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The Effects of Short-Term Propofol and Dexmedetomidine on Lung Mechanics, Histology, and Biological Markers in Experimental Obesity

Barros Heil, Luciana Boavista MD; Santos, Cíntia L. PhD; Santos, Raquel S. PhD; Samary, Cynthia S. PhD; Cavalcanti, Vinicius C. M. MD, MSc; Araújo, Mariana M. P. N. MD; Poggio, Hananda PhD; de A. Maia, Lígia PhD; Trevenzoli, Isis Hara PhD; Pelosi, Paolo MD, FERS; Fernandes, Fatima C. MD, PhD; Villela, Nivaldo R. MD, PhD; Silva, Pedro L. PhD; Rocco, Patricia R. M. MD, PhD

doi: 10.1213/ANE.0000000000001114
Anesthetic Pharmacology: Research Report

BACKGROUND: Administering anesthetics to the obese population requires caution because of a variety of reasons including possible interactions with the inflammatory process observed in obese patients. Propofol and dexmedetomidine have protective effects on pulmonary function and are widely used in short- and long-term sedation, particularly in intensive care unit settings in lean and obese subjects. However, the functional and biological effects of these drugs in obesity require further elucidation. In a model of diet-induced obesity, we compared the short-term effects of dexmedetomidine versus propofol on lung mechanics and histology, as well as biological markers of inflammation and oxidative stress modulation in obesity.

METHODS: Wistar rats (n = 56) were randomly fed a standard diet (lean) or experimental diet (obese) for 12 weeks. After this period, obese animals received sodium thiopental intraperitoneally and were randomly allocated into 4 subgroups: (1) nonventilated (n = 4) for molecular biology analysis only (control); (2) sodium thiopental (n = 8); (3) propofol (n = 8); and (4) dexmedetomidine (n = 8), which received continuous IV administration of the corresponding agents and were mechanically ventilated (tidal volume = 6 mL/kg body weight, fraction of inspired oxygen = 0.4, positive end-expiratory pressure = 3 cm H2O) for 1 hour.

RESULTS: Compared with lean animals, obese rats did not present increased body weight but had higher total body and trunk fat percentages, airway resistance, and interleukin-6 levels in the lung tissue (P = 0.02, P = 0.0027, and P = 0.01, respectively). In obese rats, propofol, but not dexmedetomidine, yielded increased airway resistance, bronchoconstriction index (P = 0.016, P = 0.02, respectively), tumor necrosis factor-α, and interleukin-6 levels, as well as lower levels of nuclear factor-erythroid 2–related factor-2 and glutathione peroxidase (P = 0.001, Bonferroni-corrected t test).

CONCLUSIONS: In this model of diet-induced obesity, a 1-hour propofol infusion yielded increased airway resistance, atelectasis, and lung inflammation, with depletion of antioxidative enzymes. However, unlike sodium thiopental and propofol, short-term infusion of dexmedetomidine had no impact on lung morphofunctional and biological variables.

Published ahead of print December 30, 2015

From the *Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Surgical and Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Faculty of Medicine, Laboratory of Experimental Surgery, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; §Laboratory of Molecular Endocrinology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy; and Division of Anesthesiology, Department of Surgery, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

Accepted for publication November 3, 2015.

Published ahead of print December 30, 2015

Funding: Brazilian Council for Scientific and Technological Development (CNPq), Rio de Janeiro State Research Foundation (FAPERJ), Coordination for the Improvement of Higher Education Personnel (CAPES), and Department of Science and Technology (DECIT)/Ministry of Health.

The authors declare no conflicts of interest.

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Address correspondence to Patricia R. M. Rocco, MD, PhD, Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Sl G01-014, Ilha do Fundão, Rio de Janeiro, RJ, Brazil 21941. Address e-mail to prmrocco@gmail.com.

© 2016 International Anesthesia Research Society