Rifampicin-associated acute renal failure: pathophysiologic, immunologic, and clinical features.

A 71-year-old woman was treated for a relapsing pulmonary tuberculosis with reinstitution of rifampicin after a medication-free interval of 2 years. After ingestion of the second dose, she developed severe hemolytic anemia and acute renal failure (ARF) necessitating dialysis. We demonstrated the presence in the patient's serum of rifampicin-dependent immunoglobulin G (IgG) and IgM antibodies, which caused red blood cell lysis through interaction with the I antigen on the erythrocyte surface. A review of the literature yielded 48 cases of rifampicin-associated renal failure. A subgroup of 37 patients could be distinguished, which, analogous to our case, suddenly developed ARF and frequently also developed hemolytic anemia and/or thrombocytopenia during intermittent or interrupted treatment. Regarding the pathogenesis of the ARF, renal biopsy consistently revealed tubular lesions. Although intravascular hemolysis with hemoglobinuria may play a role, it is not uniformly present. Our demonstration of an antibody with anti-I specificity provides a possible explanation. The I antigen is also expressed on tubular epithelium and may, therefore, be the target structure through which rifampicin-antibody complexes lead to tubular cell destruction. The other cases of rifampicin-associated ARF were unrelated to this subgroup: two cases of rapidly progressive glomerulonephritis, five cases of acute interstitial nephritis, and four cases of light chain proteinuria were recorded.

Evaluation of the hemodynamic and respiratory effects of inverse ratio ventilation with a right ventricular ejection fraction catheter.

Pc-IRV has been shown to have respiratory advantages, compared with CPPV. However, the hemodynamic effects of this ventilation mode have not yet been fully elucidated. We used a REF catheter to monitor the hemodynamic changes in the RV. Fifteen ARDS patients were included in the study. The respiratory data showed a 35 percent decrease of PIP and a 32 percent decrease of VTi and VTe with Pc-IRV 4:1 compared with CPPV. Hemodynamic parameters showed a significant incrase in CI (17 percent) in Pc-IRV 4:1, without change in REF. Observing in retrospect the pressure-volume relationship of the RV, we could differentiate a preload (group 1) and an afterload dependent group of patients (group 2), CI was significantly different in the two groups as it rose only in the preload-dependent patients. RVEDVI showed a significant change in group 1, whereas this was absent in the second group. REF was maintained in switching ventilation from CPPV to Pc-IRV with increasing I:E ratio. Pc-IRV appears to be a good alternative ventilatory mode in comparison with CPPV in a selected group of patients with preload dependency (responders); in these patients with respiratory insufficiency, close hemodynamic monitoring is required to optimize ventilation, especially in relation to the hemodynamic effects.

Penetration of netilmicin in the lower respiratory tract after once-daily dosing.

A major criticism of the use of aminoglycosides for the treatment of pneumonia is the poor penetration in infected airways. Once-daily dosing of aminoglycosides results in higher peak plasma concentrations without increasing toxic reactions and with optimization of pharmacodynamic properties. To predict intrapulmonary antimicrobial activity after once-daily dosing of aminoglycosides, it is necessary to determine the respective bronchial and alveolar disposition. We prospectively conducted a pharmacokinetic study of netilmicin following the first intravenous administration of a once-daily dosing schedule in 20 ventilated patients with pneumonia. A bronchoscopic sampling of bronchial secretions and a subsegmental bronchoalveolar lavage (BAL) were performed 60, 90, 120, and 180 min (five patients at each time point) on the first treatment day after intravenous administration over 30 min of 450 mg of netilmicin. The netilmicin concentrations in the alveolar lining fluid (ALF) were calculated using urea as an endogenous marker of dilution. In bronchial secretions, a peak concentration of 2.00 (SEM: 0.26) mg/L or 6 percent of the 30-min plasma concentration was reached at 120 min. In ALF, much higher levels were found. At 120 min, a peak ALF concentration of 14.7 (SEM: 2.22) mg/L or 41 percent of the 30-min plasma concentration was reached. Spearman's rank correlation testing failed to show a correlation between bronchial and ALF concentrations. Higher plasma concentrations of netilmicin after once-daily dosing give rise to ALF concentrations exceeding the minimum inhibitory concentration of susceptible respiratory pathogens involved in nosocomial pneumonia, while bronchial concentrations remain low. Aminoglycoside concentrations in bronchial secretions cannot be used to predict alveolar concentrations. Low diffusibility can no longer be considered as a disadvantage of aminoglycosides for treating pneumonias.

Cardiac output-changes during hemodialysis with ultrafiltration.

Cardiovascular hemodynamics were studied noninvasively before, during and after hemodialysis with ultrafiltration in 18 patients on chronic hemodialysis. The cardiac output (CO) was determined by a continuous wave Doppler method. Overall, no major CO changes were seen (7.8 +/- 0.6 l/min post- versus 7.4 +/- 0.5 l/min pre-dialysis). Mean blood pressure rose slightly but significantly from 103 +/- 4 mmHg before to 113 +/- 3 mmHg after hemodialysis (p less than 0.01). Important interindividual differences in the intradialytic evolution of CO were observed. In patients with previous myocardial infarction or dilated cardiomyopathy (n = 12), CO rose significantly from 7.3 +/- 0.7 l/min before to 8.4 +/- 0.6 l/min after hemodialysis (p less than 0.05), while in patients without manifest myocardial disease (n = 6) CO decreased from 7.5 +/- 0.7 l/min to 6.6 +/- 0.9 l/min (NS). Comparison of the evolution of CO in both groups by variance analysis revealed a significant difference (p less than 0.01). It is concluded that, in response to hemodialysis with ultrafiltration, CO probably will increase in patients with myocardial infarction or congestive cardiomyopathy, but probably will decrease in patients without.

Use of dopexamine hydrochloride in patients with septic shock.

The short and long-term hemodynamic effects of iv dopexamine hydrochloride (DPX) were studied in ten patients with septic shock. In the short-term study, a dose-dependent increase in cardiac index and heart rate, and a dose-dependent decrease in systemic vascular resistance were demonstrated. These effects diminished gradually during the long-term study, suggesting a problem of tolerance. Although the administration of DPX during septic shock appeared to be relatively safe, its hemodynamic effects suggest that it may be more indicated in selected patients with a low cardiac output.

Fatal intoxication with amlodipine.

Although poisoning with calcium channel blocking agents is frequent, to our knowledge no cases involving amlodipine have been published. We describe here a case of amlodipine intoxication, in which protracted hypotension did not respond to vasopressor therapy alone. After the addition of continuous calcium chloride and glucagon infusion, blood pressure was restored and vasopressor therapy could be tapered off substantially. When calcium and glucagon were interrupted because of severe hypercalcemia and hyperglycemia, the patient developed irreversible hypotension and died. Either glucagon or calcium or both, and to some extent vasopressors, seem to have constituted effective treatment of hypotension in this case.

Pitfalls in the diagnosis of hypereosinophilic syndrome: a report of two cases.

The idiopathic hypereosinophilic syndrome is empirically defined as the presence of prolonged eosinophilia without identifiable underlying cause, and with evidence of end-organ dysfunction. Virtually any organ system may be involved, most frequently the heart, the central and peripheral nervous system, the lungs and the skin. We report two cases where the diagnosis of hypereosinophilic syndrome was proposed although the classic criteria were not met. In the first case total peripheral eosinophil counts were relatively low, but pathological evidence clearly showed infiltration of eosinophils in the damaged tissues. An hypothesis to explain this discrepancy is formulated. The second case did not fulfil the first feature either, although the clinical presentation and disease course corresponded well with other cases reported in the literature. The delay in diagnosis was caused by early institution of corticosteroids, clearing all evidence of eosinophil involvement in the observed tissue damage.

Formic acid poisoning: case report and in vitro study of the hemolytic activity.

A case of fatal oral poisoning with formic acid resulting in shock, metabolic acidosis, and hemolysis is reported. The formic acid concentration on admission was 348 micrograms/mL, which, together with an increase in lactic acid, contributed to the metabolic acidosis. Because it has been suggested in the literature that formic acid might induce hemolysis via a direct cytotoxic action on the RBCs, an in vitro study was performed using human RBCs in saline, phosphate buffered saline, and plasma in order to define the mechanism of the hemolysis. These experiments indicate that the hemolysis is not a cytotoxic effect of formic acid but is related to the degree of acidity in itself.