title: Influence of intensive care treatment on the protein binding of sufentanil and hydromorphone during pain therapy in postoperative cardiac surgery patients.
abstract: 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.
  
  
  BACKGROUND
  EudraCT 2011-003648-31 and ClinicalTrials.gov: NCT01490268.
authors.affiliation: Anästhesiologische Klinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, PO Box 52 (Kiinamyllynkatu 4-8), 20521 Turku, Finland teijo.saari@gmail.com.
authors.forename: T I
authors.initials: TI
authors.lastname: Saari
authors.affiliation: Anästhesiologische Klinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Ihmsen
authors.affiliation: Anästhesiologische Klinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, PO Box 52 (Kiinamyllynkatu 4-8), 20521 Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Mell
authors.affiliation: Anästhesiologische Klinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Fröhlich
authors.affiliation: Anästhesiologische Klinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Fechner
authors.affiliation: Anästhesiologische Klinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schüttler
authors.affiliation: Anästhesiologische Klinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Jeleazcov
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D006348:Cardiac Surgical Procedures / Q000379:methods*; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D010149:Postoperative Pain / Q000188:drug therapy*; D011446:Prospective Studies; D011485:Protein Binding; D012044:Regression Analysis; D017409:Sufentanil / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D013908:Thoracotomy
chemical_list: D000701:Analgesics, Opioid; D017409:Sufentanil; D004091:Hydromorphone
keywords: analgesics, opioids; intensive care; pain management; pharmacokinetics; protein binding