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

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Abstract

Background

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.

Design

Controlled, block-randomized study.

Setting

University research laboratory.

Subject

Mixed breed piglets (1–3 days, 1.5–2.3 kg).

Interventions

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 μg/kg/min), dobutamine (20 μg/kg/min) or milrinone (0.75 μg/kg/min) were infused for 2 h in a blinded, block-randomized fashion (n = 6/group).

Main results

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.

Conclusions

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.

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Abbreviations

CAF:

Carotid arterial blood flow

CO:

Cardiac output

H-R:

Hypoxia-reoxygenation

MAP:

Mean arterial pressure

PAP:

Pulmonary arterial pressure

PHT:

Pulmonary hypertension

RAF:

Renal arterial blood flow

SMAF:

Superior mesenteric arterial blood flow

VR:

Vascular resistance

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Acknowledgments

The project was funded by operating grants from the Canadian Institutes of Health Research and Stollery Children’s Hospital Foundation. CJ received support from the Clinician Investigator Program of the Royal College of Physicians and Surgeons of Canada and Clinical Fellowship Program of the Alberta Heritage Foundation for Medical Research. PYC is an investigator of the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

    Chloë Joynt & Po-Yin Cheung

  2. Department of Surgery, University of Alberta, Edmonton, AB, Canada

    David L. Bigam, Gregory Korbutt & Po-Yin Cheung

  3. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada

    Gregory Charrois & Laurence D. Jewell

  4. Royal Alexandra Hospital, NICU, Room 5027, 10240 Kingsway Avenue, Edmonton, AB, T5H 3V9, Canada

    Po-Yin Cheung

Authors
  1. Chloë Joynt
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  2. David L. Bigam
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  3. Gregory Charrois
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  4. Laurence D. Jewell
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  5. Gregory Korbutt
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  6. Po-Yin Cheung
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Correspondence to Po-Yin Cheung.

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Joynt, C., Bigam, D.L., Charrois, G. et al. Milrinone, dobutamine or epinephrine use in asphyxiated newborn pigs resuscitated with 100% oxygen. Intensive Care Med 36, 1058–1066 (2010). https://doi.org/10.1007/s00134-010-1820-x

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  • DOI: https://doi.org/10.1007/s00134-010-1820-x

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