Corticosteroid Prophylaxis Research Articles

‘Low-dose’ corticosteroid prophylaxis against fat embolism

‘Low-dose’ corticosteroid prophylaxis against fat embolism

‘Low-dose’ Corticosteroid Prophylaxis against Fat Embolism

The effect of 'low-dose' corticosteroids (9 mg/kg methylprednisolone), given after skeletal trauma, on the incidence of the fat embolism syndrome and isolated arterial hypoxemia was studied in 42 controls and 40 steroid-treated subjects. Fat embolism occurred in ten controls (23.8%) and one steroid-treated subject (2.5%) (p = 0.01). A further 44 subjects developed isolated hypoxemia. This was severe (PaO2 less than 50 mm Hg) in seven of 32 controls (21.9%) and one of 39 steroid-treated subjects (2.6%) (p = 0.01). The overall incidence of hypoxemia was 67.1%, affecting 33 controls (78.6%) and 22 steroid-treated patients (55%) (p less than 0.05). The degree of hypoxemia was severe (PaO2 less than 50 mm Hg) in 12 controls (28.6%) and two (5%) of the steroid-treated subjects (p = 0.005). No control subject died or required mechanical ventilation. One steroid-treated subject without fat embolism died of a fulminant infection. Although methylprednisolone in a relatively low dose provides protection against fat embolism and pulmonary dysfunction after skeletal trauma, the safety of this therapy requires further evaluation.

Effect of corticosteroid prophylaxis on lipopolysaccharide levels associated with intestinal ischemia in cats.

Ischemia of the intestines damages the permeability of the intestinal wall, allowing lipopolysaccharide (LPS) (endotoxin) to leak from the gut lumen into the blood circulation, causing shock and death. We measured LPS levels associated with corticosteroid treatment vs. no treatment in cats whose superior mesenteric artery had been occluded for 60 min. In untreated cats, the preocclusion mean plasma LPS concentration remained stable at 0.069 +/- 0.015 ng/ml. Toward the end of the occlusion period, mean plasma LPS rose to 0.239 +/- 0.032 ng/ml (p less than .01). Release of the clamp and reperfusion with oxygenated blood was followed within 20 min by a large rise in plasma LPS concentration to 0.825 +/- 0.11 ng/ml (p less than .01), which had returned to preocclusion levels about 80 min later. Methylprednisolone (30 mg/kg) was infused into a second group of cats 1.5 h before SMA occlusion. In these cats there was a complete inhibition of the LPS rise both during and after occlusion. These data suggest that the reported beneficial effect of corticosteroids in the treatment of septic shock may be mediated, in part, by reducing LPS leakage from the gut.

Topical Corticosteroid Therapy for Corneal Toxicity from Systemically Administered Cytarabine

Eleven patients with leukemia refractory to conventional therapy were treated with high doses of cytarabine (3 g/m2 intravenously every 12 hours for six days) followed by daunorubicin (30 mg/m2/day intravenously for three days). Each patient received, in a double-masked, randomized manner, either 1% prednisolone phosphate or placebo eyedrops in each eye 12 hours before and along with the cytarabine so that we could determine whether a topical corticosteroid prevents corneal toxicity from systemic cytarabine. Ten of the 11 patients had a significant reduction in the intensity and duration of the symptoms and signs of corneal toxicity in the corticosteroid-treated eye (P less than .0005). In the placebo-treated eye, pain, photophobia, and tearing occurred at a median time of 6.5 days after initiation of therapy but resolved in approximately one week. Patients receiving high doses of intravenously administered cytarabine should receive topical corticosteroid prophylaxis to reduce the corneal toxicity associated with this treatment.

Activation of Plasma Complement by Perfluorocarbon Artificial Blood: Probable Mechanism of Adverse Pulmonary Reactions in Treated Patients and Rationale for Corticosteroid Prophylaxis

Abstract Perfluorocarbons have shown promise as clinical blood substitutes. Although early experience in Japan with one such product--Fluosol-DA-- has been uncomplicated, we observed an adverse pulmonary reaction in the first American patient to receive it and know of similar reactions in two other Americans so treated. Postulating that activation of plasma complement (C) by the perfluorocarbon emulsion might have caused the reaction, we tested the product to determine if it is an activator of complement. Incubation of Fluosol with plasma led to C3 conversion, decrement in CH50, and generation of C5a-related PMN aggregating activity; EDTA prevented such activation, while EGTA did not, suggesting that it proceeded via the alternative C pathway. Infusion of Fluosol into rabbits produced hypoxemia, neutropenia, thrombocytopenia, and pulmonary leukostasis, mimicking abnormalities previously demonstrated in rabbits receiving infusions of zymosan-activated plasma C. These deleterious responses to Fluosol were diminished by premedicating rabbits with corticosteroids (which had seemed to benefit when used empirically in our patient). In vitro and in vivo, Fluosol's effects were reproduced by Pluronic F-68, the nonionic detergent used to maintain the emulsion stability of Fluosol-DA. We conclude that adverse reactions to Fluosol are probably mediated by C activation and that steroid premedication may prevent them in susceptible patients.

Activation of plasma complement by perfluorocarbon artificial blood: probable mechanism of adverse pulmonary reactions in treated patients and rationale for corticosteroids prophylaxis

Perfluorocarbons have shown promise as clinical blood substitutes. Although early experience in Japan with one such product--Fluosol-DA--has been uncomplicated, we observed an adverse pulmonary reaction in the first American patient to receive it and know of similar reactions in two other Americans so treated. Postulating that activation of plasma complement (C) by the perfluorocarbon emulsion might have caused the reaction, we tested the product to determine if it is an activator of complement. Incubation of Fluosol with plasma led to C3 conversion, decrement in CH50, and generation of C5a-related PMN aggregating activity; EDTA prevented such activation, while EGTA did not, suggesting that it proceeded via the alternative C pathway. Infusion of Fluosol into rabbits produced hypoxemia, neutropenia, thrombocytopenia, and pulmonary leukostasis, mimicking abnormalities previously demonstrated in rabbits receiving infusions of zymosan-activated plasma C. These deleterious responses to Fluosol were diminished by premedicating rabbits with corticosteroids (which had seemed to benefit when used empirically in our patient). In vitro and in vivo, Fluosol's effects were reproduced by Pluronic F-68, the nonionic detergent used to maintain the emulsion stability of Fluosol-DA. We conclude that adverse reactions to Fluosol are probably mediated by C activation and that steroid premedication may prevent them in susceptible patients.