Department of Anesthesiology, Affiliated Hospital of Guilin Medical University, Guangxi 541001, China

CLINICAL STUDY

Study on Acupuncture for Side Effects of Etomidate Anesthesia

Jiang Yi-hong, Ni Xu-qing, Yao Xin-yu, Yang Hua, Xiong Wei-wei, Tan Yi, Huang Zhi-hua, Li Ai-guo

Department of Anesthesiology, Affiliated Hospital of Guilin Medical University, Guangxi 541001, China

Author: Jiang Yi-hong, professor.

E-mail: jiangyihong@163.com

Objective: To evaluate the effect of acupuncture therapy on the side effect of Etomidate anesthesia and to determine the best timing of acupuncture intervention during Etomidate anesthesia.

Methods: Female patients with rectal cancer scheduled to receive radical resection were randomly divided into four groups: a control group (group Ⅰ), a preoperative acupuncture group (group Ⅱ), an intraoperative acupuncture group (group Ⅲ), and a postoperative acupuncture group (group), 25 subjects in each group. The levels of serum cortisol, blood glucose, and gastrin of patients were monitored at the following time-points: preoperative (T0, when having entered the operating room), intraoperative (T1, 30 min after skin cutting), the end of operation (T2, after suturing skin), and postoperative (T3, postoperative 24 h). The cases with massive hemorrhage, unsteady vital sign during operation or operation time longer than 5 h were eliminated, and 92 cases were enrolled into the results of the study.

Results: The blood sugar in the four groups increased significantly at T2 and T3, compared to T0 (P＜0.05); the blood sugar reached ((.(((1.5() mmol(( at T2 in group, and the increase was statistically significant compared to those of the other groups (P＜0.05). The levels of serum cortisol of all patients were in normal range. Compare to T0, the cortisol level decreased in group Ⅰ, Ⅲ, Ⅳ at each point, and the decreases were statistically significant (P＜0.05). Compared to the other groups, the cortisol level was increased at T1 and T3 in group, and the change was statistically significant (P＜0.05). Compared to T0, the gastrin level at T3 increased in group Ⅰ, Ⅲ and Ⅳ, but decreased in group Ⅱ, and the changes had statistical significance (P＜0.05). Compared to the other groups, the decrease of gastrin level in groupat T3 was statistically significant (P＜0.05).

Conclusion: Acupuncture before operation can keep blood sugar and serum cortisol steady during Etomidate anesthesia and reduce gastrin after Etomidate anesthesia, hence regulating the Etomidate-related stress responses effectively.

Acupuncture Therapy; Etomidate; Anesthesia, General; Adverse Effects

Maintaining a stable stress state is very important during perioperation[1]. Excessive stress caused by surgery or excessive suppression by anesthesia could be dangerous for patient to overcome. Despite of the advantage of keeping cardiovascular system stable, Etomidate is limited for anesthesia because it may cause adrenocortical dysfunction[2], and even an increase of mortality rate in perioperative phase[3]. In recent years, Etomidate-related adrenocortical suppression has been used in clinical practice.

Crozier TA, et al[4]found that large dose of Etomidate remained cardiovascular stability in cardiac surgery, and meanwhile, Etomidate-related adrenocortical suppression was overcome by strong stress response. Greening JE, et al[5]found that low-dose intravenous infusion of Etomidate was safe for patients with Cushing's syndrome. Johnson TN, et al[6]found that continuous intravenous infusion of Etomidate at 4 mg(h (0.06 mg((kg·h) was safe for respiratory treatment. We have got abundant experiences in Etomidate-induced anesthesia since 2002, and also have conducted progressing clinical studies on regulating the relevant stress responses during perioperation period[(].

Studies showed that acupuncture could reduce postoperative pain, nausea and vomiting, analgesic requirement, and sympathoadrenal responses[(], and restrain strong cardiovascular stress reaction during the operation, adjusting the body stress state[9]. Thus, here comes a question: whether acupuncture could stabilize the Etomidate-related stress during perioperation? The current study observed the effect of acupuncture on adjusting Etomidate-related peri-anesthetic stress by monitoring the change of stress indicators (blood glucose, cortisol, and gastrin), for defining the best timing for acupuncture intervention.

1 Clinical Materials

1.1 Inclusion criteria

Patients diagnosed with rectal cancer by preoperative endoscopy and pathological biopsy and were scheduled for radical resection (Miles or Dixon surgery); female patients Graded Ⅰ-according to the American Society of Anesthesiologists (ASA); age 40 to (0 years old; patients willing to receive acupuncture intervention.

1.2 Exclusion criteria

Patients with kidney or liver dysfunction, endocrine system disease, or a relevant family history; patients using hormone before operation; patients with psychological disorders; patients with poor compliance; incomplete clinical materials which may affect the evaluation of the results.

1.3 Drop-out criteria

Allergic reactions during operation; altered anesthesia protocol; massive hemorrhage during operation; operation time exceeding 5 h.

1.4 General data

Between January 2010 and January 2012, 31( patients who had been diagnosed with rectal cancer by preoperative endoscopy and pathologic biopsy were scheduled for Miles or Dixon surgery and admitted to the Affiliated Hospital of Guilin Medical University. As gender is an influential factor for postoperative nausea and vomiting (PONV), to eliminate the potential impact of gender on stomach, only female patients (n=10() who were gradedaccording to the American Society of Anesthesiologists (ASA) were enrolled, while ( of them were excluded. They were randomized into four groups, a control group (group, Etomidate anesthesia without acupuncture), a preoperative acupuncture group (group, Etomidate anesthesia with acupuncture performed at 30 min before induction), an intraoperative acupuncture group (group, Etomidate anesthesia with acupuncture performed at the beginning of skin cut), and the postoperative acupuncture group (group, Etomidate anesthesia with acupuncture performed at the beginning of skin suture), there were 25 cases in each group.

Eight subjects dropped out during the study: GroupⅠandeach had one case dropped out due to use of dexamethasone for allergic reactions; groupandeach had one case for adopting inhalation anesthesia during the operation; groupandboth had one case due to massive hemorrhage; a case from groupdropped out for operation time exceeding 5 h. Finally, totally 92 patients completed the study. There was no significant difference in the general information including age, BMI, anesthesia time, and use of anesthetics (Etomidate and Sufentanyl) among the four groups (Table 1).

The intervention procedure is shown in Figure 1.

Table 1. Comparison of the general data

Figure.1 Intervention procedure

2 Treatment Methods

2.1 Anesthesia

For all patients, anesthesia was induced with Midazolam, Etomidate, Sufentanil and Atracurium through tracheal intubation. During perioperative period, total intravenous anesthesia (TIVA) with Etomidate [0.01-0.02 mg((kg·min)], Sufentanyl [0.0006 mg((kg·min)] and Atracurium [0.01 mg( (kg·min)] were combined with vasoactive drugs to maintain anesthesia depth (BIS 40%-50%, TOF＜20%) and stable hemodynamic state[10].

2.2 Electroacupuncture treatment

Acupuncture was performed on Neiguan (PC 6), Hegu ((I 4), Zhigou (TE 6), and Quchi ((I 11) by an attending physician with more than five-year clinical experience of traditional Chinese medicine.

The parameters of electroacupuncture apparatus for the acupuncture intervention were as follows: Sparse-dense wave, sparse wave 3 Hz, dense wave 20 Hz, peak current 15-30 mA, and fixed time 30 min[11]. Acupuncture needles (size No.2() were purchased from Suzhou Medical Appliance Factory (Huatuo brand).

3 Observation of Therapeutic Efficacies

3.1 Evaluation indexes

Blood samples were collected at four time points: Preoperation (T0, having entered the operating room), intraoperation (T1, 30 min after skin cut), the end of operation (T2, after suturing skin), and postoperation (T3, 24 h after operation). The arterial blood gas was analyzed using gas analyzer (Nova Biomedical, USA). The blood sugar was measured by sugar trace method (Roche). Meanwhile, blood samples were put into anticoagulant tube blending with Aprotinin, plasma centrifuged at 4 ℃, 3 000 r(min for 10 min, and then stored at –20 ℃ till analyses for cortisol and gastrin. The cortisol level was determined by electrochemiluminescence immunoassay (EC(IA) (Roche). The gastrin level was measured using enzyme-linked immunosorbent assay (E(ISA) (Shanghai Xitang Reagent Company, China).

3.2 Statistical analysis

The SPSS 10.0 (SPSS Inc., Chicago, Illinois, USA) was adopted for statistical analyses. The data were expressed asTwo-factor ANOVA with repeated measurement was used to compare the difference among groups. Statistical significance was defined asP＜0.05.

3.3 Treatment results

3.3.1 Blood sugar

For each group, average levels of blood sugar at different time-points were compared. In each group, higher blood sugar level was significantly higher at T2 and T3 compared to that at T0 (P＜0.05). At T2, groupwith intraoperative acupuncture achieved ((.(((1.5() mmol((, significantly higher than the other groups (P＜0.05), (Table 2).

Table 2. Comparison of blood sugar at different time points among groups (mmol/L)

Table 2. Comparison of blood sugar at different time points among groups (mmol/L)

Note: Compared with the level at T0 of the same group, 1) P＜0.05; compared with group Ⅲ at the same time point, 2) P＜0.05

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3.3.2 Serum cortisol level

The serum cortisol levels of all patients were in normal range. The serum cortisol levels of patients from groupandshowed a trend of decrease from T0 to T1 (P＜0.05). However, groupwith preoperative acupuncture intervention showed a significantly increased serum cortisol level at T1 compared to T0 (P＜0.05). At T3, all groups showed a decreased level of serum cortisol compared to that at T0 and group Ⅱ showed the highest serum cortisol level among all the groups (P＜0.05), (Table 3).

3.3.3 Serum gastrin level

The gastrin level at T3 increased in groupandcompared to that at T0, but decreased in groupand the changes were statistically significant (P＜0.05). The gastrin level in groupat T3 was significantly lower than that in the other three groups (P＜0.05), (Table 4).

Table 3. Comparison of the serum cortisol at different time points among groups (nmol/mL)

Table 3. Comparison of the serum cortisol at different time points among groups (nmol/mL)

Note: Compared with the level at T0 of the same group, 1)P＜0.05; compared with group Ⅱ at the same time point, 2)P＜0.05

Table 4. Comparison of the gastrin at different time-points among groups (pg/mL)

Table 4. Comparison of the gastrin at different time-points among groups (pg/mL)

Note: Compared with the level at T0 of the same group, 1)P＜0.05; compared with group Ⅱ at the same time point, 2)P＜0.05

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4 Discussion

In this experiment, we applied low-frequency electrical stimulation to Neiguan (PC 6), Hegu ((I 4), Zhigou (TE 6), and Quchi ((I 11), which have proven involved in endocrine regulation[12-15]. It’s been confirmed that stress response is led by both central nervous system and the production of various inflammatory mediators, such as cortisol, adrenaline, noradrenaline, blood glucose, histamine, and prostate hormone[16-1(]. It’s believed that PONV results from the physiological stress of surgery. As the objective index of PONV, gastrin also reveals the level of stress. Therefore, blood glucose, cortisol, and gastrin were chosen to be stress indicators in this study.

During the recent years, the relationship between acupuncture and anesthesia has attracted more and more attention from researchers worldwide. Acupuncture has been suggested as an effective non-pharmacologic prophylaxis for PONV[1(]. In our study, we observed the influence of acupuncture on stress reactions of patients after Etomidate anesthesia. In Table 1, the change of blood sugar seemed more regular in group, the blood sugar in the other groups waved with the process of operation and anesthesia. In Table 2, the serum cortisol levels of all patients were in normal range, but the cortisol decreased after Etomidate anesthesia with no acupuncture intervened or acupuncture performed at the start of skin cut and skin suture, and the decrease was statistically significant. When acupuncture was intervened before operation, the cortisol level changed smoothly compared to the other groups. In Table 3, when no acupuncture was intervened or acupuncture was performed at the start of skin cut and skin suture, the gastrin level increased after operation; however, when acupuncture was intervened before operation, the gastrin level decreased after operation. From the result of study, we come to a conclusion that acupuncture before operation can regulate Etomidate-induced stress reactions more significantly.

The mechanism of preoperative acupuncture in adjusting Etomidate-induced peri-anesthesia stress is still unknown. Researchers suggested that acupuncture can increase endorphine levels, stimulate brain function, and regulate the endocrine system[19-21]. The data in our study have verified these theories. It’s well known that anesthetics include sedatives, analgesics and neuromuscular relaxants. They work on the central nervous system and peripheral neuromuscular junctions, so acupuncture won’t work when patients are under anesthesia. Acupuncture before anesthesia seems to work well.

In summary, preoperative acupuncture significantly influences the Etomidate-related stress reactions via

restoring the blood sugar and cortisol level and decreasing gastrin secretion at 24 h after operation. The intraoperative and postoperative acupuncture doesn’t show obvious effect on regulating Etomidate-related side effect in patients. This study provides an evidence for using preoperative acupuncture to relieve Etomidate-caused adrenocortical dysfunction. Considering that Etomidate is a rapid acting anesthetic and has a safe cardiovascular risk evaluation, this study might promote the potential need of Etomidate in the emergency room and intensive-care unit. However, the mechanism underlying the effect of acupuncture on anesthesia-induced reaction remains unknown and expects further studies.

Conflict of Interest

There is no potential conflict of interest in this article.

Acknowledgments

All procedures were approved by the Ethics Committee of the Affiliated Hospital of Guilin Medical University, Guangxi, China. This work was supported by the Key Research Project of Guangxi Health (No. 2010053); the Traditional Chinese Medicine and National Medicine Inheritance and Innovation Project of Guangxi (No. GZZC13-20).

Statement of Informed Consent

All of the patients signed the informed consent.

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Date:October 10, 2013