L. Cole

High-volume haemofiltration in human septic shock

Abstract.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 8xa0h of high-volume haemofiltration (HVHF; 6xa0l/h) or 8xa0h of standard continuous veno-venous haemofiltration (CVVH; 1xa0l/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 70xa0mmHg and plasma concentrations of complement anaphylatoxins and several cytokines. An 8-hxa0period of HVHF was associated with a greater reduction in norepinephrine requirements than a similar period of CVVH (median reduction: 10.5 vs. 1.0xa0µg/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 2xa0h 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

An observational study fluid balance and patient outcomes in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy trial

Objective:To examine associations between mean daily fluid balance during intensive care unit study enrollment and clinical outcomes in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level (RENAL) replacement therapy study. Design:Statistical analysis of data from multicenter, randomized, controlled trials. Setting:Thirty-five intensive care units in Australia and New Zealand. Patients:Cohort of 1453 patients enrolled in the RENAL study. Interventions:We analyzed the association between daily fluid balance on clinical outcomes using multivariable logistic regression, Cox proportional hazards, time-dependent analysis, and repeated measure analysis models. Measurements and Main Results:During intensive care unit stay, mean daily fluid balance among survivors was –234 mL/day compared with +560 mL/day among nonsurvivors (p < .0001). Mean cumulative fluid balance over the same period was –1941 vs. +1755 mL (p = .0003). A negative mean daily fluid balance during study treatment was independently associated with a decreased risk of death at 90 days (odds ratio 0.318; 95% confidence interval 0.24–0.43; p < .000.1) and with increased survival time (p < .0001). In addition, a negative mean daily fluid balance was associated with significantly increased renal replacement-free days (p = .0017), intensive care unit-free days (p < .0001), and hospital-free days (p = .01). These findings were unaltered after the application of different statistical models. Conclusions:In the RENAL study, a negative mean daily fluid balance was consistently associated with improved clinical outcomes. Fluid balance may be a target for specific manipulation in future interventional trials of critically ill patients receiving renal replacement therapy.

Super high flux hemofiltration: a new technique for cytokine removal

Abstract.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 1xa0mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore polyamide super high flux hemofilter (nominal cut-off point: 100xa0kDa). Hemofiltration was conducted at 1xa0l/h or 6xa0l/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)-1β, IL-6 and IL-10 and SCs above 0.3 were achieved for IL-8 and TNF-α at 1xa0l/h. SCs of all cytokines (except IL-1) were reduced when the ultrafiltration rate was increased from 1xa0l/h to 6xa0l/h (p<0.01), but cytokine clearances still increased (p<0.01). The highest SC for albumin was 0.1 at 1xa0l/h and fell to 0.01 at 6xa0l/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.

Clearance of vancomycin during high-volume haemofiltration: impact of pre-dilution

AbstractnObjective. To measure the sieving coefficient (SC) and clearance of vancomycin during high-volume haemofiltration (HVHF) and to evaluate the impact of different pre-dilution regimens on these variables.nDesign and setting. Prospective interventional study in the intensive care unit in a tertiary university hospital.nPatients. Seven patients with septic shock and multi-organ dysfunction.nInterventions. HVHF (6xa0l/h fluid exchange) was performed in septic shock patients using variable proportions of their replacement fluid in pre- and post-dilution mode.nMeasurements and results. Pre-filter, post-filter and ultrafiltrate vancomycin concentrations were measured simultaneously, and SC and clearance calculated. The measurements were repeated following each change in the proportion of pre-dilution fluid. SC steadily decreased as the proportion of pre-dilution decreased, changing from 0.76 in pure pre-dilution to 0.57 in pure post-dilution (p=0.0004). Clearance, however, increased with decreasing pre-dilution fluid rate, from 53.9xa0ml/min at pure pre-dilution to 67.2xa0ml/min at 2xa0l/h pre-dilution with 4xa0l/h post-dilution.nConclusions. HVHF achieves high vancomycin clearances, which despite some deterioration in SC increase with the proportion of replacement fluid given post-filter. Clinicians applying HVHF need to be aware of such clearances to avoid inadequate vancomycin dosing and to adjust therapy according to variations in HVHF technique.

Who should manage CRRT in the ICU? The intensivist's viewpoint

The arrival of continuous renal replacement therapy (CRRT) has given the intensivist and the intensive care nurse the opportunity to treat acute renal failure (ARF) independently by giving them the necessary technology and taking CRRT away from absolute nephrological control. This structural shift has created a controversy between those countries where control of CRRT has completely shifted to the intensivist and those countries where nephrological input is still dominant. The argument in favor of intensivist-driven CRRT rests upon several observations, including the fact that therapy is continuous, as is the presence of the intensivist in the intensive care unit (ICU). Critically ill patients require rapid changes in treatment that are best directed by physicians who are at the bedside all the time. CRRT must be seen within the totality of patient care, and the intensivist can see the larger picture more accurately. Intensivists are successfully performing more and more procedures that were previously seen as part of other specialties and, last but not least, closed models of ICU care appear to work best. Australian intensivists have taken up CRRT from the start and now control it. Patient outcomes under such a system, as reported here, are above average, and confirm the effectiveness of such an approach.

Renal replacement therapy in the ICU: The Australian experience

The structure of health care drives medical practice in a powerful way, shaping choices of therapy and approaches, and influencing scientific evidence. The Australian experience with continuous renal replacement therapy (CRRT) confirms the importance of structure. A public health system like that of Australias contains the following variables: well-developed intensive care tradition and expertise, a dominant closed intensive care unit (ICU) model, well-developed training of intensive care nurses with established one-to-one nurse-patient ratios, salaried medical practitioners, overworked general dialysis units with inadequate nursing resources, and lack of fee-for-service incentive for nephrologists to see ICU patients with acute renal failure. The likely outcome of such a system is for CRRT to be run by intensive care staff. As shown by a recent regional survey, this approach, although somewhat unique, is dominant and appears to work well with excellent clinical results and constant clinical research output.