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Volume 3 Supplement 1

ESICM LIVES 2015

  • Poster presentation
  • Open Access

Acute haemodynamic effects of dobutamine in experimental sepsis-induced myocardial depression

  • 1, 2,
  • 1 and
  • 1
Intensive Care Medicine Experimental20153 (Suppl 1) :A799

https://doi.org/10.1186/2197-425X-3-S1-A799

  • Published:

Keywords

  • Stroke Volume
  • Dobutamine
  • Haemodynamic Effect
  • Myocardial Depression
  • Faecal Peritonitis

Introduction

Septic patients with myocardial depression are routinely treated with dobutamine[1]. Whether this strategy is desirable is questionable, as catecholamines increase cardiac work, reduce myocardial efficiency, and are cardiotoxic[2]. We can accurately predict mortality in a 72-hour fluid-resuscitated rat model of faecal peritonitis as early as 6 hours, based on the degree of myocardial depression (low stroke volume, high heart rate)[3]. This model offers a useful means of testing safety and efficacy of therapeutic interventions in predicted survivors and non-survivors.

Objectives

To compare dose-related haemodynamic effects of dobutamine at 6 hours post-insult in predicted survivors and non-survivors from faecal peritonitis.

Methods

Male Wistar rats (341 ± 33 g) were instrumented with arterial and central venous lines. Sepsis was induced (ip injection of faecal slurry), and fluid resuscitation (10 ml/kg/h) started 2 hours later. At 6 hours, animals were assigned to good prognosis or poor prognosis groups - depending on echo-derived stroke volume (cutoff value 0.20 ml, based on previous experiments). An additional fluid bolus (10 ml/kg) was given, followed by dobutamine infusion, increasing from 5 to 20 µg/kg/min in 2.5-µg/kg/min increments every 5 minutes, with haemodynamic measures recorded just prior. Repeated measures ANOVA and post-hoc Holm-Sidak test were used to seek statistically significant. differences.

Results

Stroke volume at 6 h was significantly lower in poor prognosis animals; good prognosis animals were more responsive than poor prognosis animals to dobutamine, with earlier rises in heart rate, stroke volume and cardiac output, and a fall in blood pressure (Figure 1).
Figure 1
Figure 1

*p < 0.05 vs. baseline (good prognosis group, dark blue bars, N = 4). # p < 0.05 vs. baseline (poor prognosis group, light blue bars, N = 3).

Conclusions

The early hypodynamic circulatory profile of poor prognosis septic rats is associated with catecholamine-hyporesponsiveness. This supports an underlying mechanism of impaired adrenergic signal transduction, and/or dysfunctional downstream pathways. Our data support the investigation of alternative agents for sepsis-induced myocardial depression.

Grant Acknowledgement

ESICM Basic Science Award, UK Intensive Care Society Young Investigator Award, NIHR.

Authors’ Affiliations

(1)
University College London, Bloomsbury Institute of Intensive Care Medicine, London, United Kingdom
(2)
Università degli Studi di Milano, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Milan, Italy

References

  1. Dellinger RP, et al: Intensive Care Med. 2013, 39: 165-228. 10.1007/s00134-012-2769-8.PubMedView ArticleGoogle Scholar
  2. Singer M: Lancet. 2007, 370: 636-637. 10.1016/S0140-6736(07)61317-8.PubMedView ArticleGoogle Scholar
  3. Rudiger A, et al: Clin Sci. 2013, 124: 391-401. 10.1042/CS20120334.PubMedView ArticleGoogle Scholar

Copyright

© Andreis et al.; 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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