Hemodynamic and metabolic effects of a new pediatric dobutamine formulation in hypoxic newborn pigs

Journal name:
Pediatric Research
(2017)
Volume:
81,
Pages:
511–518
DOI:
doi:10.1038/pr.2016.257
Received
Accepted
Accepted article preview online
Advance online publication

Abstract

Background:

The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans.

Methods:

Newborn pigs (n = 18) were exposed to 2-h hypoxia (10–15% oxygen) followed by reoxygenation (21–30% oxygen 4h). After 1-h reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10–15 or 15–20 µg/kg/min. Dobutamine groups received two dobutamine doses during 30min with a 60min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals, an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF.

Results:

Hypoxia significantly decreased CI, systemic vascular resistance and mean arterial blood pressure (MABP). Dobutamine doses significantly increased heart-rate, CI, and oxygen-delivery without changes in stroke-volume and MABP. Only 10–15 µg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared spectroscopy. A positive correlation was observed between SVCF and CI.

Conclusion:

The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials.

At a glance

Figures

  1. Figure 1:

    Experimental protocol. The arrows represents the points at which the data were recorded. CaO2, arterial oxygen content; CI, cardiac index; CVP, central venous pressure; CK, creatine kinase; DI, dobutamine infusion; FiO2, fraction of inspired oxygen; FTOE, systemic fractional oxygen extraction; HR, heart rate; MABP, mean arterial blood pressure; OD, oxygen delivery; pIO2, peripheral intravascular oxygenation; pTOI, peripheral tissue oxygenation index; SVI, stroke volume index; SVRI, systemic vascular resistance index; TnT, troponin T; VO2, oxygen consumption.

  2. Figure 2:

    Correlation between superior vena cava flow (SVCF) and cardiac index (CI). The regression line and correlation coefficient (r2 = 0.645) demonstrate a significant linear relationship (P < 0.0001).

  3. Figure 3:

    The effect of dobutamine infusion in systemic hemodynamic. (a) Mean arterial blood pressure (MABP) and (b) heart rate (HR) in control group (white circle), low to medium dobutamine (L-M) dose group (black triangle) and medium to high dobutamine (M-H) dose group (black square). Data are expressed as mean and SD. *P < 0.05 vs. Control group (one-way ANOVA), §P < 0.05 vs. pretreatment (Student’s paired t test) and P < 0.05 vs. control group (two-way repeated-measures ANOVA as a function of group and time).

  4. Figure 4:

    The effect of dobutamine infusion in systemic hemodynamic indexes. (a) Cardiac index, (b) systemic vascular resistance index and (c) stroke volume index in control group (white circle), low to medium dobutamine (L-M) dose group (black triangle) and medium to high dobutamine (M-H) dose group (black square). Data expressed as mean and SD. *P < 0.05 vs. control group (one-way ANOVA), §P < 0.05 vs. pretreatment (Student’s paired t-test) and P < 0.05 vs. control group (two-way repeated-measures ANOVA as a function of group and time).

  5. Figure 5:

    The effect of dobutamine infusion in systemic oxygen metabolism. (a) Oxygen delivery (OD), (b) oxygen consumption (VO2) and (c) oxygen extraction (FTOE) in control group (white circle), low to medium dobutamine (L-M) dose group (black triangle) and medium to high dobutamine (M-H) dose group (black square). Data expressed as mean and SD. *P < 0.05 vs. control group (one-way ANOVA), §P < 0.05 vs. pretreatment (Student’s paired t-test) and P < 0.05 vs. control group (two-way repeated-measures ANOVA as a function of group and time).

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Affiliations

  1. Experimental Unit, BioCruces Health Research Institute and Cruces University Hospital, Barakaldo, Bizkaia, Spain

    • Victoria E. Mielgo,
    • Adolf Valls-i-Soler,
    • Juan M. Lopez-de-Heredia &
    • Carmen Rey-Santano
  2. Academic Department of Paediatrics, Brighton and Sussex Medical School, Brighton, UK

    • Heike Rabe
  3. Adolf Valls-i-Soler is deceased in December 2013.

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