Rolf C.G. Gallandat Huet

An assessment of clinical interchangeability of TEG and RoTEM thromboelastographic variables in cardiac surgical patients.

BACKGROUND: Bedside thromboelastography is increasingly used, but an assessment of the clinical interchangeability of the 2 major systems, TEG® (Hemoscope) and RoTEM® (Pentapharm), has not been performed. METHODS: We measured blood samples from 46 cardiac surgical patients after induction of anesthesia with kaolin TEG® (kaoTEG), native TEG® (natTEG®), intrinsic RoTEM® (inTEM), and extrinsic RoTEM (exTEM). Each measurement consisted of reaction time (R), coagulation time (K), maximum amplitude (MA), and angle (&agr;). Bland–Altman plots and mixed-model analysis were used. To assess repeatability, we made 7 replicated measurements in rapid succession in 2 volunteers. RESULTS: One hundred sixty-six measurements were available for analysis. The R time of the kaoTEG® (345 ± 102 seconds, mean ± SD) was longer than that of the inTEM (179 ± 74 seconds, P < 0.001) and the exTEM (55 ± 28 seconds, P < 0.001). The K time of the kaoTEG® (78 ± 18s) was not different from that of the inTEM (75 ± 52 seconds, P = 0.60) but was longer than the K time of the exTEM (61 ± 24 seconds, P < 0.003). The MA of the kaoTEG® (71 ± 6.5 mm) was larger than the MA of the inTEM (67 ± 5.2 mm, P < 0.02) and almost similar to that of the exTEM (69 ± 6.3 mm). The &agr; of the kaoTEG® (72° ± 4.1°) was not significantly different from that of both the inTEM (76° ± 7°) and the exTEM (79° ± 4.5°). The variability for MA and &agr; was <10%. The repeatability of the R and K times was poor in both devices, whereas the repeatability of the MA and &agr; was sufficient for clinical purposes. CONCLUSIONS: The TEG® and RoTEM® measurements demonstrated a close correlation for the MA, but the &agr; did not for the R and K variables. The kaoTEG® had the best agreement with the exTEM measurement. Therefore TEG® and RoTEM® measurements are not completely interchangeable, and the clinical interpretation of thromboelastograhic data should be used with caution.

Effects of hypothermic cardiopulmonary bypass on the pharmacodynamics and pharmacokinetics of rocuronium

OBJECTIVE To study the influence of hypothermic cardiopulmonary bypass (CPB) on the pharmacodynamics and pharmacokinetics of rocuronium. DESIGN Prospective, descriptive study. SETTING Operating room at a university hospital. PARTICIPANTS Ten ASA class III and IV patients, ranging in age from 35 to 75 years, scheduled for elective coronary artery bypass grafting. INTERVENTIONS Neuromuscular transmission was monitored mechanomyographically. The time course of action of maintenance doses and plasma concentration-response relationships were determined before, during, and after CPB. The plasma concentration decay and renal elimination were studied simultaneously. Plasma and urine concentration of rocuronium were determined by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS Hypothermic CPB prolonged the duration of action of maintenance doses and coincided with a lower plasma concentration at a twitch response of 5% of control. The duration of action of maintenance doses returned to prehypothermic CPB level after rewarming to a nasopharyngeal temperature of 37 degrees C. The plasma concentration-response relationship did not return to precooling control value, probably owing to persisting peripheral hypothermia. Both the renal elimination of rocuronium and the plasma concentration decay after the last maintenance dose under normothermic conditions resembled values obtained in patients not undergoing hypothermic CPB. CONCLUSIONS Hypothermic CPB prolongs the duration of action of maintenance doses and alters the plasma concentration-response relationship of rocuronium. These changes may be the result of, on the one hand, an increased sensitivity of the neuromuscular transmission and/or decreased muscle contractility and, on the other hand, the result of a reduced plasma clearance during hypothermia.

The effect of midazolam at two plasma concentrations on hemodynamics and sufentanil requirement in coronary artery surgery

OBJECTIVES In this study, the hemodynamics and sufentanil requirement were compared at two midazolam target plasma concentrations in patients undergoing coronary artery bypass grafting (CABG). DESIGN Prospective, randomized study. SETTING University hospital, single institution. PARTICIPANTS Patients undergoing CABG. INTERVENTIONS Patients were randomly assigned to receive midazolam at a target plasma concentration of 150 ng/mL (group 1; n = 10) or 300 ng/mL (group 2; n = 10). Sufentanil infusion was titrated to maintain hemodynamic stability, defined as mean arterial pressure within 15% of baseline values. All patients received preoperative beta-blocking agents. Arterial blood samples of midazolam and sufentanil were analyzed by high-performance liquid chromatography and radioimmunoassay, respectively. MEASUREMENTS AND MAIN RESULTS The mean dose of sufentanil (7.5 +/- 1.7 microgram/kg in group 1 v 7.2 +/- 2.5 micrograms/kg in group 2) did not differ. There were no significant differences in hemodynamics between the groups in the period before or after cardiopulmonary bypass (CPB). Before CPB, in two patients in each group, hypertension was controlled with sufentanil only. One patient in group 1 required a vasodilator in addition to sufentanil. No ischemic events occurred before CPB. After CPB, one patient in group 2 required a vasodilator to control hypertension. Two patients in group 2 required treatment with nitroglycerin for myocardial ischemia. Stable plasma concentrations of sufentanil and midazolam were obtained during and after CPB. The midazolam infusion was continued in both groups at a rate of 1.25 micrograms/kg/min during the first 4 postoperative hours. The time to awakening did not differ between the groups (100 +/- 58 minutes in group 1 v 173 +/- 147 minutes in group 2) nor did the plasma concentrations of midazolam (96 +/- 28 ng/mL v 108 +/- 42 ng/mL) at the time of awakening. Intraoperative awareness was not reported. CONCLUSION In patients undergoing CABG, good hemodynamic control with a similar incidence of hemodynamic interventions was observed at midazolam target plasma concentrations of 150 and 300 ng/mL when coadministered with sufentanil. The sufentanil requirement was identical in both groups. This study suggests that a midazolam plasma concentration of 150 ng/mL is sufficient to provide satisfactory hemodynamic control and to avoid intraoperative awareness.

Bivalirudin is inferior to heparin in preservation of intraoperative autologous blood

INTRODUCTION Bivalirudin is used as an alternative to heparin in cardiac surgery, and may be superior to heparin with regard to platelet function. Bivalirudin however, is prone to cleavage by thrombin resulting in coagulation in areas of stasis. MATERIAL AND METHODS We compared the preservation of platelet function and the quality of anticoagulation in autologous blood of 26 cardiac surgical patients collected intraoperatively and anticoagulated ex vivo with either bivalirudin or heparin, with supplementation of bivalirudin over time and prevention of stasis. RESULTS We found in both preservatives a reduction in ADP-induced platelet aggregation response over a period of 105 minutes (median, IQR: 73-141) as measured by Multiplate®. Supplementation of additional bivalirudin (23 ± 1.1 μg/ml/hr) and prevention of stasis was not able to prevent thrombin generation. We found a 5-fold increase in levels of prothrombin fragment 1+2 in bivalirudin preserved autologous blood as compared to heparin preserved blood (F(1+2) levels median 8.9 nM [quartile percentiles 4.2-12.4] vs 1.3 nM [0.6-2.1], P=0.001 Mann-Whitney, n=10). CONCLUSIONS Our study suggests that preservation of platelet function in autologous blood anticoagulated with bivalirudin is not a suitable alternative to heparin.

Platelet Function in Stored Heparinised Autologous Blood Is Not Superior to in Patient Platelet Function during Routine Cardiopulmonary Bypass

Background In cardiac surgery, cardiopulmonary bypass (CPB) and unfractionated heparin have negative effects on blood platelet function. In acute normovolemic haemodilution autologous unfractionated heparinised blood is stored ex-vivo and retransfused at the end of the procedure to reduce (allogeneic) transfusion requirements. In this observational study we assessed whether platelet function is better preserved in ex vivo stored autologous blood compared to platelet function in the patient during CPB. Methodology/Principal Finding We measured platelet aggregation responses pre-CPB, 5 min after the start of CPB, at the end of CPB, and after unfractionated heparin reversal, using multiple electrode aggregometry (Multiplate®) with adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) and ristocetin activated test cells. We compared blood samples taken from the patient with samples taken from 100 ml ex-vivo stored blood, which we took to mimick blood storage during normovolemic haemodilution. Platelet function declined both in ex-vivo stored blood as well as in blood taken from the patient. At the end of CPB there were no differences in platelet aggregation responses between samples from the ex vivo stored blood and the patient. Conclusion/Significance Ex vivo preservation of autologous blood in unfractionated heparin does not seem to be profitable to preserve platelet function.

The activated clotting time in cardiac surgery: Should Celite or kaolin be used?

Objectives Both kaolin- and Celite-activated clotting times (ACT) are used to guide anticoagulation during cardiopulmonary bypass. It is unknown whether these methods lead to similar management procedures for anticoagulation in patients and are thus interchangeable in terms of bias, precision and variability. Methods We randomized 97 patients undergoing coronary artery bypass grafting or aortic valve replacement to either kaolin- or Celite-guided anticoagulation. The ACT was measured simultaneously with the other method. We administered 300 IU/kg heparin to obtain initial ACT values greater than 400 s and additional heparin in each group using the minimum value of duplicate measurements according to a predefined protocol. The primary end point was the total heparin dose and the number of heparin supplements. Results The total heparin dose per patient in the 48 Celite-guided patients was 35 271 ± 12 406 IU with 51 supplements and in the 49 kaolin-guided patients, 35 997 ± 11 540 IU ( P  = 0.77) with 56 supplements ( P  = 0.53). Postoperative thrombin generation time, fibrinolytic response time, chest tube loss and transfusion requirements were not different between the two groups. However, the methods differed in individual patients with regard to supplemental heparin ( P  = 0.002). Bias between methods at baseline was +10.3%, Celite being higher, and changed to a value of -12.9% at 2 h bypass. The coefficient of variation at baseline for individual patients was 2.6 times larger with kaolin than with Celite ( P  < 0.001). Correlation between ACT values at baseline was only 45%. Conclusions Kaolin- and Celite-guided management of anticoagulation is clinically not different, but the methods are not interchangeable. Clinical registration number www.trialregister.nl identifier 1738.