This multi-centre, parallel group, randomized, double-blind study compared the efficacy and safety of high-dose remifentanil administered by continuous infusion with an intermittent bolus fentanyl regimen, when given in combination with propofol for general anaesthesia in 321 patients undergoing elective coronary artery bypass graft surgery. A significantly lower proportion of the patients who received remifentanil had responses to maximal sternal spread (the primary efficacy endpoint) compared with those who received fentanyl (11% vs 52%; P<0.001). More patients who received remifentanil responded to tracheal intubation compared with those who received fentanyl (24% vs 9%; P<0.001). However, fewer patients who received remifentanil responded to sternal skin incision (11% vs 36%; P<0.001) and sternotomy (14% vs 60%; P <0.001). Median time to extubation was longer in the subjects who received remifentanil than for those who received fentanyl (5.1 vs 4.2 h; P=0.006). There were no statistically significant differences between the two groups in the times for transfer from intensive care unit or hospital discharge but time to extubation was significantly longer in the remifentanil group. Overall, the incidence of adverse events was similar but greater in the remifentanil group with respect to shivering (P<0.049) and hypertension (P<0.001). Significantly more drug-related adverse events were reported in the remifentanil group (P=0.016). There were no drug-related adverse cardiac outcomes and no deaths from cardiac causes before hospital discharge in either treatment group.

SUMMARY1. Intraneural electrical stimuli (0-3-1P2 mA, 0-2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in twenty-eight normal subjects. The effects on sweat glands within the innervation zone were monitored as changes of skin resistance and water vapour partial pressure (WVPP). Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects.2. At stimulation frequencies of 041 Hz each stimulus evoked a transient skin resistance reduction, the amplitude of which varied initially but reached a steady state of less than 10 kQ after, on average, nine responses. If preceded by stimulationfree intervals of 5 min or more, up to fifteen stimuli were required before the first response occurred. With higher frequencies individual responses started to merge, skin resistance levels decreased successively and levelled off around 10 Hz. The total change of resistance (0-10 Hz) was 101 + 46 (n = 9) kQ and the higher the prestimulus level, the larger the reduction (r = 0-68, P < 0 05).3. Stimulus-response latencies to the onset of a skin resistance reduction (single stimuli or trains of six impulses/20 Hz given at 0 1 Hz) shortened initially but reached steady-state values after on average nine to twelve impulses. Average conduction velocity between stimulating electrode and skin resistance recording site was 0-78 m/s and average time for electrical neuroeffector transfer in sweat glands was estimated to be 348 ms.4. In addition to direct stimulation-induced resistance responses there were also small spontaneous reductions of resistance. They were seen in all subjects and at all frequencies but were more common in some subjects and occurred predominantly at the beginning of stimulation or at changes of frequency. They occurred independently at two skin sites in the same subject and disappeared during stimulation-free periods and after atropine.5. With train stimulation (six impulses/20 Hz) at 0-1 Hz, each train evoked transient increases of WVPP of 1 mmHg or less in some subjects (latency around 1'6 s). After averaging weak increases were seen also after single stimuli in two subjects. Increases of stimulation current or frequency led to slowly developing sustained increases of WVPP concomitant with decreases in skin resistance. MS 9170M. KUNIMOTO AND OTHERS 6. Responses in skin resistance and WVPP to train stimulation at 0X1 Hz were suppressed in a dose-dependent way by i.v. injections of atropine. The cumulative dose necessary for complete inhibition of stimulus-induced responses (0-32 mg or less) had only weak effects on skin resistance responses to arousal stimuli in the opposite, non-anaesthetized hand.7. We conclude that the intraneural electrical stimulation evoked sweating mainly by direct excitation of cholinergic sudomotor nerve fibres but that a minor addition of sweat was produced by a local mechanism in sweat glands and/or terminal nerve fibres. The delayed development of skin resistance ...

Intraneural electrical stimulation of cutaneous fascicles in the median nerve was performed in 24 normal subjects and the effects on sweating within the innervation zone were monitored as changes of skin resistance and water vapour partial pressure (wvpp). The aims were: (1) to investigate the response variability between repeated stimulation sequences in the same skin site and between different sites and (2) to compare quantitative effects of regular and irregular stimulation on skin resistance and wvpp. Regional axillary anaesthesia of the brachial plexus eliminated spontaneous and reflex sympathetic activity. With repeated irregular stimulation sequences skin resistance responses from the same skin site varied only slightly between trials. Differences between response curves from two skin sites in the same subject or from different subjects were also small but significantly greater (P < 0.01) than differences between responses to repeated stimulation in the same site. Irregular stimulation with average frequencies of 0.49 Hz and 3.51 Hz gave greater resistance responses than if the same number of stimuli were delivered regularly (P < 0.01). The difference was most pronounced at 0.49 Hz. At an average frequency of 0.49 Hz the stimulation usually evoked no changes of wvpp whereas an average frequency of 3.51 Hz caused an increase of wvpp which was greater with irregular than with regular stimulation in all subjects. We conclude that: (1) sweat responses to sudomotor nerve traffic vary slightly due to local factors in the skin or the terminal nerve endings and (2) irregular sudomotor nerve traffic evokes more sweat than if the same impulses occur regularly.

Intraneural electrical stimuli (0.3 mA, 0.2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in 16 normal subjects, and the effects on the sweat glands within the innervation zone were recorded as changes of skin resistance. In order to examine the relationship between the skin resistance level and the amplitude of transient resistance responses, trains of high frequency stimulation were used to reduce the skin resistance level and then transient resistance responses were evoked by single stimuli at 0.1 Hz. Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. At high skin resistance levels response amplitudes to single stimuli were low but they increased successively to a maximum at intermediate levels and then decreased again at low resistance levels. Repeated stimulation sequences evoked qualitatively similar response curves but quantitatively both response amplitudes and skin resistance levels were slightly reduced upon repetition. We suggest that the changes of response amplitudes are due to variable resistivity of the corneal layer. The shifts of the response curves with repetition of stimulation may result from increased hydration of the corneum. It is concluded that the variability of response amplitudes to constant stimuli makes the amplitude of a skin resistance response unsuitable as an indicator of the strength of sympathetic sudomotor nerve traffic.

A high thoracic epidural anesthesia with adequate sensory blockade of upper thoracic dermatomes may be achieved without blockade of caudal parts of the sympathetic nervous system. This finding differs from that of earlier studies that used indirect methods to evaluate changes in sympathetic nerve activity.