Adverse outcomes for hospitalized patients with sarcopenia are well documented, and identification of patients at risk remains challenging. The sarcopenia index (SI), previously defined as (serum ...creatinine/serum cystatin C) × 100, could be an inexpensive, readily accessible, objective tool to predict muscle mass and risk for adverse clinical outcomes. The aim of this study was to assess the validity of the SI as a predictor of muscle mass.
Retrospective study of critically ill adults admitted to Mayo Clinic from 2012 to 2015 with suspected sepsis and an available creatinine and serum cystatin C. Muscle surface area was quantified at the L3/4 vertebral level in patients with an abdominal CT scan (CTMSA). Multivariable regression modeling was used to assess the relationship between SI and CTMSA, as well as short-term clinical outcomes.
The 171 included had a mean weight and body mass index (BMI) of 75.2 ± 16.4 kg and 26.0 ± 4.6 kg/m2 and abdominal CT scans were available for 81 (47%) patients. The SI correlated with CTMSA (r = 0.40). After adjustment for age, sex, severity of illness, and BMI, SI was independently associated with muscle mass (P = 0.001). A decrease in the SI (indicative of lower muscle mass) was also associated with frailty and worse short-term clinical outcomes.
The SI, a simple calculation from kidney function markers, is a significant predictor of muscle mass in this validation cohort of ICU patients. A low SI was associated with longer hospital length of stay and frailty. Future studies could explore whether the use of SI assists with identifying patients likely to benefit from pharmacotherapy-, nutrition-, or physical therapy-based interventions.
•Identification of patients with reduced muscle mass and sarcopenia is challenging.•The Sarcopenia Index is calculated as (serum creatinine/serum cystatin C) × 100.•It is an inexpensive, accessible, objective alternative to predict muscle mass.•A lower sarcopenia index was associated with lower muscle mass.•Lower sarcopenia index independently predicted worse clinical outcomes and frailty.
Drug-induced nephrotoxicity is a relatively common preventable cause of acute kidney injury (AKI), providing early recognition and management. The pharmacokinetics or pharmacodynamics of drug-drug ...interactions may lead to additive or synergistic toxicity. The influx of new medications or off-label use of medications in the critical care setting can lead to additional nephrotoxicities, often challenging to predict or detect. This study evaluates the patterns of medication utilization, their combinations, and the related associations with AKI.
We utilized correlation-based network analysis (CNA) to investigate the relationship between medications or their combinations with AKI in a large cohort of critically ill patients in a tertiary medical center between 2007 and 2018. Pairwise medication-AKI correlation analysis was performed to evaluate drug synergistic or additive effects. To investigate the inherent nephrotoxicity of medications, we further analyzed medications that were not paired with any other medications within 24 hours before or after their administration time (isolated medication analysis).
Among 147,289 ICU admissions, we identified 244 associations among 1,555 unique medication types. In pairwise analysis, 233 significant correlations were found among 13,150,198 medication pair instances. In isolated medication analysis, ten significant AKI associations were noted. When stratified by eGFR level, substantial differences between eGFR<90 vs. eGFR≥90 patients were observed. This highlights a need to determine eGFR as a risk factor for nephrotoxicity assessment when drug interactions are considered.
This large-scale cohort study identified an artificial intelligence model to identify patient-agnostic relationships between medication or their pairs with AKI incidence among critically ill patients. It could be used as a continuous quality assurance tool to monitor drug-associated risk nephrotoxicity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Frailty, including low muscle mass, is an emerging risk factor for poor outcomes after lung transplant. The sarcopenia index (SI)—(serum creatinine value/cystatin C value) × 100—is a novel ...blood test to approximate muscle mass. We sought to validate SI among lung transplant patients.
Methods
We retrospectively identified adult lung transplant recipients from 2000 through 2012 at our institution who underwent computed tomography within 1 year before transplant and had preserved blood samples. Creatinine and cystatin C values were measured using the samples and used to calculate SI. Muscle mass was estimated by computed tomographic measurement of skeletal muscle cross‐sectional surface area (SA) at the L1 to L3 vertebral levels. Correlation between SI and SA was evaluated.
Results
Of 28 patients meeting eligibility criteria, most were white (96%) and men (54%). Median (interquartile range) body mass index, SI, and SA were 25.9 (22‐30) kg/m2, 106 (91‐119), and 157 (113‐195) cm2, respectively. The Pearson correlation coefficient between SI and SA was significant at L2 (0.43; P = .02) and L3 (0.41; P = .03).
Conclusion
Sarcopenia index is a potentially objective measure for estimating muscle mass that is noninvasive and less expensive. Sarcopenia index could be considered in lung transplant candidate selection following prospective validation in larger cohorts.
Artificial intelligence (AI) tools are more effective if accepted by clinicians. We developed an AI-based clinical decision support system (CDSS) to facilitate vancomycin dosing. This qualitative ...study assesses clinicians' perceptions regarding CDSS implementation.
Thirteen semi-structured interviews were conducted with critical care pharmacists, at Mayo Clinic (Rochester, MN), from March through April 2020. Eight clinical cases were discussed with each pharmacist (N = 104). Following initial responses, we revealed the CDSS recommendations to assess participants' reactions and feedback. Interviews were audio-recorded, transcribed, and summarized.
The participants reported considerable time and effort invested daily in individualizing vancomycin therapy for hospitalized patients. Most pharmacists agreed that such a CDSS could favorably affect (N = 8, 62%) or enhance (9, 69%) their ability to make vancomycin dosing decisions. In case-based evaluations, pharmacists' empiric doses differed from the CDSS recommendation in most cases (88/104, 85%). Following revealing the CDSS recommendations, we noted 78% (69/88) discrepant doses. In discrepant cases, pharmacists indicated they would not alter their recommendations. The reasons for declining the CDSS recommendation were general distrust of CDSS, lack of dynamic evaluation and in-depth analysis, inability to integrate all clinical data, and lack of a risk index.
While pharmacists acknowledged enthusiasm about the advantages of AI-based models to improve drug dosing, they were reluctant to integrate the tool into clinical practice. Additional research is necessary to determine the optimal approach to implementing CDSS at the point of care acceptable to clinicians and effective at improving patient outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a ...challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2‐fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.
Clinical studies have reported additive nephrotoxicity associated with the combination of vancomycin (VAN) and piperacillin-tazobactam (TZP). This study assessed differences in glomerular filtration ...rate (GFR) and urinary biomarkers between rats receiving VAN and those receiving VAN + TZP. Male Sprague-Dawley rats (
= 26) were randomized to receive 96 h of intravenous VAN at 150 mg/kg/day, intraperitoneal TZP at 1,400 mg/kg/day, or VAN + TZP. Kidney function was evaluated using fluorescein-isothiocyanate sinistrin and a transdermal sensor to estimate real-time glomerular filtration rate (GFR). Kidney injury was evaluated via urinary biomarkers, including kidney injury molecule-1 (KIM-1), clusterin, and osteopontin. Compared to a saline control, only rats in the VAN group showed significant declines in GFR by day 4 (-0.39 mL/min/100 g body weight; 95% confidence interval CI, -0.68 to -0.10;
= 0.008). When the VAN + TZP and VAN alone treatment groups were compared, significantly higher urinary KIM-1 marginal linear predictions were observed in the VAN alone group on day 1 (18.4 ng; 95% CI, 1.4 to 35.3;
= 0.03), day 2 (27.4 ng; 95% CI, 10.4 to 44.3;
= 0.002), day 3 (18.8 ng; 95% CI, 1.9 to 35.8;
= 0.03), and day 4 (23.2 ng; 95% CI, 6.3 to 40.2;
= 0.007). KIM-1 was the urinary biomarker that most correlated with decreasing GFR on day 3 (Spearman's rho, -0.45;
= 0.022) and day 4 (Spearman's rho, -0.41;
= 0.036). Kidney function decline and increased KIM-1 were observed among rats that received VAN only but not those that received TZP or VAN + TZP. The addition of TZP to VAN does not worsen kidney function or injury in our translational rat model.
In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). The guideline was derived from evidence available ...through February 2011. Since then, new evidence has emerged that has important implications for clinical practice in diagnosing and managing AKI. In April of 2019, KDIGO held a controversies conference entitled Acute Kidney Injury with the following goals: determine best practices and areas of uncertainty in treating AKI; review key relevant literature published since the 2012 KDIGO AKI guideline; address ongoing controversial issues; identify new topics or issues to be revisited for the next iteration of the KDIGO AKI guideline; and outline research needed to improve AKI management. Here, we present the findings of this conference and describe key areas that future guidelines may address.
AKI occurs frequently in critically ill patients. Patients with AKI, including those who require KRT, experience multiple pharmacokinetic and pharmacodynamic perturbations that dynamically influence ...medication effectiveness and safety. Patients with AKI may experience both subtherapeutic drug concentrations, which lead to ineffective therapy, and supratherapeutic drug concentrations, which increase the risk for toxicity. In critically ill patients with AKI not requiring KRT, conventional GFR estimation equations, especially those based on serum creatinine, have several limitations that can limit the accuracy when used for medication dosing. Alternative methods to estimate kidney function may be informative, including use of measured urinary creatinine clearance, kinetic eGFR, and equations that integrate novel kidney biomarkers. For critically ill patients with AKI requiring KRT, physicochemical properties of the drug, the KRT prescription and circuit configuration, and patient-specific factors each contribute to medication clearance. Evidence-based guidance for medication dosing during AKI requiring KRT is often limited. A working knowledge of the basic tenets of drug elimination during KRT can provide a framework for how to approach decision making when the literature is lacking. Iterative re-evaluation of a patient's progress toward therapeutic goals with a medication must occur over the arc of critical illness, including and especially in the setting of dynamic kidney function.
The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. We retrospectively analyzed adult patients treated for cytomegalovirus (CMV) infection with ganciclovir with TDM ...between 2005 and 2015. The primary outcome was an association between ganciclovir TDM and clinical efficacy endpoints within 30 days, defined by viral load and symptomatology. Secondary outcomes included safety endpoints, evaluated within 7 days of the last administered dose of ganciclovir. Of 175 patients evaluated, 82 patients with CMV infection were included in our analysis with a median (interquartile range) baseline CMV viral load of 5,500 (3,000 to 15,200) copies/ml. The majority achieved undetectable or reduced CMV viral load below the lower limit of quantification (74.4%) with improvement in symptomatology (70.7%) at 30 days. Among patients with detectable CMV viremia at 30 days, the viral load had declined to a median of 1,000 (1,000 to 3,090) copies/ml. We did not observe significant associations between the efficacy outcomes and ganciclovir trough (
= 0.20 and
= 0.20, respectively) or peak concentrations (
= 0.14 and
= 0.14, respectively). Similarly, there was no significant association between ganciclovir trough or peak concentrations and safety endpoints, including leukopenia (
= 0.48 and
= 0.69), neutropenia (
= 0.59 and
= 0.69), thrombocytopenia (
= 0.29 and
= 0.37), anemia (
= 0.51 and
= 0.35), nephrotoxicity (
= 0.41 and
= 0.57), and neurotoxicity (
= 0.22 and
= 0.48). We did not observe any associations between ganciclovir TDM and clinical efficacy or safety endpoints. Routine ganciclovir TDM may be of limited value. Future studies may be warranted to identify specific populations with unpredictable pharmacokinetic and pharmacodynamics profiles in whom ganciclovir TDM may be of benefit.
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