Documentation of the Patient Characteristics Morbid Obesity and Bariatric Surgery in the Hospital Information System and the Influence on the Number of Medication-Related Problems.

BACKGROUND: As a result of pharmacokinetic changes, individuals with morbid obesity and/or with bariatric surgery may require dose adjustments, additional monitoring or medication should be avoided. Clinical decision support (CDS) may provide automated alerts enabling correct prescribing but requires documentation of these patient characteristics in the Hospital Information System (HIS) to prevent medication-related problems (MRPs). OBJECTIVE: The primary objective is to determine the proportion of patients with documentation of the patient characteristics morbid obesity and bariatric surgery in the HIS. The secondary objective is to compare the proportion of patients with an MRP in the group with versus without documentation. Also, the type and severity of MRPs and the medication involved are determined. METHODS: A prospective cohort study was performed. Patients admitted to the hospital were identified as morbidly obese and/or with bariatric surgery. In the identified patients, the proportion of patients with documentation of the patient characteristics in the HIS was evaluated as primary outcome. Subsequently, patient records were reviewed for MRPs, which were categorized and associated medication was registered. For the primary objective, descriptive statistics was used. For the secondary outcome, the Fisher's exact test was used. RESULTS: In 43 (21.4%, 95% confidence interval [CI]: 15.7%-27.1%) of 201 included patient (113 morbid obesity, 70 bariatric surgery and 18 both), the patient characteristics were documented. An MRP occurred in 2.3% versus 13.9% (P = 0.032) of patients with and without documentation, respectively. The most common MRP was underdosing in morbid obesity, while in patients with bariatric surgery it was prescription of contra-indicated medication. CONCLUSION AND RELEVANCE: The proportion of patients with documentation of the patient characteristics bariatric surgery and/or morbid obesity in the HIS is low, which appears to be associated with more MRPs. To improve medication safety, it is important to document these patient characteristics.

Clinical Guidance for Dosing and Monitoring Oral Antihormonal Drugs in Patients with Breast Cancer After Roux-en-Y Gastric Bypass.

ABSTRACT: Obesity is associated with an increased risk of cancers, such as breast cancer. Roux-en-Y gastric bypass (RYGB) is a common surgical intervention used to induce weight loss, reduce comorbidities, and improve overall survival. Due to alterations in the gastrointestinal tract, RYGB is associated with changes in oral drug disposition, which can affect treatment outcomes. Oral antihormonal agents were monitored in 9 patients who previously underwent RYGB. The results of therapeutic drug monitoring and estradiol concentrations were analyzed, and a review of the relevant literature was performed. As only 1 of the 6 patients prescribed tamoxifen achieved a therapeutic endoxifen concentration with the standard dose of 20 mg/d, a higher starting dose of 40 mg/d was recommended to increase the probability of attaining a therapeutic plasma concentration. All patients with decreased CYP2D6 metabolic activity could not achieve therapeutic plasma concentrations; therefore, CYP2D6 genotyping was recommended before the initiation of tamoxifen therapy to identify patients who should be switched to aromatase inhibitors. Anastrozole and letrozole exposure in patients who underwent RYGB patients appeared sufficient, with no dose adjustment required. However, until more data become available, monitoring aromatase inhibitor efficacy is recommended. Monitoring the drug concentrations is a viable option; however, only indicative data on therapeutic drug monitoring are available. Therefore, estradiol concentrations should be measured.

Oral drug dosing following bariatric surgery: General concepts and specific dosing advice.

Bariatric or weight-loss surgery is a popular option for weight reduction. Depending on the surgical procedure, gastric changes like decreased transit time and volume and increased pH, decreased absorption surface in the small intestine, decreased exposure to bile acids and enterohepatic circulation, and decreased gastrointestinal transit time may be expected. In the years after bariatric surgery, patients will also substantially lose weight. As a result of these changes, the absorption, distribution, metabolism and/or elimination of drugs may be altered. The purpose of this article is to report the general influence of bariatric surgery on oral drug absorption, and to provide guidance for dosing of commonly used drugs in this special population. Upon oral drug administration, the time to maximum concentration is often earlier and this concentration may be higher with less consistent effects on trough concentrations and exposure. Additionally, prescription of liquid formulations to bariatric patients is supported by some reports, even though the high sugar load of these suspensions may be of concern. Studies on extended-release medications result in an unaltered exposure for a substantial number of drugs. Also, studies evaluating the influence of timing after surgery show dynamic absorption profiles. Although for this group specific advice can be proposed for many drugs, we conclude that there is insufficient evidence for general advice for oral drug therapy after bariatric surgery, implying that a risk assessment on a case-by-case basis is required for each drug.

Population Pharmacokinetics of Cefuroxime in Critically Ill Patients Receiving Continuous Venovenous Hemofiltration With Regional Citrate Anticoagulation and a Phosphate-Containing Replacement Fluid.

BACKGROUND: Cefuroxime is frequently prescribed as an antimicrobial therapy in critically ill patients. The aim of this study was to develop a new intravenous dosing strategy for cefuroxime in critically ill patients undergoing continuous venovenous hemofiltration with regional citrate anticoagulation (RCA-CVVH) by analyzing its extracorporeal removal and pharmacokinetic (PK) parameters. METHODS: Nine critically ill patients treated with intravenous cefuroxime and RCA-CVVH and a phosphate-containing replacement fluid were investigated. Arterial and effluent samples were obtained from all patients and pre- and postfilter venous blood samples were obtained from a subgroup of 5 patients. Plasma cefuroxime levels were determined by ultraperformance liquid chromatography-mass spectrometry in plasma samples collected before and after intravenous infusion of either 1500 mg cefuroxime every 12 hours or 3000 mg continuously over 24 hours. Population PK analysis and dosing simulations were performed using nonlinear mixed-effects modeling and Monte Carlo simulations. RESULTS: The volume of distribution (VD) of cefuroxime in the central compartment, corrected for lean body mass, was 0.11 ± 0.056 L/kgLBMc, CVVH-mediated clearance was 49.5-50.6 mL/min, the mean elimination half-life (t½) was 90 minutes (77-103), and the mean sieving coefficient was 0.89 ± 0.01. A 2-compartment model with between-subject variability in clearance, VD, and t½ described these data adequately. Simulation of a standard dosing regimen (750 mg/12 hours) predicted failure to achieve the international target plasma cefuroxime concentration (32 mg/L). CONCLUSIONS: Cefuroxime clearance by RCA-CVVH was twice the reported clearance during standard CVVH. Our PK data predicted that a maintenance dose of 3000 mg cefuroxime, infused over 24 hours, would provide an optimal steady-state plasma concentration of 38.5 mg/L. The developed population PK model for cefuroxime has the potential to inform new dosing schedules in patients receiving cefuroxime during RCA-CVVH.

[Optimizing pharmaceutical care in bariatric surgery patients]. / Geneesmiddelengebruik aanpassen na bariatrische chirurgie.

Bariatric surgery is a popular surgical method for weight loss. Due to the operation, changes are made in the gastrointestinal tract, which can potentially cause malabsorption of orally administrated drugs. Therefore it is important to evaluate each prescription of orally administrated drugs, taking the available evidence in consideration but also the wishes of the individual patient. During the first year after surgery, monitoring patients extensively for efficacy but also for safety is important. When monitoring is not possible a risk assessment on a case-by-case basis should be made taking the risk of therapy failure but also the risk of overdosing in consideration.

A Prospective Clinical Study Characterizing the Influence of Morbid Obesity on the Pharmacokinetics of Gentamicin: Towards Individualized Dosing in Obese Patients.

BACKGROUND AND OBJECTIVE: Gentamicin is an aminoglycoside antibiotic predominantly used in bloodstream infections. Although the prevalence of obesity is increasing dramatically, there is no consensus on how to adjust the dose in obese individuals. In this prospective clinical study, we study the pharmacokinetics of gentamicin in morbidly obese and non-obese individuals to develop a dosing algorithm that results in adequate drug exposure across body weights. METHODS: Morbidly obese subjects undergoing bariatric surgery and non-obese healthy volunteers received one intravenous dose of gentamicin (obese: 5 mg/kg based on lean body weight, non-obese: 5 mg/kg based on total body weight [TBW]) with subsequent 24-h sampling. All individuals had a normal renal function. Statistical analysis, modelling and Monte Carlo simulations were performed using R version 3.4.4 and NONMEM® version 7.3. RESULTS: A two-compartment model best described the data. TBW was the best predictor for both clearance [CL = 0.089 × (TBW/70)0.73] and central volume of distribution [Vc = 11.9 × (TBW/70)1.25] (both p < 0.001). Simulations showed how gentamicin exposure changes across the weight range with currently used dosing algorithms and illustrated that using a nomogram based on a 'dose weight' [70 × (TBW/70)0.73] will lead to similar exposure across the entire population. CONCLUSIONS: In this study in morbidly obese and non-obese individuals ranging from 53 to 221 kg we identified body weight as an important determinant for both gentamicin CL and Vc. Using a body weight-based dosing algorithm, optimized exposure across the entire population can be achieved, thereby potentially improving efficacy and safety of gentamicin in the obese and morbidly obese population. TRIAL REGISTRATION: Registered in the Dutch Trial Registry (NTR6058).

Evidence based development of bedside clinical drug rules for surgical patients.

BACKGROUND: Surgical adverse events constitute a considerable problem. More than half of in-hospital adverse events are related to a surgical procedure. Medication related events are frequent and partly preventable. Due to the complexity and multidisciplinary nature of the surgical process, patients are at risk for drug related problems. Consistent drug management throughout the process is needed. OBJECTIVE: The aim of this study was to develop an evidence-based bedside tool for drug management decisions during the pre- and postoperative phase of the surgical pathway. SETTING: Tool development study performed in an academic medical centre in the Netherlands involving an expert panel consisting of a surgeon, a clinical pharmacist and a pharmacologist, all experienced in quality improvement. METHOD: Relevant medication related problems and critical pharmacotherapeutic decision steps in the surgical process were identified and prioritised by a team of experts. The final selection comprised undesirable effects or unintended outcomes related to surgery (e.g. pain, infection) and comorbidity related hazards (e.g. diabetes, cardiovascular diseases). To guide patient management, a list of bedside surgical drug rules was developed using international evidence-based guidelines. MAIN OUTCOME MEASURE: 55 bedside drug rules on 6 drug categories, specifically important for surgical practice, were developed: pain, respiration, infection, diabetes, cardiovascular diseases and anticoagulation. RESULTS: A total of 29 evidence-based guidelines were used to develop the Bedside Surgical Drug Rules tool. This tool consist of practical tables covering management regarding (1) the most commonly used drug categories during surgery, (2) comorbidities that require dosing adjustments and, (3) contra-indicated drugs in the perioperative period. CONCLUSION: An evidence-based approach provides a practical basis for the development of a bedside tool to alert and assist the care providers in their drug management decisions along the surgical pathway.