James E. Cooke

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. An inhibitory sigmoid Emax model of the maximal decrease in spectral edge produced by the opioid related spectral edge values to serum concentrations of sufentanil. The resulting data for the pharmacodynamic parameters of sufentanil were compared with fentanyl parameters that were obtained by reanalysis from an identically conducted, previously published study. The half-time of blood-brain equilibration (T1/2Keo) was not statistically different between sufentanil and fentanyl (6.2 +/- 2.8 vs. 6.6 +/- 1.7 min, mean +/- SD, respectively). The intrinsic potency of sufentanil, as measured by the serum concentration needed to cause half the maximal EEG slowing (IC50), was 12-fold greater (0.68 +/- 0.31 ng/ml) than that of fentanyl (8.1 +/- 2.2 ng/ml). The second part of the study verified the hypothesis that administration of equipotent bolus doses would produce equal onset times. Bolus injections of either 125 micrograms of sufentanil or 1,250 micrograms of fentanyl were given during EEG recording. 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.

Testing Computer-controlled Infusion Pumps by Simulation

The pharmacokinetic behavior of intravenous anesthetic drugs can be described by two- or three-compartment models. Rapid achievement and maintenance of steady plasma concentrations of these drugs requires a complicated delivery scheme, perhaps best controlled by a computer. The authors developed a method of simulating the performance of a computer-controlled infusion pump from the differential equations describing drug transfer between compartments. They also derived a mathematically simple and flexible approximate solution to these equations using Eulers numerical method. They incorporated this approximate solution into a computer-controlled infusion pump for intravenous drugs. They tested their pump by simulating the administration of fentanyl to a hypothetical patient whose fentanyl pharmacokinetics were described by a three-compartment model. The exact analytical solution served as the standard of comparison. The approximation technique, using a 15-s interval between model updates, had a maximum error of 0.35 ng.ml-1, and rapidly converged on the exact solution. The simulations revealed oscillations in the system. The authors suggest that such simulations be used to evaluate computer-controlled infusion pumps prior to clinical trials of these devices.

Anesthetic complications 14 hours after the use of crack cocaine.

PMEFV curve) is grossly distorted (Figure 2). In our study, we analyzed the initial plateau (point D) and referred to initial “peak” flow as shown in the figure in the published article. We apologize that this was not explained more clearly. Figure 2 shows the curve generated 30 min after interscalene block in the same patient from the published article, compared to the patient’s normal baseline MEFV curve. A normal PMEFV curve peak flow from the same starting volume would be expected to exceed point E. The fact that flow eventually exceeded a value on the effort independent portion of the curve at the same lung volume (point F), we believe, is of less interest. We feel that this grossly distorted curve with reduced early flow is evidence that the intact diaphragm contributes to normal forced expiration. The PEFR data referred to in Table 1 of the published article (1) indeed were measured at the same lung volume, referenced to residual volume.

Increased fluid flow through the streamline intravenous catheter

An intravenous (IV) catheter called the Streamline venous access device (Menlo Care, Palo Alto, Calif.) has been developed and approved by the FDA for use in humans. It is constructed of a new polyurethane-based hydrogel polymer blend known as Aquavene (Menlo Care). This catheter undergoes a precise and predictable increase in cross-sectional diameter and decrease in stiffness when it is hydrated. In this study, we compared the flow characteristics of 20-gauge Streamline catheters and 18-gauge CathlonIV (Critikon, Tampa, Fla.) Teflon catheters after IV placement in obstetric patients in a randomized, blinded fashion