ABSTRACT
PURPOSE: Cases of local anaesthetic systemic toxicity (LAST) periodically occur following transversus abdominal plane (TAP) blocks. The aim of this study was to characterize levobupivacaine absorption pharmacokinetics, with and without epinephrine, and estimate the risk of LAST, based on a previously reported toxic threshold. METHODS: Previously reported data from 11 volunteers receiving ultrasound-guided TAP blocks with and without epinephrine on two independent occasions were analysed. Serial venous concentrations were measured for 90 min. A pharmacokinetic analysis was performed using the NONMEM statistical programme. The use of epinephrine in the solution was included in the analysis of covariates. The associated risk of LAST symptoms associated with different levobupivacaine dose schemes with and without epinephrine was estimated in 1000 simulated subjects. RESULTS: A one-compartment first-order input and elimination model adequately fit the levobupivacaine data. Epinephrine prolonged the levobupivacaine absorption half-life {4.22 [95 % confidence interval (CI) 2.53-6.50] vs. 7.02 [95 % CI 3.74-14.1]; p < 0.05} and reduced its relative bioavailability (0.84; 95 % CI 0.72-0.97; p < 0.05) The derived model predicts that levobupivacaine dose schemes should be halved from 3 mg kg(-1) body weight with epinephrine to 1.5 mg kg(-1) without epinephrine to obtain a comparable risk of anaesthetic toxicity symptoms of approximately 0.1 %. CONCLUSIONS: Our results strongly support the addition of epinephrine to the local anaesthetic solution, especially when doses of levobupivacaine of >1.5 mg kg(-1) are required. Recommendations regarding the maximum allowable doses of local anaesthetics should consider population analysis to determine safer dosage ranges.
Subject(s)
Anesthetics, Local/pharmacokinetics , Bupivacaine/analogs & derivatives , Epinephrine/pharmacology , Abdominal Muscles/innervation , Adult , Anesthetics, Local/administration & dosage , Anesthetics, Local/adverse effects , Bupivacaine/administration & dosage , Bupivacaine/adverse effects , Bupivacaine/pharmacokinetics , Computer Simulation , Cross-Over Studies , Double-Blind Method , Half-Life , Healthy Volunteers , Humans , Levobupivacaine , Male , Models, Biological , Nerve Block , RiskABSTRACT
BACKGROUND: Postoperative vomiting (POV) is one of the most frequent complications of tonsillectomy in children. The aim of this study was to evaluate the antiemetic effect of super-hydration with lactated Ringer's solution in children undergoing elective otorhinolaryngological surgery. METHODS: One hundred ASA I-II children, aged 1-12 yr, undergoing elective tonsillectomy, with or without adenoidectomy, under general anaesthesia were studied. Induction and maintenance of anaesthesia were standardized with fentanyl, mivacurium, and sevoflurane in N(2)O/O(2). Subjects were assigned to one of the two groups: 10 ml kg(-1) h(-1) lactated Ringer's solution or 30 ml kg(-1) h(-1) lactated Ringer's solution. A multivariable logistic regression was used for assessing the effects of super-hydration on POV (defined as the presence of retching, vomiting, or both). A value of P<0.05 was considered statistically significant. RESULTS: During the first 24 h postoperative, the incidence of POV decreased from 82% to 62% (relative reduction of 24%, P=0.026). In the adjusted logistic regression model, subjects in the 10 ml kg(-1) h(-1) group had an odds ratio of POV that was 2.92 (95% confidence interval: 1.14, 7.51) for POV compared with subjects in the 30 ml kg(-1) h(-1) group. CONCLUSIONS: Intraoperative administration of 30 ml kg(-1) h(-1) lactated Ringer's solution significantly reduced the incidence of POV during the first 24 h postoperative. Our results support the use of super-hydration during tonsillectomy, as an alternative way to decrease the risk of POV in children.
Subject(s)
Fluid Therapy/methods , Postoperative Nausea and Vomiting/epidemiology , Postoperative Nausea and Vomiting/therapy , Tonsillectomy/adverse effects , Anesthesia Recovery Period , Anesthesia, General , Antiemetics/therapeutic use , Child , Child, Preschool , Cost-Benefit Analysis , Female , Fluid Therapy/economics , Humans , Infant , Logistic Models , Male , Postoperative Nausea and Vomiting/economics , Tonsillectomy/economics , Treatment OutcomeABSTRACT
BACKGROUND: The plasma-effect site equilibration rate constant (k(e0)) of propofol has been determined in children with the use of the time to maximum effect (t(peak)), however, it has not been validated. The objective was to measure the t(peak;) of propofol with two depths of anesthesia monitors in children and to evaluate these measurements with a target-controlled infusion (TCI) system. METHODS: Unpremedicated, ASA I children from 3 to 11 years were studied. In Part 1, children were monitored simultaneously with the bispectral index (BIS) and the A-Line ARX-index (AAI) from the Alaris A-Line auditory-evoked potential monitor/2. The t(peak) after a bolus dose of propofol was measured. In Part 2, the t(peak) measured was used to target the effect site with a TCI system. The median (MD) and the absolute median (MDA) difference between the predicted time of peak concentration at the effect site (Ce) and the measured time of peak effect in the index of depth of anesthesia (t(error)) was used to evaluate the performance of the system. RESULTS: The BIS recordings were of a better quality than the AAI. The mean +/- standard deviation t(peak) was 65 +/- 14 s with the BIS (n=25) and 201 +/- 74 s with the AAI (n=10)(P<0.001). Validation was only performed with the BIS monitor in 40 children, yielding an MD t(error) of -9.5 s and an MDA t(error) of 10.0 s. CONCLUSIONS: The small delay between the evolution of Ce of propofol and the observed effect suggests that this can be a useful model to target the effect site in children.
