Heinrich A. Werner

Functional characteristics of pediatric veno-venous hemofiltration

ObjectiveTo evaluate the functional characteristics of continuous veno-venous hemofiltration in a pediatric size animal model. DesignProspective trial. SettingAnimal laboratory at a large university-affiliated medical center. SubjectsFour-week old lambs (weight 12.2 ± 1.3 kg). InterventionsVeno-venous hemofiltration was performed in anesthetized lambs (n = 5, 12.2 ± 1.3 kg) using a standard pediatric hemofilter and pumped blood and ultrafiltrate. We compared postdilution, predilution, and hemofiltration with counterflow dialysis. Measurements and Main ResultsAt net ultrafiltrate flows of 200, 400, and 600 mL/hr, we measured system pressures and urea clearance. Stable blood flow could reproducibly be achieved up to 140 mL/min (10 mL/kg/min); at higher flow demand, tubing collapse occurred. At blood flow rates of 5 to 10 mL/kg/min, ultrafiltrate flow of 1 mL/kg/min would create negative filter compartment pressure but consistently less negative than −500 mm Hg. During postdilution, predilution, and counterflow dialysis, urea clearance was virtually equal to ultrafiltrate flow. There was no increase in urea clearance when adding predilution or dialysis to basic postdilution. ConclusionsVeno-venous hemofiltration, using small filters and circuits in a pediatric size animal, can achieve stable blood flow up to 10 mL/kg/min. At this flow, ultrafiltrate flow of 1 mL/kg/min can produce a urea clearance of 1 mL/kg/min while keeping filter compartment pressure above maximal recommended negative pressures. Addition of dialysis in this nonuremic model did not increase urea clearance. (Crit Care Med 1994; 22:320–325)

Platelet-activating factor antagonism improves ventricular contractility in endotoxemia

OBJECTIVES Endotoxin stimulates platelet-activating factor production and also causes a decrease in myocardial contractility within a few hours in animal models of sepsis. Platelet-activating factor by itself decreases left ventricular contractility. We investigated whether platelet-activating factor contributes substantially to the decrease in left ventricular contractility seen in sepsis. DESIGN Prospective, randomized, controlled animal study. SETTING University research laboratory. SUBJECTS Twenty-two juvenile, cross-bred pigs. INTERVENTIONS Anesthetized pigs were pretreated with a platelet-activating factor receptor antagonist (L-659,989) or vehicle (control), and then treated with endotoxin or saline (control). Hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter) were measured. Left ventricular contractility was assessed using the slope, or maximum elastance (Emax), of the end-systolic pressure-volume relationship. MEASUREMENTS AND MAIN RESULTS In the control/endotoxin group, 4 hrs after endotoxin administration, Emax had decreased by 41 +/- 4% (p < .05) and mean arterial pressure had decreased by 32 +/- 3% (p < .05). In the L-659,989/endotoxin group, the decreases in Emax (26 +/- 2%, p < .05) and mean arterial pressure (16 +/- 7%) were significantly attenuated compared with the control/endotoxin group (p < .05). CONCLUSIONS We conclude that platelet-activating factor plays a modest but statistically significant role in the early decrease in left ventricular contractility after endotoxin administration. Inhibition of platelet-activating factor during sepsis might be beneficial for left ventricular mechanics and hemodynamics.

Decreased left ventricular contractility during porcine endotoxemia is not prevented by ibuprofen.

OBJECTIVE We investigated whether ibuprofen could prevent early decrease in left ventricular contractility that occurs during porcine endotoxemia. DESIGN Prospective, randomized, controlled animal study. SETTING University research laboratory. SUBJECTS Adolescent crossbred pigs (n = 28). INTERVENTIONS Anesthetized pigs were instrumented to measure hemodynamics and left ventricular pressures (using a Millar catheter) and volumes (using a conductance catheter). Pigs were then treated in four groups, according to pretreatment using ibuprofen (15 mg/kg) or saline and subsequent treatment using endotoxin (0111:B4, 50 microg/kg) or saline. MEASUREMENTS AND MAIN RESULTS Measurements of hemodynamics and left ventricular pressures and volumes were repeated after pretreatment with ibuprofen (or saline in controls), and at hourly intervals for 4 hrs after the start of endotoxin or control saline infusions. Left ventricular contractility was primarily assessed using the slope of the end-systolic pressure-volume relationship. Data were analyzed, using a repeated-measures analysis of variance. The slope of the end-systolic pressure-volume relationship was decreased at 4 hrs by 41 +/- 9% in the saline/endotoxin group (p < .05) and by 36 +/- 14% in the ibuprofen/endotoxin group (p < .05), so that ibuprofen pretreatment had no significant effect on the decrease in left ventricular contractility. Mean arterial pressure decreased in the saline/endotoxin group by 23 +/- 12% at 1 hr (p < .05) and by 35 +/- 12% (p < .05) at 4 hrs. Ibuprofen significantly reduced the decrease in mean arterial pressure (2 +/- 6% increased at 1 hr, and 17 +/- 12% decreased at 4 hrs, both p<.05 compared with saline/endotoxin). Cardiac output increased by 25% (p < .05) in the first hour, but then decreased to be slightly (NS) below baseline at 4 hrs in both endotoxin groups. Mean pulmonary arterial pressure was increased in the saline/endotoxin group by 154 +/- 52% (p < .05) at 30 mins and by 118 +/- 40% (p < .05) at 4 hrs. Ibuprofen prevented the very acute increase in pulmonary arterial pressure (increased by 11 +/- 33% at 30 mins, p < .05 compared with saline/endotoxin) and significantly reduced the pulmonary hypertension at 4 hrs (increased by 70 +/- 25%, p < .05 compared with both baseline and saline/endotoxin). CONCLUSIONS We conclude that products of the cyclooxygenase pathway do not play a major role in the early decrease in left ventricular contractility after endotoxin. However, ibuprofen may have a role in reducing the other cardiovascular effects of sepsis.

Operating characteristics of pediatric continuous arteriovenous hemofiltration in an animal model

Continuous arteriovenous hemofiltration (CAVH) is an increasingly popular technique in the care of critically ill children. The operating characteristics of the available circuits are largely unknown. Prior to introducing CAVH into our pediatric intensive care unit, we investigated the performance of three CAVH circuits: CAVH with postfilter dilution, CAVH with prefilter dilution (CAVHpre) and CAVH with dialysis counterflow. Using a neonatal lamb model, we measured filter blood flow (QB), ultrafiltrate rate (QU), arterial, venous and ultrafiltrate compartment pressure, oncotic pressure, plus urea levels in blood and ultrafiltrate fluid for the three CAVH circuit designs. Transmembrane pressure and urea clearance were calculated for various values of QB after varying a clamp on the arterial side of the circuit. The major finding, applicable to all circuits, was the wide variability of QB. Constant attention was required in order to obtain a consistent QB. Fluid clearance was effective with all three circuits. Urea clearance averaged 5–10 ml/min and was principally dependent on QU and independent of QB. The addition of dialysis counterflow did not increase urea clearance. The most convenient circuit we tested was CAVHpre, but the problem of unstable QB is common to all unpumped arteriovenous filtrate circuits. It is a major limiting factor in the practical application of this technology to critically ill children.