Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Interest in antifibrinolytic tranexamic acid (TA) has grown since the widespread removal of aprotinin, but its dosing during cardiac surgery is still debated. The objectives of this study were to investigate the population pharmacokinetics (PK) of TA given with either low- or high-dose continuous infusion schemes in adult cardiac surgery patients during cardiopulmonary bypass (CPB). METHODS: Patients were randomized to receive either low-dose (10 mg kg(-1) followed by an infusion of 1 mg kg(-1) h(-1) throughout the operation, and 1 mg kg(-1) into the CPB) or high-dose (30 mg kg(-1), then 16 mg kg(-1) h(-1), and 2 mg kg(-1) into the CPB) TA. Serum TA concentrations were measured in 61 patients and the data were modelled using Monolix. RESULTS: TA concentrations were 28-55 µg ml(-1) in the low-dose group and 114-209 µg ml(-1) in the high-dose group throughout surgery. TA PK was best described by a two-compartment open model. The main covariate effect was bodyweight, whereas the CPB did not influence the PK. Assuming a bodyweight of 70 kg, the population estimates were 4.8 litre h(-1) for clearance, 6.6 litre for the volume of the central compartment, 32.2 litre h(-1) for the diffusional clearance, and the peripheral volume of distribution was 10.8 litre. CONCLUSIONS: The PK of TA was satisfactorily described by an open two-compartmental model, which was used to propose a dosing scheme suitable for obtaining and maintaining the desired plasma concentration in a stable and narrow range in cardiac surgery patients.

[Coagulation disorders after traumatic brain injury: pathophysiology and therapeutic implications]. / Troubles de la coagulation lors du traumatisme cranio-encéphalique: physiopathologie et conséquences thérapeutiques.

Early activation of coagulation is common after traumatic brain injury. Its origin is probably mainly intracerebral, due to tissue factor release from the injured brain. Abnormalities in blood coagulation tests are associated with poor neurological prognosis. Coagulation activation may induce disseminated intravascular coagulation and fibrinolysis. Disseminated intravascular coagulation is linked to brain ischemia caused by intravascular microthrombosis. This review will focus on pathophysiology of coagulation disorders after traumatic brain injury, and on their implications for therapeutic approaches.

Anticoagulation monitoring during vascular surgery: accuracy of the Hemochron low range activated clotting time (ACT-LR).

BACKGROUND: Activated clotting time (ACT) is currently used to monitor high concentrations of heparin anticoagulation. A new instrument, the Hemochron Jr Signature device, has been specifically designed to measure ACT in low-range heparin plasma concentrations (ACT-LR). The purpose of this study was to compare ACT-LR with anti-Xa activity in patients receiving low-dose i.v. heparin during vascular surgery. METHODS: Thirty patients, undergoing arterial vascular surgery, were included in the study and received unfractionated heparin (initial dose 50 u kg(-1)). One hundred and thirty-two pairs of blood samples were simultaneously collected during surgery to determine ACT-LR and anti-Xa activity. Pearson correlation, Kappa test, ROC curve and a specific clinical interpretation of the correlation were performed. RESULTS: ACT-LR ranged from 68 to 380 s, anti-Xa activity from 0 to 1.45 u ml(-1). We observed a strong correlation between anti-Xa activity and ACT-LR (r(2)=0.87; P<0.0001). Accuracy of ACT-LR was good for anti-Xa activity up to 0.6 u ml(-1) (Kappa, 0.94; accuracy, 97%) and 0.8 u ml(-1) (Kappa, 0.79; accuracy, 90%), and poor for anti-Xa activity above 1 u ml(-1) (Kappa, 0.59). A clinical interpretation of the correlation graph found 98% of measured ACT-LR values to be accurate. CONCLUSION: Hemochron Jr Signature provides measurements of ACT-LR, which are accurate for monitoring heparin anticoagulation at anti-Xa activity below 0.8 u ml(-1).

[Changes in blood gases with temperature: implications for clinical practice]. / Les variations thermiques modifient les paramètres des gaz du sang: quelles conséquences en pratique clinique?

OBJECTIVE: To understand changes in blood gases results with core temperature. METHODS: Analysis from two case reports. RESULTS: Hypothermia induces a decrease in PaCO(2) with a related increase in pH, thus a physiologic alkalosis. Decrease in PaCO(2) is due to an increase of gas solubility and a decrease of peripheral consumption that can be estimated from comparison between corrected and non-corrected for temperature blood gases. For O(2), variations of temperature induce variations of solubility but also of haemoglobin affinity for O(2). During hyperthermia, haemoglobin affinity for O(2) is decreased with a decreased SvO(2) for a same PvO(2). SvO(2) ischemic or therapeutic thresholds are thus modified with core temperature. CONCLUSION: Blood gases cannot be understood without patient core temperature. Physiologic variations of PaCO(2) and pH must probably be tolerated. Ischemic threshold should be estimated on PvO(2), not only on PvO(2).