Pharmacokinetics and total elimination of meropenem and vancomycin in intensive care unit patients undergoing extended daily dialysis* :

Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival. We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 mL h(-1) kg(-1) (group 1, n=146), 35 mL h(-1) kg(-1) (group 2, n=139), or 45 mL h(-1) kg(-1) (group 3, n=140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. Survival in group 1 was significantly lower than in groups 2 (p=0.0007) and 3 (p=0.0013). Survival in groups 2 and 3 did not differ significantly (p=0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of survivors in groups 1, 2, and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly. We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 mL h(-1) kg(-1).

Intermittent hemodialysis is widely used as renal-replacement therapy in patients with acute renal failure, but an adequate dose has not been defined. We performed a prospective study to determine the effect of daily intermittent hemodialysis, as compared with conventional (alternate-day) intermittent hemodialysis, on survival among patients with acute renal failure. A total of 160 patients with acute renal failure were assigned to receive daily or conventional intermittent hemodialysis. Survival was the primary end point of the study. The duration of acute renal failure and the frequency of therapy-related complications were secondary end points. The two study groups were similar with respect to age, sex, cause and severity of acute renal failure, medical or surgical intensive care setting, and the score on the Acute Physiology, Age, and Chronic Health Evaluation. Daily hemodialysis resulted in better control of uremia, fewer hypotensive episodes during hemodialysis, and more rapid resolution of acute renal failure (mean [+/-SD], 9+/-2 vs. 16+/-6 days; P=0.001) than did conventional hemodialysis. The mortality rate, according to the intention-to-treat analysis, was 28 percent for daily dialysis and 46 percent for alternate-day dialysis (P=0.01). In a multiple regression analysis, less frequent hemodialysis (on alternate days, as opposed to daily) was an independent risk factor for death. The high mortality rate among critically ill patients with acute renal failure who require renal-replacement therapy is related to both coexisting conditions and uremic damage to other organ systems. Intensive hemodialysis reduces mortality without increasing hemodynamically induced morbidity.

Extended dialysis is an increasingly used modality of renal replacement therapy that theoretically offers advantages of both intermittent and continuous therapies in the intensive care unit (ICU). We randomly treated 39 ventilated critically ill patients with oliguric acute renal failure with either continuous venovenous hemofiltration (CVVH; n = 19; age, 50.1 +/- 3.2 years; Acute Physiology and Chronic Health Assessment II [APACHE II] score, 32.3 +/- 1.2; 79% sepsis) and a substitution fluid rate of at least 30 mL/kg/h for 24 hours or with extended dialysis for 12 hours (n = 20; age, 50.8 +/- 3.6 years; APACHE II score, 33.6 +/- 1.0; 85% sepsis). The latter was performed using an easy-to-handle, single-pass, batch dialysis system. All hemodynamic parameters were monitored invasively by means of an indwelling arterial catheter. Average mean arterial blood pressure, heart rate, cardiac output, systemic vascular resistance, and catecholamine dose were not significantly different in both therapies. Urea reduction rate was similar with extended dialysis compared with CVVH therapy (53% +/- 2% versus 52% +/- 3%; P = not significant) despite an average rate of substitution fluid with the latter of 3.2 +/- 0.1 L/h. This was corroborated by the finding of similar amounts of urea eliminated in the collected spent total hemofiltration and dialysis fluid. Correction of acidosis was accomplished faster with extended dialysis than CVVH, and the amount of heparin used was significantly lower with extended dialysis (P < 0.01). Extended dialysis combines excellent detoxification with cardiovascular tolerability, even in severely ill patients in the ICU. The technically simple dialysis system used offers flexibility of treatment time.