Response shift after coronary revascularization.

PURPOSE: The aims of this study were to investigate (1) the extent to which response shift occurs among patients with coronary artery disease (CAD) after coronary revascularization, (2) whether the assessment of changes in health-related quality of life (HRQoL), controlled for response shift, yield more valid estimates of changes in HRQoL, as indicated by stronger associations with criterion measures of change, than without controlling for response shift, and (3) if occurrences of response shift are related to patient characteristics. METHODS: Patients with CAD completed the SF-36 and the Seattle Angina Questionnaire (SAQ7) at baseline and 3 months after coronary revascularization. Sociodemographic, clinical and psychosocial variables were measured with the patient version of the New York Heart Association-class, Subjective Significance Questionnaire, Reconstruction of Life Events Questionnaire (RE-LIFE), and HEXACO personality inventory. Oort's Structural Equation Modeling (SEM) approach was used to investigate response shift. RESULTS: 191 patient completed questionnaires at baseline and at 3 months after treatment. The SF-36 showed recalibration and reprioritization response shift and the SAQ7 reconceptualization response shift. Controlling for these response shift effects did not result in more valid estimates of change. One significant association was found between reprioritization response shift and complete integration of having CAD into their life story, as indicated by the RE-LIFE. CONCLUSION: Results indicate response shift in HRQoL following coronary revascularization. While we did not find an impact of response shift on the estimates of change, the SEM approach provides a more comprehensive insight into the different types of change in HRQoL following coronary revascularization.

Microvascular Alterations During Cardiac Surgery Using a Heparin or Phosphorylcholine-Coated Circuit.

OBJECTIVE: Heparin biocompatible coating frequently is used to reduce inflammation and blood coagulation during cardiopulmonary bypass (CPB) in cardiac surgery. Whether heparin coating is protective or damaging to the vascular endothelium is unclear. The authors investigated whether heparin-coated (HC) circuits are associated with better preservation of microcirculatory perfusion and glycocalyx dimensions compared with nonheparin phosphorylcholine-coated (PC) circuits. DESIGN: Prospective, randomized blinded study. SETTING: Tertiary university hospital. PARTICIPANTS: A total of 26 adults undergoing elective coronary artery bypass graft surgery with CPB. INTERVENTIONS: PC (n = 13) versus HC circuits (n = 13). MEASUREMENTS AND MAIN RESULTS: Sublingual microcirculatory perfusion was measured before, during, and after CPB using sidestream dark field imaging and analyzed for perfused vessel density and perfused boundary region, an inverse parameter for glycocalyx dimensions. Onset of CPB was associated with an increase in perfused boundary region in the PC group that continued until the third postoperative day (2.0 ± 0.2 to 2.5 ± 0.2 µm; p = 0.018). This was paralleled by increased plasma syndecan-1 levels in the PC group. Contrastingly, both parameters remained unaltered in the HC group compared with baseline levels. CPB decreased perfused vessel density in both groups (CPB v pre-CPB: PC: 17 ± 2 to 13 ± 2 mm/mm2, p = 0.006; HC: 16 ± 2 to 11 ± 2 mm/mm2, p = 0.003) and remained equally altered in the first 3 postoperative days. CONCLUSION: The use of an HC circuit is associated with better preservation of the endothelial glycocalyx compared with PC circuits, whereas microcirculatory perfusion was disturbed equally in both groups. Hence, CPB-induced microcirculatory perfusion disturbances seem to be coating independent.

Short-term LPS induces aortic valve thickening in ApoE*3Leiden mice.

BACKGROUND: Recently, it was shown that 12 weeks of lipopolysaccharide (LPS) administration to nonatherosclerotic mice induced thickening of the aortic heart valve (AV). Whether such effects may also occur even earlier is unknown. As most patients with AV stenosis also have atherosclerosis, we studied the short-term effect of LPS on the AVs in an atherosclerotic mouse model. METHODS: ApoE*3Leiden mice, on an atherogenic diet, were injected intraperitoneally with either LPS or phosphate buffered saline (PBS), and sacrificed 2 or 15 days later. AVs were assessed for size, fibrosis, glycosaminoglycans (GAGs), lipids, calcium deposits, iron deposits and inflammatory cells. RESULTS: LPS injection caused an increase in maximal leaflet thickness at 2 days (128.4 µm) compared to PBS-injected mice (67.8 µm; P = 0.007), whereas at 15 days this was not significantly different. LPS injection did not significantly affect average AV thickness on day 2 (37.8 µm), but did significantly increase average AV thickness at day 15 (41.6 µm; P = 0.038) compared to PBS-injected mice (31.7 and 32.3 µm respectively). LPS injection did not affect AV fibrosis, GAGs and lipid content. Furthermore, no calcium deposits were found. Iron deposits, indicative for valve haemorrhage, were observed in one AV of the PBS-injected group (a day 2 mouse; 9.1%) and in five AVs of the LPS-injected group (both day 2- and 15 mice; 29.4%). No significant differences in inflammatory cell infiltration were observed upon LPS injection. CONCLUSION: Short-term LPS apparently has the potential to increase AV thickening and haemorrhage. These results suggest that systemic inflammation can acutely compromise AV structure.

Microcirculatory perfusion disturbances following cardiac surgery with cardiopulmonary bypass are associated with in vitro endothelial hyperpermeability and increased angiopoietin-2 levels.

BACKGROUND: Endothelial hyperpermeability following cardiopulmonary bypass (CPB) contributes to microcirculatory perfusion disturbances and postoperative complications after cardiac surgery. We investigated the postoperative course of renal and pulmonary endothelial barrier function and the association with microcirculatory perfusion and angiopoietin-2 levels in patients after CPB. METHODS: Clinical data, sublingual microcirculatory data, and plasma samples were collected from patients undergoing coronary artery bypass graft surgery with CPB (n = 17) before and at several time points up to 72 h after CPB. Renal and pulmonary microvascular endothelial cells were incubated with patient plasma, and in vitro endothelial barrier function was assessed using electric cell-substrate impedance sensing. Plasma levels of angiopoietin-1,-2, and soluble Tie2 were measured, and the association with in vitro endothelial barrier function and in vivo microcirculatory perfusion was determined. RESULTS: A plasma-induced reduction of renal and pulmonary endothelial barrier function was observed in all samples taken within the first three postoperative days (P < 0.001 for all time points vs. pre-CPB). Angiopoietin-2 and soluble Tie2 levels increased within 72 h after CPB (5.7 ± 4.4 vs. 1.7 ± 0.4 ng/ml, P < 0.0001; 16.3 ± 4.7 vs. 11.9 ± 1.9 ng/ml, P = 0.018, vs. pre-CPB), whereas angiopoietin-1 remained stable. Interestingly, reduced in vitro renal and pulmonary endothelial barrier moderately correlated with reduced in vivo microcirculatory perfusion after CPB (r = 0.47, P = 0.005; r = 0.79, P < 0.001). In addition, increased angiopoietin-2 levels moderately correlated with reduced in vitro renal and pulmonary endothelial barrier (r = - 0.46, P < 0.001; r = - 0.40, P = 0.005) and reduced in vivo microcirculatory perfusion (r = - 0.43, P = 0.01; r = - 0.41, P = 0.03). CONCLUSIONS: CPB is associated with an impairment of in vitro endothelial barrier function that continues in the first postoperative days and correlates with reduced postoperative microcirculatory perfusion and increased circulating angiopoietin-2 levels. These results suggest that angiopoietin-2 is a biomarker for postoperative endothelial hyperpermeability, which may contribute to delayed recovery of microcirculatory perfusion after CPB. TRIAL REGISTRATION: NTR4212 .

Antithrombotic therapy after mitral valve repair: VKA or aspirin?

The optimal antithrombotic therapy following mitral valve repair (MVr) is still a matter of debate. Therefore, we evaluated the rate of thromboembolic and bleeding complications of two antithrombotic prevention strategies: vitamin K antagonists (VKA) versus aspirin. Consecutive patients who underwent MVr between 2004 and 2016 at three Dutch hospitals were evaluated for thromboembolic and bleeding complications during three postoperative months. The primary endpoint was the combined incidence of thromboembolic and bleeding complications to determine the net clinical benefit of VKA strategy as compared with aspirin. Secondary objectives were to evaluate both thromboembolic and bleeding rates separately and to identify predictors for both complications. A total of 469 patients were analyzed, of whom 325 patients (69%) in the VKA group and 144 patients (31%) in the aspirin group. Three months postoperatively, the cumulative incidence of the combined end point of the study was 9.2% (95%CI 6.1-12) in the VKA group and 11% (95%CI 6.0-17) in the aspirin group [adjusted hazard ratio (HR) 1.6, 95%CI 0.83-3.1]. Moreover, no significant differences were observed in thromboembolic rates (adjusted HR 0.82, 95%CI 0.16-4.2) as well as in major bleeding rates (adjusted HR 1.89, 95%CI 0.90-3.9). VKA and aspirin therapy showed a similar event rate of 10% during 3 months after MVr in patients without prior history of AF. In both treatment groups thromboembolic event rate was low and major bleeding rates were comparable. Future prospective, randomized trials are warranted to corroborate our findings.

Correction to: Antithrombotic therapy after mitral valve repair: VKA or aspirin?

The original version of this article unfortunately contained a mistake in the author name. The co-author name should be Frederikus A. Klok instead of Frederik A. Klok. The original article has been corrected.

Minimally Invasive Determinations of Oxygen Delivery and Consumption in Cardiac Surgery: An Observational Study.

OBJECTIVE: Evaluate minimally invasive assessment of oxygen delivery (DO2) and oxygen consumption (VO2) and determine its level of agreement with the gold standard approach of those measurements in patients undergoing cardiac surgery. DESIGN: Observational study. SETTING: Single center, VU University Medical Center (Amsterdam, The Netherlands). PARTICIPANTS: The study comprised 29 adult patients. INTERVENTION: Parallel measurements of invasive and minimally invasive parameters required for the calculation of DO2 and VO2. MEASUREMENTS AND MAIN RESULTS: Measurements were performed after anesthesia induction (T1) and before sternal closure (T2) in adult cardiac surgery. The invasive approach included arterial and pulmonary artery catheter-derived blood sampling and cardiac output measurements. The minimally invasive approach included pulse oximetry, point-of-care hemoglobin, Nexfin-based cardiac output, and central venous catheter-derived blood sampling. Level of agreement was determined using Bland-Altman analysis and percentage error. DO2 and VO2 levels were determined in patients 71 ± 8 years old. DO2 measurements showed a level of agreement of -17 ± 57 L/min/m2 and -18 ± 72 L/min/m2 with percentage errors of 35% and 38% at T1 and T2, respectively. VO2 assessment showed a level of agreement of -5 ± 18 L/min/m2 and -12 ± 22 L/min/m2, with percentage errors of 47% at T1 and T2. The highest percentage errors were for cardiac output measurements, 33% and 28% at T1 and T2, respectively. CONCLUSION: Agreement between minimally invasive and invasive DO2 and VO2 determinations is, moderate and poor, respectively. These findings may be explained by the poor agreement between minimally invasive and invasive cardiac output measurements.

PX-18 Protects Human Saphenous Vein Endothelial Cells under Arterial Blood Pressure.

BACKGROUND: Arterial blood pressure-induced shear stress causes endothelial cell apoptosis and inflammation in vein grafts after coronary artery bypass grafting. As the inflammatory protein type IIA secretory phospholipase A2 (sPLA2-IIA) has been shown to progress atherosclerosis, we hypothesized a role for sPLA2-IIA herein. METHODS: The effects of PX-18, an inhibitor of both sPLA2-IIA and apoptosis, on residual endothelium and the presence of sPLA2-IIA were studied in human saphenous vein segments (n = 6) perfused at arterial blood pressure with autologous blood for 6 hrs. RESULTS: The presence of PX-18 in the perfusion blood induced a significant 20% reduction in endothelial cell loss compared to veins perfused without PX18, coinciding with significantly reduced sPLA2-IIA levels in the media of the vein graft wall. In addition, PX-18 significantly attenuated caspase-3 activation in human umbilical vein endothelial cells subjected to shear stress via mechanical stretch independent of sPLA2-IIA. CONCLUSIONS: In conclusion, PX-18 protects saphenous vein endothelial cells from arterial blood pressure-induced death, possibly also independent of sPLA2-IIA inhibition.

Arterial Blood Pressure Induces Transient C4b-Binding Protein in Human Saphenous Vein Grafts.

BACKGROUND: Complement is an important mediator in arterial blood pressure-induced vein graft failure. Previously, we noted activation of cell protective mechanisms in human saphenous veins too. Here we have analyzed whether C4b-binding protein (C4bp), an endogenous complement inhibitor, is present in the vein wall. METHODS: Human saphenous vein segments obtained from patients undergoing coronary artery bypass grafting (n = 55) were perfused in vitro at arterial blood pressure with either autologous blood for 1, 2, 4, or 6 hr or with autologous blood supplemented with reactive oxygen species scavenger N-acetylcysteine. The segments were subsequently analyzed quantitatively for presence of C4bp and complement activation product C3d using immunohistochemistry. RESULTS: Perfusion induced deposition of C3d and C4bp within the media of the vessel wall, which increased reproducibly and significantly over a period of 4 hr up to 3.8% for C3d and 81% for C4bp of the total vessel area. Remarkably after 6 hr of perfusion, the C3d-positive area decreased significantly to 1.3% and the C4bp-positive area to 19% of the total area of the vein. The areas positive for both C4bp and C3d were increased in the presence of N-acetylcysteine. CONCLUSIONS: Exposure to arterial blood pressure leads to a transient presence of C4bp in the vein wall. This may be part of a cell-protective mechanism to counteract arterial blood pressure-induced cellular stress and inflammation in grafted veins.

Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution.

Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375-425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB (n = 9), hemodilution alone (n = 9), or a sham procedure (n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P < 0.001), and this reduction persisted throughout the experiment. Endothelial and inflammatory activation and renal histological injury were increased after CPB compared with hemodilution or sham procedure. Hemodilution leads to minor and transient disturbances in microcirculatory perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury.

Side-by-Side Alterations in Glycocalyx Thickness and Perfused Microvascular Density During Acute Microcirculatory Alterations in Cardiac Surgery.

OBJECTIVES: Endothelial glycocalyx injury causes microcirculatory perfusion disturbances in experimental studies, but the relevance in a clinical setting remains unknown. We investigated whether glycocalyx dimensions are reduced after onset of CPB and whether this is associated with alterations in microvascular perfusion. METHODS: The current observational study included 36 patients undergoing cardiac surgery without or with CPB, using either nonpulsatile or pulsatile flow. Sublingual microcirculatory perfusion was assessed perioperatively and analyzed for perfused vessel density and PBR, an inverse parameter of endothelial glycocalyx dimensions. RESULTS: Perfused vessel density decreased after onset of CPB in parallel with an increase in PBR in both pulsatile and nonpulsatile groups. In the nonpulsatile CPB group, these alterations were still persistent in the ICU (PVD: T1 19.8 ± 2.8 mm/mm(2) vs. T3 15.3 ± 2.6 mm/mm(2) ; p = 0.004. PBR: T1 2.40 ± 0.35 µm vs. T3 2.60 ± 0.31 µm; p = 0.020). In the off-pump group, perfused vessel density remained unaltered. An inverse correlation between perfused vessel density and PBR was detected. CONCLUSIONS: This study shows that endothelial glycocalyx dimensions decrease after onset of CPB and are closely related to microvascular perfusion when assessed with a novel, noninvasive technique.

Atrial fibrillation coincides with the advanced glycation end product N(ε)-(carboxymethyl)lysine in the atrium.

Presence of advanced glycation end products (AGEs) in the heart induces a proinflammatory phenotype. However, the presence of AGEs within atrial tissue of atrial fibrillation (AF) patients is unknown and was analyzed here. Left atrial appendage tissue from 33 AF patients and 9 controls was analyzed for the presence of the major AGEs N(ε)-(carboxymethyl)lysine (CML), VCAM-1, neutrophilic granulocytes, lymphocytes, and macrophages in both the fat tissue and myocardium separately. The total amount of fibrosis was also analyzed. Presence of CML was significantly higher in blood vessels of the left atrial appendage in AF patients as compared to controls, independent of diabetes mellitus. In AF patients, VCAM-1 expression in blood vessels and the numbers of infiltrated neutrophilic granulocytes, lymphocytes, and macrophages significantly increased compared to controls, and were highest in the fat tissue; there was no significant difference in fibrosis compared to controls. Interestingly, total amount of CML and fibrosis in AF and control patients correlated positively. Finally, there was no difference between AF patients based on AF type or surgical indication in the presence of CML, VCAM-1 expression, inflammatory cells, and fibrosis. Our results indicate that in AF the intramyocardial blood vessels of the left atrial appendage have an increased CML presence and proinflammatory status coinciding with a local increase in the number of inflammatory cells.

Prevention of age-induced N(ε)-(carboxymethyl)lysine accumulation in the microvasculature.

OBJECTIVE: N(ε)-(carboxymethyl)lysine (CML) is one of the major advanced glycation end products in both diabetics and nondiabetics. CML depositions in the microvasculature have recently been linked to the aetiology of acute myocardial infarction and cognitive impairment in Alzheimer's disease, possibly related to local enhancement of inflammation and oxidative processes. We hypothesized that CML deposition in the microvasculature of the heart and brain is age-induced and that it could be inhibited by a diet intervention with docosahexaenoic acid (DHA), an omega-3 fatty acid known for its anti-inflammatory and antioxidative actions. MATERIALS AND METHODS: ApoE(-/-) mice (n = 50) were fed a Western diet and were sacrificed after 40, 70 and 90 weeks. Part of these mice (n = 20) were fed a Western diet enriched with DHA from 40 weeks on. CML in cardiac and cerebral microvessels was quantified using immunohistochemistry. RESULTS: Cardiac microvascular depositions of CML significantly increased with an immunohistochemical score of 11·85 [5·92-14·60] at 40 weeks, to 33·17 [17·60-47·15] at 70 weeks (P = 0·005). At the same time points, cerebral microvascular CML increased from 6·45; [4·78-7·30] to 12·99; [9·85-20·122] (P = 0·003). DHA decreased CML in the intramyocardial vasculature at both 70 and 90 weeks, significant at 70 weeks [33·17; (17·60-47·15) vs. 14·73; (4·44-28·16) P = 0·037]. No such effects were found in the brain. CONCLUSIONS: Accumulation of N(ε)-(carboxymethyl)lysine in the cerebral and cardiac microvasculature is age-induced and is prevented by DHA in the intramyocardial vessels of ApoE(-/-) mice.

Moderate hyperoxic versus near-physiological oxygen targets during and after coronary artery bypass surgery: a randomised controlled trial.

BACKGROUND: The safety of perioperative hyperoxia is currently unclear. Previous studies in patients undergoing coronary artery bypass surgery suggest reduced myocardial damage when avoiding extreme perioperative hyperoxia (>400 mmHg). In this study we investigated whether an oxygenation strategy from moderate hyperoxia to a near-physiological oxygen tension reduces myocardial damage and improves haemodynamics, organ dysfunction and oxidative stress. METHODS: This was a single-blind, single-centre, open-label, randomised controlled trial in patients undergoing elective coronary artery bypass surgery. Fifty patients were randomised to a partial pressure of oxygen in arterial blood (PaO2) target of 200-220 mmHg during cardiopulmonary bypass and 130-150 mmHg during intensive care unit (ICU) admission (control group) versus lower targets of 130-150 mmHg during cardiopulmonary bypass and 80-100 mmHg at the ICU (conservative group). Primary outcome was myocardial injury (CK-MB and Troponin-T) at ICU admission and 2, 6 and 12 hours thereafter. RESULTS: Weighted PaO2 during cardiopulmonary bypass was 220 mmHg (interquartile range (IQR) 211-233) vs. 157 (151-162) in the control and conservative group, respectively (P < 0.0001). During ICU admission, weighted PaO2 was 107 mmHg (86-141) vs. 90 (84-98) (P = 0.03), respectively. Area under the curve of CK-MB was median 23.5 µg/L/h (IQR 18.4-28.1) vs. 21.5 (15.8-26.6) (P = 0.35) and 0.30 µg/L/h (0.25-0.44) vs. 0.39 (0.24-0.43) (P = 0.81) for Troponin-T. Cardiac index, systemic vascular resistance index, creatinine, lactate and F2-isoprostane levels were not different between groups. CONCLUSIONS: Compared to moderate hyperoxia, a near-physiological oxygen strategy does not reduce myocardial damage in patients undergoing coronary artery bypass surgery. Conservative oxygen administration was not associated with increased lactate levels or hypoxic events. TRIAL REGISTRATION: Netherlands Trial Registry NTR4375, registered on 30 January 2014.

C4b-Binding Protein Deposition is Induced in Diseased Aortic Heart Valves, Coinciding with C3d.

BACKGROUND AND AIM OF THE STUDY: It has been found recently that activated complement is more widespread in diseased aortic valves compared to the endogenous complement inhibitors C1-inhibitor and clusterin. Previously, another endogenous inhibitor of complement, C4b-binding protein (C4BP) has been described in atherosclerotic diseased coronary arteries. The study aim was to analyze C4BP levels in diseased aortic valves. METHODS: Aortic valve tissue was derived from surgical procedures and classified as 'degenerative', 'atherosclerotic' or 'atherosclerotic with bacterial infection'. Valves were stained with specific antibodies against C4BP, C3d and caspase-3. Areas of positivity were then quantified using computer- assisted morphometry. RESULTS: In atherosclerotic valves, the areas of C4BP and C3d positivity (38.8 +/- 0.4% versus 32.7 +/- 1.0%, respectively) were significantly higher compared to the degenerative and control groups. In atherosclerotic valves with bacterial infection, the area of positivity for C4BP was even further increased compared to atherosclerotic valves (65.1 +/- 1.2%; 70.1 +/- 1.9% for C3d). The areas of C4BP and C3d positivity were not significantly different in all groups. Caspase-3 was only present in <10% of endothelial cells in the atherosclerotic valves without bacterial infection and in neutrophilic granulocytes in atherosclerotic valves, with and without bacterial infection. CONCLUSION: It has been shown for the first time that C4BP is deposited in the diseased aortic valve, coinciding with C3d. The area of C4BP positivity was more extensive compared to the areas of other endogenous complement inhibitors (C1-inhibitor and clusterin).

Ten-year patterns in blood product utilization during cardiothoracic surgery with cardiopulmonary bypass in a tertiary hospital.

BACKGROUND: This retrospective analysis describes blood conservation strategies and overall consumption of red blood cells (RBCs), fresh-frozen plasma (FFP), and platelet (PLT) concentrates during nonaortic cardiac surgery with cardiopulmonary bypass (CPB) in a tertiary hospital over a 10-year period. STUDY DESIGN AND METHODS: Study variables of 6026 patients that underwent cardiac surgery between 2002 and 2011 were incorporated in the database and included hemoglobin (Hb), lowest temperature, CPB duration, 24-hour blood loss, fluid balance, and overall transfusion requirements. RESULTS: Between 2002 and 2011, the lowest intraoperative Hb levels and temperature increased from 8.5 ± 1.2 to 10.4 ± 1.4 g/dL and from 32 ± 2 to 34 ± 1°C, respectively. In addition to the steep decrease in the postoperative fluid balance over time, a reduction in 24-hour blood loss from 815 ± 588 mL (2002) to 590 ± 438 mL (2011) was observed. These changes were paralleled by a 28% reduction in overall RBC transfusion from 1443 units in 2002 to 1038 in 2011. While RBC transfusion decreased over time, there was no significant change in the use of FFP or PLT concentrate transfusion. The probability to receive RBC transfusion increased after cessation of aprotinin, but reduced after routine cell salvage in all operations. CONCLUSION: This institutional report shows a large reduction in blood loss and transfusion requirements in cardiac surgery over a 10-year period. This reduction is most probably attributed to structural cell salvage, reduced intraoperative fluid volumes, and the increase in the lowest intraoperative body temperature.

Individualized heparin and protamine management improves rotational thromboelastometric parameters and postoperative hemostasis in valve surgery.

OBJECTIVES: This study investigated whether a tailored approach to heparin and protamine management improved thromboelastometric parameters after cardiopulmonary bypass and reduced postoperative blood loss compared with activated coagulation time (ACT)-based fixed target heparin and protamine management. DESIGN: Randomized controlled study. SETTING: Tertiary university hospital. PARTICIPANTS: Patients undergoing elective valve surgery (n = 38). INTERVENTIONS: Heparin and protamine management were based either on the ACT (n = 19) or hemostasis management system (HMS) measurements (n = 19; HMS Plus; Medtronic, Minneapolis, MN). MEASUREMENTS AND MAIN RESULTS: The target ACT for initiation of cardiopulmonary bypass was 480 seconds. Study variables included rotational thromboelastometry EXTEM (extrinsic coagulation), HEPTEM (intrinsic coagulation with heparinase), and FIBTEM (fibrin part of clot formation) tests and 24-hour blood loss. The use of HMS reduced the median protamine-to-heparin ratio from 1.00 (1.00-1.00) to 0.62 (0.56-0.66; p<0.001). The ACT group showed a prolonged postbypass clotting time for both EXTEM (86 ± 13 seconds v 78 ± 10 seconds; p = 0.05) and HEPTEM (217 ± 58 seconds v 183 ± 24 seconds; p = 0.03) tests. There was a moderate correlation between protamine dosing with the EXTEM and HEPTEM clotting time (r = 0.42; p = 0.009 and r = 0.38; p = 0.02, respectively). The number of patients with more than 450 mL/24 hours was higher in the ACT than in the HMS group (42% v 12%; p = 0.04). CONCLUSIONS: Individualized heparin and protamine management decreased the protamine-to-heparin ratio, improved postbypass thromboelastometric hemostatic parameters, and reduced the incidence of severe blood loss compared with an ACT-based strategy, supporting the added value of this approach for hemostatic optimization during cardiac surgery.

Microcirculatory perfusion is preserved during off-pump but not on-pump cardiac surgery.

OBJECTIVE: This study investigated the perioperative course of microcirculatory perfusion in off-pump compared with on-pump surgery. Additionally, the impact of changes in systemic hemodynamics, hematocrit, and body temperature was studied. DESIGN: Prospective, nonrandomized, observational study. SETTING: Tertiary university hospital. PARTICIPANTS: Patients undergoing coronary artery bypass grafting with (n = 13) or without (n = 13) use of cardiopulmonary bypass. INTERVENTIONS: Microcirculatory measurements were obtained at 5 time points ranging from induction of anesthesia to ICU admission. MEASUREMENTS AND MAIN RESULTS: Microcirculatory recordings were performed with sublingual sidestream dark field imaging. Despite a comparable reduction in intraoperative blood pressure between groups, the perfused vessel density decreased more than 20% after onset of extracorporeal circulation but remained stable in the off-pump group. The reduction in microvascular perfusion in the on-pump group was further paralleled by decreased hematocrit and temperature. Although postbypass hematocrit levels and body temperature were restored to similar levels as in the off-pump group, the median microvascular flow index remained reduced after bypass (2.4 [2.3-2.7]) compared with baseline (2.8 [2.7-2.9]; p = 0.021). CONCLUSIONS: Microcirculatory perfusion remained unaltered throughout off-pump surgery. In contrast, microvascular perfusion declined after initiation of cardiopulmonary bypass and did not recover in the early postoperative phase.

Optimization of cardiopulmonary bypass prime fluid to preserve microcirculatory perfusion during on-pump coronary artery bypass graft surgery: PRIME study protocol for a double-blind randomized trial.

BACKGROUND: Acute microcirculatory perfusion disturbances and organ edema are important factors leading to organ dysfunction during cardiac surgery with cardiopulmonary bypass (CPB). Priming of the CPB system with crystalloid or colloid fluids, which inevitably leads to hemodilution, could contribute to this effect. However, there is yet no optimal evidence-based strategy for this type of priming. Hence, we will investigate different priming strategies to reduce hemodilution and preserve microcirculatory perfusion. METHODS: The PRIME study is a single-center double-blind randomized trial. Patients undergoing elective coronary artery bypass graft surgery with CPB will be randomized into three groups of prime fluid strategy: (1) gelofusine with crystalloid, (2) albumin with crystalloid, or (3) crystalloid and retrograde autologous priming. We aim to include 30 patients, 10 patients in each arm. The primary outcome is the change in microcirculatory perfusion. Secondary outcomes include colloid oncotic pressure; albumin; hematocrit; electrolytes; fluid balance and requirements; transfusion rates; and endothelial-, glycocalyx-, inflammatory- and renal injury markers. Sublingual microcirculatory perfusion will be measured using non-invasive sidestream dark field video microscopy. Microcirculatory and blood measurements will be performed at five consecutive time points during surgery up to 24 h after admission to the intensive care unit. DISCUSSION: PRIME is the first study to assess the effect of different prime fluid strategies on microcirculatory perfusion in cardiac surgery with CPB. If the results suggest that a specific crystalloid or colloid prime fluid strategy better preserves microcirculatory perfusion during on-pump cardiac surgery, the current study may help to find the optimal pump priming in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05647057. Registered on 04/25/2023. CLINICALTRIALS: gov PRS: Record Summary NCT05647057, all items can be found in the protocol.