Optimization of Vancomycin Initial Dosing Regimen in Neonates Using an Externally Evaluated Population Pharmacokinetic Model.

BACKGROUND: Vancomycin therapeutic monitoring guidelines were revised in March 2020, and a population pharmacokinetics-guided Bayesian approach to estimate the 24-hour area under the concentration-time curve to the minimum inhibitory concentration ratio has since been recommended instead of trough concentrations. To comply with these latest guidelines, we evaluated published population pharmacokinetic models of vancomycin using an external dataset of neonatal patients and selected the most predictive model to develop a new initial dosing regimen. METHODS: The models were identified from the literature and tested using a retrospective dataset of Canadian neonates. Their predictive performance was assessed using prediction- and simulation-based diagnostics. Monte Carlo simulations were performed to develop the initial dosing regimen with the highest probability of therapeutic target attainment. RESULTS: A total of 144 vancomycin concentrations were derived from 63 neonates in the external population. Five of the 28 models retained for evaluation were found predictive with a bias of 15% and an imprecision of 30%. Overall, the Grimsley and Thomson model performed best, with a bias of -0.8% and an imprecision of 20.9%; therefore, it was applied in the simulations. A novel initial dosing regimen of 15 mg/kg, followed by 11 mg/kg every 8 hours should favor therapeutic target attainment. CONCLUSIONS: A predictive population pharmacokinetic model of vancomycin was identified after an external evaluation and used to recommend a novel initial dosing regimen. The implementation of these model-based tools may guide physicians in selecting the most appropriate initial vancomycin dose, leading to improved clinical outcomes.

Tackling the Issue of High Postoperative Pacemaker Implantation Rates in Sutureless Aortic Valve Replacement: Should Balloon Inflation be Removed from the Implantation Method of the Perceval Prosthesis?

BACKGROUND: Sutureless aortic valve replacement (AVR) is an emerging alternative to standard AVR in elderly and high-risk patients. This procedure is associated with a high rate of postoperative permanent pacemaker implantation (PPI). The study aim was to assess the impact on the rate of PPI of implanting the Perceval prosthesis without using balloon inflation. METHODS: A total of 159 patients who underwent sutureless AVR using the Perceval prosthesis was included. Balloon inflation was used in 132 patients (Balloon group) and not used in the remaining 27 (No-Balloon group). Clinical, echocardiographic and electrocardiographic outcomes were assessed. RESULTS: There was no significant difference in PPI rate between the two groups (26% for Balloon group versus 22% in No-Balloon group; p = 0.700). Balloon inflation had no significant impact on the incidence of paravalvular leaks (p = 0.839), or on the need to return to cardiopulmonary bypass (CPB) intraoperatively due to paravalvular leak or unsatisfactory deployment (p >0.999). Mean and peak transaortic pressure gradients were similar between the two groups (p = 0.417 and p = 0.522, respectively). Cross-clamp and CPB times were shorter in the No-Balloon group (49.6 ± 15.9 min versus 61.1 ± 25.6 min and 64.1 ± 26.3 min versus 79.6 ± 35.4 min, respectively; p = 0.027 and p = 0.012, respectively). CONCLUSIONS: The two groups had similar postoperative PPI rates. Implanting the Perceval prosthesis without balloon inflation is safe and had no impact on paravalvular leaks, intraoperative complications or hemodynamic results. Reductions in aortic cross-clamp time and CPB time were observed when the balloon was not used.

The association of alvimopan treatment with postoperative outcomes after abdominal surgery: A systematic review across different surgical procedures and contexts of perioperative care.

BACKGROUND: Alvimopan is a Food and Drug Administration-approved treatment to accelerate gastrointestinal recovery after abdominal surgery; however, benefits may vary across different procedures and contexts of care. The purpose of this study is to summarize the evidence regarding the effect of alvimopan on postoperative outcomes after abdominal surgery. METHODS: Major databases (Medline, Embase, Biosis, Cochrane, Web of Science, and Scopus) were searched for randomized controlled trials and nonrandomized studies comparing alvimopan versus control. Risk of bias was assessed using Cochrane's risk of bias tool 2.0 (for randomized controlled trials) and Risk of Bias in Nonrandomized Studies-of Intervention tool (for nonrandomized studies). Results were appraised descriptively as heterogeneity in reporting and risk of bias hindered meta-analysis. Quality of evidence across different surgical procedures and contexts of care (ie, open versus minimally invasive surgery, traditional care versus enhanced recovery pathway) was evaluated using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Nine randomized controlled trials and 35 nonrandomized studies were identified. Evidence of low to moderate certainty supports that alvimopan reduces length of stay and improves gastrointestinal recovery after open bowel resection and open radical cystectomy. Limited evidence supports alvimopan for surgeries not listed in Food and Drug Administration labels (ie, total abdominal hysterectomy and retroperitoneal lymph node dissection). Similar effects were observed in traditional and enhanced recovery pathway settings, but enhanced recovery pathway elements varied across studies. There is very low certainty of evidence supporting alvimopan for patients undergoing minimally invasive surgery. CONCLUSION: Evidence supports that alvimopan improves outcomes after open bowel resection and open radical cystectomy. Benefits for patients undergoing minimally invasive surgery and treated in contemporary enhanced recovery pathway settings remain uncertain. These findings contribute important new knowledge to inform evidence-based alvimopan prescribing.