Alexander B.A. Vonk

Hemostatic efficacy of dipyridamole, tranexamic acid, and aprotinin in coronary bypass grafting.

Sixty patients (four groups of 15 patients) were entered in a randomized, controlled study to compare the efficacy of prophylactic treatment with dipyridamole, tranexamic acid, and aprotinin to reduce bleeding after elective coronary artery bypass grafting. Only patients with a preoperative platelet count of less than 246 x 10(9)/L were selected because a previous study showed that these individuals are at risk for increased postoperative bleeding. Compared to control subjects, postoperative blood loss 6 hours after operation was significantly reduced by tranexamic acid (674 +/- 411 versus 352 +/- 150 mL; p < 0.05) and by aprotinin (270 +/- 174 mL; p < 0.01). Dipyridamole did not reduce postoperative blood loss and was associated with complications in 3 patients. We conclude that hemostasis after cardiac operations can be improved with tranexamic acid and aprotinin. Dipyridamole appeared to be ineffective.

Inflammatory response to cardiopulmonary bypass using roller or centrifugal pumps

BACKGROUND The inflammatory response in 29 patients undergoing coronary artery bypass grafting using either roller or centrifugal (CFP) pumps was evaluated in a prospective study. METHODS Patients were randomized in roller pump (n = 15) and CFP (n = 14) groups. Terminal complement complex activation (SC5b-9) and neutrophil activation (elastase) were assessed during the operation. Cytokine production (tumor necrosis factor-alpha, interleukin-6, interleukin-8) and circulating adhesion molecules (soluble endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1) were assessed after the operation. RESULTS Release of SC5b-9 after stopping cardiopulmonary bypass and after protamine administration was higher in the CFP group (p = 0.01 and p = 0.004). Elastase level was higher after stopping cardiopulmonary bypass using CFP (p = 0.006). Multivariate analysis confirmed differences between roller pump and CFP groups in complement and neutrophil activation. After the operation, a significant production of cytokines was detected similarly in both groups, with peak values observed within the range of 4 to 6 hours after starting cardiopulmonary bypass. However, interleukin-8 levels were higher using CFP 2 hours after starting cardiopulmonary bypass (p = 0.02). Plasma levels of adhesion molecules were similar in both groups within the investigation period. CONCLUSIONS During the operation, CFP caused greater complement and neutrophil activation. After the operation, the inflammatory response was similar using either roller pump or CFP.

Pulsatile flow during cardiopulmonary bypass preserves postoperative microcirculatory perfusion irrespective of systemic hemodynamics

The onset of nonpulsatile cardiopulmonary bypass is known to deteriorate microcirculatory perfusion, but it has never been investigated whether this may be prevented by restoration of pulsatility during extracorporeal circulation. We therefore investigated the distinct effects of nonpulsatile and pulsatile flow on microcirculatory perfusion during on-pump cardiac surgery. Patients undergoing coronary artery bypass graft surgery were randomized into a nonpulsatile (n = 17) or pulsatile (n = 16) cardiopulmonary bypass group. Sublingual mucosal microvascular perfusion was measured at distinct perioperative time intervals using sidestream dark field imaging, and quantified as the level of perfused small vessel density and microvascular flow index (vessel diameter < 20 μm). Microcirculation measurements were paralleled by hemodynamic and free hemoglobin analyses. The pulse wave during pulsatile bypass estimated 58 ± 17% of the baseline blood pressure waveform. The observed reduction in perfused vessel density during aorta cross-clamping was only restored in the pulsatile flow group and increased from 15.5 ± 2.4 to 20.3 ± 3.7 mm/mm(2) upon intensive care admission (P < 0.01). The median postoperative microvascular flow index was higher in the pulsatile group [2.6 (2.5-2.9)] than in the nonpulsatile group [2.1 (1.7-2.5); P = 0.001]. Pulsatile flow was not associated with augmentation of free hemoglobin production and was paralleled by improved oxygen consumption from 70 ± 14 to 82 ± 16 ml·min(-1)·m(-2) (P = 0.01) at the end of aortic cross-clamping. In conclusion, pulsatile cardiopulmonary bypass preserves microcirculatory perfusion throughout the early postoperative period, irrespective of systemic hemodynamics. This observation is paralleled by an increase in oxygen consumption during pulsatile flow, which may hint toward decreased microcirculatory heterogeneity during extracorporeal circulation and preservation of microcirculatory perfusion throughout the perioperative period.

Intraoperative cell salvage is associated with reduced postoperative blood loss and transfusion requirements in cardiac surgery: a cohort study.

This study investigated whether implementation of cell salvage of shed mediastinal and residual blood in all patients undergoing low‐to‐moderate–risk cardiac surgery reduces the need for allogeneic red blood cell (RBC) transfusion compared to patients not subjected to cell salvage.

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.

NOX5 Expression Is Increased in Intramyocardial Blood Vessels and Cardiomyocytes after Acute Myocardial Infarction in Humans

Reactive oxygen species producing NADPH oxidases play important roles under different (patho)physiological conditions. NOX1, NOX2, and NOX4 are important sources of reactive oxygen species in the heart, but knowledge of the calcium-dependent NOX5 in the heart is lacking. The presence of NOX5 was studied via RT-PCR in heart tissue from patients with end-stage heart failure; the tissue was obtained during cardiac transplantation surgery. NOX5 positivity and cellular localization were studied via IHC and digital-imaging microscopy in heart tissues of patients who did not have heart disease and in infarction areas of patients who died of myocardial infarctions of different durations. Furthermore, NOX5 expression was analyzed in vitro by using Western blot analysis. NOX5 RNA was found in the hearts of controls and patients with ischemic cardiomyopathy. In controls, NOX5 localized to the endothelium of a limited number of intramyocardial blood vessels and to a limited number of scattered cardiomyocytes. In infarcted hearts, NOX5 expression increased, especially in infarctions >12 hours, which manifested as an increase in NOX5-positive intramyocardial blood vessels, as well as in endothelium, smooth muscle, and cardiomyocytes. NOX5 was found in cardiomyocyte cytoplasm, plasma membrane, intercalated disks, and cross striations. Western blot analysis confirmed NOX5 expression in isolated human cardiomyocytes. For the first time to our knowledge, we demonstrate NOX5 expression in human intramyocardial blood vessels and cardiomyocytes, with significant increases in the affected myocardium after acute myocardial infarction.

Changes in Microcirculatory Perfusion and Oxygenation During Cardiac Surgery With or Without Cardiopulmonary Bypass

From the Anesthesiology and Cardiothoracic Surgery, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands. Address reprint requests to Christa Boer, Department of Anesthesiology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. E-mail: c.boer@vumc.nl

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.

Red blood cell transfusion compared with gelatin solution and no infusion after cardiac surgery: effect on microvascular perfusion, vascular density, hemoglobin, and oxygen saturation.

BACKGROUND: After cardiac surgery, red blood cell (RBC) transfusion may improve systemic hemodynamics and thereby microvascular blood flow and O2 delivery (DO2).

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

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.