Metabolic and haemodynamic effects of dopamine plus domperidone in volunteers

There are no studies of the relationship between infusion rate of dopamine and the arterial and venous dopamine plasma concentration and the resulting haemodynamic and metabolic effects. Dopamine was administered to seven volunteers using five infusion rates (1, 3, 6, 9, 13 μg/kg per minute) in an escalating sequence lasting for 30 min for each step. Since dopamine can cause nausea and vomiting, this relationship was investigated after administration of domperidone for infusion rates above 3μg/kg per minute. Haemodynamic effects were assessed using 2-dimensional echocardiography. During the highest infusion rate the arterial plasma dopamine concentration reached 1,379±181 nmol/l. There was a linear correlation between the dopamine infusion rate and both the arterial and the venous plasma concentration. There was no significant change in heart rate or diastolic blood pressure. Systolic blood pressure, ejection fraction and cardiac index increased in a dose-dependent manner. Systemic vascular resistance decreased during the two low doses of dopamine and was not different from baseline values during the three high infusion rates. The plasma concentrations of glucose and non-esterified fatty acids increased from 5.3±0.4 to 6.8±0.9 nmol/l, and from 360±119 to 971±307 μmol/l, respectively, during the 13 μg/kg per minute infusion rate. As the plasma noradrenaline concentration increased up to 7.84±2.46 nmol/l in correlation to the dopamine plasma concentration, an indirect sympathomimetic effect may contribute to the actions of dopamine plasma concentration.     

Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man

1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects by, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x PNa, where PNa is plasma sodium concentration] increased (P less than 0.001), and fractional distal sodium reabsorption [(CLi-CNa)/CLi] decreased (P less than 0.001). 3. It is concluded that natriuresis during low-dose dopamine infusion is caused by an increased outflow of sodium from the proximal tubules that is not fully compensated for in the distal tubules.     

The effect of low-dose dopamine infusion on anterior pituitary hormone secretion in normal female subjects

The effect of low-dose dopamine infusion on anterior pituitary hormone secretion in a group of seven healthy female subjects is reported. Subjects were infused with NaCl solution (154 mmol/l) (control) or dopamine (0.01 and 0.1 micrograms min-1 kg-1 for 120 min at each rate) on separate days in the early follicular phase of consecutive menstrual cycles. Serum prolactin decreased during infusion of dopamine at 0.01 micrograms min-1 kg-1 but a similar fall was found in the control group. When the rate of dopamine infusion was increased to 0.1 micrograms min-1 kg-1 a further substantial decrease in prolactin concentration occurred, whereas prolactin in the control group showed no change. At the end of the period of dopamine infusion at 0.1 micrograms min-1 kg-1 serum prolactin remained significantly (P less than 0.025) lower than in the control group (85 +/- 12 vs 180 +/- 21 m-units/1). No change in thyrotrophin (TSH), growth hormone (GH) or luteinizing hormone (LH) was seen during either rate of dopamine infusion compared with control. While dopamine infusion at 0.1 micrograms min-1 kg-1 caused significant inhibition of prolactin secretion in normal female subjects, other pituitary hormone secretion was not affected: it is suggested that under the conditions of this study dopamine in hypophysial portal blood is not of primary importance in the control of basal TSH, GH and LH release.     

Effects of extracellular fluid volume changes on renal response to low-dose dopamine infusion in normal women

Summary. Dopamine (DA) i.v. infused in a low dose (0·1 (μg/kg/min) in healthy women during sustained hypotonic polyuria, produced different renal functional effects as variations in extracellular fluid volume occurred. (1) In hydro-saline retention (n= 23), induced by desoxycorticosterone acetate treatment, DA produced typical vasodilator and hydro-natriuretic effects (Goldberg, 1972). (2) In hydro-saline depletion (n= 19), induced by diuretic treatment and low dietary sodium intake, DA lost its vasodilator and natriuretic efficacy, manifesting, on the other hand, renal sodium conserving effects mainly dependent on the increase in distal sodium reabsorption and a trend towards afferent arteriolar vasoconstriction. (3) Treatment with prazosin (n= 9) or propranolol (n= 9) in hydro-saline depletion, was efficacious in partly restoring the typical vasodilator and natriuretic effects of DA. Thus, in hydro-saline depletion, DA produced sympathomimetic effects which were sufficiently intense to outweigh those due to activation of specific DA renal receptors.     

Metabolic effects of norepinephrine and dobutamine in healthy volunteers

The objective of the present study was to evaluate the effects of norepinephrine (n = 9) and dobutamine (n = 7) on carbohydrate and protein metabolism in healthy volunteers in comparison with a control group (n = 9). Norepinephrine (0.1 microg/kg min), dobutamine (5 microg/kg min), or placebo was infused for 240 min. The plasma concentration of glucose, lactate, epinephrine, norepinephrine, insulin, and glucagon were determined. Glucose and urea production and leucine flux were measured using a tracer technique. Norepinephrine caused a persisting rise in plasma glucose concentration, whereas the increase in glucose production was only transient. A minor increase in plasma lactate concentration was observed, but it did not exceed the physiological range. No change in leucine flux, urea production, or plasma concentration of insulin, glucagon, or epinephrine was found. Dobutamine slightly decreased glucose production, whereas the plasma concentration of glucose and lactate did not change. The reduction in leucine flux was paralleled by a decrease in urea production. No change in the plasma concentration of insulin, glucagon, or the catecholamines was observed. In conclusion, both norepinephrine and dobutamine have only minor metabolic effects. Because glucose production is enhanced by alpha1- and beta2-adrenoceptor stimulation, we conclude that dobutamine is only a weak agonist at these adrenoceptors. These minor metabolic actions may make both compounds suitable for critically ill patients because no further increase in metabolic rate should be caused.     

Metabolic effects of dobutamine in normal man.

1. Dobutamine in 5% (w/v) D-glucose was infused at sequential doses of 2, 5 and 10 micrograms min-1 kg-1, 45 min at each dose, into eight healthy male subjects, and the effects were compared with those produced by infusion of the corresponding volumes of 5% (w/v) D-glucose alone. 2. The energy expenditure increased and was 33% higher than control (P less than 0.001) at 10 micrograms of dobutamine min-1 kg-1. The respiratory exchange ratio decreased from 0.85 (SEM 0.02) before infusion to 0.80 (SEM 0.01) at 10 micrograms of dobutamine min-1 kg-1, but did not alter during the placebo infusion (P less than 0.001). 3. Plasma noradrenaline concentrations were lower during the dobutamine infusion compared with during the infusion of D-glucose alone (P less than 0.025). Plasma dopamine concentrations remained below 0.1 nmol/l throughout both infusions. 4. Compared with during the placebo infusion, the blood glucose concentration decreased (P less than 0.001), the plasma glycerol and free fatty acid concentrations increased by 150 and 225%, respectively (both P less than 0.001), and the plasma potassium concentration decreased from 3.8 (SEM 0.07) to 3.6 (SEM 0.04) mmol/l (P less than 0.01) during dobutamine infusion. The plasma insulin concentration increased at 2 and 5 micrograms of dobutamine min-1 kg-1 (P less than 0.001) with no further rise at 10 micrograms of dobutamine min-1 kg-1. 5. Compared with during the placebo infusion, the systolic and diastolic blood pressures and the heart rate increased during dobutamine infusion (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Maturation-related differences in regional circulatory effects of dopamine infusion in swine

The cardiovascular effects of dopamine (DPA) infusions were evaluated in developing swine, less than or equal to 1 day, 2 weeks, and 2 months of age, anesthetized with halothane in 50% N2O and O2. DPA was given by intravenous infusion in randomized doses of 2, 5, 10 and 20 micrograms/kg/min for 10 min. Depressor responses and bradycardia were observed during 2 micrograms/kg/min in 2-week-olds and during 2, 5 and 10 micrograms/kg/min in 2-month-olds. During infusion of 20 micrograms/kg/min, DPA pressor responses were observed in animals less than or equal to 2 weeks of age; in addition, tachycardia occurred in 1-day-old swine. Renal resistance decreased during infusion of 2 micrograms/kg/min in all swine. It increased during 10 and 20 micrograms/kg/min in the 1-day and 2-week groups, but not in the 2-month group. Mesenteric resistance decreased during infusion of 2, 5 and 10 micrograms/kg/min in less than or equal to 2-week-olds and at all doses in 2-month-olds. Following combined alpha- and beta-adrenergic receptor blockade, infusion of 20 micrograms/kg/min DPA inhibited renal vasoconstriction in most animals and elicited mesenteric vasodilation in all. The results indicate that dopaminergic responses undergo a postnatal maturation which has a different time course for different regional circulations.     

Morphine-6-glucuronide: effects on ventilation in normal volunteers

The respiratory responses to intravenous morphine sulphate (0.12 mg/kg), morphine-6-glucuronide (M6G: 0.03 mg/kg) and placebo were assessed in 6 healthy volunteers, using a single blind randomised crossover design. Five of these subjects underwent an additional study of M6G at 0.06 mg/kg. Respiratory rate, minute volume and end-tidal CO2 were continuously measured using a low resistance non-rebreathing circuit, a mass spectrometer and a dry gas meter. The ventilatory responses to CO2 exposures (5.5% for 4 min) were assessed 40 and 20 min before, and 20, 40 and 80 min after drug administration. Following placebo and M6G (at both doses) no change in end-tidal CO2 occurred whilst the subjects were breathing air, whereas following morphine a significant rise was seen (P less than 0.05). Morphine reduced the ventilatory response to 5.5% CO2 at all times tested (P less than 0.05) and M6G (at both doses) reduced the response to CO2 at 20 and 40 min after administration, but to a lesser degree than did morphine (P less than 0.05).     

Reinforcing and subjective effects of several anorectics in normal human volunteers

A discrete-trial choice procedure was used to examine the reinforcing and subjective effects of four anorectic drugs (mazindol, benzphetamine, phenylpropanolamine and phenmetrazine) in groups of normal healthy adults. For each experiment, subjects first sampled placebo and a dose of one of the drugs (mazindol: 0.5, 1.0 and 2.0 mg; benzphetamine: 25 and 50 mg; phenylpropanolamine: 12.5, 25 and 50 mg; phenmetrazine: 25 and 50 mg; all p.o.). Subjects were then allowed to choose between drug and placebo on five separate occasions. The relative frequency with which active drug was chosen over placebo was used as an index of the drug's reinforcing efficacy. Subjective effects were measured with an experimental version of the Profile of Mood States, a short form of the Addiction Research Center Inventory and a series of visual analog scales. The rank order for reinforcing efficacy was benzphetamine approximately phenmetrazine greater than placebo greater than phenylpropanolamine much greater than mazindol. Ratings of drug liking were positively correlated with number of drug choices for each drug. Benzphetamine and phenmetrazine produced subjective effects characteristic of amphetamine-like drugs and increased ratings of drug liking. Mazindol produced only dysphoric subjective effects and decreased ratings of drug liking. Phenylpropanolamine had no significant effects on subjective measures or drug-liking ratings. These findings are consistent with the presumed dependence potential of these compounds, and demonstrate the validity of this experimental paradigm for assessing the reinforcing effects of anorectics in normal human volunteers.     

Renal effects of low-dose dopamine during vasopressor therapy for posttraumatic intracranial hypertension

Objective: To investigate the effects of low-dose dopamine (Dop) on renal hemodynamics and function in patients with brain trauma receiving norepinephrine (NE). Design: Prospective clinical study. Setting: Surgical intensive care unit of a university hospital. Patients: 20 stable, non-septic, mechanically ventilated, sedated patients with brain trauma and normal renal function treated with intravenous NE (0.11–0.65 μg/kg per min) to maintain an adequate cerebral perfusion pressure (> 60 mm Hg). Interventions: Two successive 1-h study periods with NE alone then NE + Dop (2 μg/kg per min). During each period, creatinine (Cl_CREAT), sodium (Cl_Na), potassium (Cl_K), osmolar (Cl_OSM) and free water (Cl_{H2 O}), clearances were measured in all the patients. Effective renal blood flow (ERBF, paraaminohippurate clearance) and glomerular filtration rate (GFR, inulin clearance) were measured in 7 of the 20 patients. Results: Dop during NE infusion induced increases in urine flow and natriuresis which were not correlated with possible changes in arterial pressure. Cl_CREAT, GFR and their difference remained unchanged, whereas ERBF tended to increase. Fractional sodium excretion [100 × (Cl_Na/Cl_CREAT) ] and Cl_K increased during Dop infusion. Conclusion: The mechanism of Dop-induced natriuresis during NE infusion in brain trauma patients seems mainly related to a direct tubular effect of the drug. Received: 13 July 1998 Accepted: 7 January 1999     

小剂量多巴胺和多巴酚丁胺对非少尿型肾功能衰竭的影响

目的探讨小剂量多巴胺和多巴酚丁胺对非少尿型肾功能衰竭患者肾功能的影响。方法29例血流动力学稳定的非少尿型肾功能衰竭患者,采用随机数字表法选择给药顺序,对照组给予质量分数为5%的葡萄糖,多巴胺组给予多巴胺5μg·kg-1·min-1,多巴酚丁胺组给予多巴酚丁胺5μg·kg-1·min-1;用微量注射泵持续静脉泵入一种药物4h后更换另一种药物,为消除上一种药物对各项监测指标的影响,每种药物更换前间隔1h再进入下一种药物观察阶段。每给一种药物后用SwanGanz导管监测患者的血流动力学指标变化;同时取血、尿测定肾功能指标。结果与对照组相比多巴胺、多巴酚丁胺能明显增加心率(HR)、心排血指数(CI)、尿量和肌酐清除率(CCr),差异均有显著性;多巴胺较多巴酚丁胺能更加明显地增加尿量和钠排泄分数(FeNa),差异均有显著性;而多巴酚丁胺增加CCr的程度与多巴胺比较差异无显著性。结论多巴胺和多巴酚丁胺对非少尿型肾功能衰竭均有增加HR、CI、尿量、FeNa和CCr的作用,多巴胺较多巴酚丁胺增加尿量和FeNa更明显,多巴酚丁胺增加CCr与多巴胺相比差异无显著性。     

The effect of intravenous frusemide on urine dopamine in normal volunteers: studies with indomethacin and carbidopa

1. The urine dopamine response to intravenous frusemide (30 mg) was investigated in 15 salt replete male volunteers. The effects of oral indomethacin (100 mg) and oral carbidopa (100 mg) given before intravenous frusemide were studied in the same group of subjects. 2. Frusemide produced a significant increase in urine dopamine output within 15 min. 3. Indomethacin attenuated the natriuretic and renin responses to frusemide, but did not alter urine dopamine output. 4. Carbidopa lowered urine dopamine to undetectable levels, but did not significantly affect the natriuretic and renin responses to frusemide. 5. We conclude that urine dopamine excretion after frusemide is not directly related to increased sodium excretion or renin response and it is not mediated by the prostaglandins. In addition, dopamine does not contribute to the renal actions of frusemide under normal conditions.     

Psychomotor and cognitive effects of piribedil, a dopamine agonist, in young healthy volunteers

Piribedil is a dopamine agonist acting on D2 and D3 central nervous system dopamine receptors. This drug has been administered to 12 young healthy male volunteers (age 22 +/- 2 years) according to a single center randomized, double-blind, two ways cross-over, placebo controlled trial, including a washout period of one week. Placebo and piribedil were administered by a single intravenous infusion over 2 h (3 mg). Psychomotor performance and cognitive functions were assessed through a standardized and computerized psychometric tests battery and a continuous electroencephalogram (EEG) mapping. Piribedil improved simple reaction time (P=0.02), immediate (P=0.045 and 0.004), and delayed free recall (P=0.05), dual coding test (P=0.02) and increased theta and fast beta waves on the EEG (P < 0.05 and 0.001, respectively). No deleterious effect was observed on the tests exploring attention and concentration via the other procedures. It is concluded that a single intravenous perfusion of piribedil 3 mg improves alertness and the information processing speed within the central nervous system, in healthy volunteers.     

Effect of large volume infusion on left ventricular volumes,performance and contractility parameters in normal volunteers

Objective Characterize the normal human cardiovascular response to large volume infusion of normal saline.Design: Prospective, interventional trial.Setting ICU procedure room.Participants Healthy male volunteers (n=32).Interventions Volumetric echocardiography during 4-L saline infusion (3 L over 3 h followed by 1 L over 2 h).Measurements and results Following 3-L saline infusion, stroke volume and cardiac output increased approximately 10% without a significant change in heart rate or blood pressure. A decrease in end-systolic volume contributed to the increase in stroke volume to an extent similar to that provided by the increase in end-diastolic volume. All contractility indices except end-systolic wall stress/end-systolic volume index were increased at 3 h post-initiation of saline infusion. Stroke volume but not cardiac output remained elevated at 5 h with persistence of ventricular volume responses; only ejection fraction was significantly elevated among the contractility indices. Afterload measures including total peripheral resistance and end-systolic wall stress were significantly decreased after 3-L infusion but were unchanged compared to baseline following infusion of an additional 1 L over 2 h. Modeled blood viscosity studies demonstrate that changes in apparent contractility after 3-L saline infusion can be explained solely by viscosity reduction associated with hypervolemic hemodilution.Conclusion The initial increase in stroke volume associated with high volume saline infusion in normal volunteers is associated with increases of most load-dependent and ostensibly load-independent parameters of left ventricular contractility. This phenomenon is unlikely to represent a true increase in contractility and appears to be caused by reduced afterload as a consequence of decreased blood viscosity. This decrease in blood viscosity may complicate analysis of some previous in vivo studies examining the effect of volume loading on cardiac function using low-viscosity solutions.Electronic Supplementary Material Supplementary material is available in the online version of this article at An editorial regarding this article can be found in the same issue ()     

The renal and neurohumoral effects of the addition of low-dose dopamine in septic critically ill patients

OBJECTIVES: Dopamine exerts a complicated action on the cardiovascular-renal and neurohumoral systems. We evaluated the effects of the addition of different doses of dopamine on top of treatment with norepinephrine on the haemodynamics, renal function and neurohormones of septic shock patients. DESIGN: Open, uncontrolled, dose-finding study. SUBJECTS: Dopamine was administered, after fluid resuscitation, to septic shock patients who were more than 2 h haemodynamically and pulmonary stable with the use of a constant dose norepinephrine. Patients with a serum creatinine above 180 micromol x l were excluded. METHODS: Dopamine doses of 0, 2, 4, 6 and 0 microg x kg(-1) x min(-1) were given consecutively for 1 h each. Neurohormones were measured hourly after baseline levels had been taken. Systemic haemodynamics were measured using a pulmonary artery (PA) catheter every 30 min, whereas urine collections were examined every hour during the study period. RESULTS AND STATISTICAL ANALYSES: Eight patients (mean age 46 +/- 13 years, M/F 3/5) were included. The median norepinephrine dose at the start of the study was 0.29 microg x kg(-1) x min(-1) (range 0.07-0.48 microg x kg(-1) x min(-1)). Cardiac output (CO) rose during the dopamine infusion for all doses from 7.9 +/- 1.74 l/min to a maximum of 10.1 +/- 1.71 l/min, achieved at the 4 microg x kg(-1) x min(-1) dopamine dose, whereas systemic vascular rate (SVR) decreased slightly for all doses. Heart rate remained unchanged during the 2 microg x kg(-1) x min(-1) dose of dopamine but increased for the 4 and 6 microg x kg(-1) x min(-1) doses from 108 +/- 17 to a maximum of 124 +/- 24 beats/min. Filling pressures remained unchanged whereas the mean arterial blood pressure increased (from 83 +/- 7 to 93 +/- 11 mmHg). Plasma renin activity (PRA) was relatively high (but remained unchanged) as were aldosterone levels. Sodium excretion and diuresis increased for all doses, accompanied by an increase of fractional sodium excretion at the 4 and 6 microg x kg(-1) x min(-1) doses of dopamine. Creatinine clearances remained unchanged. All changed values returned to baseline values after cessation of the dopamine administration. CONCLUSION: During norepinephrine infusion, increasing doses of dopamine from 2 to 6 microg x kg(-1) x min(-1) augments CO, diuresis and sodium excretion in patients treated for septic shock, without changes in creatinine clearance. Higher doses of dopamine (4 and 6 microg x kg(-1) x min(-1)) also induce an increase in heart rate. PRA, aldosterone and norepinephrine levels remain unchanged during dopamine infusion.     

Renal effects of low-dose dopamine in patients with sepsis syndrome or septic shock treated with catecholamines

Objective To evaluate the renal effects of low-dose dopamine in patients with sepsis syndrome or septic shock treated with catecholamines.Design Prospective, clinical study using sequential periods.Setting A 12-bed surgical intensive care unit in a university hospital.Patients 14 patients with sepsis syndrome and 15 patients with septic shock treated with exogenous catecholamines were studied. They had no diuretic treatment.Intervention Two periods of 2 h each with and without 2g·kg^–1·min^–1 of dopamine infusion. Hemodynamic and renal data were obtained at the end of each period. Measurements were repeated after 48 h of dopamine infusion in patients with sepsis syndrome. All data were evaluated by the Wilcoxon rank test.Measurements and results In patients with sepsis syndrome, diuresis and creatinine clearance increased significantly by 100% and 60%, respectively, during low-dose dopamine infusion without any change in systemic hemodynamics. The renal response to dopamine decreased significantly after 48 h of dopamine infusion (P<0.01). In patients with septic shock treated with catecholamines, no variation of either systemic hemodynamics or renal function was noted during low-dose dopamine infusion.Conclusion The renal effects of low-dose dopamine in patients with sepsis syndrome decrease with time. No renal effect of low-dose dopamine was observed in patients with septic shock treated with catecholamines. These findings suggest a desensitization of renal dopaminergic receptors.     

Metabolic,thermal and circulatory effects of intravenous infusion of amino acids in tetraplegic patients

Summary. Metabolic, circulatory and thermal effects of intravenously (i.v.) administered amino acids were studied in eight patients with complete cervical spinal cord injuries, and compared with the effects in eight healthy subjects. Using indirect calori-metry and catheter techniques, whole-body and splanchnic oxygen consumption, blood flow and blood temperatures were measured before and at timed intervals during 2.5 h of i.v. infusion of 600 kJ of a mixture of 19 amino acids. Pulmonary oxygen uptake increased from 209±11 to 267±13 ml min^-1 in the patients and from 268±5 to 320±8 ml min^-1 in the controls. The thermic effect of amino acids was 21±3% and 16±2% in patients and controls, respectively. In both groups the splanchnic tissues accounted for approximately half of the rise in whole-body oxygen consumption. Cardiac output rose by, on average, 0.5±0-l and 0.8±0.2 1 min^-1 in patients and controls, respectively, while the hepatic blood flow remained unchanged in both groups. Pulmonary arterial blood temperature increased by 0–647±0100°C in the patients and by 0.244±0.174°C in the controls (P<0.05). The whole-body specific heat was low in the patients, its calculated maximum value being approximately 20% below the normal level. During the amino acid infusion the arterial blood concentration of amino acids rose by approximately 170% and 112% of its basal levels in patients and controls, respectively, indicating a significantly reduced capacity for cellular uptake of amino acids in tetraplegic patients. It is concluded that, in tetraplegic patients, i.v. infused amino acids induce prompt thermogenesis of normal magnitude accompanied by supranormal temperatures and amino acid concentrations in the blood, and that low whole-body specific heat contributes to the well-known thermoregulatory instability in tetraplegia.     

Relationship between infusion rates, plasma concentrations, and cardiovascular and metabolic effects during the infusion of norepinephrine in healthy volunteers.

OBJECTIVE: To determine the relationship between iv infusion rate, plasma concentrations, and hemodynamic and metabolic actions of norepinephrine. DESIGN: Norepinephrine was administered by using five iv infusion rates (0.01 to 0.2 micrograms/kg/min) for 30 mins each to eight volunteers, for the purpose of constructing cumulative plasma concentration-response curves. SETTING: Laboratory of the Department of Anesthesiology at a university hospital. MEASUREMENTS AND MAIN RESULTS: Systolic and diastolic BP, heart rate, and the plasma concentrations of norepinephrine, glucose, nonesterified fatty acids, and insulin were measured at the end of each infusion rate. During the highest infusion rate, plasma norepinephrine concentrations increased from 199 +/- 75 to 7475 +/- 1071 pg/mL (1.18 +/- 0.44 to 44.18 +/- 6.33 nmol/L). Typical hemodynamic responses, such as increases in BP and decreases in heart rate, were seen, while the plasma concentrations of glucose and nonesterified fatty acids increased from 92 +/- 10 to 132 +/- 17 mg/dL (5.1 +/- 0.6 to 7.3 +/- 0.9 mmol/L) and 11 +/- 4 to 34 +/- 6 mg/dL (0.11 +/- 0.04 to 0.34 +/- 0.06 g/L), respectively, during the 0.2 micrograms/kg/min infusion rate (p less than .05). Despite the increase in glucose concentration, insulin remained at baseline values. Metabolic and hemodynamic effects occurred at similar plasma concentrations throughout the study. CONCLUSIONS: Administration of norepinephrine showed no selective hemodynamic actions. The metabolic responses observed in this investigation were similar to those responses seen during increased endogenous sympathetic nervous system activity, such as stress, exercise, or trauma.