Immediate Hemodynamic Effect of Pharmacological Doses of Methylprednisolone in Dogs, and the Influence of Speed of Injection

Abstract

Reports of sudden death of patients during i.v. administration of methylprednisolone (M.P.) prompted the present study of the hemodynamic effect of M.P. given i.v. to dogs. Fifteen healthy, mongrel dogs were anesthetized with thiomebumal, fentanyl, droperidol, pancuronium and N2O/O2. With ventilation and circulation in steady state, M.P. 30 mg/kg b.w. was given i.v. either as a push bolus (n=7) or over a 5-min period (n=8). In the bolus group, mean aortic pressure (MAP) and systemic vascular resistance (SVR) had decreased to 72 and 60%, respectively, 1 min after the start of the steroid injection, while heart rate (HR), cardiac index (CI), mean pulmonary arterial pressure (MPAP) and left ventricular work (LVW) had not changed significantly. In the 5-min group, the HR increased by 23%, while the other parameters were unchanged during the injection period. Within 5 min after the termination of the steroid injection all hemodynamic parameters had returned to pre-injection levels in both groups. Sodium, potassium, magnesium, protein and calcium in serum were unchanged in both groups during the injection period and in the following 15 min. A significant, transient fall in ionized calcium was observed in all six dogs in which this ion was measured. It was concluded that rapid i.v. injection of pharmacological doses of M.P. in hemodynamically stable, anesthetized dogs causes immediate, transient decreases in SVR and MAP. The mechanisms may be an alpha adrenergic blocking action or a direct effect on the muscles in the peripheral vessels, combined with a negative inotropic effect on the myocardium, possibly mediated through an impeded calcium release.

Allergic-Type Reactions to Corticosteroids

“…Husum et al 44 performed a similar study in dogs and confirmed that rapid bolus administration can cause a drop in systemic vascular resistance, hypotension, and a decrease in ionized calcium. Certain patients may be intolerant of these circulatory changes.…”

Immunoglobulin e-mediated reactions to corticosteroids

“…Erstad [37] noted that patients who had adverse cardiovascular reactions to corticosteroids had received individual doses of at least 250 mg of methylprednisolone or its equivalent, usually administered over a short period of time (30 minutes or less). A study in dogs found that a rapid infusion of high-dose methylprednisolone resulted in a decrease in systemic vascular resistance, mean aortic pressure, and ionized calcium [38], all of which could lead to cardiovascular collapse. The proposed mechanism for the observed findings was an α-adrenergic blockade and a direct negative effect of the steroid on the myocardium.…”

Immediate-Type Hypersensitivity to Succinylated Corticosteroids

“…In these cases, inhibition of cyclooxygenase is suggested to cause bronchospasm by blocking prostaglandin production which results in increased leukotriene production [30,31]. Others suggested that some of these reactions, such as cardiovascular collapse, can be explained by rapid infusion of a considerable amount of corticosteroids, causing a decrease in cardiac output, secondary to α-adrenergic blockade and a negative inotropic effect [32,33]. …”