Intra-arterial injection in the rat brain: evaluation of steroids used for transforaminal epidurals.

STUDY DESIGN: Prospective in vivo experimental animal model. OBJECTIVES: To determine the effect of intra-arterial injection of the steroids commonly used for transforaminal epidurals on the central nervous system. And to determine if all of the steroids have the same effect. SUMMARY OF BACKGROUND DATA.: Transforaminal epidural steroid injection is commonly employed to treat radicular pain. This approach is associated with complications, including stroke and death. While the mechanism is unknown, the leading hypothesis is that intravascular injection of particulate steroids leads to microembolization. METHODS: To characterize the nature of steroid induced injury, a rodent model was employed. The internal carotid artery was dissected and its branches ligated. The external carotid artery was ligated, mobilized, cannulated, and injectate administered. Five solutions were tested: Depo-Medrol (N = 11), Depo-Medrol carrier (N = 6), Solu-Medrol (N = 6), Decadron (N = 8), and normal saline (N = 7). Drugs, in volume of 50 microL, were injected into the ICA via the ECA cannula at 25 microL/min. The extent of central nervous system injury was evaluated by analysis of coronal sections of the brain. RESULTS: Cerebral hemorrhage occurred in test subjects with the following frequency: 8 of 11 in the Depo-Medrol group, 7 of 8 in the Solu-Medrol group, and 3 of 6 in the Depo-Medrol carrier group; no lesions were identified in the Decadron or saline groups (P < 0.01). Evan's blue dye leakage was detected in the Depo-Medrol and Solu-Medrol groups, but not the Decadron or saline groups. CONCLUSION: This study presents the first in vivo evaluation of intra-arterial steroid injection. Data demonstrate Depo-Medrol, as well as its nonparticulate carrier, and Solu-Medrol can produce significant injury to the blood-brain barrier when injected intra-arterially. These results demonstrate that injury is produced not only by particulate obstruction of the cerebral microvasculature, but also by toxicity of the carrier or steroid (methylprednisolone).

[An auto-iatrogenic disease]. / Ein auto-iatrogenes Leiden.

A 55-year-old practitioner from an island in the northern sea felt an increasing hypersensitivity of his entire body to various ambient and nutritional allergens and toxics. He started to treat himself with increasing doses of glucocorticoids and moved to a southern climate in Lanzarote and later on to the Swiss mountains in the grisons. On admission to our hospital in December he was in a disastrous psychotic condition, trying to cool down his body by laying naked on his bed at ambient temperatures around the freezing point. He had consumed on average 250 mg prednisone daily over weeks. As we found out later his personal assistant travelling with him was giving him glucocorticoids through the infusion during his hospital stay. He developed a necrotizing septic phlebitis at the infusion site followed by a Pseudomonas aeruginosa sepsis with fatal multiorgan failure. This case illustrates the dangers of self-treatment by doctors and the difficulties in treating a physician.

The differential effect of corticosteroids on wound disruption strength in mice.

The detrimental role of corticosteroids on wound healing is well recognized. This study examined the effect of equipotent anti-inflammatory doses of dexamethasone sodium phosphate, methylprednisolone sodium succinate, or hydrocortisone sodium succinate on wound healing in mice. Mice were injected daily for 12 days; the mice were wounded on day 3 of steroid injection, with wound analysis done on day 10 after wounding. Dexamethasone and hydrocortisone significantly impaired wound healing, as assessed by wound disruption strength when compared with controls or methylprednisolone. Dexamethasone and hydrocortisone both displayed dose-dependent relationships for impairment of healing, while over comparative doses, methylprednisolone failed to affect healing significantly. Regression analysis revealed nearly identical curves for hydrocortisone and dexamethasone that differed significantly from that of methylprednisolone. Our observations suggested that these preparations possessed a differential effect on the healing wound that should be considered to minimize postsurgical or traumatic wound-healing problems.

An attempt to develop a model to study the effects of intrathecal steroids.

An attempt has been made to develop a chronic inflammatory arachnoiditis model in the rat to study the influence of subarachnoid or epidural steroids. Through chronically implanted catheters in Wistar rats (250-350 g), either triamcinolone (3.5-350 micrograms) or methylprednisolone (3.5-350 micrograms) was injected intrathecally, daily for 7 days or weekly for 7 weeks. Some rats also received 100 mg kg-1 cefoxitin and 0.5 mg deoxycortone by intramuscular injection. Equivalent control groups were included. High doses of intrathecal steroids caused marked weight loss and infection and many rats died. These effects were mitigated at a lower dosage especially by the addition of cefoxitin and deoxycortone. The effects of triamcinolone were more marked than those of methylprednisolone. No systematic histological evidence of neurotoxicity was observed after either steroid. Injections of talc failed to cause arachnoiditis or meningitis probably because sufficient particulate talc could not be injected through the narrow catheter.

Influence of 6 alpha-methylprednisolone 21-sodium succinate on the pituitary, adrenal glands, and the gastrointestinal tract in rats. (Comparative toxicity study with hydrocortisone 21-sodium succinate).

A comparative toxicity study with 6 alpha-methylprednisolone 21-sodium succinate (MPS) and hydrocortisone 21-sodium succinate (HCS) was carried out on male rats of the Wistar strain. MPS and HCS were administered intravenously to rats in dose levels of 20 or 100 mg/kg/day for 14 days. There were no significant differences in the pituitary weights in MPS and HCS groups, but weight of the adrenal glands decreased with increasing dose levels of MPS and HCS. Histopathological examination of MPS and HCS treated rats revealed atrophy of the zona fasiculata in the adrenal cortex which correlated with dose levels. The decline of serum corticosterone levels in rats correlated with increasing dose levels of MPS and HCS. It can be concluded that the inhibitory effect of MPS on the pituitary-adrenal system in rats was the same as HCS. No ulceration was observed in the gastro-intestinal tract of MPS of HCS treated rats.