Shigehiko Uchino

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.

A quantitative analysis of the acidosis of cardiac arrest: a prospective observational study

IntroductionMetabolic acidosis is common in patients with cardiac arrest and is conventionally considered to be essentially due to hyperlactatemia. However, hyperlactatemia alone fails to explain the cause of metabolic acidosis. Recently, the Stewart–Figge methodology has been found to be useful in explaining and quantifying acid–base changes in various clinical situations. This novel quantitative methodology might also provide useful insight into the factors responsible for the acidosis of cardiac arrest. We proposed that hyperlactatemia is not the sole cause of cardiac arrest acidosis and that other factors participate significantly in its development.MethodsOne hundred and five patients with out-of-hospital cardiac arrest and 28 patients with minor injuries (comparison group) who were admitted to the Emergency Department of a tertiary hospital in Tokyo were prospectively included in this study. Serum sodium, potassium, ionized calcium, magnesium, chloride, lactate, albumin, phosphate and blood gases were measured as soon as feasible upon arrival to the emergency department and were later analyzed using the Stewart–Figge methodology.ResultsPatients with cardiac arrest had a severe metabolic acidosis (standard base excess -19.1 versus -1.5; P < 0.0001) compared with the control patients. They were also hyperkalemic, hypochloremic, hyperlactatemic and hyperphosphatemic. Anion gap and strong ion gap were also higher in cardiac arrest patients. With the comparison group as a reference, lactate was found to be the strongest determinant of acidosis (-11.8 meq/l), followed by strong ion gap (-7.3 meq/l) and phosphate (-2.9 meq/l). This metabolic acidosis was attenuated by the alkalinizing effect of hypochloremia (+4.6 meq/l), hyperkalemia (+3.6 meq/l) and hypoalbuminemia (+3.5 meq/l).ConclusionThe cause of metabolic acidosis in patients with out-of-hospital cardiac arrest is complex and is not due to hyperlactatemia alone. Furthermore, compensating changes occur spontaneously, attenuating its severity.

A pilot study of high-adsorption hemofiltration in human septic shock.

Background To compare the hemodynamic and biological effects of high-adsorption continuous veno-venous hemofiltration (CVVH) with standard CVVH in septic shock. Methods: In a randomized cross-over clinical trial twelve patients with septic shock and multiple organ failure were enrolled at a tertiary intensive care unit. Patients were allocated to either 9 hours of high-adsorption hemofiltration (CVVH with 3 hourly filter change using AN69 hemofilters - 3F-CVVH) or 9 hours of standard hemofiltration (CVVH without filter change - 1F-CVVH). Results Changes in hemodynamic variables, dose of noradrenaline required to maintain a mean arterial pressure greater than 75 mmHg and plasma concentrations of cytokines (IL-6, IL-8, IL-10 and IL-18) were measured. A 9-hour period of 3F-CVVH was associated with greater reduction in noradrenaline dose than a similar period of 1F-CVVH (median reduction: 16 vs. 3.5 μg/min, p=0.036; median percentage reduction: 48.1% vs. 17.5%, p=0.028). Unlike 1F-CVVH, 3F-CVVH was associated with a reduction in the plasma concentration of IL-6, IL-10 and IL-18 at 9 hours and a significant decrease 30 minutes after additional filter changes (IL-6: p<0.01, p<0.01; IL-10: p=0.03, p=0.016 and IL-18: p=0.016, p<0.01, respectively). Both, 3F-CVVH and 1F-CVVH were associated with decreased plasma concentrations of IL-8 at 9 hours (p<0.01, p<0.01, respectively). In a confirmatory ex-vivo experiment IL-6 concentrations substantially decreased during 3F-CVVH (at baseline 511pg/mL and at end: 21pg/mL) whereas IL-6 concentrations increased in control blood (at baseline 511pg/mL and at end: 932pg/mL). Conclusions High-adsorption CVVH appears more effective than standard CVVH in decreasing noradrenaline requirements and plasma concentrations of cytokines in septic shock patients.

On-pump coronary artery surgery versus off-pump exclusive arterial coronary grafting: a matched cohort comparison

BACKGROUNDnIt is unknown whether coronary artery bypass grafting without cardiopulmonary bypass and with exclusive use of arterial grafts (arterial off-pump CABG) offers any significant short-term advantages over standard CABG with cardiopulmonary bypass. Accordingly, we performed a comparison of the short-term outcomes of arterial off-pump and standard CABG patients matched for preoperative risk and number of grafts.nnnMETHODSnWe studied 90 consecutive arterial off-pump CABG patients during a 2-year period, obtained demographic and clinical features and surgical characteristics, and calculated their predicted surgical risk (EuroSCORE). Using a database of 750 contemporaneous patients treated with standard CABG, we created a matched cohort of 90 patients using an iterative process prioritizing number of grafts, target vessels, EuroSCORE, age, and sex. We compared the two groups for baseline features and short-term clinical outcomes.nnnRESULTSnThere were no differences in age (65.9 versus 64.7 years), sex, EuroSCORE (3.3 versus 3. 6), number of grafts (2.1 versus 2.1), and preoperative left ventricular function. Arterial off-pump CABG, however, was associated with decreased duration of operation (213 versus 252 minutes; p < 0.0013), decreased peak postoperative troponin I levels (mean, 10.8 versus 29.1 ng/mL; p < 0.0001), decreased peak norepinephrine dose (2.3 versus 4.1 microg/ min; p < 0.0082), and decreased likelihood of receiving red blood cell transfusion (17.8% versus 40%; p = 0.0016). There were no differences in duration of intensive care unit or hospital stay, incidence of atrial fibrillation, or other clinical complications. There was one death in each group.nnnCONCLUSIONSnAfter matching for number of grafts and other important preoperative risk markers, arterial off-pump CABG still decreases the need for red blood cell transfusion and offers other moderate clinical advantages compared with standard on-pump CABG.

Norepinephrine for hypotensive vasodilatation after cardiac surgery: impact on renal function

ObjectivesNorepinephrine use in patients after cardiac surgery is controversial because of the fear that norepinephrine might decrease kidney function through regional vasoconstriction. Accordingly, we studied the renal effects of norepinephrine use for hypotensive vasodilatation after cardiac surgery.Design and settingRetrospective controlled study in the cardiothoracic ICU of tertiary hospital.Patients100 cardiac surgery patients with post-operative hypotensive vasodilatation and 100 control cardiac surgery patients.InterventionTreatment of hypotension (MAP<70xa0mmHg) with continuous norepinephrine infusion.Measurements and resultsWe collected data on demographic and surgical characteristics, haemodynamics, serum creatinine and mortality. Just after surgery the norepinephrine group had a significantly higher mean central venous pressure, lower mean arterial pressure, and lower systemic vascular resistance index with a similarly elevated mean cardiac index. Despite norepinephrine administration at a mean peak dose of 7.3±6.4xa0µg/min the mean post-operative change in creatinine was not different between two groups on days 0, 2 or 4 after surgery.ConclusionsNorepinephrine does not increase post-operative serum creatinine concentrations in patients with hypotensive vasodilatation after cardiac surgery. Concerns related to its potential adverse effects on the kidney function in this setting appear unjustified.

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 hemodiafiltration (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.

Electrolyte Mass Balance During CVVH: Lactate vs. Bicarbonate-Buffered Replacement Fluids

Objective: To compare the effect of lactate vs. bicarbonate‐buffered replacement fluids on electrolyte mass balance during isovolemic continuous veno‐venous hemofiltration (CVVH). Design: Randomized controlled study with double cross over. Setting: Intensive care unit of a tertiary university hospital. Patients and participants: Eight patients with acute renal failure (ARF). Interventions: Isovolemic CVVH (2L/hr of replacement fluid) was performed in random order with either bicarbonate or lactate‐buffered replacement fluid delivered pre‐filter. Measurements and Results: Sodium, potassium, chloride, magnesium, and phosphate, were measured in each sample. There was a mass gain of sodium, which was similar under both conditions (bicarbonate: 23.3 ± 4.9 mmol/hr, lactate: 22.7 ± 3.5 mmol/hr). Mass chloride gains occurred with bicarbonate‐buffered replacement fluid only (12.8 ± 5.3 mmol/hr), while there was an overall net loss of chloride with lactate fluids (− 2.5 ± 5.2 mmol/hr), resulting in a significant difference in chloride mass balance (p < 0.0001). Magnesium mass balance was negative with bicarbonate buffer only (− 0.6 ± 0.2 mmol/hr) and also differed significantly from that obtained with lactate fluids (− 0.1 ± 0.2 mmol/hr, p < 0.0001). Phosphate losses (bicarbonate: − 1.7 ± 0.7 mmol/hr, lactate: − 1.7 ± 0.5 mmol/hr) were equivalent with both buffers. Potassium mass balance was neutral. Conclusions: Mass balance during isovolemic CVVH is significantly affected by the type of replacement fluid administered pre‐filter. Isovolemic CVVH is not isonatremic and the use of bicarbonate‐buffered fluid results in a significant accumulation of chloride and a loss of magnesium.

Beta2-microglobulin clearance with super high flux hemodialysis: an ex vivo study.

Background ß2m accumulation induces disease in patients with end-stage renal failure (ESRF). Thus, its removal from patients with ESRF appears desirable. Current dialysis technology, however, has limited effectiveness. Aims To measure ß2m clearance with a novel super high flux membrane. Design Ex vivo experimental study. Setting Intensive Care Laboratory of Tertiary institution. Subjects Six volunteers. Measurements and Results At a blood flow of 300 ml/min, the clearance of ß2-MG increased from 113.5 ± 38.5 ml/min with a dialysate flow rate of 200 ml/min to 184.8 ± 61.1 ml/min with a flow rate of 300 ml/min and 195.0 ± 60.0 ml/min with a 500 ml/min flow rate. The clearance of albumin was 4.5 ml/min with a dialysate flow rate of 200 ml/min, 5.2 ml/min for a flow rate of 300 ml/min and 5.8 ml/min for a flow rate of 500 ml/min. Conclusions High levels of ß2m clearance can be achieved with a super high flux membrane while albumin losses remain limited