Anesthesiology
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Comparative Study
Pharmacokinetics, pharmacodynamics, and rational opioid selection.
Fentanyl, alfentanil, and sufentanil have important pharmacokinetic and pharmacodynamic differences. Selecting one of these opioid analgesics as an adjunct to general anesthesia requires appreciation of the relationship between the pharmacokinetic and pharmacodynamic characteristics of these drugs and the onset of and recovery from drug effect. Using a pharmacokinetic-pharmacodynamic model, the authors simulated the decrease in plasma fentanyl, alfentanil, and sufentanil concentration after intravenous administration by either bolus injection, brief infusion, or prolonged infusion. ⋯ Alfentanil may also be the most appropriate drug to provide a transient peak effect after a single bolus. Although sufentanil has longer distribution and elimination half-lives than alfentanil, recovery from sufentanil infusions may be more rapid than recovery from alfentanil infusions for operations shorter than 6-8 h. These computer simulations demonstrate that simply comparing pharmacokinetic parameters (e.g., half-lives) of different drugs will not predict the relative rates of decrease in effect site concentrations after either an intravenous bolus or a continuous infusion.
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Comparative Study
Electroencephalographic quantitation of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil.
The authors compared the pharmacodynamics of sufentanil with those of fentanyl using the electroencephalogram (EEG) as a measure of opioid drug effect. Sixteen patients were given a rapid infusion of sufentanil (18.75 micrograms/min) during EEG recording. To quantitate the opioid-induced slowing of the EEG, the authors analyzed its power spectrum and calculated the spectral edge. ⋯ The time from injection to 50% maximal EEG slowing (T50) was calculated for each patient. The values for T50 for the two groups did not differ. The authors conclude that fentanyl and sufentanil have similar pharmacodynamic profiles, the former being 12 times more potent than the latter.
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The current study evaluated the effects of tetanic stimulation on neuromuscular responses to serial train-of-four (TOF) and double-burst stimulation (DBS). For TOF monitoring (n = 13), a degree of neuromuscular blockade was achieved with an intravenous vecuronium infusion such that the ratio of fourth twitch (T4) to first twitch (T1), T4/T1, was stable at a value between 0.1 and 0.7. Four seconds after a 5-s, 50-Hz tetanic stimulus was delivered, TOF monitoring was resumed at 10-s intervals. ⋯ The posttetanic effects on D1, D2, and D2/D1 persisted for 43, 66, and 46 s, respectively. For DBS3,2, median posttetanic (50-Hz, 5-s) increases were 41, 275, and 176%, while corresponding times to recovery were 43, 43, and 43 s. Although the data indicate that the posttetanic percent increase was at least 10 times larger at greater degrees of blockade (T4/T1 = 0.1) than at lesser degrees (T4/T1 = 0.7), all T4/T1 and D2/D1 ratios returned to within 10% of baseline in 125 s or less after 5-s tetanic stimulation.
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Ten patients with parenchymal acute respiratory failure (ARF) underwent computed tomography (CT) scans while in the supine and prone positions. At equal levels of positive end-expiratory pressure, the authors measured the changes of CT density in dorsal and ventral basilar lung regions induced by the change of position as well as alterations of gas exchange. The level of venous admixture did not change with body position. ⋯ However, in patients in the supine position, lung CT density increased and regional inflation decreased from ventral to dorsal, suggesting progressive deflation of gas-containing alveoli along the gravity gradient. A similar ventral-dorsal deflation pattern occurred within 10 min in patients in the prone position. We conclude that the lung in patients with ARF behaves like an elastic body with a diffusely increased mass; dependent lung regions are compressed by the pressure of overlying structures.(ABSTRACT TRUNCATED AT 250 WORDS)