title: Dexmedetomidine and fentanyl exhibit temperature dependent effects on human respiratory cilia.
abstract: BACKGROUND
  Dexmedetomidine (dex) is commonly used in intensive care due to its effective sedation and analgesia with few adverse effects and minimal respiratory depression. However, we recently observed that exposing mouse epithelial respiratory cells to dex decreased ciliary beat frequency (CBF), suggesting dex may pose pulmonary risk.
  
  
  OBJECTIVE
  The purpose of this study is to determine the effects of dex at clinically relevant doses on CBF in human respiratory epithelia.
  
  
  METHODS
  Human nasal epithelial cilia were obtained from the inferior nasal turbinate with a rhinoprobe and placed in culture medium at 15°C and 37°C. At 5 and 30 min, video-microscopy was used to assess CBF, either without (control) or with different concentrations (1, 5, and 10 nM) of dex, fentanyl (fen), and dex + fen combination.
  
  
  RESULTS
  At 15°C, CBF was lower in the dex group compared to controls at 5 and 30 min. At 37°C, there was a significant increase in CBF with dex at 5 and 30 min, except for dex at 5 nM after 5 min, which showed a significant decrease. At 15°C the combination of dex + fen showed a positive interaction, causing less ciliary inhibition as expected. In contrast, no interaction between drugs was seen between dex and fen at 37°C.
  
  
  CONCLUSIONS
  At low temperatures, dex reduces CBF in human respiratory epithelia, whereas dex increases CBF at physiologic temperature in vitro. Whether these effects translate into clinical consequences during hypothermia, as with cardiopulmonary bypass surgery will require further studies.
authors.affiliation: Department of Pediatrics, University of Pittsburgh , Pittsburgh, PA , USA.
authors.forename: Nils
authors.initials: N
authors.lastname: Welchering
authors.affiliation: Department of Pediatrics, University of Pittsburgh , Pittsburgh, PA , USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ochoa
authors.affiliation: Office of Biostatistics Research, NHLBI , Washington, DC , USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Developmental Biology, University of Pittsburgh , Pittsburgh, PA , USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Francis
authors.affiliation: Department of Developmental Biology, University of Pittsburgh , Pittsburgh, PA , USA.
authors.forename: Maliha
authors.initials: M
authors.lastname: Zahid
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh , Pittsburgh, PA , USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Muñoz
authors.affiliation: Department of Developmental Biology, University of Pittsburgh , Pittsburgh, PA , USA.
authors.forename: Cecilia W
authors.initials: CW
authors.lastname: Lo
keywords: airway cilia motility; ciliary beat frequency; dexmedetomidine; fentanyl; human cilia; hypothermia