Uusaro A, Hartikainen J, Parviainen M, Takala J
Department of Intensive Care, Kuopio University Hospital, Finland.
Crit Care Med. 1995 Apr;23(4):674-80. doi: 10.1097/00003246-199504000-00015.
To study if metabolic stress modifies the thermogenic effect of dobutamine.
Prospective, increasing dose, pharmacologic study.
Laboratory of the Department of Intensive Care Unit at a university hospital.
Twelve normal volunteers.
Dobutamine hydrochloride was infused to 12 healthy male volunteers starting at a dose of 2 micrograms/min/kg and gradually increased to 4 and 6 micrograms/min/kg. Each dose of dobutamine was infused for 20 mins. Metabolic stress was induced in six of the 12 volunteers using a triple hormone infusion (epinephrine, cortisol, and glucagon) before dobutamine, and was continued at a constant rate during the dobutamine infusion. The remaining six volunteers served as the control group and received only dobutamine.
Oxygen consumption (VO2) was measured using a metabolic monitor. Arterial blood pressure was measured noninvasively, and cardiac output was monitored by Doppler echocardiography. Plasma concentrations of dopamine, norepinephrine, and epinephrine were measured in both groups. In the triple hormone group, blood was sampled to measure concentrations of insulin, glucagon, cortisol, free fatty acids, and glycerol to ensure the presence of a metabolic stress reaction. At the maximum dose, dobutamine induced a 19% increase (from 140 +/- 17 to 166 +/- 17 mL/min/m2) in VO2 in the control group and an 11% increase (from 167 +/- 10 to 184 +/- 13 mL/min/m2) in the triple hormone group (p < .05 between the two groups) compared with baseline. No change in the respiratory exchange ratio was seen. The triple hormone infusion alone induced hypermetabolism, a marked hemodynamic response, and increased lipolysis.
Stress, induced by a triple hormone infusion, diminishes the thermogenic effect of dobutamine. In the clinical setting, a > 10% to 15% increase in VO2 in response to dobutamine may not be explained just by the thermogenic effect of the drug.
研究代谢应激是否会改变多巴酚丁胺的产热效应。
前瞻性、递增剂量的药理学研究。
某大学医院重症监护科实验室。
12名正常志愿者。
对12名健康男性志愿者输注盐酸多巴酚丁胺,起始剂量为2微克/分钟/千克,并逐渐增加至4微克/分钟/千克和6微克/分钟/千克。每剂多巴酚丁胺输注20分钟。12名志愿者中有6名在输注多巴酚丁胺前通过输注三种激素(肾上腺素、皮质醇和胰高血糖素)诱导代谢应激,并在多巴酚丁胺输注期间以恒定速率持续。其余6名志愿者作为对照组,仅接受多巴酚丁胺。
使用代谢监测仪测量耗氧量(VO2)。无创测量动脉血压,通过多普勒超声心动图监测心输出量。测量两组中多巴胺、去甲肾上腺素和肾上腺素的血浆浓度。在三联激素组中,采集血样以测量胰岛素、胰高血糖素、皮质醇、游离脂肪酸和甘油的浓度,以确保存在代谢应激反应。在最大剂量时,与基线相比,多巴酚丁胺在对照组中使VO2增加了19%(从140±17增加至166±17毫升/分钟/平方米),在三联激素组中增加了11%(从167±10增加至184±13毫升/分钟/平方米)(两组间p<0.05)。呼吸交换率未见变化。单独输注三联激素会导致代谢亢进、显著的血流动力学反应和脂肪分解增加。
三联激素输注诱导的应激会减弱多巴酚丁胺的产热效应。在临床环境中,多巴酚丁胺引起的VO2增加>10%至15%可能不能仅由药物的产热效应来解释。