Evaluating Muscle Mass by Using Markers of Kidney Function: Development of the Sarcopenia Index.

OBJECTIVES: Sarcopenia is associated with a poor prognosis in the ICU. The purpose of this study was to describe a simple sarcopenia index using routinely available renal biomarkers and evaluate its association with muscle mass and patient outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary-care medical center. PATIENTS: High-risk adult ICU patients from October 2008 to December 2010. INTERVENTIONS: The gold standard for muscle mass was quantified with the paraspinal muscle surface area at the L4 vertebrae in the subset of individuals with an abdominal CT scan. Using Pearson's correlation coefficient, serum creatinine-to-serum cystatin C ratio was found to be the best performer in the estimation of muscle mass. The relationship between sarcopenia index and hospital and 90-day mortality, and the length of mechanical ventilation was evaluated. MEASUREMENTS AND MAIN RESULTS: Out of 226 enrolled patients, 123 (54%) were female, and 198 (87%) were white. Median (interquartile range) age, body mass index, and body surface area were 68 (57-77) years, 28 (24-34) kg/m, and 1.9 (1.7-2.2) m, respectively. The mean (± SD) Acute Physiology and Chronic Health Evaluation III was 70 (± 22). ICU, hospital, and 90-day mortality rates were 5%, 12%, and 20%, respectively. The correlation (r) between sarcopenia index and muscle mass was 0.62 and coefficient of determination (r) was 0.27 (p < 0.0001). After adjustment for Acute Physiology and Chronic Health Evaluation III, body surface area, and age, sarcopenia index was independently predictive of both hospital (p = 0.001) and 90-day mortality (p < 0.0001). Among the 131 patients on mechanical ventilator, the duration of mechanical ventilation was significantly lower on those with higher sarcopenia index (-1 d for each 10 unit of sarcopenia index [95% CI, -1.4 to -0.2; p = 0.006]). CONCLUSIONS: The sarcopenia index is a fair measure for muscle mass estimation among ICU patients and can modestly predict hospital and 90-day mortality among patients who do not have acute kidney injury at the time of measurement.

Cystatin C Falsely Underestimated GFR in a Critically Ill Patient with a New Diagnosis of AIDS.

Cystatin C has been suggested to be a more accurate glomerular filtration rate (GFR) surrogate than creatinine in patients with acquired immunodeficiency syndrome (AIDS) because it is unaffected by skeletal muscle mass and dietary influences. However, little is known about the utility of this marker for monitoring medications in the critically ill. We describe the case of a 64-year-old female with opportunistic infections associated with a new diagnosis of AIDS. During her course, she experienced neurologic, cardiac, and respiratory failure; yet her renal function remained preserved as indicated by an eGFR ≥ 120 mL/min and a urine output > 1 mL/kg/hr without diuresis. The patient was treated with nephrotoxic agents; therefore cystatin C was assessed to determine if cachexia was resulting in a falsely low serum creatinine. Cystatin C measured 1.50 mg/L which corresponded to an eGFR of 36 mL/min. Given the >60 mL/min discrepancy, serial 8-hour urine samples were collected and a GFR > 120 mL/min was confirmed. It is unclear why cystatin C was falsely elevated, but we hypothesize that it relates to the proinflammatory state with AIDS, opportunistic infections, and corticosteroids. More research is needed before routine use of cystatin C in this setting can be recommended.

Levetiracetam Pharmacokinetics in a Patient Receiving Continuous Venovenous Hemofiltration and Venoarterial Extracorporeal Membrane Oxygenation.

Levetiracetam is a first-line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67-year-old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO. His course was complicated by multiorgan dysfunction including acute renal failure requiring CVVH. On hospital day 6, intravenous levetiracetam, at a loading dose of 2000 mg followed by a maintenance dose of 1000 mg every 12 hours, was initiated for new-onset seizures. The volume of distribution was 0.65 L/kg, and clearance was measured with peak (ranging from 26.5-39.8 µg/ml) and trough (ranging from 13.9-18.2 µg/ml) concentrations. Elimination half-life ranged from 8.7-10.1 hours. Renal dysfunction reduces levetiracetam clearance, and dosage reductions are recommended to prevent accumulation. Current CVVH dosing recommendations are based on predicted removal without clinical data. The volume of distribution and clearance in this case were similar to those of a normal healthy patient. Based on these results, we recommend considering an initial levetiracetam dose of 1000 mg every 12 hours for patients receiving CVVH, with dosage adjustments based on therapeutic drug monitoring.

Serum cystatin C predicts vancomycin trough levels better than serum creatinine in hospitalized patients: a cohort study.

INTRODUCTION: Serum cystatin C can improve glomerular filtration rate (GFR) estimation over creatinine alone, but whether this translates into clinically relevant improvements in drug dosing is unclear. METHODS: This prospective cohort study enrolled adults receiving scheduled intravenous vancomycin while hospitalized at the Mayo Clinic in 2012. Vancomycin dosing was based on weight, serum creatinine with the Cockcroft-Gault equation, and clinical judgment. Cystatin C was later assayed from the stored serum used for the creatinine-based dosing. Vancomycin trough prediction models were developed by using factors available at therapy initiation. Residuals from each model were used to predict the proportion of patients who would have achieved the target trough with the model compared with that observed with usual care. RESULTS: Of 173 patients enrolled, only 35 (20%) had a trough vancomycin level within their target range (10 to 15 mg/L or 15 to 20 mg/L). Cystatin C-inclusive models better predicted vancomycin troughs than models based upon serum creatinine alone, although both were an improvement over usual care. The optimal model used estimated GFR by the Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) creatinine-cystatin C equation (R(2) = 0.580). This model is expected to yield 54% (95% confidence interval 45% to 61%) target trough attainment (P <0.001 compared with the 20% with usual care). CONCLUSIONS: Vancomycin dosing based on standard care with Cockcroft-Gault creatinine clearance yielded poor trough achievement. The developed dosing model with estimated GFR from CKD-EPIcreatinine-cystatin C could yield a 2.5-fold increase in target trough achievement compared with current clinical practice. Although this study is promising, prospective validation of this or similar cystatin C-inclusive dosing models is warranted.