Sustained low-efficiency dialysis (SLED) with prostacyclin in critically ill patients with acute renal failure.

BACKGROUND: Prostacyclin is an easy-to-use and safe antihaemostatic drug for continuous renal replacement therapies (RRTs). No study has been performed so far about its use in critically ill patients with acute renal failure (ARF) treated with sustained low-efficiency dialysis (SLED), a hybrid modality between conventional intermittent and continuous RRTs. METHODS: We studied 35 consecutive ICU patients with ARF, in whom data on safety and efficacy were prospectively collected in a single-centre experience over 15 months since August 2001. There were 25 males and 10 females; mean age, 72.1 (SD 11.4); mean APACHE II score at ICU admission, 24 (range 14-43); at RRT start, 27.4 (20-43); 28 patients (80%) were on mechanical ventilation and 17 (48.6%) had sepsis. SLED was performed using a conventional dialysis machine, with blood flow at 200 ml/min, bicarbonate-based ultrapure dialysate running at 100 ml/min, dialysate temperature 35 degrees C and low-flux polysulfone filters. Prostacyclin, under the form of its synthetic analogue epoprostenol, was infused at 6 ng/kg/min before the filter. RESULTS: Out of 185 daily sessions performed (8-10 h, median 4 per patient, range 1-19), 19 (in 11 patients) were prematurely interrupted (10.3%; 95% CI: 5.4-18.6), after an average 58.5% of the prescribed treatment time (nine sessions in six patients for circuit clotting). This finding compared favourably with the experience we had at our unit using SLED with saline flushes. With the use of prostacyclin, two episodes of upper gastrointestinal bleeding were observed in 2/35 patients during SLED (5.7%; 95% CI: 0.7-19.2), corresponding to 1.1 episodes per 100 person-day on SLED. Therapeutic intervention for hypotension (fluids and/or vasopressor increase) was required in 45/185 (in 20 patients) of the sessions monitored (24.3%; 95% CI: 17.4-32.9); two sessions had to be interrupted because of refractory hypotension. Urea reduction ratio was 0.50 (SD 0.12); mean prescribed and obtained net ultrafiltration were 1.96 l (range 0.5-5.0) and 1.99 l (0.5-5.0), respectively. In-hospital mortality was 46%; mortality predicted by the APACHE II model at ICU admission was 42%; at SLED start, 51%. CONCLUSIONS: Prostacyclin is a safe and effective antihaemostatic agent for SLED.

Does haemodialysis significantly affect serum linezolid concentrations in critically ill patients with renal failure? A pilot investigation.

BACKGROUND: Previous studies have shown that a single haemodialysis (HD) session removes about one-third of the linezolid dose administered, but it is unknown whether in critically ill patients with renal failure on intermittent HD, this removal adversely affects serum antibiotic concentrations. METHODS: Five male critically ill patients (mean age 75 years, range 68-82; APACHE II score 26.4, range 23-29; survival 2/5) with sepsis and renal failure on haemodialysis, were administered i.v. linezolid, 600 mg every 12 h. Serum antibiotic levels were measured by high-performance liquid chromatography/mass spectrometry. We classified trough concentrations as 'with HD' when a HD session was performed after linezolid infusion, and 'without HD' otherwise. We also computed population pharmacokinetics while patients were on-dialysis and off-dialysis. RESULTS: A total of 222 serum linezolid concentrations were available over 36 days of antibiotic therapy, during which patients underwent 31 HD sessions. Trough serum linezolid levels averaged 5.83 mg/l (range 1.48-15.84), exceeding 4.0 mg/l in 68.9% of the samples; however, the trough levels 'with HD' were lower than those 'without HD' (4.68 mg/l [range 1.48-9.07] vs 6.74 mg/l [range 2.04-15.84], P<0.001). Clearance and half-life were 6.0 l/h and 4.0 h, respectively, while patients were on-dialysis, and 4.4 l/h and 7.3 h, respectively, when they were off-dialysis. CONCLUSIONS: HD can significantly reduce serum linezolid levels in critically ill patients with renal failure.

Effects of different energy intakes on nitrogen balance in patients with acute renal failure: a pilot study.

BACKGROUND: Thus far, there have been no controlled studies to examine optimal levels of energy provision in critically ill patients with acute renal failure (ARF) receiving artificial nutrition. METHODS: After a 24 h nitrogen-free regimen (20% dextrose), we assigned during an open-label, AB/BA-crossover-trial, 10 ARF patients receiving both total parenteral nutrition (TPN) and renal replacement therapy (seven males; mean age 72 years, range 60-83; mean APACHE II score 27.1, range 23-34, mechanical ventilation 8/10) to a lower calorie-TPN regimen (30 kcal/kg/day) and to a higher calorie-TPN regimen (40 kcal/kg/day), each for 3 days. Nitrogen intake was 0.25 g/kg/day for both regimens. We estimated nitrogen balance, protein catabolic rate and urea generation rate by urea kinetic methods based on both timed blood samples of serum urea and direct urea quantification from dialysis fluid. RESULTS: Two patients were excluded from the analysis (due to death and serum triglycerides above 5.1 mmol/l, respectively). Compared with the lower calorie-TPN, the higher calorie-TPN regimen did not improve estimated nitrogen balance [+1.55 g/day (95% confidence interval: -0.95 to +4.05, P = 0.18)], protein catabolic rate [-0.10 g/kg/day (-0.33 to +0.14, P = 0.35)], or urea generation rate [-1.3 mg/min (-5.2 to +2.7, P = 0.46)], whereas it increased serum triglycerides [+1.36 mmol/l (+0.53 to +2.19, P = 0.007)], glucose [+1.15 mmol/l (+0.07 to +2.24, P = 0.041)], insulin need [+20.4 U/day (+8.3 to +32.6, P = 0.006)] and nutritional fluid administration [+468 ml/day (+370 to +566, P<0.001)]. CONCLUSIONS: The present study, conducted in a small group of subjects, shows that in critically ill patients with ARF on a nitrogen intake of 0.25 g/kg/day, an energy provision of 40 kcal/kg/day does not improve nitrogen balance estimates compared with a 30 kcal/kg/day intake; instead, it may increase the risk of artificial nutrition-related side-effects.

Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure.

OBJECTIVE: To study the removal of linezolid, a new oxazolidinone antibiotic, by renal replacement therapy in patients with acute renal failure. DESIGN: Prospective, single-dose pharmacokinetic study. SETTING: Renal intensive care unit of a tertiary university hospital. PATIENTS: Fifteen critically ill patients with oliguric acute renal failure on renal replacement therapy (seven males, mean age 72.3 yrs, range 60-94; Acute Physiology and Chronic Health Evaluation II score 24.9, range 18-36; mechanical ventilation ten of 15). INTERVENTIONS: All patients received 600 mg of intravenous linezolid before starting renal replacement therapy, which consisted of intermittent hemodialysis lasting 3-4 hrs in eight patients, sustained low-efficiency dialysis lasting 8 hrs in five patients, and continuous venovenous hemofiltration lasting 10.5-12 hrs in two patients. MEASUREMENTS AND MAIN RESULTS: Linezolid concentrations were measured by liquid chromatography/mass spectrometry methods on serum and dialysate/ultrafiltrate samples. At the start of renal replacement therapy, serum levels averaged 11.91 mg/L (range 5.49-21.52) and dropped at the end to levels <4 mg/dL (90% minimum inhibitory concentration values for Staphylococcus aureus) in three of eight patients on hemodialysis, three of five patients on sustained low-efficiency dialysis, and two of two patients on continuous venovenous hemofiltration. Mean removal of the drug was 193.7 mg with hemodialysis (32.3% of the dose administered), 205 mg with sustained low-efficiency dialysis (33.9%), and 74.8 mg (12.4%) and 105 (17.5%) mg following a continuous venovenous hemofiltration session lasting 10.5 and 12 hrs, respectively. CONCLUSIONS: In patients with acute renal failure, serum levels of linezolid can be reduced to the subtherapeutic range following renal replacement therapy.

Plasma and urinary free 3-nitrotyrosine following cardiac angiography procedures with non-ionic radiocontrast media.

BACKGROUND: Radiocontrast media (RCM) administration is a common cause of hospital-acquired acute renal failure, especially in high-risk patients, but mechanisms of nephrotoxicity have not been fully elucidated. Reactive oxidant species recently have been shown to play a role in experimental RCM nephropathy, while there is clinical evidence that acetylcysteine, an antioxidant drug, has a protective effect against RCM nephropathy in humans. However, no study has been published showing that RCM administration elicits oxidative stress in humans. METHODS: In an unselected series of patients undergoing elective cardiac catheterization for coronary artery angiography and/or angioplasty, we monitored the time course of plasma and urinary levels of free 3-nitrotyrosine (3-NT), a stable marker of peroxynitrite generation resulting from the in vivo reaction of superoxide and nitric oxide. Urinary 3-NT levels were measured as the ratio of urinary 3-NT to urinary creatinine. Measurements were taken at baseline, immediately after the procedure and at 24, 48 and 72 h. RESULTS: Twenty-six patients were studied (median age 67.5 years, range 42-86; baseline serum creatinine 1.0 mg/dl, 0.6-1.5; RCM dose 215 ml, 100-580). Plasma 3-NT levels slightly increased over the 72 h following the procedure (P<0.001), while urinary 3-NT levels peaked at the end of the procedure (P<0.001). Urinary 3-NT levels reached at the end of the procedure were proportional to the RCM dose administered (P = 0.017). CONCLUSIONS: The present study provides indirect evidence that RCM administration in humans is associated with an increased production of 3-NT. Further studies are needed to ascertain whether oxygen- and nitrogen-derived radical species play a major role in the pathogenesis of RCM-associated nephrotoxicity in the clinical setting.

Enteral nutrition in patients with acute renal failure.

BACKGROUND: Systematic studies on safety and efficacy of enteral nutrition in patients with acute renal failure (ARF) are lacking. METHODS: We studied enteral nutrition-related complications and adequacy of nutrient administration during 2525 days of artificial nutrition in 247 consecutive patients fed exclusively by the enteral route: 65 had normal renal function, 68 had ARF not requiring renal replacement therapy, and 114 required renal replacement therapy. RESULTS: No difference was found in gastrointestinal or mechanical complications between ARF patients and patients with normal renal function, except for high gastric residual volumes, which occurred in 3.1% of patients with normal renal function, 7.3% of patients with ARF not requiring renal replacement therapy, 13.2% of patients with ARF on renal replacement therapy (P= 0.02 for trend), and for nasogastric tube obstruction: 0.0%, 5.9%, 14%, respectively (P < 0.001). Gastrointestinal complications were the most frequent cause of suboptimal delivery; the ratio of administered to prescribed daily volume was well above 90% in all the three groups. Definitive withdrawal of enteral nutrition due to complications was documented in 6.1%, 13.2%. and 14.9% of patients, respectively (P= 0.09 for trend). At regimen, mean delivered nonprotein calories were 19.8 kcal/kg (SD 4.6), 22.6 kcal/kg (8.4), 23.4 kcal/kg (6.5); protein intake was 0.92 g/kg (0.21), 0.87 g/kg (0.25), and 0.92 g/kg (0.21), the latter value being below that currently recommended for ARF patients on renal replacement therapy. Median fluid intake with enteral nutrition was 1440 mL (range 720 to 1960), 1200 (720 to 2400), and 960 (360 to 1920). CONCLUSION: Enteral nutrition is a safe and effective nutritional technique to deliver artificial nutrition in ARF patients. Parenteral amino acid supplementation may be required, especially in patients with ARF needing renal replacement therapy.

Continuous haemofiltration in acute renal failure with prostacyclin as the sole anti-haemostatic agent.

OBJECTIVE: To investigate the safety and efficacy of a synthetic prostacyclin analogue (epoprostenol) for circuit maintenance during continuous veno-venous haemofiltration (CVVH) in patients with acute renal failure (ARF). DESIGN: Observational case study. SETTING: University-affiliated six-bed intermediate renal care unit in a nephrology and internal medicine department of a 1300-bed teaching hospital. PATIENTS: A consecutive series of critically ill ARF patients in whom prostacyclin was the sole anti-haemostatic agent used for CVVH. INTERVENTIONS: Bicarbonate-based CVVH in pre-dilution (1.5 l/h); blood flow rate at 200 ml/min; prostacyclin at 4 ng/kg per min infusion in the extracorporeal circuit before the haemofilter. MEASUREMENTS AND MAIN RESULTS: Fifty-one ARF patients (mean APACHE II 27.2, SD 7.8; acute tubular necrosis in 44/51, 83%; mechanical ventilation 14/51, 21%; in-hospital mortality 28/51, 54%) underwent CVVH for a total of 4040 h (230 circuits, median number 4 circuits per patient, range 1-13). Four patients out of 51 (7.8%) experienced major bleeding during CVVH (1.0 episode per 1000 patient-hours of treatment; 95%CI, 0.4-2.6); no death could be attributed to haemorrhage. Therapeutic intervention for hypotension (fluids and/or vasopressors) was required in 15.5% of the CVVH sessions monitored. The median duration of the circuit was 15.0 h (95% CI, 13.0-16.5). CONCLUSIONS: The use of prostacyclin as the sole anti-haemostatic agent for CVVH entails a low risk of haemorrhagic complications, while maintaining the patency of the circuit long enough to allow the delivery of an adequate dose of renal replacement therapy. Further studies are needed to compare this technique to other anti-haemostatic strategies for CVVH.