Kim, H.J., Kim W.Y., Lee, Y.S., Chang, M.S., Kim, J.H., & Park, Y.C. The effect of cranial electrotherapy stimulation on preoperative anxiety and hemodynamic responses. Korean Journal of Anesthesiology. 2008; 55:657-661.

Funding Source, Location of Study or Author’s Affiliation
Department of Anesthesiology and Pain Medicine, Korea University College of Medicine, Seoul, Korea.

Device
Alpha-Stim^® 100

Key Variable
Preoperative anxiety.

Objective
To evaluate the effect of a specified treatment course with cranial electrotherapy stimulation (CES) on patients’ preoperative anxiety levels when compared to sham treatment under the same experimental conditions in subjects meeting the inclusion and exclusion criteria.

Design
This was an IRB approved randomized, investigator-blinded, clinical trial. The investigators were masked to which subjects received CES or were controls.

Primary Outcome Measure
The primary outcome measure was the change from baseline in the post-treatment scores on the Likert anxiety scale compared to the sham group at the end point of the study.

Secondary Outcome Measure
None reported.

Key Inclusion Criteria

• Preoperative patients ages of 18-65 years awaiting surgery under general anesthesia.
• Must meet American Association of Anesthesiology Physical Classification Criteria 1 & 2.

Key Exclusion Criteria

• Pregnancy
• Presence of implanted pacemakers, pumps, or stimulators.
• BMI over 25, and having endocrinological, musculoskeletal, liver and kidney or vascular disorders.
• Individuals awaiting high anxiety procedures such as tumor removal or amputation.
• Individuals who were taking antidepressant and other psychotropic medications.

Protocol Summary

• Patients were told that they will be held for 20-30 minutes in the pre-surgical waiting area and they will either receive or not receive CES and what sensation to expect from CES pretreatment to reduce anxiety.
• All subjects were given glycopyrrolate 0.2 mg IM as a premedication about one hour before induction of anesthesia. They were brought to the waiting area to be evaluated by the same anesthesiologist who visited them the night before.
• They were asked about their level of anxiety and blood pressure and pulse rate was measured as a physiological index of anxiety. Anxiety was rated using a Likert Scale measuring the subjective experience of anxiety on a scale of 1 (low) to 5 (high).
• Subjects were randomly assigned to either a control group (n=30) who received supportive nursing care or a CES group (n=30) who received a 20-minute CES pretreatment in the operating room waiting area by Alpha-Stim fixed at below 200 μA, 0.5 Hz.

Device Application Protocol
The active CES device was pre-set at just below 200 µA. Anxiety was assessed in the preoperative holding area after the CES treatment.

Statistical Analysis Plan
Apriori hypothesis was that application of an Alpha-Stim would reduce anxiety. Data were analyzed using t-test to compare the CES and control groups on anxiety scores.

Results

Subjects

• Sixty (60) adults between the ages of 18-65 were subjects in this study. Subjects were waiting for surgery under general anesthesia and met the American Association of Anesthesiology Physical Classification Criteria 1 and 2.
• Subjects were having orthopedic, gynecological, and ear, nose and throat procedures requiring about 2 hours and the surgical procedures had similar risk factors.
• There were no statistically significant differences at baseline between active CES and control groups on the outcome anxiety measure.
• There were no differences in age, gender, height, and weight distribution between the 2 groups.

Data Analysis
There was no difference in the waiting room between the CES and control groups in anxiety measures. Once in the operating room, the control group showed a significant elevation in anxiety, whereas the CES group showed a significant reduction in anxiety levels from the waiting room measurements. As seen in the figure below, the CES group had lower anxiety scores on the Likert scale compared to the control group in the operating room (p<0.01, d=-.88).

Hemodynamic changes in blood pressure and pulse rate in the operating room were significantly elevated for both groups when compared to the waiting room. However, the CES group had significantly lower hemodynamic responses compared to the control group.

Mean Preoperative Anxiety Score by Group.

Conclusions
Strengths of this study include: (1) The randomized controlled clinical trial design (2) An adequate N of 60 to detect differences between the active and control groups and (3) The blinding of the investigators to which subjects received CES treatments. The results of this study indicate CES significantly reduces preoperative anxiety and hemodynamic responses, such as blood pressure and pulse rate. By suppressing sympathetic activation, CES pretreatment modulates both the affective and physical symptoms of anxiety. The findings of this study that CES decreases anxiety are consistent with other RCTs using Alpha-Stim CES technology.

Limitations
The use of a sham CES device would have increased the strength of this study. The CES treatment group received 20 minutes of treatment at just under 200 µA. At that current, 60 minutes of treatment is optimal. The authors indicate limitations of the study include the absence of correlation between objective measurements of stress hormone levels, such as cortisol and catecholamines. The fact that the surgeries were not confined to the same types of procedures is another limitation to this study.

Study Quality: GOOD