Takala J, Ruokonen E, Webster N R, Nielsen M S, Zandstra D F, Vundelinckx G, Hinds C J
Critical Care Research Program, Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Finland.
N Engl J Med. 1999 Sep 9;341(11):785-92. doi: 10.1056/NEJM199909093411102.
The administration of growth hormone can attenuate the catabolic response to injury, surgery, and sepsis. However, the effect of high doses of growth hormone on the length of stay in intensive care and in the hospital, the duration of mechanical ventilation, and the outcome in critically ill adults who are hospitalized for long periods is not known.
We carried out two prospective, multicenter, double-blind, randomized, placebo-controlled trials in parallel involving 247 Finnish patients and 285 patients in other European countries who had been in an intensive care unit for 5 to 7 days and who were expected to require intensive care for at least 10 days. The patients had had cardiac surgery, abdominal surgery, multiple trauma, or acute respiratory failure. The patients received either growth hormone (mean [+/-SD] daily dose, 0.10 +/- 0.02 mg per kilogram of body weight) or placebo until discharge from intensive care or for a maximum of 21 days.
The in-hospital mortality rate was higher in the patients who received growth hormone than in those who did not (P<0.001 for both studies). In the Finnish study, the mortality rate was 39 percent in the growth hormone group, as compared with 20 percent in the placebo group. The respective rates in the multinational study were 44 percent and 18 percent. The relative risk of death for patients receiving growth hormone was 1.9 (95 percent confidence interval, 1.3 to 2.9) in the Finnish study and 2.4 (95 percent confidence interval, 1.6 to 3.5) in the multinational study. Among the survivors, the length of stay in intensive care and in the hospital and the duration of mechanical ventilation were prolonged in the growth hormone group.
In patients with prolonged critical illness, high doses of growth hormone are associated with increased morbidity and mortality.
生长激素的使用可减轻机体对损伤、手术及脓毒症的分解代谢反应。然而,大剂量生长激素对长期住院的危重症成年患者在重症监护病房及医院的住院时间、机械通气时间及预后的影响尚不清楚。
我们进行了两项前瞻性、多中心、双盲、随机、安慰剂对照的平行试验,涉及247名芬兰患者和其他欧洲国家的285名患者,这些患者在重症监护病房已住院5至7天,预计至少需要10天的重症监护。患者接受了心脏手术、腹部手术、多发伤或急性呼吸衰竭。患者接受生长激素(平均[±标准差]每日剂量,0.10±0.02毫克/千克体重)或安慰剂,直至从重症监护病房出院或最长21天。
接受生长激素治疗的患者的院内死亡率高于未接受生长激素治疗的患者(两项研究P均<0.001)。在芬兰的研究中,生长激素组的死亡率为39%,而安慰剂组为20%。多国研究中的相应死亡率分别为44%和18%。在芬兰的研究中,接受生长激素治疗的患者的死亡相对风险为1.9(95%置信区间,1.3至2.9),在多国研究中为2.4(95%置信区间,1.6至3.5)。在幸存者中,生长激素组在重症监护病房及医院的住院时间和机械通气时间延长。
在危重症持续时间较长的患者中,大剂量生长激素与发病率和死亡率增加相关。