LAUSR

The objective of our study was to establish in sedated rats the consequences of high-dose fentanyl-induced acute muscle rigidity on the mechanical properties of the respiratory system and on the metabolic rate. Doses of fentanyl that we have previously shown to produce persistent rigidity of the muscles of the limbs and trunk in the rat (150 -300 microg/kg iv), were administered in 23 volume-controlled mechanically ventilated and sedated rats. The effects of a low dose of the FDA approved central alpha-2 agonist, dexmedetomidine (3 microg/kg iv), which has been suggested to oppose fentanyl-induced muscle rigidity, were determined after fentanyl administration. Fentanyl produced a significant decrease in Crs in the 23 rats that were studied. In 13 rats, an abrupt response occurred within 90 seconds, consisting in rapid rhythmic contractions of most skeletal muscles, that were replaced by persistent tonic/tetanic contractions leading a significant decrease of Crs (from 0.51 ± 0.11 ml/cmH2O to 0.36 ± 0.08 ml/cmH2O, 3 minutes after fentanyl injection). In the other 10 animals, a Crs progressively decreased to 0.26 ± 0.06 ml/cmH2O at 30 minutes. There was a significant rise in V̇O2 during muscle tonic contractions (from 8.48 ± 4.31 to 11.29 ± 2.57 ml/min), which contributed to a significant hypoxemia, despite ventilation being held constant. Dexmedetomidine provoked a significant and rapid increase in Crs towards baseline levels, while decreasing the metabolic rate and restoring normoxemia. We propose that the changes in respiratory mechanics and metabolism produced by opioid-induced muscle rigidity contribute to fentanyl lethality.