Model-Informed Clinical Practice - Determining an Appropriate Ampicillin-Sulbactam Redosing Regimen in Surgical Patients by Utilizing Population Pharmacokinetics and Target Attainment Analysis.

In the current study, population pharmacokinetic (PK) of ampicillin-sulbactam was performed based on the clinical pharmacokinetics data collected from a prospective study conducted in 40 surgical patients undergoing prolonged surgery where antibiotic redosing was implemented. A population PK model was successfully developed to characterize the disposition of ampicillin and sulbactam. The final models were two-compartment models for both drugs, with creatinine clearance and heart failure affecting clearance and body surface area having an impact on the central volume of distribution of both ampicillin and sulbactam. Comprehensive Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of 24 different redosing scenarios. Simulation results indicated that the ampicillin-sulbactam 2-h redosing scheme recommended by ASHP guidelines is likely too conservative given that 3-g dose (2-g ampicillin/1-g sulbactam) with 4-h redosing interval can reach the breakpoint of 2 mg/L for ampicillin in all populations even with the aggressive pharmacokinetic/pharmacodynamic (PK/PD) target of 100% fT > MIC. With the target 50% fT > MIC, all redosing schemes evaluated, including the 8-h redosing scenario, are predicted to be able to reach the breakpoint of 64 mg/L in all patients. According to our findings, redosing of ampicillin-sulbactam should be every 4 h instead of the currently recommended 2-h redosing schedule. Our PTA results should inform future updates to existing general antibiotic redosing guidelines; and, when used in combination with the availability of institution- and/or unit-specific ampicillin susceptibility patterns, our PTA results may be used to customize SSI prophylaxis redosing recommendations for ampicillin-sulbactam at individual hospitals.

Development and validation of a simple and sensitive LC-MS/MS method for the quantification of cefazolin in human plasma and its application to a clinical pharmacokinetic study.

Cefazolin is widely used during surgery to prevent surgical site infections (SSIs). Although cefazolin redosing is often needed due to its short half-life, the appropriate redosing schedule remains controversial and there is limited information on cefazolin disposition following repeated doses during surgery. In parallel with an ongoing cefazolin redosing clinical study, we have developed and fully validated a simple and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of cefazolin in human plasma. A simple protein precipitation was used for sample preparation. MS/MS analysis was performed using multiple reaction monitoring (MRM) under a positive ionization mode. The lower limit of quantification (LLOQ) for cefazolin was evaluated at 0.25 µg/mL and a linearity ranging from 0.25 to 300 µg/mL. Accuracy was ≤ 114.3% for quality controls and ≤ 118.2% for LLOQ; intra-day and inter-day precision ranging from 1.9% to 14.2% for all quality controls and LLOQ. Matrix effect, extraction recovery, stability testing, dilution integrity, hemolysis effects and whole blood stability have all been investigated. A total of 17 parameters were validated and passed their validation criteria. The method was applied in the quantification of cefazolin in clinical plasma samples and was able to successfully determine the concentrations in patients undergoing various surgeries. In comparison with other prior published methods, our method has a simple sample preparation combined with a short analysis run time, a wide dynamic range and low limit of quantification, and is a fully validated assay that abides by FDA guidance.

Development and validation of a simple and sensitive LC-MS/MS method for quantification of ampicillin and sulbactam in human plasma and its application to a clinical pharmacokinetic study.

Ampicillin-sulbactam is a broad-spectrum combination antibiotic used for a variety of clinical applications, including as a prophylactic agent to reduce the risk of surgical site infection. The pharmacokinetics of ampicillin-sulbactam after redosing during prolonged surgeries remains incompletely understood. In anticipation of further studying the intra-operative pharmacokinetics of this drug, we have developed a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of ampicillin and sulbactam. The plasma samples were prepared using a simple protein precipitation method. Gradient chromatographic elution was used to separate analytes, and MS/MS analysis was performed in negative ionization mode for both analytes via multiple reaction monitoring (MRM). All validation parameters were evaluated under a good laboratory practice (GLP) environment. For both ampicillin and sulbactam, the lower limit of quantitation (LLOQ) was established as 0.25 µg/mL. The calibration curve ranged from 0.25 to 200 µg/mL for ampicillin and 0.25-100 µg/mL for sulbactam. Inter- and intra-day precisions for both analytes were ≤11.5 % for quality controls and ≤17.4 % for LLOQ; accuracies ranged from -11.5 to 12.5% for 3 quality control levels and -18.1-18.7% for LLOQ. In addition to sensitivity, accuracy and precision, 13 other parameters were also validated for both analytes, and the results met the acceptance criteria. Our method was successfully applied to quantify ampicillin and sulbactam concentrations in patients undergoing surgery.

Implementation of a multifaceted program to sustainably improve appropriate intraoperative antibiotic redosing.

BACKGROUND: National guidelines recommend intraoperative redosing of prophylactic antibiotics at defined intervals to reduce the risk of surgical site infections. Compliance with these guidelines is poor. METHODS: A quality improvement project-including education, progress reports, and automated redosing reminders in the anesthesia electronic health record-was implemented at a large university-affiliated hospital to increase rates of intraoperative antibiotic redosing for surgeries lasting more than 4 hours. A retrospective, observational study was then conducted. The primary outcome was the compliance rate with intraoperative antibiotic redosing criteria for all surgeries lasting more than 4 hours in the pre- and post-project period. The effect of the intervention was assessed by an interrupted time-series Poisson regression model. RESULTS: A total of 13,695 surgical procedures were evaluated. Time-series analysis demonstrated that the project was associated with significant improvement of compliance rates (incidence rate ratio [IRR]: 1.16; P = .002) with no significant change in underlying improvement trend (IRR: 1.00; P = .22). DISCUSSION: Few peer-reviewed manuscripts describe effective methods to ensure appropriate antibiotic redosing during prolonged surgeries. We demonstrated that a multipronged approach was very effective at producing immediate and sustained improvements in guideline compliance. CONCLUSIONS: Implementation of a multifaceted intervention improved rates of guideline-concordant redosing of intraoperative prophylactic antibiotics.

Evidence-based management assessment of return on investment from anesthesia information management systems.

A systematic and comprehensive review of the scientific literature revealed 4 evidence-based methods that contribute to a positive return on investment from anesthesia information management systems (AIMS): reducing anesthetic-related drug costs, improving staff scheduling and reducing staffing costs, increasing anesthesia billing and capture of anesthesia-related charges, and increased hospital reimbursement through improved hospital coding. There were common features to these interventions. Whereas an AIMS may be the ideal choice to achieve these cost reductions and revenue increases, alternative existing systems may be satisfactory for the studied applications (i.e., the incremental advantage to the AIMS may be less than predicted from applying each study to each facility). Savings are likely heterogeneous among institutions, making an internal survey using standard accounting methods necessary to perform a valid return on investment analysis. Financial advantages can be marked for the anesthesia providers, although hospitals are more likely to purchase the AIMS.

Assigning surgical cases with regional anesthetic blocks to anesthetists and operating rooms based on operating room efficiency.

The popularity of regional anesthesia blocks for both intraoperative anesthesia and postoperative pain management supports the inclusion of the administration of regional anesthesia into discussions about operating room (OR) efficiency. This article reviews the literature on OR efficiency with a focus on day-of-surgery decision making. Vignettes show regional anesthesia block placement is a variable that can affect the efficiency of use of OR time. Clinical examples highlight OR management issues and staff assignment decisions on the day of surgery. Regional anesthetic block placement can affect surgical schedules, and thus OR efficiency. When patient safety is unaffected, rearranging OR schedules on the day of surgery to place regional blocks, meet surgeon requests, or move up incision times should generally not be done if doing so results in otherwise unnecessary increases in overutilized OR time.

Breaking Through the Economic Barriers of Anesthesia Information Management Systems.

Anesthesia information management systems (AIMS) are being increasingly used to assist the delivery and documentation of anesthesia services in the United States. The major benefits of AIMS cited in the literature are the ability to (1) reduce costs, (2) facilitate quality assurance and quality improvement processes, (3) increase the accuracy and completeness of the anesthesia record, and (4) improve adherence to recommended guidelines. The major drawback, especially for rural hospitals, is the cost. This article identifies 2 of the main elements of AIMS that exist in information technology and data systems already present in a hospital. In this project, the medication dispensing system was used to achieve a 70% reduction in drug costs, and a simple electronic database was created, which detected adverse events that were missed with the legacy quality assurance system. There was no additional cost to the hospital to realize these benefits because this project utilized technologies and data systems already in place and staff time was part of the normal workload. This project showed that it is possible to achieve 2 of the major benefits of an AIMS without the major cost of purchasing one.

Economics and the education of nurse anesthetists: Part 2.

Economic assumptions and other factors affecting the economics of nurse anesthesia education are presented in Part 2 of this 2-part column. In Part 1, published in the October 2004 issue of the AANA Journal, general economic principles and healthcare economic principles in particular were described, explained, and related to the current US healthcare system.