Hemodialysis membrane with a high-molecular-weight cutoff and cytokine levels in sepsis complicated by acute renal failure: a phase 1 randomized trial.

BACKGROUND: Sepsis is the leading cause of acute renal failure. Intermittent hemodialysis (IHD) is a common treatment for patients with acute renal failure. However, standard hemodialysis membranes achieve only little diffusive removal of circulating cytokines. Modified membranes may enable both successful IHD treatment and simultaneous diffusive cytokine removal. STUDY DESIGN: Double-blind, crossover, randomized, controlled, phase 1 trial. SETTING & PARTICIPANTS: Tertiary intensive care unit. 10 septic patients with acute renal failure according to RIFLE class F. INTERVENTION: Each patient was treated with 4 hours of high-cutoff (HCO)-IHD and 4 hours of high-flux (HF)-IHD. OUTCOMES & MEASUREMENTS: We chose relative change in plasma interleukin 6 (IL-6) concentrations from baseline to 4 hours as the primary outcome for effective cytokine removal. We measured plasma and effluent concentrations of cytokines (IL-6, IL-8, IL-10, and IL-18) and albumin. RESULTS: Median age was 53 years (25(th) to 75(th) percentiles, 43 to 71 years). Both treatments achieved equal control of uremia. Four hours of HCO-IHD accomplished a greater decrease in plasma IL-6 levels (-30.3%) than 4 hours of HF-IHD (1.1%; P = 0.05). HCO-IHD, but not HF-IHD, achieved substantial diffusive clearance of several cytokines (IL-6, 14.1 mL/min; IL-8, 75.2 mL/min; and IL-10, 25.5 mL/min). Such clearance also was associated with greater relative decreases in plasma IL-8 and IL-10 levels in favor of HCO-IHD (P = 0.02, P = 0.04). We found significantly greater relative changes from prefilter to postfilter plasma IL-6, IL-8, and IL-10 values in favor of HCO-IHD (P = 0.02, P = 0.01, P < 0.01). During HCO-IHD, cumulative albumin loss into the effluent was 7.7 g (25(th) to 75(th) percentiles, 4.8 to 19.6) versus less than 1.0 g for HF-IHD (P < 0.01). LIMITATIONS: Small phase 1 trial. CONCLUSION: In septic patients with acute renal failure, HCO-IHD achieved simultaneous uremic control and diffusive cytokine clearances and a greater relative decrease in plasma cytokine concentrations than standard HF-IHD.

The SAFE study: a landmark trial of the safety of albumin in intensive care.

High-quality primary evidence from an Australian and New Zealand study provides a definitive answer.

A comparison of albumin and saline for fluid resuscitation in the intensive care unit.

BACKGROUND: It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival. We conducted a multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU. METHODS: We randomly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days. The primary outcome measure was death from any cause during the 28-day period after randomization. RESULTS: Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and 3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 percent confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups (P=0.85). There were no significant differences between the groups in the mean (+/-SD) numbers of days spent in the ICU (6.5+/-6.6 in the albumin group and 6.2+/-6.2 in the saline group, P=0.44), days spent in the hospital (15.3+/-9.6 and 15.6+/-9.6, respectively; P=0.30), days of mechanical ventilation (4.5+/-6.1 and 4.3+/-5.7, respectively; P=0.74), or days of renal-replacement therapy (0.5+/-2.3 and 0.4+/-2.0, respectively; P=0.41). CONCLUSIONS: In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days.

Appropriateness of red blood cell transfusion in Australasian intensive care practice.

OBJECTIVE: To determine the incidence and appropriateness of use of allogenic packed red blood cell (RBC) transfusion in Australian and New Zealand intensive care practice. SETTING: Intensive care units of 18 Australian and New Zealand hospitals: March 2001. DESIGN: Prospective, observational, multicentre study. METHODS: All admissions to participating intensive care units were screened and all patients who received a transfusion of RBC were enrolled. The indications for transfusion were recorded and compared with Australian National Health and Medical Research Council guidelines. Transfusions conforming to these guidelines were deemed appropriate. MAIN OUTCOME MEASURES: RBC transfusion in intensive care and transfusion appropriateness. RESULTS: 1808 admissions to intensive care units were screened: 357 (19.8%) admissions (350 patients) received an RBC transfusion while in intensive care. Overall, 1464 RBC units were administered in intensive care on 576 transfusion days. The most common indications for transfusion were acute bleeding (60.1%; 880/1464) and diminished physiological reserve (28.9%; 423/1464). The rate of inappropriate transfusion was 3.0% (44/1464). Diminished physiological reserve with haemogloblin level > or = 100 g/L was the indication in 50% (22/44) of inappropriate transfusions; no indication was provided for 31% (15/44). CONCLUSION: The rate of inappropriate transfusion in Australian and New Zealand intensive care units in 2001 was remarkably low.