The pathologic effects of intrathecal betamethasone.
METHODS
The histopathologic effects of the intrathecal injection of betamethasone (Celestone Chronodose; Schering Corporation, Kenilworth, New Jersey) were assessed after the injection of various volumes of the preparation in 20 sheep.


OBJECTIVE
To assess the safety of Celestone Chronodose injected into the intrathecal space.


BACKGROUND
The safety and efficacy of epidural steroid have received considerable attention in the medical literature in recent years. In Australia, reports of possible adverse effects of Depo-Medrol (methylprednisolone), including the complication of arachnoiditis, have been followed by statements from the manufacturers of commonly used steroid preparations recommending they should not be administered epidurally. Previous evidence suggests that arachnoiditis does not result from epidural administration of steroids, but may develop from the intrathecal administration of Depo-Medrol. There are no reports concerning the safety of Celestone Chronodose (beta-methasone).


METHODS
Twenty-three adult merino sheep had lumbar punctures performed at the L6-S1 level, and different volumes of Celestone Chronodose or normal saline were injected into the subarachnoid space. The animals were killed after 6 weeks, and the spinal cord, meninges, and nerve roots of the lumbar spine were examined for evidence of pathologic changes.


RESULTS
There were no abnormalities demonstrated in three sheep injected with up to 18 ml of normal saline solution. Eleven sheep injected with 1 ml (5.7 mg) of Celestone Chronodose even when repeated at weekly intervals (five sheep, three injections) did not demonstrate pathologic changes. One of six sheep injected with 2 ml of Celestone Chronodose and all of three sheep injected with greater volumes showed histopathologic changes of arachnoiditis.


CONCLUSIONS
Given that the volume of cerebrospinal fluid in the sheep is approximately one third of that in humans, this study suggests that small volumes (up to 2 ml) of Celestone Chronodose injected intrathecally in humans are unlikely to cause arachnoiditis, but that the risk of this complication increases substantially with higher doses.
Latham
J M
JM
Department of Orthopaedic Surgery and Trauma, Royal Adelaide Hospital, Australia.
Fraser
R D
RD
Moore
R J
RJ
Blumbergs
P C
PC
Bogduk
N
N
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001623:Betamethasone / Q000031:analogs & derivatives / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D004824:Epidural Space / Q000187:drug effects / Q000473:pathology; D005260:Female; D007278:Injections, Spinal; D008297:Male; D008578:Meninges / Q000187:drug effects* / Q000473:pathology*; D012449:Safety; D012756:Sheep; D013346:Subarachnoid Space / Q000187:drug effects / Q000473:pathology
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; C018230:betamethasone acetate phosphate; D001623:Betamethasone