Increased rejection rates in cardiac transplant associated with dexamethasone.
BACKGROUND
Peri-operative immunosuppression in cardiac transplantation includes the use of intravenous methylprednisolone. During a national shortage, intravenous dexamethasone was substituted for methylprednisolone at standard equivalencies. Methylprednisolone and dexamethasone are used interchangeably in many clinical settings; however, their equivalency has not been demonstrated.


METHODS
Forty-two consecutive cardiac transplant patients were studied retrospectively. All patients received standard triple immunosuppression. Eighteen patients received dexamethasone and 24 methylprednisolone. Twelve patients were included for comparison after the methylprednisolone shortage resolved. Endomyocardial biopsy (EMB) results graded as > or =1B (ISHLT classification) were considered positive for acute cellular rejection.


RESULTS
More patients who received dexamethasone as induction had cellular rejection (12/17; (70%) vs. 14/33; (42%); p=0.05). Four patients were excluded because of deaths unrelated to cardiac function. The increased rate of rejection seen during dexamethasone substitution declined after reinstitution of methylprednisolone (p=0.05).


CONCLUSIONS
Peri-operative high-dose dexamethasone in cardiac transplants was associated with higher rates of acute cellular rejection. The equivalencies of dexamethasone and methylprednisolone differ from accepted standards when used in pulse doses. Peri-operative use of glucocorticoids may rely on mechanisms that are different from those considered in the standard equivalency measures. Pulse doses of dexamethasone and methylprednisolone in transplantation may not be interchangeable at standard equivalencies.
Cochrane
Adam B
AB
Department of Pharmacology, University of Chicago, Chicago, IL 60637, United States.
Husain
Aliya N
AN
Anderson
Allen S
AS
Kim
Antony Y
AY
Fedson
Savitri E
SE
D000328:Adult; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006084:Graft Rejection / Q000139:chemically induced*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D012189:Retrospective Studies
D005938:Glucocorticoids; D003907:Dexamethasone; D008775:Methylprednisolone