Remifentanil is a newly synthesized 4-anilido-piperidine with an ester side chain susceptible to esterase metabolism. We evaluated the safety, analgesic efficacy, and pharmacokinetics of remifentanil in 48 male volunteers. Volunteers were randomized to receive increasing doses of remifentanil, alfentanil, or placebo. Analgesic efficacy was evaluated by increasing tolerance to a spring-loaded rod measured at the tibia and sternum at multiple time points. Respiratory depression was measured by changes in arterial blood gas tensions and peripheral hemoglobin oxygen saturation. Hemodynamics were continuously monitored by means of an intra-arterial catheter. Both remifentanil and alfentanil produced a dose-dependent increase in analgesia and respiratory depression. Remifentanil was 20 to 30 times more potent (milligram to milligram) than alfentanil when assessed by either analgesic efficacy or respiratory measures. The pharmacokinetics of remifentanil were best described by a biexponential decay curve. Remifentanil had a small volume of distribution of 0.39 (SD, +/- 0.25) L/kg (alfentanil, 0.52 +/- 2 L/kg), with a rapid distribution phase of 0.94 (SD, +/- 0.57) min and an extremely short elimination half-life of 9.5 (SD, +/- 4) min compared with an elimination half-life of alfentanil of 58 (SD, +/- 7.6) min. The t1/2 ke0 (half-time for equilibration between plasma and the effect compartment) of remifentanil for analgesia was calculated as 1.3 min. Thus, remifentanil appears to have a pharmacologic profile similar to other potent mu agonists, but with exceptionally short-lasting pharmacokinetics, which is likely to make it a very useful opioid for clinical practice.

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We have compared short axis images of the left ventricle (LV) obtained with transoesophageal echocardiography (TOE) to assess LV size and function with those obtained by radionuclide angiography (RNA). Simultaneous TOE and RNA images were attempted in 14 patients and results obtained in 12 patients undergoing repair of abdominal aortic aneurysms. The area of the LV cavity seen in the short axis images at a mid-papillary muscle level at end-systole (ESA) and end-diastole (EDA) were compared with volumes measured by RNA at end-systole (ESV) and end-diastole (EDV). An area ejection fraction (AEF) calculated from the TOE images (AEF = EDA-ESA/EDA) was compared with the RNA ejection fraction (EF) where EF = EDV-ESV/EDV. Good correlations were found between TOE log EDA and RNA log EDV (r = 0.86), TOE log ESA and RNA log ESV (r = 0.92) and TOE AEF and RNA EF (r = 0.96). This suggests that TOE short axis imaging at a mid-papillary muscle level is generally adequate for monitoring LV function during operation.