Effect of carvedilol on survival and hemodynamics in patients with atrial fibrillation and left ventricular dysfunction: retrospective analysis of the US Carvedilol Heart Failure Trials Program.

BACKGROUND: Atrial fibrillation (AF) is present in a significant number of patients with congestive heart failure (CHF) caused by left ventricular dysfunction and is associated with significant morbidity and increased mortality rates. Thus it is necessary to establish therapy to improve the outcome in this high-risk population. METHODS: We conducted a retrospective analysis of data from the US Carvedilol Heart Failure Trials Program and identified patients with AF at the time of enrollment. In these trials, 1094 patients with at least 3 months of heart failure symptoms and an ejection fraction < or = 0.35 were randomly assigned to receive carvedilol or placebo in a double-blind, stratified program according to performance on an exercise test. RESULTS: One hundred thirty-six patients with concomitant AF and CHF were identified during the screening visit (84 assigned to carvedilol and 52 to placebo). Therapy with carvedilol resulted in a significant improvement in left ventricular ejection fraction (from 23% to 33% with carvedilol and from 24% to 27% with placebo, P =.001). The physician global assessment improved in a greater number of patients treated with carvedilol than in those treated with placebo (71% vs 48%, P =.025). A trend toward a reduction in the combined end point of death or CHF hospitalization was also observed (19% in patients treated with placebo and 7% in patients on carvedilol; relative risk, 0.35; 95% confidence interval, 0.12, 1.02; P =.055). CONCLUSIONS: In patients with AF complicating CHF, carvedilol significantly improves left ventricular ejection fraction and physician global assessment and probably reduces the combined end point of CHF hospitalizations or death.

Effect of concomitant digoxin and carvedilol therapy on mortality and morbidity in patients with chronic heart failure.

We retrospectively performed stepwise logistic regression analysis on 1,509 patients with chronic heart failure in 4 multicenter United States studies and 1 Australia-New Zealand study to examine the effect of digoxin in patients randomized to carvedilol or placebo. Patients receiving digoxin had more advanced heart failure, the incidence of hospitalization for any cause and the combination of all-cause death and all-cause hospitalization were the same in the digoxin versus no-digoxin groups.

Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism.

BACKGROUND: Endothelin is a potent vasoconstrictor that has been implicated in the pathogenesis of radiocontrast nephrotoxicity. Endothelin antagonists may reduce the renal hemodynamic abnormalities following radiocontrast administration. METHODS: One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242. 3 to +/- 92.8 micromol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo. All patients received intravenous hydration with 0.45% saline before and after radiocontrast administration. Serum creatinine concentrations were measured at baseline, 24 hours, 48 hours, and 3 to 5 days after radiocontrast administration. The primary end point was the mean change in serum creatinine concentration from baseline at 48 hours; the secondary end point was the incidence of radiocontrast nephrotoxicity, defined as an increase in serum creatinine of > or =0.5 mg/dL (44 micromol/L) or > or = 25% from baseline within 48 hours of radiocontrast administration. RESULTS: The mean increase in serum creatinine 48 hours after angiography was higher in the SB 209670 group [0.7 +/- 0. 7 mg/dL (63.5 +/- 58.6 micromol/L)] than in the placebo group [0.4 +/- 0.6 mg/dL (33.6 +/- 55.1 micromol/L), P = 0.002]. The incidence of radiocontrast nephrotoxicity was also higher in the SB 209670 group (56%) compared with placebo (29%, P = 0.002). This negative effect of SB 209670 was apparent in both diabetic and nondiabetic patients. Adverse effects, especially hypotension or decreased blood pressure, were more common in the SB 209670 group. CONCLUSIONS: In patients with chronic renal insufficiency who were undergoing cardiac angiography, endothelin receptor antagonism with SB 209670 and intravenous hydration exacerbate radiocontrast nephrotoxicity compared with hydration alone.

The PRESTO (Prevention of restenosis with tranilast and its outcomes) protocol: a double-blind, placebo-controlled trial.

BACKGROUND: Tranilast is a unique drug in clinical development for the prevention of restenosis after percutaneous transluminal coronary revascularization (PTCR). Tranilast interferes with proliferation and migration of vascular medial smooth muscle cells induced by platelet-derived growth factor and transforming growth factor beta1. Collagen synthesis in vascular medial smooth muscle cells is inhibited by tranilast, which also inhibits the release or production of cyclooxygenase-2 and restores cytokine-induced nitric oxide production. These mechanisms may contribute to the reduction of angiographic restenosis after coronary intervention previously reported in clinical studies. METHODS: The primary objective of this multicenter study of 11,500 patients is to compare the composite clinical event rate of death, myocardial infarction, or the need for ischemia-driven target vessel revascularization of tranilast (300 and 450 mg twice daily) for 1 or 3 months with that of placebo in patients undergoing PTCR with or without stenting for single or multiple vessels over a 9-month period. The lesions can be de novo or restenotic. All revascularization procedures and the use of glycoprotein IIb/IIIa agents are permitted. The inclusion criteria are meant to allow an "all comer" approach for generalization of results to the broadest possible PTCR population. A subset population (n = 2000) will undergo 9-month follow-up angiography, 1000 of which will also undergo intravascular ultrasound (n = 1000). This study is the first tranilast trial to be conducted in a Western population to confirm the improved angiographic findings reported in Japanese patients and to determine if the clinical sequelae of restenosis are also reduced. CONCLUSION: This multicenter study is the largest restenosis trial planned to date. It will test whether tranilast, a drug with multiple actions aimed at affecting proliferation and migration of vascular smooth muscle cells, can reduce clinical, angiographic, and intravascular ultrasound assessments of restenosis.

Safety and efficacy of eprosartan, a new angiotensin II receptor blocker.

Angiotensin-converting enzyme inhibitors have been used extensively in the management of hypertension and related cardiovascular conditions. However, this treatment approach is limited by lack of specificity and continued production of angiotensin II by other routes. Antagonism of the angiotensin II receptor offers the possibility of improved control of hypertension by providing a more complete blockade of the renin-angiotensin system than angiotensin-converting enzyme inhibition without bradykinin-related effects. Eprosartan is the only nonbiphenyl, nontetrazole competitive angiotensin II receptor antagonist clinically available and is highly selective for the AT1 receptor subtype. In clinical trials, eprosartan has been shown to lower blood pressure effectively in a once-daily regimen in hypertensive patients. In the recommended dose range of 600 to 1200 mg once daily, eprosartan is effective in patients with all grades of hypertension irrespective of age, sex, or race. Furthermore, the tolerability profile of eprosartan is comparable to that of placebo, and there are no known clinically relevant drug-drug interactions. A number of large-scale clinical studies are currently underway or planned to determine which of the increasing number of AT1 receptor antagonists may reduce cardiovascular morbidity and mortality rates in different groups of hypertensive patients. Meanwhile, current evidence suggests that the AT1 receptor antagonists represent a significant new approach to cardiovascular therapy and merit a fuller assessment in hypertension and other cardiovascular diseases.

The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency.

INTRODUCTION: Carvedilol, a chiral compound possessing nonselective beta- and alpha1-blocking activity, is used for the treatment of hypertension and congestive heart failure (CHF). The enantiomers of carvedilol exhibit similar alpha1-blocking activity; only S-carvedilol possesses beta-blocking activity. Carvedilol is primarily hepatically metabolized, with less than 2% of the dose excreted renally as unchanged drug. METHODS: The pharmacokinetics of carvedilol, R-carvedilol, and S-carvedilol were studied in hypertensive patients (control; n = 13) versus patients with hypertension and advanced renal insufficiency not yet on dialysis [GFR < or = 30 ml x min(-1) (CRI, chronic renal insufficiency), n = 12] following single (12.5 mg, Day 1) and multiple (25 mg once daily, Days 2 9) dosing. RESULTS: Mean with (SD) AUC(0-24h) (ng x h x ml(-1)) for carvedilol was 220 (120) and 618 (335) in CRI compared with 165 (83.5) and 413 (247) in controls on Days 1 and 9, respectively, primarily due to higher R-carvedilol concentrations. Mean with (SD) Cmax (ng x ml(-1)) for carvedilol were 53.4 (31.4) and 128 (63.3) in CRI compared with 46.7 (23.3) and 104 (58.9) in controls on Days 1 and 9, respectively. The difference in group mean values was characterized by considerable overlap in individual AUC(0-24h) and Cmax values between groups. There was no apparent difference in mean terminal elimination half-life for carvedilol between groups on each study day. Less than 1% of the dose was excreted in urine as unchanged carvedilol in both groups. Blood pressure and heart rate declined in both groups to a similar degree. CONCLUSION: Compared with controls, average AUC(0-24 h) values for carvedilol were approximately 40% and 50% higher on study Days 1 and 9 in patients with renal insufficiency, primarily due to higher R-carvedilol concentrations with only a small change (<20%) in S-carvedilol concentrations, the isomer possessing beta-blocking activity. These changes in pharmacokinetics are modest in view of the large interindividual variability. Carvedilol was well tolerated in both groups. Although the present study cannot provide a final conclusion, based on the results of the present study, no changes in dosing recommendations for carvedilol are warranted in patients with moderate/severe renal insufficiency.

Fenoldopam, a selective dopamine-1 receptor agonist, raises intraocular pressure in males with normal intraocular pressure.

Recent studies have suggested that intravenous infusion of fenoldopam, a selective dopamine-1 receptor agonist, elevates intraocular pressure (IOP) in man. This study evaluated the effect of intravenous fenoldopam on IOP, aqueous humor outflow facility and gonioscopy in 12 healthy human subjects. Three doses (0.2, 0.5 and 1.0 microg/kg/min) were infused for 120 minutes in a double masked, placebo controlled, four-way crossover design. IOP was measured every 20 minutes in the supine position and every 40 minutes while sitting during the drug and placebo infusions. Tonography and gonioscopy were performed at baseline and after 120 minutes of infusion. Compared to placebo, IOP increased by 3.5 mm Hg (32%) for the lowest dose, 5.8 mm Hg (46%) for the intermediate dose, and 6.9 mm Hg (55%) for the highest dose (p<0.05 for all three doses). IOP returned to baseline within 30 minutes of stopping the infusion. The outflow facility decreased from baseline by 26% after 120 minutes of infusion for all drug doses. In contrast, outflow facility increased from baseline by 11% during placebo infusion. Compared to placebo, the fenoldopam induced changes in outflow were statistically significant (p<0.05). There was no change in the gonioscopic appearance of the anterior chamber angle during the infusion. This study shows that systemic administration of a selective dopamine-1 receptor agonist causes a significant dose-dependent increase in IOP that can be explained in part by diminished outflow facility. These results support a role for the dopamine-1 receptor in the modulation of IOP in general and suggest modulation of aqueous humor outflow by dopaminergic receptors.

Efficacy and safety of carvedilol in patients with chronic heart failure receiving concomitant amiodarone therapy. Australia/New Zealand Heart Failure Research Collaborative Group.

BACKGROUND: The beta-blocker/vasodilator carvedilol is found to have beneficial effects in patients with chronic heart failure. However, the safety and efficacy of this agent in the presence of concomitant amiodarone therapy has not been previously determined. METHODS AND RESULTS: We retrospectively analyzed the Australia/New Zealand Carvedilol Heart Failure Research Collaborative Group study of 415 patients with mild to moderate ischemic heart failure where amiodarone was administered as part of the treatment therapy (in 52 patients). After the open-label carvedilol run-in, patients received carvedilol (target dose 25 mg twice daily) or placebo for an average of 19 months. The main adverse events during this double-blind period were worsened heart failure, hypotension/dizziness, bradycardia/atrioventricular block, and aggravation of angina. By Chi square analysis, carvedilol and amiodarone together were not associated with a greater overall incidence of adverse effects than either drug alone. The beneficial effects of carvedilol on left ventricular ejection that were observed in the main trial were preserved in the presence of amiodarone. CONCLUSIONS: Carvedilol is a useful additional therapy for patients with chronic heart failure already receiving amiodarone. Carvedilol can be added to amiodarone in these patients without expectation of increased adverse effects or loss of clinical efficacy.

Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise.

BACKGROUND: Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. METHODS AND RESULTS: We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction < or = 0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n = 145) or carvedilol (n = 133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P = .014) or by a global assessment of progress judged either by the patient (P = .002) or by the physician (P < .001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P < .001) and a significant decrease in the combined risk of morbidity and mortality (P = .029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. CONCLUSIONS: These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.

Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators.

BACKGROUND: We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a "third-generation" beta -blocking agent with vasodilator properties, in chronic heart failure. METHODS AND RESULTS: Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive treatment with placebo, 6.25 mg BID carvedilol (low-dose group), 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction [EF] units in the low-, medium-, and high-dose carvedilol groups, respectively, compared with 2 EF units with placebo, P < .001 for linear dose response) and survival (respective crude mortality rates of 6.0%, 6.7%, and 1.1% with increasing doses of carvedilol compared with 15.5% in the placebo group, P < .001). When the three carvedilol groups were combined, the all-cause actuarial mortality risk was lowered by 73% in carvedilol-treated subjects (P < .001). Carvedilol also lowered the hospitalization rate (by 58% to 64%, P = .01) and was generally well tolerated. CONCLUSIONS: In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose-related reductions in mortality and hospitalization rate.

The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group.

BACKGROUND: Controlled clinical trials have shown that beta-blockers can produce hemodynamic and symptomatic improvement in chronic heart failure, but the effect of these drugs on survival has not been determined. METHODS: We enrolled 1094 patients with chronic heart failure in a double-blind, placebo-controlled, stratified program, in which patients were assigned to one of the four treatment protocols on the basis of their exercise capacity. Within each of the four protocols patients with mild, moderate, or severe heart failure with left ventricular ejection fractions < or = 0.35 were randomly assigned to receive either placebo (n = 398) or the beta-blocker carvedilol (n = 696); background therapy with digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor remained constant. Patient were observed for the occurrence death or hospitalization for cardiovascular reasons during the following 6 months, after the beginning (12 months for the group with mild heart failure). RESULTS: The overall mortality rate was 7.8 percent in the placebo group and 3.2 percent in the carvedilol group; the reduction in risk attributable to carvedilol was 65 percent (95 percent confidence interval, 39 to 80 percent; P < 0.001). This finding led the Data and Safety Monitoring Board to recommend termination of the study before its scheduled completion. In addition, as compared with placebo, carvedilol therapy was accompanied by a 27 percent reduction in the risk of hospitalization for cardiovascular causes (19.6 percent vs. 14.1 percent, P = 0.036), as well as a 38 percent reduction in the combined risk of hospitalization or death (24.6 percent vs, 15.8 percent, P < 0.001). Worsening heart failure as an adverse reaction during treatment was less frequent in the carvedilol than in the placebo group. CONCLUSIONS: Carvedilol reduces the risk or death as well as the risk of hospitalization for cardiovascular causes in patients with heart failure who are receiving treatment with digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor.

The de novo diagnosis of systemic lupus erythematosus in a hemodialysis patient.

We present the first reported case of a patient who developed de novo systemic lupus erythematosus (SLE) after the initiation of dialysis for chronic renal failure. The etiology of his renal failure was secondary to biopsy-proven idiopathic membranoproliferative glomerulonephritis in conjunction with accelerated hypertension. The physical, biochemical or serologic findings of SLE did not become apparent until 4 years after the initiation of hemodialysis. This deviates from the natural history of SLE; typically, once dialysis is initiated, disease and serologic activity diminish with time to the point where therapy is no longer required. Therefore, this first diagnosis of SLE after years on dialysis represents a novel observation.

Fenoldopam, but not nitroprusside, improves renal function in severely hypertensive patients with impaired renal function.

PURPOSE: Patients with hypertensive crises often experience reduced renal function that may worsen as the elevated blood pressure is treated. Fenoldopam, a novel, peripherally acting dopamine-1 agonist, lowers blood pressure through arteriolar vasodilation, with particularly prominent effects on the renal vascular bed. This study was conducted to examine the effects of fenoldopam on blood pressure and renal function compared to those of sodium nitroprusside in severely hypertensive patients with impaired renal function. PATIENTS AND METHODS: Renal function and systemic hemodynamics were studied in 19 severely hypertensive patients (diastolic blood pressure greater than or equal to 120 mm Hg) with impaired renal function (creatinine clearance less than or equal to 70 mL/min) enrolled in clinical trials of fenoldopam and sodium nitroprusside. For comparison, an additional 22 severely hypertensive patients with nonimpaired renal function were studied under the same conditions. Blood pressure and heart rate were measured at baseline before treatment and periodically during treatment. Renal function was determined before and during drug infusion by collection of timed urine specimens and blood samples. Creatinine clearance, urine flow rate, and sodium and potassium excretions were measured and compared. RESULTS: In patients with impaired renal function, blood pressure (mean +/- SEM) was reduced successfully in both groups (fenoldopam: 214 +/- 8/139 +/- 6 mm Hg to 176 +/- 8/107 +/- 3 mm Hg, p < 0.001 for systolic and diastolic comparisons; nitroprusside: 226 +/- 4/145 +/- 5 mm Hg to 171 +/- 6/108 +/- 2 mm Hg, p < 0.001 for systolic and diastolic comparisons). Results of renal function studies showed significant increases in creatinine clearance (from 39 +/- 7 mL/min to 75 +/- 16 mL/min, p < 0.05), urine flow (from 119 +/- 37 mL/h to 275 +/- 84 mL/h, p < 0.01), and sodium excretion (from 75 +/- 22 microEq/min to 227 +/- 60 microEq/min, p < 0.01) in patients with impaired renal function treated with fenoldopam. No significant changes were seen in patients treated with nitroprusside. In patients with nonimpaired renal function, blood pressure was reduced by both agents, but only patients who received fenoldopam experienced significant increases in creatinine clearance, urine flow rate, and sodium excretion. CONCLUSION: Fenoldopam, but not nitroprusside, improved renal function in severely hypertensive patients at all levels of baseline renal function while lowering blood pressure. Because of these effects, fenoldopam may be particularly useful in treating severely hypertensive patients with impaired renal function.

Fenoldopam reverses cyclosporine-induced renal vasoconstriction in kidney transplant recipients.

Cyclosporine causes renal vasoconstriction and reduced renal blood flow that may contribute to chronic nephrotoxicity. This effect has not been consistently reversed by available pharmacologic agents. The efficacy of orally administered fenoldopam, a dopamine-1 (DA-1) agonist with renal vasodilator properties, was evaluated in six patients whose condition was stable 3 to 6 months following renal transplantation. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate (PAH) clearances, respectively, at baseline, after the acute oral administration of 100 mg of fenoldopam, and following 3 weeks of chronic oral fenoldopam therapy (100 mg thrice daily). Mean ERPF increased from 3.15 +/- 0.17 mL/s/1.73 m2 (189 +/- 10 mL/min/1.73 m2) at baseline to 3.48 +/- 0.17 mL/s/1.73 m2 (209 +/- 10 mL/min/1.73 m2) 4 hours after acute administration of fenoldopam (P = 0.04). Urine flow rate and fractional excretion of sodium also increased after acute administration, but not significantly. Mean systolic (SBP) and diastolic blood pressure (DBP) decreased maximally by 18 and 6 mm Hg, respectively, and mean pulse rate increased maximally by 8 bpm between 75 and 90 minutes after both acute and chronic administration. GFR was unchanged following both acute and chronic administration. The increase in ERPF was not maintained to the end of the dosing interval during chronic administration, probably due to the short half-life of fenoldopam. However, the renal vasodilatory response was still observed 3 to 4 hours after readministration of the drug following 3 weeks of oral dosing. Thus, fenoldopam significantly reverses the renal vasoconstriction caused by cyclosporine in renal transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of refractory peritonitis to maintain the peritoneum for subsequent dialysis.

Peritonitis and its sequelae remain major clinical problems in treating peritoneal dialysis (PD) patients. One of these sequelae is the formation of intra-abdominal adhesions, preventing a patient from returning to peritoneal dialysis after a Tenckhoff catheter is removed for refractory peritonitis. We have recently applied a technique that appears to reduce the incidence of this severe complication. When it is determined that a catheter will be removed for refractory peritonitis, hourly peritoneal dialysis exchanges are performed for 12 hr prior to surgery. Postoperatively, the abdomen is rested for 48 hr, after which a temporary peritoneal dialysis catheter is placed at the bedside and hourly exchanges (with antibiotics) are performed for 2-3 days or until the dialysis fluid white blood cell count improves. Then the temporary catheter is removed and the abdomen is rested until the Tenckhoff catheter is replaced in 10-14 days. We treated 5 consecutive patients with refractory peritonitis (2 Pseudomonas, 1 Proteus, 1 Candida, 1 S. aureus) with this technique. All 5 patients were able to return successfully to peritoneal dialysis. At our institution over the past five years, 9 patients with refractory peritonitis due to the same organisms have had their catheters removed. Only 5 (56%) were able to return to PD. Although preliminary, our technique holds promise for those patients wishing to return to peritoneal dialysis after having a catheter removed for refractory peritonitis.

Intraoperative versus routine hemodialysis in end-stage renal disease patients undergoing open-heart surgery.

Of 13 chronic hemodialysis end-stage renal disease (ESRD) patients undergoing open-heart surgery, 7 received intraoperative hemodialysis (IHD) during cardiopulmonary bypass and 6 received hemodialysis on a routine basis (RHD). Within the groups, IHD patients had significantly lower post-operative mean serum potassium and mean plasma creatinine concentrations compared to mean preoperative values. Postoperative mean BUN tended to decrease and mean serum bicarbonate concentration was unchanged as compared to mean preoperative values. In the RHD group, however, post-operative mean serum potassium concentration tended to increase, mean serum bicarbonate concentration significantly declined and mean BUN was unchanged as compared to mean preoperative values. An average of 2.1 +/- 0.5 liters of fluid was removed from the IHD patients during cardiopulmonary bypass. Post-operatively, 0 of 7 IHD patients versus 4 of 6 RHD patients required parenteral sodium bicarbonate therapy (chi 2, p less than 0.01). On average, RHD patients required hemodialysis 1 day after surgery, whereas IHD patients were hemodialyzed 2 days after surgery (p = 0.009). We conclude that IHD lessened postoperative hyperkalemia and metabolic acidosis and delayed postoperative hemodialysis by an additional day. IHD should be considered as an adjunct to RHD therapy in the management of ESRD patients undergoing open-heart surgery.

Illness in hemodialysis patients after exposure to chloramine contaminated dialysate.

In September 1987, patients at an outpatient dialysis center were exposed to chloramine contaminated dialysate when the carbon filter in a recently modified water treatment system failed. Forty-one patients required transfusion to treat the resultant hemolytic anemia. Epidemiologic investigation demonstrated that the mortality rate among dialysis center patients increased during the 5 months after chloramine exposure when compared with the 12 months before chloramine exposure, but no deaths could be attributed to the exposure. Chloramine is commonly used as a disinfectant in municipal water supplies, and has previously been reported to cause hemolytic anemia in patients undergoing dialysis. Hemodialysis centers in cities that use chloramine in water supplies must design water treatment systems with adequate means for removing chloramine and must monitor processed water closely to ensure that chloramine contamination does not occur. Dialysis centers that make changes in their water processing systems should evaluate all components of the system before changes are made, and must ensure that after modifications are made, processed water meets the standards set by the Association for Advancement of Medical Instrumentation.

Reprocessing of hemodialyzers: a critical appraisal.

The reprocessing of hemodialysis equipment was originally developed to conserve scarce resources and to reduce the time necessary to construct early dialyzers. Although most dialyzers in current use are marketed as disposable items, the majority of dialysis facilities in the United States reprocess these devices and use them multiple times on the same patient. Recent studies have shown that certain reprocessing techniques confer improved biological properties on dialyzers compared with new membranes as prepared by manufacturers. Several studies have suggested that these biological properties may lead to improved clinical outcomes. However, critics of dialyzer reprocessing argue that it may expose patients to risks that produce increased morbidity and mortality. This article critically reviews the available scientific information regarding reprocessing hemodialyzers.

The clinical utility of the Tc-99m SC intraperitoneal scan in CAPD patients.

The intraperitoneal instillation of dialysate increases intra-abdominal pressure and consequently predisposes to subcutaneous infiltration, leaks, and herniations through defects in the abdominal wall. In this setting, the incidence of abdominal hernias ranges between 9% and 24%. Life-threatening complications (incarceration/strangulation) occur in up to 13.2% of hernias. Therefore, the authors evaluated the efficacy of the Tc-99m sulfur colloid (SC) intraperitoneal scan in the detection of abdominal leaks and hernias in 11 continuous ambulatory peritoneal dialysis (CAPD) patients over a 2-year period at the Hospital of the University of Pennsylvania. Eleven patients (7M, 4F) ranging in age from 24 to 72 (mean = 50.8), on CAPD, were evaluated for clinically suspected abdominal hernias or dialysate leaks with intraperitoneally administered Tc-99m SC. After the injection of 3-5 mCi of Tc-99m into a standard 2 liter dialysate bag, multiple sequential anterior images of the abdomen were obtained in the supine position over the course of one hour. Delayed images were obtained after ambulation and post-drainage two or more hours postinjection in multiple projections and positions in order to demonstrate any abnormal focal accumulations of fluid to the best advantage. Any detected abnormalities were marked and correlated with the physical examination and the patient's symptoms. Two patients had normal scans. Of the nine abnormal scans, five hernias were identified in four patients and six leaks were detected in the other five patients.(ABSTRACT TRUNCATED AT 250 WORDS)