Alterations of phenytoin protein binding with in vivo haemodialysis in dialysis encephalopathy

Summary Protein binding of phenytoin was assessed in one patient with dialysis encephalopathy before and after haemodialysis. Phenytoin concentrations were measured by radioimmunoassay and continuous ultrafiltration was used to assess phenytoin binding. At a serum concentration of 60 µmol.1^–1 the percentage of phenytoin bound to serum albumin was considerably lower in the patient serum (79.95% predialysis; 92.09% postdialysis) than that in three normal sera (97.90±0.17%). Analysis of Scatchard plots indicated two classes of binding sites. In class I both the affinity and capacity for binding phenytoin were reduced in the pre and post-dialysis serum, whereas in class II the capacity of the uraemic serum was increased although the intrinsic association constant was greatly reduced. It was concluded that in vivo haemodialysis is associated with large fluctuations in the protein binding of phenytoin, in which the concentration of endogenous dialysible metabolites are strongly implicated.     

Isolated Ultrafiltration in the Treatment of Dialysis Ascites

Three patients with dialysis ascites improved markedly after treatment with isolated ultrafiltrations. This simple, noninvasive technique should be applied first to patients with dialysis ascites before resorting to more drastic therapeutic measures.     

Current status of dosing and quantification of acute renal replacement therapy. Part 1: mechanisms and consequences of therapy under-delivery

The dosing and quantification of acute renal replacement therapy has emerged as one of the most pressing issues in the management of critically-ill patients with acute kidney injury. Although there is ongoing debate as to the best marker of uraemic injury in this setting, several landmark studies have identified clearance-related expressions of acute renal replacement therapy dose as important determinants of survival. Part 1 of this review examines the factors affecting delivery of prescribed acute renal replacement therapy dose. The review continues in Part 2 and examines the implications of recent advances in this area for clinical practice.     

Use of the Hemobag for modified ultrafiltration in a Jehovah's Witness patient undergoing cardiac surgery

Modified ultrafiltration is an important technique to concentrate the patient's circulating blood volume and the residual whole blood in the extracorporeal circuit post-cardiopulmonary bypass. The Hemobag system is a device cleared by the US Food and Drug Administration and represents a novel and safe modification of traditional modified ultrafiltration systems. It is quick and easy to operate by the perfusionist during the hemoconcentration process. Hemoconcentration is accomplished by having the Hemobag "recovery loop" circuit separate from the extracorporeal circuit. This allows the surgeons to continue with surgery, decannulate, and administer protamine simultaneously while the Hemobag is in use. The successful use of the Hemobag in a Jehovah's Witness patient has not been previously described in the literature. This case report describes how to set up and operate the Hemobag in a Jehovah's Witness patient undergoing cardiac surgery that requires an extracorporeal circuit.     

Effects of conventional ultrafiltration on renal performance during adult cardiopulmonary bypass procedures

Ultrafiltration has been used successfully in a variety of applications in the perioperative setting to assist in hemoconcentration and volume reduction. This study was designed to investigate the effects of aggressive conventional hemofiltration on bypass urine production, fluid balance, and renal performance in the 24 hours after bypass procedures in the adult population. A prospective, randomized study was designed to determine the effects of conventional ultrafiltration (CUF) during bypass while monitoring urine dynamics intraoperatively and in the 24-hour post-bypass period. Study group 1 (CUF, n = 49) was compared to control group 2 (non-CUF, n = 47) by monitoring urine values, volume additions, and packed red cell (PRC) use throughout the procedure. The mean total CUF volume removed from group 1 was 5781 +/- 2612. There were no differences in pre-bypass, total bypass, or total operating room (OR) urine between the two groups. The 24-hour urine totals were significantly higher in group 2 (2389 +/- 895) than in group 1 (2035 +/- 895). The ending bypass hematocrit was also lower in group 2 (26 +/- 2.0) than in group 1 (30 +/- 6.0). OR PRC additions were higher in group 2 (395 +/- 699) than group 1 (204 +/- 300). The non-CUF control group 2 experienced significantly greater ending fluid balance (3006 +/- 868) compared with group 1 (744 +/- 1271). No significant differences in pre- or postoperative creatinine values were observed. Aggressive CUF can be safely used during cardiopulmonary bypass in the adult population to reduce fluid accumulation and elevate bypass hematocrit without effecting bypass or intraoperative urine production.     

The glomerulus,passive filter or regulatory organ?

Summary This review summarizes recent evidence that glomerular filtration rate is highly regulated and not merely the passive consequence of uncontrolled renal and non-renal factors. Changes in the rate of nephron plasma flow and, under certain circumstances, the glomerular permeability coefficient are the major determining factors which influence the rate of glomerular ultrafiltration. Recent studies suggest that a variety a hormonal substances, when infused, share the capacity to affect glomerular filtration rate by influencing nephron plasma flow and specifically by decreasing the glomerular permeability coefficient. Angiotensin II appears to be the important final common pathway mediating many of these hormonal effects on the glomerular permeability coefficient. Of the hormonal substances examined, only ADH appears to exert an independent effect. Also, in certain normal and altered physiologic states, it has been demonstrated that certain hormonal substances, notably angiotensin II, participate in the active regulation of the rate of glomerular filtration through the capacity to influence and regulate the rate of nephron plasma flow and affect reduction in the glomerular permeability coefficient.     

Clinical Evaluation of a Pre-Set Ultrafiltration Rate Controller Available for Single Pass and Hemodiafiltration Systems

Introduction of high flux-type dialyzers, such as the RP-6, makes it necessary to devise an ultrafiltration rate controller for a single pass system. For this purpose, a new pre-set ultrafiltration rate controller has been developed and examined experimentally and clinically. The controller has twin chambers, each of which is divided into two symmetrical parts by a vertically-placed diaphragm. The diaphragm shifts repeatedly from right to left, aspirating in and driving out fresh or used dialysate alternately. If one removes a certain amount of used dialysate from a branch of the efferent line, negative pressure develops and aspirates an equal amount of water from the dialyzer. Therefore, extra dialysate obtained by a pump precisely reflects ultrafiltration rate. The controller has been used on five patients. The scheduled ultrafiltration rate was easily obtainable. The apparatus is also available for hemodiafiltration. Initial clinical trial has been promising.     

Controlled Ultrafiltration During Single-Pass Dialysis with the RP-6 Dialyzer and Evaluation of Its Time-Dependent Ultrafiltration Index

A simple and inexpensive method is described for controlling ultrafiltration when using the high flux RP-6 dialyzer. When the RP-6 is operated in the co-current mode and with single-pass dialysate delivery, (P_bo-P_dn) can be used to accurately and safely control ultrafiltration. Combined results from ten dialyses indicate there is a pressure-dependent concentration polarization which affects ultrafiltration as reported previously, and in addition, a time-dependent effect indicating a more complex dialyzer/blood interaction. The ultrafiltration index decreases linearly with time. The ultrafiltration can be adequately predicted by
Q v =16.1 ml/hr-mmHg [1–0.0761/hr t] (P_Bo-P_Do)     

Influence of assay methods on serum concentrations of digoxin during fab fragment treatment

Introduction: Sodium diethyldithiocarbamate and disulfiram have been proposed as effective nickel chelators. This paper examines the value of these compounds in the treatment of acute nickel carbonyl poisoning by reviewing published experimental and clinical data. Review: In 2 studies, parenteral administration of diethyldithiocarbamate 50–100 mg/kg to rats immediately following nickel carbonyl exposure ensured the survival of all animals: Mortality fell from 73% to 8% when diethyldithiocarbamate was administered at 10 minutes in a third study. In the same study, there was no protection when diethyldithiocarbamate was administered at 6 hours, and the mortality was greater, though not significantly different, when diethyldithiocarbamate was administered at 24 hours. In another study in mice, total protection was afforded by diethyldithiocarbamate given at 8 hours but this protection was limited when diethyldithiocarbamate was administered at 24 hours, with diethyldithiocarbamate 100 mg/kg apparently being less protective than diethyldithiocarbamate 50 mg/kg. In 3 studies, oral diethyldithiocarbamate administration was less effective than parenteral administration. There are no adequately controlled clinical studies of the use of diethyldithiocarbamate in acute nickel carbonyl poisoning despite claims that this therapy has been effective in the treatment of several hundred such patients. Disulfiram, a metabolite of diethyldithiocarbamate, offered complete protection against nickel carbonyl-induced toxicity when administered in a dose of 1000 mg/kg to rats immediately following nickel carbonyl exposure. In contrast, disulfiram 500 mg/kg offered no protection and disulfiram 1500 mg/kg appeared to enhance mortality, possibly by increasing brain nickel accumulation. Conclusion: Animal studies demonstrate that diethyldithiocarbamate is an effective antidote in acute nickel carbonyl poisoning when it is administered parenterally soon after exposure. However, as no adequately controlled clinical studies have been performed, further clinical data are required before diethyldithiocarbamate can be recommended routinely in acute nickel carbonyl poisoning. If diethyldithiocarbamate is to be employed, it should be administered parenterally soon after exposure as delay in administration may increase nickel carbonyl toxicity. There are currently insufficient data to recommend disulfiram as an alternative to diethyldithiocarbamate even when diethyldithiocarbamate is not available.     

离心沉淀-离心超滤法测定盐酸青藤碱脂质体的包封率

目的 建立盐酸青藤碱（sinomenine hydrochloride,SM-HCl）脂质体包封率的测定方法,并阐明药物在脂质体中的滞留特性。方法 采用薄膜分散法制备SM-HCl脂质体。以HPLC法测定脂质体药物的量,色谱柱为Kromasil ODS C₁₈柱（250 mm×4.6 mm,5 μm）,流动相为甲醇-水-乙二胺（55∶45∶0.225）,体积流量1.0 mL/min,检测波长265 nm。以离心沉淀-离心超滤法测定SM-HCl脂质体的包封率,并与以枸橼酸缓冲液（pH 7.0）水化的脂质体样品稀释前后的包封率进行对比。结果 辅料与溶剂对青藤碱的定量测定无干扰,青藤碱在9.82～78.56 μg/mL线性关系良好（r＝0.999 7）,平均回收率在99.29%～100.8%,日内与日间精密度良好（RSD≤2.1%）。50 μL药液可使超滤膜对药物的吸附达到饱和。以枸橼酸缓冲液（pH 7.0）水化的脂质体样品的包封率为33.16%,稀释1倍后该样品的包封率降至14.75%。结论 HPLC法与离心沉淀-离心超滤法结合可用于测定SM-HCl脂质体的包封率,该方法快速、准确;离心超滤中应弃去50 μL初滤液以确保滤液与脂质体外水相药物浓度一致;青藤碱与脂质双分子层有一定的亲和力,但在脂质体中的滞留性较差。