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Background: The subjective and psychomotor effects of remifentanil have not been evaluated. Accordingly, the authors used mood inventories and psychomotor tests to characterize the effects of remifentanil in healthy, non-drug-abusing volunteers. Alfentanil was used as a comparator drug., Methods: Ten healthy volunteers were enrolled in a randomized, double-blinded, placebo-controlled, crossover trial in which they received an infusion of saline, remifentanil, or alfentanil for 120 min. The age- and weight-adjusted infusions (determined with STANPUMP, a computer modeling software package) were given to achieve three predicted constant plasma levels for 40 min each of remifentanil (0.75, 1.5, and 3 ng/ml) and alfentanil (16, 32, and 64 ng/ml). Mood forms and psychomotor tests were completed, and miosis was assessed, during and after the infusions. In addition, analgesia was tested at each dose level using a cold-pressor test., Results: Remifentanil had prototypic micro-like opioid subjective effects, impaired psychomotor performance, and produced analgesia. Alfentanil at the dose range tested had more mild effects on these measures, and the analgesia data indicated that a 40:1 potency ratio, rather than the 20:1 ratio we used, may exist between remifentanil and alfentanil. A psychomotor test administered 60 min after the remifentanil infusion was discontinued showed that the volunteers were still impaired, although they reported feeling no drug effects., Conclusions: The notion that the pharmacodynamic effects of remifentanil are extremely short-lived after the drug is no longer administered must be questioned given our findings that psychomotor effects were still apparent 1 h after the infusion was discontinued.

We studied the time to postoperative micturition and the duration of analgesia in 82 children aged 6 mo to 10 yr undergoing herniorrhaphy or orchiopexy under general anesthesia with N2O and halothane. All received D5 lactate Ringer's solution equivalent to 6 h maintenance intraoperatively, and oral fluids postoperatively ad libitum. At the end of surgery, patients were randomly assigned to receive one of three regional anesthetic injections using 0.25% bupivacaine: caudal, 0.75 mL/kg (group I); caudal with 1:200,000 epinephrine, 0.75 mL/kg (group II); or ilioinguinaliliohypogastric nerve block with epinephrine through the wound by the surgeon (group III). Postoperatively, blinded observers scored pain at 30 min, hourly until discharge, and by telephone at 24-36 h. In the 74 patients with successful blocks (mean age 2.5 +/- 2.4 yr), the times to micturition (group I, 202 +/- 130 min; group II, 262 +/- 164 min; group III, 196 +/- 101 min) did not differ significantly among groups. Seven patients who took more than 8 h to void required no intervention. There was no difference in the numbers without pain for > or = 4 h (74%, 64%, and 69% of groups I, II, and III), or those requiring analgesics by 24 h (66% overall). The time to postoperative voiding in children is variable and not prolonged by caudal analgesia; caudal bupivacaine with or without epinephrine and ilioinguinaliliohypogastric nerve block are equally effective for postoperative analgesia.

We studied the time course, magnitude and homogeneity of the change in extracellular myocardial potassium activity after acute ligation of the left anterior descending coronary artery in pigs using potassium-sensitive electrodes made from a valinomycin-polyvinyl chloride matrix membrane. We also studied the relationship between the changes in potassium activity and the simultaneous changes in ventricular activation using the reference barrel of the K+ electrode to record ventricular electrograms. We found that the K+ rose sooner, more rapidly and to higher levels than previously reported. The K+ changes occurred in three phases: a phase of rapidly rising K+ that began within seconds of the ligation and lasted 5-15 minutes, a plateau phase that lasted approximately 15 minutes and a phase of slowly rising K+ that extended throughout the longest occlusion (60 minutes) used in this study. The K+ changes were reversed by release of the occlusion during the rapidly rising and plateau phases, but were not reversed by release of the occlusion during the phase of slowly rising K+. Inhomogeneities in the K+ rise appeared between the center and lateral margins of the midmyocardial ischemic zone, between the subendocardium and the subepicardium in the center of the ischemic zone, and between closely spaced electrodes located in the midmyocardial center of the ischemic zone. Thus, the change in K+ activity, as recorded by our electrodes, can be considered an excellent marker of ischemia. Changes in ventricular activation paralleled the K+ rise, the inhomogeneities of K+ rise and the reversal of the K+ rise after release but could not be entirely explained by the change in K+.

To determine if collateral ventilation (CV) occurs in pigs and dogs during intermittent positive-pressure ventilation (IPPV) and high-frequency oscillation (HFO), seven pigs and seven dogs were studied by measuring Xenon 133 washout (XeW) from an occluded subsegmental bronchus. The rate constant/min (K) for Xe blood uptake (KXeb) was derived, and when subtracted from K for XeW (KXeW) gave K for removal of Xe by CV (KXecv). Pig XeW were single exponentials with mean KXew = 0.25/min during IPPV and 0.12/min with HFO. In pigs, mean K of XeW was no different from KXeb so that all XeW occurred by blood uptake and none by CV. XeW in dogs had two exponentials. Dogs had over 11 times greater mean KXeW than pigs during IPPV and over 24 times greater during HFO. In dogs, on average, 79% (IPPV) and 87% (HFO) of XeW occurred by CV. CV is a means of gas exchange during HFO and IPPV in dogs but not in pigs.

We studied the individual and combined effects of extracellular acidosis and increases in extracellular potassium on action potential characteristics and conduction in order to gain a better understanding of the effects of acute ischemia. At each level of potassium between 2.7 and 17 mm, acidosis induced by increasing Pco2 (respiratory acidosis) and by decreasing HCO3- (metabolic acidosis) decreased resting membrane potential, the maximum rate of rise of the action potential upstroke (Vmax), and slowed conduction. Metabolic acidosis consistently and significantly lengthened the steady state action potential duration whereas respiratory acidosis did not. Respiratory acidosis caused changes in resting membrane potential, Vmax, and conduction velocity; which occurred more rapidly and were of greater magnitude than the changes induced by metabolic acidosis. The changes in Vmax induced both types of acidosis were due to a change in the resting membrane potential-Vmax relationship as well as to the changes in the resting membrane potential. The conduction slowing induced by acidosis was greater when potassium was 9 and 13 mM than when potassium was 5.4 mm. Our results suggest that acidosis causes important changes in the electrophysiological properties of ventricular fibers and that many of the known electrophysiological effects of acute ischemia can be mimicked by the combined effects of extracellular acidosis and an increase in extracellular potassium.