Biomedical subjects
R Bellomo
Publications and source records attributed to R Bellomo.
Coupled plasma filtration adsorption in the treatment of septic shock.
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Use of sorbents in acute renal failure and sepsis.
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Comparison of three methods to estimate plasma bicarbonate in critically ill patients: Henderson-Hasselbalch, enzymatic, and strong-ion-gap.
We have previously found poor agreement between Henderson-Hasselbalch and enzymatic methods for estimating plasma bicarbonate concentration in critically ill patients. In this study we compared these two established methods with a new method for estimating bicarbonate using the strong-ion-gap equation. The strong-ion-gap is derived from the Stewart approach to acid-base physiology. One hundred data sets were collected from records of routine daily blood samples in critically ill patients. Bland-Altman analyses were used to compare the three methods. We proposed that bias greater than +/- 1 mmol/l and limits of agreement wider than bias +/- 2 mmol/l were clinically important, Comparing the Henderson-Hasselbalch method to the enzymatic method, the bias was 2.1 mmol/l and the limits of agreement were -1.8 mmol/l to 5.9 mmol/l. Comparing the Henderson-Hasselbalch method to the strong-ion-gap method, the bias was -9.1 mmol/l and the limits of agreement were -17.1 mmol/l to -1.1 mmol/l. Comparing the enzymatic to the strong-ion-gap method, the bias was -11.2 mmol/l and the limits of agreement were -18.2 mmol/l to -4.2 mmol/l. This study found poor agreement between the two established bicarbonate assays and worse agreement between the established assays and the strong-ion-gap method. The strong-ion-gap method is currently too inaccurate for clinical application, but may have future use.
Phosphatemic control during acute renal failure: intermittent hemodialysis versus continuous hemodiafiltration.
BACKGROUND: Achieving "adequacy of dialysis" includes the maintenance of normal serum phosphate concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. METHODS: We compared the effects of continuous veno-venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum phosphate concentrations using daily morning blood tests in 88 consecutive intensive care patients half of which were treated with IHD and half with CRRT RESULTS: Mean patient age was 54+/-14 years for IHD and 60+/-14 years for CVVHDF (NS). However, patients who received CVVHDF were more critically ill (mean APACHE II scores: 24.4+/-5.1 for IHD vs. 29.2+/-5.7 for CVVHDF, p<0.003). Before treatment, the serum phosphate concentration was 2.04+/-0.16 mmoll L for IHD and 1.96+/-0.17 mmoll L for CVVHDF (NS), with abnormal values in 79.4% of IHD patients and in 64.8% of CVVHDF patients (NS). During treatment, CVVHDF induced a greater reduction in serum phosphate (p=0.02) during the first 48 hours and conferred superior subsequent control of hyperphosphatemia (achieved in 64.6% of observations during CVVHDF vs. 41.8% during IHD; p<0.0001). The serum phosphate concentration was also more likely to be within the normal range during CVVHDF (55.3% vs.36.2%; p<0.0001). There was a trend toward more frequent hypophosphatemia (9.3% vs. 5.6%; P<0.1) during CVVHDF CONCLUSIONS: Abnormal serum phosphate concentrations are frequent in ARF patients before and during renal replacement, however, normalization of phosphatemia is achieved more frequently with CVVHDF.
Effect of ventilation equipment on imposed work of breathing.
OBJECTIVE: To determine the imposed work of different ventilation systems at 3 levels of pressure support. DESIGN: Laboratory study. SETTING: Teaching hospital respiratory laboratory. PARTICIPANTS: Healthy, human volunteers. INTERVENTIONS: Measurement of imposed work of breathing (WOB(i)) in six ventilators with alteration of ventilatory settings, humidification device, and triggering mechanisms. RESULTS: At 0 cmH2O CPAP and 0 cmH2O PSV, clinically significant (> 0.1 joules per litre or J/L) WOB(i )occurred in all systems. At 5 cmH2O pressure support ventilation (PSV) median WOB(i) ranged from 0.01 to 0.11 J/L. Removal of the pleated membrane heat and moisture exchanger (HME) significantly reduced WOB(i) (0.38 vs. 0.11 J/L, p < 0. 0001). Drawover humidification marginally increased WOB(i) (0.16 vs. 0.11 J/L, p = 0. 0001). Flow triggering reduced WOB(i) with the Servo (p < 0.0001) and Bennett ventilators (p = 0.001) but not with the Bear 1000 ventilator. CONCLUSIONS: Up to 7 cmH2O of PSV may be required to reduce WOB(i) related to the ventilator, circuit and humdification devices. This pressure support does not address the additional resistive effect of the endotracheal or tracheotomy tube. Higher levels of PSV may therefore be required to offset WOB(i).
Blood purification in sepsis: reasonable scientific hypothesis or pipe dream?
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Has renal-dose dopamine finally been relegated to join the long list of medical myths?
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Continuous haemofiltration in the intensive care unit.
Continuous renal replacement therapy (CRRT) was first described in 1977 for the treatment of diuretic-unresponsive fluid overload in the intensive care unit (ICU). Since that time this treatment has undergone a remarkable technical and conceptual evolution. It is now available in most tertiary ICUs around the world and has almost completely replaced intermittent haemodialysis (IHD) in some countries. Specially made machines are now available, and venovenous therapies that use blood pumps have replaced simpler techniques. Although, it remains controversial whether CRRT decreases mortality when compared with IHD, much evidence suggests that it is physiologically superior. The use of CRRT has also spurred renewed interest in the broader concept of blood purification, particularly in septic states. Experimental evidence suggests that this is a promising approach to the management of septic shock in critically ill patients. The evolution and use of CRRT is likely to continue and grow over the next decade.
Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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).
Hemofiltration in sepsis: where do we go from here?
Hemofiltration as an adjunct to therapy for sepsis is now 10 years old. Despite early successes and significant theoretical advantages, the treatment remains experimental. Although feasibility has been established, efficacy has proved to be much more difficult. Clinical as well as technical difficulties remain important considerations to future studies. These issues are discussed and the brief history of hemofiltration in sepsis is reviewed.
Continuous veno-venous hemofiltration without anticoagulation in high-risk patients.
OBJECTIVE: To study the safety and operative efficacy of continuous veno-venous hemofiltration (CVVH) without anticoagulation in patients at high risk of bleeding. DESIGN: Prospective cohort study and comparison to control group. SETTING: Tertiary, multidisciplinary intensive care unit. PATIENTS: Forty hemofiltration circuits in 12 patients with severe acute renal failure (ARF) deemed at high risk of bleeding. Forty control circuits in 14 patients treated with low-dose pre-filter heparin infusion. INTERVENTIONS: CVVH at 21/h of pump-controlled ultrafiltration without anticoagulation or saline flush in patients at high risk of bleeding. Collection of data at the bedside. MEASUREMENTS AND MAIN RESULTS: Mean circuit life was 32 h (95% CI: 20-44.4) in patients receiving CVVH without anticoagulation. Forty-three per cent of filters lasted longer than 30 h. Circuit lifespan did not correlate with international normalized ratio (INR), activated partial thromboplastin time (APTT) or platelet count. There were no bleeding complications and azotemic control was not compromised by lack of circuit anticoagulation with a mean serum urea of 16.0 mmol/l (95% CI: 14.9-18.1) during treatment. A control group of consecutive similarly ill patients not at high risk of bleeding received low-dose pre-filter heparin (mean dose 716 IU; 95% CI: 647-785). Their mean filter life was 19.5 h (95% CI: 14.2-23.8), significantly shorter than in the study patients (p = 0.017). CONCLUSIONS: Critically ill patients at high risk of bleeding who require continuous renal replacement therapy (CRRT) can be safely managed without circuit anticoagulation. This strategy minimizes bleeding risks and is associated with an acceptable filter life. CRRT without anticoagulation should be strongly considered in high-risk patients.
Bioethical issues related to continuous renal replacement therapy in intensive care patients.
OBJECTIVE: To examine the ethical approach of intensivists and nephrologists to continuous renal replacement therapy (CRRT). DESIGN: A questionnaire. SETTING: The First International Course on Critical Care Nephrology. PARTICIPANTS: The participants in the course (around 500). RESULTS: Most participants think that establishing ethical criteria for managing CRRT is a medical task, as clinicians have adequate criteria for defining futility. However, many responders would grant the request of starting futile CRRT or would maintain it if requested by the family. Only 55% believe that informed consent is necessary for initiating CRRT; one out of four would start or maintain unwanted life-saving CRRT. In case of lack of equipment, the majority would select the patients, excluding the worst one or on a "first-come, first-served" basis. Withholding and withdrawing are regarded differently by most responders. Again, most think that every vital support should be withdrawn when futile, but practical and psychological aspects still influence the final decision. Responders think that ethics critical care committees can help in the management of ethical problems in ICU. CONCLUSIONS: Our results show that several ethical questions are still unsolved and that practical and psychological aspects of the treatment process can be stronger than bioethical principles.
Expression of HLA class I-specific inhibitory receptors in human cytolytic T lymphocytes: a regulated mechanism that controls T-cell activation and function.
Different families of major histocompatibility complex (MHC)-specific inhibitory receptors (NKRs) play a major role in natural killer (NK) cell function, allowing discrimination between normal cells and cells that do not express adequate amounts of MHC class I antigens. This occurs in most instances as a consequence of viral infection or tumor transformation. In T lymphocytes, expression of NKR is mostly confined to activated CD8+ cytolytic T lymphocytes (CTLs). While NKR expression by CTLs may be viewed as a mechanism preventing damages to normal cells by those CTLs that have acquired NK-like activity, it may also down regulate TCR-mediated T cell activation, thus, impairing CTL functions. The finding that certain cytokines can modulate killer inhibitory receptor expression in CTLs is of major interest and might be instrumental in novel therapeutic approaches aimed at the down regulation ofT-cell function in transplantation or autoimmunity.
Phenotypic and functional analysis of the HLA-class I-specific inhibitory receptors of natural killer cells isolated from peripheral blood of patients undergoing bone marrow transplantation from matched unrelated donors.
INTRODUCTION: Limited information is available on the natural killer cell reconstitution after bone marrow transplantation and on the possible role of these cells in graft-versus-host-disease. MATERIALS AND METHODS: Blood samples were collected at different time intervals after transplantation. Lymphocytes were analyzed for informative markers by immunocytofluorimetric analysis. Natural killer cells derived from patients undergoing matched unrelated donor transplant were cloned by limiting dilution in the presence of phytohemoagglutinin and IL2. The natural killer cell clones were analyzed for cytolytic activity. RESULTS: In the nine patients analyzed undergoing transplantation from sibling donors, the majority of peripheral blood lymphocytes during the first 80 d after BMT were represented by T lymphocytes, while in the 15 patients undergoing matched unrelated donor transplant natural killer cells consistently outnumbered T lymphocytes. During the early phases after transplantation, most CD56+CD3- natural killer cells did not express CD16 which was expressed at later intervals. Analysis of the inhibitory receptors specific for HLA-class I molecules showed that CD94/NKG2A, specific for HLA-E, unlike normal donors, was expressed by all natural killer cells including the early appearing CD16-negative ones. Killer inhibitory receptors of the Ig superfamily were expressed late and in low percentages after transplantation and were always coexpressed with CD94/NKG2A. Natural killer-cell clones efficiently lysed the HLA-class I-negative cell lines K562 and 721-221. Natural killer-cell populations or clones isolated from patients with graft-versus-host-disease, failed to lyse donor or recipient derived phytohemoagglutinin-induced lymphoblasts. CONCLUSION: Our analysis shows that (1) recipients of matched unrelated donors transplants exhibit a high proportion of NK cells (2) all NK cells express CD94/NKG2A while the HLA-class I-specific inhibitory receptors of Ig superfamily appear at later stages and (3) donor NK cells do not lysed donor or recipient target cells.
Adsorption in sepsis.
The pathophysiology of sepsis offers a highly complicated scenario. In sepsis, endotoxin or other gram-positive-derived products induce a complex and dynamic cellular response, giving rise to several mediators known to be relevant in the pathogenesis of septic shock such as specific mediators, substances responsible for up- or down-regulation of cytokine receptors and cytokine antagonists, inactivators of translational or transductional pathways, and precursor molecules. In this review, we delve into some new concepts stemming up from the use of sorbents in continuous plasma filtration. Nonspecific simultaneous removal of several mediators of the inflammatory cascade have led to improved outcomes in animal models of septic shock and to improved hemodynamics in a pilot clinical study. It seems of great importance to explore all possible treatment techniques that may have a direct impact on circulating mediators of sepsis and that also may interfere with the imbalance between proinflammatory and anti-inflammatory substances in the critically ill patient with multiple organ failure. In this view, the application of sorbents appears to open new and interesting therapeutic options. The search for innovative treatments specifically targeted to the special needs of the critically ill patients seems therefore more important than the attempt to adjust concepts and technologies that are normally applied to patients with chronic renal failure.
A prospective study of thromboelastography (TEG) and filter life during continuous veno-venous hemofiltration.
Anticoagulants are commonly used to prolong circuit life during continuous hemofiltration. However, a clear correlation between routinely performed blood coagulability tests and circuit life has not been demonstrated. This lack of correlation may derive from the limited ability of such tests to describe the likelihood of in vivo clotting. We hypothesized that thromboelastography (TEG), which derives its variables from a closer reproduction of in vivo coagulation, would significantly correlate with filter life. Accordingly, we conducted a prospective pilot study of the correlation between filter life and TEG-derived variables in 21 hemofilters used in 6 critically ill patients admitted to a tertiary intensive care unit. It involved the performance of TEG during steady state anticoagulation, measurement of circuit life, and of routine coagulation variables. The results showed that the mean circuit life was 20.7+/-4.0 h despite an average aPTT of 67.7+/-12.8 s and a mean heparin dose of 472.5+/-96.2 IU/h. The mean INR was 1.4+/-1 and the mean platelet count was 118+/-16 x 10(3)/mm3. Although several TEG variables correlated with heparin dose (p < 0.03), no correlation was found between any of the routine coagulation variables or any of the TEG variables and circuit life. In conclusion, no significant correlation between TEG derived variables or routinely measured coagulation variables and circuit life could be demonstrated. These findings suggest that such tests are not useful indicators of circuit anticoagulation adequacy and that factors other than blood coagulability may play a role in circuit failure.
Saline infusion, acidosis, and the Stewart approach.
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