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R Bellomo

Publications and source records attributed to R Bellomo.

At least 19 recordsLinked to original sources

Artificial organ treatment for multiple organ failure, acute renal failure, and sepsis: recent new trends.

Sepsis remains the major cause of mortality worldwide, claiming millions of lives each year. The past decade has seen major advances in the understanding of the biological mechanisms involved in this complex process. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. At variance with targeting single mediators, therapeutic intervention aimed at the nonselective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extracorporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials that lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. Additionally, we will review novel information related to other blood purification techniques using large pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance.

Acute Kidney Injury↗

Defining death in non-heart beating organ donors.

Protocols for retrieving vital organs in consenting patients in cardiovascular arrest (non-heart beating donors, NHBD) rest on the assumptions that irreversible asystole a) identifies the instant of biological death, and b) is clinically assessable at the time when retrieval of vital organs is possible. Unfortunately both assumptions are flawed. We argue that traditional life/death definitions could be actually inadequate to represent the reality of dying under intensive support, and we suggest redefining NHBD protocols on moral, social, and anthropological criteria, admitting that irreversible (however defined) asystole can only equate a clinically determinable point of no return in the process of dying, where organ retrieval can be morally and socially accepted in previously consenting patients.

Attitude to Death↗

Cryoprecipitate for the correction of coagulopathy associated with liver disease.

In patients with liver disease at risk of pulmonary oedema, cryoprecipitate (small volume) might be a viable alternative to fresh frozen plasma (FFP, large volume) in the correction of coagulopathy. However, the efficacy of cryoprecipitate in these patients has not been tested. We evaluated the role of cryoprecipitate in the correction of the coagulopathy of liver disease. To establish initial evidence of efficacy, six consecutive patients with hepatic failure and coagulopathy received five units of cryoprecipitate. Then, using a crossover design, 11 consecutive patients were randomized to receive either four units of FFP or five units of cryoprecipitate. Pre and post infusion International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT), fibrinogen D-dimers, Factors V and IX, and reptilase time were measured. In the first six patients, cryoprecipitate improved the INR, aPTT and fibrinogen concentration (P = 0.03). In the crossover study, FFP administration produced a greater improvement in INR (P = 0.007) and aPTT (P = 0.005) than cryoprecipitate. However, there were no differences in any of the other measured variables. One patient developed acute pulmonary oedema while receiving FFP. Cryoprecipitate improves the coagulopathy of liver disease. Four units of FFP are more efficacious than five units of cryoprecipitate. Cryoprecipitate may have a role in correction of the coagulopathy associated with liver disease where concerns about pulmonary oedema exist.

Adult↗

Impact of continuous veno-venous hemofiltration on acid-base balance.

BACKGROUND: Continuous veno-venous hemofiltration (CVVH) appears to have a significant and variable impact on acid-base balance. However, the pathogenesis of these acid-base effects remains poorly understood. The aim of this study was to understand the nature of acid-base changes in critically ill patients with acute renal failure during continuous veno-venous hemofiltration by applying quantitative methods of biophysical analysis (Stewart-Figge methodology). METHODS: We studied forty patients with ARF receiving CVVH in the intensive care unit. We retrieved the biochemical data from computerized records and conducted quantitative biophysical analysis. We measured serum Na+, K+, Mg2+, Cl-, HCO3-, phosphate, ionized Ca2+, albumin, lactate and arterial blood gases and calculated the following Stewart-Figge variables: Strong Ion Difference apparent (SIDa), Strong Ion Difference Effective (SIDe) and Strong Ion Gap (SIG). RESULTS: Before treatment, patients had mild acidemia (pH: 7.31) secondary to metabolic acidosis (bicarbonate: 19.8 mmol/L and base excess: -5.9 mEq/L). This acidosis was due to increased unmeasured anions (SIG: 12.3 mEq/L), hyperphosphatemia (1.86 mmol/L) and hyperlactatemia (2.08 mmol/L). It was attenuated by the alkalinizing effect of hypoalbuminemia (22.5 g/L). After commencing CVVH, the acidemia was corrected within 24 hours (pH 7.31 vs 7.41, p<0.0001). This correction was associated with a decreased strong ion gap (SIG) (12.3 vs. 8.8 mEq/L, p<0.0001), phosphate concentration (1.86 vs. 1.49 mmol/L, p<0.0001) and serum chloride concentration (102 vs. 98.5 mmol/L, p<0.0001). After 3 days of CVVH, however, patients developed alkalemia (pH: 7.46) secondary to metabolic alkalosis (bicarbonate: 29.8 mmol/L, base excess: 6.7 mEq/L). This alkalemia appeared secondary to a further decrease in SIG to 6.7 mEq/L (p<0.0001) and a further decrease in serum phosphate to 0.77 mmol/L (p<0.0001) in the setting of persistent hypoalbuminemia (21.0 g/L; p=0.56). CONCLUSIONS: CVVH corrects metabolic acidosis in acute renal failure patients through its effect on unmeasured anions, phosphate and chloride. Such correction coupled with the effect of hypoalbuminemia, results in the development of a metabolic alkalosis after 72 hours of treatment.

Acid-Base Equilibrium↗

Continuous renal replacement therapy: does technique influence electrolyte and bicarbonate control?

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on electrolyte and acid-base control. The aim of this study was to determine whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) achieve better control of serum sodium, potassium and bicarbonate concentrations. 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 sodium and potassium values and arterial bicarbonate levels from computerized biochemical records before and after the initiation of CRRT for up to 2 weeks of treatment. Statistical comparison of findings. MEASUREMENTS AND RESULTS: Before treatment, abnormal (high or low) values were frequently observed for sodium (65.1% for CVVHDF vs. 80.0% for CVVH; NS), potassium (45.9% vs. 34.0%; NS), and bicarbonate (73.3% vs. 68.0%; NS). After treatment, however, CVVHDF was more likely to achieve serum sodium concentrations within the normal range (74.1% vs. 62.9%; p=0.0026). Both treatments decreased the mean serum potassium concentration over the first 48 h (p=0.0059 and p<0.0001, respectively), but there was no difference in terms of the normalization of serum potassium concentration during the entire treatment period (88.3% vs. 90.5%; NS). Both treatments increased the mean arterial bicarbonate concentration over the first 48 hours (p=0.011 and p<0.0001, respectively). However, CVVH was associated with a lower incidence of metabolic acidosis (13.8% for CVVH vs. 34.5% for CVVHDF; p<0.0001) and a higher incidence of metabolic alkalosis (38.9% vs. 1.1%; p<0.0001) during the entire treatment period. CONCLUSIONS: CRRT strategies based on different techniques have a significantly different impact on sodium and bicarbonate control.

Acute Kidney Injury↗

The acid-base effects of continuous hemofiltration with lactate or bicarbonate buffered replacement fluids.

OBJECTIVE: To evaluate, quantify and compare the effects of continuous veno-venous hemofiltration (CVVH) with lactate or bicarbonate-buffered replacement fluids on acid-base balance. DESIGN: Randomized double crossover study. SETTING: Intensive Care Unit of Tertiary Medical Center. PARTICIPANTS: Eight patients with severe acute renal failure. INTERVENTIONS: Random allocation to either 2 hours of isovolemic lactate-buffered (treatment A) CVVH or 2 hours of bicarbonate-buffered (treatment B) CVVH with cross over and with same procedure repeated the following day (double cross over). MEASUREMENTS AND RESULTS: Timed collections of arterial blood and ultrafiltrate (UF), measurement of blood and UF gases and lactate concentrations and calculation of buffer-base mass balance. At baseline, both groups of patients had a similar, slight metabolic alkalosis (pH: 7.45 vs. 7.45; BE 3.9 mEq/L for treatment A and 4.0 for treatment B) and a serum bicarbonate of 28.1 mmol/L for treatment A vs. 28.3 mmol/L for treatment B; all NS. This alkalosis was present despite slight hyperlactatemia in both groups (A: 2.4 mmol/L vs. B 2.8 mmol/; NS). Within 60 minutes of treatment, however, treatment A led to a significantly higher lactate concentration (3.9 vs 2.5 mmol/L; p = 0.0011), a significantly lower BE (2.3 vs 4.1 mEq/L; p = 0.0019) and a significantly lower bicarbonate concentration (26.7 vs. 28.3 mmol/L; p = 0.0038) in the presence of an unchanged PaCO2. These differences persisted during the study period. The UF of patients receiving treatment A contained more lactate (10.2 vs 2.9 mmol/L; p < 0.0001) and less bicarbonate (25.6 vs. 30.8 mmol/L; p < 0.0001) than treatment B resulting in a mean buffer-base balance of +20.4 mEq/h compared to -2.6 mEq/h for treatment B; p < 0.0001). CONCLUSIONS: CVVH with lactate-buffered replacement fluids induces iatrogenic hyperlactatemia. Such hyperlactatemia is associated with an acidifying effect despite a positive buffer-base balance.

Acid-Base Equilibrium↗

Super high flux hemofiltration: a new technique for cytokine removal.

OBJECTIVE: To test whether hemofiltration using a hemofilter with large pores (super high flux hemofiltration) achieves effective cytokine removal. DESIGN: : Ex vivo study. SETTING: Laboratory of an intensive care unit in a tertiary hospital. PATIENTS AND PARTICIPANTS: Five healthy volunteers. INTERVENTIONS: Blood was spiked with 1 mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore polyamide super high flux hemofilter (nominal cut-off point: 100 kDa). Hemofiltration was conducted at 1 l/h or 6 l/h of ultrafiltrate flow. Samples were taken from the arterial, venous and ultrafiltration sampling ports. MEASUREMENTS AND RESULTS: Sieving coefficients (SC) above 0.6 were achieved for interleukin (IL)-1beta, IL-6 and IL-10 and SCs above 0.3 were achieved for IL-8 and TNF-alpha at 1 l/h. SCs of all cytokines (except IL-1) were reduced when the ultrafiltration rate was increased from 1 l/h to 6 l/h ( p<0.01), but cytokine clearances still increased ( p<0.01). The highest SC for albumin was 0.1 at 1 l/h and fell to 0.01 at 6 l/h. No adsorption of cytokines and albumin was observed. CONCLUSION: High volume ultrafiltration using a super high flux filter achieved cytokine clearances comparable to, or greater than, those currently achieved for urea during standard continuous renal replacement therapy.

Albumins↗

Estimating unmeasured anions in critically ill patients: anion-gap, base-deficit, and strong-ion-gap.

We used 100 routine blood samples from critically ill patients to establish whether correcting the anion-gap and base-deficit for decreased plasma albumin improves agreement with the strong-ion-gap for estimating unmeasured anions and whether the modifications increase the proportion of samples with levels of anion-gap or base-deficit above the reference ranges. We used Bland-Altman analyses to compare the methods of estimating unmeasured ions. Compared with the strong-ion-gap, modification reduced the limits of agreement for both the anion-gap and the base-deficit. The bias for the base-deficit was also reduced but the bias for the anion-gap was increased. The proportion of samples with an anion-gap > 22 meq.l(-1) increased from 4 to 29% (p < 0.001), and the proportion with a base-deficit > 5 meq.l(-1) increased from 8 to 42% (p < 0.001). Consequently, metabolic acidosis from unmeasured ions in critically ill patients maybe more frequent than often recognised.

Acid-Base Equilibrium↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗