Pediatric ambulatory anesthesia: an update
CURRENT OPINION IN ANESTHESIOLOGY
Authors: Lerman, Jerrold
Abstract
Purpose of review Ambulatory surgery is the standard for the majority of pediatric surgery in 2019 and adenotonsillectomy is the second most common ambulatory surgery in children so it is an apt paradigm. Preparing and managing these children as ambulatory patients requires a thorough understanding of the current literature. Recent findings The criteria for undertaking pediatric adenotonsillectomy on an ambulatory basis, fasting after clear fluids, postoperative nausea and vomiting (PONV), perioperative pain management and discharge criteria comprise the themes addressed in this review. Three criteria determine suitability of adenotonsillectomy surgery on an ambulatory basis: the child's age, comorbidities and the severity of the obstructive sleep apnea syndrome (OSAS). Diagnosing OSAS in children has proven to be a challenge resulting in alternate, noninvasive techniques, which show promise. Abbreviating the 2 h clear fluid fasting guideline has garnered attention, although the primary issue is that parents do not follow the current clear fluid fasting regimen and until that is resolved, consistent fasting after clear fluids will remain elusive. PONV requires aggressive prophylactic measures that fail in too many children. The importance of unrecognized genetic polymorphisms in PONV despite prophylactic treatment is understated as are the future roles of palonosetron and Neurokinin-1 receptor antagonists that may completely eradicate PONV when combined with dexamethasone. Pain management requires test doses of opioids intraoperatively in children with OSAS and nocturnal desaturation to identify those with reduced opioid dosing thresholds, an uncommon practice as yet. Furthermore, postdischarge nonsteroidal anti-inflammatory agents as well as other pain management strategies should replace oral opioids to prevent respiratory arrests in those who are ultra-rapid CYP2D6 metabolizers. Finally, discharge criteria are evolving and physiological-based criteria should replace time-based, reducing the risk of readmission.
Predicting steady-state endoxifen plasma concentrations in breast cancer patients by CYP2D6 genotyping or phenotyping. Which approach is more reliable?
PHARMACOLOGY RESEARCH & PERSPECTIVES
Authors: Gusella, Milena; Pasini, Felice; Corso, Barbara; Bertolaso, Laura; De Rosa, Giovanni; Falci, Cristina; Modena, Yasmina; Barile, Carmen; Da Corte, Donatella Z.; Fraccon, AnnaPaola; Toso, Silvia; Cretella, Elisabetta; Brunello, Antonella; Modonesi, Caterina; Segati, Romana; Oliani, Cristina; Minicuci, Nadia; Padrini, Roberto
Abstract
In previous studies, steady-state Z-endoxifen plasma concentrations (ENDOss) correlated with relapse-free survival in women on tamoxifen (TAM) treatment for breast cancer. ENDOss also correlated significantly withCYP2D6 genotype (activity score) andCYP2D6 phenotype (dextromethorphan test). Our aim was to ascertain which method for assessingCYP2D6 activity is more reliable in predicting ENDOss. The study concerned 203 Caucasian women on tamoxifen-adjuvant therapy (20 mg q.d.). Before starting treatment,CYP2D6 was genotyped (and activity scores computed), and the urinary log(dextromethorphan/dextrorphan) ratio [log(DM/DX)] was calculated after 15 mg of oral dextromethorphan. Plasma concentrations of TAM, N-desmethyl-tamoxifen (ND-TAM), Z-4OH-tamoxifen (4OH-TAM) and ENDO were assayed 1, 4, and 8 months after first administering TAM. Multivariable regression analysis was used to identify the clinical and laboratory variables predicting log-transformed ENDOss (log-ENDOss). Genotype-derivedCYP2D6 phenotypes (PM, IM, NM, EM) and log(DM/DX) correlated independently with log-ENDOss. Genotype-phenotype concordance was almost complete only for poor metabolizers, whereas it emerged that 34% of intermediate, normal, and ultrarapid metabolizers were classified differently based on log(DM/DX). Multivariable regression analysis selected log(DM/DX) as the best predictor, with patients' age, weak inhibitor use, andCYP2D6 phenotype decreasingly important: log-ENDOss = 0.162 - log(DM/DX) x 0.170 + age x 0.0063 - weak inhibitor use x 0.250 + IM x 0.105 + (NM + UM) x 0.210; (R-2 = 0.51). In conclusion, log(DM/DX) seems superior to genotype-derivedCYP2D6 phenotype in predicting ENDOss.