Severe Lactic Acidosis Treated With Prolonged Hemodiafiltration in a Disseminated Histoplasmosis

Infections with Histoplasma are rarely seen in immunocompromized patients. We report the case of a renal transplant recipient who presented with disseminated histoplasmosis 3.5 years after transplant He presented severe lactic acidosis (LA), sepsis complicated by circulatory failure, renal failure, and liver dysfunction. We describe the successful use of continuous venovenous hemodiafiltration (CVVHDF) with regional citrate anticoagulation, treatment that stabilized our patient until infectious focus was identified and treated. The lactate was decreasing, concomitant with hemodynamic improvement, with reduction and suspension of the norepinephrine. The serum lactate level normalized 52 hours after CVVHDF initiated (from 28.9 to 2.2 mmol/L). Continuous renal replacement therapy was safely applied and can be recommended as an efficient method on adjuvant treatment of hyperlactatemia. ASAIO Journal 2009; 55:123-125.

Copper, selenium, zinc, and thiamine balances during continuous venovenous hemodiafiltration in critically ill patients.

BACKGROUND: Acute renal failure is a serious complication in critically ill patients and frequently requires renal replacement therapy, which alters trace element and vitamin metabolism. OBJECTIVE: The objective was to study trace element balances during continuous renal replacement therapy (CRRT) in intensive care patients. DESIGN: In a prospective randomized crossover trial, patients with acute renal failure received CRRT with either sodium bicarbonate (Bic) or sodium lactate (Lac) as a buffering agent over 2 consecutive 24-h periods. Copper, selenium, zinc, and thiamine were measured with highly sensitive analytic methods in plasma, replacement solutions, and effluent during 8-h periods. Balances were calculated as the difference between fluids administered and effluent losses and were compared with the recommended intakes (RI) from parenteral nutrition. RESULTS: Nineteen sessions were conducted in 11 patients aged 65 +/- 10 y. Baseline plasma concentrations of copper were normal, whereas those of selenium and zinc were below reference ranges; glutathione peroxidase was in the lower range of normal. The replacement solutions contained no detectable copper, 0.01 micromol Se/L (Bic and Lac), and 1.42 (Bic) and 0.85 (Lac) micromol Zn/L. Micronutrients were detectable in all effluents, and losses were stable in each patient; no significant differences were found between the Bic and Lac groups. The 24-h balances were negative for selenium (-0.97 micromol, or 2 times the daily RI), copper (-6.54 micromol, or 0.3 times the daily RI), and thiamine (-4.12 mg, or 1.5 times the RI) and modestly positive for zinc (20.7 micromol, or 0.2 times the RI). CONCLUSIONS: CRRT results in significant losses and negative balances of selenium, copper, and thiamine, which contribute to low plasma concentrations. Prolonged CRRT is likely to result in selenium and thiamine depletion despite supplementation at recommended amounts.

Osteoprotegerin and bone mineral density in hemodiafiltration patients.

A newly identified cytokine, osteoprotegerin (OPG) appears to be involved in the regulation of bone remodeling. In vitro studies suggest that OPG, a soluble member of the TNF receptor family of proteins, inhibits osteoclastogenesis by interrupting the intercellular signaling between osteoblastic stromal cells and osteoclast progenitors. As patients with chronic renal failure (CRF) often have renal osteodystrophy (ROD), we investigated the role of osteoprotegerin (OPG) in ROD, and investigated whether there was any relationship between serum OPG, intact parathyroid (PTH) (iPTH), vitamin D, and trabecular bone. Serum OPG combined with iPTH might be a useful tool in the noninvasive diagnosis of ROD, at least in cases in which the range of PTH values compromises reliable diagnosis. Thirty-six patients on maintenance hemodiafiltration (HDF) and a control group of 36 age and sex matched healthy subjects with no known metabolic bone disease were studied. The following assays were made on serum: iPTH, osteocalcin (BGP), bone alkaline phosphatase, 25(OH)-cholecalciferol, calcium, phosphate, OPG, IGF-1, estradiol, and free testosterone. Serum Ca++, P, B-ALP, BGP, IGF-1, iPTH, and OPG levels were significantly higher in HDF patients than in controls, while DXA measurements and quantitative ultrasound (QUS) parameters were significantly lower. On grouping patients according to their mean OPG levels, we observed significantly lower serum IGF-1, vitamin D3 concentrations, and lumbar spine and hip bone mineral density in the high OPG groups. No correlation was found between OPG and bone turnover markers, whereas a negative correlation was found between serum OPG and IGF-1 levels (r=-0.64, p=0.032). Serum iPTH concentrations were positively correlated with bone alkaline phosphatase (B-ALP) (r=0.69, p=0.038) and BGP (r=0.92, p<0.001). The findings made suggest that an increase in OPG levels may be a compensatory response to elevated bone loss. The low bone mineral density (BMD) levels found in the high OPG group might have been due to the significant decrease in serum IGF-1 and vitamin D3 observed. In conclusion, the findings made in the present study demonstrate that increased OPG in hemodiafiltration patients is only partly due to decreased renal clearance. As it may partly reflect a compensatory response to increased bone loss, this parameter might be helpful in the identification of patients with a marked reduction in trabecular BMD.

Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.

OBJECTIVE: To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. DESIGN AND SETTINGS: Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. PATIENTS: Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. INTERVENTION: Each patient received the two buffers in a randomized sequence over two consecutive days. MEASUREMENTS AND RESULTS: The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. CONCLUSION: Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.

When drugs disappear from the patient: elimination of intravenous medication by hemodiafiltration

Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.

Treatment of acute renal failure in the intensive care unit: lower costs by intermittent dialysis than continuous venovenous hemodiafiltration

Intermittent and continuous renal replacement therapies (RRTs) are available for the treatment of acute renal failure (ARF) in the intensive care unit (ICU). Although at present there are no adequately powered survival studies, available data suggest that both methods are equal with respect to patient outcome. Therefore, cost comparison between techniques is important for selecting the modality. Expenditures were prospectively assessed as a secondary end point during a controlled, randomized trial comparing intermittent hemodialysis (IHD) with continuous venovenous hemodiafiltration (CVVHDF). The outcome of the primary end points of this trial, that is, ICU and in-hospital mortality, has been previously published. One hundred twenty-five patients from a Swiss university hospital ICU were randomized either to CVVHDF or IHD. Out of these, 42 (CVVHDF) and 34 (IHD) were available for cost analysis. Patients' characteristics, delivered dialysis dose, duration of stay in the ICU or hospital, mortality rates, and recovery of renal function were not different between the two groups. Detailed 24-h time and material consumption protocols were available for 369 (CVVHDF) and 195 (IHD) treatment days. The mean daily duration of CVVHDF was 19.5 +/- 3.2 h/day, resulting in total expenditures of Euro 436 +/- 21 (21% for human resources and 79% for technical devices). For IHD (mean 3.0 +/- 0.4 h/treatment), the costs were lower (Euro 268 +/- 26), with a larger proportion for human resources (45%). Nursing time spent for CVVHDF was 113 +/- 50 min, and 198 +/- 63 min per IHD treatment. Total costs for RRT in ICU patients with ARF were lower when treated with IHD than with CVVHDF, and have to be taken into account for the selection of the method of RRT in ARF on the ICU.

Pharmacokinetics of meprobamate in overdose treated with continuous venovenous hemodiafiltration (CVVHDF)

We report a case of massive suicidal overdose of meprobamate leading to cardiovascular collapse, respiratory failure, and severe central nervous system depression. We observed first-order elimination kinetics despite significant overdose, and demonstrated effectiveness of continuous venovenous hemodiafiltration (CVVHDF) for extracorporeal removal of meprobamate in this patient. Total body clearance was calculated to be 87 mL/minute, with 64 mL/minute (74%) due to CVVHDF. CVVHDF was stopped after 36 hours, and the patient made an uneventful recovery.

Effect of Aging in the Perception of Health-Related Quality of Life in End-Stage Renal Disease Patients under Online-Hemodiafiltration

This work aimed to evaluate how aging could influence patients' perception of health quality of life (HRQOL), as well as, the effect of aging on dialysis adequacy and in hematological, iron status, inflammatory and nutritional markers. In this transversal study were enrolled 305 ESRD patients under online-hemodiafiltration (OL-HDF) (59.67% males; 64.9 ± 14.3 years old). Data about comorbidities, hematological data, iron status, dialysis adequacy, nutritional and inflammatory markers were collected from patient's records. Moreover, HRQOL score, by using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), was assessed. Analyzing the results according to quartiles of age, significant differences were found for some parameters evaluated by the KDQOL-SF instrument, namely for work status, physical functioning and role-physical, which decreased with increasing age. We also found a higher proportion of diabetic patients, a decrease in creatinine, iron, albumin serum levels, transferrin saturation and nPCR, with increasing age. Moreover, significant negative correlations were found between age and mean cell hemoglobin concentration, iron, transferrin saturation, albumin, nPCR, work status, physical functioning and role-physical. In conclusion, our results showed that aging is associated with a decreased work status, physical functioning and role-physical, with a decreased dialysis adequacy, iron availability and nutritional status, and with an increased proportion of diabetic patients and of patients using central venous catheter, as the vascular access. The knowledge of these changes associated with aging, which have impact in the quality of life of the patients, could be useful in their management.

Pharmacokinetics of ciprofloxacin in ICU patients on continuous veno-venous haemodiafiltration

Objectives: To investigate the pharmacokinetics of intravenous ciprofloxacin 200 mg every 8 h in critically ill patients on continuous veno-venous haemodiafiltration (CVVHDF), one form of continuous renal replacement therapy (CRRT). Design and setting: Open, prospective clinical study in a multidisciplinary, intensive care unit in a university-affiliated tertiary referral hospital. Patients: Sis critically ill patients with acute renal failure on CVVHDF. Interventions: Timed blood and ultrafiltrate samples were collected to allow pharmacokinetics and clearances to be calculated of initial and subsequent doses of 200 mg intravenous ciprofloxacin. CVVHD was performed with 1 l/h of dialysate and 2 l/h of predilution filtration solution, producing 3 lih of dialysis effluent. The blood was pumped at 200 ml/min using a Gambro BMM-10 blood pump through a Hospal AN69HF haemofilter,. Measurements and results: Ten pharmacokinetic profiles were measured. The CVVHDF displayed a urea clearance of 42 +/- 3 ml/min, and removed ciprofloxacin with a clearance of 37 +/- 7 ml/min. This rate was 2-2.5 greater than previously published for ciprofloxacin in other forms of CRRT. On average the CVVHDF was responsible for clearing a fifth of all ciprofloxacin eliminated (21 +/- 10%). The total body clearance of ciprofloxacin was 12.2 +/- 4.3 l/h. The trough concentration following the initial dose was 0.7 +/- 0.3 mg/l. The area under the plasma concentration time curves over a 24-h period ranged from 21 to 55 mg .h l(-1). Conclusions: Intravenous ciprofloxacin 600 mg/day in critically ill patients using this form of CRRT produced adequate plasma levels for many resistant microbes found in intensive care units.

Caracterização microbiológica de águas utilizadas em hemodiálise

A insuficiência renal crónica tem como possível tratamento a hemodiálise de alto-fluxo de hemodiafiltração. Este estudo tem por objectivo caracterizar a qualidade de águas de diálise, provenientes de 4 clínicas. Realizou-se um estudo observacional descritivo transversal com base nos resultados das análises de águas de diálise, de 07-2009 a 04-2010. Nas amostras, à entrada do tratamento, verificou-se que 100% destas se encontravam nãoconformes nos parâmetros microbiológicos e 53,85% apresentavam-se não-conformes nos parâmetros químicos. Após tratamento, 6,41% continuavam não-conformes nos parâmetros microbiológicos e todas as amostras apresentaram-se conformes nos parâmetros químicos. Conclui-se que o tratamento tem elevado grau de efectividade.

A Comparative Study of Cardiovascular Tolerability with Slow Extended Dialysis Versus Continuous Haemodiafiltration in the Critical Patient

Background: In the haemodynamically unstable patient the method of treatment of acute renal failure is still largely controversial. The purpose of our study was to compare slow extended dialysis with continuous haemodiafiltration in the critical patient with indication for renal replacement therapy and haemodynamic instability. Patients and Methods: This is a cohort study comparing in 63 ventilated critical patients a 12 month period when only continuous haemodiafiltration was used (n=25) with an equal period of slow extended dialysis (n=38). Our primary objective was to evaluate the impact of the dialytic procedure on cardiovascular stability in those patients. As secondary aims we considered system coagulation/thrombosis and predictors of mortality. In the two groups we analysed the first session performed, the second session performed and the average of all the sessions performed in each patient. Results: In these patients, mortality in the intensive care unit was high (68% in the continuous haemodiafiltration group and 63% in the slow extended dialysis group). We did not find any association between the dialytic technique used and death; only the APACHE score was a predictor of death. Slow extended dialysis was a predictor of haemodynamic stability, a negative predictor of sessions that had to be interrupted for haemodynamic instability, and a predictor of achieving the volume removal initially sought. Slow extended dialysis was also associated with less coagulation of the system. Conclusions: Our data suggested that slow extended dialysis use was not inferior to continuous haemodiafiltration use in terms of cardiovascular tolerability.

Producing on-line ultrapure dialysis fluid.

The process of on-line generation of ultrapure dialysis fluid is a core prerequisite for the safe execution of modern renal replacement therapies such as on-line hemodiafiltration and high-flux hemodialysis. In these extracorporeal treatments with variable degrees of convection, significant volumes of plasma water are removed and replaced with dialysis fluid, which must occur without causing harm to the patient. Historically, on-line generation of sterile and pyrogen-free physiological substitution fluid by the process of membrane ultrafiltration of fresh dialysis fluid has its origin in hemofiltration, a purely convective therapy. Development of this and later therapies is described in the historical context of a successful effort over decades to overcome the above formidable challenge, which was provided jointly by pioneering clinical investigators and a resourceful dialysis industry.

Determination of meropenem in plasma and filtrate-dialysate from patients under continuous veno-venous haemodiafiltration by SPE-LC.

Meropenem, a carbapenem antibiotic displaying a broad spectrum of antibacterial activity, is administered in Medical Intensive Care Unit to critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF). However, there are limited data available to substantial rational dosing decisions in this condition. In an attempt to refine our knowledge and propose a rationally designed dosage regimen, we have developed a HPLC method to determine meropenem after solid-phase extraction (SPE) of plasma and dialysate fluids obtained from patients under CVVHDF. The assay comprises the simultaneous measurement of meropenem's open-ring metabolite UK-1a, whose fate has never been studied in CVVHDF patients. The clean-up procedure involved a SPE on C18 cartridge. Matrix components were eliminated with phosphate buffer pH 7.4 followed by 15:85 MeOH-phosphate buffer pH 7.4. Meropenem and UK-1a were subsequently desorbed with MeOH. The eluates were evaporated under nitrogen at room temperature (RT) and reconstituted in phosphate buffer pH 7.4. Separation was performed at RT on a Nucleosil 100-5 microm C18 AB cartridge column (125 x 4 mm I.D.) equipped with a guard column (8 x 4 mm I.D.) with UV-DAD detection set at 208 nm. The mobile phase was 1 ml min(-1), using a step-wise gradient elution program: %MeOH/0.005 M tetrabutylammonium chloride pH 7.4; 10/90-50/50 in 27 min. Over the range of 5-100 microg ml(-1), the regression coefficient of the calibration curves (plasma and dialysate) were >0.998. The absolute extraction recoveries of meropenem and UK-1a in plasma and filtrate-dialysate were stable and ranged from 88-93 to 72-77% for meropenem, and from 95-104 to 75-82% for UK-1a. In plasma and filtrate-dialysate, respectively, the mean intra-assay precision was 4.1 and 2.6% for meropenem and 4.2 and 3.7% for UK-1a. The inter-assay variability was 2.8 and 3.6% for meropenem and 2.3 and 2.8% for UK-1a. The accuracy was satisfactory for both meropenem and UK-1a with deviation never exceeding 9.0% of the nominal concentrations. The stability of meropenem, studied in biological samples left at RT and at +4 degrees C, was satisfactory with < 5% degradation after 1.5 h in blood but reached 22% in filtrate-dialysate samples stored at RT for 8 h, precluding accurate measurements of meropenem excreted unchanged in the filtrate-dialysate left at RT during the CVVHDF procedure. The method reported here enables accurate measurements of meropenem in critically ill patients under CVVHDF, making dosage individualisation possible in such patients. The levels of the metabolite UK-1a encountered in this population of patients were higher than those observed in healthy volunteers but was similar to those observed in patients with renal impairment under hemodialysis.

Accesos vasculares para hemodiálisis, cuál es el más costo efectivo?

Marco conceptual: La enfermedad renal crónica es un serio problema de salud pública en nuestro país por la gran cantidad de recursos económicos que requiere su atención. La hemodiálisis es el tratamiento más usado en nuestro medio; el acceso vascular y sus complicaciones derivadas son el principal aspecto que incrementa los costos de atención en éstos pacientes. Materiales y métodos: Se realizó un estudio económico de los accesos vasculares en pacientes incidentes de hemodiálisis en el año 2012 en la agencia RTS-Fundación Cardio Infantil. Se estableció el costo de creación y mantenimiento del acceso con catéter central, fístula arteriovenosa nativa, fístula arteriovenosa con injerto; y el costo de atención de las complicaciones para cada acceso. Se determinó la probabilidad de ocurrencia de complicaciones. Mediante un árbol de decisiones se trazó el comportamiento de cada acceso en un período de 5 años. Se establecieron los años de vida ajustados por calidad (QALY) en cada acceso y el costo para cada uno de éstos QALY. Resultados: de 36 pacientes incidentes de hemodiálisis en 2012 el 100% inició con catéter central, 16 pacientes cambiaron a fístula arteriovenosa nativa, 1 a fístula arteriovenosa con injerto que posteriormente pasó a CAPD, 15 continuaron su acceso con catéter y 4 pacientes fallecieron. En 5 años se obtuvieron 2,36 QALY para los pacientes con catéter central que costarían $ 24.813.036,39/QALY y 2,535 QALY para los pacientes con fístula nativa que costarían $ 6.634.870,64/QALY. Conclusiones: el presente estudio muestra que el acceso vascular mediante fístula arteriovenosa nativa es el más costo-efectivo que mediante catéter