Addition Of Dobutamine Research Articles

Risky Business: Angiotensin II Use In A Heartmate 3 LVAD Patient In The Setting Of Refractory Vasoplegia

Introduction :Vasoplegia is a well-described post-operative complication, defined as hypotension due to a decline in systemic vascular resistance in the setting of normal cardiac output and filling pressures. Angiotensin II is a vasoconstrictor with a potential for thrombosis. We present a case of vasoplegia refractory to standard therapy in a patient status post Left Ventricular Assist Device (LVAD) placement in which angiotensin II was utilized successfully. Case Description A 44-year-old African American man with history of stage D idiopathic dilated cardiomyopathy and chronic kidney disease status post HeartMate 3 (HM3) LVAD placement three months ago, complicated by right ventricular failure requiring home milrinone infusion, presented to clinic for follow-up. He was found to have Class IV heart failure symptoms and anasarca, despite an increase in his home diuretic regimen, requiring hospital admission. He denied fever, productive cough or infectious exposures, LVAD alarms, or changes in urine output. Despite an increase of his milrinone and addition of dobutamine, epinephrine, bumetanide, and intravenous chlorothiazide on admission, his hemodynamics on right heart catheterization revealed elevated biventricular filling pressures and a low systemic vascular resistance (SVR) without evidence of right ventricular failure on these therapies (Table 1). The patient maintained poor urine output and required continuous dialysis. However, due to continued vasoplegia, fluid removal was not possible despite maximizing ionotropic and pressor support. A trial of angiotensin II was attempted after discussion with the patient and family about the associated thrombotic risk to HM3. With optimized dosing of angiotensin II, SVR improved (Table 1), and fluid was successfully removed with continuous dialysis. Ionotropic and pressor support was then weaned. The patient did not develop any thromboembolic events or pump thrombosis of the LVAD. The patient was discharged home and one month later underwent a successful heart and kidney transplantation. Conclusion : Angiotensin II use carries significant thromboembolic risk for some patients, with the ATHOS-3 trial showing 12.9% risk versus 5% for placebo. Although this can raise concerns among patients with mechanical circulatory support, significant hemodynamic improvement can be achieved with those facing refractory vasoplegia. Clinicians should be aware of the risks of angiotensin II use and be prepared to utilize the medication in the appropriate patient following a discussion of the potential risks and benefits. :Vasoplegia is a well-described post-operative complication, defined as hypotension due to a decline in systemic vascular resistance in the setting of normal cardiac output and filling pressures. Angiotensin II is a vasoconstrictor with a potential for thrombosis. We present a case of vasoplegia refractory to standard therapy in a patient status post Left Ventricular Assist Device (LVAD) placement in which angiotensin II was utilized successfully. A 44-year-old African American man with history of stage D idiopathic dilated cardiomyopathy and chronic kidney disease status post HeartMate 3 (HM3) LVAD placement three months ago, complicated by right ventricular failure requiring home milrinone infusion, presented to clinic for follow-up. He was found to have Class IV heart failure symptoms and anasarca, despite an increase in his home diuretic regimen, requiring hospital admission. He denied fever, productive cough or infectious exposures, LVAD alarms, or changes in urine output. Despite an increase of his milrinone and addition of dobutamine, epinephrine, bumetanide, and intravenous chlorothiazide on admission, his hemodynamics on right heart catheterization revealed elevated biventricular filling pressures and a low systemic vascular resistance (SVR) without evidence of right ventricular failure on these therapies (Table 1). The patient maintained poor urine output and required continuous dialysis. However, due to continued vasoplegia, fluid removal was not possible despite maximizing ionotropic and pressor support. A trial of angiotensin II was attempted after discussion with the patient and family about the associated thrombotic risk to HM3. With optimized dosing of angiotensin II, SVR improved (Table 1), and fluid was successfully removed with continuous dialysis. Ionotropic and pressor support was then weaned. The patient did not develop any thromboembolic events or pump thrombosis of the LVAD. The patient was discharged home and one month later underwent a successful heart and kidney transplantation. : Angiotensin II use carries significant thromboembolic risk for some patients, with the ATHOS-3 trial showing 12.9% risk versus 5% for placebo. Although this can raise concerns among patients with mechanical circulatory support, significant hemodynamic improvement can be achieved with those facing refractory vasoplegia. Clinicians should be aware of the risks of angiotensin II use and be prepared to utilize the medication in the appropriate patient following a discussion of the potential risks and benefits.

Left Ventricular Assist Device Implantation in a COVID-19 Positive Patient

IntroductionCoronavirus disease-2019 (COVID) in patients with advanced heart failure presents unprecedented challenges in management of cardiogenic shock. Recommendations for perioperative triaging of cardiac surgery have been proposed but none regarding LVAD implantation. To our knowledge, we are the first to report on LVAD implantation in a patient with COVID and cardiogenic shockCase ReportA 37-year-old-male with Stage D, NYHA class IV heart failure on chronic milrinone was admitted for cardiogenic shock. Despite uptitration of milrinone and addition of dobutamine,the patient remained in cardiogenic shock . Our Selection Committee discussed and approved him for an LVAD.Institutional protocol required COVID screening prior to surgery and returned positive. Given the absence of clinical signs of COVID infection contrasted with the severity of shock, the decision was made to proceed with implantation. Temporary mechanical support was considered but not thought to mitigate risks of thrombosis rather adding procedural risk with ECMO cannulation and left ventricular unloading. He successfully underwent LVAD implantation as INTERMACS 1. He required high doses of heparin to achieve ACT for cardiopulmonary bypass. On day 2, he developed left-sided weakness with imaging revealing multifocal acute cerebral infarcts. Despite normal LVAD function, the embolic infarcts to multiple organs led to further deterioration and deathSummaryLVAD implantation in COVID patients appears inevitable. Centers must risk stratify this cohort to reduce susceptibility to thrombosis and improve outcomes. We propose an algorithm that triages patients for elective and urgent LVAD implantation based on specific coagulation and inflammatory markers (figure 1) and have successfully implanted an LVAD in a COVID patient using this. We acknowledge this method has not been validated in a large cohort and are unable to recommend anticoagulation protocols. Further research is necessary to address safety of LVAD implantation in COVID patients

İzole sıçan aortunda dobutaminin vazokonstriktör etkisinde beta adrenerjik reseptörler rol oynar

Purpose: Experimental evidence exists that cardiac action of dobutamine is mediated by alfa-1 and beta- adrenergic receptors. However, uncertainty remains regarding the vascular effect of dobutamine and contribution of beta-adrenergic receptors to this effect. The aim of the present study was to investigate the direct effect of dobutamine in the rat aorta and the role of beta-adrenergic receptors in this effect. Materials and methods: The isolated thoracic aortic rings were mounted in organ bath containing Krebs-Henseleit solution. After an equilibiration period, endothelial integrity was then checked by the response to acetylcholine (10 μM) in aortic rings pre-contracted with phenylephrine (1 μM). After washout, dobutamine (0.001-10 μM) was added to generate cumulative concentration–response curves (CCRCs). To investigate the role of alfa- and beta- adrenergic receptors in the dobutamine-induced vascular response, prazosin (0.0003 µM) or propranolol (1 µM) was added to the bath medium 30 min before the addition of dobutamine in some experiments.. Results: Dobutamine produced concentration-dependent contraction in the endothelium-intact isolated rat aorta. This effect was significantly inhibited by either propranolol or prazosin (p<0.05). Prazosin also significantly supressed the maximum vascular response obtained by dobutamine (p<0.05). Conclusion: The results, to the best of my knowledge, demonstrates for the first time that beta-adrenergic receptors are involved in the vasoconstrictor effect of dobutamine in the endothelium-intact rat aorta.

Dobutamine reverses the cardio-suppressive effects of terlipressin without improving renal function in cirrhosis and ascites: a randomized controlled trial.

Acute kidney injury and hepatorenal syndrome (HRS) are frequent complications in patients with cirrhosis and ascites. First-line treatment is terlipressin, which reverses HRS in ~40% of patients but also lowers cardiac output (CO). We aimed to investigate whether reversing the cardio-suppressive effect of terlipressin with the β-adrenoceptor agonist dobutamine would increase CO and thereby increase the glomerular filtration rate (GFR). We randomized 25 patients with cirrhosis, ascites, and impaired renal function (2:2:1): group A received terlipressin followed by the addition of dobutamine; group B received dobutamine and terlipressin as monotherapies; and group C received placebo. Renal and cardiac functions were assessed during 8 clearance periods of 30 min, and concentrations of vasoactive hormones were measured. Dobutamine as a monotherapy increased CO (1.03 L/min, P < 0.01) but had no significant effects on GFR. Renin (P < 0.05), angiotensin II (P < 0.005), and aldosterone (P < 0.05) increased after dobutamine infusion. Terlipressin as a monotherapy improved GFR (18.9 mL·min-1·m-2, P = 0.005) and mean arterial pressure (MAP) (14 mmHg, P = 0.001) but reduced CO (-0.92 L/min, P < 0.005) and renin (P < .005). A combined treatment of dobutamine and terlipressin had a positive effect on CO (1.19 L/min, P < 0.05) and increased renin (P < 0.005), angiotensin II (P < 0.005), and aldosterone (P < 0.05), but it had no significant effects on MAP or GFR. Dobutamine reversed the cardio-suppressive effect of terlipressin in cirrhosis, ascites, and impaired renal function. However, dobutamine reduced peripheral vascular resistance, activated renin-angiotensin-aldosterone system, and did not improve GFR compared with terlipressin as a monotherapy. Therefore, dobutamine cannot be recommended in cirrhosis and ascites.NEW & NOTEWORTHY This study shows that the cardio-suppressive effects of the vasopressin receptor agonist terlipressin can be reversed by dobutamine. This is a novel observation in patients with decompensated cirrhosis. Furthermore, we show that dobutamine reduced the peripheral vascular resistance and activated the renin-angiotensin system, whereas renal function was not further improved by terlipressin alone.

A comparative study between terlipressin alone and dobutamine and terlipressin in septic shock patients

Background The use of terlipressin, a long-acting synthetic analog of vasopressin, is associated with reduction in cardiac output and oxygen delivery. The present study was designed to determine whether dobutamine may reverse the terlipressin-induced depression in central venous oxygen saturation (SvO 2 ) in patients with catecholamine-dependent septic shock. Patients and methods This clinical trial was conducted in Ain Shams University hospital’s surgical ICU. In total, 90 septic shock patients requiring a continuous infusion of norepinephrine reaching 0.6 µg/kg/min to maintain mean arterial pressure at greater than or equal to 65 mmHg were randomly allocated to three groups be treated as follows: (i): group I, treated with norepinephrine infusion (control); (ii) group II, treated with a single bolus of terlipressin 1 mg, intravenous; (iii) and group III, treated with a single bolus of terlipressin 1 mg, followed by a dobutamine infusion. Results The use of terlipressin (with and without dobutamine) resulted in maintaining mean arterial pressure above 65 mmHg with reduction in norepinephrine requirements to 0.2 (0.1) µg/kg/min in group II and 0.15 (0.1) µg/kg/min in group III ( P in each 2 to 58 (3)% ( P P vs. control=0.013 at 2 h, 0.001 at 4 h, and 0.01 at 6 h). The addition of dobutamine in group III resulted in an increase in central SvO 2 to 70 (3)% ( P Conclusion Administration of terlipressin bolus was effective in increasing mean arterial blood pressure and reducing norepinephrine requirements in catecholamine-dependant septic shock patients. Its use was associated with significant reductions in central SvO 2 , which was reversed by using dobutamine.

Clinical review: What are the best hemodynamic targets for noncardiac surgical patients?

Perioperative hemodynamic optimization, or goal-directed therapy (GDT), has been show to significantly decrease complications and risk of death in high-risk patients undergoing noncardiac surgery. An important aim of GDT is to prevent an imbalance between oxygen delivery and oxygen consumption in order to avoid the development of multiple organ dysfunction. The utilization of cardiac output monitoring in the perioperative period has been shown to improve outcomes if integrated into a GDT strategy. GDT guided by dynamic predictors of fluid responsiveness or functional hemodynamics with minimally invasive cardiac output monitoring is suitable for the majority of patients undergoing major surgery with expected significant volume shifts due to bleeding or other significant intravascular volume losses. For patients at higher risk of complications and death, such as those with advanced age and limited cardiorespiratory reserve, the addition of dobutamine or dopexamine to the treatment algorithm, to maximize oxygen delivery, is associated with better outcomes.

Effects of Combination Dobutamine and Vasopressin Therapy on Microcirculatory Blood Flow in a Porcine Model of Severe Endotoxic Shock

Dobutamine (DB) has been recommended in combination with vasopressor therapy in septic shock, given its reported ability to improve mesenteric and microcirculatory perfusion. Vasopressin (VP) is typically reserved as a second-line agent due to the concern of ischemia. The purpose of our study was to determine whether combination DB and VP therapy improved microcirculatory blood flow in severe endotoxic shock. Septic shock was induced in 20 anesthetized piglets with injection of E. coli endotoxin. DB (10 μg/kg/min, n = 5) and VP (0.04 units/min, n = 10) were administered alone and in combination (n = 15). Measurements were compared at baseline, following endotoxin administration, and following treatment. Microcirculatory blood flow was determined via the injection of colored microspheres. VP completely reversed endotoxin-mediated hypotension with a mean arterial pressure (MAP) of 85 ± 4.5 mm Hg, which was not significantly altered with the addition of DB (77 ± 4.9 mm Hg). Endotoxin uniformly depressed cardiac output (CO) from baseline (227 ± 10.7 versus 174 ± 12.4 mL/min/kg) despite treatment with VP alone or in combination with DB. The addition of DB did not improve the CO in this severe septic shock model. VP was found to shunt microcirculatory flow from the skin and GI tract to vital organs such as the brain, liver, and kidneys, which was not altered with the addition of DB. Results indicate that DB is ineffective in increasing CO or improving mesenteric blood flow when used with physiologic replacement doses of VP. In combination, DB is unable to overcome the blood flow distribution achieved with VP administration alone in severe endotoxic shock.

The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide

Within hibernating myocardium, it is uncertain whether a normal energetic state is present at baseline and whether maintaining that energy state during a catecholamine challenge is dependent on ATP-dependent potassium channel opening. In this study, 16 swine underwent a thoracotomy with placement of an external constrictor on the left anterior descending coronary artery (LAD) (hibernation model). Seven additional swine underwent a sham operation. At 10 wk, the myocardial energetic state in the LAD region was assessed by (31)P-NMR spectroscopy, and the ratio of phosphocreatine to ATP (PCr/ATP) was determined at baseline, during glibenclamide treatment (0.5 mg/kg bolus with 50 microg/min iv), and during addition of dobutamine (40 microg x kg(-1) x min(-1) iv). At baseline, transmural blood flow in the LAD and remote region was 0.75 +/- 0.11 and 0.88 +/- 0.09 ml x min(-1) x g(-1), respectively (P < 0.01), in hibernating hearts and 0.83 +/- 0.12 and 0.88 +/- 0.15 ml x min(-1) x g(-1), respectively (not significant), in sham-operated hearts. Under basal conditions, PCr/ATP in the LAD region of hibernating and sham pigs was 2.15 +/- 0.04 and 2.11 +/- 0.05, respectively (not significant). In sham pigs, addition of dobutamine to glibenclamide increased the double product from 10.4 +/- 0.8 to 23.9 +/- 4.0 mmHg x beats x min(-1) x 1,000 (P < 0.05) and decreased transmural PCr/ATP from 2.06 +/- 0.06 to 1.69 +/- 0.06 (P < 0.05). Dobutamine increased the double product in hibernating pigs in a similar fashion and, despite a 40% lower blood flow response, induced an equivalent decrease in PCr/ATP from 2.04 +/- 0.04 to 1.73 +/- 0.08 (P < 0.05). In conclusion, we found that, in chronic hibernating swine myocardium with reduced basal blood flow and perfusion reserve, the transmural energetic state, defined by PCr/ATP, is normal during addition of dobutamine, despite inhibition of ATP-dependent potassium channel opening with glibenclamide. These data suggest that important adaptations other than the ATP-dependent potassium channel opening allow hibernating myocardium to operate over a lower range of the oxygen supply-demand relationship to protect against myocardial ischemia.

Effects of inotropic stimulation on energy metabolism and systolic function of ischemic right ventricle.

This study determined whether dobutamine enhances regional systolic function in the ischemic right ventricle (RV) at the cost of adverse effects on regional energy metabolism. Seventeen alpha-chloralose-anesthetized, open-chest pigs were studied under four conditions: 1) control; 2) dobutamine infusion (mean dose 9 micrograms.kg-1.min-1); 3) RV ischemia (45 +/- 5% reduction in RV free wall blood flow for 100 min); and 4) continued ischemia with dobutamine. Regional RV free wall high-energy phosphate metabolites were measured by 31P nuclear magnetic resonance (NMR) spectroscopy or by high-speed drill biopsies of the RV free wall. Regional RV free wall substrate and O2 consumption were measured using coronary venous blood sampling. Global RV systolic function was assessed by the maximal first derivative of RV pressure (dP/dtmax), and regional RV free wall systolic function was assessed by systolic segment shortening in the ischemic zone. Right coronary artery constriction caused markedly depressed regional RV systolic function, net lactate production, and coronary venous acidosis. Surprisingly, high-energy phosphates were unchanged compared with control. Addition of dobutamine caused a further decline in coronary venous pH and continued lactate production but did not reduce high-energy phosphates. While dobutamine markedly enhanced global RV systolic function (RV dP/dtmax 201 +/- 19% of control), systolic shortening in the ischemic RV free wall remained severely depressed (47 +/- 18% of control) despite dobutamine. The mechanism of high-energy phosphate preservation is likely due to diminished consumption of ATP in the hypocontractile ischemic region.

Hyperdynamic therapy for focal cerebral ischemia of rats: Use of colloidal volume expansion and dobutamine

The effects of hyperdynamic therapy with colloidal volume expansion and pharmacological augmentation of cardiac function with dobutamine on local cerebral blood flow (CBF) and the size of ischemic injury were investigated in rats subjected to 6 h of middle cerebral artery (MCA) occlusion. At 45 min after MCA occlusion, each rat was randomly assigned to one of the following treatment groups: (1) control; (2) hetastarch infusion (HES); and (3) hetastarch plus dobutamine (12 μg/kg/min) infusion (HES/DOB). In both the HES and HES/DOB groups, cardiac output and local CBF in ischemic brain markedly increased after treatment and infarction volumes were significantly reduced as compared to the control group. There were, however, no significant differences between both groups apart from a dobutamine-induced tachycardia. Colloidal volume expansion augmented cardiac output, increased CBF in ischemic brain, and substantially modified the extent of ischemic injury. However, the addition of dobutamine did not bring about adjunctive beneficial effects of cardiac performance, CBF, or the degree of ischemic brain damage in the rat focal ischemic model

Direct effect of dobutamine on action potential duration in ischemic compared with normal areas in the human ventricle

Background and Objectives. The arrhythmogenic effect of beta-adrenoceptor stimulation is complex and may differ in ischemic and normal myocardium. In this study we examined the differential effect of beta-adrenergic stimulation on ventricular action potential duration and, hence, dispersion of repolarization in potentially ischemic versus nonischemic human ventricular myocardium.Methods. Simultaneous biventricular monophasic action potentials were recorded in 14 patients (28 recording sites) during infusion of dobutamine in incremental doses (low dose 5 μg/kg per min, high dose 10 to 15 μg/kg per min) during atrial pacing. Perfusion at the action potential recording site was assessed by incorporating myocardial perfusion scintigraphy with injection of technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrite during the recording at peak doses of dobutamine. Action potential duration during dobutamine infusion was compared with that during atrial pacing to identical rates in the absence of dobutamine.Results. In 21 normal zone recordings, dobutamine produced a variable effect over that produced by atrial pacing to identical heart rates, either lengthening or shortening the action potential duration. The mean (± SEM) value for the additional effect of debutamine was 0.9 ± 2.5 ms with low doses and -4 ± 2.6 ms with high doses (p = NS). In seven recordings from potentially ischemic zones, low dose dobutamine had a similar effect (mean change -3.4 ± 6.5 ms; p = NS vs. normal zone values). However, the high dose dobutamine invariably shortened the action potential duration by a mean of -22.9 ± 2.9 ms. (p < 0.05 vs. low dose in ischemic areas, p < 0.01 vs. normal zone recordings). Pacing alone or the addition of dobutamine had no significant effect on the normal dispersion of action potential duration between two nonischemic recording sites. In recordings in a normal and an abnormally perfused site, high dose dobutamine significantly altered the dispersion of action potential duration.Conclusions. These results suggest a different effect of beta adrenergic stimulation in potentially ischemic compared with nonischemic human ventricular myocardium. The abnormal dispersion of repolarization thus created may well be important in beta-receptor-mediatedarrhythmogenesis during myocardial Ischemia

Effect of dobutamine on oxygen consumption and fluid and protein losses after endotoxemia

To determine the effect of a dobutamine infusion on the relationship between oxygen consumption (VO2) and oxygen delivery (DO2) after endotoxin administration, as well as the rate of fluid and protein loss from permeability-injured tissue. Unanesthetized adult sheep with lung and soft-tissue lymph fistulas were given 5 micrograms/kg Escherichia coli endotoxin alone, or E. coli endotoxin plus a continuous infusion of dobutamine (10 to 15 micrograms/kg.min) beginning at 3 hrs. Lymph flow reflected the vascular permeability and surface area perfused. Data were compared with dobutamine alone and with controls. Filling pressures were maintained at baseline. Dobutamine alone produced a 75% increase in DO2, a transient 10 +/- 4% increase in VO2, but no increase in lung or soft-tissue lymph flow. Beginning at 3 hrs after endotoxin alone, a significant increase in protein-rich lung and soft-tissue lymph flow was noted, but only a transient 14 +/- 5% increase in VO2. Plasma proteins were slightly decreased. With the addition of dobutamine at 3 hrs postendotoxin, DO2 increased by greater than 50% for the 3-hr infusion period, while VO2 increased for a 30-min period by 25 +/- 8%, which was not different than endotoxin alone. Lung and soft-tissue lymph flow did not increase further, but plasma proteins did decrease significantly compared with controls and with endotoxin alone. Increasing DO2 with dobutamine postendotoxin does not increase the surface area perfused or the edema process, at least in lung and soft tissue. Therefore, no microvessels in these tissues are reopened with dobutamine when normal filling pressures are present. Dobutamine administration does not increase VO2 more than the increase seen with endotoxin alone.

Interventricular redistribution of myocardial blood flow during metabolic vasodilation

To determine the effect of metabolic vasodilation on the blood flow distribution within the hypoperfused left anterior descending coronary artery (LAD) of the pig (a perfusion bed containing both left and right ventricular myocardium), 28 anesthetized (isoflurane) pigs were studied during intracoronary dobutamine infusion (2.5 +/- 1, SD, micrograms/min) at two levels of reduced, constant coronary inflow. In 8 pigs, coronary inflow was reduced from 59 +/- 9 ml/min to 42 +/- 10 ml/min; coronary perfusion pressure fell to 62 +/- 2 mm Hg (8260 +/- 260 Pa) and then fell further to 54 +/- 6 mm Hg (7190 +/- 800 Pa) during dobutamine infusion. Subendocardial blood flow in the anterior wall of the left ventricle perfused by the LAD decreased from 0.64 +/- 0.12 ml min-1 g-1 with hypoperfusion alone, to 0.40 +/- 0.14 ml min-1 g-1 (P less than 0.002) with the addition of dobutamine. Conversely, blood flow to the right ventricular region supplied by the LAD increased significantly from 0.78 +/- 0.40 ml min-1 g-1 (hypoperfusion alone) to 0.92 +/- 0.50 ml min-1 g-1 (P less than 0.008) with dobutamine. In 10 pigs, a more severe reduction of coronary inflow to 26 +/- 12 ml/min and subsequent dobutamine infusion resulted in a similar redistribution of blood flow from the left to the right ventricular portion of the perfusion bed. Infusion of dobutamine during hypoperfusion, but with a pressure-constant perfusion system, was associated with increases in blood flow to both the right and left ventricular portions of the perfusion territory.(ABSTRACT TRUNCATED AT 250 WORDS)