Milrinone, dobutamine or epinephrine use in asphyxiated newborn pigs resuscitated with 100% oxygen

Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
European Journal of Intensive Care Medicine (Impact Factor: 5.54). 03/2010; 36(6):1058-66. DOI: 10.1007/s00134-010-1820-x
Source: PubMed

ABSTRACT After resuscitation, asphyxiated neonates often develop poor cardiac function with hypotension, pulmonary hypertension and multiorgan ischemia. In a swine model of neonatal hypoxia-reoxygenation, effects of epinephrine, dobutamine and milrinone on systemic, pulmonary and regional hemodynamics and oxygen transport were compared.
Controlled, block-randomized study.
University research laboratory.
Mixed breed piglets (1-3 days, 1.5-2.3 kg).
In acutely instrumented piglets, normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either saline (placebo), epinephrine (0.5 microg/kg/min), dobutamine (20 microg/kg/min) or milrinone (0.75 microg/kg/min) were infused for 2 h in a blinded, block-randomized fashion (n = 6/group).
All medications similarly improved cardiac output, stroke volume and systemic oxygen delivery (vs. placebo-controls, p < 0.05). Epinephrine and dobutamine significantly increased, while milrinone maintained, mean arterial pressure over pretreatment values while placebo-treated piglets developed hypotension and shock. The mean arterial to pulmonary arterial pressures ratio was not different among groups. All medications significantly increased carotid and intestinal, but not renal, arterial blood flows and oxygen delivery, whereas milrinone caused lower renal vascular resistance than epinephrine and dobutamine-treated groups. Plasma troponin I, plasma and myocardial lactate levels, and histologic ischemic features were not different among groups.
In newborn piglets with hypoxia-reoxygenation, epinephrine, dobutamine and milrinone are effective inotropes to improve cardiac output, carotid and intestinal perfusion, without aggravating pulmonary hypertension. Milrinone may also improve renal perfusion.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Epinephrine remains the primary vasopressor for neonatal resuscitation complicated by asystole or prolonged bradycardia not responsive to adequate ventilation and chest compressions. Epinephrine increases coronary perfusion pressure primarily through peripheral vasoconstriction. Current guidelines recommend intravenous epinephrine administration (0.01-0.03 mg/kg). Endotracheal epinephrine administration results in unpredictable absorption. High-dose intravenous epinephrine poses additional risks and does not result in better long-term survival. Vasopressin has been considered an alternative to epinephrine in adults, but there is insufficient evidence to recommend its use in newborn infants. Future research will focus on the best sequence for epinephrine administration and chest compressions.
    Clinics in perinatology 12/2012; 39(4):843-55. DOI:10.1016/j.clp.2012.09.005 · 2.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of the use of dobutamine in juvenile animals to determine whether the evidence from juvenile animal experiments with dobutamine supported the design of clinical trials in neonatal/paediatric population. Studies were identified by searching MEDLINE (1946-2012) and EMBASE (1974-2012). Articles retrieved were independently reviewed by three authors and only those concerning efficacy and safety of the drug in juvenile animals were included. Only original articles published in English and Spanish were included. Following our literature search, 265 articles were retrieved and 24 studies were included in the review: 17 focused on neonatal models and 7 on young animal models. Although the aims and design of these studies, as well as the doses and ages analysed, were quite heterogeneous, the majority of authors agree that dobutamine infusion improves cardiac output in a dose dependent manner. Moreover, the cardiovascular effects of dobutamine are influenced by postnatal age, as well as by the dose used and the duration of the therapy. There is inadequate information about the effects of dobutamine on cerebral perfusion to draw conclusions. There is enough preclinical evidence to ensure that dobutamine improves cardiac output, however to better understand its effects in peripheral organs, such as the brain, more specific and well designed studies are required to provide additional data to support the design of clinical trials in a paediatric population.
    PLoS ONE 04/2014; 9(4):e95644. DOI:10.1371/journal.pone.0095644 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Severe perinatal asphyxia with hypoxic ischaemic encephalopathy occurs in approximately 1-2/1000 live births and is an important cause of cerebral palsy and associated neurological disabilities in children. Multiorgan dysfunction commonly occurs as part of the asphyxial episode, with cardiovascular dysfunction occurring in up to a third of infants. This narrative paper attempts to review the literature on the importance of early recognition of cardiac dysfunction using echocardiography and biomarkers such as troponin and brain type natriuretic peptide. These tools may allow accurate assessment of cardiac dysfunction and guide therapy to improve outcome.
    Archives of Disease in Childhood 07/2011; 97(4):372-5. DOI:10.1136/adc.2011.214205 · 2.91 Impact Factor