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Early Bayesian Dose Adjustment of Vancomycin Continuous Infusion in Children: a Randomized Controlled Trial.

ABSTRACT: Methicillin-resistant staphylococcal infections are a global burden. Area under the serum concentration-time curve to minimum inhibitory concentration (AUC/MIC) ratio is the pharmacokinetic (PK) parameter that best predicts vancomycin efficacy. Its therapeutic range is narrow, difficult to achieve because of a wide intersubject variability, especially in children, and is not routinely targeted since the AUC is rarely available. We investigated if an early Bayesian dose adjustment would increase the rate of vancomycin target attainment, in the first 24 hours of treatment (H24), in children.We conducted a single-centre randomized controlled trial in 4 pediatric departments of Necker-Enfants Malades hospital (Paris, France). Patients aged 3 months to 17 years for whom intravenous vancomycin was started were eligible and randomized in a 1:1 ratio: routine care were compared with an early vancomycin therapeutic drug monitoring (3h after treatment initiation) followed by an early Bayesian dose adjustment using a previously published population-based PK model that included age, bodyweight and serum creatinine as covariates. The primary outcome was the proportion of patients of each group achieving vancomycin therapeutic range at H24, defined by AUC0-24/MIC?400 and AUC0-24 ?800mg-h/L.Ninety-nine patients were enrolled: 49 were randomized to the Bayesian group and 50 to the control group. Modified intention-to-treat analysis included 82 patients: 85% of Bayesian group patients achieved H24 vancomycin target versus 57% of control group patients (p=0.007) with no difference regarding iatrogenic events. Early Bayesian dose adjustment increased the proportion of children achieving vancomycin target at H24, which may improve clinical outcomes of methicillin-resistant staphylococcal infections.

SUBMITTER: Berthaud R

PROVIDER: S-EPMC6879247 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Early Bayesian Dose Adjustment of Vancomycin Continuous Infusion in Children: a Randomized Controlled Trial.

Berthaud Romain R Benaboud Sihem S Hirt Déborah D Genuini Mathieu M Oualha Mehdi M Castelle Martin M Briand Coralie C Artru Solène S Norsa Lorenzo L Boyer Olivia O Foissac Frantz F Bouazza Naïm N Tréluyer Jean-Marc JM

Antimicrobial agents and chemotherapy 20190901 12

Methicillin-resistant staphylococcal infections are a global burden. Area under the serum concentration-time curve to minimum inhibitory concentration (AUC/MIC) ratio is the pharmacokinetic (PK) parameter that best predicts vancomycin efficacy. Its therapeutic range is narrow, difficult to achieve because of a wide intersubject variability, especially in children, and is not routinely targeted since the AUC is rarely available. We investigated if an early Bayesian dose adjustment would increase ...[more]

PMID: 31591117

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Project description:IntroductionRecent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements.MethodsWe enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 microg.kg-1.h-1), vasopressin (.03 U.min-1) or norepinephrine (15 microg.min-1; n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA.ResultsThere were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of .03 U of vasopressin or 15 microg.min-1 of norepinephrine, 1.3 microg.kg-1.h-1 of terlipressin allowed a marked reduction in catecholamine requirements (0.8 +/- 1.3 and 1.2 +/- 1.4 vs. 0.2 +/- 0.4 microg.kg-1.min-1 at 48 hours; each P < 0.05) and was associated with less rebound hypotension (P < 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 +/- 2.8 and 2.8 +/- 2.5 vs. 0.9 +/- 0.3 mg.dL-1; each P < 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P < 0.001 48 hours vs. BL).ConclusionsThe present study provides evidence that continuous infusion of low-dose terlipressin--when given as first-line vasopressor agent in septic shock--is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements.

Project description:Background: Combination of dexmedetomidine and opioid may be an alternative to high-dose opioid in attenuating cough during emergence from anesthesia, while also reducing the adverse effects of high-dose opioid. We tested the hypothesis that a single-dose of dexmedetomidine combined with low-dose remifentanil infusion during emergence would not be inferior to high-dose remifentanil infusion alone in attenuating cough after thyroidectomy. Methods: One hundred sixty-nine patients undergoing thyroidectomy were enrolled and randomized in a 1:1 ratio into group DR or group R. Each patient received an infusion of dexmedetomidine (0.5 μg/kg) and low-dose remifentanil infusion of effect-site concentration (Ce) at 1 ng/mL or normal saline and high-dose remifentanil infusion of Ce at 2 ng/mL for 10 min at the end of surgery. Remifentanil was maintained until tracheal extubation. Primary endpoint was the severity of coughing, which was assessed for non-inferiority using a four-point scale at the time of extubation. For comparison of coughing incidence during emergence, coughing grade was also measured at three times: before extubation, at extubation, and after extubation. Time to awakening, hemodynamic and respiratory profile, pain, and postoperative nausea and vomiting were also evaluated for superiority. Results: The 95% confidence intervals for differences in cough grade during tracheal extubation were <0.9, indicating non-inferiority of the single dose of dexmedetomidine combined with low-dose remifentanil infusion. The incidence of coughing was similar in the two groups. Hemodynamic changes during tracheal extubation were attenuated, but emergence from anesthesia was delayed, in group DR. Use of rescue antiemetic was similar in both groups, but the incidence of vomiting was less in group DR. Conclusion: A single-dose of dexmedetomidine (0.5 μg/kg) combined with low-dose remifentanil infusion at 1 ng/mL of Ce during emergence from sevoflurane-remifentanil anesthesia was not inferior to high-dose remifentanil infusion alone at 2 ng/mL of Ce with regard to suppressing cough.

Project description:PurposeA subcostal flank incision is required for open radical nephrectomy, which is a surgical procedure used to remove tumors of the kidney that are malignant. The erector spinae plane block (ESPB) and continuous catheter use in children are receiving more and more support by paediatric regional anaesthesiologists. Our objective was to compare systemic analgesic to continuous ESPB for pain relief in paediatric patients undergoing open radical nephrectomy.MethodsSixty children with cancer ASA I or II and undergoing open radical nephrectomy between the ages of two and seven participated in this prospective, randomized, controlled, and open label study. The cases were divided into two equal groups (E and T groups); Group E received ipsilateral continuous ultrasound-guided ESPB at T9 (thoracic vertebrae), with a bolus of 0.4 mL/kg bupivacaine 0.25%. Immediately postoperatively, Group E (ESPB group) received continuous ESPB with a PCA (patient controlled analgesia) pump at a rate of 0.2 mL/kg/hour bupivacaine 0.125%. Group T (Tramadol group), Tramadol hydrochloride was administered intravenously at a dose of 2 mg/kg/8hour, which could be increased to 2 mg/kg/6hours. Then, we followed up on patients' total analgesic consumption for 48 hours following surgery, as well as the time it took for them to request rescue analgesic, their FLACC and sedation scores, and their hemodynamics and side effects immediately following surgery as well as at 2, 4, 6, 8, 12, 18, 24, 36, and 48 hours.ResultsA highly significant difference in total tramadol consumed in group T 11.97 ± 1.13 mg/kg while group E was 2.07± 1.54 mg/kg (p < 0.001). 100% patients in group T requested analgesia compared to 46.7% patients in group E (p < 0.001). From 2 to 48 hour, FLACC significantly decreased in E compared to T group (p≤ 0.006) at all-time points.ConclusionUltrasound-guided continuous ESPB significantly provided better postoperative pain relief, reduced postoperative tramadol consumption and reduced pain scores compared with the use of tramadol alone, in paediatric cancer patients undergoing nephrectomy.

Project description:BackgroundIn epidemiological studies explanatory variables are frequently subject to measurement error. The aim of this paper is to develop a Bayesian method to correct for measurement error in multiple continuous exposures in individually matched case-control studies. This is a topic that has not been widely investigated. The new method is illustrated using data from an individually matched case-control study of the association between thyroid hormone levels during pregnancy and exposure to perfluorinated acids. The objective of the motivating study was to examine the risk of maternal hypothyroxinemia due to exposure to three perfluorinated acids measured on a continuous scale. Results from the proposed method are compared with those obtained from a naive analysis.MethodsUsing a Bayesian approach, the developed method considers a classical measurement error model for the exposures, as well as the conditional logistic regression likelihood as the disease model, together with a random-effect exposure model. Proper and diffuse prior distributions are assigned, and results from a quality control experiment are used to estimate the perfluorinated acids' measurement error variability. As a result, posterior distributions and 95% credible intervals of the odds ratios are computed. A sensitivity analysis of method's performance in this particular application with different measurement error variability was performed.ResultsThe proposed Bayesian method to correct for measurement error is feasible and can be implemented using statistical software. For the study on perfluorinated acids, a comparison of the inferences which are corrected for measurement error to those which ignore it indicates that little adjustment is manifested for the level of measurement error actually exhibited in the exposures. Nevertheless, a sensitivity analysis shows that more substantial adjustments arise if larger measurement errors are assumed.ConclusionsIn individually matched case-control studies, the use of conditional logistic regression likelihood as a disease model in the presence of measurement error in multiple continuous exposures can be justified by having a random-effect exposure model. The proposed method can be successfully implemented in WinBUGS to correct individually matched case-control studies for several mismeasured continuous exposures under a classical measurement error model.

Dataset Information

Early Bayesian Dose Adjustment of Vancomycin Continuous Infusion in Children: a Randomized Controlled Trial.

Publications

Early Bayesian Dose Adjustment of Vancomycin Continuous Infusion in Children: a Randomized Controlled Trial.

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