Michael I. Meesters

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.

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.

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.

Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery. A randomised clinical trial.

While experimental data state that protamine exerts intrinsic anticoagulation effects, protamine is still frequently overdosed for heparin neutralisation during cardiac surgery with cardiopulmonary bypass (CPB). Since comparative studies are lacking, we assessed the influence of two protamine-to-heparin dosing ratios on perioperative haemostasis and bleeding, and hypothesised that protamine overdosing impairs the coagulation status following cardiac surgery. In this open-label, multicentre, single-blinded, randomised controlled trial, patients undergoing on-pump coronary artery bypass graft surgery were assigned to a low (0.8; n=49) or high (1.3; n=47) protamine-to-heparin dosing group. The primary outcome was 24-hour blood loss. Patient haemostasis was monitored using rotational thromboelastometry and a thrombin generation assay. The low protamine-to-heparin dosing ratio group received less protamine (329 ± 95 vs 539 ± 117 mg; p<0.001), while post-protamine activated clotting times were similar among groups. The high dosing group revealed increased intrinsic clotting times (236 ± 74 vs 196 ± 64 s; p=0.006) and the maximum post-protamine thrombin generation was less suppressed in the low dosing group (38 ± 40 % vs 6 ± 9 %; p=0.001). Postoperative blood loss was increased in the high dosing ratio group (615 ml; 95 % CI 500-830 ml vs 470 ml; 95 % CI 420-530 ml; p=0.021) when compared to the low dosing group, respectively. More patients in the high dosing group received fresh frozen plasma (11 % vs 0 %; p=0.02) and platelet concentrate (21 % vs 6 %; p=0.04) compared to the low dosing group. Our study confirms in vitro data that abundant protamine dosing is associated with increased postoperative blood loss and higher transfusion rates in cardiac surgery.

Systemic endotoxin activity correlates with clot formation: an observational study in patients with early systemic inflammation and sepsis

IntroductionInflammation and coagulation are closely linked, and both can be triggered by endotoxin. Thrombelastometry and impedance aggregometry are of diagnostic and predictive value in critically ill patients. In this observational study we investigated the correlation of endotoxin activity with thrombelasometric and aggregometric variables in patients with systemic inflammation.MethodsBased on a daily screening on a tertiary academic surgical ICU, patients, as soon as they fulfilled two or more criteria for systemic inflammatory response syndrome (SIRS), were included. In whole blood we performed endotoxin activity (EA) assay, thrombelastometry (ROTEM®) and impendance aggregometry (Multiplate®).ResultsIn total, 49 patients were included with a broad spread of EA levels of (median (minimum to maximum)) 0.27 (0.01 to 0.72), allowing expedient correlative analysis. Clot formation time (CFT) (263 s (60 to 1,438 s)) and clotting time (CT) (1,008 s (53 to 1,481 s)) showed a significant negative correlation with EA level (r = -0.38 (P < 0.005) and r = -0.29 (P < 0.05)). Positive correlations were found for alpha-angle (50° (17 to 78°), r = 0.40 (P < 0.005)) and maximum clot firmness (MCF) (55 mm (5/76), r = 0.27 (P < 0.05)). No significant correlations were found between Lysis Index at 60 minutes (LI60) and EA levels. There was no correlation between EA level and aggregometric values, or classical coagulation parameters.ConclusionsIn patients with systemic inflammation, increasing endotoxin concentrations correlate with increased clot formation.

Level of agreement between laboratory and point-of-care prothrombin time before and after cardiopulmonary bypass in cardiac surgery

BACKGROUND Hemostasis monitoring in cardiac surgery could benefit from an easy to use and fast point-of-care coagulation monitor, since routine laboratory tests have a delay of 30-45minutes. This study investigated the level of agreement between the point-of-care prothrombin time (PT) with central laboratory PT before and after cardiopulmonary bypass. METHODS Bland Altman and error grid analysis were used to analyze the agreement between the point-of-care Coaguchek XS Pro device (POC-PT) and the central laboratory prothrombin time (LAB-PT) before cardiopulmonary bypass (CPB) and 3minutes after protamine administration. Prothrombin times were expressed in international normalized ratios (INR). RESULTS The average POC-PT and LAB-PT values of 73 patients were 1.06±0.14 and 1.09±0.13 (P=0.10) before CPB. POC-PT measurements before CPB showed a good agreement with the LAB-PT, with a bias of -0.02±0.07 INR and 94% of the values being represented in the clinical acceptable zone of error grid analysis. The mean POC-PT 3minutes after protamine administration was significantly lower than the LAB-PT (1.35±0.12 vs. 1.70±0.18; P<0.001). The PT at 3minutes after protamine administration showed a bias of 0.36±0.14, and 82% of the values were located outside of the clinical acceptable zone in the error grid analysis. CONCLUSIONS Point-of-care prothrombin time testing was in concordance with conventional laboratory PT prior to cardiopulmonary bypass. At 3minutes following protamine administration, PT values of the point-of-care device were structurally lower than the laboratory PT values, leading to a disagreement between both tests at that time point.

A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass

OBJECTIVE This study investigated postoperative hemostasis of patients subjected to conventional protamine dosing compared with protamine dosing based on a pharmacokinetic (PK) model following cardiopulmonary bypass. DESIGN Retrospective case-control study. SETTING Tertiary university hospital. PARTICIPANTS Patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS In 56 patients, protamine was dosed in a fixed ratio (CD), while 62 patients received protamine based on the PK model. MEASUREMENTS AND MAIN RESULTS There was no difference in heparin administration (414±107 mg (CD) v 403±90 mg (PK); p = 0.54), whereas protamine dosing was considerably different with a protamine-to-heparin dosing ratio of 1.1±0.3 for the CD group and 0.5±0.1 for the PK group (p<0.001). The changes in activated coagulation time (ΔACT) values (ACT after protamine minus preoperative ACT;+17±77 s v+6±15 s; p = 0.31) were equal between groups. Yet, the thromboelastometric intrinsically activated coagulation test clotting time (CT; 250±76 s v 203±44 s; p<0.001) and intrinsically activated coagulation test without the heparin effect CT (275±105 v 198±32 s; p<0.001) were prolonged in the CD group. Median packed red blood cell transfusion (0 [0-2] v 0 [0-0]), fresh frozen plasma transfusion (1 [0-2] v 0 [0-0]), and platelet concentrate transfusion (0 [0-1] v 0 [0-0]) were different between the fixed ratio and PK group, respectively (all p<0.001). CONCLUSIONS This study showed that patient-tailored protamine dosing based on a PK model was associated with a reduction in protamine dosing, with better hemostatic test results when compared with fixed-ratio protamine dosing.

Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review

&NA; Neutralisation of systemic anticoagulation with heparin in cardiac surgery with cardiopulmonary bypass requires protamine administration. If adequately dosed, protamine neutralises heparin and reduces the risk of postoperative bleeding. However, as its anticoagulant properties are particularly exerted in the absence of heparin, overdosing of protamine may contribute to bleeding and increased transfusion requirements. This narrative review describes the mechanisms underlying the anticoagulant properties and side‐effects of protamine, and the impact of protamine dosing on the activated clotting time and point‐of‐care viscoelastic test results, and explains the distinct protamine dosing strategies in relation to haemostatic activation and postoperative bleeding. The available evidence suggests that protamine dosing should not exceed a protamine‐to‐heparin ratio of 1:1. In particular, protamine‐to‐heparin dosing ratios >1 are associated with more postoperative 12 h blood loss. The optimal protamine‐to‐heparin ratio in cardiac surgery has, however, not yet been elaborated, and may vary between 0.6 and 1.0 based on the initial heparin dose.

Validation of a point‐of‐care prothrombin time test after cardiopulmonary bypass in cardiac surgery

Point‐of‐care coagulation monitoring can be used for the guidance of haemostasis management. However, the influence of time on point‐of‐care prothrombin time testing following protamine administration after cardiopulmonary bypass has not been investigated. Bland–Altman and error grid analysis were used to analyse the level of agreement between prothrombin time measurements from point‐of‐care and laboratory tests before cardiopulmonary bypass, and then 3 min, 6 min and 10 min after protamine administration. Prothrombin times were expressed as International Normalised Ratios. While the point‐of‐care and laboratory prothrombin time measurements showed a high level of agreement before bypass, this agreement deteriorated following protamine administration to a mean (SD) bias of −0.22 (0.13) [limits of agreement 0.48–0.04]. Error grid analysis revealed that 35 (70%) of the paired values showed a clinically relevant discrepancy in international normalised ratio. At 3 min, 6 min and 10 min after cardiopulmonary bypass there is a clinical unacceptable discrepancy between the point‐of‐care and laboratory measurement of prothrombin time.

Instability of the non-activated rotational thromboelastometry assay (NATEM) in citrate stored blood

INTRODUCTION The non-activated rotational thromboelastometric assay (NATEM) is increasingly used as sensitive test for the evaluation of the endogenous activation of haemostasis. The reproducibility of the test results in citrate stored blood has never been investigated. MATERIALS AND METHODS The NATEM assay was performed in citrated blood samples stored for 0, 45 and 90minutes using ROTEM® (TEM International, Munich, Germany). Blood samples were drawn from healthy volunteers and a population of patients admitted to the intensive care (ICU). In 10 ICU patients, citrate concentrations were measured at baseline and after 90minutes of storage. RESULTS The NATEM clotting time shortened in stored citrated blood from healthy volunteers (t=0 1226±160; t=45 986±171; t=90 903±177; p<0.001) and ICU patients (t=0 986±318; t=90 750±187; p<0.001). A similar decrease in clot formation time (CFT) was seen whereas the MCF remained unaffected. Citrate concentration did not change over time, baseline 13.3±0.5mmol/l; after 90minutes 13.2±0.7mmol/l; n.s.. CONCLUSIONS The non-activated rotational thromboelastometric assay test results change over time in citrate stored blood. The NATEM test should be initiated at a standardised time point, in order to prevent bias by different test initiation times, preferably directly after blood withdrawal.