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R Bellomo

Publications and source records attributed to R Bellomo.

At least 181 records · Page 10Linked to original sources

A prospective comparative study of moderate versus high protein intake for critically ill patients with acute renal failure.

Critically ill patients with acute renal failure are traditionally treated with low-protein diets to help control uremia. This dietary approach may be deleterious to the patient's nutritional status and unnecessary, especially if continuous renal placement therapies (CRRT) are used. However, the optimal amount of protein supplementation during CRRT is unknown. In patients receiving CRRT, a high protein intake may result in a positive nitrogen balance in the absence of uncontrolled uremia. Accordingly, we studied nitrogen metabolism in two consecutive cohorts of acute renal failure patients receiving equal amounts of calories but variable amounts of nitrogen. One group received protein according to the preferences of the attending clinician, the other a high and fixed amount of protein (2.5 g/kg/day). Patients treated according to attending clinician preferences received significantly less dietary protein (1.2 g/kg/day vs. 2.5 g/kg/day; p < 0.0001) and had a negative mean nitrogen balance of -5.5 g/day. Patients receiving a high and fixed amount of protein had a less negative mean nitrogen balance (-1.92 g/day). Such patients were more likely to experience a positive nitrogen balance during any 24-h period (53.6% vs. 36.7%; p < 0.05). They also required more aggressive hemofiltration to maintain control of uremia (mean ultradiafiltrate volume: 2145 mL/h vs. 1658 mL/h; p < 0.0001) and had a significantly higher but still acceptable mean plasma urea level (26.6 mmol/L vs. 18 mmol/L; p < 0.0001). Survival was not significantly different in the two groups (37.5% vs. 31.3%). We conclude that a high-protein diet can be safely administered to critically ill patients with acute renal failure receiving continuous renal replacement therapy. Such a high protein intake improves nitrogen balance when compared to moderate protein intake. A low protein intake is unnecessary in patients treated with CRRT.

Acute Kidney Injury↗

[Continuous "high flux" dialysis: an effective renal replacement therapy for intensive care patients].

Currently available replacement therapies for the treatment of acute renal failure are reviewed. Particular interest is focused on their application in intensive care, especially in septic patients. Underlying principles and mechanisms of action are explained. The continuous "High flux-dialysis" is shown to be a particularly effective form of renal replacement therapy.

Acute Kidney Injury↗

Effect of superantigens on human thymocytes: selective proliferation of V beta 2+ cells in response to toxic shock syndrome toxin-1 and their deletion upon secondary stimulation.

The effects of toxic shock syndrome toxin-1 (TSST-1) on human thymocytes and their CD4/CD8-defined subsets have been analyzed. Postnatal thymocyte cell suspensions were cultured with 5 ng/ml TSST-1 for different time intervals. A strong cell proliferation of CD3+/TCR+ cells, characterized by selective expansion of cells expressing TCR V beta 2, occurred. In these cultured thymocytes, V beta 2+ cells were detected in all subsets including CD4-CD8+ cells. CD4-CD8+ thymocyte populations (obtained by depletion of CD4+ cells) were further analyzed for their ability to directly respond to TSST-1. An efficient cell proliferation occurred; however, it was completely abrogated upon removal of HLA class II+ cells (representing 10% of fresh thymocytes depleted of CD4+ cells). The HLA class II dependency of TSST-1 mediated functions was further documented at the clonal level. Thus, in the presence of TSST-1, CD4-CD8+ V beta 2+ clones efficiently lysed the HLA class II+ Raji target cells but not the corresponding HLA class II- variant RJ 2.2.5. Analysis of the effect of TSST-1-induced secondary stimulation on cultured (V beta 2+-enriched) thymocytes resulted in a selective depletion of V beta 2+ cells due to apoptotic cell death.

Bacterial Toxins↗

Transvisceral lactate fluxes during early endotoxemia.

The pathogenesis of hyperlacticemia during sepsis is poorly understood. We investigated the role of lung, kidney, gut, liver, and muscle in endogenous lactate uptake and release during early endotoxemia in an intact, pentobarbital-anesthetized dog model (n = 14). Ultrasonic flow probes were placed around the portal vein and hepatic, renal, and femoral arteries. After splenectomy, catheters were inserted into the pulmonary artery, aorta, and hepatic, left renal, and femoral veins. Whole blood lactate and blood gases from all catheters, organ flows, and cardiac output were measured before and 30 to 45 min after a bolus infusion of Eacherichia coli endotoxin (1 mg/kg). After endotoxin infusion, mean arterial blood lactate level increased from 0.92 +/- 0.11 to 1.60 +/- 0.15 mmol/L (p < 0.0001). Lung lactate flux changed from uptake to release of lactate adding a mean of 9.97 +/- 16.23 mmol/h (p < 0.05) to the systemic circulation. Liver and muscle lactate fluxes remained neutral at all times, while kidney and gut took up lactate from the circulation both before and after endotoxin infusion (mean renal uptake, 2.73 +/- 3.85 mmol/L; p < 0.001; mean gut uptake, 2.46 +/- 2.31 mmol/h; p < 0.002). Except for the kidney, where a decrease in blood flow correlated with diminished uptake, there was no correlation between changes in transvisceral lactate fluxes and organ or systemic oxygen delivery during endotoxemia. A positive correlation between lactate uptake and oxygen consumption during endotoxemia was seen for both gut (p < 0.0001) and kidney (p < 0.002). We conclude that, in the dog, the pathogenesis of endotoxin-induced hyperlacticemia is complex. The lung may be responsible for significant lactate release, and other viscera that normally take up lactate are unable to adequately clear this increased lactate.

Animals↗

Resuscitation from severe hemorrhage.

The potential to be successfully resuscitation from severe traumatic hemorrhagic shock is not only limited by the "golden 1 hr", but also by the "brass (or platinum) 10 mins" for combat casualties and civilian trauma victims with traumatic exsanguination. One research challenge is to determine how best to prevent cardiac arrest during severe hemorrhage, before control of bleeding is possible. Another research challenge is to determine the critical limits of, and optimal treatments for, protracted hemorrhagic hypotension, in order to prevent "delayed" multiple organ failure after hemostasis and all-out resuscitation. Animal research is shifting from the use of unrealistic, pressure-controlled, hemorrhagic shock models and partially realistic, volume-controlled hemorrhagic shock models to more realistic, uncontrolled hemorrhagic shock outcome models. Animal outcome models of combined trauma and shock are needed; a challenge is to find a humane and clinically realistic long-term method for analgesia that does not interfere with cardiovascular responses. Clinical potentials in need of research are shifting from normotensive to hypotensive (limited) fluid resuscitation with plasma substitutes. Topics include optimal temperature, fluid composition, analgesia, and pharmacotherapy. Hypotensive fluid resuscitation in uncontrolled hemorrhagic shock with the addition of moderate resuscitative (28 degrees to 32 degrees C) hypothermia looks promising in the laboratory. Regarding the composition of the resuscitation fluid, despite encouraging results with new preparations of stroma-free hemoglobin and hypertonic salt solutions with colloid, searches for the optimal combination of oxygen-carrying blood substitute, colloid, and electrolyte solution for limited fluid resuscitation with the smallest volume should continue. For titrating treatment of shock, blood lactate concentrations are of questionable value although metabolic acidemia seems helpful for prognostication. Development of devices for early noninvasive monitoring of multiple parameters in the field is indicated. Molecular research applies more to protracted hypovolemic shock followed by the systemic inflammatory response syndrome or septic shock, which were not the major topics of this discussion.

Animals↗

Hepatic anion flux during acute endotoxemia.

We sought to determine the role the liver might play in the regulation of anion-cation balance during both stable baseline conditions and acute endotoxemia. Ten pentobarbital sodium-anesthetized dogs were instrumented at laparotomy with ultrasonic flow probes around the left renal artery, portal vein, and hepatic artery, and catheters were inserted into the hepatic vein, portal vein, pulmonary artery, left renal vein, and abdominal aorta. Measurements were obtained from each site at baseline and 30-45 min after the intravenous infusion of endotoxin. The total anion flux across the liver was calculated from the strong-ion difference. At baseline, the liver removed anions from the circulation (-0.34 meq/min). With early endotoxemia, however, the liver switched to the release of anions (0.12 meq/min; P = 0.0046). After endotoxin administration, the gut, which was neutral at baseline, began to take up anions (-0.47 meq/min; P = 0.008). Anion flux across the lung and kidney was unchanged. We conclude that in the dog the liver, which removes anions at baseline, switches to release anions during early endotoxemia and may be a major site of acid production in early sepsis.

Acid-Base Equilibrium↗

Treatment of sepsis-associated severe acute renal failure with continuous hemodiafiltration: clinical experience and comparison with conventional dialysis.

The syndrome of sepsis-associated severe acute renal failure is a frequent component of sepsis-induced multiorgan failure. Continuous hemofiltration techniques are often used in its dialytic management but little is known about their impact. The aim of this study is to define the biochemical and clinical impact of continuous hemodiafiltration (CHD) in the management of this syndrome and to retrospectively compare it to that of conventional dialysis. A prospective, cohort study and retrospective comparison with historical controls was conducted at an intensive care unit (ICU) of a tertiary institution. Eighty-seven consecutive septic patients with acute renal failure were treated by continuous hemodiafiltration and 40 consecutive similar patients by conventional dialysis. All new cases of severe acute renal failure with sepsis were treated by means of continuous hemodiafiltration. Historical controls were treated by means of conventional dialysis. Illness and sepsis severity were assessed on admission and prior to initiation of treatment. Biochemical variables were assessed daily. Outcome was measured as discharge from the ICU, duration of oliguria and discharge from hospital. Of the 87 patients treated by hemodiafiltration, 86 had multiorgan failure, 71 (81.6%) septic shock and 52 (59.8%) bacteremia/fungemia. Their APACHE II score on admission was 29.9 and their mean organ failure score prior to treatment was 4.3. Hemodiafiltration resulted in a significant fall in mean urea and creatinine levels within 24 h and in the correction of acidosis. The mean alveolar-arterial gradient fell from 276 to 211 mm Hg (p < 0.02) within 24 h of therapy. Complications were few and mostly related to vascular access.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Severe acute renal failure: a comparison of acute continuous hemodiafiltration and conventional dialytic therapy.

It is unknown whether continuous renal replacement techniques result in diminished morbidity and mortality when compared to conventional dialytic techniques. To investigate this issue a previously described, retrospectively studied group of critically ill patients with severe acute renal failure treated by conventional dialysis (CD) was compared to a prospectively studied group of similar patients treated by acute continuous hemodiafiltration (ACHD). A combined retrospective and prospective clinical and laboratory investigation was carried out for 234 consecutive critically ill patients with severe acute renal failure in the intensive care unit of a tertiary institution. Biochemical, clinical and outcome data in all patients treated by conventional dialytic techniques (intermittent hemodialysis and/or peritoneal dialysis) during a 5-year period were retrospectively analyzed, and a prospective analysis of the same biochemical, clinical and outcome data in all patients treated by acute continuous hemodiafiltration was done over a similar time span, with statistical comparison of findings. One hundred and fifty patients were treated by ACHD and 84 by CD. ACHD patients were more severely ill (mean APACHE II score: 28.2 vs. 25.8; p < 0.01) and older (mean age: 59.9 vs. 55.5 years; p < 0.01). There were no significant differences in the incidence of sepsis, bacteremia and need for mechanical ventilation. ACHD resulted in better control of uremia (mean steady-state plasma urea level: 20.1 vs. 31.7 mmol/l; p < 0.001) and hyperphosphatemia (mean serum phosphate: 1.26 vs. 1.95 mmol/l) after 24 h of initiation of therapy. It also allowed the administration of full nutritional support in a significantly greater percentage of patients (91.3 vs. 64.8%; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Interleukin-6 and interleukin-8 extraction during continuous venovenous hemodiafiltration in septic acute renal failure.

OBJECTIVES: To determine whether continuous venovenous hemodialfiltration (CVVHD) is associated with the extraction of interleukin-6 (IL-6) and interleukin-8 (IL-8) from the circulation of critically ill patients with septic acute renal failure. To quantitate their clearance and assess any possible effect of CVVHD on these cytokines' serum concentrations. DESIGN: Prospective controlled study of IL-6 and IL-8 removal by CVVHD in patients with septic acute renal failure. SETTING: Intensive care unit of a tertiary institution. PATIENTS: Ten critically ill patients with sepsis, acute renal failure, and multiorgan failure. A control group of five patients experiencing an acute illness while undergoing chronic hemodialysis. INTERVENTIONS: Collection of blood samples before CVVHD. Simultaneous collection of prefilter blood and ultradiafiltrate after 4 and 24 h of treatment. IL-8 concentrations were measured in blood and ultradiafiltrate. Their clearances and daily extractions were calculated. MEASUREMENTS AND MAIN RESULTS: IL-6 and IL-8 were detected in the blood of all patients with septic acute renal failure prior to CVVHD. The median IL-6 blood level was 103 pg/mL (range: 19 to 900) and the median IL-8 blood level was 200 (range: 32 to 2925). Both cytokines were cleared by the hemofilter during CVVHD. The median hemofilter clearance of IL-6 were 1.99 L/day (range: 0 to 8.5) and the median clearance of IL-8 was 3.95 L/day (range: 0.31 to 42.8). These blood levels and clearances resulted in median daily extraction rates of 194 ng of IL-6 (range: 0 to 9031) and of 915 ng of IL-8 (range 47.5 to 3562). Control patients had negligible amounts of either IL-6 or IL-8 in their ultrafiltrate. The rate of extraction for IL-6 correlated with its blood levels (p < 0.0001). This was not true for IL-8. A correlation between IL-6 levels and the patients' white cell counts was found after 24 h of hemofiltration. CONCLUSIONS: CVVHD is associated with the extraction of IL-6 and IL-8 from the circulation of patients with septic multiorgan and renal failure. The biological significance of such extraction is undetermined, but such cytokine removal highlights the complexity of the effect of continuous hemofiltration on the soluble mediators of inflammation activated during human sepsis.

APACHE↗

Continuous hemofiltration as blood purification in sepsis.

Continuous hemofiltration was first described as a new form of renal replacement for critically ill patients in the late 1970s. Since then, it has undergone remarkable technical and conceptual modifications and has become a widely used form of dialytic therapy in the ICU. More recent insights into the pathogenesis of sepsis and the role of soluble molecules in the mediation of organ injury during septic shock have led to a resurgence of the concept of blood purification during life-threatening infection. Recent studies have confirmed that cytokine extraction occurs in vivo in humans during continuous hemofiltration and that other smaller, potentially noxious molecules such as platelet-activating factor, complement factors C5a and C3a, and thromboxane are also removed from the circulation of septic patients or animals. Experimental studies have shown that continuous hemofiltration has beneficial hemodynamic effects in septic animals and that such effects may correlate with the intensity of ultrafiltration. Cardiac function also appears to improve and myocardial depressant factors are removed from the circulation. Continuous hemofiltration offers some promise as an adjunctive form of treatment in severe sepsis.

Animals↗

Acute renal replacement in the intensive care unit: now and tomorrow.

Although acute renal failure (ARF) requiring dialysis affects only approximately 4% to 7% of patients admitted to the ICU, such individuals tend to be the sickest and most challenging patients in the ICU. The presence of ARF dramatically complicates their care and mandates the use of extracorporeal renal replacement therapy (RRT). The use of such therapy, with its technical and physiological demands, further complicates treatment. Not surprisingly, therefore, several controversies surround the management of these patients: the techniques of RRT, the indications and timing for their application, the intensity of their use, the selection of suitable patients, the nature of appropriate monitoring and physiologic targets for their application, the type of specialist best suited for the daily management of such patients, the cost-effectiveness of RRT, and the expansion of its use to treat patients without ARF. In many ways, the response to these controversies has diverged between Europe, Australia, and New Zealand on the one hand, and the United States on the other. In this article, we illustrate these sometimes quite different philosophies by presenting two perspectives (from Australia and the United States) on a number of important issues pertaining to RRT.

Acute Kidney Injury↗

Combined acute respiratory and renal failure: management by continuous hemodiafiltration.

OBJECTIVES: To study the impact of continuous hemodiafiltration (CHD) on the morbidity and mortality of acute combined respiratory and renal failure in critically ill patients. DESIGN: Prospective clinical study. SETTING: Intensive Care Unit of a tertiary institution. PATIENTS: One-hundred fifteen critically ill patients with combined acute respiratory and renal failure. INTERVENTIONS: Treatment of all patients with either continuous arteriovenous hemodiafiltration (CAVHD) or continuous venovenous hemodiafiltration (CVVHD). MEASUREMENTS: Assessment of illness severity, measurement of plasma urea, serum creatinine, electrolytes and arterial blood gases prior to and during treatment. Duration of oliguria, ICU stay, hospital stay, and final outcome. RESULTS: One hundred fifteen critically ill patients with combined respiratory and renal failure (mean APACHE II score, 28.1; mean number of failing organs, 4.1) were studied. Thirty-five were treated with CAVHD and 80 with CVVHD for a mean treatment duration of 13.1 days per patient (range 2-47). Blood urea concentration fell from a mean of 29.4 mmol/l to a mean of 19.1 mmol/l (P < 0.001) and the serum creatinine concentration fell from a mean of 520 mumol/l to a mean of 374 mumol/l after 24 h of therapy (P < 0.001). The A-a gradient fell from a mean of 301 mmHg to a mean of 242 mmHg (P < 0.05). Despite the high degree of illness severity and the need for vasoactive drug infusion in 105 patients (91.3%), survival to hospital discharge was achieved in 33 patients (28.7%). For patients who required > 72 h of combined mechanical ventilation, survival was 22% (22 of 100 patients). Complications of continuous hemodiafiltration were few and all related to arterial vascular access. CONCLUSIONS: In critically ill patients with combined acute respiratory and renal failure, continuous hemodiafiltration controlled azotemia without hypotension and with early improvement in gas exchange. PATIENTS treated with this approach achieved promising survival rates. Our findings support the view that CHD is safe and effective and that it offers important advantages over intermittent hemodialysis. It may be the dialytic therapy of choice in critically ill patients with combined acute respiratory and renal failure.

Acute Kidney Injury↗