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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of propofol and remifentanil on phrenic nerve activity and nociceptive cardiovascular responses in rabbits.

BACKGROUND: The effects of propofol, remifentanil, and their combination on phrenic nerve activity (PNA), resting heart rate (HR), mean arterial pressure (MAP), and nociceptive cardiovascular responses were studied in rabbits. METHODS: Basal anesthesia and constant blood gas tensions were maintained with alpha-chloralose and mechanical ventilation. PNA, HR, MAP, and maximum changes in HR and MAP (deltaHR, deltaMAP) evoked by electrical nerve stimulation of tibial nerves were recorded. The comparative effects were observed for propofol at infusion rates from 0.05 to 3.2 mg x kg(-1) x min(-1) (group I) and remifentanil from 0.0125 to 12.8 microg x kg(-1) x min(-1) alone (group II), and during constant infusions of propofol at rates of 0.1 and 0.8 mg x kg(-1) x min(-1) (groups III and IV, respectively). Finally, the effect of remifentanil on propofol blood levels was observed (group V). RESULTS: The infusion rates for 50% depression (ED50) of PNA, deltaHR, and deltaMAP were 0.41, 1.32, and 1.58 mg x kg-(1) x min(-1) for propofol, and 0.115, 0.125, and 1.090 microg x kg(-1) x min(-1) for remifentanil, respectively. The ratios for the ED50 values of deltaHR and deltaMAP to PNA were 3.2 and 3.9 for propofol, and 1.1 and 9.5 for remifentanil, respectively. Analysis of the expected and observed responses and isobologrms showed that although their combined effects on PNA, resting HR, and MAP, and deltaMAP were synergistic for deltaHR, they were merely additive. Remifentanil had no effect on propofol blood levels. CONCLUSION: PNA was abolished by propofol and remifentanil, alone and in combination, before significant depression of nociceptive pressor responses occurred. Their combined effects on PNA, HR, MAP, and deltaMAP are greater than additive, ie., synergistic. Unlike propofol, remifentanil obtunded pressor responses more than the resting circulation.[1]


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