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OBJECTIVE: This study was undertaken to assess whether different filter types or ultrafiltration methods influence inflammatory markers in pediatric cardiac surgery. METHODS: Forty-one children younger than 5 years were prospectively randomized to groups A (polyamid filter with conventional ultrafiltration), B (polyamid filter with modified ultrafiltration), C (polysulfon filter with conventional ultrafiltration), and D (polysulfon filter with modified ultrafiltration). Interleukin 6, interleukin 10, tumor necrosis factor, terminal complement complex, and lactoferrin were measured before the operation (T0), before rewarming (T1), after ultrafiltration (T2), at 6 (T3) and 18 hours (T4) after the operation, and in the ultrafiltrate. RESULTS: All markers changed with both ultrafiltration methods, both filter types, and in all groups (except tumor necrosis factor) along the T0 to T4 observation time (P <.0001). Their patterns of changes were different for terminal complement complex, with less decrease after use of the polysulfon filter (P <.05), and among groups A through D for interleukin 6 (P =.01), with more decrease in group C than group A (P <.02). Interleukin 10 decreased with the polyamid filter (P <.001) but not with the polysulfon filter. In the ultrafiltrate, tumor necrosis factor was higher with the polysulfon filter than the polyamid filter (6.8 +/- 5 pg/mL vs 4.0 +/- 3.7 pg/mL, P <.05). The ultrafiltrate/plasma ratio of interleukin 6 was higher with conventional ultrafiltration than modified ultrafiltration (0.018 +/- 0.017 vs 0.004 +/- 0.007, P <.005). CONCLUSIONS: The polysulfon filter showed a filtration profile for inflammatory mediators superior to that of the polyamid filter for interleukin 6, tumor necrosis factor, and interleukin 10. Interleukin 6 was most efficiently removed by conventional ultrafiltration with a polysulfon filter, and tumor necrosis factor was best removed by modified ultrafiltration with a polysulfon filter, whereas other inflammatory mediators were not influenced by filter type or ultrafiltration method. Therefore combined conventional and modified ultrafiltration with a polysulfon filter may currently be the most effective strategy for removing inflammatory mediators in pediatric heart surgery.
BACKGROUND: Modified ultrafiltration has been touted as superior to conventional ultrafiltration for attenuating the consequences of hemodilution after cardiac surgery with cardiopulmonary bypass in children. We conducted a prospective randomized study to test the hypothesis that modified and conventional ultrafiltration have similar clinical effects when a standardized volume of fluid is removed. METHODS: From October 1998 to September 1999, 110 children weighing 15 kg or less (median weight 6.1 kg, median age 6.3 months) undergoing surgery with cardiopulmonary bypass for functionally biventricular congenital heart disease were randomized to conventional (n = 67) or arteriovenous modified ultrafiltration (n = 43) for hemoconcentration. The volume of fluid removed with both methods was standardized as a percentage of effective fluid balance (the sum of prime volume and volume added during cardiopulmonary bypass minus urine output): in patients weighing less than 10 kg, 50% of effective fluid balance was removed, whereas 60% was removed in patients weighing 10 to 15 kg. Hematocrit, hemodynamics, ventricular function, transfusion of blood products, and postoperative resource use were compared between groups. RESULTS: There were no significant differences between groups in age, weight, or duration of cardiopulmonary bypass. The total volume of fluid added in the prime and during bypass was greater in patients undergoing conventional ultrafiltration than in those receiving modified ultrafiltration (205 +/- 123 vs 162 +/- 74 mL/kg; P =.05), although the difference was due primarily to a greater indexed priming volume in patients having conventional ultrafiltration. There was no difference in the percentage of effective fluid balance that was removed in the 2 groups. Accordingly, the volume of ultrafiltrate was greater in patients receiving conventional than modified ultrafiltration (95 +/- 63 vs 68 +/- 28 mL/kg; P =.01). Preoperative and postoperative hematocrit levels were 35.6% +/- 6.6% and 36.3% +/- 5.6% in patients having conventional ultrafiltration and 34.4% +/- 6.7% and 38.7% +/- 7.5% in those having modified ultrafiltration. By repeated-measures analysis of variance, patients receiving modified and conventional ultrafiltration did not differ with respect to hematocrit value (P =.87), mean arterial pressure (P =.85), heart rate (P =.43), or left ventricular shortening fraction (P =.21) from baseline to the postbypass measurements. There were no differences between groups in duration of mechanical ventilation, stay in the intensive care unit, or hospitalization. CONCLUSIONS: When a standardized volume of fluid is removed, hematocrit, hemodynamics, ventricular function, requirement for blood products, and postoperative resource use do not differ between pediatric patients receiving conventional and modified ultrafiltration for hemoconcentration after cardiac surgery.
Uremic patients with suppressed food intake may regain appetite soon after starting dialysis, presumably because of the removal of one or more toxic factors that suppress appetite. To investigate this matter, this study used a new experimental model in free-moving, unstressed male Wistar rats (300 to 350 g) with feeding catheters channeled from the top of the skull to the oral cavity. When the rats recovered from surgery, they were tested under standardized conditions by being given an intraoral infusion (1 mL/min) of a 1 M sucrose solution or a 97 g/L protein solution or a mixed solution of carbohydrate, protein, and fat (Fortimel (Nutricia Nordica AB, Stockholm, Sweden)) while the time (volume) of ingestion was recorded. Solutions to be tested for their ability to inhibit ingestion were injected intraperitoneally (lp) and the intraoral infusion was started 20 min later. Plasma ultrafiltrate was collected from end-stage renal failure patients by isolated ultrafiltration at the beginning of their first hemodialysis and pooled. Ultrafiltrate was also obtained by filtering pooled plasma from healthy volunteers in vitro, using the same type of dialyzer and cellulose acetate membranes as those used in the uremic patients. Morning urine samples from healthy volunteers were pooled and subjected to the same in vitro filtration procedure as the normal plasma. Intraperitoneal injection of 20 mL normal ultrafiltrate had no effect on sucrose ingestion, whereas injection of 20 mL uremic ultrafiltrate reduced the ingestion of sucrose solution by 23% and the ingestion of Fortimel by 17%. Ten mL of ultrafiltrate from normal urine reduced the sucrose intake by 42%. The pooled ultrafiltrates from normal and uremic plasma and normal urine were subjected to molecular filtrations using a series of membranes with known cut-off points. The filtrations yielded four concentrated fractions with molecular weight ranges of 0.1 to 0.5 kilodaltons (kd), 0.5 to 1 kd, 1 to 5 kd, and 5 to 10 kd, respectively; the plasma fractions were concentrated a factor of about 25:1 and the urine fractions by about 15:1. After an ip injection of 2 mL of each concentrated plasma fraction, only the 1 to 5 kd fraction from the uremic ultrafiltrate inhibited sucrose intake, whereas the corresponding fraction from the normal ultrafiltrate had no effect. After injection of 1, 3, and 5 mL of the concentrated fractions of uremic ultrafiltrate, a dose-dependent inhibition of sucrose intake was achieved with the 1 to 5 kd fraction and, to a lesser extent, with the 5 to 10 kd fraction. Intraperitoneal injection of 0.5, 1.0, and 2 mL of the concentrated 1 to 5 kd fraction, but not of the other fractions from normal urine, also resulted in a dose-dependent inhibition of sucrose intake. The 1 to 5 kd fractions from the uremic ultrafiltrate and the normal urine ultrafiltrate also inhibited protein intake in a dose-dependent manner. These results suggest that one or more toxic compounds in the middle-molecule weight range, which are normally excreted in the urine, accumulate in uremia and suppress food intake.
BACKGROUND: The present study was performed to assess the role of the extracorporeal blood temperature in the disparate cardiovascular response between isolated ultrafiltration and combined ultrafiltration-haemodialysis. METHODS: In twelve stable dialysis patients (21-77 years), blood pressure and heart rate (Finapres) as well as forearm vascular resistance and venous tone (strain-gauge plethysmography) were measured during 1-h isolated ultrafiltration and 1-h combined ultrafiltration-haemodialysis (bicarbonate, sodium 141 mmol/l) at a fixed ultrafiltration rate of 0.91 l/h. The sequence of both treatment modalities was randomly defined within each patient. Serving as his or her own control, each patient was studied at two different dialysate temperatures: 37.5 and 35.0 degrees C. RESULTS: At a dialysate temperature of 35.0 degrees C extracorporeal blood cooling during combined ultrafiltration-haemodialysis was comparable to isolated ultrafiltration. The cardiovascular response in isolated ultrafiltration was characterized by a significant increase in both forearm vascular resistance and venous tone, while heart rate even decreased. As a result, blood pressure remained unchanged or even increased. In contrast, during combined ultrafiltration-haemodialysis at a dialysate temperature of 37.5 degrees C the increase in forearm vascular resistance was only small and insignificant, while venous tone decreased significantly. Heart rate tended to increase. Combined ultrafiltration-haemodialysis at a dialysate temperature of 35.0 degrees C was also associated with a small increase in forearm vascular resistance. However, venous tone remained stable while heart rate decreased. At both dialysate temperatures, blood pressure was well maintained. CONCLUSIONS: We conclude that differences in cardiovascular reactivity between isolated ultrafiltration and combined ultrafiltration-haemodialysis are only partially explained by differences in the extracorporeal blood temperature. In addition, especially venous reactivity is improved by lowering the dialysate temperature.
BACKGROUND: Conventional and modified ultrafiltration was used in pediatric cardiac operations to reduce volume overload and total body water. The purpose of this study was to compare the efficacy of these techniques in removing inflammatory mediators during cardiopulmonary bypass. METHODS: Fifty pediatric patients undergoing cardiac operations were randomized into a modified or conventional ultrafiltration group. Blood samples were obtained before and after ultrafiltration to assess the plasma concentrations of leukocyte elastase, tumor necrosis factor-alpha, interleukin-6, and interleukin-8. RESULTS: Except for plasma concentrations of tumor necrosis factor-alpha in the modified ultrafiltration group, the plasma concentrations of all the mediators measured increased after ultrafiltration in both groups of patients. The volume of ultrafiltrate and the total amounts of tumor necrosis factor-alpha and interleukin-6 removed by ultrafiltration were significantly greater in the modified group. The concentrations of mediators in the ultrafiltrate and the ratio of ultrafiltrate to plasma concentrations of the mediators did not differ between the groups. Ultrafiltration was more efficient in removing tumor necrosis factor-alpha than the other mediators. CONCLUSIONS: The efficacy in removing the inflammatory mediators generated during cardiopulmonary bypass did not differ between modified and conventional ultrafiltration.
OBJECTIVES: To demonstrate the efficacy of compartment syndrome ultrafiltration for the treatment of acute compartment syndrome in an animal model. Our hypothesis is the removal of interstitial fluid will result in a reduction of intramuscular pressure compared with untreated controls in a model of bilateral induced compartment syndrome. DESIGN: Controlled experimental model. SETTING: Animal research facility. PATIENTS/PARTICIPANTS: Three pairs of porcine hindlimbs. INTERVENTION: Acute compartment syndrome was created in the pig hindlimb by infusion of saline to maintain the intramuscular pressure 30 mm Hg greater than the animal's mean arterial pressure for 8 hours. After a 2-hour reperfusion interval, ultrafiltration (removal of fluid through 1 mm diameter porous catheters, connected to -500 mm Hg suction) was commenced in 1 limb only and continued for 9.5 hours. MAIN OUTCOME MEASURES: Intramuscular pressure, ultrafiltrate volume, ultrafiltrate and serum levels of creatine kinase and lactate dehydrogenase, histologic measurement of extracellular and intracellular edema, as well as the degree of cellular necrosis. RESULTS: Intramuscular pressure tended to be lower on the treated side at the end of the treatment period [treated leg: 9.3 +/- 4.0 mm Hg (+/- SE), control leg: 19.3 +/- 1.4 mm Hg, P = 0.03]. Analysis of ultrafiltrate fluid showed that levels of creatine kinase and lactate dehydrogenase were elevated compared with serum levels. Creatine kinase levels in serum were measured at 4150 +/- 780 U/L, whereas ultrafiltrate levels of creatine kinase were 28,700 +/- 17,700 U/L (+/- SE) (P = 0.1). Lactate dehydrogenase was measured at 1950 +/- 180 U/L in serum, but markedly elevated in ultrafiltrate [160,000 +/- 88,900 U/L (+/- SE), P = 0.05]. Quantification of cellular and interstitial dimensions showed no difference in control and experimental limbs. Quantification of the degree of muscle necrosis revealed 6.1 +/- 2.7% necrosis in the treated limb compared to 11.3 +/- 1.6% necrosis in the control group (P = 0.02, df = 2, 1-tailed paired t test). CONCLUSION: This pilot study demonstrates the feasibility of tissue ultrafiltration for reduction of intramuscular pressure in this porcine model. Further studies are underway. Compartment syndrome ultrafiltration may be useful prophylactically in patients at risk for acute compartment syndrome. Sampling of interstitial fluid and frequent measurement of intramuscular pressure may allow earlier diagnosis and treatment of acute compartment syndrome, whereas the reduction of tissue pressure by compartment syndrome ultrafiltration may prevent acute compartment syndrome from occurring. Additionally, compartment syndrome ultrafiltration will not hinder the ability of clinicians to use the clinical examination and pressure monitoring as the gold standard.
The contribution of peritoneal cavity lymphatic absorption to ultrafiltration kinetics and solute clearances in continuous ambulatory peritoneal dialysis was evaluated in patients with normal (group 1) and high (group 2) peritoneal permeability X area during 4-h exchanges using 2 liters 2.5% dextrose dialysis solution with 30 g added albumin. Cumulative lymphatic drainage in all continuous ambulatory peritoneal dialysis (CAPD) patients averaged 358 +/- 47 ml per 4-h exchange and reduced cumulative net transcapillary ultrafiltration at the end of the exchange by 58 +/- 7.2%. The peak ultrafiltration volume was observed before osmotic equilibrium between serum and dialysate was reached and occurred when the net transcapillary ultrafiltration rate had decreased to equal the lymphatic absorption rate. Thereafter the lymphatic absorption rate exceeded the net transcapillary ultrafiltration rate, and intraperitoneal volume decreased. Extrapolated to 4 X 2 liters, 2.5% dextrose, 6-h exchanges per d, lymphatic drainage reduced potential daily net ultrafiltration by 83.2 +/- 10.2%, daily urea clearance by 16.9 +/- 1.9%, and daily creatinine clearance by 16.5 +/- 1.9%. Although lymphatic absorption did not differ between the two groups, lymphatic drainage caused a proportionately greater reduction in net ultrafiltration in group 2 (P less than 0.025), because these patients had more rapid dialysate glucose absorption (P less than 0.05) and less cumulative transcapillary ultrafiltration (P less than 0.01). These findings indicate that cumulative lymphatic drainage significantly reduces net ultrafiltration and solute clearances in CAPD and that ultrafiltration failure in CAPD occurs when daily lymphatic absorption equals or exceeds daily transcapillary ultrafiltration. Reduction of lymphatic absorption may provide a means for future improvement in the efficiency of CAPD.