Increased mortality in groups of cattle administered the -adrenergic agonists ractopamine hydrochloride and zilpaterol hydrochloride.
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abstract
The United States Food and Drug Administration (FDA) approved two -adrenergic agonists (AA) for in-feed administration to cattle fed in confinement for human consumption. Anecdotal reports have generated concern that administration of AA might be associated with an increased incidence of cattle deaths. Our objectives, therefore, were to a) quantify the association between AA administration and mortality in feedlot cattle, and b) explore those variables that may confound or modify this association. Three datasets were acquired for analysis: one included information from randomized and controlled clinical trials of the AA ractopamine hydrochloride, while the other two were observational data on zilpaterol hydrochloride administration to large numbers of cattle housed, fed, and cared for using routine commercial production practices in the U.S. Various population and time at-risk models were developed to explore potential AA relationships with mortality, as well as the extent of confounding and effect modification. Measures of effect were relatively consistent across datasets and models in that the cumulative risk and incidence rate of death was 75 to 90% greater in animals administered the AA compared to contemporaneous controls. During the exposure period, 40 to 50% of deaths among groups administered the AA were attributed to administration of the drug. None of the available covariates meaningfully confounded the relationship between AA and increased mortality. Only month of slaughter, presumably a proxy for climate, consistently modified the effect in that the biological association was generally greatest during the warmer months of the year. While death is a rare event in feedlot cattle, the data reported herein provide compelling evidence that mortality is nevertheless increased in response to administration of FDA-approved AA and represents a heretofore unquantified adverse drug event.
