Determinants of vancomycin clearance by continuous venovenous hemofiltration and continuous venovenous hemodialysis

The clearance of vancomycin is significantly reduced in patients with acute, as well as, chronic renal failure. Although multiple-dosage regimen adjustment techniques have been proposed for these patients, there is little quantitative data to guide the individualization of vancomycin therapy in acute renal failure patients who are receiving continuous renal replacement therapy (CRRT). To determine appropriate vancomycin dosing strategies for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies in five stable hemodialysis patients with three hemofilters: an acrylonitrile copolymer 0.6 m2 (AN69), polymethylmethacrylate 2.1 m2 (PMMA), and polysulfone 0.65 m2 (PS). Patients received 500 mg of vancomycin intravenously at least 12 hours before the start of the clearance study. The concentration of vancomycin in multiple plasma and dialysate/ultrafiltrate samples was determined by EMIT (Syva, Palo Alto, CA). The diffusional clearance and sieving coefficient (SC) of vancomycin were compared by a mixed-model repeated-measures analysis of variance (ANOVA) with filter and blood (Q(B)), dialysate inflow (Q(DI)), or ultrafiltration rate (Q(UF)) as the main effects and patient as a random effect. Vancomycin was moderately protein bound in these patients; free fraction ranged from 49% to 83%. The SCs of the three filters were similar and significantly correlated with the free fraction of vancomycin (P = 0.01; r2 = 0.465). Significant linear relationships were observed between the diffusional clearance of vancomycin and Q(DI) for all three filters: AN69 (slope = 0.482; r2 = 0.880); PMMA (slope = 0.853; r2 = 0.966); and PS (slope = 0.658; r2 = 0.887). The slope of this relationship for the PMMA filter was significantly greater than that of the AN69 and PS filters. The clearance of vancomycin, urea, and creatinine, however, was essentially constant at all Q(B)s for all three filters. Thus, the clearance of vancomycin was not membrane dependent during CVVH. However, during CVVHD, membrane dependence of vancomycin clearance was noted at a Q(DI) greater than 16.7 mL/min; vancomycin clearance with PMMA at a Q(DI) of 25 mL/min was 66% and 43% greater than that with the AN69 and PS filters, respectively. CVVH (62% to 262%) and CVVHD (90% to 540%) can significantly augment the clearance of vancomycin in acute renal failure patients. Dosing strategies for individualization of vancomycin therapy in patients receiving CVVH and CVVHD are proposed.     

Diverticular abscesses: percutaneous drainage

Percutaneous catheter drainage was performed in 16 patients with diverticulitis complicated by abscesses. Each patient had resolution of fever within 72 hours. Eleven patients subsequently underwent simultaneous sigmoid resection and operative anastomosis 10-40 days after percutaneous drainage. One patient required a three-stage procedure after percutaneous drainage, and one patient was too unstable for operation at any time during her course and eventually died of respiratory failure. Three patients did not undergo resection after catheter drainage and have remained asymptomatic for 1-2 1/2 years. Ten of 16 patients had fistulas, eight of which closed spontaneously. Experience with percutaneous drainage of diverticular abscesses suggests that it obviates surgical abscess drainage and permits a single operation (sigmoid resection and closure) to be performed safely. Percutaneous abscess drainage has cost-saving implications, since one or two operations may be avoided in most patients, and in some high-risk elderly patients all operations may be obviated.     

Adenosine dialdehyde and nitrous oxide induce HL-60 differentiation

Adenosine dialdehyde and nitrous oxide, specific S-adeno- sylhomocysteine hydrolase and methionine synthetase inhibitors, respectively, induced differentiation of the human promyelocytic cell line HL-60. Their effect did not appear to be mediated through changes in transmethylation or decreased S-adenosylmethionine synthesis because (1) there was little correlation between the concentrations of adenosine dialdehyde that induced differentiation and those that changed the ratio of the intracellular concentrations of S- adenosylmethionine to S-adenosylhomocysteine, and (2) inhibition of methionine adenosyltransferase by cycloleucine did not induce differentiation. The differentiation induced by adenosine dialdehyde was prevented by homocysteine and that by nitrous oxide was inversely related to the medium methionine concentration. This suggested that differentiation was secondary to decreased methionine synthesis.     

Orthotopic cardiac transplantation: evaluation with CT

As cardiac transplantation has become widely available, computed tomography (CT) of the chest has played a useful role in the examination of patients after heart transplantation. To determine anatomic features related to the procedure, the authors evaluated 59 scans in 46 patients who had undergone orthotopic cardiac transplantation. Aortic anastomosis (seen in 98% of scans) and altered spacing between the great vessels (83%) proved to be the most common and most reliable findings. Other features including atrial anastomosis, high main pulmonary artery segment, remnant superior vena cava, and cardiac reorientation were also seen. Accurate interpretation of adenopathy, mediastinal abscess, and pericardial effusion will be enhanced in these patients through a better understanding of the cardiovascular-pericardial complex, which is afforded by CT.     

Palytoxin induces a relatively non-selective cation permeability in frog sciatic nerve which can be inhibited by cardiac glycosides

The effect of palytoxin (PTX) on compound resting potential and compound action potential of frog sciatic nerve was studied using the sucrose-gap technique. PTX irreversibly depolarized the compound resting potential and reduced the amplitude of the compound action potential. PTX evoked a marked depolarization when extracellular Na+ was replaced by Li+, Cs+ and the organic cations methylammonium, hydroxylammonium, and methylhydroxylammonium but not by tetramethylammonium, tetraethylammonium, choline or the divalent cations, Ca2+ and Ba2+. The maintained depolarization was not sensitive to inhibition by saxitoxin (300 nM) or procaine (10 mM). The depolarization was inhibited by ouabain or cymarin but not by the aglycon, strophanthidin. However, strophanthidin did antagonize the inhibitory action of cymarin which suggests that PTX and cardiac glycosides do not share an identical binding site but there may be some overlap. We conclude that in frog sciatic nerve, PTX interacts with the (Na+-K+) pump to induce the opening or formation of a relatively non-selective cation pore within or near the pump protein.     

Gallbladder and bile duct stones: percutaneous therapy with primary MTBE dissolution and mechanical methods

The authors describe percutaneous treatment of gallbladder or bile duct stones in 18 patients who were poor surgical candidates or in whom conventional therapy failed. Dissolution was performed in most cases with methyl tert-butyl ether (MTBE) because of its potent dissolution properties; other solvents used included monooctanoin or chelating solutions. Gallbladder stones were eliminated in 11 of 13 patients (six of seven with dissolution alone, four of four with dissolution and basket extraction, one with basket removal alone). In five patients with stones in the common bile duct (n = 3), cystic duct remnant (n = 1), and intrahepatic bile ducts (n = 1), stones were eliminated with dissolution alone in two and with dissolution plus basket extraction in one. In two patients percutaneous therapy failed due to complications (vagal hypotension with bile peritonitis and transient respiratory arrest) that occurred during catheter placement. Preliminary results suggest that MTBE is effective for dissolution of many gallbladder stones and some bile duct stones. Noncholesterol solvents and adjuvant mechanical maneuvers are valuable adjuncts to achieve complete stone elimination.