Background: Sepsis and septic shock are still major causes of morbidity and mortality in spite of the availability of powerful and broadly active antibiotics. Methods: A prospective, open and randomized trial of the effect of immobilized polymyxin fibers (PMX-F) on the survival of patients with sepsis throughout a follow-up period of 28 days or until discharge, if earlier, was carried out. Ninety-eight patients were included who met at least 4 of the criteria for systemic inflammatory response syndrome due to infection. The patients were classified into three groups based on their Acute Physiology and Chronic Health Evaluation (APACHE) II score. Results: The overall survival rate was significantly improved by using PMX-F compared to the control group (41 vs. 11%) (p = 0.002). In patients with an APACHE II score less than 20, treatment with PMX-F was shown to improve outcome (65 vs. 19%) (p = 0.01). In cases of more severe sepsis with an APACHE II score of 20–29, PMX-F still maintained efficacy in improving outcome (40 vs. 11%) (p = 0.04). However, PMX-F treatment did not improve the survival rate in patients with an APACHE II score of greater than 30 (survival rate 7 vs. 0%) (p = 0.59). Conclusion: From these results, it is concluded that treatment with PMX-F in patients with sepsis is effective and prolongs the survival rate when applied at an early stage of sepsis. However, in severe sepsis, this therapy does not improve the survival rate.
The aim of this study was first, to evaluate the effects of continuous hemodiafiltration (CHDF) alone or combined with CHDF and polymyxin-B immobilized fiber (PMX) on survival rates of patients with sepsis and acute renal failure, and second, to evaluate the changes in plasma levels of inflammatory cytokines before and after treatment with CHDF and PMX and CHDF alone in these patients. Forty-eight patients with septic shock and acute renal failure were enrolled in this study. The survival rate of all patients at 28 days was 25% for those with CHDF and 75% for those with PMX and CHDF treatment. Combination treatment produced a significant reduction of plasma levels of endotoxin and interleukin-6 compared to the basal values and to the treatment with CHDF alone. From these data, it is suggested that the combined therapy with PMX and CHDF is effective in improvement of survival rate of patients with septic shock and acute renal failure.
In patients with accelerated (malignant) hypertension, end-organ damage is the determinant factor for prognosis. Although recent advances in antihypertensive therapy have improved the outcome of patients with accelerated hypertension, the effectiveness of antihypertensive therapy still remains less convinced.In this study, we followed 13 patients clinically diagnosed with accelerated hypertension (defined as diastolic blood pressure > 130 mmHg, retinopathy with K-W IV and accelerated renal impairment) for 3 yr. One patient died due to acute myocardial infarction arising from poor compliance with antihypertensive therapy. One patient was maintained on hemodialysis for 3 yr. One patient was introduced for continuous ambulatory peritoneal dialysis (CAPD) for a year and then lived without dialysis therapy. The remaining 10 patients were followed for 3 yr. All patients were initially treated with intravenous administration of calcium antagonist for reduction of blood pressure, followed by hemodialysis therapy if needed. After stabilization of blood pressure, combination therapy with extended release nifedipine (40 to 80 mg daily) and arotinolol (20 mg daily) was started. The targets for blood pressure control were a systolic pressure of 135 mmHg and a diastolic pressure of 80 mmHg. If blood pressure control was unsatisfactory, guanabenz (2 to 4 mg before bedtime), a central acting drug, was added. At presentation, the mean diastolic blood pressure (mDBP) among the 10 remaining patients was 134±2 mmHg, the mean serum creatinine (mScr) was 4.5±0.7 mg/dl and the left ventricular mass index (LVMi) as measured by echocardiography was 150±9 g/m2. At 1 yr, the mDBP was reduced to 90±3 mmHg, the mScr to 2.9±0.9 mg/dl and the LVMi to 140± 9 g/m2. At 3 yr, the mDBP was stabilized at 79 ± 3 mmHg, the mScr maintained at 2.2 ± 0.4 mg/dl, and the LVMi reduced to 128 ± 9 g/m2. These results indicate that appropriate blood pressure control is important for improvement of renal impairment and cardiac damage in patients with accelerated hypertension.Moreover, combination therapy with arotinolol and extended release nifedipine may be beneficial for this purpose. (Hypertens Res 2000; 23:159-166)
The effects of a combined therapy with a calcium channel antagonist and a$-blocker in patients with accelerated-malignant hypertension on blood pressure and renal function were examined. Thirteen patients presented with the clinical features of malignant hypertension (diastolic blood pressure >130 mmHg, retinal damage and progressive renal failure) at our hospital, over the 3 yr period from 1995 to 1997. These patients were treated with both a calcium antagonist, 60-80 mg/d dose of long acting nifedipine, and an a/9-blocker, 20 mg/d dose of arotinolol, for over 12 mo. At admission, the average blood pressure of the patients was 233 ± 8/144 ± 3 mmHg. The level of serum creatinine in these patients was 6.2 ± 1.0 mg/dl. Intermittent hemodialysis therapy was introduced in 7 patients. Three days after treatment, blood pressure decreased to 162 ± 4/ 102 ± 4 mmHg. A month later, blood pressure decreased to 148 ± 3/89 ± 2 mmHg and serum creatinine levels were 3.6 ± 0.4 mg/dl. Renal function in these patients improved, and they completely recovered from renal dysfunction, allowing withdrawal of haemodialysis therapy. One year later, the blood pressure in all of these patients was well controlled and no further renal deterioration was observed, except in one patient. Despite the reduction in blood pressure, one patient was on hemodialysis three times a week after 8 mo of treatment. From these finding, it is concluded that combination therapy with a calcium antagonist and ai9-blocker is effective in both the reduction of highly elevated blood pressure and protection of the kidneys, resulting in amelioration of accelerated-malignant hypertension. (Hypertens Res 1999; 22: 75-'80)
Background. No satisfactory treatment exists for IgA nephropathy (IgAN), especially in patients with severe histologic damage. Several trials using steroids combined with other therapies such as warfarin have demonstrated unremarkable results. We investigated the renoprotective effects of warfarin and steroids in IgAN patients with crescent formation. Methods. Fifteen Japanese patients with IgAN were followed for up to 3 years. Crescent formation was recognized in over half of their glomeruli from renal biopsy specimens. Treatments consisted of either 0.5 mg/kg per day of prednisolone, or warfarin monotherapy. Blood pressure was controlled with long-acting calcium channel blockers and alpha-beta blockers. Serum creatinine and urinary protein excretion were evaluated at least every 2 months for 36 months. Results. Ten of the 15 patients completed the study. The serum creatinine levels had increased in both groups by 3 years, but significantly more so in the group treated with warfarin. However, they were not significantly different between the two groups as measured at the beginning and end of the study. Blood pressure for all patients in the study was maintained below 130/85 mmHg. Excluded from the study were 5 patients who experienced either peptic ulcers (n ϭ 2, steroid group) or bleeding problems (n ϭ 3, warfarin group). Conclusions. These results suggest that corticosteroid therapy may assist in preventing deterioration of renal function in patients with IgAN accompanied by crescent formation. However, further study would be required to decide its usefulness.
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