting for the selected covariates, the average difference in total case time between the two departments was - 30.67 min (p = 0.001). CONCLUSIONS: A significantly shorter total case time was measured for operations in the CT department. Plausible explanations may be more beneficial organizational factors, such as staffing ratio, skill mix in the operating room team, and working behavioral aspects regarding resource utilization.

Can We Rely on the Activated Clotting Time to Measure Heparin Anticoagulation? A Clinical Evaluation of Two ACT Monitors.

The sensitivity to heparin during cardiopulmonary bypass (CPB) is determined by patient-specific characteristics and is assessed by the whole blood activated clotting time (ACT). We aimed to examine reliability measures between two different ACT monitors using Bland-Altman analysis: bias should not exceed 50 ± 50 seconds for measurements performed during CPB or 10 ± 10 seconds before and after CPB. The ACT response should be linear in relation to the concentration of heparin in plasma. Twenty patients (n = 20) aged 20-80 years and admitted for coronary artery bypass surgery were enrolled to this clinical observational study. ACT values and antifactor Xa were sampled: 1) before induction of anesthesia, 2) after heparin bolus, 3) during CPB at the start of rewarming, 4) at weaning from CPB, and 5) after heparin reversal. The evaluation comprised the Hemostasis Management System Plus™ (HMS, Medtronic Inc., Minneapolis, MN) and i-STAT™ (Abbott, Point of Care Inc., Princeton, NJ). Bias for the HMS Plus™ vs. i-STAT™ was +105 ± 119 seconds for measurements during CPB and +2.8 ± 11.7 seconds before and after CPB. Associated limits of agreement for the observed bias were ±235 and ±23 seconds, respectively. Inter-device correlation of ACT values was .46 (p < .001) during CPB; otherwise .48 (p = .02). Both devices produced ACT values unrelated (<10%) to the measured heparin concentration. The use of multivariable regression analysis demonstrated an independent association between the ACT measurement and hematocrit, however, not with the plasma concentration of heparin. ACT monitors demonstrate unacceptable bias differences, combined with wide limits of agreement. The ACT response correlated with hematocrit, but not with the actual heparin concentration.

Cardiopulmonary bypass and dual antiplatelet therapy: a strategy to minimise transfusions and blood loss.

BACKGROUND: Patients with preoperative dual antiplatelet therapy prior to coronary artery bypass surgery are at risk of bleeding and blood component transfusion. We hypothesise that an optimised cardiopulmonary bypass strategy reduces postoperative blood loss and transfusions. METHODS: In total, 60 patients admitted for coronary artery bypass grafting with ticagrelor and aspirin medication withdrawn <96 hours before surgery were prospectively randomised into two equal sized groups. Cardiopulmonary bypass combined a closed Cortiva® heparin-coated circuit with low systemic heparinisation (activated clotting time < 250 seconds) and intraoperative cell salvage in the study group, whereas the control group used a Balance® coated open circuit, full systemic heparinisation (activated clotting time > 480 seconds) and conventional cardiotomy suction. This perfusion strategy was evaluated by the chest drain volume after 24 hours, perioperative haemoglobin and platelet loss accompanied by global coagulation assessments. RESULTS: Patients in the study group demonstrated significantly better outcomes signified by lower blood loss 554 ± 224 versus 1,100 ± 989 mL (p < 0.001), reduced packed red cell transfusion 7% versus 53% (p < 0.001), reduced haemoglobin -28 ± 15 versus -40 ± 14 g/L (p = 0.004) and platelet loss -35 ± 36 versus -82 ± 67 × 109/L (p = 0.001). Indices of rotational thromboelastometry indicated shorter clotting times within the internal and external pathways. Adenosine diphosphate activated platelet function was within normal range based on Multiplate® aggregometry, while ROTEM® platelet analyses indicated inhibited function both preoperatively and post-bypass. Platelet inhibition by aspirin was verified throughout the perioperative period. Platelet function showed no intergroup differences. CONCLUSION: A stringent perfusion strategy reduced blood loss and transfusions in dual antiplatelet therapy patients requiring urgent surgery.

Cardiopulmonary bypass prime composition: beyond crystalloids versus colloids.

INTRODUCTION: In the literature addressing cardiopulmonary bypass (CPB) prime composition, there is a considerable lack of discussion concerning plasma osmolality changes induced by using a hyperosmolar prime. With this study, we try to determine the magnitude and temporal relationship of plasma osmolality changes related to the use of a hyperosmolar CPB prime. METHOD: In this prospective observational study performed in a university hospital setting, we enrolled thirty patients scheduled for elective coronary bypass surgery. Plasma osmolality was analysed on eight occasions. A hyperosmolar CPB prime was used. RESULTS: Analyses of the perioperative plasma osmolality on eight occasions gave the following results: the preoperative osmolality level was normal (297±4 mOsm/kg); a significant increase to 322±17 mOsm/kg (p<0.001) was observed at the commencement of CPB and remained elevated after 30 minutes (310±4 mOsm/kg) and throughout the procedure (309±4 mOsm/kg); the osmolality level returned to 291±5 mOsm/kg on day 1 postoperatively and remained normal the following day (291±6 mOsm/kg). CONCLUSIONS: Use of hyperosmolar CPB prime resulted in a dramatic and instant elevation of the plasma osmolality. Rapid changes in plasma osmolality are associated with organ dysfunction (e.g. osmotic demyelination syndrome), therefore, effects on plasma osmolality related to the CPB prime composition should be recognised. Influence on organ function and clinical outcome warrants further investigations. - Clinical Trials.gov (NCT03060824). Changes in Plasma Osmolality Related to the Use of Cardiopulmonary Bypass With Hyperosmolar Prime. URL: https://clinicaltrials.gov/ct2/show/NCT03060824?term=cpb&cond=osmolality&rank=1.

Disturbances in Oxygen Balance During Cardiopulmonary Bypass: A Risk Factor for Postoperative Delirium.

OBJECTIVE: The aim of this study was to determine risk factors for postoperative delirium after cardiac surgery, specifically associated with the conduct of cardiopulmonary bypass (CPB). DESIGN: Prospective observational study. SETTING: Heart Centre, University Hospital. PARTICIPANTS: The study included 142 patients aged 70 years and older scheduled for elective cardiac surgery with CPB. INTERVENTIONS: Risk factor analysis comprised information collected from the hospital clinical and CPB dedicated databases in addition to the medical chart. Delirium was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criterion using the Mini Mental State Examination and the Organic Brain Syndrome scale. MEASUREMENTS AND MAIN RESULTS: Assessments of delirium diagnosis were executed preoperatively and on the following first and fourth postoperative days. Delirium occurred in 55% (78/142) of the patients. Patients with delirium were identified with significantly higher body weight and body surface area preoperatively, accompanied with longer CPB time, higher positive fluid balance per CPB, and lower systemic pump flow related to body surface area. Furthermore, the duration of the mixed venous oxygen saturation (SvO2) below 75% was significantly longer during CPB. The result from the multivariable logistic regression analysis included the duration of SvO2 below 75%, fluid balance per CPB and patient age as independent risk factors for postoperative delirium. CONCLUSIONS: The influence of the SvO2 level during CPB, fluid balance, and patient age should be recognized as risk factors for postoperative delirium after cardiac surgery in patients 70 years and older.

Implementing a Statistical Model for Protamine Titration: Effects on Coagulation in Cardiac Surgical Patients.

OBJECTIVES: To implement a statistical model for protamine titration. DESIGN: Prospective randomized trial. SETTING: University hospital. PARTICIPANTS: Sixty (n = 30+30) patients scheduled for elective coronary artery bypass surgery were randomly assigned to 2 groups. INTERVENTIONS: Protamine dose calculated according to an algorithm established from a statistical model or to a fixed protamine-heparin dose ratio (1:1). MEASUREMENTS AND MAIN RESULTS: Both groups demonstrated comparable patient demographics and intraoperative data. Coagulation effects were evaluated using rotational thromboelastometry. Using the statistical model reduced (p<0.01) the protamine dose from 426±43 mg to 251±66 mg, followed by significantly (p<0.01) shorter intrinsic clotting time (208±29 seconds versus 244±52 seconds) and stronger clot firmness (p = 0.01), and effects on indices of extrinsic or fibrinogen coagulation pathways were insignificant. Test of residual heparin was negative in all patients after protamine administration, aligned with insignificant (p = 0.27) intergroup heparinase-verified clotting time differences. CONCLUSIONS: The statistical model for protamine titration is clinically feasible and protects the patient from exposure to excessive doses of protamine, with advantageous effects on coagulation as measured using rotational thromboelastometry. Significance regarding clinical outcome is yet to be defined.

Reversal of heparin after cardiac surgery: protamine titration using a statistical model.

OBJECTIVE: To establish a statistical model for determination of protamine dose in conjunction with cardiopulmonary bypass. DESIGN: Prospective. SETTING: University hospital. PARTICIPANTS: Ninety consecutive cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A series of clinically oriented variables were introduced into a statistical model for projection of the protamine dose after cardiopulmonary bypass. The following significant predictors were identified using multivariable regression analysis: The patient's body surface area, the administered dose of heparin, heparin clearance, and the preoperative platelet count. The statistical model projected the protamine dose within 3±23 mg of the point-of-care test used as reference. CONCLUSION: Protamine dosing based on statistical modeling represents an alternative to point-of-care tests.

Can the oxygenator screen filter reduce gaseous microemboli?

Gaseous microemboli (GME) define small bubbles as < 200 microm in size. GME are reported to increase morbidity after cardiopulmonary bypass (CPB) and cardiac surgery. To prevent intrusion of GME into the systemic circulation during CPB, arterial line filtration is generally recommended. New trends in oxygenator design promote location of arterial filtration as an integral part of the oxygenator housing. The present experimental study aimed to evaluate the GME removal properties of an integrated arterial screen filter in a standard microporous oxygenator. The GME properties of Terumo Capiox FX25 with an integrated arterial screen filter was assessed in an experimental setup and compared with Capiox RX25, in which no arterial screen filter is present. A blood analog prime solution was recirculated using a roller pump at 4 and 6 L per minute flow rate, respectively, through a customized CPB circuit comprising oxygenator, reservoir, and connecting tubing. A controlled volume of air was introduced into the circuit. The GME activity was measured and computed using a Gampt BCC200 ultrasonic device placing one probe at the venous inlet and one other at the arterial outlet of the oxygenator. Transmembrane delta values of GME activity were used to calculate the removal efficacy based on counts and volume of GME. Use of screen filtration reduced the GME volume by 99.1% +/- .1% compared with 98.0% +/- .1% for controls at 4 L/min flow rate (p < .001). At 6 L/min, the reduction was 97.9% +/- .1% compared with 97.0% +/- .1% (p < .001). In contrast, the reduction of GME counts was less effective after screen filtration compared with controls: 89.6 +/- .6% versus 91.4 +/- .4% at 4 L/min and 55.6% +/- 1.6% versus 76.0% +/- 1.4% at 6 L/min, respectively (p < .001). The tested oxygenator with incorporated arterial screen filter reduced GME activity based on the calculated volume at the same time as counts of GME increased.

Fat contamination of pericardial suction blood and its influence on in vitro capillary-pore flow properties in patients undergoing routine coronary artery bypass grafting.

OBJECTIVE: Neurologic dysfunction after cardiopulmonary bypass might be due to arterial microembolization. Pericardial suction blood is a possible source of embolic material. Our aim was to determine the capillary-pore flow ability of pericardial suction blood. METHODS: Pericardial suction blood from patients undergoing coronary bypass was collected, and pericardial suction blood and venous blood were sampled at the end of cardiopulmonary bypass and before reinfusion of pericardial suction blood. Pericardial suction blood was (n = 10) or was not (n = 10) prefiltered through a 30-microm cardiotomy screen filter before capillary in vitro analysis. Additionally, in 8 patients the plasma viscosity was measured, and in 5 of these patients, pericardial suction blood capillary deposits were evaluated by using a microscopy-imprint method and fat staining. Capillary flow was tested through 5-microm pore membranes. Tested components were plasma, plasma-eliminated whole-blood resuspension, and leukocyte/plasma-eliminated erythrocyte resuspension. Initial filtration rate and clogging slope expressed the blood-to-capillary interaction. RESULTS: The plasma-flow profile of pericardial suction blood was highly impaired, with a 47% reduction in initial filtration rate (P <.001) and a 142% steeper clogging slope flow deceleration (P <.01). This difference was not due to a change in pericardial suction blood viscosity, such as by free hemoglobin, which corresponded to 5.7% of the erythrocytes. There were no differences in resuspended whole blood or erythrocytes. The cardiotomy filter had no effect. Microscopy suggested the presence of capillary fat deposits in pericardial suction blood that were not seen with venous plasma (P <.05). The pericardial suction blood volume was 458 +/- 42 mL and contained 95.6 +/- 9.3 g/L hemoglobin. CONCLUSIONS: The pericardial suction blood plasma capillary flow function was highly impaired by liquid fat. Pericardial suction blood hemoglobin appears worth recovering after fat removal, despite profound hemolysis.

Fat content in pericardial suction blood and the efficacy of spontaneous density separation and surface adsorption in a prototype system for fat reduction.

OBJECTIVE: Fat embolization to the brain is a potential problem in cardiac surgery, assumed to originate from retransfused pericardial suction blood. Our aim was to measure the fat content in pericardial suction blood and to determine how it can be reduced by simple spontaneous density separation and surface absorption. METHODS: Pericardial suction blood was collected during routine coronary bypass procedures and analyzed for blood-suspended fat and plastic surface binding. A single-chamber bag (n = 10) was compared with a fat-reducing system having a stacked 2-chamber design (n = 10). The fat-reducing system was also tested experimentally (n = 12) with heat-extracted liquid wound fat (1.25%) mixed with mediastinal drain blood. RESULTS: Pericardial suction blood contained 1.5 mL (0.63/2.19) of fat suspended in 418 mL (269/631) of blood (median and quartiles). Surface-bound fat accounted for 24% (12/35). Experimental analysis of the new system revealed an 83% (71/92) fat-reduction rate (P < .001). This rate was confirmed under clinical conditions, suggesting 80% reduction (72/86; P = .001). The fat-reducing system also gave a small but significant red blood cell concentrating effect (P = .001). CONCLUSIONS: It was confirmed that pericardial suction blood contains fat, possibly having an embolic potential. The new system allowed fat to separate by density while pericardial suction blood was temporally retained and incubated. A significant portion of fat adheres to the plastic surface, which added to the reduction. The method appeared efficient. It is proposed that pericardial suction blood should be collected during surgery to evaluate the need for retransfusion and to allow fat reduction.

Fat reduction in pericardial suction blood by spontaneous density separation: an experimental model on human liquid fat versus soya oil.

Pericardial suction blood (PSB) contains mediastinal liquid wound fat with an embolic potential to cause brain damage after cardiopulmonary bypass (CPB). The aims were to measure how fat separates spontaneously from blood by density and how temperature and fat surface adhesion affect the results under experimental conditions. Human liquid fat was heat-extracted from retrieved pericardial fat tissue of coronary artery bypass graft (CABG) patients (n = 10). Human fat or soya oil, 5% and 10%, respectively, were mixed with postoperatively shed mediastinal blood (n = 20). The mixture was loaded into a temperature-controlled (37 degrees C, 20 degrees C, 10 degrees C) vertical separation column. At 1, 2.5, 5 and 10 minutes, the blood was collected in five fractions, representing layers of density separation, followed by centrifugation. Human fat solidified at 8 degrees C. Soya oil remained liquid below 0 degrees C. Soya oil separated fast in water, but was slower in blood. At 10 minutes and 37 degrees C 73 +/- 6% of added soya oil was found in the top 20% fraction. Human fat at 37 degrees C behaved similarly to soya oil, with 58 +/- 2% separation at 10 minutes. However, at lower temperatures the density separation became less efficient (p < 0.001), whereas human fat more effectively adhered to the walls of the column, which added to the removal. In total, 66%-78% of the human fat was removed, depending on temperature. In conclusion, fat in PSB can be reduced by simple density separation and surface adhesion while it is temporarily retained from the CPB circuit.

Mechanisms behind operating room blood transfusions in coronary artery bypass graft surgery patients with insignificant bleeding.

OBJECTIVE: To investigate situations in cardiac surgery when transfusions are sometimes used for indications other than to compensate for surgical bleeding. DESIGN: Retrospective study. SETTING: Cardiac surgery unit at a university teaching hospital. PARTICIPANTS: Patients scheduled for coronary artery bypass graft surgery (n = 2,469). INTERVENTIONS: A subgroup of patients with surgical bleeding of < or = 400 mL (n = 982) was selected to identify mechanisms leading to perioperative erythrocyte transfusion. MEASUREMENTS AND MAIN RESULTS: Bleeding of >400 mL triggered transfusion. At less than this bleeding volume, other indications were noted: unstable angina, use of blood cardioplegia, and bad surgical outcome, such as inotropic support. After exclusion of these predictors and anemic patients, the strongest predictors were female gender (p < 0.001), weight < or = 70 kg (p < 0.001), cardiopulmonary bypass (CPB) time > or = 90 minutes (p = 0.002), CPB cooling < or = 32 degrees C (p = 0.038), and advanced age (p < 0.001). Results from a more detailed study of medical records showed that within its normal concentration range, the operating room-transfused patients had lower hemoglobin levels. When followed postoperatively in the intensive care unit and ward, these patients continued to receive more transfusions (p < 0.05) even though their bleeding in the intensive care unit did not differ from the control subjects. CONCLUSION: Some patients are transfused because of institutional bias of an anticipated need rather than for true surgical bleeding. A concern of hemodilution from standard CPB circuits suggests a possible advantage with low-priming volume for smaller adult female patients.