title: The hemodynamic effects of dobutamine during reoxygenation after hypoxia: a dose-response study in newborn pigs.
abstract: Asphyxiated neonates usually have myocardial stunning and hypotension and require inotropic support. A randomized controlled study was designed to examine the dose-response effect of dobutamine (5-20 microg x kg(-1) x min(-1)) on systemic and regional circulations and oxygen metabolism in a neonatal swine model of hypoxia/reoxygenation. Thirty-eight anesthetized newborn piglets were acutely instrumented for continuous monitoring of heart rate, systemic and pulmonary arterial pressures, and pulmonary (surrogate for cardiac index), right common carotid, and superior mesenteric and left renal arterial flows. After stabilization, they were exposed to normocapnic alveolar hypoxia (10%-15% oxygen) for 2 h followed by reoxygenation with 100% oxygen for 1 h, then 21% for 3 h. Piglets were block randomized to receive dobutamine infusion (5, 10, or 20 microg x kg(-1) x min(-1)) or saline (control) at 2 to 4 h of reoxygenation (n = 8 each). A nonasphyxiated, sham-operated group was included (n = 6). Blood samples were collected for blood gas analysis, arterial and venous co-oximetry, and plasma lactate concentration determination. At 2-h reoxygenation after hypoxia, there was hypotension (systemic arterial pressure, 27 to 36 mmHg) and myocardial dysfunction (cardiac index from 178-209 to 134-156 mL x kg(-1) x min(-1)). Cardiac index improved significantly with 20 microg x kg(-1) x min(-1) of dobutamine (P < 0.05) and modestly in the treatment groups of 5 and 10 microg x kg(-1) x min(-1) (P < 0.1) (at 120 min, 172 +/- 35, 160 +/- 30, and 158 +/- 56 mL x kg(-1) x min(-1) vs. 119 +/- 33 mL x kg(-1) x min(-1) of controls, respectively), with corresponding increases in stroke volume. Pulmonary vascular resistance was lower in all dobutamine-treated groups (vs. controls, P < 0.05) There were no differences in heart rate, systemic and pulmonary arterial pressures, systemic vascular resistance, and regional flows between groups. The group of 20 mug.kg.min of dobutamine also had higher systemic oxygen delivery (at 120 min, 18 +/- 5 vs. 11 +/- 3 O(2) mL x kg(-1) x min(-1) of controls, P < 0.05) with no significant differences in systemic oxygen consumption and regional oxygen delivery between groups. After the reoxygenation of newborn piglets with severe hypoxia, high dose of dobutamine is effective to treat myocardial stunning and low cardiac output with no significant effect on blood pressure or regional circulation. Further clinical studies are needed to confirm these findings in the human neonate.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Zakariya
authors.initials: Z
authors.lastname: Al-Salam
authors.forename: Scott
authors.initials: S
authors.lastname: Johnson
authors.forename: Sameh
authors.initials: S
authors.lastname: Abozaid
authors.forename: David
authors.initials: D
authors.lastname: Bigam
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004280:Dobutamine / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology*; D007231:Infant, Newborn; D019344:Lactic Acid / Q000097:blood; D010100:Oxygen / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D019344:Lactic Acid; D004280:Dobutamine; D010100:Oxygen