Search

Background: A recent study demonstrated that pharmacists presented with multiple estimating equations deviated from recommended dosing guidance more often than pharmacists who were presented with a single estimate on clinical vignettes. Objectives: To identify characteristics associated with an increased tendency to deviate from approved recommendations. Methods: Participant data were split into 2 cohorts: pharmacists who chose a dose that was inconsistent with dosing recommendations on at least 1 of the 4 vignettes and pharmacists who did not deviate on a single case. Bivariate analysis of demographic- and practice-related variables were conducted between groups using the χ2, Mann-Whitney U, or Student t -test for nominal, ordinal, and continuous variables, respectively. Statistically different covariates between groups (P < 0.05) were assessed using multivariable linear regression. Results: Survey data from 154 inpatient pharmacists, 71 of whom deviated on at least 1 clinical vignette, were analyzed. On univariate analysis, deviator pharmacists were more likely to have completed postgraduate residency training (68% vs 41%; P < 0.05) and board certification (39% vs 20%; P < 0.05). Deviator pharmacists were also more likely to have been presented with multiple renal estimates as opposed to a single estimate and had differing renal dosing practices at baseline (P < 0.05). Following multivariable regression, residency training, mismatched baseline renal practices, and multiple renal estimates remained independent predictors (P < 0.05) of dosing deviation. Conclusion and Relevance: Higher clinical training, practice variation, and multiple renal estimates may affect renal dosing practices. Prospective, statistically powered studies are needed to verify these hypotheses. [ABSTRACT FROM AUTHOR]

Background: Assessment of kidney function is fundamental to optimize drug dosing. The Cockcroft-Gault (CG) equation is widely used but has questionable validity for females, changing renal function, and the critical ill. Eight-hour urine collections (U8h) offer direct measurement of creatinine clearance (CrCl) but lack the data for drug dosing. The primary objective of this study was to determine if there was a difference in renal drug dosing based on the estimation of CG CrCl (CrClCG) versus 8-h CrCl (CrCl8h). Methods: This was an observational, retrospective cohort study of adult patients admitted between March 2018 and September 2018 with a collection U8h during hospitalization. The primary outcome was discordance of renal drug dosing defined as the percentage of U8h for which at least one different active medication CrCl dosing cutoff would result using the CrClCG versus CrCl8h. The secondary outcomes were correlation between CrClCG and CrCl8h and percentage of CrClCG values outside ± 20% of the CrCl8h. Results: One hundred collections drawn from 85 unique patients (50.6% male, median age 55 [41-70] years, intensive care unit 88%) were included in the analysis. Median serum creatinine was 0.76 (0.52-1.06) mg/dL and blood urea nitrogen was 20 (14-28) mg/dL at time of collection8h. Median CrCl8h was 86.2 (43.5-140.3) mL/min versus 99.7 (56.5-166.9) mL/min CrClCG (P < 0.001) and discordance was 25%. The correlation between CrCl8h and CrClCG was 0.76 (P < 0.001). Only 31% of CrClCG values were within ± 20% of the CrCl8h value. Conclusion: We found 25% discordance for drug dosing between CrCl8h and CrClCG. Further studies are needed to determine the impact on clinical outcomes. [ABSTRACT FROM AUTHOR]

Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against both gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Cefepime is most commonly used for urinary tract infections, soft tissue infections, and febrile neutropenia. Up to 15% of ICU patients on cefepime may experience cefepime-induced neurotoxicity (CIN), with risk factors including renal dysfunction, excessive dosage, elevated serum cefepime concentrations, and history of prior brain injury. The adverse effects of CIN, including encephalopathy, seizures, and coma can be resolved with drug cessation, antiepileptics, or hemodialysis. Here, we present the case of CIN in a 59-year-old female patient with long-term cefepime antibiotic prescription for Pseudomonas bacteremia and endocarditis with multiple risk factors for reduced renal function. We discuss the relevant risk factors and preventive measures that may have prevented her from developing CIN, as well as the importance of early recognition and prevention of CIN in patient care., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Smith et al.)

Cefepime-induced non-convulsive status epilepticus (NCSE) is a recognized adverse event of cefepime. Risk factors for this adverse event include older age, underlying renal dysfunction, previous brain injury, diabetes, and severe infection. We present a case of a 79-year-old woman with no prior seizure history, who was admitted for Pseudomonas aeruginosa surgical wound infection for which she was on cefepime. She developed acute encephalopathy with associated, occasional, right-sided myoclonic facial twitches 11 days into her admission. Electroencephalogram (EEG) confirmed NCSE as evident by epileptiform activity described as generalized periodic discharges with predominantly triphasic morphology. Cefepime was substituted with piperacillin-tazobactam> 24 hours after symptom onset. NCSE completely resolved two days after the discontinuation of cefepime. This case highlights the fact that NCSE can occur even when precautions such as renal dosing of cefepime are observed. Clinicians need to have a high index of suspicion for the condition when taking care of at-risk patients on cefepime, as delayed diagnosis correlates with potentially fatal outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Allihien et al.)

Abstract Introduction A disconnect appears to exist for medical students between learning drug facts in a basic science context and applying those facts in a clinical context when they begin working with authentic patients. In patients with kidney dysfunction, dosages of medications that are renally eliminated often need to be adjusted, due to potentially toxic accumulation in the body. To gain insight into the thought processes and gaps underlying student thinking, we developed this standardized patient (SP) case featuring a patient with drug-related renal dysfunction. Methods This activity was conducted in a simulation center, in a setting reminiscent of an emergency department. It took place over 2 days, with all 23 third-year medical students at our regional campus. After reporting to the simulation center at their assigned time, students completed four different medication scenarios. This specific case involved two parts. The first part, an SP-student encounter, was allotted 15 minutes, followed by 1 minute to walk to a computer station. For the second part, writing a SOAP (subjective, objective, assessment, and plan) note, 15 minutes were allotted. This was followed by 3 minutes for the SP to provide student feedback and 1 minute to rotate to the next station. In total, 35 minutes were allotted for each student to complete the case. Results All third-year medical students at our regional campus completed this activity at the midpoint of their academic year. Students were well prepared to gather necessary background information from the standardized patient. However, few made the connection between the patient's symptoms and the way in which her medications were contributing. Nor did they recommend an appropriate course of action for medications that required adjustment. Discussion From this activity, we gained insight into the student thought process with regard to medication management and have been able to develop new ways of revisiting basic science concepts in clinically relevant contexts to help bridge the gap between the basic and clinical components of pharmacology education.

Abstract Introduction At the Medical College of Wisconsin, geriatricians, nephrologists, and medical educators worked together to create and implement a geriatric nephrology objective structured clinical examination (OSCE) for nephrology fellows. Key curriculum content gaps (pathophysiology of the aging kidney, medication and renal dosing, and renal toxicity in elderly patients) were identified through a needs assessment including ACGME nephrology requirements, nephrology fellows' in-service exam scores, survey of fellows and faculty to identify areas of perceived weakness, literature review, and brief multiple-choice questions of basic science linked to clinical case questions. Methods Curriculum content was delivered using the OSCE educational method. The curriculum session highlighted kidney injury and pharmacology topics: drug toxicity and underlying science through an OSCE session with postsession debriefing provided by faculty. Fellows were evaluated by faculty using a checklist, and fellows evaluated the session prior to the end. Results The OSCE curriculum session (N = 6) showed strong learner evaluations (1 = poor, 7 = excellent), including “Session objectives were clearly stated and accomplished” = 6.8, “Feedback provided in debriefing will improve my ability to care for geriatric patients” = 5.8, and “Overall effectiveness of session in improving my ability to care for geriatric patients” = 6.5. Discussion Fellow performance from the OSCE rater checklists completed by faculty and standardized patients showed the fellows' extent of completion/inclusion of OSCE elements to range between 69% and 80% complete. The program director identified a discrepancy between fellows' knowledge and some communication skills in summarizing the information and providing closure to the session. The ability of the OSCE to provide direct observation of the fellows' performance was highly valued by the program director and has led to further adjustments in teaching and assessment over time.

Despite prescribing guidance, limited data exist to describe the use of apixaban in patients with end-stage renal disease ( ESRD) requiring hemodialysis ( HD). Current apixaban dosing recommendations for this patient population are based largely on a single-dose pharmacokinetic study of eight patients. We describe the clinical application and pharmacodynamic monitoring of apixaban in a 62-year-old 156-kg African-American woman with nonvalvular atrial fibrillation and ESRD requiring hemodialysis who developed calciphylaxis while receiving warfarin therapy. Based on a multidisciplinary clinical judgment decision due to concern for drug accumulation after multiple doses in patients with ESRD receiving HD, she was anticoagulated with apixaban 2.5 mg twice/day, as opposed to 5 mg twice/day as recommended by the package insert. Antifactor Xa monitoring was used, and resultant peak and trough apixaban concentrations were above the upper limit of detection for our clinical laboratory (more than 2.00 IU/ml). On day 7 of her hospitalization, the patient developed gastrointestinal bleeding, and apixaban was discontinued; no further clinical signs of bleeding occurred during her subsequent hospitalization course. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between apixaban exposure and the manifestation of gastrointestinal bleeding. The patient ultimately died 44 days after the acute bleeding event; however, coagulation concerns were not implicated in the patient's death. To our knowledge, this is the first case report that describes apixaban use and associated antifactor Xa monitoring in a patient with ESRD receiving HD, and it provides concern for current apixaban dosing recommendations in this patient population. Further pharmacokinetic and clinical data are likely necessary to better characterize apixaban use in these patients to optimize safety and efficacy. [ABSTRACT FROM AUTHOR]

What is known and objective Adjustment of drug dosage in patients with end-stage renal disease prevents serious adverse effects, which occur due to the accumulation of drugs or other toxic metabolites. Nevertheless, dosing errors occur most commonly among patients with end-stage renal disease. The aim of this study was to assess the quality of care for end-stage renal disease outpatients using their renal dosing adjustment status. Methods A cross-sectional study was performed using the data collected from 43 South Korean medical institutions via questionnaires. A total of 2428 patients on haemodialysis, who were at least 18 years of age, were included. Among these patients, the study population was confined to patients who were taking medications and required renal dosing adjustments from three therapeutic classes: antihypertensives, antihyperglycaemics and lipid-modifying agents. The study population ( n = 828) was prescribed a total of 1097 drug orders for the target drugs. Determination of appropriate dosage adjustment was based on GFR (glomerular filtration rate) using the Modification of Diet in Renal Disease revised 4-variable equation. The primary outcome was non-adherence to drug dosing requirements for end-stage renal disease patients with consideration to their renal function. Results and discussion Among the study population ( n = 828), 469 haemodialysis patients were identified as having drug orders that were adherent to renal dosing recommendations. There were significant differences between the patient groups who received recommendation-adherent and non-adherent drug orders in the characteristics of the medical institutions they visited, causes of chronic renal failure and prevalence of concurrent diabetes mellitus. The primary factor of non-adherence to renal dosing adjustment recommendations was characteristics of medical institutions. Compared to tertiary hospitals, secondary hospitals and primary care clinics were 1·16 and 1·22 times, respectively, more non-adherent in accordance with the multivariate analysis ( OR: 1·16, 95% CI: 1·02-1·20, OR: 1·22, 95% CI: 1·00-1·36, respectively). What is new and conclusions Dosing error is one of the most common problems among patients with renal failure. To decrease the dosing errors, an improvement needs to be made in medical institutions. This can be accomplished by implementing the clinical decision support systems that educate physicians on appropriate renal dosing and help them prescribe appropriate drug dosages. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to determine the impact of a pharmacy-managed pharmacokinetic dosing program on appropriate dosing of famotidine, enoxaparin, and ketorolac. Methods: A large community teaching hospital implemented a pharmacy-managed pharmacokinetic dosing program for famotidine, enoxaparin, and ketorolac. Subjects were included if they received famotidine and had a creatinine clearance (CrCl) of <50 mL/min; received therapeutic enoxaparin and had a CrCl of <30 mL/min; or received ketorolac and had a CrCl <30 mL/min, age > 65 years or weight <50 kg. Results: One hundred and forty-six patients were included in the preimplementation group (famotidine [n = 50], enoxaparin [n = 46], and ketorolac [n = 50]) and 143 patients were included in the postimplementation group (famotidine [n = 50], enoxaparin [n = 43], and ketorolac [n = 50]). In all, 66% of patients were dosed appropriately in the preimplementation group (famotidine 28%, enoxaparin 85%, and ketorolac 86%) compared to 94% in the postimplementation group (famotidine 92%, enoxaparin 95%, and ketorolac 94%), P < .001. Conclusion: Implementation of a pharmacy-managed pharmacokinetic dosing program significantly improved appropriate dosing of famotidine, enoxaparin, and ketorolac. These findings could justify expansion of pharmacist autonomy through institution–approved, pharmacy-managed programs for other medications to improve appropriate dosing. Analyses specifically evaluating patient-oriented or financial outcomes may provide additional support for expansion. [ABSTRACT FROM AUTHOR]

There are 2 major categories of patients with seizures and chronic kidney disease (CKD): patients who develop acute symptomatic seizures in the setting of CKD and patients with epilepsy who at some point develop CKD. The incidence of uremic seizures with kidney failure is ∼10%. These seizures are often nonconvulsive and may mimic uremic encephalopathy. Recognition and management of such situations may be challenging for treating physicians who are non-neurologists. Furthermore, practitioners caring for patients with seizures with or without an established diagnosis of epilepsy in the setting of CKD frequently encounter challenges in the selection, loading, titration, and maintenance of antiepileptic drugs (AEDs) due to potentially altered pharmacokinetics of the AEDs. We review the pathophysiology of uremia, uremic seizures, and other neurologic complications of kidney failure; management approaches to the treatment of such complications; the relevant mechanisms of action and pharmacokinetics of AEDs with their use in CKD; and in particular, the management of AEDs in patients requiring hemodialysis therapy., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Renal dosing clinical decision support (CDS) systems have demonstrated clinical effectiveness and potential benefits for patient outcomes. However, the high override rates consistently reported are problematic and undesirable. To understand providers' use patterns of renal dosing CDS, we investigated the override reasons obtained from primary care practices affiliated with two teaching hospitals. We selected a stratified random sample of 300 alerts and reviewed electronic medical records. Appropriateness criteria and an inter-rater reliability process were used. We found that two thirds of alerts were overridden inappropriately, and this proportion was similar for frequent over-riders as compared to the remainder of physicians. These findings imply that strategies are needed to convince providers to accept more clinically appropriate suggestions, though they need to be broadly targeted. [ABSTRACT FROM AUTHOR]