Influence of intensive care treatment on the protein binding of sufentanil and hydromorphone during pain therapy in postoperative cardiac surgery patients

Background: Our objective was to evaluate the effect of intensive care treatment on the protein binding of sufentanil and hydromorphone in cardiac surgery patients during postoperative analgesia using a target-controlled infusion (TCI) and patient-controlled analgesia (PCA). Methods: Fifty adult patients were enrolled in this prospective randomized study; of which, 49 completed the study (age range 40–81 yr). Sufentanil was administered as an analgesic intraoperatively, and hydromorphone was dosed after operation with TCI and PCA until 8 a.m. on the first postoperative day. Arterial plasma samples were collected for drug and protein concentration measurements up to 24 h after cardiac surgery. Corresponding patient data were collected from the electronic patient data system. After explorative data analysis with principal component analysis, multivariate regression analysis and non-linear mixed effects modelling was used to study the effect of treatment on protein binding. Results: Data of 35 patients were analysed. The median protein binding of sufentanil and hydromorphone was 88.4% (IQ range 85.7–90.5%) and 11.6% (IQ range 9.5–14.3%), respectively. Free fraction of sufentanil increased towards the end of the study period, whereas hydromorphone free fraction remained nearly constant. The total sufentanil concentration and volume balance were identified as significant covariates for the protein binding of sufentanil. For the protein binding of hydromorphone, no significant covariate effects were found. Conclusions: Sufentanil protein binding was significantly dependent on changes in the total drug concentration and volume balance addressing the importance of adequate dosing and fluid-guided therapy. Hydromorphone protein binding was nearly constant throughout the study period. Clinical trial registration: EudraCT 2011-003648-31 and ClinicalTrials.gov: NCT01490268

[Target-controlled infusion. Clinical relevance and special features when using pharmacokinetic models],[Target-controlled infusion. Clinical relevance and special features when using pharmacokinetic models]

Contains fulltext : 79741.pdf (publisher's version ) (Closed access)Since its commercial introduction in 1996, target-controlled infusion (TCI) has become an established technique for administration of intravenous anaesthetics. Modern TCI systems, however, are characterized by an increasing number of additional options and features, such as the choice between different pharmacokinetic models and modes of application, which may confuse the less experienced user. This review describes the differences between pharmacokinetic models, modes of application and the effect of covariates as well as the consequences for dosing. The aim is to explicate for the user of modern TCI systems the underlying scientific concepts and the relevance for clinical practice

Influence of intensive care treatment on the protein binding of sufentanil and hydromorphone during pain therapy in postoperative cardiac surgery patients

Background: Our objective was to evaluate the effect of intensive care treatment on the protein binding of sufentanil and hydromorphone in cardiac surgery patients during postoperative analgesia using a target-controlled infusion (TCI) and patient-controlled analgesia (PCA). Methods: Fifty adult patients were enrolled in this prospective randomized study; of which, 49 completed the study (age range 40–81 yr). Sufentanil was administered as an analgesic intraoperatively, and hydromorphone was dosed after operation with TCI and PCA until 8 a.m. on the first postoperative day. Arterial plasma samples were collected for drug and protein concentration measurements up to 24 h after cardiac surgery. Corresponding patient data were collected from the electronic patient data system. After explorative data analysis with principal component analysis, multivariate regression analysis and non-linear mixed effects modelling was used to study the effect of treatment on protein binding. Results: Data of 35 patients were analysed. The median protein binding of sufentanil and hydromorphone was 88.4% (IQ range 85.7–90.5%) and 11.6% (IQ range 9.5–14.3%), respectively. Free fraction of sufentanil increased towards the end of the study period, whereas hydromorphone free fraction remained nearly constant. The total sufentanil concentration and volume balance were identified as significant covariates for the protein binding of sufentanil. For the protein binding of hydromorphone, no significant covariate effects were found. Conclusions: Sufentanil protein binding was significantly dependent on changes in the total drug concentration and volume balance addressing the importance of adequate dosing and fluid-guided therapy. Hydromorphone protein binding was nearly constant throughout the study period. Clinical trial registration: EudraCT 2011-003648-31 and ClinicalTrials.gov: NCT01490268