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

Anesth Analg. 2016 Apr;122(4):1015-23. doi: 10.1213/ANE.0000000000001114.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Dexmedetomidine / administration & dosage*
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology*
  • Male
  • Obesity / drug therapy
  • Obesity / metabolism
  • Obesity / pathology*
  • Propofol / administration & dosage*
  • Rats
  • Rats, Wistar
  • Respiration, Artificial / adverse effects
  • Respiratory Mechanics / drug effects*
  • Respiratory Mechanics / physiology
  • Treatment Outcome

Substances

  • Biomarkers
  • Dexmedetomidine
  • Propofol