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R Bellomo

Publications and source records attributed to R Bellomo.

At least 73 records · Page 4Linked to original sources
PubMed2002

Importance of increased ultrafiltration volume and impact on mortality: sepsis and cytokine story and the role for CVVH.

There is growing interest in extracorporeal blood purification therapies (EBPT) as adjuvants in the complex therapy of sepsis and multiple organ dysfunction syndrome (MODS). Nowadays the only routinely used purification technique is 'renal replacement therapy' (RRT) during acute renal failure (ARF), one of the almost inevitable and deadly components of MODS. RRT has been the first and still is the most utilised and effective type of EBPT. Evidence is growing about its ability to maintain homeostatic balance in critically ill patients, and specifically in septic patients with MODS. Clinical trials have been recently designed to modify or improve these therapies. In detail, the following issues have been currently addressed: effects on blood purification provided by different therapies, adequacy of prescription and delivery of therapy, toxins and solutes to be removed with these techniques. Based on these speculations we will briefly review the current understanding of these issues and the rationale for application of RRT in the intensive care unit (ICU). In particular, we will focus on the importance of increased ultrafiltration volume and its impact on mortality in the general ICU population and in septic patients.

Acute Kidney Injury↗
PubMed2002

Coupled plasma filtration adsorption.

Both pro-inflammatory and anti-inflammatory mediators participate in the pathogenesis of sepsis and explain the failure of specific therapies to improve survival. Continuous extracorporeal therapies have been proposed as a therapeutic option in sepsis. We have studied the effects of plasma filtration associated with adsorption in patients with septic shock. We have shown that such treatment may lead to improved survival in a rabbit model of sepsis and to improved hemodynamics, reduced norepinephrine dose and restoration of near-to-normal responsiveness of blood leukocytes to endotoxin in humans. It is anticipated that treatment of plasma, as a device modular to conventional hemofiltration, may pave the way to innovative approaches to the extracorporeal treatment of septic patients.

Adsorption↗
PubMed2002

How to feed patients with renal dysfunction.

Renal dysfunction is common in critically ill patients and its presence has, in the past, posed serious challenges to nutritional support. Such challenges were due to the increased azotemia induced by protein or amino acid administration, the fluid overload caused by the administration of nutrients and the difficulties associated with the control of these complications by means of conventional dialytic techniques. The development and increasing application of continuous renal replacement therapy (CRRT) has removed such concerns, because control of azotemia and fluid balance can be predictably and reliably achieved in all patients. Accordingly, the presence of renal failure should in no way influence the amount or type of nutritional support administered to a critically ill patient. We recommend that approximately 30-35 kcal/kg/day be administered enterally and begun within the first few hours of admission to the intensive care unit and that protein intake be kept in the 1.5-2 g/kg/day range. Accumulating evidence also suggests that immune-enhancing enteral preparations decrease the duration of hospital stay, the number of infections and perhaps mortality. Such preparations should be used in these patients. Finally adequate vitamin and trace element supplementation is recommended to counterbalance the decrease in antioxidants and the loss of some vitamins during CRRT. Available evidence suggests that if these steps are applied as part of a protocol-based approach to the nutritional support of patients with renal failure, their morbidity and perhaps mortality can be significantly decreased.

Amino Acids↗
PubMed2002

Pharmacological principles of antibiotic prescription in the critically ill.

The goal of antimicrobial prescription is to achieve effective drug concentrations. Standard antimicrobial dosing regimens are based on research performed often decades ago and for the most part with patients who were not critically ill. More recent insights into antibiotic activity (e.g. the importance of high peak/MIC ratios for aminoglycosides and time above MIC for beta-lactam antibiotics), drug pharmacokinetics (e.g. increased volume of distribution and altered clearances) and the pathogenesis of sepsis (e.g. third space losses and altered creatinine clearances) have made re-evaluation of dosing regimens necessary for the critically ill. The inflammatory response associated with sepsis results in a rapid decrease in serum albumin levels, large fluid shifts and third space losses, initially with a high cardiac output. In turn these changes result in increased creatinine clearance and increased renal drug clearance. Unless these effects are offset by ensuing renal and/or hepatic impairment, with subsequent drug accumulation, antibiotic levels may be too low for optimal efficacy. The institution of continuous renal replacement therapy separately affects antibiotic clearances, and therefore dosing, even further. This article reviews relevant literature and offers principles for more effective and appropriate antibiotic dosing in the critically ill, based on the pharmacokinetic and pharmacodynamic principles of the main antibiotic groups (aminoglyosides, glycopeptides, beta-lactams, carbapenems and quinolones) and knowledge of the pathophysiology of the inflammatory response syndrome. Finally it also provides some guidance on the basic principles of drug prescription for patients receiving continuous renal replacement therapy.

Acute Kidney Injury↗
PubMed2002

Cytokine removal with a large pore cellulose triacetate filter: an ex vivo study.

OBJECTIVE: To test the hypothesis that hemofiltration using a new large pore cellulose triacetate hemofilter can achieve effective ultrafiltration of cytokines. DESIGN: Ex-vivo study. SETTING: Laboratory of Intensive Care Unit in tertiary hospital. SUBJECTS: Six healthy volunteers. INTERVENTIONS: Blood from 6 volunteers was incubated for 4 hours with 1 mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore cellulose triacetate hemofilter (nominal cut-off point: 60 kilodaltons). Hemofiltration was conducted at 1 L/h or 6 L/h of ultrafiltrate (UF) flow at the start of extra-corporeal circulation, and after 2 and 4 hours. Samples were taken from the arterial, venous and UF sampling ports. MEASUREMENTS AND MAIN RESULTS: IL-Ibeta, IL-6, IL-8, IL-10, TNFalpha, and albumin were measured. Sieving coefficients (SC) above 0.6 were achieved for IL-Ibeta and IL-6 and SCs above 0.3 were achieved for IL-8 and TNF-alpha at 1 L/h. Sieving coefficients of all cytokines (except IL-10, p=0.22) were reduced when the ultrafiltration rate was increased from IL/h to 6 L/h (p<0.01), but the increase in ultrafiltration rate resulted in an overall increase in the clearance of all cytokines (p<0.001). The highest SC for albumin was 0.07 at 4 hours at 1 L/h, and fell to 0.01 at 6 L/h. The SCs for IL-8 fell at 4 hours (p<0.01), but the SCs for other cytokines did not change. No adsorption of cytokines and albumin was observed. CONCLUSION: High volume hemofiltration (HVHF) using a new large pore cellulose triacetate filter achieved cytokine clearances greater than those reported with currently available hemo filters.

Albumins↗
PubMed2002

High protein intake during continuous hemodiafiltration: impact on amino acids and nitrogen balance.

AIMS: To study the effect of combined continuous veno-venous hemodiafiltration (CVVHDF) and high (2.5 g/kg/day) parenteral amino acid supplementation on nitrogen balance, amino acid losses and azotemic control in a cohort of patients with severe acute renal failure (ARF). METHODS: We administered 2.5 grams/kg/day of amino acids intravenously to seven critically ill patients with ARF. We obtained paired blood and ultrafiltrate (UF) samples (n=20) and calculated amino acid clearances and losses, nitrogen balance, protein catabolic rate and total nitrogen losses. RESULTS: The median total serum amino acid concentration was high at 5.2 mmol/L with particularly high concentrations of ornithine, lysine, and phenylalanine, but a low level of histidine. The median overall amino acid clearance was 18.6 ml/min (range: 12 to 29 ml/min). UF losses as percentage of administered dose were high for tyrosine (53.6%) but low for methionine (3.0%) and arginine (2.3%). A positive nitrogen balance was achieved in 7 (35%) of the 20 study days with an overall median nitrogen balance of -1.8 g/day. Urea levels were maintained at a median of 26.6 mmol/L. CONCLUSIONS: High protein intake increases the serum concentrations of most amino acids. Such protein supplementation, when coupled with CVVHDF achieves a slightly negative overall nitrogen balance in extremely catabolic patients while still allowing adequate azotemic control.

Acute Kidney Injury↗
PubMed2002

Continuous veno-venous hemodiafiltration or hemofiltration: impact on calcium, phosphate and magnesium concentrations.

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on calcium, phosphate and magnesium concentrations. Accordingly, we tested whether continuous veno-venous hemodia filtration (CVVHDF) or continuous venovenous hemofiltration (CVVH) would achieve better control of these electrolytes. DESIGN: Retrospective controlled study SETTING: Two tertiary Intensive Care Units PATIENTS: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n=49) or CVVH (n=50) INTERVENTIONS: Retrieval of daily morning ionized calcium, phosphate and magnesium before and after the initiation of CRRT for up to 2 weeks of treatment. MEASUREMENTS AND RESULTS: Before treatment, both groups had a high incidence of abnormal ionized calcium concentrations (57.2% for CVVHDF vs 46.0% for CVVH; NS). After treatment, both groups showed a significant increase in serum calcium concentration over the first 48 h (p=0.041 vs p=0.0048) but hypercalcemia was more common during CVVHDF (15.3% vs 0.4%; p<0.0001). However, in both groups, hypocalcemia remained common (30.9% vs 36.7%; NS). Before treatment, abnormal serum phosphate concentrations were also common (65.1% for CVVHDF vs 78.1% for CVVH; NS). After treatment, both groups achieved a significant reduction of serum phosphate within 48 hours (p<0.0001 in both groups). There was no difference in the prevalence of abnormal phosphate levels during treatment (45.5% vs 42.4%; NS). Before treatment, both groups had a high incidence of abnormal magnesium concentrations (50.0% for CVVHDF vs 51.2% for CVVH; NS). During treatment, there was no significant change in serum magnesium concentrations during the first 48 hours or in the prevalence of abnormal magnesium concentrations (56.3% vs 63.4%; p=0.13). However CVVHDF was associated with a higher prevalence of hypomagnesemia (8.1% vs 0.4%; p<0.0001) and a lower incidence of hypermagnesemia (48.2% vs. 63.0%; p=0.0014). CONCLUSIONS: In critically ill patients with ARF, calcium, phosphate and magnesium were commonly abnormal and they were only partly corrected by CRRT. CVVH and CVVHDF had a different effect on serum magnesium concentrations.

Acute Kidney Injury↗
PubMed2002

Acute renal failure and multiple organ dysfunction in the ICU: from renal replacement therapy (RRT) to multiple organ support therapy (MOST).

Renal replacement therapy (RRT) has evolved from the concept that we need to treat the dysfunction of a single organ (the kidney). As intensive care units have become more and more complex, it has become clear that the majority of patients with acute renal failure often have dysfunction of several other organs. In order to facilitate single organ support in this setting, continuous renal replacement therapy (CRRT) techniques have been developed. However, CRRT has opened the door to the concept that targeting renal support as the only goal of extracorporeal blood purification may be a simplistic view of our therapeutic aims. In this article we argue that it is now time to move from the simple goal of achieving adequate renal support. The proper goal of extracorporeal blood purification in ICU should be multi-organ support therapy (MOST). We explain why MOST represents the most logical future conceptual and practical evolution of CRRT and illustrates the biological rationale, supplying animal and clinical evidence that confirms the need to move rapidly in this direction theoretically, practically and technologically.

Acute Kidney Injury↗
PubMed2002

The effect of circuit "down-time" on uraemic control during continuous veno-venous haemofiltration.

OBJECTIVE: The term continuous veno-venous haemofiltration (CVVH) suggests a treatment without interruption. However, interruptions do occur and the duration of the haemofiltration circuit "down-time" may influence uraemic control. We conducted a prospective study to ascertain the percentage of operative "down-time" for CVVH in our intensive care unit and to test the hypothesis that it significantly affected uraemic control. PATIENTS AND METHODS: Prospective data measuring the time spent off the filter in ten patients receiving CVVH were collected. Continuous veno-venous haemofiltration was performed at 2 litres per hour of ultrafiltration. Anticoagulation was maintained using unfractionated heparin administered pre-filter and infused at a rate to achieve a systemic APTT varying between 30-45 seconds. The circuit functional life was documented for each CVVH circuit as progressive cumulative hours of operation. The time off treatment was calculated for each 24-hour period. These data were then correlated with the change in plasma urea and creatinine concentrations for each 24-hour cycle. The APTT, INR, haemoglobin and platelet count were measured and levels were correlated with the filter duration. RESULTS: Ninety three days of CVVH treatment were assessed in 4 female and 6 male patients. The mean circuit "down-time" in these patients for this period was 22% or 5.27 hours per day. The most common cause of circuit "down-time" was circuit clotting, followed by a need for radiological procedures, time spent in the operating theatre and catheter malfunction requiring replacement. There was a strong correlation between circuit "down-time" and increase in plasma urea (p = 0.0017) and creatinine (p = 0.0451) concentrations. Circuit "down-time" was also inversely correlated with the platelet count (p = 0.0048) but not significantly correlated with the APTT, INR or haemoglobin values. CONCLUSIONS: In our study the average daily duration of an interruption in CVVH (i.e. circuit "down-time") represented > 20% of the potential operative time. There was a strong correlation between time without treatment and solute control during CVVH. The percentage of "down-time" may be a useful marker of operative quality during CVVH.

Journal Article↗
PubMed2002

Prolonged intermittent renal replacement therapy in the intensive care unit.

OBJECTIVE: To present a review on the use of prolonged intermittent renal replacement therapy in the intensive care patient. DATA SOURCES: Articles and abstracts reporting the use of renal replacement therapy. SUMMARY OF REVIEW: Standard intermittent haemodialysis (IHD) has significant shortcomings in the treatment of the acute renal failure (ARF) of critical illness. These shortcomings include haemodynamic instability, the need to remove excess fluid over a short period of time, the episodic nature of small solute control, the limited ability to achieve middle molecular weight solute control and the episodic nature of acid-base control. Over the last 20 years, these limitations have stimulated the evolution and increased application of continuous renal replacement therapy (CRRT) which provides major biochemical, biological and physiological advantages compared with IHD, although it remains unclear as to whether such advantages translate into a survival advantage. However, CRRT is technically demanding, requires supervision 24 hr per day and is often associated with the need for continuous anticoagulation, which, in some patients, might be undesirable. In some institutions, CRRT changes the nurse to patient ratio from 1:2 to 1:1, an alteration which has cost implications and might affect resource availability for other patients. Accordingly, techniques which prolong the duration of intermittent therapy and avoid the need for 24 hr treatment may offer "best value" in the management of ARF in the intensive care unit (ICU). These techniques will be referred to as prolonged intermittent renal replacement therapies (PIRRT) in this article. They are characterised by several fundamental principles: 1. Use of a modified or standard dialysis machines, 2. Use of diffusion, convection or any combination of the two, 3. Application of a decreased intensity of solute removal compared with IHD, 4. Extended duration of treatment beyond the typical 3 or 4 hr of standard IHD (hence the term prolonged) but not beyond an 8-12 hr period (hence the term intermittent) and 5. Use of "on-line" generation of dialysate or replacement fluid from tap water. CONCLUSIONS: Information is now being obtained on the efficacy and safety of PIRRT in the ICU. Several units in Australia have started applying this technology to patient care. It is now important that critical care physicians and nurses become familiar with its principles and practice.

Journal Article↗
PubMed2001

Noradrenaline and the kidney: friends or foes?

Septic shock, systemic inflammation and pharmacological vasodilatation are often complicated by systemic hypotension, despite aggressive fluid resuscitation and an increased cardiac output. If the physician wishes to restore arterial pressure (>80-85 mmHg), with the aim of sustaining organ perfusion pressure, the administration of systemic vasopressor agents, such as noradrenaline, becomes necessary. Because noradrenaline induces vasoconstriction in many vascular beds (visibly in the skin), however, it may decrease renal and visceral blood flow, impairing visceral organ function. This unproven fear has stopped clinicians from using noradrenaline more widely. In vasodilated states, unlike in normal circulatory conditions, however, noradrenaline may actually improve visceral organ blood flow. Animal studies show that the increased organ perfusion pressures achieved with noradrenaline improve the glomerular filtration rate and renal blood flow. There are no controlled human data to define the effects of noradrenaline on the kidney, but many patient series show a positive effect on glomerular filtration rate and urine output. There is no reason to fear the use of noradrenaline. If it is used to support a vasodilated circulation with a normal or increased cardiac output, it is likely to be the kidney's friend not its foe.

Acute Kidney Injury↗
PubMed2001

Intermittent versus continuous renal replacement therapy in the ICU: impact on electrolyte and acid-base balance.

OBJECTIVES: The maintenance of normal serum sodium, potassium and bicarbonate concentrations is a therapeutic goal of renal replacement therapy (RRT) in acute renal failure (ARF). The aim of this study was to determine whether this goal is best achieved with intermittent hemodialysis (IHD) or continuous venovenous hemodiafiltration (CVVHDF). DESIGN: Retrospective controlled study. SETTING: Tertiary intensive care unit. PATIENTS: Consecutive patients with ARF treated with IHD (n = 47) or CVVHDF (n = 49). INTERVENTIONS: Measurement of daily morning sodium, potassium and bicarbonate concentrations after the initiation of RRT for up to 2 weeks of treatment. MEASUREMENTS AND RESULTS: Before RRT, abnormal (high or low) values were frequently observed for sodium (42.6% vs 39.6%; NS) potassium (23.4% vs 45.8%; NS) and bicarbonate (63.2 % vs 54.3 %; NS). After treatment, however, CVVHDF, but not IHD, significantly increased mean sodium concentrations (p = 0.0001). CVVHDF was also more likely to normalize the serum sodium than IHD (76.2 % vs 47.8% p = 0.0001). The mean potassium concentrations of both groups significantly decreased (p = 0.019 vs p = 0.0075, difference: NS). However, CVVHDF more frequently reduced the incidence of hypokalemia (1.9 % vs 7.1%, p = 0.0006). CVVHDF but not IHD significantly increased mean bicarbonate concentrations (p = 0.016) in the first 48 h, and more frequently normalized them (71.5% vs 59.2, p = 0.0073). CONCLUSIONS: Serum sodium and potassium, and arterial bicarbonate, concentrations are frequently abnormal in ARF patients before and during renal replacement. Normalization of these values, however, is achieved more frequently with CVVHDF than with IHD.

APACHE↗
PubMed2001

High-volume haemofiltration in human septic shock.

OBJECTIVE: To evaluate whether high volume haemofiltration improves haemodynamics and affects serum cytokine and complement concentrations in human septic shock. DESIGN AND SETTING: Randomized cross-over clinical trial in a tertiary intensive care unit. PATIENTS: Eleven patients with septic shock and multi-organ failure. INTERVENTIONS: Patients were assigned to either 8 h of high-volume haemofiltration (HVHF; 6 l/h) or 8 h of standard continuous veno-venous haemofiltration (CVVH; 1 l/h) in random order. MEASUREMENTS AND MAIN RESULTS: We measured changes in haemodynamic variables, dose of norepinephrine required to maintain a mean arterial pressure greater than 70 mmHg and plasma concentrations of complement anaphylatoxins and several cytokines. An 8-h period of HVHF was associated with a greater reduction in norepinephrine requirements than a similar period of CVVH (median reduction: 10.5 vs. 1.0 microg/min; p = 0.01; median percentage reduction: 68 vs. 7%; p = 0.02). Both therapies were associated with a temporary reduction (p < 0.01) in the plasma concentration of C3a, C5a, and interleukin 10 within 2 h of initiation. HVHF was associated with a greater reduction in the area under the curve for C3a and C5a (p < 0.01). The concentration of the measured soluble mediators in the ultrafiltrate was negligible. CONCLUSIONS: HVHF decreases vasopressor requirements in human septic shock and affects anaphylatoxin levels differently than standard CVVH.

APACHE↗
PubMed2001

Blood purification in the intensive care unit: evolving concepts.

Until relatively recently surgeons were familiar with the concept that some of their patients admitted to the intensive care unit require dialysis to deal with the development of severe acute renal failure. Under such circumstances the nephrology team would then attend the patient and take over that aspect of management. More recently, however, this situation has undergone a significant evolution because of the advent of continuous renal replacement therapy (CRRT). First introduced as "last ditch" therapy in the most critically ill patients who were hemodynamically intolerant of hemodialysis, CRRT has become more and more widely used. It is now the dominant form of artificial renal support in Australia and close to being the dominant treatment of the severe acute renal failure of critical illness in most European countries. The use of CRRT in the United States is rapidly growing. The arrival of CRRT has also renewed interest in the wider concept of blood purification during critical illness. Experimental and preliminary human data suggest that such blood purification therapies may indeed have beneficial immunomodulatory effects. Accordingly, CRRT is now being considered as a potential adjuvant treatment of septic shock and has even moved into the operating room as a tool for antiinflammatory therapy and volume control. The intensivist-surgeon and the general surgeon need to be aware of and understand these developments in extracorporeal therapy if they wish to make the full armamentarium of modern treatment available to their sickest patients.

Blood Component Removal↗
PubMed2001

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery.

BACKGROUND: The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS: Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS: Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS: Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

Acute Kidney Injury↗