A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock. High-volume haemofiltration in human septic shock. Serum IL-6 and IL-1-ra with sequential organ failure assessment scores in septic patients receiving high-volume haemofiltration and continuous venovenous haemofiltration.
High volume hemofiltration (HVHF) has shown potential benefits in septic animals and a few reports suggested a hemodynamic improvement in humans. However, randomized studies are still lacking. Our goal was to evaluate the hemodynamic effects of HVHF in septic shock patients with acute renal failure (ARF).
                Prospective randomized study in an intensive care unit (ICU).
                Twenty patients with septic shock and ARF.
                Patients were randomized to either high volume hemofiltration [HVHF 65 ml/(kg h)] or low volume hemofiltration [LVHF 35 ml/(kg h). Vasopressor dose was adjusted to reach a mean arterial pressure (MAP) > 65 mmHg.
                We performed six hourly measurements of MAP, norepinephrine dose, PaO(2)/FiO(2) and lactate, and four daily urine output and logistic organ dysfunction (LOD) score. Baseline characteristics of the two groups were comparable on randomization. Mean norepinephrine dose decreased more rapidly after 24 h of HVHF treatment compared to LVHF treatment (P = 0.004) whereas lactate and PaO(2)/FiO(2) did not differ between the two treatment groups. During the 4-day follow-up, urine output was slightly increased in the HVHF group (P = 0.059) but the LOD score evolution was not different. Duration of mechanical ventilation, renal replacement therapy and ICU length of stay were also comparable. Survival on day 28 was not affected.
                HVHF decreased vasopressor requirement and tended to increase urine output in septic shock patients with renal failure. However, a larger trial is required to confirm our results and perhaps to show a benefit in survival. To evaluate whether high volume haemofiltration improves haemodynamics and affects serum cytokine and complement concentrations in human septic shock.
                Randomized cross-over clinical trial in a tertiary intensive care unit.
                Eleven patients with septic shock and multi-organ failure.
                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.
                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.
                HVHF decreases vasopressor requirements in human septic shock and affects anaphylatoxin levels differently than standard CVVH. Sepsis is characterized by an uncontrolled release of pro-inflammatory and anti-inflammatory mediators leading to immunoparalysis, cellular and humoral dysfunction, multiorgan dysfunction and death. This study evaluated the efficacy of high-volume haemofiltration (HVHF) compared with continuous venovenous haemofiltration (CVVH) in removing these inflammatory mediators. Clinical responses were assessed with the sequential organ failure assessment (SOFA) score.
                Septic patients with an end-organ dysfunction or septic shock were randomized to receive 6 h of CVVH (ultrafiltration dose of 2 L/h equivalent to about 35 mL/kg per hour or HVHF (ultrafiltration dose of 100 mL/kg per hour or 6 L/h, whichever was higher). The sequential organ failures were scored for the 24 hours preceding recruitment; at day 1, day 7, at discharge from the intensive care unit and at hospital discharge.
                Thirty-three patients were enrolled. Fifteen received HVHF and 18 received CVVH. The serum IL-6 levels (pg/mL) at baseline were similarly elevated in both groups (P = 0.745). The HVHF group showed a significant reduction after 6 h of treatment with a median interquartile range (IQR) of 20.62 (49.21) pg/mL (P = 0.025) with no similar result in the CVVH group. Non-survivors showed a higher baseline serum IL-6 compared with the survivors (median (IQR) 172.31 (261.34) vs 58.9 (104.21), P = 0.044). In the HVHF group there was a positive association between the IL-6 levels at 6 h with the SOFA scores at day 1 (r = 0.392, P = 0.001) but not at day 7. After 6 h of treatment in the HVHF group there was a direct correlation between the IL-6 levels and number of hospital days (r = 0.90, P = 0.040). The maximum SOFA scores were persistently recorded before treatment. The SOFA scores reduced in both groups from baseline to day 7 (HVHF P = 0.048; CVVH P = 0.006). The SOFA scores at day 1 is significantly higher in the non-survivors compared with the survivors (P = 0.038).
                High-volume haemofiltration at 6 L/h may seem to successfully remove some inflammatory cytokines in septic patients. The improvement in the SOFA scores at day 7 promises benefit of continuous renal replacement therapy in septic patients, but after 20 days this effect may be lost. In addition, the baseline serum IL-6 and IL-1-ra were independent predictors of a poor outcome as reflected by the higher SOFA scores at day 1.
There were no adverse effects of HVHF reported.There is insufficient evidence to recommend the use of HVHF in critically ill patients with severe sepsis and or septic shock except as interventions being investigated in the setting of a randomized clinical trial. These trials should be large, multi-centred and have clinically relevant outcome measures. Financial implications should also be assessed.