RESUMO
Target controlled infusion (TCI) is a clinically-available and widely-used computer-controlled method of drug administration, adjusting the drug titration towards user selected plasma- or effect-site concentrations, calculated according to pharmacokinetic-pharmacodynamic (PKPD) models. Although this technology is clinically available for several anaesthetic drugs, the contemporary commercialised PKPD models suffer from multiple limitations. First, PKPD models for anaesthetic drugs are developed using deliberately selected patient populations, often excluding the more challenging populations, such as children, obese or elderly patients, of whom the body composition or elimination mechanisms may be structurally different compared to the lean adult patient population. Separate PKPD models have been developed for some of these subcategories, but the availability of multiple PKPD models for a single drug increases the risk for invalid model selection by the user. Second, some models are restricted to the prediction of plasma-concentration without enabling effect-site controlled TCI or they identify the effect-site equilibration rate constant using methods other than PKPD modelling. Advances in computing and the emergence of globally collected databases has allowed the development of new "general purpose" PKPD models. These take on the challenging task of identifying the relationships between patient covariates (age, weight, sex, etc) and the volumes and clearances of multi-compartmental pharmacokinetic models applicable across broad populations from neonates to the elderly, from the underweight to the obese. These models address the issues of allometric scaling of body weight and size, body composition, sex differences, changes with advanced age, and for young children, changes with maturation and growth. General purpose models for propofol, remifentanil and dexmedetomidine have appeared and these greatly reduce the risk of invalid model selection. In this narrative review, we discuss the development, characteristics and validation of several described general purpose PKPD models for anaesthetic drugs.
RESUMO
This study measured the number of complications after deep inferior epigastric perforator (DIEP) flap reconstruction performed under opioid-free anesthesia (OFA) combined with goal-directed fluid therapy or opioid anesthesia with liberal fluid therapy (OA). This retrospective cohort study consisted of 204 patients who underwent DIEP flap reconstruction at AZSint Jan Brugge between April 2014 and March 2019. Primary outcomes were complications, according to the Clavien-Dindo classification and the length of hospital stay (LOS). The secondary outcomes were flap failure, postoperative nausea and vomiting (PONV), postoperative pain, postoperative opioid consumption, and postoperative skin flap temperature. OFA included a combination of dexmedetomidine, lidocaine, and ketamine without any opioid administered pre- or intraoperatively. OA included a combination of sufentanil and remifentanil. OFA patients received strict goal-directed fluid therapy, whereas OA patients received liberal fluids to maintain perfusion pressure. All patients except 7 (TIVA with remifentanil) received inhalation anesthesia combined with an infusion of propofol. Of the 204 patients, 55 received OFA and 149 received OA. There were no differences in major complications, but fewer minor complications in the OFA group (17.9% vs. 51.4% and P < 0.001). Flap failure occurred in three patients of the OA group. Six patients developed flap thrombosis (five OA patients and one OFA patient). OFA was associated with fewer postoperative opioids, shorter LOS, less PONV, and less pain. In patients without previous nausea, the PONV incidence was higher in the OA group than in the OFA group (12.7% vs. 43.6% and P < 0.001). Patients with previous nausea more frequently required postoperative opioids and had a nausea rate of 60.87%.
