Acupuncture for labour pain - A randomized controlled trial
Diarienummer : RFR-31691
Ny ansökan RFR oktober 2008
Ansökan påbörjad av : Erica Schytt, 2008-09-26
Yrkestitel vid ansökningstillfället : Vårdutvecklare
Arbetsplats vid ansökningstillfället : Kvinnokliniken Falun, Centrum för klinisk forskning Dalarna, Karolinska Institutet Inst för kvinnors
Senast ändrad/åtgärdad av : RFR Beslutare, 2010-07-26
Ansökan inkommen till : Regionala forskningsrådet i Uppsala- och Örebroregionen
Beslutad - beviljad, slutförd

Sökanden: Erica Schytt
Barnmorska, Centrum för klinisk forskning Dalarna, Karolinska Institutet Inst för kvinnors

A Övergripande projektinformation

Kön på huvudsökanden

kvinna

För projekt som beviljats medel av RFR

RFR-11956, 120 000 SEK, 2007-12-19

Sammanfattning

Acupuncture is used extensively in Swedish obstetric care in spite of insufficient evidence of its potential to reduce labour pain. The findings of the published trials are contradictory, which may reflect methodological limitations such as small samples and insufficient needle stimulation. This study will be conducted as a randomized controlled trial in two Swedish labour wards. The women will be randomly allocated to one of three groups: Manual acupuncture (MA), High frequency electro-acupuncture (EA) and Standard care (SC). The study protocol will follow the Consort and STRICTA recommendations. The aim is to evaluate the effect of MA and EA during spontaneous labour on the following primary outcomes: 1)experience of labour pain and 2) use of epidural analgesia. The aim is also to evaluate the effect of MA and EA on the following secondary outcomes: Experience of relaxation, experience of social support, biological markers of pain and stress (IL-1β, IL-6, TNF-α), labour outcomes (mode of delivery, pain relief, augmentation of labour, duration of labour, perineal lacerations), infant outcomes (Apgar score, pH, BE, neonatal transfer), memory of pain and childbirth overall after the birth and costs.

The power calculation, which showed that 100 women in each group will be sufficient, is based on the two primary outcomes. Pain will be measured by VAS and Borg CR 100. Information on women’s birth experiences and pain relief will be collected by means of questionnaires. Blood samples will be collected and the samples will be estimated for IL-1, IL-6 and TNF- alpha. This study will add to current knowledge and contribute with new knowledge of acupuncture treatment. If the acupuncture proves to be effective, an additional non-pharmacological method may contribute to effective care of women in labour. Acupuncture is cheap and easy to administer and may be appropriate in obstetric care worldwide, preventing suffering.

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Medarbetare/Medsökande

Ove Axelsson
Läkare, FoU centrum/CKFD Eskilstuna

Länstillhörighet:

Uppsala

Projektledning:

Delaktig i design av projektet, framförallt inom de obstetriska frågorna. Delaktig i manusets färdigställande.

Patientrekrytering:

Nej

Arbetsenhet:

Uppsala Universitet

Lena Mårtensson
Lärare, Göteborgs universitet, Sahlgrenska akademin, Arbetsterapi

Länstillhörighet:

Skaraborgs län, Västra Götaland

Projektledning:

Delaktig i projektets alla delar (design, metodutveckling, analys, författande, rekrytering, utbildning mm). Huvudhandledare till doktoranden.

Patientrekrytering:

Ja

Arbetsenhet:

NÄL Trollhättan (patientrekrytering, datainsamling) Högskolan i Skövde, Sahlgrenska Akademin

Elisabet Stener-Victorin
Annan tjänstetitel, Institutionen för Neurovetenskap och Fysiologi, Sektionen för Fysiologi

Länstillhörighet:

Västra Götaland

Projektledning:

Delaktig i design, metodutveckling, undervisning av barnmorksor (Falun), analys och manusets färdigställande. Bihandledzare till doktoranden.

Patientrekrytering:

Nej

Arbetsenhet:

Sahlgrenska Akademin

Ulla Waldenström
Barnmorska, Karolinska Instituet, Institutionen för kvinnors och barns hälsa

Länstillhörighet:

Karolinska Institutet, Stockholms län

Projektledning:

Delaktig i de flesta av projektets delar (design, metodutveckling, författande, bidragit till utbildning mm). Bihandledare.

Patientrekrytering:

Nej

Arbetsenhet:

Kvinnors och Barns Hälsa

Anna Hjelmstedt
Verksamhetschef, Enheten för reproduktiv och perinatal omvårdnad, Institutionen för kvinnor och barns hälsa, Karolins

Länstillhörighet:

Stockholms län, Karolinska Institutet

Projektledning:

Delaktig i design, framförallt den biomedicinska delen.

Patientrekrytering:

Nej

Arbetsenhet:

Kvinnors och Barns Hälsa

Linda Vixner
Annan tjänstetitel, Institutionen Hälsa och Samhälle, Högskolan Dalarna

Länstillhörighet:

Dalarna

Projektledning:

Delaktig i projektets alla delar som doktorand (design, metodutveckling, analys, författande, rekrytering, utbildning mm).

Patientrekrytering:

Ja

Arbetsenhet:

Högskolan Dalarna

Utbildning

doktorandutbildning

Översikt av projektorganisation

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Projektstart

2007-11-15

Beräknat projektslut

2012-12-31

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B Projektbeskrivning

Bakgrund

Acupuncture is used extensively in Swedish obstetric care in spite of insufficient evidence of its potential to reduce labour pain. Although several studies have been published the results are still not convincing.

Six randomized controlled trials were published in 2002-2007, in three of these, pain intensity or the need for pharmacological pain relief was reduced. In two studies 1,2 acupuncture with needles placed at recognised acupuncture points was compared with a treatment where needles were placed at false points, i.e. non-recommended points, and women in the first group experienced less pain. However, a third study with similar design 3 found no such effect. Further, when comparing acupuncture with standard obstetric care where acupuncture was not an option, lower rates of Pethidin, epidural analgesia, nitrous oxide and injections by sterile water was reported 4. Of the remaining two studies, one did not report any effect of acupuncture on women’s experience of labour pain but a higher degree of relaxation 5 when compared with standard care, and one reported that sterile water papules were was more effective in reducing pain in comparison with acupuncture 6.

The findings of the published trials are contradictory, which may reflect methodological limitations, such as small samples and lack of power calculation. Detailed information about the treatment, such as timing and intensity, was sparse or lacking. Another limitation of previous studies was insufficient information about the training and skills of the person giving the treatment. Finally, control procedures that are meant to be inert (minimal, superficial, sham, or ‘placebo’ acupuncture), are in fact activating tactile afferents and consequently result in the alleviation of the affective component of pain. This could explain why control interventions are equally effective as acupuncture.

Acupuncture entails penetration of the skin with thin needles at certain points on the surface of the body. These points follow a predictable pattern and the lines linking the points are known as meridians. Local acupuncture points are used to stimulate pain inhibition at the segmental level by inserting the needles in the painful area. For stimulation of the central nervous system, both segmental and distal points are used. It is possible that the intensity from the manual acupuncture technique is insufficient to decrease such strong pain as women experience during labour. Higher intensity of the acupuncture may be reached by using electrical stimulation of the needles, generally referred to as electro-acupuncture (EA).

Labour pain is caused by dilation of the cervix and the lower uterine segment. The internal organs are sparsely supplied with A-delta and C afferents; the pain is thus often experienced as diffuse and aching and pain localisation may vary. The most common way to assess labour pain is to use a visual analogue scale (VAS). This instrument has its limitations by measuring an overall experience of pain only, and by having a fixed end point of worst conceivable pain, not allowing for higher ratings even when a woman has already used the most extreme endpoint. The scale may also be sensitive to the response shift phenomenon, i.e. that the basis on which an individual forms her judgement changes with time. Consequently, there is a need for development of other instruments for assessing labour pain. Finally, several investigations show that the nervous system, the immune system and the endocrine system are involved in the regulation of pain and stress response. Pain enhancement is mediated by glial activation and release of proinflammatory cytokines. Stressful experiences increase circulating levels of the proinflammatory cytokines IL-1β IL-6 and TNF- α. Thus, it is of interest to investigate possible associations between labour pain management, stress and cytokines.

Syfte/frågeställning/hypotes

The aim of this study is to evaluate the effect of manual acupuncture (MA) and electro-acupuncture (EA) during spontaneous labour on the following outcomes:

Primary outcomes:
Experience of labour pain and use of epidural analgesia

Secondary outcomes:
Experience of relaxation, experience of social support, biological markers of pain and stress such as: IL-1β, IL-6 and TNF-α,labour outcomes: mode of delivery, pain relief, augmentation of labour, duration of labour and perineal lacerations, infant outcomes: Apgar score, pH, BE and neonatal transfer, memory of pain and childbirth overall after the birth and finally costs

Design och urval (ex. urval, gruppindelning)

The study will be conducted as a randomized controlled trial (RCT), and located in two delivery wards in Sweden, Norra Älvsborgs Länssjukhus and Falu lasarett. The women will be randomly allocated to one of three groups; 1/ Manual acupuncture (MA), 2/ High frequency electro-acupuncture (EA), and 3/ Standard care (SC). Study protocols will follow the Consort 28 and STRICTA 29, recommendations, the latter a complementary document to Consort for reporting studies using acupuncture.

All women attending the regular check-ups by a midwife at the antenatal clinics linked to the two hospitals, at 34-36 weeks’ gestation, will receive oral and written information about the study and an invitation to participate. Women will be asked for consent to participate in the study on admission to the labour ward.
Inclusion criterias:
•Admission to the labour ward in spontaneous onset of labour
•Nulliparity
•Singleton pregnancy, cephalic presentation
•Gestation: 37+0 to 41+6 (weeks + days)
•Expressed need for pain relief
•Swedish speaking (understanding written and oral instructions)

Exclusion criterias:
•Pharmacological pain relief within 24 hours of inclusion
•Severe preeclampsia
•Treatment with oxytocin at the time point of allocation
•Treatment with anticoagulant
•Pacemaker
Eligible women will be randomized to one of the three groups. Randomization will be conducted in blocks of 9, 12 and 15, blocks that are varied randomly. The assignment code will be obtained by a computer random number generator and be kept in sequentially numbered, opaque, sealed envelopes, prepared by the research team. At the time for allocation, the assisting midwife will pick a sequential envelope, write the participant’s name and personal registration number on the envelope, and then open it.

The midwives participating in this study will undergo a training program including MA, EA and research methodology with focus on RCT, before commencement of the study.

The power calculation is based on the primary outcomes: experience of labour pain and use of epidural analgesia. For experience of labour pain the calculation is based on the results from a previous study of MA. To detect a difference of 15 mm on VAS between the groups, with a standard deviation of 20.4 mm and a power of 80 % at a 1.7 % significant level due to the three-arm design (0.05 divided by 3), 41 women in each group will be needed. For epidural analgesia, the power calculation is based on a study by Ramnerö et al who found a reduction in epidural rates from 50% in the control group to 26% in the acupuncture group. To detect such a difference (power 80 %, significant level 1.7 %), 84 women in each group will be needed. We estimated a dropout rate of approximately 20 %, and consequently 100 women in each group would be sufficient. In the analyses, the principle of intention to treat (ITT) will be used.

Redovisning av interventionen

All women in the trial will receive care, according to Swedish clinical practice. Women in the SC group will receive standard care only, which access pharmacological and non-pharmacological analgesia. Women in the MA and EA groups will receive treatment on bilateral distal and local points, chosen according to the literature and in collaboration with experienced clinicians and tutors. Thin, sterile, stainless steel needles will be used. In the MA group the needles will be manually stimulated to reach De Qi(a feeling of numbness reflecting activation of A-delta and C-fibres). In the EA group all needles will be manually stimulated to reach De Qi, and eight needles in the painful area (local points) will thereafter be connected to an electro-stimulator (CEFAR ACUS 4) and stimulated with high frequency pulses. The woman will adjust the intensity her self. The distal points will be manually stimulated as in the MA group. The number of needles will be the same in both the MA and EA groups: 4-8 local points all of them bilateral chosen from this list: BL23, BL24, BL 25, BL 26, BL27, BL28, BL54, GB25, GB26, GB27, GB28, GB29 and KI11. Three of the distal points LI4, PC 6, LR3, SP6 and GV20, all bilateral, will be chosen. In total the woman will be treated with 13-21 needles.

The needles will be removed after 40 minutes and the treatment will be repeated two hours after completion of the first treatment. The midwives will administer the treatment in both groups. Data on frequency and intensity of treatment, acupuncture point, number of needles well be recorded . After the two treatments, additional treatment will be available on request. All women will have access to standard forms of analgesia in all three groups.

Metod och datainsamling/ -bearbetning

The midwife will prospectively record all relevant co-interventions through established protocols, such as the presence of staff and other support persons and additional pain relief. Data on obstetric background, present pregnancy and labour and birth, will be retrieved from the hospital records. Information on women’s socio-demographic background, pain history, birth experiences and pain relief will be collected by means of questionnaires.

Measurements of pain and relaxation will be conducted before treatment, immediately after treatment and then every 30 minutes during the following five hours. Thereafter measurements will be conducted every hour until delivery. A different person (second midwife or nurse assistant) will assist the woman in the procedure of measuring pain and relaxation.

Visual Analogue Scale
A Visual Analogue Scale (VAS) is a 100 mm long vertical or horizontal line with the suggested end points “no pain” and “worst conceivable pain”. The pain experience will be recorded by a mark on the line. VAS has been shown to be sensitive to pain intensity and most individuals have no difficulties using it. VAS has also been used to measure relaxation.

Borg CR 100
The Borg CR 100 is a verbally level-anchored ratio scale. It consists of a variation in numbers from 0 to 100 with the first anchor at 1,5 “Minimum” and the last anchor at 100 “Maximal”. The principles behind verbally level-anchored ratio scaling, also called CR scaling, is a combination between ration scaling and category scaling. Precise verbal descriptors used as anchors are placed on such portions on the ratio scale that congruence is obtained between the meaning of the anchors and the numbers. In the Borg CR100 scale the number 100 are anchored in “Maximal”. All other scale values are set in comparison to this point of reference. If the pain exceeds “Maximal” the scale allows values over 100.

Blood sampling
Blood samples will be collected before treatment, and 30 minutes after treatment. An indwelling intravenous catheter will be inserted according to routine care. From this, 5 ml blood will be drawn and collected in a standard tube. The tubes will be centrifuged for 3000 rpm for 15 minutes. Aliquots of serum and plasma will be frozen at -70º. Samples will be estimated for IL-1, IL-6 and TNF- alpha, by using commercially available ELIZA kits.

Questionnaires
Questionnaires will be answered before (Q1) and immediately after the birth (Q2), the day after (Q3) and a follow-up postal questionnaire approximately two months postpartum (Q4).
Q1 will ask about socio-demographic background, earlier experience of acupuncture and experience of menstruation pain. Q2 will ask about the effects of the interventions and negative side effects if any. Q3 and Q4 asks about data on overall experience of childbirth and pain relief, the memory of pain, emotional health, and support. Protocols, interventions, sampling procedures and questionnaires will be pilot tested.

Studiens genomförande

The study will be described on a website www.akupunkturstudien.se, for women and midwives separately. Information to the participating women will be presented on an open access site. Midwives participating in the study will recieve a password to a "closed" website with additional information, such as detailed verbal instructions of the intervention, instructive videos showing the acupuncure technique, number of included participants and so on.

Additionally, the midwifes at the antenatal clinics will recieve oral and written information about the study as well as a lecture on acupuncture before commencement of the study.

The midwives at the labour wards will undergo training in both MA and EA before commencement of the study. The training will be a continuation course, based on the midwives’ earlier education in acupuncture. The training program will also include research methodology with focus on randomized controlled trials.

All women attending the regular check-ups by a midwife at the antenatal clinics linked to the respective hospital, at 34-36 weeks’ gestation, will receive oral and written information about the study and an invitation to participate. Women will be asked for consent to participate in the study on admission to the labour ward.

The director of the departments have given their consent to conducting the study in the respective labour ward and a suffientent number of midwives have applied for participating in the study, the course included.

Process evaluation will be conducted by intermittent check-ups in order to assure that the intervention procedures are performed correctly and follow the protocol.

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Forskningsetiska överväganden

The study has no foreseeable risks but may cause minor discomfort such as tiredness and small bruises. The women will be informed that 1) participation in the study is voluntary, 2) their decision whether or not to participate will not affect their current or future treatment, 3) if they decide to participate they are free to withdraw at any time and 4) all questionnaires and blood samples will be unidentified. The women who agree to participate in the study will sign a consent form.

Etisk prövning

Ansökan till etikprövningsnämnden är gjord eller planeras

Datum för beslut från etikprövningsnämnden

2008-05-15

Diarienummer på beslut från etikprövningsnämnden

136-08

Etisk prövning behövs ej

Ansvarig forskningsledare bedömer att etisk prövning ej behövs.

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Referenser

1. Skilnand E, Fossen D, Heiberg E. Acupuncture in the management of pain in labor. Acta Obstet Gynecol Scand 2002;81(10):943-8.
2. Hantoushzadeh S, Alhusseini N, Lebaschi AH. The effects of acupuncture during labour on nulliparous women: a randomised controlled trial. Aust N Z J Obstet Gynaecol 2007;47(1):26-30.
3. Ziaei S, Hajipour L. Effect of acupuncture on labor. Int J Gynaecol Obstet. 2006;92(1):71-2.
4. Nesheim BI, Kinge R, Berg B, et al. Acupuncture during labor can reduce the use of meperidine: a controlled clinical study. Clin J Pain 2003;19(3):187-91.
5. Ramnero A, Hanson U, Kihlgren M. Acupuncture treatment during labour--a randomised controlled trial. Br J Obstet Gynaecol 2002;109(6):637-44.
6. Martensson L, Stener-Victorin E, Wallin G. Acupuncture versus subcutaneous injections of sterile water as treatment for labour pain. Acta Obstet Gynecol Scand 2008;87(2):171-7.
7. Wall PD, Melzack R, Koltzenburg M, McMahon SB. Wall and Melzack's textbook of pain. 5. ed. Philadelphia: Elsevier/Churchill Livingstone, 2006.
8. MacPherson H, White A, Cummings M, Jobst KA, Rose K, Niemtzow RC. Standards for Reporting Interventions in Controlled Trials of Acupuncture: the STRICTA recommendations. J Altern Complement Med 2002;8(1):85-9.
9. Altman D, Schulz K, Moher D, et al. The Revised CONSORT Statement for Reporting Randomized Trials: Explanation and Elaboration. Annals of Internal Medicine 2001;134(8):663-686.
10. Andersson S, Lundeberg T. Acupuncture--from empiricism to science: functional background to acupuncture effects in pain and disease. Med Hypotheses 1995;45(3):271-81.

C Bilagor

Bilagor

Protokoll Elakupunktur 080929.doc

Protokoll EA
Filstorlek: 152 kB

Protokoll SB, 080929.doc

Protokoll SC
Filstorlek: 169 kB

Protokoll, Manuell akupunktur 080929.doc

Protokoll MA
Filstorlek: 154 kB

Enkät 1 080925.doc

Enkät 1
Filstorlek: 48 kB

Enkät 2, EA, slutverison 080220.doc

Enkät 2
Filstorlek: 45 kB

Enkät 3 EA 080929.doc

Enkät 3
Filstorlek: 61 kB

Information Förlossningen 080926.doc

Information förlossningsbarnmorskor
Filstorlek: 72 kB

Patientinformation.pdf

Patientinformation
Filstorlek: 250 kB

Information MVC 080926.doc

Information MVCbarnmorskor
Filstorlek: 90 kB

Enkät 4, EA, 080929.doc

Enkät 4
Filstorlek: 77 kB

Eventuella bilagor som skickas in i pappersformat

Bifogar enkäterna 2-4 för endast elektroakupunkturgruppen då de andra är snarlika.

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D Sammanfattande kostnadsbeskrivning / budget för projektet

Total budget

Total summa

2 648 493

Andra bidragsgivare

Andra bidragsgivare

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Äskade medel från Regionala forskningsrådet i Uppsala- och Örebroregionen

Personal

Sökanden: Lön motsvarande 2 månader för att praktiskt delta i projektet samt handledning av doktorand.

Medarbetare: Doktorandlön

Assisterande personal: 20% för forskningsansvarig barnmorska som på förl. avd ansvarar för koordinering av projektet.

Utrustning

Utrustning består av kostnader för tryck av informationsblad, protokoll och enkäter samt provrör för blodprovstagning.

Övrigt

Övriga kostnader är porto för utskick av enkäter inklusive påminnelser samt resor, hudvudsakligen för möten med projektgruppen.

E Projektledarens egen bedömning

Bedömning i vad mån projektet är patientnära

This is a clinical trial that involves women in labour whom will actively make assessments of pain, relaxation and birth experience through validated instruments and questionnaires. The interventions will be performed by midwifes at the delivery ward.

Bedömning av projektets kliniska betydelse

Currently, acupuncture is used for labour pain without sufficient evidence for its effectiveness. The study will add to current knowledge and contribute with new knowledge that may form a basis for decisions about whether to use or not to use the treatment. If the acupuncture proves to be effective, an additional non-pharmacological method may contribute to effective care of women in labour. Acupuncture is cheap and easy to administer and may be appropriate in obstetric care worldwide, preventing suffering.

Bedömning av det regionala samarbetet och dess betydelse

Ett aktivt samarbete kommer att ske mellan forskare i Dalarna, Uppsala Universitet,Karolinska Instituet och Sahlgenska Akademin. En av forskarna (LM) är anställd på Högskolan i Skövde, vilken har ett samarbetsavtal gällande forskarutbildning och forskning med Örebro Universitet. Huvudsökande kommer att vara bihandledare för en doktorand från regionen. Samarbetet mellan Falun-Uppsala framförallt ske inom den obstetriska delen av projektets design och genomförande. Datainsamlingen i Falun kompletteras med NÄL Trollhättan pga geografisk närhet till LM och Lisa Stener-Victoring, experter inom ämnet akupuktur-förlossning. Projektet har genererat nya forskningsfrågor tex inventering av gällande riktlinjer för akupunkturanvändning vid samtliga svenska förlossningskliniker, en studie som genomförs av barnmorskor från Mora under handledning av huvudsökande och LM. Det finns ett stort intresse för studiens resultat från Socialstyrelsen och barnmorskor/obstetriker i hela landet.

Publicering

The results will be reported in peer reviewed obstetrical journals, such as BMJ (British Medical Journal), Obstetrics and Gynecology, British Journal of Obstetrics or Gynaecology. To reach also Swedish "non-english reading" professionals, the study will later also be reported in Läkartidningen and Jordemodern.

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F Vetenskaplig redovisning - gäller endast för fortsättningsansökningar

Rapporteringsläge

Lägesrapport

Publikationer

Planned publications:

1.Effect of acupuncture on labour pain and the use of epidural analgesia;
2.Comparing two methods of pain assessment during labour; VAS and Borg CR100;
3.Effect of acupuncture on women’s overall experience of childbirth and long-term memory of labour pain;
4.Effect of acupuncture on anti-inflammatory cytokines

Vetenskaplig progress och studiens genomförande

The trial has been designed, questionnaires been developed, information about the study to the midwives involved has been given. The courses to the widwives has been planned and dates are settled. Information to women at the antenatal clinic will be starting from 15 october 2008.

Ekonomisk redovisning

Kostnader för projektet har hittills bestått av postdocmånader från CKF Dalarna för sökande (Erica Schytt), litteratur och resor. F o m september 2008 doktorandlön (CKF) för Linda Vixner. Under oktorber och november kommer projektet att ha kostnader för utrustning, tryck, utbildning osv.

Planerad spridning och implementering

The results of the study will be presented at staff meetings, midwifery meetings and meetings for medical doctors at the respective clinic as well as through lectures at the midwife education in Högskolan Dalarna and elsewhere. The results will also be presented at conferences nationally and internationally and through publication as described above. Tthe results will be implemented at the two delivery wards in Dalarna and NÄL Trollhättan; by either continuing to offer the method or not.

Webblänk

www.akupunkturstudien.se (available soon)