Estimulación del punto de acupuntura PC6 de la muñeca para la prevención de las náuseas y los vómitos en el período posoperatorio
Resumen
Antecedentes
Las náuseas y los vómitos en el período posoperatorio (NVPO) son complicaciones frecuentes después de la cirugía y la anestesia. Los fármacos antieméticos solamente tienen una efectividad parcial para prevenir las NVPO. Un enfoque alternativo es estimular el punto de acupuntura PC6 en la muñeca. Ésta es una actualización de una revisión Cochrane publicada por primera vez en 2004, actualizada en 2009 y ahora en 2015.
Objetivos
Determinar la efectividad y la seguridad de la estimulación del punto de acupuntura PC6 con o sin fármacos antieméticos versus tratamiento simulado o antieméticos para la prevención de las NVPO en pacientes sometidos a cirugía.
Métodos de búsqueda
Se realizaron búsquedas en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL) (Cochrane Library, número 12, 2014), MEDLINE (enero de 2008 a diciembre de 2014), EMBASE (enero de 2008 a diciembre de 2014), ISI Web of Science (enero de 2008 a diciembre de 2014), Registro de Ensayos Clínicos de la Organización Mundial de la Salud, ClinicalTrials.gov y las listas bibliográficas de los artículos para identificar estudios adicionales. No se aplicaron restricciones de idioma.
Criterios de selección
Todos los ensayos aleatorizados de las técnicas de estimulación del punto de acupuntura PC6 en comparación con tratamiento simulado o tratamiento farmacológico, o una combinación del punto de acupuntura PC6 y tratamiento farmacológico en comparación con tratamiento farmacológico, para la prevención de las NVPO. Las intervenciones utilizadas en estos ensayos incluyeron acupuntura, electroacupuntura, estimulación eléctrica transcutánea del punto de acupuntura, estimulación nerviosa transcutánea, estimulación láser, emplasto de capsicum, dispositivos de acuestimulación y acupresión en pacientes a los que se les realizó cirugía. Los resultados primarios fueron las incidencias de náuseas y vómitos después de la cirugía. Los resultados secundarios fueron la necesidad de tratamiento antiemético de rescate y los efectos adversos.
Obtención y análisis de los datos
Dos autores de la revisión, de forma independiente, extrajeron los datos y evaluaron los dominios de riesgo de sesgo de cada ensayo. Se utilizó un modelo de efectos aleatorios y se informó el riesgo relativo (RR) con los intervalos de confianza del 95% (IC del 95%) asociados. Se utilizaron los análisis secuenciales de ensayos para ayudar a proporcionar información sobre cuándo se había obtenido evidencia sólida en los metanálisis acumulativos de los resultados primarios, sobre la base de una reducción del riesgo relativo del 30% en las NVPO.
Resultados principales
Se incluyeron 59 ensayos con 7667 participantes. Dos ensayos se consideraron con riesgo bajo de sesgo en todos los dominios (selección, deserción, informe, cegamiento y otros). Veinticinco ensayos se consideraron con riesgo alto en uno o más dominios del riesgo de sesgo. En comparación con el tratamiento simulado, la estimulación del punto de acupuntura PC6 redujo significativamente la incidencia de náuseas (RR 0,68; IC del 95%: 0,60 a 0,77; 40 ensayos, 4742 participantes), los vómitos (RR 0,60; IC del 95%: 0,51 a 0,71; 45 ensayos, 5147 participantes) y la necesidad de antieméticos de rescate (RR 0,64; IC del 95%: 0,55 a 0,73; 39 ensayos, 4622 participantes). Debido a que la heterogeneidad entre los ensayos fue significativa y hubo limitaciones en los estudios, la calidad de la evidencia de consideró baja. Mediante el análisis secuencial de los ensayos, se alcanzó el tamaño de información requerido y el límite del beneficio para ambos resultados primarios.
La estimulación del punto de acupuntura PC6 se comparó con seis tipos diferentes de fármacos antieméticos (metoclopramida, ciclizina, proclorperazina, droperidol, ondansetrón y dexametasona). En comparación con el tratamiento simulado, la estimulación del punto de acupuntura PC6 redujo significativamente la incidencia de náuseas (RR 0,91; IC del 95%: 0,75 a 1,10; 14 ensayos, 1332 participantes), los vómitos (RR 0,93; IC del 95%: 0,74 a 1,17; 19 ensayos, 1708 participantes) y la necesidad de antieméticos de rescate (RR 0,87; IC del 95%: 0,65 a 1,16; 9 ensayos, 895 participantes). La calidad de la evidencia se consideró moderada debido a las limitaciones de los estudios. Mediante los análisis secuenciales de los ensayos, el límite de futilidad se cruzó antes de que se sobrepasara el tamaño de información necesario para ambos resultados primarios.
En comparación con los fármacos antieméticos, la combinación de la estimulación del punto de acupuntura PC6 y el tratamiento antiemético redujo la incidencia de vómitos (RR 0,56; IC del 95%: 0,35 a 0,91; nueve ensayos, 687 participantes), pero no las náuseas (RR 0,79; IC del 95%: 0,55 a 1,13; ocho ensayos, 642 participantes). La calidad de la evidencia se consideró muy baja debido a la heterogeneidad significativa entre los ensayos, las limitaciones de los estudios y la imprecisión. Mediante el análisis secuencial de los ensayos, no se cruzaron los límites de los efectos beneficiosos, los efectos perjudiciales o la futilidad para las NVPO. La necesidad de antieméticos de rescate fue menor en el grupo que combinó estimulación del punto de acupuntura PC6 y antieméticos que en el grupo de antieméticos (RR 0,61; IC del 95%: 0,44 a 0,86; cinco ensayos, 419 participantes).
Los efectos secundarios asociados con el punto de estimulación de acupuntura PC6 fueron leves, transitorios y desaparecieron de forma espontánea (p.ej., irritación de la piel, formación de ampollas, enrojecimiento y dolor) en 14 ensayos. El sesgo de publicación no fue evidente en los gráficos en embudo de contorno mejorado.
Conclusiones de los autores
Hay evidencia de calidad baja para apoyar el uso de la estimulación del punto de acupuntura PC6 sobre el tratamiento simulado. En comparación con la última actualización de 2009 no se necesitan ensayos adicionales de comparación con tratamiento simulado. Se encontró que hay evidencia de calidad moderada que no muestra diferencias entre la estimulación del punto de acupuntura PC6 y los fármacos antieméticos para prevenir las NVPO. Sería inútil realizar ensayos adicionales sobre la estimulación del punto de acupuntura PC6 versus antieméticos para mostrar una diferencia significativa, el cual es un nuevo resultado en esta actualización. Hay evidencia no concluyente para apoyar el uso de una estrategia combinada de estimulación del punto de acupuntura PC6 y fármacos antieméticos sobre la profilaxis con fármacos, y se necesitan ensayos de alta calidad adicionales.
PICO
Resumen en términos sencillos
Estimulación del punto de acupuntura PC6 de la muñeca para prevenir las náuseas y los vómitos después de la cirugía
Pregunta de la revisión
¿La revisión de la evidencia apoya el uso de la estimulación del punto de acupuntura PC6 de la muñeca (punto de acupuntura PC6) y la considera efectiva para reducir las náuseas y los vómitos después de la cirugía (NVPO), en comparación con el tratamiento simulado (estimulación simulada del punto de acupuntura) o los antieméticos (fármacos que alivian las náuseas y los vómitos) en pacientes sometidos a cirugía? Esta revisión actualiza la evidencia publicada en 2009 y está actualizada hasta diciembre de 2014.
Antecedentes
Las náuseas y los vómitos son dos de las complicaciones más frecuentes (en hasta el 80%) tras la anestesia y la cirugía. Los antieméticos solamente tienen una efectividad parcial y pueden causar efectos adversos como sedación y cefalea. Se ha informado que la estimulación del punto de acupuntura PC6 (un método alternativo) reduce las NVPO con pocos efectos secundarios graves.
Características de los estudios
Se encontraron 59 estudios relevantes realizados entre 1986 y 2015 con 7667 participantes sometidos a cirugía electiva. Siete de los ensayos se realizaron en 727 niños. La estimulación del punto de acupuntura PC6 varió de técnicas invasivas como agujas de acupuntura tradicionales, a técnicas no invasivas como pulseras de acupresión. La estimulación del punto de acupuntura PC6 se comparó con seis tipos diferentes de fármacos antieméticos (metoclopramida, ciclizina, proclorperazina, droperidol, ondansetrón y dexametasona).
Hallazgos clave y calidad de la evidencia
Efectos de la estimulación del punto de acupuntura PC6 versus tratamiento simulado en las NVPO
Se encontró un efecto de tamaño moderado en los niños y los adultos, aunque hubo preocupación en cuanto a las limitaciones de los estudios y a la variación no explicada en los efectos. No se necesitan estudios adicionales de comparaciones con tratamiento simulado para confirmar este efecto beneficioso.
Efectos de la estimulación del punto de acupuntura PC6 versus antieméticos sobre las NVPO
No se encontraron diferencias en la incidencia de NVPO. La calidad de esta evidencia se consideró moderada debido a las limitaciones de los estudios. Es poco probable que los estudios adicionales muestren una diferencia.
Efectos de la combinación de la estimulación del punto de acupuntura PC6 y antiemético versus antiemético en las NVPO
Se encontró un efecto de tamaño moderado sobre los vómitos posoperatorios, pero no sobre las náuseas posoperatorias. Sin embargo, hubo inquietudes en cuanto a las limitaciones de los estudios, la variación no explicada en los efectos entre los estudios y el número insuficiente de estudios. Se necesitan estudios de investigación adicionales de alta calidad sobre las combinaciones de estimulación del punto de acupuntura PC6 y antieméticos para reducir las dudas acerca de este efecto sobre las NVPO.
En general, los efectos secundarios relacionados con la estimulación del punto de acupuntura PC6 fueron leves, transitorios y desaparecieron de forma espontánea (p.ej., irritación de la piel, formación de ampollas, rubor y dolor) en 14 estudios.
Conclusión
Para la prevención las NVPO, el efecto de la estimulación del punto de acupuntura PC6 es equivalente al de los antieméticos.
Authors' conclusions
Summary of findings
| Acupoint PC6 stimulation versus sham for preventing postoperative nausea and vomiting | ||||||
| Patient or population: People at risk of postoperative nausea and vomiting Comparison: Sham | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Sham | Acupoint PC6 stimulation | |||||
| Nausea ‐ All trials | Low | RR 0.68 | 4742 | ⊕⊕⊝⊝ | ||
| 200 per 1000 | 136 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 272 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 408 per 1000 | |||||
| Vomiting ‐ All trials | Low | RR 0.60 | 5147 | ⊕⊕⊝⊝ | ||
| 200 per 1000 | 120 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 240 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 360 per 1000 | |||||
| Rescue antiemetics | 329 per 1000 | 210 per 1000 | RR 0.64 | 4622 | ⊕⊕⊝⊝ | |
| Adverse effects | Not estimable | Not estimable | Not estimable | 35 studies6 | Not applicable | See footnote6 |
| *The basis for the assumed risks for nausea and vomiting is from a consensus panel (Gan 2014) using Apfel's simplified risk score (Apfel 1999). The assumed risk for rescue antiemetic is the median sham group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Of the 40 trials, 13 had one or more high risk of bias domains (downgrade 1 point due to study limitations). | ||||||
| Acupoint PC6 stimulation versus antiemetic drug for preventing postoperative nausea and vomiting | ||||||
| Patient or population: People at risk of postoperative nausea and vomiting Comparison: Antiemetic drug | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Antiemetic | Acupoint PC6 stimulation | |||||
| Nausea ‐ All antiemetics combined | Low | RR 0.91 | 1332 | ⊕⊕⊕⊝ | ||
| 200 per 1000 | 182 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 364 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 546 per 1000 | |||||
| Vomiting ‐ All antiemetics combined | Low | RR 0.93 | 1708 | ⊕⊕⊕⊝ | ||
| 200 per 1000 | 186 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 372 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 558 per 1000 | |||||
| Rescue antiemetic | 150 per 1000 | 130 per 1000 | RR 0.87 | 895 | ⊕⊕⊕⊝ | |
| Adverse effects | See comment | See comment | Not estimable | 11 studies4 | Not applicable | See footnote4 |
| *The basis for the assumed risks for nausea and vomiting is from a consensus panel (Gan 2014) using Apfel's simplified risk score (Apfel 1999). The assumed risk for rescue antiemetic is the median antiemetic group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Of the 14 trials, 5 had one or more high risk of bias domains (downgrade 1 point due to study limitations). | ||||||
| Acupoint PC6 stimulation and antiemetic combination compared to antiemetic for preventing postoperative nausea and vomiting | ||||||
| Patient or population: People at risk of postoperative nausea and vomiting | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Antiemetic | Acupoint PC6 stimulation and antiemetic combination | |||||
| Nausea | Low | RR 0.79 | 642 | ⊕⊝⊝⊝ | ||
| 200 per 1000 | 158 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 316 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 474 per 1000 | |||||
| Vomiting | Low | RR 0.56 | 687 | ⊕⊝⊝⊝ | ||
| 200 per 1000 | 112 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 224 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 336 per 1000 | |||||
| Rescue antiemetic | 316 per 1000 | 193 per 1000 | RR 0.61 | 419 | ⊕⊕⊝⊝ | |
| Adverse effects | See comment | See comment | Not estimable | 6 studies7 | Not applicable | See footnote7 |
| *The basis for the assumed risks for nausea and vomiting is from a consensus panel (Gan 2014) using Apfel's simplified risk score (Apfel 1999). The assumed risk for rescue antiemetic is the median antiemetic group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Of the 8 trials, 2 had one or more high risk of bias domains (downgrade 1 point due to study limitations). | ||||||
Background
Description of the condition
Postoperative nausea and vomiting (PONV) are common complaints after general, regional, or local anaesthesia (Watcha 1992), with incidences up to 80% (Sadhasivam 1999). PONV may lead to delayed recovery from anaesthesia and surgery, unanticipated readmission to hospital and increased overall healthcare costs (Gan 2014).
Drug therapy is only partially effective in preventing or treating PONV (Gin 1994). A systematic review of antiemetic drugs for PONV (Carlisle 2006) showed that eight drugs effectively prevented PONV when compared to placebo: droperidol, metoclopramide, ondansetron, tropisetron, dolasetron, dexamethasone, cyclizine, and granisetron. The risk ratios (RRs) varied between 0.60 and 0.80, depending on the drug and the outcome (Carlisle 2006). Evidence for side effects was sparse: droperidol was sedative (RR 1.32, 95% confidence interval (CI) 1.16 to 1.51) and headache was more common after ondansetron (RR 1.16, 95% CI 1.03 to 1.30) (Carlisle 2006). More recently, a multidisciplinary panel of experts produced guidelines for the prevention or minimization of PONV using prophylactic or rescue therapy, either separately or in combination with non‐pharmacological approaches (Gan 2014).
Description of the intervention
As anaesthetists continue to search for more cost‐effective approaches to improving patient outcomes, attention has focused on simple, inexpensive, and non‐invasive methods to prevent PONV. Concern about the cost and side effects of drugs has led to interest in the use of alternative approaches to preventing emesis.
Various non‐pharmacological techniques have been examined in trials as alternatives to antiemetic drugs. These include acupuncture, electro‐acupuncture, laser acupuncture, transcutaneous electrical nerve stimulation (TENS), electro‐acupoint stimulation, acupressure, and capsicum plaster. Most non‐pharmacological studies have focused on stimulation of the wrist at the 'Pericardium (PC6) acupuncture point' to reduce nausea and vomiting. The PC6 acupoint lies between the tendons of the palmaris longus and flexor carpi radialis muscles, 4 cm proximal to the wrist crease (Yang 1993).
How the intervention might work
The mechanism by which PC6 acupoint stimulation prevents PONV has not been established in 'Western' evidence‐based methodology. However, according to Traditional Chinese Medicine theory, surgery interrupts the balanced state of the human body by disturbing the movement of both qi (energy flow) and blood, leading to stomach qi going upward to cause nausea and vomiting (Lv 2013). By regulating the function of the stomach to reduce the adverse flow of qi, PC6 acupoint stimulation may prevent nausea and vomiting (Lv 2013). Other acupoints believed to prevent PONV include Shenmen (H7) (Ming 2002) and Shang Wen (CV13) (Somri 2001).
Why it is important to do this review
Despite supportive literature for the use of PC6 acupoint stimulation in recent consensus guidelines for the management of PONV (Gan 2014), there is currently a lack of widespread uptake of the technique. This may be due to a lack of evidence on the optimal timing, duration and method of PC6 acupoint stimulation (Streitberger 2011), and preference of anaesthesiologists for an immediate pharmacokinetic effect of an antiemetic over a slower onset of PC6 acupoint stimulation effect.
One of the earliest systematic review (Vickers 1996), using a 'vote counting' approach, suggested that acupuncture may not be effective in the prevention of PONV. However, the vote‐counting approach is not considered an acceptable method of summarizing the results of a systematic review (Petitti 1994).
Our previous systematic review of trials (Lee 1999), including trials published up to 1997, showed no difference between PC6 acupoint stimulation and commonly‐used antiemetic drugs in preventing PONV after surgery. This review also indicated that the technique was more effective than placebo (sham treatment or no treatment) in preventing PONV in adults but not in children. However, these results in children were questionable, as they were based largely on trials in which PC6 acupoint stimulation occurred while the central nervous system was depressed by general anaesthesia (White 1999). Another major limitation of our earlier review was that we included both no‐treatment and sham‐treatment groups. Therefore, we may have overestimated the treatment effect of PC6 acupoint stimulation.
In the last Cochrane review update (Lee 2009) of 40 trials (n = 4858), we showed that there were significant reductions in the incidences of nausea (RR 0.71, 95% CI 0.61 to 0.83), vomiting (RR 0.70, 95% CI 0.59 to 0.83), and the need for rescue antiemetics (RR 0.69, 95% CI 0.57 to 0.83) in the PC6 acupoint stimulation group compared with the sham treatment group. Compared to antiemetic drugs, the incidence of nausea (RR 0.82, 95% CI 0.60 to 1.13), vomiting (RR 1.01, 95% CI 0.77 to 1.31) or the need for rescue antiemetics (RR 0.82, 95% CI 0.59 to 1.13) were similar in the PC6 acupoint stimulation group. Publication bias may have affected the risk ratio estimated for postoperative nausea but not for vomiting (Lee 2006) in the first version of the review published in 2004 (Lee 2004). However, in the next version (Lee 2009), publication bias was not apparent from the contour‐enhanced funnel plots.
The rationale for conducting this Cochrane review update was to establish if there is firm evidence for the effect of PC6 acupoint stimulation in reducing the incidence of PONV using trial sequential analysis methodology. We were concerned that repeated updates (Lee 2004; Lee 2009) may introduce spuriously significant results (type 1 error) due to repeated significance testing.
Objectives
To determine the effectiveness and safety of PC6 acupoint stimulation with or without antiemetic drug versus sham or antiemetic drug for the prevention of PONV in people undergoing surgery.
Methods
Criteria for considering studies for this review
Types of studies
We included all randomized controlled trials (RCTs) of techniques intended to stimulate the PC6 acupoint, compared with either sham treatment or antiemetic drugs, for the prevention of PONV. We defined 'sham treatment' as a device applied in a non‐PC6 location, or any attempt to imitate (give the illusion of) PC6 acupoint stimulation. Therefore, for trials that assessed acupressure wristbands, we considered wristbands without studs placed at the PC6 acupoint as adequate sham treatment, and we included these trials in the review.
We excluded studies that only reported the severity of postoperative nausea or vomiting or both, and had not reported the incidence of postoperative nausea and vomiting or the need for rescue antiemetic.
Types of participants
We included all surgical patients without age limitation in the review. The age limits for children were defined by each study. We considered all types of surgery.
Types of interventions
Techniques intended to stimulate the PC6 acupoint: acupuncture, electro‐acupuncture, laser acupuncture, transcutaneous electrical stimulation, conventional peripheral nerve stimulation, acu‐stimulation device, acupressure, and capsicum plaster; versus sham treatment or drug therapy for the prevention of PONV. We grouped these diverse techniques as one entity in the main analysis, consistent with the concept that stimulating the correct acupuncture point is more important than the nature of the stimulus (Mann 1987). There was no restriction on the duration of PC6 acupoint stimulation or when it was applied.
Types of outcome measures
We performed separate meta‐analyses for each of the following primary and secondary outcomes. Trials could report more than one primary or secondary outcome:
Primary outcomes
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Incidence of postoperative nausea.
-
Incidence of postoperative vomiting, defined as either retching or vomiting, or both.
We did not combine postoperative nausea and vomiting as we could not be certain that participants who vomited were also nauseated. If the authors reported several incidences of the outcome measure (for example 0 to six hours, six to 24 hours, 0 to 24 hours), we used the longest cumulative follow‐up data from the end of surgery (in this case, 0 to 24 hours).
Secondary outcomes
-
Need for rescue antiemetic drug when prophylaxis failed.
-
Adverse effects from PC6 acupoint stimulation or antiemetic drug, or both.
Search methods for identification of studies
Electronic searches
We searched the following for relevant trials on 31st December 2014:
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The Cochrane Central Register of Controlled Trials (CENTRAL; Issue 12, 2014), in Appendix 1.
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Electronic databases: OVID MEDLINE (January 2008 to December 2014), in Appendix 2; OVID EMBASE (January 2008 to December 2014), in Appendix 3; ISI Web of Science (January 2008 to December 2014), in Appendix 4)
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World Health Organization Clinical Trials Registry and ClinicalTrial.gov
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Reference lists of relevant articles, reviews, and trials.
We combined the following MeSH and text words with the filters for identifying randomized controlled trials: 'postoperative complications', 'nausea and vomiting', 'acupuncture', 'acupuncture therapy', 'acupuncture points', 'acupressure', 'transcutaneous electric nerve stimulator', and 'electro‐acupuncture'. There was no language restriction. We excluded studies of PC6 acupoint stimulation to treat established PONV, or to prevent intraoperative nausea or vomiting.
Searching other resources
We did not search for conference proceedings or seek unpublished trials. Grey literature has not been peer‐reviewed and there is some evidence that it is of lower quality than published studies (McAuley 2000). Searching unpublished trials may not be worthwhile, as many unpublished trials are of poor or unclear methodological quality (Van Driel 2009).
Data collection and analysis
Selection of studies
We screened titles and abstracts of publications identified from the search, and selected trials that fulfilled our inclusion criteria. There was one disagreement between review authors for inclusion into this systematic review. The third review author adjudicated and decided that the study (Zhu 2010) met the inclusion criteria. We examined all selected trials for duplicate data; where we found duplication, we used the results of the main trial report.
Data extraction and management
We extracted data independently, using a standardized data collection form, and resolved any discrepancies in data extraction by discussion. We collected data on the type, duration, and timing of PC6 acupoint stimulation, as well as the type and dose of prophylactic antiemetic drug. We recorded general details of the participant population and type of surgery. We collected outcome measures as described above for each study group. We did not consider factors such as the severity of PONV or the number of episodes of vomiting. In studies with more than two groups, we avoided double‐counting of participants by following the guidelines for analysis in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
Assessment of risk of bias in included studies
We assessed the quality of the included trials independently, under open conditions. We graded the risk of bias for each study in the domains of sequence generation, allocation concealment, blinding of participants, healthcare providers, and outcome assessors, incomplete outcome data, selective outcome reporting, and comparison of baseline characteristics for each group in a 'Risk of bias' table (Higgins 2011). We graded each domain as low risk of bias, unclear (uncertain risk of bias) or high risk of bias, according to the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). For summary assessment of the risk of bias within and across studies, we followed the approach outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and rated it as low, unclear or high risk of bias.
We used the GRADE approach to describe the overall quality of the outcome, rating it as high, moderate, low or very low (Guyatt 2011). To make this assessment, we examined the study limitations (risk of bias), indirectness of evidence, serious inconsistency, imprecision of effect estimates and potential publication bias (Guyatt 2011). We downgraded the quality of evidence from high if there were deficiencies in these domains.
We included the following outcomes in summary of findings Table for the main comparison, summary of findings Table 2 and summary of findings Table 3: incidence of postoperative nausea, incidence of postoperative vomiting, need for rescue antiemetic, and adverse effects.
Measures of treatment effect
For dichotomous data, we reported the risk ratio (RR) and the associated 95% confidence interval (95% CI).
Unit of analysis issues
None.
Dealing with missing data
We analysed data according to the intention‐to‐treat principle.
Assessment of heterogeneity
We measured heterogeneity using the I² statistic, a measure of the proportion of total variation in the estimates of treatment effect that is due to heterogeneity between studies rather than due to chance. We described the level of heterogeneity as not important (I² statistic from 0% to 40%), moderate (I² statistic from 30% to 60%), substantial (I² statistic from 50% to 90%) and considerable (I² statistic from 75% to 100%) (Higgins 2011).
Assessment of reporting biases
We used the contour‐enhanced funnel plot to differentiate asymmetry due to publication bias from that due to other factors (Peters 2008), using STATA statistical software (Stata Corporation, College Station, Texas, version 14). Contour‐enhanced funnel plots display the area of statistical significance on a funnel plot to improve the correct identification of the presence or absence of publication bias. We used this in conjunction with the 'trim and fill' method (Duval 2000) to inform the likely location of missing studies, using STATA statistical software, as suggested by Peters 2008. Publication bias would be expected when the usual funnel plot is asymmetrical but assessment of the contour‐enhanced funnel plot indicates that missing studies are located where non‐significant studies would be plotted (Peters 2008).
Data synthesis
We used Review Manager 5 to perform the DerSimonian and Laird random‐effects model meta‐analyses of risk ratios, as we expected that the treatments and conditions in these trials would be heterogeneous. This model incorporates both between‐study (different treatment effects) and within‐study (sampling error) variability (Mosteller 1996).
We estimated the number needed to treat for an additional beneficial outcome (NNTB) for different baseline risks for nausea and vomiting, using the RR (Smeeth 1999) to assess whether PC6 acupoint stimulation is worthwhile for individuals. We estimated the 95% CI around the NNTB using the method outlined by Altman 1998.
We undertook trial sequential analysis (TSA) to estimate the required information size in meta‐analysis, that is, the number of participants needed to provide a reliable and conclusive estimate (Afshari 2015). The required information size was based on a risk ratio reduction of 30% (Apfel 2007), an overall type 1 error of 5%, power at 80%, incidence in the control arm and a model‐based heterogeneity correction, using Trial Sequential Analysis software (Thorlund 2011).
Subgroup analysis and investigation of heterogeneity
We undertook exploratory a priori subgroup analyses, which included trials in adults versus children, and trials according to type of PC6 acupoint stimulation (invasive versus noninvasive). To test whether the subgroups were different from one another, we tested the interaction using the technique outlined by Altman 2003.
Sensitivity analysis
We conducted sensitivity analyses to estimate the robustness of results according to the risk of bias (low, unclear, high) and to the control event rate (≤ 20%, > 20%).
Results
Description of studies
Results of the search
The search identified 43 studies for full‐text review. Sixty‐seven trials (40 included and 27 excluded) from our previous Cochrane review (Lee 2009) were brought forward for this systematic review. The flow chart (Figure 1) shows the results of the literature search (the number of hits) and the culling process to reduce the total to 59 included studies for meta‐analysis. Ongoing trials are described in Characteristics of ongoing studies.
Study flow diagram.
Included studies
We include 59 trials conducted between 1986 and 2015, involving 7667 participants (see Characteristics of included studies). The median sample size of trials was 104 (interquartile range: 75 to 156). All trials but three (Gieron 1993; Kim 2004; Zhu 2010) were published in English. Most trials recruited healthy adults undergoing elective surgery. Seven trials recruited children (Butkovic 2005; Lewis 1991; Rusy 2002; Schlager 1998; Shenkman 1999; Wang 2002; Yentis 1992). Three trials recruited both children and adults (Amir 2007; Ebrahim Soltani 2010; Ravi 2010). Most participants had general anaesthesia. Women having elective Caesarean delivery received spinal anaesthesia in six studies (Direkvand‐Moghadam 2013; Duggal 1998; El‐Deeb 2011; Habib 2006; Harmon 2000; Ho 1996).
There were 10 types of PC6 acupoint stimulation: needle acupuncture (Dundee 1986; Dundee 1989; Sharma 2007; Streitberger 2004; Yentis 1992); infiltration of dextrose (Ravi 2010; Tavlan 1996; Wang 2002; Yang 1993) or with droperidol (Zhu 2010); semipermanent needles (Andrzejowski 1996); electrical stimulation of needles (Amir 2007; Dundee 1989; El‐Deeb 2011; Gan 2004; Ho 1990; Rusy 2002); transcutaneous electrical nerve stimulation (Fassoulaki 1993; Ho 1990), transcutaneous electrical acupoint stimulation (Habib 2006; Wang 2010; Xu 2012), laser stimulation (Butkovic 2005; Schlager 1998); acu‐stimulation device (Ertas 2015; Frey 2009a; Frey 2009b; Kim 2004; White 2002; Zárate 2001); and acupressure (Adib‐Hajbaghery 2013; Agarwal 2000; Agarwal 2002; Alkaissi 1999; Alkaissi 2002; Allen 1994; Barsoum 1990; Direkvand‐Moghadam 2013; Duggal 1998; Ebrahim Soltani 2010; Ferrara‐Love 1996; Gieron 1993; Harmon 1999; Harmon 2000; Ho 1996; Iqbal 2012; Klein 2004; Lewis 1991; Majholm 2011; Nilsson 2015; Sadighha 2008; Samad 2003; Schultz 2003; Turgut 2007; White 2012). Three studies used conventional peripheral nerve stimulation (Arnberger 2007; Kim 2011; Liu 2008). One trial used both acupressure and acupuncture (Shenkman 1999). Capsicum plaster at PC6 acupoint was used in two studies (Koo 2013; Misra 2005). The type of surgery; type, timing, and duration of stimulation of the PC6 acupoint; and the follow‐up time for assessing PONV varied greatly.
PC6 stimulation was compared with six antiemetic drugs: metoclopramide (Butkovic 2005; Direkvand‐Moghadam 2013; Dundee 1989; Ebrahim Soltani 2010; Sadighha 2008); cyclizine (Dundee 1989); prochlorperazine (Barsoum 1990; Ho 1990); droperidol (Schultz 2003; Wang 2002; Yang 1993; Yentis 1992; Zhu 2010); ondansetron (Agarwal 2002; Ebrahim Soltani 2010; El‐Deeb 2011; Gan 2004; Misra 2005; Ravi 2010; Sharma 2007; Tavlan 1996; White 2002), dexamethasone plus ondansetron (White 2012).
A combination of PC6 stimulation and antiemetic drug was used as a multimodal therapy in several trials (Schultz 2003; Sharma 2007; Wang 2010; White 2002; White 2012; Xu 2012; Yentis 1992; Zhu 2010).
Excluded studies
We excluded 49 trials. Please see 'Characteristics of excluded studies' for more information.
Studies awaiting classification
There are no studies awaiting classification
Ongoing studies
There are two ongoing studies (Cooke 2014; Lv 2013). Please see Characteristics of ongoing studies for more information.
Risk of bias in included studies
A 'Risk of bias' graph captures the review authors' judgements about each 'Risk of bias' item, presented as percentages across all included trials (Figure 2). A 'Risk of bias' summary captures the review authors' judgements about each risk of bias item for each included trial (Figure 3). There were two studies with an overall low risk of bias (Gan 2004; Xu 2012), as we rated all key domains 'low risk'. Of the 25 studies with a high risk of bias (one or more key domains were rated 'high risk'), 20 of these were due to selective reporting.
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Allocation
Allocation sequence was provided using a computer‐generated random numbers table (Agarwal 2000; Amir 2007; Arnberger 2007; Ertas 2015; Gan 2004; Harmon 1999; Ho 1996; Klein 2004; Misra 2005; Ravi 2010; Wang 2010; White 2002; White 2012; Xu 2012; Zárate 2001), a table of random numbers (Agarwal 2002; Direkvand‐Moghadam 2013; Duggal 1998; Liu 2008; Samad 2003; Schultz 2003), a block‐design procedure (Rusy 2002), a yoking randomization based on a computer‐generated list (Wang 2002) and the toss of a dice (Adib‐Hajbaghery 2013). Two trials had high risk of selection bias from inadequate sequence generation (Ferrara‐Love 1996; Sadighha 2008). Eight of the 59 trials reported adequate allocation concealment (Arnberger 2007; Ertas 2015; Gan 2004; Majholm 2011; Nilsson 2015; Schultz 2003; Streitberger 2004; Xu 2012). In 49 trials the allocation concealment was unclear, and in two trials (Ferrara‐Love 1996; Sadighha 2008) it was inadequate.
Blinding
Participants were not blinded in one study (Sharma 2007) because acupuncture needles inserted before induction of anaesthesia had to be kept in situ in the operating room in two of the three intervention groups. There was no blinding of healthcare providers in two studies (Arnberger 2007; Sharma 2007). As an outcome assessor was not blinded in three studies (Adib‐Hajbaghery 2013; Gieron 1993; Sharma 2007), detection bias was likely to have occurred.
Incomplete outcome data
Three trials were at high risk of attrition bias (Fassoulaki 1993; Harmon 1999; Schultz 2003).
Selective reporting
Twenty trials did not report all four outcomes: postoperative nausea, postoperative vomiting, rescue antiemetic drugs, and adverse events in their studies (Adib‐Hajbaghery 2013; Alkaissi 1999; Allen 1994; Barsoum 1990; Butkovic 2005; Direkvand‐Moghadam 2013; Ertas 2015; Fassoulaki 1993; Ferrara‐Love 1996; Frey 2009a; Habib 2006; Harmon 2000; Ho 1990; Koo 2013; Lewis 1991; Ravi 2010; Sadighha 2008; Schultz 2003; Yang 1993; Yentis 1992).
Other potential sources of bias
All studies except one (Dundee 1989) reported the between‐group comparisons of baseline characteristics.
Effects of interventions
See: Summary of findings for the main comparison Acupoint PC6 stimulation versus sham for preventing postoperative nausea and vomiting; Summary of findings 2 Acupoint PC6 stimulation versus antiemetic drug for preventing postoperative nausea and vomiting; Summary of findings 3 Acupoint PC6 stimulation and antiemetic combination compared to antiemetic for preventing postoperative nausea and vomiting
PC6 acupoint stimulation versus sham treatment
In the few studies (Frey 2009a; Frey 2009b; Streitberger 2004) that directly compared the timing of PC6 acupoint stimulation (pre‐ versus post‐induction), the risk reduction of PONV was similar irrespective of when the acupoint stimulation occurred. Compared to sham acu‐stimulation, the odds of nausea within 24 hours after hysterectomy for pre‐induction acu‐stimulation and post‐induction acu‐stimulation were 0.31 (95% CI 0.14 to 0.68) and 0.33 (95% CI 0.15 to 0.73) respectively (Frey 2009a). Similarly, compared to sham acu‐stimulation, the odds of vomiting within 24 hours after hysterectomy for pre‐induction acu‐stimulation and post‐induction acu‐stimulation were 0.37 (95% CI 0.18 to 0.79) and 0.26 (95% CI 0.13 to 0.56) respectively (Frey 2009a). There was no significant difference in the incidence of PONV at two hours after laparoscopic cholecystectomy in the group of acu‐stimulation pre‐induction compared to post‐induction of anaesthesia (Frey 2009b). There was no significant difference in the incidence of PONV at 24 hours when acupuncture was given before induction (RR 0.88, 95% CI 0.60 to 1.28) or after induction (RR 0.82, 95% CI 0.53 to 1.27) (Streitberger 2004).
Primary outcomes
1. Incidence of postoperative nausea
(see Analysis 1.1)
Forty trials examined PC6 acupoint stimulation for the prevention of nausea, in a total of 4742 participants (Analysis 1.1). PC6 acupoint stimulation reduced the incidence of nausea (RR 0.68, 95% CI 0.60 to 0.77) but there was substantial heterogeneity (I² statistic = 67%). The 'trim and fill' method did not trim or add any more studies to the contour‐enhanced funnel plot (Figure 4). The estimated NNTB for different baseline risks of nausea is shown in Additional Table 1.
Contour‐enhanced funnel plot of comparison: PC6 acupoint stimulation versus sham for nausea. Contour lines are at 1%, 5% and 10% levels of statistical significance.
| Control event rate | Nausea | 95% CI | Vomiting | 95% CI |
| 10% | 31 | 25 to 43 | 25 | 20 to 34 |
| 20% | 16 | 13 to 22 | 13 | 10 to 17 |
| 30% | 10 | 8 to 14 | 8 | 7 to 11 |
| 40% | 8 | 6 to 11 | 6 | 5 to 9 |
| 50% | 6 | 5 to 9 | 5 | 4 to 7 |
| 60% | 5 | 4 to 7 | 4 | 3 to 6 |
| 70% | 4 | 4 to 6 | 4 | 3 to 5 |
| 80% | 4 | 3 to 5 | 3 | 3 to 4 |
| 90% | 3 | 3 to 5 | 3 | 2 to 4 |
CI = confidence interval
NNTB = number needed to treat for an additional beneficial outcome
PC6= pericardium acupoint
PONV = postoperative nausea and vomiting
There was no interaction effect between the subgroup analyses that were prespecified: children versus adults (Analyses 1.1.2, 1.1.3: Chi² statistic 0.48, df = 1, P = 0.49); invasive versus noninvasive PC6 acupoint stimulation (Analyses 1.1.4, 1.1.5: Chi² statistic 1.52, df = 1, P = 0.22). There was also no interaction between trials at low, unclear and high risk of bias (Analyses 1.1.6, 1.1.7, 1.1.8; Chi² statistic 1.46, df = 2, P = 0.48) or for control event rates (up to 20% or more than 20%) (Analyses 1.1.9, 1.1.10: Chi² statistic 0.44, df = 1, P = 0.51).
As the heterogeneity among trials was substantial and there were study limitations, we downgraded the evidence from high to low quality. Using trial sequential analysis, the required information size and boundary for benefit were reached for nausea (Figure 5).
Trial sequential analysis of 40 trials comparing PC6 acupoint stimulation versus sham (despite risk of bias) for postoperative nausea, with control event proportion of 46.8%, diversity of 71%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
2. Incidence of postoperative vomiting, defined as either retching or vomiting, or both
(see Analysis 1.2)
Forty‐five trials examined PC6 acupoint stimulation for the prevention of vomiting, in 5147 participants. PC6 acupoint stimulation reduced the incidence of vomiting (RR 0.60, 95% CI 0.51 to 0.71) but there was substantial heterogeneity (I² statistic = 64%). The 'trim and fill' method did not trim or add any more studies to the contour‐enhanced funnel plot (Figure 6). The estimated NNTB for different baseline risks of vomiting is shown in Additional Table 1.
Contour‐enhanced funnel plot of comparison: PC6 acupoint stimulation versus sham for vomiting. Contour lines are at 1%, 5% and 10% levels of statistical significance.
There was no interaction effect between subgroup analyses that were prespecified: children versus adults (Analyses 1.2.2, 1.2.3: Chi² statistic 0.33, df = 1, P = 0.63); invasive versus noninvasive PC6 acupoint stimulation (Analyses 1.2.4, 1.2.5: Chi² statistic 0.56, df = 1, P = 0.45). There was also no interaction between trials at low, unclear and high risk of bias (Analyses 1.2.6, 1.2.7, 1.2.8; Chi² statistic 0.30, df = 2, P = 0.86) or for control event rates (up to 20% or more than 20%) (Analyses 1.2.9, 1.2.10: Chi² statistic 1.39, df = 1, P = 0.24).
As the heterogeneity among trials was substantial and there were study limitations,we downgraded the evidence from high to low quality. Using trial sequential analysis, the required information size and boundary for benefit were reached for vomiting (Figure 7).
Trial sequential analysis of 45 trials comparing PC6 acupoint versus sham (despite risk of bias) for postoperative vomiting, with control event proportion of 32.9%, diversity of 74%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
Secondary outcomes
1.Need for rescue antiemetic drug when prophylaxis failed
The need for a rescue antiemetic was less after PC6 stimulation compared to sham treatment in 39 trials involving 4622 participants (RR 0.64, 95% CI 0.55 to 0.73). There was moderate heterogeneity (I² statistic = 44%). Three trials did not specify the type of rescue antiemetic drug used (Alkaissi 2002; Duggal 1998; Ferrara‐Love 1996). We included the data excluded by one trial for persistent vomiting (Fassoulaki 1993). We downgraded the evidence from high to low quality because of inconsistency between trials and study limitations.
2. Adverse effects from PC6 acupoint stimulation and/or antiemetic drug
Overall, the side effects associated with PC6 acupoint stimulation were minor and self limiting. There were no side effects for participants receiving acupuncture (Dundee 1986; Dundee 1989; Sharma 2007; Wang 2002; Zhu 2010); electroacupuncture (El‐Deeb 2011); acupressure (Agarwal 2000; Agarwal 2002; Gieron 1993; Harmon 1999; Ho 1996; Klein 2004; Lewis 1991; Samad 2003); or transcutaneous electro‐acupoint stimulation (Arnberger 2007; Gan 2004; Kim 2011; Liu 2008; Wang 2010; Xu 2012).
Haematomas occurred in one participant in the acupuncture group and in two participants in the placebo acupuncture group (Streitberger 2004). Pain was reported at the acupuncture site in one trial (Yang 1993). There was no significant difference in the incidence of redness and irritation at the puncture site between PC6 acupoint stimulation and sham treatment groups (Shenkman 1999). Participants complained of feeling tired and sleepy during electro‐acupuncture stimulation (Ho 1990) or had erythema (Amir 2007).
Although no side effects were reported with acu‐stimulation (Ertas 2015; White 2002), another trial reported mild cutaneous irritation (Zárate 2001). Three trials (Alkaissi 2002; Barsoum 1990; Duggal 1998) reported that acupressure bands felt uncomfortable, produced red indentation or itching, headache and dizziness, swollen wrists, and blistering at the site of the button. One participant in the acupressure group withdrew from a trial due to swelling and erythema of the wrist (Turgut 2007). The incidence of redness, tenderness, paraesthesia and swelling was similar between active and sham acupressure wristband groups (Majholm 2011; Nilsson 2015). One participant complained of mild irritation at the site of capsicum plaster application (Misra 2005).
PC6 acupoint stimulation versus antiemetic drug
Primary outcomes
1. Incidence of postoperative nausea
Compared to antiemetic drugs, there was no difference in the incidence of postoperative nausea associated with PC6 acupoint stimulation (Analysis 2.1.5: RR 0.91, 95% CI 0.75 to 1.10) in 14 trials involving 1332 participants. There was minor heterogeneity between the trials (I² statistic = 16%). The 'trim and fill' method did not trim or add any more studies to the contour‐enhanced funnel plot (Figure 8). We found no interaction effect between the different types of antiemetic drugs (ondansetron, metoclopramide, cyclizine, droperidol) for comparison with PC6 acupoint stimulation (Analyses 2.1.1 to 2.1.4: Chi² statistic 1.10, df = 3, P = 0.78).
Contour‐enhanced funnel plot of comparison: PC6 acupoint stimulation versus antiemetic for nausea. Contour lines are at 1%, 5% and 10% levels of statistical significance.
There was no interaction effect between subgroup analyses that were prespecified: children versus adults (Analyses 2.1.6, 2.1.7: Chi² statistic 1.49, df = 1, P = 0.22); invasive versus noninvasive PC6 acupoint stimulation (Analyses 2.1.8, 2.1.9: Chi² statistic 1.38, df = 1, P = 0.24). There was weak evidence for an interaction effect between trials at low, unclear and high risk of bias (Analyses 2.1.10, 2.1.11, 2.1.12; Chi² statistic 5.36, df = 2, P = 0.07). There was no interaction effect between control event rate groups (up to 20% or more than 20%) (Analyses 2.1.13, 2.1.14: Chi² statistic 0, df = 1, P = 0.97).
As there were study limitations, we downgraded the evidence from high to moderate quality. Using trial sequential analysis, the boundary for futility was reached for nausea (Figure 9).
Trial sequential analysis of 14 trials of PC6 acupoint stimulation versus antiemetic (despite risk of bias) for postoperative nausea, with control event proportion of 25.0%, diversity of 40%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
2. Incidence of postoperative vomiting, defined as either retching or vomiting, or both
Compared to antiemetic drugs, there was no difference in the incidence of postoperative vomiting associated with PC6 acupoint stimulation (Analysis 2.2.6: RR 0.93, 95% CI 0.74 to 1.17) in 19 trials involving 1708 participants. Trial results were homogeneous (I² = 0%). The 'trim and fill' method did not trim or add any more studies to the contour‐enhanced funnel plot (Figure 10). There was no interaction effect between the different types of antiemetic drugs used for comparisons with PC6 acupoint stimulation (Chi² statistic 0.71, df = 4, P = 0.95).
Contour‐enhanced funnel plot of comparison: PC6 acupoint stimulation versus antiemetic for vomiting. Contour lines are at 1%, 5% and 10% levels of statistical significance.
There was no interaction effect between subgroup analyses that were prespecified: children versus adults (Analyses 2.2.7, 2.2.8: Chi² statistic 0.03, df = 1, P = 0.87); invasive versus noninvasive PC6 acupoint stimulation (Analyses 2.2.9, 2.2.10: Chi² statistic 0.19, df = 1, P = 0.66). There was no interaction effect between trials at low, unclear and high risk of bias (Analyses 2.2.11, 2.2.12, 2.2.13; Chi² statistic 0.32, df = 2, P = 0.85). There was no interaction effect between control event rate groups (up to 20% or more than 20%) (Analyses 2.2.14, 2.2.15: Chi² statistic 0.01, df = 1, P = 0.94).
As there were study limitations, we downgraded the evidence from high to moderate quality. Using trial sequential analysis, the boundary for futility was reached for vomiting (Figure 11).
Trial sequential analysis of 19 trials comparing PC6 acupoint stimulation versus antiemetic (despite risk of bias) for postoperative vomiting, with control event proportion of 14.7%, diversity of 0%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
Secondary outcomes
1. Need for rescue antiemetic drug when prophylaxis failed
There was no difference in the incidence of requiring rescue antiemetics for PC6 acupoint stimulation compared to pooled antiemetic drugs (RR 0.87, 95% CI 0.65 to 1.16) in nine trials involving 895 participants. Trial results were homogeneous (I² statistic = 0%). The evidence was of moderate quality due to study limitations.
2. Adverse effects from PC6 acupoint stimulation or antiemetic drug, or both
Restlessness was less frequent in the acupuncture group than after droperidol (RR 0.47, 95% CI 0.26 to 0.87) (Yentis 1992). While there was no puncture site redness, irritation or vasovagal effects (Sharma 2007; Wang 2002), another study reported pain associated with acupuncture (Yang 1993). There was no drowsiness, anxiety or extrapyramidal reactions found in participants given acupuncture or droperidol (Zhu 2010). No complications associated with electro‐acupuncture, electro‐acupuncture stimulation, acu‐stimulation, acupressure, ondansetron were noted in several trials (Agarwal 2002; El‐Deeb 2011; Gan 2004; Misra 2005; White 2002). Of the 49 participants in the acupressure wristband group, four reported some local tightness and discomfort (Barsoum 1990).
PC6 acupoint stimulation and antiemetic combination versus sham
One trial examined this comparison of wristband and droperidol versus sham wristband and placebo drug (Schultz 2003). There was no difference between groups for the incidence of nausea (RR 1.19, 95% CI 0.91 to 1.55) and vomiting (RR 1.18, 95% CI 0.63 to 2.21).
PC6 acupoint stimulation and antiemetic combination versus antiemetic
Primary outcomes
1. Incidence of postoperative nausea
Analysis (Analysis 3.1)
The eight trials (n = 642) evaluating the combination of PC6 acupoint stimulation and antiemetic versus antiemetic for preventing postoperative nausea were all conducted in adults. There was no difference in the incidence of postoperative nausea between groups (Analysis 3.1.4: RR 0.79, 95% CI 0.55 to 1.13). There was substantial heterogeneity between the trials (I² statistic = 72%), which may be explained by the level of invasiveness of the PC6 acupoint stimulation (Analysis 3.1.5 and 3.1.6: subgroup interaction effect was significant, P = 0.03). We found no interaction effect between the different types of PC6 acupoint stimulation antiemetic drug combinations (Chi² statistic 0.23, df = 2, P = 0.89); level of risk of bias of trials (Chi² statistic 2.14, df = 2, P = 0.34) or control event rate groups (Chi² statistic 1.35, df = 1, P = 0.25).
We downgraded the evidence from high to very low quality due to substantial heterogeneity among the trials, study limitations and imprecision of the summary estimate. Using trial sequential analysis, none of the boundaries for benefit, harm or futility were crossed and the required information size of 1743 was far from being reached (Figure 12).
Trial sequential analysis of 8 trials comparing PC6 acupoint and antiemetic versus antiemetic (despite risk of bias) for postoperative nausea, with control event proportion of 47.5%, diversity of 79%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
2. Incidence of postoperative vomiting, defined as either retching or vomiting, or both
Analysis (Analysis 3.2)
Compared to the antiemetic control groups, the combination of PC6 acupoint stimulation and antiemetic reduced the incidence of vomiting in nine trials involving 687 participants (Analysis 3.2.4: RR 0.56, 95% CI 0.35 to 0.91). There was substantial heterogeneity between the trials (I² = 61%). There was no interaction effect between different age groups (Analysis 3.2.5 and 3.2.6: Chi² statistic 1.17, df = 1, P = 0.28), level of invasiveness of the PC6 acupoint stimulation (Analysis 3.2.7 and 3.2.8: Chi² statistic 0.73, df = 1, P = 0.39), level of risk of bias of trials (Chi² statistic 0.01, df = 2, P = 1.00) or control event rate (Chi² statistic 1.97, df = 1, P = 0.16).
As there was substantial heterogeneity among trials, study limitations and imprecision of the summary estimate, we downgraded the evidence from high to very low quality. Using trial sequential analysis, none of the boundaries for benefit, harm or futility were crossed and the required information size of 2058 was far from being reached (Figure 13).
Trial sequential analysis of 9 trials comparing PC6 acupoint stimulation and antiemetic versus antiemetic (despite risk of bias) for postoperative vomiting, with control event proportion of 32.9%, diversity of 68%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
Secondary outcomes
1. Need for rescue antiemetic drug when prophylaxis failed
Analysis (Analysis 3.3)
The most common type of rescue antiemetic used for PC6 acupoint stimulation and antiemetic combination was metoclopramide (Sharma 2007; Wang 2010; White 2002; Xu 2012). One trial used both metoclopramide and prochlorperazine as rescue antiemetics (White 2012). Overall, participants in the PC6 acupoint stimulation and antiemetic combination group were less likely to require rescue antiemetic than the antiemetic‐only comparison group (RR 0.61, 95% CI: 0.44 to 0.86) with no heterogeneity (I² statistic = 0%) in five trials involving 419 participants. As there were study limitations and imprecision, we rated the overall quality of evidence as low.
2. Adverse effects from PC6 acupoint stimulation and/or antiemetic drug
No major adverse effects were reported in several trials (Sharma 2007; Wang 2010; White 2002; Xu 2012; Zhu 2010). The incidence of headache, fatigue, drowsiness, dizziness, constipation and local discomfort were similar between groups (White 2012).
Discussion
Summary of main results
We have shown that PC6 acupoint stimulation reduced the incidence of postoperative nausea and vomiting (PONV) compared to sham treatment. PC6 acupoint stimulation prevented postoperative nausea, vomiting, and need for antiemetic rescue by similar amounts that can be considered clinically significant (see summary of findings Table for the main comparison). However, the reasons for substantial heterogeneity are unclear and do not appear to be related to age, invasiveness level of the PC6 acupoint stimulation, risk of bias levels or control event rate, since there were no significant subgroup interactions effects. Nevertheless, compared to sham treatment, the reduction in the incidences of nausea, vomiting, and need for rescue antiemetics with PC6 acupoint stimulation may reduce costs (such as antiemetic drug cost, length of stay in hospital) as well as improve quality of patient care. However, the costs and quality of patient care were not outcomes examined in this systematic review.
Our results suggest that the PC6 acupoint stimulation was as effective as an antiemetic prophylaxis therapy for reducing the incidences of PONV (see summary of findings Table 2). However, there was inconclusive evidence for combining PC6 acupoint stimulation and antiemetic as a multimodal approach for preventing PONV (see summary of findings Table 3). Many trials either reported no adverse side effects or minor, transient side effects associated with PC6 acupoint stimulation.
New highlights of this review include the results of the trial sequential analyses: (1) no further PC6 acupoint stimulation versus sham trials are needed, and (2) further PC6 acupoint stimulation versus antiemetic trials are futile in showing a significant difference.
Overall completeness and applicability of evidence
The participants included this systematic review are representative of people with varying underlying risk factors for PONV undergoing a range of surgical procedures with various prophylactic antiemetic regimens. The trials were conducted in middle‐ and high‐income countries. Therefore, the results of this systematic review are directly applicable to clinical practice.
A lack of evidence on the optimal timing, duration and method of PC6 acupoint stimulation (Streitberger 2011) may explain the low uptake of PC6 acupoint stimulation in current clinical practice. In the few studies (Frey 2009a; Frey 2009b; Streitberger 2004) that have directly compared the timing of PC6 acupoint stimulation (pre‐ versus post‐induction), the risk reduction of PONV was similar irrespective of when the PC6 acupoint stimulation occurred. No trials in this systematic review compared different durations of PC6 acupoint stimulation. The noninvasive techniques may be more acceptable to anaesthesiologists and patients, as little training is needed to accurately locate the site of PC6 acupoint and administer the stimulation via appropriate devices. Generally, we found no subgroup interaction effects between invasive and noninvasive PC6 acupoint stimulation techniques in all the comparisons examined in this systematic review.
Although outside the scope of this systematic review, the cost effectiveness of PC6 acupoint stimulation has not been examined and would require the collection of direct and indirect healthcare costs related to PC6 acupoint stimulation and antiemetic prophylaxis, and data on the length of stay in hospital, and time to resume normal diet, sleep pattern and normal activities.
Quality of the evidence
The quality of evidence was variable, depending on the PC6 acupoint stimulation intervention and comparison group examined. The degree of risk of biases across trials also varied, with few trials (Gan 2004; Xu 2012) rated at low risk of bias. Selective reporting of outcomes was the most common risk of bias. The need for rescue antiemetic and side effects associated with PC6 acupoint stimulation and antiemetics were outcomes not always collected and reported. Thus, the impact of selective reporting bias on the summary effect estimates is unknown. When there was substantial heterogeneity, the reasons were often unknown. There may be subtle differences between inactive ReliefBand and SeaBands with studs removed, when placed over the PC6 acupoint. Despite possible differences in sham efficacy and intrinsic bias, we analysed these sham treatments as one group. The evidence base is likely to remain low when PC6 acupoint stimulation is compared to sham, since the threshold for a statistically significant treatment effect has been reached. The evidence base for PC6 acupoint stimulation as an alternative to antiemetic is likely to remain moderate, as the threshold for futility has been reached.
Potential biases in the review process
Publication bias may be common for RCTs of Traditional Chinese Medicine (Tang 1999). The contour‐enhanced funnel plots for nausea and vomiting showed no evidence of publication bias. The addition of another 19 studies examining PC6 acupoint stimulation for PONV since the previous version of this review (Lee 2009) did not change the relative risk estimates much. Thus, we are confident that publication bias is minimal in this review.
Agreements and disagreements with other studies or reviews
The results of this updated Cochrane review cannot be directly compared with those reported by Cheong 2013, as the methodology was different. For example, there were differences in the selection of controls, inclusion of other acupoints with PC6, timing of PONV and types of PC6 acupoint stimulation technique subgroup analyses chosen. Nevertheless, the results of PC6 electro‐acupoint stimulation versus sham for postoperative nausea (RR 0.49, 95% CI 0.38 to 0.63) and postoperative vomiting (RR 0.50, 95% CI 0.36 to 0.70) in the first 24 hours (Cheong 2013) are in agreement with our review.
Study flow diagram.
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Contour‐enhanced funnel plot of comparison: PC6 acupoint stimulation versus sham for nausea. Contour lines are at 1%, 5% and 10% levels of statistical significance.
Trial sequential analysis of 40 trials comparing PC6 acupoint stimulation versus sham (despite risk of bias) for postoperative nausea, with control event proportion of 46.8%, diversity of 71%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
Contour‐enhanced funnel plot of comparison: PC6 acupoint stimulation versus sham for vomiting. Contour lines are at 1%, 5% and 10% levels of statistical significance.
Trial sequential analysis of 45 trials comparing PC6 acupoint versus sham (despite risk of bias) for postoperative vomiting, with control event proportion of 32.9%, diversity of 74%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
Contour‐enhanced funnel plot of comparison: PC6 acupoint stimulation versus antiemetic for nausea. Contour lines are at 1%, 5% and 10% levels of statistical significance.
Trial sequential analysis of 14 trials of PC6 acupoint stimulation versus antiemetic (despite risk of bias) for postoperative nausea, with control event proportion of 25.0%, diversity of 40%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
Contour‐enhanced funnel plot of comparison: PC6 acupoint stimulation versus antiemetic for vomiting. Contour lines are at 1%, 5% and 10% levels of statistical significance.
Trial sequential analysis of 19 trials comparing PC6 acupoint stimulation versus antiemetic (despite risk of bias) for postoperative vomiting, with control event proportion of 14.7%, diversity of 0%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
Trial sequential analysis of 8 trials comparing PC6 acupoint and antiemetic versus antiemetic (despite risk of bias) for postoperative nausea, with control event proportion of 47.5%, diversity of 79%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
Trial sequential analysis of 9 trials comparing PC6 acupoint stimulation and antiemetic versus antiemetic (despite risk of bias) for postoperative vomiting, with control event proportion of 32.9%, diversity of 68%, α of 5%, power of 80%, and relative risk reduction of 30% (Apfel 2007).
Comparison 1 Acupoint PC6 stimulation versus sham, Outcome 1 Nausea.
Comparison 1 Acupoint PC6 stimulation versus sham, Outcome 2 Vomiting.
Comparison 1 Acupoint PC6 stimulation versus sham, Outcome 3 Rescue antiemetics.
Comparison 2 Acupoint PC6 stimulation versus antiemetic drug, Outcome 1 Nausea.
Comparison 2 Acupoint PC6 stimulation versus antiemetic drug, Outcome 2 Vomiting.
Comparison 2 Acupoint PC6 stimulation versus antiemetic drug, Outcome 3 Rescue antiemetic.
Comparison 3 Acupoint PC6 stimulation and antiemetic combination vs antiemetic, Outcome 1 Nausea.
Comparison 3 Acupoint PC6 stimulation and antiemetic combination vs antiemetic, Outcome 2 Vomiting.
Comparison 3 Acupoint PC6 stimulation and antiemetic combination vs antiemetic, Outcome 3 Rescue antiemetic.
| Acupoint PC6 stimulation versus sham for preventing postoperative nausea and vomiting | ||||||
| Patient or population: People at risk of postoperative nausea and vomiting Comparison: Sham | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Sham | Acupoint PC6 stimulation | |||||
| Nausea ‐ All trials | Low | RR 0.68 | 4742 | ⊕⊕⊝⊝ | ||
| 200 per 1000 | 136 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 272 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 408 per 1000 | |||||
| Vomiting ‐ All trials | Low | RR 0.60 | 5147 | ⊕⊕⊝⊝ | ||
| 200 per 1000 | 120 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 240 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 360 per 1000 | |||||
| Rescue antiemetics | 329 per 1000 | 210 per 1000 | RR 0.64 | 4622 | ⊕⊕⊝⊝ | |
| Adverse effects | Not estimable | Not estimable | Not estimable | 35 studies6 | Not applicable | See footnote6 |
| *The basis for the assumed risks for nausea and vomiting is from a consensus panel (Gan 2014) using Apfel's simplified risk score (Apfel 1999). The assumed risk for rescue antiemetic is the median sham group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Of the 40 trials, 13 had one or more high risk of bias domains (downgrade 1 point due to study limitations). | ||||||
| Acupoint PC6 stimulation versus antiemetic drug for preventing postoperative nausea and vomiting | ||||||
| Patient or population: People at risk of postoperative nausea and vomiting Comparison: Antiemetic drug | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Antiemetic | Acupoint PC6 stimulation | |||||
| Nausea ‐ All antiemetics combined | Low | RR 0.91 | 1332 | ⊕⊕⊕⊝ | ||
| 200 per 1000 | 182 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 364 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 546 per 1000 | |||||
| Vomiting ‐ All antiemetics combined | Low | RR 0.93 | 1708 | ⊕⊕⊕⊝ | ||
| 200 per 1000 | 186 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 372 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 558 per 1000 | |||||
| Rescue antiemetic | 150 per 1000 | 130 per 1000 | RR 0.87 | 895 | ⊕⊕⊕⊝ | |
| Adverse effects | See comment | See comment | Not estimable | 11 studies4 | Not applicable | See footnote4 |
| *The basis for the assumed risks for nausea and vomiting is from a consensus panel (Gan 2014) using Apfel's simplified risk score (Apfel 1999). The assumed risk for rescue antiemetic is the median antiemetic group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Of the 14 trials, 5 had one or more high risk of bias domains (downgrade 1 point due to study limitations). | ||||||
| Acupoint PC6 stimulation and antiemetic combination compared to antiemetic for preventing postoperative nausea and vomiting | ||||||
| Patient or population: People at risk of postoperative nausea and vomiting | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Antiemetic | Acupoint PC6 stimulation and antiemetic combination | |||||
| Nausea | Low | RR 0.79 | 642 | ⊕⊝⊝⊝ | ||
| 200 per 1000 | 158 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 316 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 474 per 1000 | |||||
| Vomiting | Low | RR 0.56 | 687 | ⊕⊝⊝⊝ | ||
| 200 per 1000 | 112 per 1000 | |||||
| Moderate | ||||||
| 400 per 1000 | 224 per 1000 | |||||
| High | ||||||
| 600 per 1000 | 336 per 1000 | |||||
| Rescue antiemetic | 316 per 1000 | 193 per 1000 | RR 0.61 | 419 | ⊕⊕⊝⊝ | |
| Adverse effects | See comment | See comment | Not estimable | 6 studies7 | Not applicable | See footnote7 |
| *The basis for the assumed risks for nausea and vomiting is from a consensus panel (Gan 2014) using Apfel's simplified risk score (Apfel 1999). The assumed risk for rescue antiemetic is the median antiemetic group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Of the 8 trials, 2 had one or more high risk of bias domains (downgrade 1 point due to study limitations). | ||||||
| Control event rate | Nausea | 95% CI | Vomiting | 95% CI |
| 10% | 31 | 25 to 43 | 25 | 20 to 34 |
| 20% | 16 | 13 to 22 | 13 | 10 to 17 |
| 30% | 10 | 8 to 14 | 8 | 7 to 11 |
| 40% | 8 | 6 to 11 | 6 | 5 to 9 |
| 50% | 6 | 5 to 9 | 5 | 4 to 7 |
| 60% | 5 | 4 to 7 | 4 | 3 to 6 |
| 70% | 4 | 4 to 6 | 4 | 3 to 5 |
| 80% | 4 | 3 to 5 | 3 | 3 to 4 |
| 90% | 3 | 3 to 5 | 3 | 2 to 4 |
| CI = confidence interval | ||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Nausea Show forest plot | 40 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| 1.1 All trials | 40 | 4742 | Risk Ratio (IV, Random, 95% CI) | 0.68 [0.60, 0.77] |
| 1.2 Children | 2 | 258 | Risk Ratio (IV, Random, 95% CI) | 0.63 [0.51, 0.80] |
| 1.3 Adults | 36 | 4344 | Risk Ratio (IV, Random, 95% CI) | 0.70 [0.61, 0.79] |
| 1.4 Invasive PC6 stimulation | 7 | 896 | Risk Ratio (IV, Random, 95% CI) | 0.56 [0.39, 0.80] |
| 1.5 Noninvasive PC6 stimulation | 33 | 3846 | Risk Ratio (IV, Random, 95% CI) | 0.71 [0.62, 0.81] |
| 1.6 Low risk of bias trials | 2 | 169 | Risk Ratio (IV, Random, 95% CI) | 0.40 [0.17, 0.93] |
| 1.7 Unclear risk of bias trials | 20 | 2496 | Risk Ratio (IV, Random, 95% CI) | 0.68 [0.56, 0.82] |
| 1.8 High risk of bias trials | 11 | 1090 | Risk Ratio (IV, Random, 95% CI) | 0.68 [0.55, 0.85] |
| 1.9 Trials with control event rate less than or equal to 20% | 4 | 454 | Risk Ratio (IV, Random, 95% CI) | 0.81 [0.49, 1.33] |
| 1.10 Trials with control event rate more than 20% | 36 | 4288 | Risk Ratio (IV, Random, 95% CI) | 0.68 [0.59, 0.77] |
| 2 Vomiting Show forest plot | 45 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| 2.1 All trials | 45 | 5147 | Risk Ratio (IV, Random, 95% CI) | 0.60 [0.51, 0.71] |
| 2.2 Children | 6 | 542 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.46, 0.97] |
| 2.3 Adults | 37 | 4465 | Risk Ratio (IV, Random, 95% CI) | 0.61 [0.51, 0.72] |
| 2.4 Invasive PC6 stimulation | 7 | 896 | Risk Ratio (IV, Random, 95% CI) | 0.51 [0.34, 0.76] |
| 2.5 Noninvasive PC6 stimulation | 37 | 4151 | Risk Ratio (IV, Random, 95% CI) | 0.60 [0.50, 0.73] |
| 2.6 Low risk of bias trials | 2 | 169 | Risk Ratio (IV, Random, 95% CI) | 0.52 [0.31, 0.88] |
| 2.7 Unclear risk of bias trials | 26 | 3583 | Risk Ratio (IV, Random, 95% CI) | 0.59 [0.48, 0.72] |
| 2.8 High risk of bias trials | 14 | 1373 | Risk Ratio (IV, Random, 95% CI) | 0.62 [0.45, 0.83] |
| 2.9 Trials with control event rate less than or equal to 20% | 12 | 1556 | Risk Ratio (IV, Random, 95% CI) | 0.75 [0.51, 1.11] |
| 2.10 Trials with control event rate more than 20% | 33 | 3591 | Risk Ratio (IV, Random, 95% CI) | 0.58 [0.48, 0.69] |
| 3 Rescue antiemetics Show forest plot | 39 | 4622 | Risk Ratio (IV, Random, 95% CI) | 0.64 [0.55, 0.73] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Nausea Show forest plot | 14 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| 1.1 Ondansetron | 9 | 843 | Risk Ratio (IV, Random, 95% CI) | 0.86 [0.65, 1.13] |
| 1.2 Metoclopramide | 4 | 334 | Risk Ratio (IV, Random, 95% CI) | 0.72 [0.38, 1.36] |
| 1.3 Cyclizine | 1 | 62 | Risk Ratio (IV, Random, 95% CI) | 0.5 [0.14, 1.82] |
| 1.4 Droperidol | 2 | 143 | Risk Ratio (IV, Random, 95% CI) | 1.02 [0.47, 2.19] |
| 1.5 All antiemetics combined | 14 | 1332 | Risk Ratio (IV, Random, 95% CI) | 0.91 [0.75, 1.10] |
| 1.6 Children | 1 | 99 | Risk Ratio (IV, Random, 95% CI) | 0.68 [0.41, 1.13] |
| 1.7 Adult | 11 | 1033 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.78, 1.17] |
| 1.8 Invasive PC6 stimulation | 5 | 559 | Risk Ratio (IV, Random, 95% CI) | 0.69 [0.41, 1.14] |
| 1.9 Noninvasive PC6 stimulation | 9 | 773 | Risk Ratio (IV, Random, 95% CI) | 0.95 [0.78, 1.16] |
| 1.10 Low risk of bias trials | 1 | 51 | Risk Ratio (IV, Random, 95% CI) | 0.48 [0.19, 1.21] |
| 1.11 Unclear risk of bias trials | 8 | 975 | Risk Ratio (IV, Random, 95% CI) | 0.81 [0.63, 1.04] |
| 1.12 High risk of bias trials | 5 | 306 | Risk Ratio (IV, Random, 95% CI) | 1.07 [0.89, 1.29] |
| 1.13 Trials with control event rate less than or equal to 20% | 6 | 685 | Risk Ratio (IV, Random, 95% CI) | 0.89 [0.52, 1.52] |
| 1.14 Trials with control event rate more than 20% | 8 | 647 | Risk Ratio (IV, Random, 95% CI) | 0.88 [0.69, 1.13] |
| 2 Vomiting Show forest plot | 19 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| 2.1 Ondansetron | 9 | 843 | Risk Ratio (IV, Random, 95% CI) | 1.02 [0.68, 1.54] |
| 2.2 Metoclopramide | 5 | 414 | Risk Ratio (IV, Random, 95% CI) | 0.87 [0.43, 1.74] |
| 2.3 Prochlorperazine | 2 | 173 | Risk Ratio (IV, Random, 95% CI) | 1.15 [0.48, 2.77] |
| 2.4 Cyclizine | 1 | 62 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.21, 2.13] |
| 2.5 Droperidol | 4 | 266 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.64, 1.43] |
| 2.6 All antiemetics combined | 19 | 1708 | Risk Ratio (IV, Random, 95% CI) | 0.93 [0.74, 1.17] |
| 2.7 Children | 3 | 237 | Risk Ratio (IV, Random, 95% CI) | 0.98 [0.61, 1.56] |
| 2.8 Adult | 14 | 1271 | Risk Ratio (IV, Random, 95% CI) | 0.94 [0.72, 1.22] |
| 2.9 Invasive PC6 stimulation | 8 | 734 | Risk Ratio (IV, Random, 95% CI) | 0.99 [0.70, 1.41] |
| 2.10 Noninvasive PC6 stimulation | 12 | 974 | Risk Ratio (IV, Random, 95% CI) | 0.90 [0.67, 1.21] |
| 2.11 Low risk of bias trials | 1 | 51 | Risk Ratio (IV, Random, 95% CI) | 1.44 [0.26, 7.92] |
| 2.12 Unclear risk of bias trials | 8 | 975 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.66, 1.40] |
| 2.13 High risk of bias trials | 10 | 682 | Risk Ratio (IV, Random, 95% CI) | 0.91 [0.68, 1.21] |
| 2.14 Trials with control event rate less than or equal to 20% | 15 | 1440 | Risk Ratio (IV, Random, 95% CI) | 0.95 [0.70, 1.29] |
| 2.15 Trials with control event rate more than 20% | 4 | 268 | Risk Ratio (IV, Random, 95% CI) | 0.93 [0.60, 1.43] |
| 3 Rescue antiemetic Show forest plot | 9 | 895 | Risk Ratio (IV, Random, 95% CI) | 0.87 [0.65, 1.16] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Nausea Show forest plot | 8 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| 1.1 PC6 acupoint stimulation and droperidol | 2 | 128 | Risk Ratio (IV, Random, 95% CI) | 0.77 [0.15, 4.10] |
| 1.2 PC6 acupoint stimulation and ondansetron | 4 | 295 | Risk Ratio (IV, Random, 95% CI) | 0.79 [0.47, 1.33] |
| 1.3 PC6 acupoint stimulation, dexamethasone and ondansetron | 2 | 219 | Risk Ratio (IV, Random, 95% CI) | 0.69 [0.50, 0.93] |
| 1.4 All PC6 acupoint stimulation and antiemetic combinations | 8 | 642 | Risk Ratio (IV, Random, 95% CI) | 0.79 [0.55, 1.13] |
| 1.5 Invasive PC6 stimulation | 2 | 120 | Risk Ratio (IV, Random, 95% CI) | 0.28 [0.11, 0.75] |
| 1.6 Noninvasive PC6 stimulation | 6 | 522 | Risk Ratio (IV, Random, 95% CI) | 0.88 [0.62, 1.25] |
| 1.7 Low risk of bias trials | 1 | 119 | Risk Ratio (IV, Random, 95% CI) | 0.58 [0.38, 0.88] |
| 1.8 Unclear risk of bias trials | 4 | 355 | Risk Ratio (IV, Random, 95% CI) | 0.86 [0.61, 1.20] |
| 1.9 High risk of bias trials | 3 | 168 | Risk Ratio (IV, Random, 95% CI) | 0.58 [0.12, 2.66] |
| 1.10 Trials with control event rate less than or equal to 20% | 1 | 40 | Risk Ratio (IV, Random, 95% CI) | 0.14 [0.01, 2.60] |
| 1.11 Trials with control event rate more than 20% | 7 | 602 | Risk Ratio (IV, Random, 95% CI) | 0.81 [0.56, 1.16] |
| 2 Vomiting Show forest plot | 9 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| 2.1 PC6 acupoint stimulation and droperidol | 3 | 173 | Risk Ratio (IV, Random, 95% CI) | 0.62 [0.19, 1.99] |
| 2.2 PC6 acupoint stimulation and ondansetron | 4 | 295 | Risk Ratio (IV, Random, 95% CI) | 0.51 [0.20, 1.30] |
| 2.3 PC6 acupoint stimulation and dexamethasone and ondansetron | 2 | 219 | Risk Ratio (IV, Random, 95% CI) | 0.49 [0.30, 0.79] |
| 2.4 All PC6 acupoint stimulation and antiemetic combinations | 9 | 687 | Risk Ratio (IV, Random, 95% CI) | 0.56 [0.35, 0.91] |
| 2.5 Children | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 0.83 [0.43, 1.63] |
| 2.6 Adult | 8 | 627 | Risk Ratio (IV, Random, 95% CI) | 0.51 [0.29, 0.91] |
| 2.7 Invasive PC6 stimulation | 3 | 180 | Risk Ratio (IV, Random, 95% CI) | 0.34 [0.08, 1.40] |
| 2.8 Noninvasive PC6 stimulation | 6 | 507 | Risk Ratio (IV, Random, 95% CI) | 0.65 [0.38, 1.11] |
| 2.9 Low risk of bias trials | 1 | 119 | Risk Ratio (IV, Random, 95% CI) | 0.53 [0.30, 0.94] |
| 2.10 Unclear risk of bias trials | 4 | 355 | Risk Ratio (IV, Random, 95% CI) | 0.52 [0.25, 1.09] |
| 2.11 High risk of bias trials | 4 | 213 | Risk Ratio (IV, Random, 95% CI) | 0.56 [0.19, 1.64] |
| 2.12 Trials with control event rate less than or equal to 20% | 2 | 120 | Risk Ratio (IV, Random, 95% CI) | 0.13 [0.02, 1.04] |
| 2.13 Trials with control event rate more than 20% | 7 | 567 | Risk Ratio (IV, Random, 95% CI) | 0.61 [0.37, 1.00] |
| 3 Rescue antiemetic Show forest plot | 5 | 419 | Risk Ratio (IV, Random, 95% CI) | 0.61 [0.44, 0.86] |
