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Konrad Reinhart - One of the best experts on this subject based on the ideXlab platform.
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Dopexamine increases splanchnic blood flow but decreases gastric mucosal ph in severe septic patients treated with dobutamine
Critical Care Medicine, 1999Co-Authors: Andreas Meierhellmann, Donald L. Bredle, Martin Specht, Lutz Hannemann, Konrad ReinhartAbstract:Objective: To assess the effects of Dopexamine on splanchnic blood flow and splanchnic oxygen uptake in septic patients. Design: A prospective, controlled trial. Setting: A ten-bed intensive care unit (ICU) in a university hospital. Patients: Twelve patients with severe sepsis (according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference) being stabilized by volume loading and treated to an elevated oxygen delivery by dobutamine infusion. Interventions: Infusion of increasing dosages of Dopexamine (0.5, 1.0, 2.0, and 4.0 ig/kg/min). Measurements and Main Results: Systemic and splanchnic hemodynamic and oxygen transport parameters as well as gastric mucosal pH (pHi) were measured. A hepatic venous catheter technique with indocyanine green dye dilution was used to determine splanchnic blood flow . Dopexamine increased global and splanchnic oxygen delivery without affecting oxygen consumption ( O2). Splanchnic blood flow increased proportionally to cardiac output, indicating that there was no selective effect of Dopexamine on the splanchnic flow. Dopexamine decreased pHi in a dose-dependent fashion in all 12 patients. Conclusions: In hemodynamically stable, hyperdynamic septic patients being treated with dobutamine, Dopexamine has no selective effect on splanchnic blood flow. In fact, a decreased pHi suggests a harmful effect on gastric mucosal perfusion. Because the gut has been proposed as a genesis of multiple organ failure, much attention has been given to the adequacy of splanchnic perfusion in patients with sepsis (1-3). It is well known that in patients with sepsis the metabolic demand in the splanchnic region is elevated (1), and therefore, therapeutic strategies that try to increase blood flow to the splanchnic area are reasonable (4). For example, low -dose dopamine has been infused with the intent to increase splanchnic circulation and oxygenation (5, 6). Nevertheless, the common practice of many intensivists to treat septic patients with low -dose dopamine to elevate renal and splanchnic perfusion is becoming suspect, because to date neither the prevention of renal failure (7) nor a beneficial effect on splanchnic circulation (8) has really been proven. Moreover, Giraud and MacCannell (9) demonstrated that low -dose dopamine may induce a redistribution of blood flow from the gut mucosa to the gut muscularis. We found that low dose dopamine could increase splanchnic blood flow in some septic patients, but in patients with an already elevated splanchnic blood flow, low -dose dopamine either failed to increase or even reduced splanchnic flow (10). Furthermore, it is well known that prolonged dopamine infusion suppresses the circulating concentrations of pituitary-dependent hormones, which may be harmful to the already -threatened metabolic and immunologic homeostasis in critically ill patients (11-13). Because of these potential disadvantages of low -dose dopamine, the newer synthetic catecholamine Dopexamine, which also has dopaminergic properties, may serve as a logical alternative. Dopexamine has a potency relative to that of dopamine as a DA -1 agonist of 0.34, as a DA -2 agonist of 0.17, and as a â-1 agonist of 0.1, but it has 60 times the â-2 agonist activity. In addition, Dopexamine has no a-adrenergic receptor activity (14). When compared with dobutamine, Dopexamine has less effect on cardiac â1-receptors but stronger effects on vascular â2-receptors, as well as some dopaminergic effects. Theoretically, this would give Dopexamine an advantage in increasing selective regional blood in the treatment of sepsis. Dopexamine has been advocated for hemodynamic stabilization and increasing renal and splanchnic perfusion in patients with heart failure (15, 16), chronic renal dysfunction (17), and hypertension (18); after liver transplantation (19); and also in septic patients (20). Nevertheless, the value of Dopexamine as primary or adjunct therapy to improve splanchnic blood flow in septic patients is still unknown. Therefore, we investigated the effects of increasing dosages of Dopexamine on global hemodynamics, splanchnic blood flow, oxygen consumption ( O2), and gastric mucosal pH (pHi) in 12 patients with severe sepsis.
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Dopexamine hydrochloride in septic shock
Chest, 1996Co-Authors: L. Hannemann, Konrad Reinhart, Gero Wallenfang, Andreas Meierhellmann, Donald L. BredleAbstract:Objective To test whether Dopexamine hydrochloride, by its β 2 -adrenoceptor and dopaminergic 1 (DA 1 ) and dopaminergic 2 (DA 2 ) agonistic properties, can improve oxygen consumption ( V ˙ o 2 ) in hyperdynamic patients with septic shock. Design Prospective, single-cohort study. Setting ICU, university hospital. Patients Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. Interventions Short-term application (30 min) of Dopexamine hydrochloride at a dose of 2 μg/kg/min. Measurements Complete hemodynamic profile with O 2 transport-related variables at baseline, 30 min after starting the Dopexamine infusion, and 30 min after stopping the infusion. Main results The Dopexamine infusion resulted in significant increases in cardiac index (17%) (p 2 delivery (Do 2 ) (16%) (p<0.001). V ˙ o 2 increased slightly but significantly about 4% (p 2 extraction ratio decreased about 8% (0.001). Conclusions The addition of Dopexamine hydrochloride at a dose of 2 μg/kg/min resulted in significant increases of Do 2 and to a lesser extent V ˙ o 2 . Much of the global Do 2 increase was not utilized, because O 2 extraction ratio decreased. Direct calorigenic effects of Dopexamine and an increase in myocardial V ˙ o 2 likely account for a large portion of the increase in global V ˙ o 2 . Whether any of the V ˙ o 2 increase reflects improvement in regions of jeopardized tissue oxygenation remains to be clarified before the definite value of this drug in septic shock can be established.
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Dopexamine Hydrochloride in Septic Shock
Chest, 1996Co-Authors: L. Hannemann, Konrad Reinhart, Andreas Meier-hellmann, Gero Wallenfang, Donald L. BredleAbstract:Objective To test whether Dopexamine hydrochloride, by its β 2 -adrenoceptor and dopaminergic 1 (DA 1 ) and dopaminergic 2 (DA 2 ) agonistic properties, can improve oxygen consumption ( V ˙ o 2 ) in hyperdynamic patients with septic shock. Design Prospective, single-cohort study. Setting ICU, university hospital. Patients Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. Interventions Short-term application (30 min) of Dopexamine hydrochloride at a dose of 2 μg/kg/min. Measurements Complete hemodynamic profile with O 2 transport-related variables at baseline, 30 min after starting the Dopexamine infusion, and 30 min after stopping the infusion. Main results The Dopexamine infusion resulted in significant increases in cardiac index (17%) (p 2 delivery (Do 2 ) (16%) (p
Donald L. Bredle - One of the best experts on this subject based on the ideXlab platform.
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Dopexamine increases splanchnic blood flow but decreases gastric mucosal ph in severe septic patients treated with dobutamine
Critical Care Medicine, 1999Co-Authors: Andreas Meierhellmann, Donald L. Bredle, Martin Specht, Lutz Hannemann, Konrad ReinhartAbstract:Objective: To assess the effects of Dopexamine on splanchnic blood flow and splanchnic oxygen uptake in septic patients. Design: A prospective, controlled trial. Setting: A ten-bed intensive care unit (ICU) in a university hospital. Patients: Twelve patients with severe sepsis (according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference) being stabilized by volume loading and treated to an elevated oxygen delivery by dobutamine infusion. Interventions: Infusion of increasing dosages of Dopexamine (0.5, 1.0, 2.0, and 4.0 ig/kg/min). Measurements and Main Results: Systemic and splanchnic hemodynamic and oxygen transport parameters as well as gastric mucosal pH (pHi) were measured. A hepatic venous catheter technique with indocyanine green dye dilution was used to determine splanchnic blood flow . Dopexamine increased global and splanchnic oxygen delivery without affecting oxygen consumption ( O2). Splanchnic blood flow increased proportionally to cardiac output, indicating that there was no selective effect of Dopexamine on the splanchnic flow. Dopexamine decreased pHi in a dose-dependent fashion in all 12 patients. Conclusions: In hemodynamically stable, hyperdynamic septic patients being treated with dobutamine, Dopexamine has no selective effect on splanchnic blood flow. In fact, a decreased pHi suggests a harmful effect on gastric mucosal perfusion. Because the gut has been proposed as a genesis of multiple organ failure, much attention has been given to the adequacy of splanchnic perfusion in patients with sepsis (1-3). It is well known that in patients with sepsis the metabolic demand in the splanchnic region is elevated (1), and therefore, therapeutic strategies that try to increase blood flow to the splanchnic area are reasonable (4). For example, low -dose dopamine has been infused with the intent to increase splanchnic circulation and oxygenation (5, 6). Nevertheless, the common practice of many intensivists to treat septic patients with low -dose dopamine to elevate renal and splanchnic perfusion is becoming suspect, because to date neither the prevention of renal failure (7) nor a beneficial effect on splanchnic circulation (8) has really been proven. Moreover, Giraud and MacCannell (9) demonstrated that low -dose dopamine may induce a redistribution of blood flow from the gut mucosa to the gut muscularis. We found that low dose dopamine could increase splanchnic blood flow in some septic patients, but in patients with an already elevated splanchnic blood flow, low -dose dopamine either failed to increase or even reduced splanchnic flow (10). Furthermore, it is well known that prolonged dopamine infusion suppresses the circulating concentrations of pituitary-dependent hormones, which may be harmful to the already -threatened metabolic and immunologic homeostasis in critically ill patients (11-13). Because of these potential disadvantages of low -dose dopamine, the newer synthetic catecholamine Dopexamine, which also has dopaminergic properties, may serve as a logical alternative. Dopexamine has a potency relative to that of dopamine as a DA -1 agonist of 0.34, as a DA -2 agonist of 0.17, and as a â-1 agonist of 0.1, but it has 60 times the â-2 agonist activity. In addition, Dopexamine has no a-adrenergic receptor activity (14). When compared with dobutamine, Dopexamine has less effect on cardiac â1-receptors but stronger effects on vascular â2-receptors, as well as some dopaminergic effects. Theoretically, this would give Dopexamine an advantage in increasing selective regional blood in the treatment of sepsis. Dopexamine has been advocated for hemodynamic stabilization and increasing renal and splanchnic perfusion in patients with heart failure (15, 16), chronic renal dysfunction (17), and hypertension (18); after liver transplantation (19); and also in septic patients (20). Nevertheless, the value of Dopexamine as primary or adjunct therapy to improve splanchnic blood flow in septic patients is still unknown. Therefore, we investigated the effects of increasing dosages of Dopexamine on global hemodynamics, splanchnic blood flow, oxygen consumption ( O2), and gastric mucosal pH (pHi) in 12 patients with severe sepsis.
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Dopexamine hydrochloride in septic shock
Chest, 1996Co-Authors: L. Hannemann, Konrad Reinhart, Gero Wallenfang, Andreas Meierhellmann, Donald L. BredleAbstract:Objective To test whether Dopexamine hydrochloride, by its β 2 -adrenoceptor and dopaminergic 1 (DA 1 ) and dopaminergic 2 (DA 2 ) agonistic properties, can improve oxygen consumption ( V ˙ o 2 ) in hyperdynamic patients with septic shock. Design Prospective, single-cohort study. Setting ICU, university hospital. Patients Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. Interventions Short-term application (30 min) of Dopexamine hydrochloride at a dose of 2 μg/kg/min. Measurements Complete hemodynamic profile with O 2 transport-related variables at baseline, 30 min after starting the Dopexamine infusion, and 30 min after stopping the infusion. Main results The Dopexamine infusion resulted in significant increases in cardiac index (17%) (p 2 delivery (Do 2 ) (16%) (p<0.001). V ˙ o 2 increased slightly but significantly about 4% (p 2 extraction ratio decreased about 8% (0.001). Conclusions The addition of Dopexamine hydrochloride at a dose of 2 μg/kg/min resulted in significant increases of Do 2 and to a lesser extent V ˙ o 2 . Much of the global Do 2 increase was not utilized, because O 2 extraction ratio decreased. Direct calorigenic effects of Dopexamine and an increase in myocardial V ˙ o 2 likely account for a large portion of the increase in global V ˙ o 2 . Whether any of the V ˙ o 2 increase reflects improvement in regions of jeopardized tissue oxygenation remains to be clarified before the definite value of this drug in septic shock can be established.
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Dopexamine Hydrochloride in Septic Shock
Chest, 1996Co-Authors: L. Hannemann, Konrad Reinhart, Andreas Meier-hellmann, Gero Wallenfang, Donald L. BredleAbstract:Objective To test whether Dopexamine hydrochloride, by its β 2 -adrenoceptor and dopaminergic 1 (DA 1 ) and dopaminergic 2 (DA 2 ) agonistic properties, can improve oxygen consumption ( V ˙ o 2 ) in hyperdynamic patients with septic shock. Design Prospective, single-cohort study. Setting ICU, university hospital. Patients Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. Interventions Short-term application (30 min) of Dopexamine hydrochloride at a dose of 2 μg/kg/min. Measurements Complete hemodynamic profile with O 2 transport-related variables at baseline, 30 min after starting the Dopexamine infusion, and 30 min after stopping the infusion. Main results The Dopexamine infusion resulted in significant increases in cardiac index (17%) (p 2 delivery (Do 2 ) (16%) (p
G. Hempelmann - One of the best experts on this subject based on the ideXlab platform.
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Effects of Dopexamine and volume loading on hemodynamics and oxygenation parameters in patients undergoing pulmonary resection.
Acta anaesthesiologica Scandinavica, 2000Co-Authors: Matthias J. Müller, W. Padberg, J. Sticher, E. Schindler, S. Jänich, G. HempelmannAbstract:Background: Pulmonary resection may result in a reduction in arterial oxygen pressure as well as in cardiac output. Since cardiac index, oxygen delivery, and oxygen consumption are considered as important determinants of patients' outcome, we evaluated the effects of Dopexamine and volume loading on cardiopulmonary variables in patients undergoing pulmonary resection. Methods: Forty adult patients undergoing pulmonary resection for lung or bronchial tumors were included in an open placebo-controlled study. The patients were selected according to a randomized sequence to group A (n=20) or group B (n=20). Dopexamine (2 μg.kg -1 min -1 ) was started when steady state conditions were achieved after induction of anesthesia in group A. Saline 0.9% was given as control (group B). Hemodynamic monitoring was performed using a pulmonary artery catheter. Results: Dopexamine increased heart rate, cardiac output and oxygen delivery compared with control without increasing oxygen consumption during anesthesia and surgery. Furthermore, Dopexamine was found not to alter the course of PaO 2 /F i O 2 values. Conclusion: In patients undergoing pulmonary resection, Dopexamine can be used perioperatively to increase cardiac index without decreasing the PaO 2 /F i O 2 ratio.
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Influence of Dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery
Acta anaesthesiologica Scandinavica, 1998Co-Authors: Joachim Boldt, Michael Papsdorf, S. Piper, W. Padberg, G. HempelmannAbstract:BACKGROUND Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. METHODS The influence of perioperative administration of Dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 micrograms.kg-1.min-1 of Dopexamine (n = 15) or placebo (n = 15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. RESULTS Cardiac index (CI) increased significantly in the Dopexamine group (from 2.61 +/- 0.41 to 4.57 +/- 0.78 l.min-1.m-2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I) were also significantly increased in the Dopexamine group (DO2I: from 416 +/- 91 to 717 +/- 110 ml/m2.m2; VO2I: from 98 +/- 25 to 157 +/- 22 ml/m2.m2), being significantly higher than in the control group. pHi remained stable only in the Dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37 +/- 1.1 to 35.9 +/- 12.1 pg/ml; ET-1: from 2.88 +/- 0.91 to 6.91 +/- 1.20 pg/ml). CONCLUSION Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of Dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.
R. Gordon Murray - One of the best experts on this subject based on the ideXlab platform.
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Comparison of the haemodynamic effects of Dopexamine and dobutamine in patients with severe congestive heart failure.
International journal of cardiology, 1991Co-Authors: Lip-bun Tan, William A. Littler, R. Gordon MurrayAbstract:Abstract Dopexamine hydrochloride is a novel compound with properties of DA 1 -dopaminergic and β 2 -adrenergic receptor agonism and neuronal noradrenaline uptake inhibition. It has been shown to produce beneficial renal and haemodynamic effects in patients with severe heart failure. We compared the haemodynamic effects of Dopexamine (0.5 to 6 μg/kg/min) with those of dobutamine (5 to 25 μg/kg/min) in 9 patients with severe congestive heart failure. The two drugs were similar in their effects at peak infusion rates: heart rate increased (Dopexamine 87 ± 17 to 100 ± 14; dobutamine 91 ± 18 to 103 ± 17 min −1 ), cardiac index increased (Dopexamine 1.7 ± 0.5 to 2.8 ± 1.1; dobutamine 1.8 ± 0.5 to 3.0 ± 1.1 l · min −1 · m −2 ) and systemic vascular resistance decreased (Dopexamine 1553 ± 221 to 1117 ± 432; dobutamine 1721 ± 347 to 1280 ± 433 dyne · s · cm −5 ). Neither drug affected pulmonary artery wedge pressure (Dopexamine 24 ± 6 to 22 ± 6; dobutamine 25 ± 9 to 24 ± 10 mm Hg). Dopexamine had significantly lower peak effects on left ventricular stroke work index (Dopexamine 20 ± 9, dobutamine 27 ± 15 g · m · m −2 , P
Andreas Meierhellmann - One of the best experts on this subject based on the ideXlab platform.
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Dopexamine increases splanchnic blood flow but decreases gastric mucosal ph in severe septic patients treated with dobutamine
Critical Care Medicine, 1999Co-Authors: Andreas Meierhellmann, Donald L. Bredle, Martin Specht, Lutz Hannemann, Konrad ReinhartAbstract:Objective: To assess the effects of Dopexamine on splanchnic blood flow and splanchnic oxygen uptake in septic patients. Design: A prospective, controlled trial. Setting: A ten-bed intensive care unit (ICU) in a university hospital. Patients: Twelve patients with severe sepsis (according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference) being stabilized by volume loading and treated to an elevated oxygen delivery by dobutamine infusion. Interventions: Infusion of increasing dosages of Dopexamine (0.5, 1.0, 2.0, and 4.0 ig/kg/min). Measurements and Main Results: Systemic and splanchnic hemodynamic and oxygen transport parameters as well as gastric mucosal pH (pHi) were measured. A hepatic venous catheter technique with indocyanine green dye dilution was used to determine splanchnic blood flow . Dopexamine increased global and splanchnic oxygen delivery without affecting oxygen consumption ( O2). Splanchnic blood flow increased proportionally to cardiac output, indicating that there was no selective effect of Dopexamine on the splanchnic flow. Dopexamine decreased pHi in a dose-dependent fashion in all 12 patients. Conclusions: In hemodynamically stable, hyperdynamic septic patients being treated with dobutamine, Dopexamine has no selective effect on splanchnic blood flow. In fact, a decreased pHi suggests a harmful effect on gastric mucosal perfusion. Because the gut has been proposed as a genesis of multiple organ failure, much attention has been given to the adequacy of splanchnic perfusion in patients with sepsis (1-3). It is well known that in patients with sepsis the metabolic demand in the splanchnic region is elevated (1), and therefore, therapeutic strategies that try to increase blood flow to the splanchnic area are reasonable (4). For example, low -dose dopamine has been infused with the intent to increase splanchnic circulation and oxygenation (5, 6). Nevertheless, the common practice of many intensivists to treat septic patients with low -dose dopamine to elevate renal and splanchnic perfusion is becoming suspect, because to date neither the prevention of renal failure (7) nor a beneficial effect on splanchnic circulation (8) has really been proven. Moreover, Giraud and MacCannell (9) demonstrated that low -dose dopamine may induce a redistribution of blood flow from the gut mucosa to the gut muscularis. We found that low dose dopamine could increase splanchnic blood flow in some septic patients, but in patients with an already elevated splanchnic blood flow, low -dose dopamine either failed to increase or even reduced splanchnic flow (10). Furthermore, it is well known that prolonged dopamine infusion suppresses the circulating concentrations of pituitary-dependent hormones, which may be harmful to the already -threatened metabolic and immunologic homeostasis in critically ill patients (11-13). Because of these potential disadvantages of low -dose dopamine, the newer synthetic catecholamine Dopexamine, which also has dopaminergic properties, may serve as a logical alternative. Dopexamine has a potency relative to that of dopamine as a DA -1 agonist of 0.34, as a DA -2 agonist of 0.17, and as a â-1 agonist of 0.1, but it has 60 times the â-2 agonist activity. In addition, Dopexamine has no a-adrenergic receptor activity (14). When compared with dobutamine, Dopexamine has less effect on cardiac â1-receptors but stronger effects on vascular â2-receptors, as well as some dopaminergic effects. Theoretically, this would give Dopexamine an advantage in increasing selective regional blood in the treatment of sepsis. Dopexamine has been advocated for hemodynamic stabilization and increasing renal and splanchnic perfusion in patients with heart failure (15, 16), chronic renal dysfunction (17), and hypertension (18); after liver transplantation (19); and also in septic patients (20). Nevertheless, the value of Dopexamine as primary or adjunct therapy to improve splanchnic blood flow in septic patients is still unknown. Therefore, we investigated the effects of increasing dosages of Dopexamine on global hemodynamics, splanchnic blood flow, oxygen consumption ( O2), and gastric mucosal pH (pHi) in 12 patients with severe sepsis.
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Dopexamine hydrochloride in septic shock
Chest, 1996Co-Authors: L. Hannemann, Konrad Reinhart, Gero Wallenfang, Andreas Meierhellmann, Donald L. BredleAbstract:Objective To test whether Dopexamine hydrochloride, by its β 2 -adrenoceptor and dopaminergic 1 (DA 1 ) and dopaminergic 2 (DA 2 ) agonistic properties, can improve oxygen consumption ( V ˙ o 2 ) in hyperdynamic patients with septic shock. Design Prospective, single-cohort study. Setting ICU, university hospital. Patients Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. Interventions Short-term application (30 min) of Dopexamine hydrochloride at a dose of 2 μg/kg/min. Measurements Complete hemodynamic profile with O 2 transport-related variables at baseline, 30 min after starting the Dopexamine infusion, and 30 min after stopping the infusion. Main results The Dopexamine infusion resulted in significant increases in cardiac index (17%) (p 2 delivery (Do 2 ) (16%) (p<0.001). V ˙ o 2 increased slightly but significantly about 4% (p 2 extraction ratio decreased about 8% (0.001). Conclusions The addition of Dopexamine hydrochloride at a dose of 2 μg/kg/min resulted in significant increases of Do 2 and to a lesser extent V ˙ o 2 . Much of the global Do 2 increase was not utilized, because O 2 extraction ratio decreased. Direct calorigenic effects of Dopexamine and an increase in myocardial V ˙ o 2 likely account for a large portion of the increase in global V ˙ o 2 . Whether any of the V ˙ o 2 increase reflects improvement in regions of jeopardized tissue oxygenation remains to be clarified before the definite value of this drug in septic shock can be established.