Glucarpidase treatment for methotrexate intoxication: a case report and review of the literature.

High-dose methotrexate (MTX) induced acute kidney injury can lead to sustained high systemic MTX levels and severe toxicity. A 39-year-old man with lymphoblastic T-cell lymphoma was admitted to our intensive care unit with elevated serum creatinine and prolonged high serum MTX levels. Standard supportive care was complemented by the addition of a relatively novel agent, glucarpidase, which rapidly lowered the extracellular levels of MTX. Several case series support this effect of glucarpidase, but no randomised controlled trial has been performed to show this leads to better outcome. Furthermore, glucarpidase might negatively affect leucovorin rescue therapy. Lastly, glucarpidase carries a significant financial burden. Based on the current evidence we cannot recommend glucarpidase until further research elucidates its role in the treatment of MTX toxicity. There is no randomised clinical evidence to support its use in severe cases and theoretical evidence suggests that after prolonged exposure to high MTX levels glucarpidase administration is unable to reverse high intracellular MTX. We recommend that new randomised controlled studies be aimed at early administration of glucarpidase in patients with high MTX levels shortly after administration to prevent direct toxic effects of MTX on kidney function and further uptake into cells.

Transient versus persistent acute kidney injury and the diagnostic performance of fractional excretion of urea in critically ill patients.

AIMS: To evaluate the performance of fractional excretion of urea (FeU) for differentiating transient (T) from persistent (P) acute kidney injury (AKI) and to assess performance of FeU in predicting AKI in patients admitted to the ICU. METHODS: We performed secondary analysis of a multicenter prospective observational cohort study on the predictive performance of biological markers for AKI in critically ill patients. AKI was diagnosed according to RIFLE staging. RESULTS: Of 150 patients, 51 and 41 patients were classified as having T-AKI and P-AKI, respectively. The diagnostic performance for FeU to discriminate T-AKI from P-AKI on the day of AKI was poor (AUC-ROC = 0.61; 95% CI: 0.49-0.73). The diagnostic performance of FeU to predict AKI 1 and 2 days prior to AKI was poor as well (AUC-ROC = 0.61; 95% CI: 0.47-0.74, and 0.58; 95% CI: 0.43-0.73, respectively). CONCLUSIONS: FeU does not seem to be helpful in differentiating T- from P-AKI in critically ill patients and it is a poor predictor of AKI.

Dosing of antimicrobial agents in critically-ill patients with acute kindey injury and continuous venvenous haemofiltration.

OBJECTIVE: To summarize the general guidelines for drug dosing in critically-ill patients with acute kidney injury and continuous venovenous haemofiltration (CVVH), and to discuss whether the predicted dose adjustment is an as reliable estimate than one based on observed data, considering the recent literature. METHODS: Literature search was done in PubMed database for human studies. CONCLUSIONS: In critically-ill patients receiving CVVH, dosing of antibiotics based on the predicted clearances yield rough estimates. Because of interpatient variability observed in the clearance of many antibiotics, monitoring of plasma concentration is highly recommended whenever possible, and especially for those antibiotics that are eliminated predominantly by the kidney, and that have a low therapeutic threshold such as aminoglycosides and glycopeptides, or in patients requiring protracted treatment. However, for many antibiotics, monitoring of blood concentrations is not routinely available and adequate concentrations can only be inferred from clinical response. Therefore, it is important to realize that among many other causes, failure to respond within the first few days of antibiotic treatment may be due to inadequate dosing.

Cytokine filtration and adsorption during pre- and postdilution hemofiltration in four different membranes.

In the present in vitro study we investigated filtration and adsorption of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) during predilution and postdilution hemofiltration with polysulfone, polyacrylonitrile, polyamide and cellulose triacetate membranes. The median sieving coefficient (SC) for all membranes was 0.0 for TNF-alpha, below 0.15 for IL-6 and below 0.15 for IL-8 during postdilution hemofiltration. Differences in SC between filtration modes were less than 0.05. Maximal differences in SC between membranes were 0.11 for IL-6, 0.0 for TNF-alpha, and 0.11 for IL-8. The progressive decrease in cytokine concentrations was identical between the two filtration modes and most pronounced with the polyacrylonitrile membrane (reduction 77% for IL-6, 39% for TNF-alpha and 95% for IL-8 after 4 h of hemofiltration). The relative contribution of adsorption to the reduction in cytokines was 100% for TNF-alpha for all membranes, between 53 (cellulose triacetate) and 83% (polyacrylonitrile) for IL-6, and for IL-8 between 0 (polysulfone) and 100% (polyacrylonitrile). In conclusion, the reduction in TNF-alpha, IL-6 and IL-8 was most impressive with the polyacrylonitrile membrane after 4 h of hemofiltration and was largely due to adsorption. Adsorption of TNF-alpha, IL-6 and IL-8 was also seen with the other membranes. None of the membranes filtered TNF-alpha. Sieving of IL-6 and IL-8 was low for all membranes with only marginal differences between membranes or between filtration modes.

Comparison of the efficacy of D-dimer, fibrin degradation products and prothrombin fragment 1+2 in clinically suspected deep venous thrombosis.

The diagnostic efficacy of D-dimer, fibrin degradation products (FbDP) and prothrombin fragment 1+2 (F1+2) in patients with clinically suspected deep venous thrombosis (DVT) was investigated. 161 patients suspected of DVT were investigated. The diagnosis DVT was made in 58 patients using isotope leg scanning and ultrasonic duplex scanning. In all patients D-dimer, FbDP and F1+2 levels were determined using a latex method for D-dimer and enzyme-linked immunosorbent assays (EIA) for FbDP and F1+2. For the D-dimer latex assay sensitivity was 69% and specificity 92% (cut-off level 500 ng/ml). For the FbDP assay sensitivity was 100% and specificity 8% (cut-off level 250 ng/ml). For the F1+2 assay sensitivity was 100% and specificity 17% (cut-off level 0.3 nM). Specificity could not be improved by the combination of FbDP and F1+2. We conclude that in our population the use of the latex D-dimer assay, FbDP and F1+2 EIA's have no value as screening tests to rule out the diagnosis DVT in clinically suspected patients.

High volume hemofiltration improves hemodynamics and survival of pigs exposed to gut ischemia and reperfusion.

This study assesses the influence of high volume continuous hemofiltration on hemodynamics of pigs subjected to bowel ischemia/reperfusion. Twelve anesthetized and ventilated pigs were studied for 60 min during clamping of the superior mesenteric artery (SMA) and subsequently for 90 min after release of the clamp, while measuring global hemodynamics, SMA flow, and jejunal pCO2. They were randomly divided into two groups: pigs in "control" group were subjected to SMA clamping only. Pigs in "hemofiltered" group received zero-balanced, high volume, veno-venous hemofiltration with the removal of 6000 ml of ultrafiltrate/h, starting 30 min before clamping until 90 min after removal of the SMA clamp. Thereafter, pigs were allowed to awake and sacrificed after 24 h for macroscopic assessment of bowel damage. The drop in cardiac output (CO) during SMA clamping in the hemofiltered group was 2.5 +/- .3 L/min (mean +/- SE) (1.1/4.0; 95% confidence interval) smaller than in the control group. At the end of the experiment, mean arterial pressure (MAP) in the hemofiltered group was 33 +/- 6 (19/48) mmHg higher than in the control group, CO was 2.0 +/- .2 (1.2/2.8) L/min higher in the hemofiltered group. After 60 min of SMA clamping, left ventricular stroke work in the hemofiltered group was 35 +/- 4 (14/56) g higher than in the control group, and higher by 33 +/- 3 (21/46) g at 90 min after release of the SMA clamp. The mean pulmonary artery pressure, right atrial pressure, pulmonary artery wedge pressure, SMA flow and bowel wall pCO2 at different time points did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)