n2o effects on rocuronium

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were included in the study. All patients were freefrom neuromuscular disease and had a body massindex 32.5. The protocol was approved by our hos-pitals Human Subject Review Committee and in-formed patient consent was obtained. Patients were

randomly divided into two groups.In Group 1 (total IV anesthesia, TIVA) (n 35), anes-thesia was induced with remifentanil 3 g/kg pluspropofol 2.0 mg/kg IV, and tracheal intubation wasaccomplished without the use of neuromuscular block-ing drugs. Anesthesia was maintained with air-oxygen,and infusions of propofol 75100 g kg1 min1 andremifentanil 0.150.20 g kg1 min1. Ventilation wascontrolled, and end-tidal Pco2 was maintained between3440 mm Hg.

The indirectly evoked integrated compound actionpotential of the first dorsal interosseous muscle tosupramaximal stimulation of the ulnar nerve at the

wrist was measured and recorded using a DatexNMT 100 monitor (Datex Instrumentarium, Helsinki,Finland). Single stimuli at 0.10 Hz were administeredduring the period of observation, and twitch depres-sion was continuously recorded. Control twitch heightwas established after a 15-min period of baseline sta-

bilization. Immediately after twitch height calibration,a single dose of rocuronium was administered. Anupper body forced air warming blanket maintainedhand temperature33C and esophageal temperature35C in all subjects.

The first patient received a bolus of 0.17 mg/kg

rocuronium. This dose was selected to approximatewhat we anticipated (from previous work in our de-partment) to be an ED50 dose. Using the Hill equation(with a postulated log-dose/logit slope of 4.50), theED50 was calculated for this patient. The second sub-

ject received a dose that approximated the calculatedED50 for patient 1. Each successive subject was given adose that equaled the running average of the esti-mated ED50 of the previously studied subjects. Noattempt was made to administer larger or small mul-tiples of the ED50 dose because we wished to avoidresponses (0% or 100%) that could not be plotted on alogit scale. For each subject the estimated ED50 was

computed from the Hill equation by a method previ-ously described (3). The arithmetic mean, median,standard deviation, and standard error of the meanwere then calculated from the individual ED50 values.

In Group 2 (N2O) (n 35), the protocol was iden-tical to that used in Group 1 except that each patientwas ventilated with a mixture of 70% N2O and 30%oxygen after tracheal intubation. Initial gas flows were10 L/min. Flows were decreased to 5 L/min when theend-tidal N2O concentration exceeded 65%. Anesthe-sia was supplemented with a propofol infusion of5075 g kg1 min1 and additional IV opioids as

required.

The mean estimated ED50 values in Groups 1 and 2were compared using an unpaired Students t-test. AP value 0.05 was considered to be statistically sig-nificant. The 95% confidence limits for the respectiveaverage values were also calculated.

ResultsThere were no important differences in the demo-graphics of the 2 groups studied (Table 1). The ED50for rocuronium in the N2O group (0.166 0.041 [sd]mg/kg) was less than in the TIVA group (0.209 0.051 [sd] mg/kg) (P 0.001) (Table 2; Fig. 1).

DiscussionWe have previously published a full description anddiscussion of our method for estimating ED50/95 val-ues (3). Briefly, a line can be defined if one point andthe slope of the line is known. Because the slope of thedose-response relationship for all neuromuscular

blocking drugs is essentially parallel, once a singlepoint along that line is known, the ED50 and ED95 fora patient can be calculated. Based on our previousexperience with rocuronium (3), we chose to use alog-dose/logit slope of 4.5 for estimating the ED50 andED95 of rocuronium. If this approach is correct, there isno logical reason for administering doses other thanthe estimated ED50 when constructing dose-responserelationships. Because linear regression analysis is notused, there is no reason to give doses such as theestimated ED10 or ED90. Avoiding these latter dosesmarkedly reduces the frequency with which eitherzero or 100% twitch depression may occur, responsesthat cannot be plotted using log-dose/logit analysis.In the present study, we did not encounter any suchunplottable values. Our final estimate of rocuroni-ums ED50 in the N2O group (0.166 mg/kg) is notdifferent from the value we calculated in our previouselectromyographic study (3) of 40 subjects using asimilar protocol. In that study, we calculated an ED50of 0.174 0.039 mg/kg (at a slope of 4.50, P 0.01).

Perhaps our calculations of potency are only ap-proximate because the actual slope of the dose-response relationship was never measured. However,fairly wide variations in the log-dose/logit slope have

very little effect on the estimated ED50. Our present

Table 1. Patient Demographics

Nitrous oxideTotal IV

anesthesia

n 35 35Sex (M/F) 11/24 14/21

Age (yr) 42.4 11.8 40.1 12Body mass index 27.3 3.9 26.3 3.6

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usually obtained during N2O anesthesia) must be readwith an awareness that they may underestimate drugrequirements at the time of induction of anesthesia.

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n2o effects on rocuronium

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