A comparison of a prototype electromyograph vs. a mechanomyograph and an acceleromyograph for assessment of neuromuscular blockade.

The extent of neuromuscular blockade during anaesthesia is frequently measured using a train-of-four stimulus. Various monitors have been used to quantify the train-of-four, including mechanomyography, acceleromyography and electromyography. Mechanomyography is often considered to be the laboratory gold standard of measurement, but is not commercially available and has rarely been used in clinical practice. Acceleromyography is currently the most commonly used monitor in the clinical setting, whereas electromyography is not widely available. We compared a prototype electromyograph with a newly constructed mechanomyograph and a commercially available acceleromyograph monitor in 43 anesthetised patients. The mean difference (bias; 95% limits of agreement) in train-of-four ratios was 4.7 (-25.2 to 34.6) for mechanomyography vs. electromyography; 14.9 (-13.0 to 42.8) for acceleromyography vs. electromyography; and 9.8 (-31.8 to 51.3) for acceleromyography vs. mechanomyography. The mean difference (95% limits of agreement) in train-of-four ratios between opposite arms when using electromyography was -0.7 (-20.7 to 19.3). There were significantly more acceleromyography train-of-four values > 1.0 (23%) compared with electromyography or mechanomography (2-4%; p < 0.0001). Electromyography most closely resembled mechanomyographic assessment of neuromuscular blockade, whereas acceleromyography frequently produced train-of-four ratio values > 1.0, complicating the interpretation of acceleromyography results in the clinical setting.

The effects of an aviation-style computerised pre-induction anaesthesia checklist on pre-anaesthetic set-up and non-routine events.

This prospective, observational study compared the proportion of cases with missing critical pre-induction items before and after the implementation of an aviation-style computerised pre-induction anaesthesia checklist. Trained observers recorded the availability of critical pre-induction items and evaluated the characteristics of the pre-induction anaesthesia checklist performance including provider participation and distraction level, resistance to the use of the checklist and the time required for completion. Surgical cases that met the criteria for inclusion in the National Surgical Quality Improvement Program at a single academic hospital were selected for observation. A total of 853 cases were observed before and 717 after implementation of the checklist. The proportion of cases with failure to perform all pre-induction steps decreased from 10.0% to 6.4% (p = 0.012). There was also a significant decrease in the proportion of cases with non-routine events from 1.2% cases before to none after checklist implementation (p = 0.003). In 17 cases, the checklist alerted the anaesthesia provider to correct a mistake in pre-induction preparation.

Clinical and economic effects of pulmonary artery catheterization in nonemergent coronary artery bypass graft surgery.

OBJECTIVE: To examine the association between use of pulmonary artery catheterization with hospital outcomes and costs in nonemergent coronary artery bypass graft (CABG) surgery. DESIGN: Retrospective cohort study. SETTING: Fifty-six community-based hospitals in 26 states. PARTICIPANTS: A total of 13,907 patients undergoing nonemergent CABG surgery between January 1, 1997, and December 31, 1997. MEASUREMENTS AND MAIN RESULTS: Discharge abstracts for each patient were examined. Stratified and multivariate analyses were used to assess the impact of pulmonary artery catheters (PACs) on in-hospital mortality, length of stay in the intensive care unit, total length of stay, and hospital costs. Outcomes were adjusted for patient demographic factors, hospital characteristics, and hospital volume of PAC use in the year of analysis. Fifty-eight percent of the patients received a PAC. After adjustment, the relative risk of in-hospital mortality was 2.10 for the PAC group compared with the patients who did not receive a PAC (95% confidence interval [CI], 1.40 to 3.14; p < 0.001). The mortality risk was significantly higher in hospitals with the lowest third of PAC use (odds ratio, 3.35; 95% CI, 1.74 to 6.47; p < 0.001) and not significantly increased in the highest two thirds of users (odds ratio, 1.62; 95% CI, 0.99 to 2.66; p = 0.09). Days spent in critical care were similar; however, total length of hospital stay was 0.26 days longer in the PAC group (p < 0.001). Hospital costs were $1,402 higher in the PAC group. CONCLUSION: In the setting of nonemergent CABG surgery, pulmonary artery catheterization was associated with an increased risk of in-hospital mortality, greater length of stay, and higher total costs, particularly in hospitals with low volume of PAC use.

The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions.

BACKGROUND: There is considerable unexplained variability in alfentanil pharmacokinetics, particularly systemic clearance. Alfentanil is extensively metabolized in vivo, and thus systemic clearance depends on hepatic biotransformation. Cytochrome P450 3A4 was previously shown to be the predominant P450 isoform responsible for human liver microsomal alfentanil metabolism in vitro. This investigation tested the hypothesis that P450 3A4 is responsible for human alfentanil metabolism and clearance in vivo. METHODS: Nine healthy male volunteers who provided institutionally approved written informed consent were studied in a three-way randomized crossover design. Each subject received alfentanil (20 micrograms/kg given intravenously) 30 min after midazolam (1 mg injected intravenously) on three occasions: control; high P450 3A4 activity (rifampin induction); and low P450 3A4 activity (selective inhibition by troleandomycin). Midazolam is a validated selective in vivo probe for P450 3A4 activity. Venous blood was sampled for 24 h and plasma concentrations of midazolam and alfentanil and their primary metabolites 1'-hydroxymidazolam and noralfentanil were measured by gas chromatography-mass spectrometry. Pharmacokinetic parameters were determined by two-stage analysis using both noncompartmental and three-compartment models. RESULTS: Plasma alfentanil concentration-time profiles depended significantly on P450 3A4 activity. Alfentanil noncompartmental clearance was 5.3 +/- 2.3, 14.6 +/- 3.8, and 1.1 +/- 0.5 ml.kg-1.min-1, and elimination half-life was 58 +/- 13, 35 +/- 7, and 630 +/- 374 min, respectively, in participants with normal (controls), high (rifampin), and low (troleandomycin) P450 3A4 activity (means +/- SD; P < 0.05 compared with controls). Multicompartmental modeling suggested a time-dependent inhibition-resynthesis model for troleandomycin effects on P450 3A4 activity, characterized as k10(t) = k10[1-phi e-alpha(t-tzero)], where k10(t) is the apparent time-dependent rate constant, k10 is the uninhibited rate constant, phi is the fraction of P450 3A4 inhibited, and alpha is the apparent P450 3A4 reactivation rate. Alfentanil clearance was calculated as V1 k10 for controls and men receiving rifampin, and as V1.average k10(t) for men receiving troleandomycin. This clearance was 4.9 +/- 2.1, 13.2 +/- 3.6, and 1.5 +/- 0.8 ml.kg-1.min-1, respectively, in controls and in men receiving rifampin or troleandomycin. There was a significant correlation (r = 0.97, P < 0.001) between alfentanil systemic clearance and P450 3A4 activity. CONCLUSIONS: Modulation of P450 3A4 activity by rifampin and troleandomycin significantly altered alfentanil clearance and disposition. These results strongly suggest that P450 3A4 is the major isoform of P450 responsible for clinical alfentanil metabolism and clearance. This observation, combined with the known population variability in P450 3A4 activity, provides a mechanistic explanation for the interindividual variability in alfentanil disposition. Furthermore, known susceptibility of human P450 3A4 activity to induction and inhibition provides a conceptual framework for understanding and predicting clinical alfentanil drug interactions. Finally, human liver microsomal alfentanil metabolism in vitro is confirmed as an excellent model for human alfentanil metabolism in vivo.

A pulmonary artery catheter does not affect the intravascular electrocardiogram from the air aspiration introducer sheath.

The air aspiration introducer sheath allows the use of a pulmonary artery (PA) catheter for monitoring during sitting neurosurgical procedures while providing a means of air aspiration that is more efficient than aspiration from the proximal and distal ports of the PA catheter alone. To place the 25-cm long introducer sheath safely into the right atrium, the PA catheter should be positioned first and used as a guide for the introducer sheath, which is then advanced into the atrium and positioned by observation of the intravascular electrocardiogram (IVECG). Placement of the introducer sheath with the IVECG has been described previously without a PA catheter in the lumen of the introducer sheath. In this study, performed in dogs, we have demonstrated that the presence of a PA catheter in the lumen of the introducer sheath does not affect the IVECG recorded from the introducer sheath.

Valproic acid dosage and plasma protein binding and clearance.

Valproic acid clearance was determined in six normal subjects during a single-dose (250-mg) study and multiple-dose experiments of 500, 1,000, and 1,500 mg/day. Eight consecutive oral doses were taken at 12-hr intervals at each dosing level. Valproate levels and protein binding were determined at steady state. Clearance declined 20% from 8.33 +/- 2.44 to 6.67 +/- 1.25 ml/hr/kd between the single-dose and the 500-mg/day steps (p = 0.05). Clearance was unchanged between the 500- and 1,000-mg/day steps despite a 44% increase in mean free fraction (0.0703 +/- 0.0381 vs 0.1011 +/- 0.0438, p < 0.05), implying a balanced opposing decline in intrinsic clearance (from 89.2 +/0 71.0 to 72.0 +/- 20.8 ml/hr/kg; p = 0.025). In four subjects completing the 1,500-mg/day step, clearance increased from 6.76 +/- 1.48 ml/hr/kg (1,000- mg/day) to 8.20 +/- 1.62 ml/hr/kg, corresponding to a further increase in free fraction. Free fraction varied within a single dosing interval (%SD = 11% to 49%). The apparent dose-related decline in intrinsic clearance suggests autoinhibition or saturation of metabolism.