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Anesthesia & Analgesia:
doi: 10.1213/ane.0b013e31816d1864
Obstetric Anesthesiology: Review Article

P6 Stimulation for the Prevention of Nausea and Vomiting Associated with Cesarean Delivery Under Neuraxial Anesthesia: A Systematic Review of Randomized Controlled Trials

Allen, Terrence K. MBBS, FRCA; Habib, Ashraf S. MBBCh, MSc, FRCA

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From the Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina.

This study was presented in part at the 39th Annual Meeting of the Society for Obstetric Anesthesia and Perinatology, Alberta, Canada, May 16–19, 2007.

Financial support: This study was supported by departmental funds.

Address correspondence and reprint requests to Ashraf S. Habib, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710. Address e-mail to habib001@mc.duke.edu.

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Abstract

BACKGROUND: A number of studies investigated the use of P6 stimulation for the prevention of intraoperative and postoperative nausea and vomiting (IONV and PONV) in women having cesarean delivery under neuraxial anesthesia. We performed a systematic review to determine the overall efficacy of these techniques in preventing IONV and PONV in this patient population.

METHODS: We performed a literature search of all randomized controlled trials (1966–2007) that compared different methods of P6 stimulation with placebo in women having cesarean delivery under neuraxial anesthesia. Data were extracted on the primary outcomes including the incidence of nausea, vomiting, and the need for rescue antiemetic therapy, both intraoperatively and postoperatively.

RESULTS: Six studies involving 649 patients were included in this review. Five studies reported on intraoperative outcomes. Of these, two studies reported a significant reduction in the incidence of intraoperative nausea with P6 stimulation, and one study reported a significant reduction in rescue antiemetic requirement. However, none of the studies reported any differences between the treatment and control groups with respect to vomiting. Four studies reported postoperative outcomes. Of these, one study reported a significant reduction in postoperative nausea, two studies reported a significant reduction in postoperative vomiting, and one study reported a significant reduction in the need for postoperative rescue antiemetic therapy.

CONCLUSIONS: While some studies showed a benefit of P6 stimulation, this finding was not consistent. The presence of heterogeneity and inconsistent results among the included trials prevents any definitive conclusions on the efficacy of P6 stimulation in reducing IONV and PONV associated with cesarean delivery performed under neuraxial anesthesia.

Nausea and vomiting are common intraoperative and postoperative complications in women having cesarean delivery under neuraxial anesthesia.1,2 The etiology of intraoperative and postoperative nausea and vomiting (IONV and PONV) is multifactorial. The physiologic changes of pregnancy, intraoperative hypotension, increased vagal activity, visceral stimulation, as well as administration of neuraxial opioids and oxytocic drugs, may all play a role.3 Nonpharmacological techniques such as acupuncture, acupressure, and transcutaneous acupoint electrical stimulation of the pericardium 6 (P6) Neiguan point have been studied for the prevention of IONV and PONV.4–12 The increasing popularity of these modalities is, in part, due to their low cost and simplicity, and in obstetrics, concern about placental transfer and secretion in breast milk of drugs.13 Several physiological mechanisms have been proposed for the antiemetic effect of P6 stimulation. These include stimulation of the endogenous opioid system, serotonin release, increased vagal modulation, direct stimulation of gut smooth muscle, and stimulation of somatovisceral and somatosympathetic reflexes that affect lower esophageal sphincter and gastric relaxation.14

A number of studies have investigated P6 stimulation for preventing PONV and IONV in women undergoing cesarean delivery under neuraxial anesthesia. We performed this systematic review to assess the efficacy of P6 stimulation in this patient population.

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METHODS

We followed the recommendations of the QUOROM statement.15

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Literature Search

We searched MEDLINE (1966–2007), the Cochrane Central Register of Controlled Trials, Scopus and CINAHL for randomized controlled trials (RCTs) that investigated the perioperative use of P6 stimulation for the prevention of PONV and IONV in women having cesarean delivery under neuraxial anesthesia. The terms “acupuncture,” “acupressure,” “electroacupuncture,” and “transcutaneous acupoint electrical stimulation” were exploded as MeSH terms and combined with the search terms “cesarean section,” “cesarean delivery,” “intraoperative,” “postoperative,” “nausea,” “vomiting,” “emesis,” “spinal anesthesia,” and “epidural anesthesia.” The search was performed without language restrictions and limited to RCTs involving human subjects. The date of the last computer search was September 2007. In addition, the bibliographies of retrieved articles were searched for additional studies.

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Methodological Quality Assessment

Both authors reviewed the abstracts of retrieved articles and excluded those that did not meet the selection criteria. Both reviewers then independently read the selected articles and assessed their methodological quality using the 7 point modified Oxford scale.16,17 Any discrepancies were resolved by discussion.

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Data Handling and Analyses

We designed a data collection form and collected data from the included studies on: (i) type of nonpharmacological technique, (ii) unilateral versus bilateral application, (iii) timing of administration of therapy, (iv) duration of therapy, (v) incidence of intraoperative hypotension and use of vasopressors, (vi) exteriorization of the uterus, and (vii) intraoperative and postoperative outcome measures including the incidence and severity of nausea and vomiting, need for rescue antiemetics, and complete response to therapy (no nausea, vomiting, or need for rescue antiemetics).

It was our initial intention to combine the data using classic methods of meta-analysis and report summary estimates with 95% confidence intervals. However, because the relevant trials were clinically heterogeneous, meta-analysis was deemed inappropriate. Instead the primary outcome data extracted from the original studies were compared qualitatively. The results of statistical significance between the intervention and control groups were reported as in the original manuscripts.

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RESULTS

Thirteen publications were initially identified. All studies were in English. Seven publications were subsequently excluded (Fig. 1). The remaining 6 RCTs yielded 649 patients for analysis. Of these, 326 patients received P6 stimulation and 323 sham or placebo. The characteristics of the included studies are shown in Table 1. The minimum Oxford scale score of an included trial was 4 and the maximum score was 6.

Figure 1
Figure 1
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Table 1
Table 1
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Bilateral acupressure was used in four studies,5,9,11,18 unilateral acupressure in one study,8 and unilateral transcutaneous acupoint electrical stimulation in one study.19 Interventions in the control and treatment groups were instituted preoperatively 5 to 60 min before the induction of neuraxial anesthesia. Placebo bands were used as the control in all the included studies. In two studies, the stimulating buttons were removed in the placebo group.5,11 In another two studies, these buttons were blunted.9,18 In the two remaining studies, the placebo groups received stimulation at nonacupuncture points.8,19

Neuraxial opioids were used in all studies except one. The latter study only reported intraoperative outcomes.9 In four studies, opioids were administered intrathecally5,8,11,19 and, in one study, opioids were administered via an epidural catheter postoperatively for pain relief.18

The included studies reported no difference between the P6 stimulation and control groups in the rate of uterine exteriorization,5,11,19 or the incidence of intraoperative opioid supplementation,5,8,9,19 postoperative opioid consumption,5,8,18,19 intraoperative vasopressor use,5,8,9,11,19 or intraoperative hypotension.5,8,11

Side effects were reported in five of the six studies with no differences between the active and control groups.5,8,9,18,19 In two studies, no adverse effects were reported.9,18 In the remaining studies, application of bands caused localized discomfort, itching, swollen hands, and problems with IV infusions.5,8,19

The outcomes are as follows:

Nausea: Five studies reported on the incidence of intraoperative nausea.5,8,9,11,19 Two studies reported a significant reduction in intraoperative nausea with P6 stimulation,8,11 whereas the remaining three studies reported no difference compared with the control group.5,9,19 The incidence of postoperative nausea was reported by four studies.5,8,18,19 Only one study reported a significant reduction in the incidence of postoperative nausea with P6 stimulation.18 However, in a subgroup analysis in one of the other studies, Duggal et al.5 demonstrated that P6 acupressure significantly reduced the incidence of postoperative nausea in patients with a history of PONV. The only study reporting nausea scores found no differences between the treatment and control groups.19

Vomiting: Of the five studies reporting on the incidence of intraoperative vomiting, none were able to demonstrate an improvement with P6 stimulation.5,8,9,11,18,19 Of the four studies reporting the incidence of postoperative vomiting,5,8,18,19 only two reported a significant reduction with P6 stimulation.8,18 Again Duggal et al.,5 in a subgroup analysis, reported a statistically significant reduction in the incidence of postoperative vomiting with P6 stimulation in women who had a history of PONV.

Use of Rescue Antiemetics: The need for intraoperative rescue antiemetics was reported in four studies.5,9,19 Only one study reported a significant reduction in antiemetic requirement during surgery with P6 simulation.8 Four studies reported on the need for postoperative antiemetic rescue.5,8,18,19 Of these, only one was able to demonstrate a significant reduction in the need for rescue antiemetic therapy in the P6 stimulation group.8

Complete Response to Therapy: Only one study reported on the rate of intraoperative and postoperative complete response to P6 stimulation, but found no differences between the treatment and control groups.19

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DISCUSSION

The trials included in this review reported inconsistent results regarding the efficacy of P6 stimulation for the prevention of IONV and PONV in women undergoing cesarean delivery under neuraxial anesthesia. Of note, of the three studies reporting some benefit of P6 stimulation, two were the smallest studies included in this review.11,18 These results should be interpreted with caution, since small trials may detect a beneficial treatment effect by random chance.20 Additionally, one of the included studies suggested that the negative finding might have been due to inadequate power.19

While our original intent was to perform a meta-analysis, this was deemed inappropriate because of clinical heterogeneity among the included trials. For instance, intraoperative hypotension, a known risk factor for IONV, might have been managed differently in the included studies as reflected by the difference in the incidence of pre-delivery hypotension and need for vasopressors (40%–76%). While fluid preloading was used in all the studies, prophylactic ephedrine was used in addition in one study,8 and bilateral leg wrapping was used in another study.9 Furthermore, while ephedrine was the primary vasopressor for the treatment of intraoperative hypotension for all five studies investigating IONV,5,8,9,11,19 phenylephrine was also used either alone or in combination with ephedrine in one study.5 The control event rates were also different among the included studies. For instance, intraoperative nausea in the control group ranged from 30% to 76%. Two of the included studies investigating IONV failed to describe the technique for uterine repair despite the fact that uterine exteriorization is a major risk factor for IONV.8,9 While the studies reporting postoperative outcomes used mostly intrathecal morphine 200–250 μg,5,8,19 one study18 involved the administration of multiple boluses of epidural morphine postoperatively. The duration of P6 stimulation also varied among the different studies.

There are currently no data comparing the efficacy of different P6 stimulation techniques. It is also not clear if bilateral P6 stimulation offers advantages compared with unilateral stimulation. Of interest, of the four trials using bilateral stimulation, two reported a beneficial effect of P6 stimulation,11,18 and of the two trials using unilateral stimulation, one reported better results with the active intervention.8 It is also not known whether continuous stimulation of the P6 point is needed to maintain the antiemetic effect of these techniques or whether a brief period of stimulation would be adequate. For instance, in a previous study in patients undergoing breast surgery under general anesthesia, intraoperative P6 stimulation produced an antiemetic effect for 24 h.7

A larger number of studies have investigated the antiemetic effect of P6 stimulation in the general surgical population, and generally found it to be effective at reducing PONV.21,22 P6 stimulation might be particularly effective for prophylaxis against nausea.7,23,24 The antiemetic efficacy of modalities stimulating the P6 point was reported to be comparable to currently available drugs,7,25 and resulted in enhanced prophylaxis when combined with antiemetics.25

This review highlights several areas where future research in the obstetric population is needed. Future large trials comparing different P6 stimulation modalities are needed. In a post hoc analysis, Duggal et al. reported an increased efficacy of P6 stimulation in reducing PONV in patients with a history of PONV, and this requires further investigation. The efficacy of unilateral versus bilateral P6 stimulation, as well as the optimal duration of P6 stimulation, also need to be established. The efficacy of P6 stimulation in combination with other acupuncture points with known antiemetic effects such as the St36 point and the Korean K9 point also requires further investigation. Finally, because IONV and PONV are multifactorial, and multimodal therapy is more effective than single-mode therapy, the efficacy of nonpharmacological techniques used in combination with drug therapy for reducing the incidence and severity of IONV and PONV in obstetric anesthesia practice is another area of future research.

In conclusion, while some studies showed improved antiemetic prophylaxis with P6 stimulation, this finding was not consistent. The heterogeneity among the trials and the inconsistent results prevent any definitive conclusions on the efficacy of perioperative P6 stimulation as a method of prophylaxis for IONV and PONV in women having cesarean delivery under neuraxial anesthesia.

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