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ANESTHETIC PHARMACOLOGY

Electro-Acupuncture at the Zusanli, Yanglingquan, and Kunlun Points Does Not Reduce Anesthetic Requirement

Nobutada Morioka, MD^*, Ozan Akça, MD^*, Anthony G. Doufas, MD, PhD^*, Gregory Chernyak, MD^*, and Daniel I. Sessler, MD^*

*Department of Anesthesiology, University of Louisville, Kentucky; and Ludwig Boltzmann Institute, University of Vienna, Austria

Address correspondence and reprint requests to Daniel I. Sessler, MD, Outcomes Research^TM Institute, 501 E. Broadway, Louisville, KY 40202. Address e-mail to sessler{at}louisville.edu

	Abstract

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We tested the hypothesis that electro-acupuncture at the Zusanli, Yanglingquan, and Kunlun acupuncture points on the legs decreases anesthetic requirement. Fourteen young, healthy volunteers were anesthetized with desflurane on two separate days. Needle electrodes were positioned at the three acupuncture points thought to produce a generalized sedative and analgesic effect. Needles were percutaneously placed on treatment days; on control days, they were insulated and taped near the insertion points. The electrodes were stimulated on the treatment day. Stimulation consisted of 2-Hz and 100-Hz currents alternated at 2-s intervals. When the end-tidal desflurane concentration of 5.5% was stable for 15 min, noxious electrical stimuli were administered via 25-gauge needles on both thighs (70 mA at 100 Hz for 10 s). Desflurane concentration was increased 0.5% when movement occurred and decreased 0.5% when it did not. An investigator, blinded to treatment, determined movement. These up-and-down sequences were continued until volunteers crossed from movement to no movement four times. A logistic regression determined the partial pressure of desflurane that produced a 50% likelihood of movement in response to noxious stimulation and consequently identified the minimum alveolar anesthetic concentration equivalent for desflurane. There was no significant difference in minimum alveolar anesthetic concentration equivalents between the electro-acupuncture (4.6% ± 0.6%, mean ± SD) and control (4.6% ± 0.8%) days (P = 0.8). These data provided an 80% power for detecting a difference of 0.35 volume-percent between the groups.

IMPLICATIONS: Electro-stimulation of three general acupuncture points on the leg did not reduce desflurane requirements. This type of acupuncture is thus unlikely to facilitate general anesthesia or decrease the need for anesthetic drugs.

	Introduction

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Various forms of acupuncture are often used in the Orient and are becoming increasingly popular in western countries. It is likely, for example, that more than a million Americans have been treated with acupuncture for chronic pain. Well over 5000 papers have been published about acupuncture, but few have been fully double-blinded, placebo-controlled trials.

We have recently developed a method of completely double-blinding acupuncture studies to evaluate the effect of acupuncture on anesthetic requirement (1). Advantages of this method include: (a) starting treatment after the induction of anesthesia, which assures that the subject is blinded, (b) using an objective measure of anesthetic requirement, and (c) having a blinded investigator determine the anesthetic requirement. A further advantage is that the studies are conducted on volunteers; consequently, each can participate on a treatment and control study day. This crossover design provides considerable statistical power.

Successful anesthesia provides analgesia, prevents intraoperative awareness, and forestalls patient movement. To the extent that acupuncture provides analgesia, it might be expected to reduce the need for conventional anesthetic drugs. Reduced drug use would not only directly decrease cost, but also would indirectly decrease cost and improve patient care by speeding up postoperative recovery. We have used our method of evaluating acupuncture efficacy in a previous trial that demonstrated a highly statistically significant reduction in anesthetic requirement (1). The reduction was approximately 10%, an amount that provides proof-of-concept but is of questionable clinical importance (A. Taguchi, N. Sharma, S. Ali, et al., unpublished observations).

To be clinically useful, the benefit probably needs to exceed the previously observed magnitude by a factor of two or three. Thus, our study purpose was to evaluate additional acupoints in an effort to identify a combination that provides a clinically useful reduction in anesthetic requirement. We chose the Zusanli, Yanglingquan, and Kunlun points because they are believed to produce a generalized sedative and analgesic effect (2,3). We used electrical stimulation of these acupoints because it may be more effective than needles alone (2,4). Accordingly, we tested the hypothesis that simultaneous electrical stimulation of the Zusanli, Yanglingquan, and Kunlun points reduces anesthetic requirement by at least 20%.

	Methods

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With approval from the Human Research Committee at the University of Louisville, Kentucky, we studied 22 healthy volunteers. Fourteen of the volunteers (4 women and 10 men) completed the protocol. This sample size was determined from an estimate based on our previous results that indicated that 10 subjects would provide an 80% power for identifying a statistically significant difference of 0.5% desflurane at a two-tailed, paired of 0.05.

The volunteers were 30 ± 5 (mean ± SD) yr old, weighed 75 ± 5 kg, and were 172 ± 10 cm tall. None had a history of drug addiction or took any drugs other than oral contraceptives. The volunteers had no history of chronic pain. Menstrual cycle was not controlled because cycle status has little or no influence on perception of experimental pain (5).

The volunteers fasted and refrained from smoking for at least 8 h before arriving at the laboratory. No premedication was given. The volunteers who completed the trial participated on 2 study days separated by 48 h (8 ± 5 days). Each set of studies began at the same time of day because circadian rhythms can influence anesthetic requirement (6,7).

On each study day, anesthesia was induced with approximately 3 mg/kg of IV propofol. A laryngeal mask airway (Laryngeal Mask Co, Henley-on-Thames, UK) was inserted. Ventilation was assisted until spontaneous breathing was re-established. Anesthesia was initially maintained with desflurane (5.5 volume-percent) in 80% oxygen and 20% nitrogen. After the induction of anesthesia on the initial study day, volunteers were randomly assigned to electro-acupuncture or no treatment. We used a crossover study design in which each volunteer was given the alternative treatment (electro-acupuncture or control) on the second study day.

We stimulated the Zusanli, Yanglingquan, and Kunlun points. Zusanli is 6 cm below the lower margin of the patella and 3 cm lateral to the tibia. Yanglingquan is in the depression just at the anterior edge of the round head of the fibula in the angle of the lower edge of the head of the tibia and posterior edge of the insertion of the extensor digitorum longus muscle (8). Kunlun is in the hollow between the lateral malleolus and the Achilles tendon. An advantage of these three points is that they are relatively broad and thus require less precise stimulator positioning than other sites. Furthermore, they are safe to use because they are not adjacent to critical structures. These points are thought to produce a generalized sedative and analgesic effect and to be effective for surgical procedures on the thigh (2).

An expert acupuncturist (GC) inserted the KN-107JL acupuncture electrodes, which have a diameter of 0.18 mm and are 40 mm long (Seirin, Ltd, Shizuoka, Japan). The electrodes were connected to an IC-4107 (ITO, Ltd, Tokyo, Japan), and the stimulating frequency was set to 2 Hz and 100 Hz, with the frequencies being alternated at 2-s intervals (9,10). On acupuncture days, the initial stimulation intensity was 2 mA but was gradually increased until muscular twitching was observed in the legs. Because this twitching could unblind the study, the intensity was subsequently decreased to a current just less than that triggering mechanical activity. This stimulation intensity was then maintained for the duration of the study.

The acupuncture needles were percutaneously inserted (on appropriate days), and the electrodes were connected by an investigator who was not otherwise involved in the study. The stimulator was activated on both study days, and the wires were taped near the putative acupuncture needle-insertion sites that were kept fully covered throughout the study period. However, acupuncture needles were inserted and the electrodes were connected only on treatment days; on control days, electrodes were connected without the acupuncture needles. Consequently, the investigators evaluating anesthetic requirement could not determine whether acupuncture was being used. Both acupuncture needle insertion and electrical stimulation were started after the induction of anesthesia so the volunteers would not sense the tingling sensation produced by the electric current. Thus, the study was fully double blinded.

Anesthetic requirement was defined by the average partial pressure of desflurane required to prevent movement in response to noxious electrical stimulation. Electrical stimulation was via two 25-gauge needles that were intradermally inserted into the lower portion of each anterior thigh. A bilateral 70 mA, 100-Hz tetanic electrical current, maintained for 10 s, provided the noxious stimulus. A tetanic stimulus of even 20% of this intensity is unbearable to unanesthetized subjects. To prevent desensitization at the insertion site, the electrodes were cranially moved by 1 cm after each stimulation. Stimulation was started 1 h after the anesthetic induction to allow sufficient time for the effects of propofol to dissipate.

We used the Dixon up-and-down method, which is the standard paradigm for evaluating anesthetic depth (11,12). The initial end-tidal desflurane concentration (5.5 volume-percent) was maintained for 15 min to assure alveolar-brain equilibration. If the subject moved in response to noxious electrical stimulation, the anesthetic concentration was subsequently increased by 0.5 volume-percent. In contrast, the desflurane concentration was reduced by the same amount when the subjects did not move. A positive response to noxious electrical stimulation was defined by purposeful movement of one or more extremities within 1 min of stimulation. Grimacing and head movement were not considered purposeful responses. The new end-tidal desflurane partial pressure was then maintained for 15 min, and the process was repeated. This up-and-down sequence was continued until the subject crossed over from movement to nonmovement four times.

We recorded morphometric and demographic characteristics of the volunteers. End-tidal desflurane volume-percent and carbon dioxide (CO₂) were mea-sured using an Ohmeda Rascal monitor (Ohmeda Inc, Salt Lake City, UT) that was calibrated daily. The resolution of this device is 0.1% desflurane. End-tidal concentrations of volatile anesthetics and CO₂ are virtually identical to alveolar concentrations (13).

All standard anesthetic safety values were monitored and recorded. These included heart rate and blood pressure, which were oscillometrically determined at 5-min intervals and before each tetanic stimulation. A pulse oximeter continuously determined arterial oxygen saturation. Core body temperature was measured from the tympanic membrane using Mon-a-Therm thermocouples (Tyco-Mallinckrodt, Inc, St Louis, MO).

Hemodynamic responses and core temperature were first averaged over each study day for each volunteer and then averaged among the volunteers given each treatment. All desflurane concentrations, with and without movement, were entered into a logistic regression. The regression determined the partial pressure of desflurane that produced a 50% likelihood of movement in response to noxious stimulation in each volunteer on each study day. Values on the acupuncture and control days were compared with two-tailed, paired t-tests. Results are presented as mean ± SD; P < 0.05 was considered statistically significant.

	Results

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Eight women and 14 men were enrolled onto the trial. Nine men were initially assigned to electro-acupuncture and five to control; four dropped out of the study after the first day. Two women were initially assigned to electro-acupuncture, both of whom dropped out of the study after the first day. Six women were initially assigned to a control day; two dropped out of the study after the first day. Ten men and four women thus completed both study days. Data analysis was restricted to these 14 volunteers.

Total duration of the study was 252 ± 51 min on the electro-acupuncture day and 252 ± 64 min on the control day (P = 0.5). Potential confounding factors were similar on the acupuncture and control study days (Table 1). Desflurane requirement on the acupuncture (4.6% ± 0.6%) and the control (4.6% ± 0.8%) days did not differ significantly (P = 0.8; Fig. 1). The data were normally distributed. Using a two-sided, one-sample t-test with an of 0.05, these data provided an 80% power to detect a difference of 0.35 volume-percent between the groups.

View larger version (16K): [in this window] [in a new window]   Figure 1. Circles show the individual concentrations of desflurane required to prevent movement in response to intense electrical stimulation with (Acupuncture) and without (Control) electro-acupuncture. Squares show the mean ± SD concentrations with each treatment. The anesthetic requirements did not differ significantly.

	Discussion

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An equivalent of MAC can be determined in individuals using repeated noxious electrical stimulation (16). The resulting partial pressures are uniformly smaller than obtained with skin incision (12), but electrical stimulation nonetheless provides a reasonable measure of anesthetic need and has been used in numerous previous studies (17). We used the technique in the current study because it has the advantage of allowing crossover study designs that are especially sensitive for detecting treatment-induced changes in anesthetic requirement. In previous studies, for example, we were able to identify highly statistically significant reductions in anesthetic requirement of only approximately 10%.

This study is our third evaluating the effect of acupuncture on anesthetic requirement. The first used electro-acupuncture of a single auricular acupoint and identified an 11% reduction in anesthetic requirement (1). The second used dry needles at four auricular acupoints and identified an 8% reduction in anesthetic requirement (A. Taguchi, N. Sharma, S. Ali, et al., unpublished observations). In contrast, our current study, which stimulated three acupoints on the leg, failed to reduce anesthetic need.

An obvious conclusion from these three studies is that electrical stimulation of the Zusanli, Yanglingquan, and Kunlun points is less effective than electrical stimulation or dry needles at auricular points. However, a more important conclusion is that none of these techniques produced clinically important reductions in anesthetic requirement. It remains a possibility that other acupuncture techniques are more effective, although it has yet to be determined whether any produces clinically important reductions in anesthetic requirement. In contrast, at least some acupuncture techniques provide substantial postoperative analgesia and significantly reduce opioid requirement (18).

A benefit of our model is that acupuncture needles are inserted after the induction of anesthesia. This allows full blinding of the volunteers, as well as the investigators evaluating the response, to noxious stimulation. Although, a disadvantage of this method is that the acupuncturist cannot elicit the typical "Qi" sensation that is associated with proper needle positioning and may even be critical for eliciting an acupuncture effect. It is thus possible that the needles were suboptimally positioned. Nonetheless, the points we chose are relatively broad so that exact needle positioning is less critical than at other sites. Needle positioning is also far less critical with electrical stimulation than without because the current stimulates a relatively wide area. Another disadvantage of our model is that volatile anesthetics per se may interfere with effective acupuncture, especially when acupuncture is started after the induction of anesthesia (19,20).

In summary, electro-stimulation of the Zusanli, Yanglingquan, and Kunlun acupuncture points on the leg did not reduce desflurane requirement. This type of acupuncture is thus unlikely to facilitate general anesthesia or decrease the need for anesthetic drugs.

	Acknowledgments

 
Supported, in part, by Jewish Hospital Foundation (Louisville, KY), NIH Grant GM 58273 (Bethesda, MD), the Joseph Drown Foundation (Los Angeles, CA), and the Commonwealth of KY Research Challenge Trust Fund (Louisville, KY). Tyco-Mallinckrodt, Inc. (St. Louis, MO) donated the thermocouples we used.

	Footnotes

 
Presented, in part, at the 2001 annual meeting of the American Society of Anesthesiologists, New Orleans, October 13–17.

None of the authors has any financial interest in products related to this study.

	References

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