P.G.G. Gerlag

Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion.

OBJECTIVES The efficacy of high dose furosemide as a continuous infusion was compared with a bolus injection of equal dose in patients with severe heart failure. BACKGROUND The delivery rate of furosemide into the nephron has been proved to be a determinant of diuretic efficacy in healthy volunteers. METHODS In a randomized crossover study we compared the efficacy of a continuous infusion of high dose furosemide (mean daily dosage 690 mg, range 250 to 2,000) versus a single bolus injection of an equal dose in 20 patients with severe heart failure. The patients received an equal dosage, either as a single intravenous bolus injection or as an 8-h continuous infusion preceded by a loading dose (20% of total dosage). RESULTS Mean (+/- SEM) daily urinary volume (infusion 2,860 +/- 240 ml, bolus 2,260 +/- 150 ml, p = 0.0005) and sodium excretion (infusion 210 +/- 40 mmol, bolus 150 +/- 20 mmol, p = 0.0045) were significantly higher after treatment with continuous infusion than with bolus injection, despite significantly lower urinary furosemide excretion (infusion 310 +/- 60 mg every 24 h, bolus 330 +/- 60 mg every 24 h, p = 0.0195). The maximal plasma furosemide concentration was significantly higher after bolus injection than during continuous infusion (infusion 24 +/- 5 micrograms/ml, bolus 95 +/- 20 micrograms/ml, p < 0.0001). Short-term, completely reversible hearing loss was reported only after bolus injection in 5 patients. CONCLUSIONS We conclude that in patients with severe heart failure, high dose furosemide administered as a continuous infusion is more efficacious than bolus injection and causes less ototoxic side effects.

Continuous infusion of furosemide in the treatment of patients with congestive heart failure and diuretic resistance

Objectives. To assess the value of treatment with continuous intravenous infusion of furosemide (F) in patients with refractory congestive heart failure.

Combination Diuretic Therapy in Severe Congestive Heart Failure

SummarySevere congestive heart failure (CHF) is often characterised by fluid retention. A (chronic) state of overhydration has a negative influence on both the quality of life and prognosis of these patients. Therefore, the use of diuretics remains a cornerstone in the treatment of heart failure. However, diuretic resistance, a failure to correct the hydration state adequately with the use of conventional dosages of loop diuretics, is a frequently occurring complication in the treatment of advanced stages of CHF.Several intra- and extrarenal mechanisms may be involved in the development of diuretic resistance. An important pathophysiological mechanism leading to diuretic resistance seen after chronic use of loop diuretics is the functional adaptation of the distal tubule. Studies in animals demonstrate that the sodium reabsorption capacity of this nephron segment increases significantly when the sodium delivery to this segment is augmented, as is the case during administration of loop diuretics.The use of combinations of diuretics acting on different segments of the nephron appears to be an effective option in the treatment of diuretic resistance. Several combinations have been used; however, the combination of a loop diuretic and a thiazide drug acting on the distal tubule appears to be the most effective. However, since the use of this combination may lead to serious adverse effects such as hypokalaemia, metabolic alkalosis and dehydration, careful monitoring of the patient on combination diuretic therapy is necessary.

Clinical features and outcome in patients with glomerulonephritis and antineutrophil cytoplasmic autoantibodies.

We investigated the clinical features and outcome of 60 patients with antineutrophil cytoplasmic autoantibodies with cytoplasmic staining (C-ANCA)- and with (peri)nuclear staining (P-ANCA)-associated glomerulonephritis. Virtually all patients with C-ANCA had antibodies against proteinase 3, which corresponded with a clinical and/or histological diagnosis of Wegeners granulomatosis (WG). P-ANCA were associated with antibodies against myeloperoxidase. Although more often associated with renal-limited disease, a significant number of patients with P-ANCA had also symptoms of organs known to be preferentially affected with WG. The majority of patients presented with rapidly progressive glomerulonephritis which responded favorably to immunosuppressive therapy, albeit at the expense of a considerable number of fatal infections. Furthermore, a more protracted form of glomerulonephritis was recognized. A kidney biopsy scoring system appeared to be of value in predicting which patients would benefit most from treatment. C-ANCA and P-ANCA appear to identify a subset of patients with vasculitis that share common clinical features and a favorable response to immunosuppressive therapy.

Blood Volume Control by Biofeedback and Dialysis-Induced Symptomatology

In earlier studies, a reduction in intradialytic procedures was observed in patients with severe intradialytic hypotension symptomatology by the use of blood volume controlled biofeedback systems. However, few data are present on the use of biofeedback-controlled treatments in patients experiencing minor intradialytic symptoms. In the present study, 157 standard and 158 biofeedback-controlled treatments were compared during a 2-month period in 16 hemodialysis patients. Both the percentage of hypotensive episodes (6.3 ± 11.3 vs. 15.8 ± 18.3%; p < 0.05) as well as other intradialytic symptoms (cramps, nausea, headache, abdominal pain) (11.0 ± 12.8 vs. 18.1 ± 16.9%; p < 0.05) were significantly less during biofeedback-controlled treatments compared to standard dialysis treatments, despite a similar decline in relative blood volume (8.8 ± 3.5 vs. 8.3 ± 3.1%; p = n.s.). Interdialytic weight gain and intradialytic rise in plasma sodium levels were comparable. Concluding, in this short-term preliminary study, blood volume controlled biofeedback improved dialysis tolerance also in patients with minor intradialytic symptomatology.

Acute and Long-Term Effects of Therapy with High-Dose Furosemide in Chronic Hemodialysis Patients

The effects of daily administration of 250-2,000 mg furosemide (F) were studied in patients on hemodialysis who still had residual renal function. In a short study, 10 patients (endogenous creatinine clearance 0.6-5.3 ml/min/1.73 m2) used 1,000 mg F twice daily during 7 days, and in a long-term study 13 patients (endogenous creatinine clearance 0.7-6.8 ml/min/1.73 m2) were treated during 1 year with 250-1,000 mg F orally each day. In the short study, we observed an increase in the 24-hour volume excretion with a median of 109% (p < 0.005). Urinary sodium excretion increased 210%, chloride 346% and potassium 65% when compared with the control period. In the long-term study, a marked initial rise in diuresis and electrolyte excretion was found. However, during a 1-year follow-up, a gradual decrease in response with time was found caused by progression of renal disease. There were no signs of ototoxicity. Side effects were bollous dermatosis on the limbs after exposure to sunlight during the summer (3 patients). We conclude that high-dose F is effective in patients on hemodialysis with residual urinary production. However, in the long term, the diuretic effects diminish because of progression of the underlying renal disease.

Hepatic sinusoidal dilatation with portal hypertension during azathioprine treatment after kidney transplantation

An unusual hepatic disease developed in 3 patients with a well-functioning kidney graft 16-24 months after transplantation. Vague abdominal pain, increased bleeding tendency and edema were initial complaints, and hepato- or splenomegaly and ascites were found as well. Liver function tests were not or only mildly disturbed; hemolysis and pancytopenia were always present. Colloid uptake was absent at liver scintigraphy and the hepatic venous wedge pressure was increased. Esophageal varices were demonstrated. Liver biopsy showed extensive midzonal and pericentral sinusoidal dilatation. After discontinuation of azathioprine the symptoms and the extent of sinusoidal dilatation disappeared gradually, but after 1-3 years fibrosis or micronodular cirrhosis had developed and splenomegaly with hypersplenism remained. These observations strongly suggest an association between chronic use of azathioprine and the development of venous congestion of the liver with sinusoidal dilatation, eventually resulting in chronic liver disease.

Renal replacement therapy in the elderly

BACKGROUND AND METHODS In a retrospective study the medical records of 122 patients aged over 65 years at the start of renal replacement therapy (RRT) in our dialysis centre were analysed. RESULTS The mean age at the start of RRT was 72.7 +/- 5.7 years (range 65.0-90.3). Seventy-six percent were treated with haemodialysis, 21% with haemofiltration and 3% with continuous ambulatory peritoneal dialysis. There was no significant difference in survival between the different modes of treatment. The median survival was 23.8 months, the actuarial survival rates at 2, 5 and 7 years were 50, 27 and 18%, respectively. Patients aged between 65 and 75 years had a median survival of 36.4 months, patients above 75 years of 12.5 months (P = 0.009). Patients with tubulo-interstitial nephritis had a significantly longer survival than patients with other renal diseases. When chronic obstructive pulmonary disease or peripheral vascular disease was present, there was a significantly shorter survival. There was no difference in survival between patients with malignancy, cardiac diseases, diabetes mellitus or cerebrovascular diseases before the start of RRT and others. After the start of RRT there was a significant increase of infectious and psychiatric disease. During the study period 70% died, most frequently from cardiovascular causes (28%), discontinuation of dialysis treatment (28%) or infection (19%). CONCLUSIONS We think that both survival and quality of life in elderly patients during RRT are acceptable, and that neither age nor comorbidity should be a contraindication to RRT.

Effect of hemodialysis on serum concentrations of HPLC-analyzed accumulating solutes in uremia

The concentration changes, during hemodialysis treatment, of 18 characteristic uremia compounds, analyzed by high-pressure liquid chromatography in sera of renal patients were studied. Pre- to postdialysis concentration ratios (dialysis ratio, D) varied from 0.83 to 3.04 for the different solutes. A division into three solute groups, on the basis of their D values, could be rationalized qualitatively from data on protein binding and dialyzer clearance. One group showed low dialysis ratios which could be explained from plasma protein binding. The second group had intermediate D values, comparable to those of creatinine. For some of the members of the third group, high D values might indicate a compartmentalization and resistance to mass transfer across biological membranes. Among the latter are the tubularly secreted hippuric acid and p-hydroxyhippuric acid. For most of the (protein-bound) solutes, protein binding was shown to decrease during hemodialysis. Protein binding levels were higher after dialysis only for hippuric acid and the as yet unidentified fluorescent solute designated UFK8. In conclusion, the change of serum concentrations and of protein binding resulting from hemodialysis treatment are presented and are compared for 18 accumulating solutes in sera of patients with end-stage renal failure.

Prednisone-Induced Fluctuations of Proteinuria in Patients with a Nephrotic Syndrome

We studied the effect of prednisone on urinary protein excretion in 19 patients with a nephrotic syndrome, who were treated with prednisone (125-150 mg) on alternate days. We found a typical, fluctuating pattern of proteinuria resulting from an increased protein excretion rate on prednisone days and a decreased protein excretion rate on nonprednisone days. The urinary protein excretion on prednisone days was 9.9 +/- 3.3 g/24 h, as compared to 5.7 +/- 3.8 g/24 h on nonprednisone days (mean +/- SD). In the whole group of patients the percentual change in proteinuria was significantly correlated with the endogenous creatinine clearance. However, systematic differences between creatinine excretion rates on prednisone and nonprednisone days were not found in individual patients. In 6 patients, renal hemodynamics were studied more precisely, using a single injection technique. Only a slight and nonsignificant decrease in glomerular filtration rate was found on nonprednisone days (delta = -9.6 +/- 16.3%; mean +/- SD). Filtration fraction remained unchanged. It is therefore suggested that the effects of prednisone on proteinuria are not simply mediated by overall changes in renal hemodynamics.