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Background: Unfractionated heparin (UFH) is commonly used during cardiac surgery with a cardiopulmonary bypass to prevent blood clotting. However, empirical administration of UFH leads to variable responses. Pharmacokinetic and pharmacodynamic modeling can be used to optimize UFH dosing and perform real-time individualization. In previous studies, many factors that could influence UFH pharmacokinetics/pharmacodynamics had not been taken into account such as hemodilution or the type of UFH. Few covariates were identified probably owing to a lack of statistical power. This study aims to address these limitations through a meta-analysis of individual data from two studies. Methods: An individual patient data meta-analysis was conducted using data from two single-center prospective observational studies, where different UFH types were used for anticoagulation. A pharmacodynamic/pharmacodynamic model of UFH was developed using a non-linear mixed-effects approach. Time-varying covariates such as hemodilution and fluid infusions during a cardiopulmonary bypass were considered. Results: Activities of UFH's anti-activated factor/anti-thrombin were best described by a two-compartment model. Unfractionated heparin clearance was influenced by body weight and the specific UFH type. Volume of distribution was influenced by body weight and pre-operative fibrinogen levels. Pharmacodynamic data followed a log-linear model, accounting for the effect of hemodilution and the pre-operative fibrinogen level. Equations were derived from the model to personalize UFH dosing based on the targeted activated clotting time level and patient covariates. Conclusions: The population model effectively characterized UFH's pharmacokinetics/pharmacodynamics in cardiopulmonary bypass patients. This meta-analysis incorporated new covariates related to UFH's pharmacokinetics/pharmacodynamics, enabling personalized dosing regimens. The proposed model holds potential for individualization using a Bayesian estimation. [ABSTRACT FROM AUTHOR]

The venous-arterial difference in CO2 (ΔCO2) has been proposed as an index of the adequacy of tissue perfusion in shock states. We hypothesized that the variation in PaCO2 (hyper- or hypocapnia) could impact ΔCO2, partly through microcirculation adaptations. Fifteen healthy males volunteered to participate. For hypocapnia condition (hCO2), the subjects were asked to hyperventilate, while they were asked to breathe a gas mixture containing 8 % CO2 for hypercapnia condition (HCO2). The 2 conditions were randomly assigned. Blood gases were measured at baseline before each condition, and after 5-7 min of either hCO2 or HCO2 condition. Microcirculation was assessed by the muscle reoxygenation slope measured with near infrared spectroscopy following a vascular occlusion test and by skin circulation with in vivo reflectance confocal microscopy. ΔCO2 was significantly increased with hCO2 while it tended to decrease with HCO2 (non-significant). HCO2 induced a moderate increase of the resaturation slope of NIRS oxygenation. Skin microcirculatory blood flow significantly dropped with hCO2, while it remained unchanged with hypercapnia. Our results warrant cautious interpretation of ΔCO2 as an indicator of tissue perfusion during respiratory alkalosis. [ABSTRACT FROM AUTHOR]

Alteration of tissue perfusion is a main contributor of organ dysfunction. In cardiac surgery, the importance of organ dysfunction is associated with worse outcome. Central venous-arterial difference in CO2 tension (ΔCO2) has been proposed as a global marker of the adequacy of tissue perfusion in shock states. We hypothesized that ΔCO2 could be increased in case of postoperative organ failure or worse outcome. In this monocentric retrospective cohort study, we retrieved, from our database, 220 consecutive patients admitted in intensive care after an elective cardiac surgery. Four time points were formed: ICU admission, and 6, 24 and 48 h after. A ΔCO2 below 6 mmHg defined the normal range values. The SOFA score, intensive care unit and hospital length of stay, hospital and 6-month mortality rate were recorded. We compared patient with low ΔCO2 (<6 mmHg) and high ΔCO2 (≥6 mmHg). We included 55 (25 %) and 165 patients in low and high ΔCO2 groups, respectively. The SOFA score, the hospital and 6 months mortality rate were higher in patients with low ΔCO2. Surprisingly, we did not find results previously published in other surgical settings. In cardiac surgery, ΔCO2 has a low predictive value of outcome. [ABSTRACT FROM AUTHOR]

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