Increased Mortality Associated with Growth Hormone Treatment in Critically Ill Adults
Jukka Takala, M.D., Ph.D., Esko Ruokonen, M.D., Ph.D., Nigel R. Webster, M.D., Michael S. Nielsen, M.D., Durk F. Zandstra, M.D., Guy Vundelinckx, M.D., and Charles J. Hinds, M.D.
Background The administration of growth hormone can attenuatethe catabolic response to injury, surgery, and sepsis. However,the effect of high doses of growth hormone on the length ofstay in intensive care and in the hospital, the duration ofmechanical ventilation, and the outcome in critically ill adultswho are hospitalized for long periods is not known.
Methods We carried out two prospective, multicenter, double-blind,randomized, placebo-controlled trials in parallel involving247 Finnish patients and 285 patients in other European countrieswho had been in an intensive care unit for 5 to 7 days and whowere expected to require intensive care for at least 10 days.The patients had had cardiac surgery, abdominal surgery, multipletrauma, or acute respiratory failure. The patients receivedeither growth hormone (mean [±SD] daily dose, 0.10±0.02mg per kilogram of body weight) or placebo until discharge fromintensive care or for a maximum of 21 days.
Results The in-hospital mortality rate was higher in the patientswho received growth hormone than in those who did not (P<0.001for both studies). In the Finnish study, the mortality ratewas 39 percent in the growth hormone group, as compared with20 percent in the placebo group. The respective rates in themultinational study were 44 percent and 18 percent. The relativerisk of death for patients receiving growth hormone was 1.9(95 percent confidence interval, 1.3 to 2.9) in the Finnishstudy and 2.4 (95 percent confidence interval, 1.6 to 3.5) inthe multinational study. Among the survivors, the length ofstay in intensive care and in the hospital and the durationof mechanical ventilation were prolonged in the growth hormonegroup.
Conclusions In patients with prolonged critical illness, highdoses of growth hormone are associated with increased morbidityand mortality.
Source Information
From the Critical Care Research Program, Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland (J.T., E.R.); and the Intensive Care Units at Aberdeen Royal Infirmary, Aberdeen, United Kingdom (N.R.W.); Southampton General Hospital, Southampton, United Kingdom (M.S.N.); Onze Lieve Vrouwe Gasthuis, Amsterdam (D.F.Z.); St. Jans Hospital, Genk, Belgium (G.V.); and St. Bartholomew's Hospital, West Smithfield, London (C.J.H.).
Address reprint requests to Dr. Takala at the Department of Anesthesiology and Intensive Care, Kuopio University Hospital, FIN-70210 Kuopio, Finland.
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