Serafino Garella

Renal effects of prostaglandins and clinical adverse effects of nonsteroidal anti-inflammatory agents.

Non-steroidal anti-inflammatory agents ( NSAIA ) are increasingly used in clinical practice. They exert the majority of their therapeutic and adverse effects by inhibiting prostaglandin synthesis. A variety of clinically important side effects have been described following their administration. We review the renal complications, which include sodium retention, interference with the effectiveness of diuretics, impairment of water excretion, development of hyperkalemia, interference with the therapy of hypertension, and induction of at least four different forms of renal failure. The hemodynamic variety of renal failure and the side effects affecting fluid and electrolyte homeostasis are most likely to become manifest in the context of conditions leading to decreased renal perfusion. Guidelines for use of NSAIA , detection of patients at risk, and therapeutic approaches are provided.

Severity of Metabolic Acidosis as a Determinant of Bicarbonate Requirements

Abstract In the treatment of metabolic acidosis, the dose of sodium bicarbonate is usually calculated on the assumption that administered bicarbonate distributes in a space equivalent to 50 per cent of body weight. In a patient with profound metabolic acidosis the apparent space of distribution of bicarbonate was over 200 per cent of body weight, although no excessive ongoing acid production or external bicarbonate losses were evident, suggesting that the pre-existing plasma bicarbonate concentration can influence the apparent space of distribution of bicarbonate. This hypothesis was tested with a standard dose of bicarbonate (2.5 mmoles per kilogram of body weight) in 16 dogs with low, normal or high plasma bicarbonate concentration. The concentration increased by 2.8, 5.0 and 5.6 mmoles per liter in the three groups respectively, indicating that the proportion of administered bicarbonate passing into the intracellular space increases with decreasing concentration. In conditions of profound metabolic aci...

Hemoperfusion to Treat Intoxications

Hemoperfusion is being increasingly proposed and used for the treatment of a large variety of exogenous intoxications. This procedure has been shown to achieve high clearance rates of most common intoxicants, and case reports have claimed that its application has been, on occasion, life-saving. We tabulated our experience in the treatment of 94 consecutive patients with severe intoxications who were treated with supportive management only; this group constituted 25% of all patients admitted with a diagnosis of drug overdose. Of the 94 patients only one died; all others were discharged without sequelae resulting from the intoxication or its complications; only 21% required more than a 48-hour stay in the intensive care unit. We propose that supportive management must remain the mainstay of therapy even in severely intoxicated patients; with few exceptions, hemoperfusion must be considered an as yet unproven form of therapy; further controlled studies are necessary to establish its range of indications, potential benefits, and cost effectiveness.

Prolonged Hemolysis from Overheated Dialysate

A patient with chronic renal failure exposed to overheated dialysate (50 degrees C) for 20 minutes developed evidence of delayed and protracted hemolysis, which continued for several days. By contrast, in the only previously reported similar case, sudden gross hemolysis followed by cardiac arrest occurred. It is emphasized that the rapidity and severity of hemolysis due to thermal injury to erythrocytes are dependent upon the duration of exposure and the height of temperature to which extracorporeal blood is exposed. Methods of preventing such incidents and therapeutic approaches are outlined.

Trimethadione (Tridione(R))-induced nephrotic syndrome: A report of a case with unique ultrastructural renal pathology

Abstract The nephrotic syndrome developed in a 15 year old boy with petit mal epilepsy after he received a total dose of approximately 835 g trimethadione (Tridione®) over a three year period. Proteinuria disappeared without specific treatment approximately six months after administration of the drug was discontinued. A review of the clinical course in this patient and in the previously described patients reveals that trimethadione-induced nephrotic syndrome usually responds to withdrawal of the drug. The renal pathology of trimethadione-induced nephrotic syndrome has not been well defined in the past. In our patient the major finding observed by light microscopy was selective infiltration of glomerular capillary loops with eosinophils. Electron microscopy revealed irregular thickening of the basement membrane which contained heteromorphous granular deposits and membranous-bound structures. Processes of eosinophils were adherent to and occasionally infiltrated through the endothelial layer. Although immunofluorescent stains demonstrated the absence of immunoglobulins G (IgG), M (IgM) and A (IgA) or C′3, the cellular localization of eosinophils in the glomeruli suggests an allergic process. We postulate that the unique ultrastructural alterations observed in this patient represented a hypersensitivity reaction to trimethadione.

Hemoperfusion for Intoxication

Excerpt To the editor: We were delighted that Dr. Better and 14 colleagues (1) took the trouble to comment in their letter in the December issue on our article concerning hemoperfusion (2). Unfortu...

Influence of the Severity of Metabolic Acidosis on the Response to Bicarbonate Administration.

Excerpt In the treatment of metabolic acidosis the amount of NaHCO3needed to produce the desired increment in plasma bicarbonate concentration (HCO3-) is usually calculated assuming an apparent spa...