Document Detail

The pharmacodynamic effect of a remifentanil bolus on ventilatory control.
MedLine Citation:
PMID:  10691225     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: In doses typically administered during conscious sedation, remifentanil may be associated with ventilatory depression. However, the time course of ventilatory depression after an initial dose of remifentanil has not been determined previously. METHODS: In eight healthy volunteers, the authors determined the time course of the ventilatory response to carbon dioxide using the dual isohypercapnic technique. Subjects breathed via mask from a to-and-fro circuit with variable carbon dioxide absorption, allowing the authors to maintain end-tidal pressure of carbon dioxide (PET(CO2)) at approximately 46 or 56 mm Hg (alternate subjects). After 6 min of equilibration, subjects received 0.5 microg/kg remifentanil over 5 s, and minute ventilation (V(E)) was recorded during the next 20 min. Two hours later, the study was repeated using the other carbon dioxide tension (56 or 46 mm Hg). The V(E) data were used to construct two-point carbon dioxide response curves at 30-s intervals after remifentanil administration. Using published pharmacokinetic values for remifentanil and the method of collapsing hysteresis loops, the authors estimated the effect-site equilibration rate constant (k(eo)), the effect-site concentration producing 50% respiratory depression (EC50), and the shape parameter of the concentration-response curve (gamma). RESULTS: The slope of the carbon dioxide response decreased from 0.99 [95% confidence limits 0.72 to 1.26] to a nadir of 0.27 l x min(-1) x mm Hg(-1) [-0.12 to 0.66] 2 min after remifentanil (P<0.001); within 5 min, it recovered to approximately 0.6 l x min(-1) x mm Hg(-1), and within 15 min of injection, slope returned to baseline. The computed ventilation at PET = 50 mm Hg (VE50) decreased from 12.9 [9.8 to 15.9] to 6.1 l/min [4.8 to 7.4] 2.5 min after remifentanil injection (P<0.001). This was caused primarily by a decrease in tidal volume rather than in respiratory rate. Estimated pharmacodynamic parameters based on computed mean values of VE50 included k(eo) = 0.24 min(-1) (T1/2 = 2.9 min), EC50 = 1.12 ng/ml, and gamma = 1.74. CONCLUSIONS: After administration of 0.5 microg/kg remifentanil, there was a decrease in slope and downward shift of the carbon dioxide ventilatory response curve. This reached its nadir approximately 2.5 min after injection, consistent with the computed onset half-time of 2.9 min. The onset of respiratory depression appears to be somewhat slower than previously reported for the onset of remifentanil-induced electroencephalographic slowing. Recovery of ventilatory drive after a small dose essentially was complete within 15 min.
H D Babenco; P F Conard; J B Gross
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  92     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-06     Completed Date:  2000-03-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  393-8     Citation Subset:  AIM; IM    
Department of Anesthesiology, University of Connecticut School of Medicine, Farmington, 06030-2015, USA.
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MeSH Terms
Analgesics, Opioid / pharmacokinetics,  pharmacology*
Carbon Dioxide / blood,  pharmacology
Depression, Chemical
Injections, Intravenous
Piperidines / pharmacokinetics,  pharmacology*
Respiratory Mechanics / drug effects*
Tidal Volume / physiology
Reg. No./Substance:
0/Analgesics, Opioid; 0/Piperidines; 124-38-9/Carbon Dioxide; 132875-61-7/remifentanil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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