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Effects of Intraoperative Infusion of Esmolol on Systemic and Pulmonary Inflammation in a Porcine Experimental Model of Lung Resection Surgery

Garutti, Ignacio MD, PhD*; Rancan, Lisa PhD; Abubakra, Selma PhD*; Simón, Carlos MD, PhD; Paredes, Sergio Damian PhD§; Ortega, Javier PhD; Huerta, Luis MD, PhD; Ramos, Silvia PhD*; Vara, Elena PhD

doi: 10.1213/ANE.0000000000003737
Basic Science: Original Laboratory Research Report
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BACKGROUND: Lung resection surgery (LRS) is associated with systemic and pulmonary inflammation, which can affect postoperative outcomes. Activation of β-adrenergic receptors increases the expression of proinflammatory and anti-inflammatory mediators, and their blockade may attenuate the systemic inflammatory response. The aim of this study was to analyze the effect of a continuous perioperative intravenous perfusion of esmolol on postoperative pulmonary edema in an experimental model of LRS requiring periods of one-lung ventilation (OLV).

METHODS: Twenty-four large white pigs were randomly assigned to 3 groups: control (CON), esmolol (ESM), and sham. The ESM group received an intravenous esmolol bolus (0.5 mg/kg) and then an esmolol infusion (0.05 mg·kg−1·minute−1) throughout the procedure. The CON group received the same volume of 0.9% saline solution as the ESM group plus a continual infusion of saline. The sham group underwent a left thoracotomy without LRS or OLV. At the end of the LRS, the animals were awakened, and after 24 hours, they underwent general anesthesia again. Lung biopsies and plasma samples were obtained to analyze the levels and expression of inflammatory mediators, and the animals also received a bronchoalveolar lavage.

RESULTS: At 24 hours after the operation, the ESM group had less lung edema and lower expression of the proinflammatory biomarkers tumor necrosis factor (TNF) and interleukin (IL)-1 compared to the CON group for both lung lobes. For the mediastinal lobe biopsies, the mean difference and 95% confidence interval (CI) between the groups for edema, TNF, and IL-1 were 14.3 (95% CI, 5.6–23.1), P = .002; 0.19 (95% CI, 0.07–0.32), P = .002; and 0.13 (95% CI, 0.04–0.22), P = .006, respectively. In the left upper lobe, the mean differences for edema, TNF, and IL-1 were 12.4 (95% CI, 4.2–20.6), P = .003; 0.25 (95% CI, 0.12–0.37), P < .001; and 0.3 (95% CI, 0.08–0.53), P = .009.

CONCLUSIONS: Our results suggest that esmolol reduces lung edema and inflammatory responses in the intraoperative and postoperative periods in animals that underwent LRS with OLV.

From the *Department of Anesthesiology, Gregorio Marañón University General Hospital, Madrid, Spain

Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Madrid, Spain

Department of Thoracic Surgery, Gregorio Marañón University General Hospital, Madrid, Spain

§Department of Physiology, School of Medicine, Complutense University of Madrid, Madrid, Spain.

Accepted for publication July 3, 2018.

Published ahead of print 3 July 2018.

Funding: This work was supported by Spanish Health Ministry (Grant FIS PI10/01900).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Reprints will not be available from the authors.

Address correspondence to Ignacio Garutti, MD, PhD, Department of Anesthesiology, Gregorio Marañón University General Hospital, Doctor Esquerdo, 46, 28009, Madrid, Spain. Address e-mail to ngaruttimartinez@yahoo.es.

Copyright © 2018 International Anesthesia Research Society
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