Methods

Computer‐generated list of random numbers were prepared by an uninvolved 3rd party. Randomisation was accomplished by selection of the next in a series of opaque, sealed envelopes.
All women were accounted for.
Intention‐to‐treat analysis was used.

Participants

100 women recruited (epidural N = 49, narcotics N = 51)
Eligibility: nulliparous women at 36 ‐ 42 weeks' gestation, in spontaneous labour (at least 4 cm dilated)
Exclusion: women with insulin‐dependant diabetes, chronic hypertension, PIH or twin pregnancy

Interventions

Epidural: preload given 500 ‐ 1000 mL sodium lactate 0.25% bupivacaine ± 50 ‐ 100 mg fentanyl until T10 sensory analgesia achieved, then continuous infusion 0.125% bupivacaine with 1.5 mg/mL fentanyl. Continued in 2nd stage
Narcotic: 1 ‐ 2 mg butophanol (1 ‐ 2 hourly) IV

Outcomes

Maternal: pain scores measured hourly, length of 1st and 2nd stage of labour, oxytocin in labour, malposition, amniotomy, nausea and vomiting, operative vaginal delivery, caesarean section, caesarean section for dystocia and fetal distress
Neonatal: Apgar scores (mean), arterial cord pH, naloxone administration

Notes

University of Mississippi, USA
Active management of labour protocol. 33 of 39 operative vaginal deliveries in epidural group and 17 of 28 operative vaginal deliveries in opoid group were performed for purposes of resident training.
12 (24%) women randomised to narcotic received epidural as well, due to inadequate pain relief. 2 women randomised to epidural delivered before receiving it.

Dates: Trial carried out 1995 ‐ 1996

Funding: Supported by the Vicksburg Hospital Medical Foundation

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated list of random numbers

Allocation concealment (selection bias)

Unclear risk

Selection of the next in a series of opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2 women in the epidural group were delivered before obtaining regional analgesia and 12 women in the parenteral analgesia received "epidural rescue", but these participants remain in their group for all statistical considerations.

Selective reporting (reporting bias)

Low risk

All outcomes in the Methods section have been reported on in the results.

Other bias

High risk

More white women in the narcotic group (P = 0.008)

Methods

All participants randomised according to a random number scheme with instructions contained in sequentially numbered, opaque envelopes

Participants

24 women were recruited (sufentanil intrathecal N = 9, epidural N = 8, IV N = 7).
Eligibility: ASA physical status 1 or 2 parturients requesting epidural analgesia during active labour. All participants were at term and had uncomplicated pregnancies and normal fetal heart tracings.
Exclusion: not reported

Interventions

Sufentanil 10 µg either intrathecally (N = 9), epidurally (N = 8) or intravenously (N = 7), using a CSE technique. The sufentanil was administered alone without concomitant local anaesthetics. Participants could request additional analgesia (bupivacaine 0.25% via the epidural catheter) if pain relief was unsatisfactory by 15 mins after injection of study drug.

Outcomes

1. Pain intensity: assessed using a 10 cm linear visual analogue scale at time of study drug injection and 10, 20, 30, 40, 60, 90, 120, 180 minutes thereafter

2. Maternal blood pressure: at 10, 20, 30, 40, 60, 90, 120, 180 minutes thereafter

3. Additional analgesia: participants could request additional analgesia (bupivacaine 0.25% via epidural catheter) if pain relief unsatisfactory by 15 mins after injection of study drug.

4. Time from study drug administration until request for additional analgesia

5. Side effects (pruritus, nausea, and somnolence) assessed using a 4‐point scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.

6. Continuous electronic fetal monitoring throughout labour

Notes

Brigham and Women's Hospital, Harvard Medical School, USA
The study was terminated early "We had originally planned to enrol more patients in this protocol but terminated the study when it became clear that a large number of the subjects had clearly unsatisfactory analgesia" page 885, 1st paragraph within Discussion

Dates: Not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomised according to a random number scheme.

Allocation concealment (selection bias)

Low risk

All participants randomised in a double‐blind fashion according to a random number scheme with instructions contained in sequentially numbered, opaque envelopes.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Presume so ‐ states "double‐blind"

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Probably ‐ "All injectates were prepared by an anaesthesiologist not involved in subsequent data collection" ‐ implies people collecting data would not have been aware of drug allocation.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants randomised appear to have been accounted for within the results, although only a small number of women were recruited because the study was stopped early.

Selective reporting (reporting bias)

High risk

They did not report the results for the following outcomes:

1. maternal blood pressure: at 10, 20, 30, 40, 60, 90, 120, 180 minutes thereafter

2. additional analgesia: participants could request additional analgesia (bupivacaine 0.25% via epidural catheter) if pain relief unsatisfactory by 15 mins after injection of study drug.

Other bias

High risk

The study was stopped early because "it became clear that a large number of the subjects had clearly unsatisfactory analgesia" so the number of participants in the study was small.

Methods

RCT

Parallel design

Single centre

Tongji Hospital, Wuhan, Hubei, China

Participants

200 women were randomly divided into 2 groups.

Group 1 (N = 100) ‐ labour analgesia group ‐ ropivacaine 3.75 mg and fentanyl 20 µg injected into subarachnoid space while utero‐cervical was opened 2 ‐ 3 cm and then ropivacaine 0.1% plus fentanyl 2 µg/mL was used in epidural space.

Group II (N = 100) ‐ natural delivery without analgesia

Eligibility: ASA physical status I ‐ II parturients
Exclusion: not reported

Interventions

Group 1 (N = 100) ‐ labour analgesia group ‐ ropivacaine 3.75 mg and fentanyl 20 µg injected into subarachnoid space while utero‐cervical was opened 2 ‐ 3 cm and then ropivacaine 0.1% plus fentanyl 2 µg/mL was used in epidural space.

Group II ‐ natural delivery without analgesia

Outcomes

1. Serum PRL level measured with radioimmunoassay before analgesia and at 2, 24 hrs after labour

2. Pain intensity (analgesia effect)

3. Breastfeeding (initial time of lactation)

Notes

Abstract only ‐ so results limited

Dates: Not stated

Funding: Not stated

Declarations of Interest: None

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not reported

Selective reporting (reporting bias)

Unclear risk

Not reported

Other bias

Unclear risk

Not reported

Methods

Reported to be single‐centre RCT with individual allocation but no information on methods

Participants

124 women anticipating vaginal delivery were recruited and divided into 2 groups: PCA epidural ropivacaine (N = 75), versus 'no pain relieving methods' (N = 49).

Eligibility: women anticipating vaginal delivery (it was not clear whether any women subsequently had CS)

Exclusion: pregnancy complications

Interventions

Group 1 ‐ PCA epidural Ropivacaine ‐ 3 mL ropivacaine (0.125%) injected through an epidural catheter and another 12 mL 5 minutes later if there was no total spinal anaesthesia. The block level was controlled to be below the T10 level. Then 5 mL (0.104 mg/min) per hour until full dilatation. (N = 75).

Group 2 ‐ control ‐ "no pain relieving measures” (N = 49)

Outcomes

Prolactin levels at delivery and 2 hours later and time of the start of lactation

Mean newborn weight reduction in the 1st day following delivery. No relevant outcomes reported

Notes

Trial conducted in China, women attending a hospital in Bejing

Dates of trial: January 2006 – June 2007

Funding: not stated

Conflicts of Interest: not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Translated notes state "controlled clinical trial" and that women were “randomly divided” into groups but no further information.

Allocation concealment (selection bias)

Unclear risk

Translated notes state "controlled clinical trial" and that women were “randomly divided” into groups but no further information.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

No blinding: women in the control group had no analgesia whereas the intervention group had epidural; staff would be aware of study group.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Not stated, although outcomes were measured immediately after delivery, so it is likely outcome assessors were aware of analgesia.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

It was not stated whether or not there was any loss to follow‐up, translated notes report that numbers in tables report the same numbers as those randomised.

Intention‐to‐treat analysis: not reported. It was not stated whether any women had CS or whether these women were excluded post‐randomisation.

Selective reporting (reporting bias)

High risk

We have no protocol and assessment is from stated notes. Although this was reported as an RCT there was considerable imbalance between groups (75 vs 49). There was no explanation for this.

Other bias

Unclear risk

Insufficient information to make a judgement. The control group were reported to receive no analgesia; it is not clear whether this was at the point of randomisation or whether women requesting pain relief were denied it.

Methods

Computer‐generated, random‐number tables, group assignments were placed in sealed, opaque, sequentially‐numbered envelopes.
All women accounted for.
Intention‐to‐treat analysis used.

Participants

318 women recruited (epidural N = 156, meperidine N = 162)
Eligibility: nulliparous women in spontaneous labour (at least 50% cervical effacement or ruptured membranes, at least 2 contractions every 15 mins) at 36 weeks' gestation or more, vertex presentation
Exclusion: maternal or fetal conditions precluding trial of labour, thrombocytopenia or coagulation disorder, or multiple pregnancy

Interventions

Epidural: IV fluid bolus of 1 litre normal saline solution following by placement of the epidural catheter through the L2 ‐ 3 or L3 ‐ 4 interspace.
A test dose of 3 mL 1% lignocaine with epinephrine was administered, followed by 9 mL 0.25% bupivacaine with 50 µg fentanyl in 3 divided doses at 10‐min intervals; if vital signs remained stable during the subsequent 15 mins, a continuous infusion of 0.125% bupivacaine with 1 µg/mL fentanyl was initiated at 12 mL/hr and titrated to maintain anaesthesia to the T10 dermatome level.
IV meperidine: 50 to 75 mg meperidine every 90 mins as needed. These participants did not receive pre‐analgesic hydration.

Outcomes

Maternal: oxytocin use, length of 1st and 2nd stages of labour, 2nd stage labour, mode of delivery, caesarean for dystocia, caesarean for fetal distress
Neonatal: Apgar score at 5 minutes, meconium, umbilical cord pH/BE (arterial and venous), umbilical artery pH < 7.15

Notes

University of Louisville Hospital, Kentucky, USA
84 (52%) women in opioid group did not receive intervention (no reason given in paper), but received an epidural. 9 women in epidural group did not receive intervention (5 inability to site catheter, 4 delivered before epidural inserted).

Dates: Trial carried out 1995 ‐ 1996

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number tables

Allocation concealment (selection bias)

Low risk

Sealed, opaque, sequentially‐numbered envelopes

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

Because of the large number of cross‐over participants (52%), the data were subsequently analysed with respect to those who were compliant with the assigned analgesic method. 78 of 162 (48.1%) received IV meperidine and 147 of 156 (94.2%) of the epidural group.

Selective reporting (reporting bias)

High risk

Additional outcomes reported in tables (Apgar scores, meconium) not specified in the Methods section. 

Other bias

Low risk

10 participants were excluded from the data analysis because of protocol violations.

Methods

Randomised controlled trial using individual randomisation

Participants

70 women randomised (combined spinal anaesthesia, n = 35; continuous support, n = 35). Women admitted to the antepartum unit of the Instituto de Medicina Integral Prof Fernando Figueira, Brazil

Eligibility: pregnant women, singleton, full‐term fetus with cephalic presentation and cervical dilatation of 3 ‐ 6 cm

Excluded: women with fever before or at the time of randomisation, those using antibiotics, those with high‐risk pregnancies (placenta previa, placental abruption, severe pre‐eclampsia/eclampsia, premature delivery, HIV‐positive), and those with an indication of immediate caesarean section

Interventions

CSE anaesthesia: 2.5 mg of 0.5% heavy bupivacaine associated with 5 mg of sufentanil was injected into the subarachnoid space. Immediately afterwards, the epidural space was punctured using an 18 G Tuohy needle and a catheter was inserted into the same interspinous space used for subarachnoid puncture. Only 30 mins after subarachnoid puncture, administration of 5 mL of a solution containing 0.05% bupivacaine and sufentanil 0.2 mg mL–1 was initiated through the epidural catheter. This solution was administered intermittently every 30 mins until delivery of the infant.

CSE was initiated only when requested by participants. 1 woman did not request epidural.

Women in both groups received continuous support during delivery provided by a doula or trained lay person, and Swiss exercise balls, massage, and music therapy.

Outcomes

Satisfaction

Loss of control

Mode of birth

Oxytocin augmentation

Fever

Notes

Setting: hospital in Brazil

Dates of trial: February – May 2010

Funding: unclear

CoI: none declared

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A table of random numbers generated using the Random Allocation Software program

Allocation concealment (selection bias)

Low risk

Sealed open envelopes contained the allocation group to which each participant was to be assigned

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not feasible ‐ women and staff would have been aware of intervention groups

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Outcome assessor: insufficient information, labour outcome probably assessed by caregivers

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up occurred after randomisation.

Selective reporting (reporting bias)

Low risk

All prespecified outcomes are reported.

Other bias

Low risk

Women in both the groups were balanced for all the baseline characteristics.

Methods

Randomly selected from block group of sealed, opaque envelopes. Primary analysis: intention‐to‐treat analysis. Secondary analysis of compliant participants only, randomisation stratification into spontaneous and induced labour. All women accounted for

Participants

992 women recruited (epidural N = 493, continuous midwifery support group N = 499)

Eligibility: nulliparous women at term with singleton cephalic presentation in spontaneous labour (cervix < 5 cm dilated) and induced labour

Interventions

CSE: needle‐through‐needle approach. Preload 500 ‐ 1000 mL crystalloids. Spinal block achieved with fentanyl 25 micrograms and bupivacaine 2 mg. Following onset of analgesia epidural catheter dosed with 0.125% bupivacaine ‐6 mL then participant‐controlled epidural analgesia until delivery with 0.1% bupivacaine and 2 micrograms of pethidine. 136 women did not receive epidural.
Continuous midwifery support group was 1:1 midwife:participant ratio, IM pethidine, nitrous oxide inhalation, TENS, and/or non‐pharmacological forms of pain relief.

Outcomes

Maternal: pain scores, caesarean section, duration of 1st and 2nd stages of labour. operative vaginal delivery, vomiting, catheterisation during labour, fever (> 37.5 ºC) and satisfaction with childbirth (median VAS); breastfeeding reported on compliant participants only
Neonatal: Apgar scores, cord pH

Long‐term outcomes (Orlikowski 2006) ‐ back pain, headache, migraine, mod‐severe back pain, severe headache, severe migraine before pregnancy, during pregnancy, and at 2 (N = 576) and at 6 months (N = 521) postpartum

Notes

King Edward Memorial Hospital for Women, Perth, Western Australia, between May 1997 and October 1999

Funding: supported by NH&MRC Grant 970076

Conflicts of interest: not mentioned
137 (27%) women randomised to epidural received continuous midwifery support.
306 (62%) women randomised continuous midwifery support received epidural.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Selection from a blocked group of 8 sealed opaque envelopes replenished from blocks of 12

Allocation concealment (selection bias)

Low risk

Sealed opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Women were encouraged to manage their labour with the assistance of a midwife and with the intention of avoiding the use of epidural analgesia.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

The cross‐over rate from the EPI to the CMS group was 27.8% (N = 137) and cross‐over rate from CMS to EPI analgesia was 61.3% (N = 306).

Selective reporting (reporting bias)

Unclear risk

Insufficient information

Other bias

High risk

As the compliance rate was approximately 40% in the CMS group and 75% in the EPI group, it would not be possible to distinguish between the caesarean section rates, as hypothesised, without 12,000 participants. As it was not feasible to recruit the number of women required to demonstrate such a difference, enrolment into the trial was stopped.

Methods

RCT with individual randomisation

Participants randomly allocated to 2 intervention groups, control group recruited by observational cohort. Control group data not included in this review.

Participants

116 women recruited to 2 treatment groups but data reported only for 98 (epidural analgesia n = 49; intravenous remifentanil patient‐controlled analgesia n = 49).

Eligibility: women who are classed as ASA class I or II parturients with a singleton pregnancy, between 37 and 42 weeks of gestation

Excluded: BMI ≥ 40 kg/m², insulin‐dependent diabetes, severe pre‐eclampsia (proteinuria ≥ 5 g/24 hr), use of antibiotics during delivery, initial maternal SpO2 < 98%, initial maternal temperature ≥ 38 ^oC, cervical dilation of > 7 cm and ruptured membranes for > 24 hrs at the time of inclusion. If delivery occurred within 1 hr of starting the study, women were excluded from analysis.

Interventions

Epidural analgesia: EA (n = 49)

A catheter was inserted at the L2 – 3 or L3 – 4 interspace using a 17‐gauge Tuohy needle. Parturients received a loading dose of ropivacaine 25 mg (0.2% ropivacaine 12.5 mL), followed by a continuous infusion of 0.1% ropivacaine and sufentanil 0.5 µg/mL at 10 mL/h. In case of inadequate analgesia, additional 10 mL boluses were given. In case of epidural catheter dislodgement, the catheter was replaced.

rPCA (n = 49)

Received a 40 µg bolus (lockout 2 mins, bolus duration 36 s) using a Graseby 3300 syringe pump. The maximum dose permitted was 1200 µg/h. No background infusion was added. Because of concerns about the potential for neonatal respiratory depression, the pump was stopped when the woman reached full cervical dilatation. When parturients were dissatisfied with analgesia, EA was offered as alternative.

Outcomes

Mode of birth

Side effects

Apgar scores

Umbilical cord gases

Duration of labour

Satisfaction scores

Notes

Country and setting: Netherlands, Leiden University Medical Center

Dates of trial: November 2008 – October 2010

Funding: Department of Anesthesiology, Leiden University Medical Centre

Conflicts of interest: none

Neonatal fever 2/49 EA; 2/49 rPCA

Sepsis follow‐up 4/49 EA; 3/49 rPCA

Positive blood culture 0/49 EA; 0/49 rPCA

Overall satisfaction measured post‐delivery 8.4 (SD 1.2)/49 EA; 8.1 (SD 1.2)/49 rPCA

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation list

Allocation concealment (selection bias)

Low risk

Randomisation list was kept in a numbered opaque sealed envelope that was opened upon the request for analgesia.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not feasible for these interventions

Blinding of outcome assessment (detection bias)
All outcomes

High risk

No information on who collected or analysed the outcome given, but probably collected by care provider in labour

Satisfaction score was by self‐administered questionnaire

Incomplete outcome data (attrition bias)
All outcomes

High risk

10 women were excluded from the analysis in EA group: 7 delivered < 1 hour of analgesia; 3 met exclusion criteria post‐randomisation but reasons not explicit.

8 women were excluded from the analysis in rPCA group: 6 delivered < 1 hr; 2 "met exclusion criteria".

"Continuous saturation data were not always available and this information is reported for only 114 women." 1 women lost to follow‐up in labour in each group.

Selective reporting (reporting bias)

Low risk

All prespecified outcomes are reported as per protocol.

Other bias

Unclear risk

Similar baseline characteristics. Some reporting of results is not clear.

Methods

RCT

Parallel design

Single centre

Cairo, Egypt

Participants

30 nulliparous pre‐eclamptic parturient women were randomly divided into 2 equal groups.

Epidural group: N = 15

Remifentanil group: N = 15

Eligibility: ≧ 32 weeks' gestation, normal cephalic presentation, < 5 cm cervical dilatation, clinical diagnosis of pre‐eclampsia
Exclusion: remifentanil allergy, progression to eclampsia, evidence of increased intracranial pressure or focal neurologic deficit, women with a platelet count of less than 80 x 10⁹/L, or evidence of pulmonary oedema, non‐reassuring fetal heart rate tracing requiring imminent delivery

Interventions

Epidural group (N = 15): received epidural analgesia according to a standardised protocol using bupivacaine plus fentanyl.

Remifentanil group (N = 15): PCA was set up to deliver remifentanil 0.5 µg/kg as a loading bolus infused over 20 s, lockout time of 5 mins, PCA bolus of 0.25 µg/kg, continuous background infusion of 0.05 µg/kg/min, and maximum dose is 3 mg in 4 hrs. Women were advised to start the PCA bolus when they felt signs of a coming uterine contraction.

Outcomes

1. Oxygen saturation, heart rate, blood pressure, respiratory rate ‐ at baseline, 1 hr after analgesia, after delivery (mean ± SD)

2. Pain intensity ‐ pain VAS score at baseline, 1 hr, after delivery (mean ± SD)

3. Sedation score (1 ‐ 4) ‐ at baseline, 1 hr, after delivery (mean ± SD)

4. Satisfaction with pain relief ‐ (overall participant satisfaction within 24 hrs of delivery) ‐ 1: poor, 2: fair, 3: good, 4: excellent

5. Requirement for pharmacologic interventions to treat hypotension and incidence of complications

6. Neonatal side effects:

• • FHR abnormalities at 1 hr after analgesia

  • Apgar score ≦ 7 ‐ 1 minute, 5 minutes

  • Naloxone

  • Umbilical cord gas

  • Seizure

  • Mechanical ventilation

7. Maternal side effects:

• Nausea

• Vomiting

• Itching

• Hypotension

8. Assisted vaginal delivery

9. Caesarean section

10. Normal delivery

Notes

Cairo University, Egypt

Dates: Not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No missing outcome data

Selective reporting (reporting bias)

Low risk

All expected outcomes are reported.

Other bias

Low risk

Baseline characteristics of groups were similar.

Methods

RCT

Parallel design

Single centre

Department of Obstetrics and Gynecology, The Edith Wolfson Medical Center, Israel

Participants

60 women recruited ‐ 4 excluded (epidural N = 29, iv meperidine N = 27)

Eligibility: healthy, ASA physical status I and II primiparous women in spontaneous labour with singleton cephalic presentation at term
Exclusion: not stated

Interventions

PCEA with 0.2 % ropivacaine (N = 29)

Patient‐controlled IV analgesia (PCA) with meperidine (N = 27)

Outcomes

1. Increased intrapartum temperature (≥ 37.6 °C) (%)

2. Increased intrapartum temperature ((≥ 38 °C) (%)

3. Increased white blood cell count during labour (> 15,000/µL)(%)

4. Number of vaginal examinations

5. Intrauterine pressure monitoring (%)

6. Fetal weight (g)

7. Apgar score (1 min)

8. Apgar score (5 min)

9. Umbilical arterial blood pH

Notes

Department of Obstetrics and Gynecology, The Edith Wolfson Medical Center, Israel

4 exclusions (3 caesarean deliveries performed for non‐reassuring FHRs and 1 parturient in the meperidine group demanded epidural analgesia)

Dates: Trial carried out February to September 2003

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation was based on computer‐generated codes.

Allocation concealment (selection bias)

Low risk

Randomisation was based on computer‐generated codes, maintained in sequentially numbered opaque envelopes until just before use.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Dummy IV saline and dummy epidural catheter were used.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Pathologist who examined placenta and umbilical cord was blinded to parturient's temperature.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

4 exclusions (3 caesarean deliveries performed for non‐reassuring FHRs and 1 parturient in the meperidine group demanded epidural analgesia) ‐ outcome data available for all remaining participants (N = 56).

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported within the Methods section are available within the Results.

Other bias

Low risk

Baseline characteristics similar between groups.

Methods

RCT

Parallel design

Single centre

The Wolfson Medical Center, affiliated to Tel‐Aviv University, Israel

Participants

213 women recruited to the study, 201 completed it. The remaining 12 completed the delivery quickly and did not require any analgesia. All participants (N = 192) with at least 2 hrs of labour were included in the data analysis.

Analgesia was randomly provided for 1 of 4 treatment groups:

1. epidural ropivacaine alone (N = 50);

2. IV remifentanil alone (N = 44);

3. epidural ropivacaine plus IV remifentanil (N = 49);

4. epidural ropivacaine plus IV acetaminophen (N = 49).

Eligibility: healthy women with singleton cephalic presentation at term and presenting in spontaneous active labour.
Exclusion: Women were excluded if they initially had a fever (oral temperature ≥ 38 °C), signs of infection, or ruptured membranes for more than 24 hrs. Also excluded if caesarean delivery was anticipated.

Interventions

Analgesia was randomly provided for 1 of 4 treatment groups:

1. epidural ropivacaine alone;

2. IV remifentanil alone;

3. epidural ropivacaine plus IV remifentanil;

4. epidural ropivacaine plus IV acetaminophen.

Outcomes

1. Pain intensity

2. Temperature ‐ maximal forearm‐finger gradient temperature (°C)/temperature at baseline (°C)/maximum increase from baseline temperature (°C)/hyperthermic participants (n, %)

3. Neonatal ‐ sepsis (complete blood count and cultures followed by antibiotic administration), heart rate, blood pressure, oxygen saturation, rectal temperatures, Apgar scores at 1, 5 and 10 mins, umbilical blood gases)

4. Assisted vaginal delivery

5. Caesarean section

6. Membrane rupture duration (hrs)

7. Cervical dilation at study entry (cm)

Notes

The Wolfson Medical Center, affiliated to Tel‐Aviv University, Israel

The remaining 12 completed the delivery quickly and did not require any analgesia. All participants (N = 192) with at least 2 hrs of labour were included in the data analysis.

Dates: Not stated

Funding: "Supported by NIH Grant GM 061655 (Bethesda, MD), the Gheens Foundation (Louisville, KY), the Joseph Drown Foundation (Los Angeles, CA), and the Commonwealth of Kentucky Research Challenge Trust Fund (Louisville, KY). Mallinckrodt Anesthesiology Products, Inc. (St. Louis, MO) donated the thermocouples we used. Exergen, Inc. (Boston, MA) donated the infrared skin‐temperature thermometer."

Declarations of Interest: "None of the authors has any personal financial interest in this research."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation was based on computer‐generated codes.

Allocation concealment (selection bias)

Low risk

Randomisation was based on computer‐generated codes that were maintained in sequentially numbered opaque envelopes until just prior to use. The randomisation envelopes were opened and the designated treatment started when the visual analogue pain score (VAPS) reached 30 mm.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

The treatment regimen was blinded for the evaluator anaesthesiologists by using 2 patient‐controlled analgesia machine devices (PCIA and PCEA) for every participant. A "dummy" IV saline infusion (PCIA) was attached to parturients with PCEA and the other was a "dummy" epidural catheter attached superficially to the skin and connected to a PCEA syringe in the group with PCIA with remifentanil.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Pathologist was blinded to participant group allocation.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

213 women recruited to the study, 201 completed it. The remaining 12 completed the delivery quickly and did not require any analgesia. All patients (N = 192) with at least 2 hrs of labour were included in the data analysis.

Selective reporting (reporting bias)

High risk

Actual figures for Apgar scores, heart rate, blood pressure and oxygen saturation not given ‐ just mentioned in narrative, last paragraph page 108 before Discussion.

Other bias

Low risk

All groups appear to be similar according to baseline characteristics.

Methods

Multicentre randomised controlled trial with individual randomisation

Participants

1414 women randomised (remifentanil PCA n = 709; epidural n = 705) (data analysed for 3158 women). Dutch consortium for women’s health and reproductivity. Academic hospitals, and general hospital

Eligibility: women in secondary and tertiary care (intermediate or high risk), i.e. they have illnesses in their medical history that can affect pregnancy or that are affected by pregnancy or if they have complications in this or previous pregnancies or deliveries.

Women were eligible to participate if they were healthy or had a mild systemic disease, aged 18 or older, and were scheduled to deliver vaginally after 32 weeks.

Excluded: contradictions for epidural analgesia or hypersensitivity to 1 of the drugs used

Interventions

Epidural analgesia: women could request this when they requested pain relief, according to local protocol.

If pain relief was judged inadequate, women could receive patient‐controlled remifentanil instead of epidural analgesia.

Remifentanil: patient‐controlled device was programmed to deliver 30 μg remifentanil (solution 20 µg/mL) on request with a lockout time of 3 mins. The dose could be increased to 40 μg in case of insufficient pain relief or decreased to 20 μg in case of excessive side effects. If pain relief was inadequate, women could request epidural analgesia. They were advised to discontinue using the device during the 2nd stage of labour to minimise the risk of neonatal side effects.

Women did not receive any advice about continuing epidural analgesia during 2nd stage of labour.

"Of the 709 women randomised to patient controlled remifentanil, 447 (65%) actually received analgesia during labour, compared with 52% (347) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48)."

For data analysis in this review we used the number randomised. We did not count the women removed for elective caesarean section. Denominators used: Epidural ‐ 676 women; remifentanil ‐ 687

Difficult to interpret as only 347/676 received epidural, and 447/687 received rPCA.

Outcomes

Mode of birth

Satisfaction scores

Oxytocin augmentation

Maternal hypotension

Maternal respiratory depression

Side effects

Apgar scores

Admission to neonatal special care

Notes

Country and setting: Netherlands, secondary care

Dates of trial: May 2011 – October 2012

Funding: grant from ZonMW (Dutch Organization for Health Care Research and Development)

Conflict of interest declared. All authors completed the ICMJE uniform disclosure form: "no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Web‐based randomised programme, randomised in fixed blocks of 3, stratified for centre and parity

Allocation concealment (selection bias)

Unclear risk

Allocation code appears after a participant’s initials were entered in to the randomisation programme. Research nurses/midwives as well as attending medical staff performed randomisation.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding was not possible because of the nature of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

There is no information on who assessed or analysed the outcomes. Labour outcomes likely to have been recorded by caregiver.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Of 709 allocated to remifentanil, 22 were excluded from final analysis due to elective planned caesarean, while in the epidural group 29 were excluded due to elective planned caesarean.

In the epidural group, 3 women were lost to follow‐up, while 2 withdrew informed consent after randomisation.

Used multiple imputation to correct for missing primary outcome data, imputed missing AUC values for satisfaction with pain relief and pain intensity using 20 imputed datasets. Other missing values were not imputed.

Some outcomes were only reported for the women who received the analgesia. Number randomised was used for this review.

Selective reporting (reporting bias)

Low risk

Protocol is available and all prespecified outcomes are reported in the main trial.

Other bias

Unclear risk

No baseline imbalance but denominators unclear following exclusions for CS. Not all women received analgesia allocated.

Methods

Computer‐generated, in groups of 100, allocation was secured in a numbered and sealed envelope. Intention‐to‐treat analysis used. All women accounted for.

Participants

1223 women recruited (epidural N = 616, meperidine = 607). Eligibility: nulliparous and parous women in spontaneous labour (regular contractions, at least 3 cm dilated), singleton, cephalic presentation, cervix < 5 cm dilated
Exclusion: pregnancy complication (not specified), more than 5 cm dilated, multiple pregnancy, non‐cephalic presentation

Interventions

CSE: preload with 500 mL sodium lactate. Catheter L2 ‐ 3 or L3 ‐ 4 interspace. Spinal block with 10 µg sufentanil in 2 mL normal saline. Needle‐through‐needle approach. Following dissipation of spinal analgesia, epidural analgesia achieved with 0.25% bupivacaine in 3 ‐ 5 mL increments to achieve T10 ‐ T8 sensory level. This was followed by epidural infusion 0.125% bupivacaine and 2 microgram per mL fentanyl at 8 mL/h. Rate of infusion halved during 2nd stage of labour.
Meperidine group: 50 mg meperidine + 25 mg promethazine hydrochloride intravenously. Further 50 mg IV meperidine on request hourly to a maximum of 200 mg in 4 hrs. All women had IV fluid administration.

Outcomes

Maternal: intrapartum visual analogue pain score and postpartum overall satisfaction with labour analgesia, oxytocin, mode of delivery, hypotension, meconium, surgical amniotomy, motor block, fever, itch, operative vaginal delivery
Neonatal: Apgar score, birthweight, cord arterial pH

Notes

University of Texas, USA. Amniotomy routinely performed in active labour when fetal head is well applied to cervix. Intrauterine pressure catheter used to assess adequacy of contraction if progress < 1 cm/hr and oxytocin augmentation employed if uterine pressure < 200 montevideo units.
216 (35%) women randomised to epidural did not receive it (82 received meperidine, 52 declined any analgesia, 43 rapid delivery, 39 non‐study drug used). For 255 (42%) women randomised to meperidine: 102 received epidural as well, 57 received epidural only, 42 declined any analgesia, 30 rapid delivery, 24 non‐study drug used.

Dates: Trial carried out 1994 ‐ 1995

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated in groups of 100

Allocation concealment (selection bias)

Unclear risk

Numbered sealed envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Cross‐over participants were analysed in their original groups.

Selective reporting (reporting bias)

High risk

Additional outcome (Apgar score) reported in tables not specified in the Methods section.

Other bias

Low risk

None evident

Methods

Reported to be a prospective randomised controlled study but methods not described. Women randomised into equal‐sized groups.

Participants

100 women randomised (epidural, N = 50; no epidural, N = 50)

Eligibility: healthy, nulliparous women in active labour with 3 ‐ 5 cm cervical dilatation, 3 ‐ 5 contractions in 10 mins, healthy with singleton fetus at term (37 ‐ 41 weeks’ gestation), no evidence of cephalopelvic disproportion

Exclusion: amniotic fluid deficiency or fetal heart rate non‐reactivity

Interventions

Group 1: epidural. N = 50

2 cc test with 40 mg lidocaine; after 5 mins provided woman had no motor block and experienced pain relief, 4 cc of 0.5 bupivacaine and 50 mg of fentanyl were diluted in 0.9% saline and administered as a bolus injection. 5 ‐ 10 cc further administered as needed. Women were in bed in left lateral position. If they had fewer than 3 contractions in 10 mins labour was augmented with oxytocin.

Group 2: not described. No epidural analgesia. N = 50

It was not clear whether women received other pharmacological analgesia or whether the same protocol was followed in case of any delay in labour.

Outcomes

Mode of birth

Side effects

Duration of labour

Hypotension

Notes

Trial conducted at hospital in Izmir, Turkey.

Dates of trial: July 2012 ‐ August 2014

Funding: not reported

Conflicts of Interest: the authors reported no conflicts of interest.

It was stated for women in the epidural group that if contractions were less than 3 in 10 mins oxytocin was administered. Not clear if the same protocol was used for the control group, so length of 1st stage may be meaningless (more in the ED group may have had oxytocin – this was not clear). Epidural mean 217.9 min (166.33); no epidural 258.87 (158.48)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described although there were equal‐sized groups

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Participants and staff would be aware of the intervention.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Most outcomes were recorded during labour by staff providing care, so susceptible to bias.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Women who had CS were excluded from the analysis. No other loss to follow‐up was reported. Not clear

Selective reporting (reporting bias)

Unclear risk

We have no protocol for this study. The intervention was not well described for the comparison group. There did not seem to be a power calculation.

Other bias

Unclear risk

The main outcome was duration of labour. There was a clear description of what happened for any delay for women in the intervention group (oxytocin augmentation). It was not clear that women in the non‐epidural group had the same treatment in case of delay.

Methods

Random allocation by drawing lots. All women accounted for

Participants

90 women recruited (epidural N = 30, phenoperidine N = 30, no analgesia N = 30)
Eligibility: women at 38 ‐ 42 weeks' gestation, para 1 or para 2 in spontaneous labour, at 4 cm dilatation with no obstetric complications

Interventions

Epidural: preload not mentioned. Epidural delivery of 12 mL of 1.5% lidocaine in 1:20,000 adrenaline. Followed by top‐ups of 6 mL lignocaine as needed
Phenoperidine: IV injection of 1 mg followed by infusion of 34 micrograms per min, with 3l/min humidified oxygen intranasally

Outcomes

Maternal: mode of delivery, blood gases and pH
Fetal/neonatal: fetal heart rate, Apgar scores, fetal blood pH and gases, umbilical artery pH

Notes

Toulouse, France
Paper does not state if any women did not receive their allocated treatment.

Dates: Year trial carried out not stated

Funding: Not stated in translation

Declarations of Interest: Not stated in translation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Insufficient information

Allocation concealment (selection bias)

Unclear risk

Participants were drawn by lots, no further information given

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Insufficient information

Selective reporting (reporting bias)

Unclear risk

Insufficient information

Other bias

Unclear risk

Insufficient information

Methods

RCT

Parallel design

Multicentre

Canada

Participants

242 parturients enrolled and assigned to the PCIA group (N = 118) and the PCEA group (N = 124)

Eligibility: nulliparous women with healthy term (37 ‐ 42 weeks' gestation) pregnancies from 4 tertiary‐care Canadian centres. ASA I or II in spontaneous labour with singleton pregnancy in vertex presentation
Exclusion: pre‐eclampsia, antenatal haemorrhage, a BMI > 35 kg/m², multiple gestation, abnormal presentation, known fetal anomalies, or fetal distress

Interventions

Patient‐controlled epidural analgesia (PCEA) with 0.08% bupivacaine and fentanyl 1.6 µg/mL; N = 124

Patient‐controlled IV opioid analgesia (PCIA) with fentanyl; N = 118

Outcomes

1. Pain intensity

2. Satisfaction with pain relief

3. Caesarean section

4. Assisted vaginal birth

5. Spontaneous vaginal deliveries

6. Duration of 2nd stage of labour

7. Side effects (mother ‐ drowsiness, respiratory depression, maternal fever, need for medication for nausea and vomiting)

8. Side effects (neonate ‐ resuscitation with oxygen, neonatal fever)

9. Apgar score at 1 and 5 minutes

10. Umbilical artery cord pH, PCO₂, BE

11. Use of naloxone

Notes

Multicentre ‐ 4 tertiary‐care centres, Canada

51 participants (43%) in the PCIA group received epidural analgesia: 39 (33%) because of inadequate pain relief and 12 (10%) to facilitate operative delivery.

Dates: Trial carried out September 1997 ‐ December 1999

Funding: Supported by Physicians Services Incorporated Foundation, Toronto; Alberta Heritage Fund; Clinical Teaching and Research Grant, College of Medicine, University of Saskatchewan; Medical Services Incorporated of Alberta; Grace Maternity Research Foundation Grant; and Dalhousie University Department of Anaesthesia

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Randomly assigned to one of two treatment allocations by using a computer‐generated random number system."

Allocation concealment (selection bias)

Low risk

"Each centre was randomised separately at a central location. Each centre received sealed, consecutively numbered opaque envelopes that were randomised in blocks of 20."

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

The data were analysed according to group assignment (intention‐to‐treat).

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported within the Methods section are available within the Results.

Other bias

High risk

According to sample size calculation ‐ 485 participants per group needed ‐ actually recruited 242 patients. "A priori we decided to inspect neonatal data after enrolling 200 patients to ensure neonatal safety. We also decided to stop the study after 2 yr of enrolment, regardless of the number of patients."

All groups appear to be similar according to baseline characteristics.

Methods

Computer‐generated block randomisation, stratified according to gestational age (< 35 weeks versus ≥ 35 weeks). Numbered, sealed, opaque envelopes. Intention‐to‐treat analysis used. All women accounted for

Participants

116 women recruited (meperidine N = 60, epidural N = 56).
Eligibility: women > 24 weeks' gestation with severe pre‐eclampsia having singleton vertex presentation and at least 2 cm dilated to 6 cm cervical dilatation

Interventions

Epidural: preload 250 ‐ 500 mL sodium lactate over 20 mins. Epidural catheter placed in L3 ‐ L4 interspace. Test dose of 0.25% bupivacaine 3 mL, then incremental bolus doses of 3 ‐5 mL 0.25% bupivacaine to obtain T‐10 sensory level, maintained by continuous infusion of 0.125% bupivacaine with 2 microgram fentanyl at rate of 10 mL/hr.
Meperidine: PCA IV meperidine dose of 10 mg and lockout interval of 10 mins. Maximum dose of 240 mg in 6 hrs also had IV promethazine 25 mg 4‐hourly. All women received IV crystalloid 100 mL/h and magnesium sulphate 4 g bolus followed by infusion of 2 g/hr til 24 hrs postpartum.

Outcomes

Maternal: intrapartum visual analogue pain score, mode of delivery, woman's satisfaction with pain relief, hypotension, headache, eclampsia, acute renal dysfunction
Neonatal: Apgar scores, seizure, naloxone administration, neonatal intensive care admission, fetal heart rate abnormalities, umbilical cord pH, birthweight

Notes

Alabama, USA
42 women in the epidural group and 41 women, in control group received opioid prior to randomisation. 25 women in epidural group and 19 women in control group received hydralazine.
7 women did not receive their allocated treatment (5 from opioid group). 1 woman randomised to opioid had epidural as well.
1 woman randomised to opioid had epidural instead.
Year trial carried out not stated.

Dates: "42 month study period"

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated block randomisation schedule

Allocation concealment (selection bias)

Low risk

Consecutively‐numbered, sealed opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

10 women did not receive the assigned treatment, 3 in the epidural group and 7 in the opioid group. Rapid labour was the most common event that precluded the assigned treatment (epidural, n = 3 versus opioid, n = 5). 1 woman assigned to the opioid group received epidural analgesia at the discretion of the attending anaesthesiologist. Another woman who was assigned to opioids received epidural analgesia after experiencing severe nausea.

Selective reporting (reporting bias)

Low risk

All outcomes in the Methods section have been reported on in the Results section.

Other bias

Low risk

None evident

Methods

"Randomized clinical trial."
No further detail in abstract.
Intention‐to‐treat analysis used. All women accounted for

Participants

105 women recruited (epidural N = 53, meperidine N = 52)
Eligibility: labouring women with severe pre‐eclampsia at > 24 weeks' gestation

Interventions

Epidural analgesia versus IV PCA with meperidine. No further information in abstract

Outcomes

Maternal: caesarean section, pain score, satisfaction score, maternal ephedrine administration
Neonatal: naloxone administration, birthweight, cord pH, NICU admission, deaths

Notes

Birmingham, Alabama, USA
8 of the 105 women did not receive assigned treatment due to rapid labour. 2 in the meperidine group received epidural as well.
Year trial carried out not stated

Dates: Not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Insufficient information

Allocation concealment (selection bias)

Unclear risk

Insufficient information

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

10 participants did not received the assigned intervention.

Selective reporting (reporting bias)

Unclear risk

Insufficient information

Other bias

Unclear risk

Insufficient information

Methods

Computer‐generated randomisation at the time of request for pain relief. Intention‐to‐treat analysis used. Outcome assessor for backache blinded. All women accounted for, with the exception of backache (17% loss to follow‐up at 26 months).

Participants

369 women recruited (epidural N = 184, non‐epidural N = 185). Eligibility: labouring nulliparous women at term with singleton pregnancy and cephalic presentation, with no contraindication to either form of analgesia.

Interventions

Preload not stated. 10 mL of 0.25% bupivacaine. Followed by top‐ups of 0.25% 5 ‐ 10 mL as required. Pethidine: 50 ‐ 100 mg IM pethidine, repeated according to standard midwifery practice. Women in both groups allowed to use Entonox.

Outcomes

Maternal: mode of delivery, length of labour, use of oxytocin, maternal satisfaction with pain relief, backache, postnatal depression, not feeling in control, drowsiness, concerns regarding pain relief, catheterisation postdelivery, postnatal haemoglobin, maternal blood loss at delivery
Fetal/neonatal: Apgar scores, umbilical cord pH

Notes

North Staffordshire, UK
52 (28%) women randomised to non‐epidural received epidural. 61 (33%) women randomised to epidural did not receive it.

Dates: Trial carried out 1992 ‐ 1997

Funding: "The study was funded by WellBeing, and Ms P. Upton was supported by a grant from the North Staffordshire Medical Institute. The clinical trials work of Mr Richard Johanson and Ms Linda Lucking is supported by a grant from the NHS(E) West Midlands Research and Development Programme."

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated

Allocation concealment (selection bias)

Low risk

Allocation was displayed on the computer screen.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Women in the epidural and non‐epidural groups remain in the group to which they were initially allocated, regardless of the eventual method of pain relief given during labour.

Selective reporting (reporting bias)

High risk

Outcomes not all prespecified in Methods section.

Other bias

Low risk

None evident

Methods

3‐armed RCT with individual randomisation

3 blocks of 380 participants.

Participants

1140 women recruited (epidural anaesthesia, N = 380; remifentanil group by patient‐controlled IV analgesia, N = 380; combined spinal‐epidural, N = 380).

Eligibility: healthy nulliparous pregnant women (with term, singleton pregnancies), who spontaneously went into established labour (with at least 2 painful uterine contractions in 10 mins and the cervix is at least 80% effaced and up to 3 cm dilated) and requesting labour analgesia.

Exclusion:

(1) Allergy to opioids, a history of the use of centrally‐acting drugs of any sort, chronic pain, and psychiatric diseases records

(2) Participants < 18 years or > 40 years

(3) Those who were not willing to or could not finish the whole study

(4) Alcohol‐ or opioid‐dependent women were excluded for their influence on the analgesic efficacy of the epidural analgesics

(5) Women with a non‐vertex presentation or scheduled induction of labour

(6) Women with diabetes mellitus and pregnancy‐induced hypertension

(7) Twin gestation and breech presentation

(8) Any contraindication to neuraxial or systemic opioid analgesia

(9) Cervical dilation of 4 cm or more

(10) Estimated fetal weight above 4000 g and abnormal fetal heart rate tracing on admission

Interventions

Group 1: epidural anaesthesia (N = 380)

All blocks were performed in the sitting position. The epidural space was located at the L3 – L4 interspace using loss of resistance to air (an 18‐gauge Tuohy needle was used). In both groups, a 3‐mL epidural test dose of 2% lidocaine was given through the epidural catheter. In the EA (Group I), after the test dose, an 8‐mL dose of 0.125 % levobupivacaine with 2 lg/mL fentanyl was administered through the epidural catheter. Then the catheter was connected to an electronic pump set to deliver a continuous infusion of 8 mL/hr of 0.125 % levobupivacaine and 2 lg/mL fentanyl. Further boluses of 5 – 10 mL of 0.125 % levobupivacaine were given by the attending anaesthesiologist upon request.

Group 2: remifentanil group by patient‐controlled IV analgesia (N = 380)

The PCIA device was set to deliver 0.1 ug/kg of Ultiva (remifentanil hydrochloride, Glaxo Operations UK Ltd, Barnard Castle, Durham, UK), diluted with saline and given as a solution of 25 ug/mL as a bolus infused during a period of 1 min, with a lockout time of 1 min, into an IV catheter attached to a 1‐way line providing continuous infusion of saline at approximately 100 mL/hr. During the study, the IV PCIA bolus was increased following a dose escalation scheme (0.1 – 0.2 – 0.3 – 0.5 – 0.7 – 0.9 ug/kg) after every 2nd contraction until the parturient answered ‘no’ to the question whether she would like to get more efficient pain relief or until a maximum dose of 0.9 ug/kg was achieved.

Group 3: combined spinal–epidural (N = 380)

A needle‐through‐needle technique was performed with 2 mg levobupivacaine and 15 lg fentanyl (total volume of 2 mL) injected intrathecally and the spinal needle removed. Then the epidural catheter was inserted and connected to an electronic pump set to deliver the same previously‐mentioned mixture.

Outcomes

Pain score

Mode of birth

Oxytocin augmentation

Side effects

Duration of labour

Satisfaction with pain relief

Apgar scores

Cord blood gases

Notes

Motor block levels according to the Bromage scale (Groups I and III) and sedation levels according to the Ramsay scale (Group II) were observed.

Decisions regarding obstetric management were made by the obstetricians.

Artificial rupture of membranes was performed (if there was no ROM), and oxytocin infusions were titrated according to our hospital protocol.

All participants had continuous external electronic fetal heart rate monitoring and tocodynamometry.

Trial conducted at TAIBA Hospital in Kuwait.

Dates of trial: September 2009 ‐ August 2011

Funding: not stated

Conflicts of Interest: none declared

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

The participants were randomised (in 3 blocks of 380 participants per block) through a computer‐generated, random‐number list to receive either EA (Group I), or patient‐controlled IV analgesia (PCIA) with remifentanil (Group II) or combined spinal–epidural (CSE) analgesia (Group III). The random‐number list was generated by means of the QuickCalcs (GraphPad Software Inc., La Jolla, CA, USA).

Allocation concealment (selection bias)

Low risk

The group assignment numbers were sealed in an envelope and kept by the study supervisor.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not feasible to blind participants or caregivers as mode of administration varied.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Outcome data reported to be collected at time of delivery or the day after by assessors not involved in the woman’s care. However, labour outcomes would be recorded by staff providing care. ? e.g. VAS completed hourly during labour.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No post‐randomisation exclusions, no loss to follow‐up reported. 320 excluded prior to randomisation because they did not fit the inclusion criteria.

Intention‐to‐treat analysis: no loss to follow‐up or protocol deviations reported (it was not clear how many women actually received the allocated analgesia).

Selective reporting (reporting bias)

Low risk

No, no protocol available but all outcomes reported from Methods text and all expected outcomes reported.

Other bias

Low risk

No baseline imbalance. Funding source not disclosed

Methods

Randomisation with Tippets random number table into 3 groups. Allocation was concealed using sealed, opaque envelopes (information obtained directly from trial authors). All women accounted for

Participants

126 women recruited (epidural N = 43, meperidine N = 39, tramadol N = 44)
Eligibility: nulliparous women in spontaneous labour at > 36 weeks' gestation with singleton pregnancy and cephalic presentation
Exclusion: cervical dilatation more than 5 cm, evidence of cephalic disproportion, utero placental insufficiency, any medical/surgical complications

Interventions

Preload not mentioned.
Test dose 0.25% bupivacaine with adrenaline 1:200,000. Followed by 10 mL bolus of 0.15% bupivacaine and 30 micrograms fentanyl. If further analgesia required after 2 hrs same bolus given. If within 2 hrs the fentanyl reduced to 15 µg, if > 2 top‐ups requested in 1 hr, a continuous infusion of 0.1% bupivacaine and 1 µg fentanyl per mLbegun at rate of 10 mL/hr.
Meperidine: 50 ‐ 100 mg IM depending on maternal weight, repeated 4‐hourly.
If analgesia requested in < 4 hrs, 1 of above dose is given. Each injection of meperidine is given with 25 mg promethazine. No meperidine is given after cervical dilatation of 8 cm.
Tramadol: IM injection of 1 mg/kg weight and not exceeding 200 mg in 24 hrs

Outcomes

Maternal: mode of delivery, pain score, maternal satisfaction with pain relief, duration of 1st and 2nd stages of labour, hypotension, urinary retention, respiratory depression, desire to use same pain relief in future
Neonatal: Apgar score, cord pH, naloxone administration

Notes

Chandigarh, India
All women received assigned allocation.
Year trial carried out not stated

Dates: Not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Tippets random table

Allocation concealment (selection bias)

Low risk

Allocation was concealed using sealed, opaque envelopes (information obtained directly from trial authors).

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2 from group I delivered by caesarean section before analgesia could be given.

Selective reporting (reporting bias)

High risk

Outcomes documented in Methods section not reported ‐ PPH and neonatal sepsis

Other bias

Low risk

None evident

Methods

RCT. Unit of randomisation not clear, probably individual

Participants

36 women (Samanta), and 20 women (Jain) randomised (epidural N = ?, tramadol N = ?).

Eligibility: pregnant women at term gestation with sonographic evidence of umbilical artery systolic‐diastolic ratio ≥ 3 (FGR)

Interventions

Epidural parturients received an incremental bolus of 10 mL ropivacaine 0.1% with 2ì/mL fentanyl followed by 5 ‐ 15 mL/hr continuous infusion of the same drug. Tramadol parturients received intramuscular tramadol 1 mg/kg repeated every 4 hrs.

Outcomes

Changes in doppler pulsality index

Apgar scores

Cord blood gases

Notes

Authors contacted for more information

Trial conducted in India but no further detail given.

Dates of trial: not stated

Funding: not stated

Conflicts of Interest: not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Infeasible to blind this intervention.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Outcome collection during labour so likely recorded by staff providing care that would be aware of allocation.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Jain reports 20 women randomised – data only analysed for 14.

Samanta reports 36 women randomised – data only analysed for 30.

Not clear how many women were in this study or why 6 were excluded post‐randomisation.

Selective reporting (reporting bias)

Unclear risk

Unable to assess from abstract

Other bias

Unclear risk

Unable to assess from abstract

Methods

3‐arm RCT with individual randomisation

Participants

90 women randomised (tramadol via epidural N = 30, tramadol IV N = 30, control N = 30)

Eligibility: 37 ‐ 41 weeks of pregnancy, primipararous and multipararous women in established active stage of labour (uterine contraction 2 per 10 mins, lasting for 30 to 40 s and cervical dilation > 3 cm) with vertex presentation and willing for analgesia

Exclusion: malpresentation, cephalopelvic disproportion, previous caesarean section, antepartum haemorrhage, any medical complications (diabetes, asthma, primary pulmonary hypertension, hypertensive disorders of pregnancy, etc.)

Interventions

Tramadol via epidural: tramadol in doses of 1 mg/kg body weight along with 8 ‐ 10 mL of 0.25% bupivacaine was given by epidural route, N = 30

Tramadol IV: tramadol in doses of 1 mg/kg body weight IV bolus and 100 mg in 500 ml Ringer’s lactate drip at the rate of 8 ‐ 24 drops/min was given, N = 30

Control Group: control not described. No information whether women in the control group received any analgesia or whether they were denied analgesia (all of this group reported moderate to intolerable pain), N = 30

Outcomes

Pain intensity

Satisfaction with pain relief

Spontaneous birth

Notes

No information whether women in the control group received any analgesia or whether they were denied analgesia (all of this group reported moderate to intolerable pain).

Conducted in the Department of Obstetrics & Gynaecology, S.N.Medical College, Agra, India

Dates of trial: not stated. Study accepted by journal 2010

Funding: not stated

Conflicts of Interest: not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

States “randomly divided”, although also says that the study group was subdivided into 2 groups. Not clear whether this was done randomly or not, or how many went into each group (although in tables results are reported for 30 women in each group).

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Infeasible to blind women or staff

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Not mentioned – probably high, as outcomes relate to labour and staff providing care would also have recorded outcomes.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Appears to report all, but numbers in each group not clearly stated. Not clear in tables whether all data are reported. Unclear if ITT

Selective reporting (reporting bias)

Unclear risk

Outcomes not prespecified in Method text

Other bias

Unclear risk

Similar baseline characteristics. The methods were generally not clear

Methods

RCT with individual randomisation

Participants

192 women randomised (epidural n = 94; pethidine n = 98)

Eligible: women in labour with ASA 1 ‐ 11, gravida 2 ‐ 5 with tested pelvis, spontaneous onset of labour, age between 18 ‐ 40 years old, singleton fetus with cephalic presentation, presenting OS 3 ‐ 5 cm, height more than 150 cm, and weight less than 100 kg

Excluded: bad obstetric history, post‐date, history of allergy to local anaesthetic, patient refusal, failed epidural and those who had contraindications for epidural analgesia

Interventions

Epidural (n = 94)

Received IV fluid bolus of at least 500 mL of Ringer’s Lactate solution. Lumber epidural analgesia was achieved using an indwelling catheter inserted by 18‐gauge Tuohy needle at L2 ‐ L3 or L3 ‐ L4 interspaces. A 3‐mL test dose of 0.2% ropivacaine was given followed by a bolus dose making the total dose of 12 mL. This was followed by continuous epidural infusion of 0.2% ropivacaine with 2 ug/mL fentanyl at 7 ‐ 10 mL/hr.

Pethidine IM (n = 98)

75 ‐ 100 mg IM pethidine with 25 mg promethazine hydrochloride at first request of pain relief. Additional 75 mg of pethidine were given by request to a maximum of 300 mg in 4 hrs.

Both groups were able to self‐administer nitrous oxide.

Outcomes

Mode of birth

Oxytocin administration

Apgar scores

Pain score

Satisfaction score

Duration of labour

Notes

Setting: hospital setting in Malaysia

Dates of trial: 2005 ‐ 2006

Funding: Universiti Sains Malaysia short‐term grant no. 304/ppsp/613131

Conflicts of interest: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

“A trained staff nurse would choose an envelope to allocate the patient randomly (closed envelope technique).”

Allocation concealment (selection bias)

Unclear risk

“A trained staff nurse would choose an envelope to allocate the patient randomly (closed envelope technique).”

It was not stated how the sequence was generated, whether the envelopes were sealed, in sequential order and all accounted for.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Authors say women were blinded to the expected effects of epidural but they cannot have been blind to intervention.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Not clear who recorded outcomes, assuming it was care provider in labour

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up reported, data reported for each participant. It was not stated if there were any missing data for any outcomes.

Selective reporting (reporting bias)

Low risk

Outcomes prespecified in the Methods are all reported clearly. We did not have a study protocol. All expected outcomes reported.

Other bias

Unclear risk

Baseline characteristics similar in both groups. The clinical management of women in the 2 groups varied and this made it difficult to interpret some results.

Methods

RCT with individual randomisation

Participants

86 women randomised (epidural n = 42; inhaled nitrous oxide n = 44)

Eligibility: nulliparous women, consent given for analgesia, no contraindication for vaginal delivery, single pregnancy, gestational age ≥ 37 weeks, cephalic presentation, active phase of labour (cervical dilatation 3 ‐ 5 cm with contractions occurring at least once every 3 mins), no contraindication for regional analgesia (coagulopathy disorder, infections in the site of catheter insertion, and haemodynamic instability)

Excluded: labour arrest, maternal or fetal problems which need caesarean, previous caesarean

Interventions

Epidural (n = 42)

Epidural group were placed in sterile conditions, and after hydration by 500 mL ringer lactate, epidural was entered to epidural space from lumbar site L3 ‐ L4 or L4 ‐ L5 with Tuohy needle size 18, then it was entered 4 ‐ 6 cm into the space and then epidural needle was removed and catheter was fixed in the site using suture. The participant was controlled in the view of labour development and fetal heart monitoring. When dilatation was 5 cm, 1st dose including bupivacaine 0.125%, fentanyl 1 μg/mL in volume of 8 ‐ 10 mL was injected at the beginning. Then dilution solution was infused with speed of 8 ‐ 15 mL/h related to the participant’s need. If it was required, the concentration of bupivacaine was increased to 0.25%.

Inhaled nitrous oxide (n = 44, data for 42)

Inhaled nitrous oxide by a mask simultaneously with beginning of feeling contraction by mother. In pain intervals, mask was removed and room air was inhaled by mother.

"2 mothers didn't continue the study due to giddiness and they were excluded from the study."

Outcomes

Satifaction with pain relief

Mode of birth

Notes

Describe setting: hospital setting in Iran

Dates of trial: 10 May 2010 – 10 May 2011

Funding: Women’s Health Research Center of Mashhad University of Medical Sciences

Conflicts of interest: not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomly divided into 2 groups by means of random numbers of calculator

Allocation concealment (selection bias)

Unclear risk

Concealment not mentioned

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Infeasible to blind

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Not mentioned, assuming not blinded and caregiver collected information

Incomplete outcome data (attrition bias)
All outcomes

High risk

2 women withdrew consent following randomisation – no reason given. Women who had a caesarean section for fetal distress were excluded, although unclear how many women this applied to. 2 women were excluded due to ‘giddiness’ in the Entonox group. Difficult to assess this domain due to poor reporting.

Selective reporting (reporting bias)

Unclear risk

Protocol not available and although outcomes are reported as prespecified in Methods section, outcome data are not reported clearly

Other bias

Unclear risk

Similar baseline characteristics but poor reporting

Methods

RCT

Parallel design

China

Participants

75 voluntary pregnancies were randomised: group A (N = 25), Group B (N = 25), Group C (N = 25).

Eligibility: ASA I ‐ II, primiparous with completely normal pregnancy and labour stage of cervical os opening 2 ‐ 3 cm
Exclusion: not reported (abstract only)

Interventions

Group A (N = 25) ‐ control ‐ no medicine to ease pain

Group B (N = 25) ‐ epidural analgesia ‐ combination of ropivacaine and fentanyl firstly with a dose of 10 mL by way of cavitas epiduralis, then additional 5 mL was carried over with the assurance of uncavitas subarachnoidealis

Group C (N = 25) ‐ CSE analgesia

Outcomes

1. Pain intensity ‐ (presents VAS scores ‐ but does not mention pain?)

2. Length of 1st active stage of delivery

3. Length of 2nd stage of delivery

4. Length of 3rd stage of delivery

5. Caesarean section

6. Apgar score at 1 and 5 minutes

7. Blood volume of parturients

8. Level of PGE₂

9. Level of NO from cord blood

Notes

Data limited as only abstract available.

Dates: Not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Abstract only available

Allocation concealment (selection bias)

Unclear risk

Abstract only available

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Abstract only available. Insufficient information

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Abstract only available. Insufficient information

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Abstract only available

Selective reporting (reporting bias)

Unclear risk

Abstract only available

Other bias

Unclear risk

Abstract only available

Methods

Reported to be randomised trial with individual women randomised.

Participants

120 women randomised (epidural PCEA, N = 30; PCIA ondansetron, N = 30; Acu‐stimulation, N = 30; no analgesia, N = 30)

Eligibility: no previous poor obstetric outcome, no experience of Hans acupoint nerve stimulator and TENS, term pregnancy (> 37 weeks’ gestation), active stage of 1st stage with cervical dilatation 3 cm

Exclusion: allergy to study drugs, maternal morbidity such as mental or neurological disease affecting evaluation of pain, pregnancy complications such as gestational hypertension, gestational diabetes, gestational thyroid disease, had already taken analgesia or had long‐term use of analgesic drugs, had already used sedative drugs in labour, had low or high BMI (< 18.5 or > 25 kg/m²)

Interventions

3 study groups: all treatments stopped at full dilatation.

30 women in each

Group 1 ‐ epidural PCEA. Combined spinal 3 mg ropivacaine, epidural 100 mL 0.1% ropivacaine and 50 mcg of sufentanil; background infusion 5 mL, PCA dose 5 mL with 10 minute lockout

Group 2 ‐ PCIA ondansetron 8 mg, 5 mins later 1.5 mg/kg tramadol, with 50 mL 0.7 tramadol and 8 mg ondansetron background and 2 mL PCA dose, with 10‐min lockout

Group 3 ‐ Acu‐stimulation. Pulse stimulus at acupoints – Jiaji points (T 10 ‐ L3) and Ciliao (BL 32). 100 Hz with burst frequency 2 Hz, intensity 15 ‐ 30 mA, pulse duration 30 minutes

Group 4 ‐ control. No analgesia

Outcomes

Pain

Duration of labour

Mode of birth

Oxytocin augmentation

Maternal hypotension

Side effects

Neonatal asphyxia

Notes

Trial conducted at hospital in Bejing, China.

Dates of trial: August 2010 – November 2013

Funding: not stated

Conflicts of Interest: not reported

Data from groups 2, 3, and 4 combined to form overall comparison group.

Maternal hypotension EA 1/30, Control 0/90

Neonatal asphyxia EA 1/30, Control 6/90

Pain after 1 hour EA 20 (6), Acu 65 (12), Opiate 45 (8), Control 97 (14)

Duration of 1st stage EA 423.3 (181.2), Acu 430.1 (119.8), Opiate 425.2 (198.7), Control 439.6 (200.3)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Reports using random‐number tables

Allocation concealment (selection bias)

Unclear risk

Not described, reports using random‐number tables but there were 4 equal‐sized study groups (30 women in each)

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Participants and caregivers would be aware of interventions.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Not reported although most outcomes were recorded in labour by staff providing care.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

There were some discrepancies between tables, While the study flow diagram suggests there were 40 women in each group, the results tables report results for 120 women (30 in each group). There was no report of any missing data. The denominators for mean duration of labour appear to include all women (i.e. women having CS were not excluded).

Selective reporting (reporting bias)

Unclear risk

No protocol. There was no power calculation.

Other bias

Unclear risk

Groups appeared similar at baseline. The equal‐sized study groups, discrepancies between tables and lack of clarity regarding denominators make the results difficult to interpret.

Methods

Multicentre open‐label randomised trial with individual randomisation (described as randomised equivalence trial) in 18 midwifery practices in the Netherlands, positioned within the Dutch Obstetric Consortium for women’s health research

Participants

418 randomised before labour (IV remifentanil, n = 208; epidural, n = 210).

Eligibility: low‐risk women beyond 32 weeks of gestation under the care of primary‐care midwives were eligible.

Excluded: women < 18 years, women with a contraindication for epidural analgesia or a hypersensitivity to opioid and women in whom labour had already started were not eligible.

Interventions

Intravenous remifentanil patient‐controlled analgesia (RPCA) (n = 208 – 203 analysed): Intravenous remifentanil 30‐lg boluses (solution 20 lg/mL) with a lockout time of 3 mins and without background infusion. A doctor or a midwife and a nurse were responsible for providing and monitoring the RPCA. The RPCA was administered by the parturient herself after instruction on how to use RPCA in the most beneficial way, which is to use the bolus dose just before the anticipated contraction. It was possible to increase the bolus dosage to 40 lg in case of insufficient pain relief, or to decrease the dose to 20 lg in case of excessive side effects.

Epidural anaesthesia (n = 210 – 206 analysed): EA with a loading dose of 25 mg (12.5 mL ropivacaine 0.2%) and continuous infusion of ropivacaine 0.1% plus sufentanil 0.5 lg/mL was administered. Continuous infusion was used at a variable rate defined by the anaesthetist and the local protocol. Additional boluses were used for inadequate levels of analgesia.

Outcomes

Pain intensity

Satisfaction

Mode of birth

Maternal respiratory depression

Headache

Fever

PPH

Apgar scores

Duration of 2nd stage

Notes

Country and setting: Netherlands

Dates of trial: November 2012 ‐ June 2013

Funding: no funding sources stated. “For this study we did not receive funding or supplies (such as financial supply or supply of drugs).”

ZonMW (www.zonmw.nl)
Dossier number 80‐82310‐97‐11039

Conflicts of interest: stated on website – cannot find.

Only 94/203 received RPCA, and 76/206 received EA ‐ authors contacted for more information.

Data for pain intensity reported as "area under the curve" ‐ unusable data. Reports that "among women who actually received analgesia scores for satisfaction with pain relief were significantly lower in the rPCA group compared with the EA group."

23/94 women in Epidural group, and 35/76 women in rPCA reported satisfaction with analgesia.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Performed using a web‐based randomisation programme stratified for midwifery practice and parity

Randomisation was done before labour.

Allocation concealment (selection bias)

Unclear risk

"Both the woman and the midwife knew the randomisation allocation in case a request for pain relief should occur during labour."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Women and midwife knew the randomisation allocation. Not feasible to blind these interventions.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Not mentioned, assumed not blinded.

Incomplete outcome data (attrition bias)
All outcomes

High risk

9 removed after randomisation for elective section (5 in RPCA group, 4 in EA group).

“If analgesia with the randomly allocated pain method was insufficient according to the woman, a switch to the other trial arm was allowed.”

Reported to be intention‐to‐treat with only ElCS women excluded from analysis, although side effects were only reported for those women receiving allocated intervention? There were missing data for some outcomes.

Some outcomes were only reported for the women who received the analgesia. We used number randomised for this review.

Selective reporting (reporting bias)

Unclear risk

All outcomes reported. The primary outcome was changed before analysis from satisfaction with pain relief at given time points to area under the curve.

Other bias

Unclear risk

Similar baseline characteristics

94/203 women in RPCA group received analgesia (105 requested pain relief).

76/206 women in epidural group received analgesia (101 requested pain relief).

Results from this study were very difficult to interpret as fewer than half of the women received the allocated intervention.

(Authors contacted for more information)

Methods

"Randomly divided into 3 groups." No further information. Intention‐to‐treat analysis used. All women accounted for

Participants

80 women recruited (CSE N = 30, tramadol N = 20, no analgesia N = 30).

Eligibility: women at 37 ‐ 41 weeks' gestation in spontaneous, uncomplicated labour, aged between 23 and 32 years, ASA I ‐ II and expected to have vaginal delivery
Exclusion: ASA physical status at least III, clinical contraindications to epidural

Interventions

Group 1 CSE: preload not mentioned, spinal administration of 2.5 mg ropivacaine with 5 micrograms of fentanyl. Epidural mixture of 0.1% ropivacaine and 1.5 micrograms of fentanyl PCEA infusing at 4 mL/h with PCEA dose of 4 mL and lockout time of 15 mins
Group 2 Tramadol: 1 mg/kg loading dose IV followed by PCIA with 0.75% tramadol. PCA dose of 2 mL infusing at 2 mL/hr with 10 mins lockout, maximum dose of 400 mg. 5 mg navoban given IV to prevent nausea and vomiting
Group 3 received no analgesia.

Outcomes

Maternal: pain scores, motor block assessed with modified Bromage score, duration of 1st and 2nd stages of labour, caesarean section, sedation, nausea and vomiting, urinary retention, post‐dural puncture headache
Neonatal: Apgar score

Notes

Beijing, China
Paper does not state if any women did not receive their allocated treatment.

Trial did not record side effect data for no‐analgesia group.

Dates: Year trial carried out not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Participants randomly divided in to 3 groups.

Allocation concealment (selection bias)

Unclear risk

Insufficient information

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Insufficient information

Selective reporting (reporting bias)

Low risk

All outcomes in the Methods section have been reported on in the Results section.

Other bias

Unclear risk

Insufficient information

Methods

Computerised random‐number allocation, sealed, opaque envelopes. Intention‐to‐ treat analysis used; however, backache (at 6 months) analysed on data of women who responded to questionnaire only. Secondary analysis based on actual analgesia received. All women accounted for, with the exception of backache (17% loss to follow‐up at 6 months).

Participants

614 women recruited (epidural N = 304, pethidine N = 310).
Eligibility: nulliparous women with term singleton pregnancy, cephalic presentation, in spontaneous or induced labour, with no evidence of cephalic pelvic disproportion
Exclusion: any medical/obstetric complications.

Interventions

Epidural: 0.25% bupivacaine 10 mL followed by infusion of 0.125% bupivacaine at 10 mL/hr until 2nd stage Lignocaine 2% was administered for instrumental or caesarean delivery
Pethidine: 100 mg IM injection

Outcomes

Maternal: mode of delivery, long‐term backache, duration of 1st and 2nd stages of labour, oxytocin augmentation, pain scores
Neonatal: admission to NICU

Notes

Northwick Park, England
86 (28%) women randomised to pethidine received epidural as well. 89 (29%) of women on pethidine received epidural instead and 3 used Entonox.
13 (4%) women randomised to epidural received pethidine as well, 44 (14%) received pethidine alone and 3 used Entonox alone.

Dates: Trial carried out 1992 ‐ 1995

Funding: National Health Service Executive, North Thames

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computerised number generation

Allocation concealment (selection bias)

Low risk

Sealed opaque envelope

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants analysed in their original groups with no loss

Selective reporting (reporting bias)

Low risk

All outcomes in the Methods section have been reported on in the Results section.

Other bias

Low risk

No obvious signs of other bias

Methods

Computer‐generated numbers, in opaque, sealed envelopes
Intention‐to‐treat analysis used. All women accounted for

Participants

738 women randomised (epidural N = 372, meperidine PCIA N = 366)
Eligibility: parous and nulliparous women with PIH (diastolic at least 90 mmHg) in spontaneous or induced labour 20 women in the epidural group and 18 in the control group had gestation < 36 weeks.
Exclusion: chronic hypertension, or received any analgesia/sedation prior

Interventions

Epidural: preload with 500 mL sodium lactate. Epidural analgesia achieved with boluses of 0.25% bupivacaine to T10 level of sensory analgesia, followed by continuous infusion of 0.125% bupivacaine with 2 mg/mL of fentanyl titrated to maintain analgesia
Meperidine: IV bolus of 50 mg meperidine with 25 mg promethazine followed by PCA infusion up to 15 mg every 10 mins
All women received a loading dose of IM magnesium sulphate 10 g and maintenance dose of 5 g every 4 hrs to prevent eclampsia

Outcomes

Maternal: duration of 1st and 2nd stages of labour, hypotension, fever, oxytocin augmentation, mode of delivery, ephedrine use, pulmonary oedema, postpartum oliguria, postpartum weight loss
Neonatal: Apgar scores, umbilical artery pH, naloxone administration, birthweight, NICU, ventilation/24 hrs

Notes

Texas, USA
3 women in each group required additional analgesia.

Dates: Trial carried out 1996 ‐ 1998

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Low risk

Sealed, numbered opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

77 women did not receive treatment as specified by the protocol, but analyses were reported as to intention‐to‐treat.

Selective reporting (reporting bias)

High risk

Outcomes documented in Methods section not reported ‐ serial laboratory values that included haematocrit level, platelet count, creatinine level, and liver enzymes.

Other bias

High risk

Nulliparous women, more of whom were assigned to the PCIA group (P = 0.005).

Methods

"Randomised into 2 groups", no further information given. Intention‐to‐treat analysis used

Participants

129 women recruited (epidural N = 69, no analgesia N = 63)
Eligibility: primiparous women in "beginning of active phase of labour".

Interventions

Epidural bupivacaine versus no analgesia. No further information in abstract

Outcomes

Maternal: duration of 1st and 2nd stages of labour, pain scores
Neonatal: Apgar scores, Silverman score

Notes

Sinaloa, Mexico
Paper does not state if any women did not receive their allocated treatment.

Dates: Trial carried out 1997 ‐ 1998

Funding: Not stated in translation

Declarations of Interest: Not stated in translation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomised into 2 groups

Allocation concealment (selection bias)

Unclear risk

Randomly divided

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Insufficient information

Selective reporting (reporting bias)

Low risk

All outcomes in the Methods section have been reported on in the Results section.

Other bias

Unclear risk

Insufficient information

Methods

RCT

Double‐blind, randomised, cross‐over fashion

Single centre

University of Saskatchewan, Canada

Participants

100 labouring parturients assigned to IV fentanyl group (N = 50) or the epidural fentanyl group (N = 50)

Eligibility: ASA I and II labouring parturients requesting epidural
Exclusion: "There were no specific exclusion criteria apart from drug allergy".

Interventions

IV fentanyl group (N = 50) ‐ 100 µg fentanyl IV and saline by an epidural catheter

Epidural fentanyl group (N = 50) ‐ saline IV and 100 µg fentanyl by an epidural catheter

Outcomes

1. Correct guess of route of administration of the fentanyl by anaesthetists

2. Blood pressure systolic

3. Pulse rate

4. O₂ saturation

5. Fetal heart rate

6. Apgar score at 1 minute, 5 minutes

7. Symptoms of sedation or dizziness in response to fentanyl administration

Notes

Single centre ‐ Canada

Cross‐over ‐ at 2 hrs those participants who had not yet delivered were crossed over to the other study medication by the alternate route. Out of 100 labouring parturients, 41 crossed over to receive fentanyl by the alternate route ‐ does not specify how many from each group crossed over.

Dates: Not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported

Allocation concealment (selection bias)

Low risk

An anaesthetist initially prepared the syringes with either fentanyl or saline. These were then allocated by a separate study nurse: "These syringes together with labels enclosed in a randomisation envelope were given to an attending nurse who then re‐labelled the syringes, "epidural" or "intravenous", according to instructions within the envelope".

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Described as "double blind".

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

"An anaesthetist blinded to the route of administration questioned each patient with regard to changes in analgesia, level of sedation, dizziness, or euphoria. He or she then guessed as to whether this patient had received intravenous fentanyl" within abstract.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants randomised appear to have been accounted for within the results ‐ although 41 crossed over and it does not specify from and to which group.

Selective reporting (reporting bias)

Low risk

All prespecified outcomes reported within the Methods section are available within the Results.

Other bias

Low risk

Baseline characteristics of groups were similar ‐ "There were no differences between the groups at initial randomisation with regard to age, height, weight, parity, or racial origin (Table I)".

Methods

Women "prospectively randomised", no further information given

Participants

50 women recruited (epidural N = 28, meperidine N = 22)
Eligibility: uncomplicated primiparous women in spontaneous labour

Interventions

Epidural method: preload not stated
Bupivacaine 0.125% with adrenaline, 10 ‐ 15 mL, plus pethidine 25 mg, followed by PCA (bupivacaine 0.125% with adrenaline plus pethidine 0.5 mg/mL, 4 mL boluses, lockout 15 mins)
2nd stage: epidural use not stated
Control method: IV pethidine by PCA pump (up to 1 mg/kg loading dose, followed by 10 mg boluses, lockout 10 mins

Outcomes

Maternal: pain scores, motor and sensory block, duration of labour, cervical dilation, use of oxytocin, mode of delivery, maternal satisfaction, temperature
Neonatal: Apgar score, cord pH < 7.15 (epidural 1/28, control 2/22) and NACS score at 2 and 24 hrs

Notes

Canada
11 (50%) women randomised to meperidine received epidural.
An additional 3 women were enrolled into the trial, all were excluded for technical or equipment failures (group not stated).

Dates: Year trial carried out not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomised

Allocation concealment (selection bias)

Unclear risk

Randomised

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Insufficient information

Selective reporting (reporting bias)

High risk

Outcome documented in Methods section not reported ‐ oxytocin use

Other bias

Unclear risk

Insufficient information

Methods

Participants randomly assigned to receive PCEA or PCIA. Computer‐generated random number system concealed in consecutively‐numbered sealed, opaque envelopes (further information was obtained directly from trial authors).
Intention‐to‐treat analysis was used. All women accounted for

Participants

185 women recruited (epidural = 97, IV fentanyl = 88)
Eligibility: healthy, nulliparous, spontaneous labour, requesting analgesia
Exclusions: any condition known to increase incidence of operative delivery

Interventions

Epidural: 0.08% bupivacaine + 1.67 mcg/mL fentanyl ‐ loading dose of 10 ‐ 15 mL followed by 5 mL every 10 minutes as needed
IV fentanyl ‐ loading dose of 1 ‐ 2 µg followed by 50 µg every 10 mins as needed

Outcomes

Maternal: pain scores, satisfaction with analgesia, need for further analgesia, duration of analgesia, caesarean section rate
Infant: Apgar scores, NICU admission, cord pH, neuro‐adaptive scores, cord fentanyl levels

Notes

Canada. Multicentre trial. 18 (20%) women in the IV fentanyl group received an epidural also.

Dates: Year trial carried out not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomised

Allocation concealment (selection bias)

Low risk

Computer‐generated random‐number system concealed in consecutively‐numbered sealed, opaque envelopes (further information was obtained directly from trial authors).

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Insufficient information

Selective reporting (reporting bias)

High risk

Safety outcomes documented in Methods section not reported.

Other bias

Unclear risk

Insufficient information

Methods

"Randomised" method not specified
Intention‐to‐treat analysis used. All women were accounted for.

Participants

20 women recruited (epidural N = 10, fentanyl N = 10)
Healthy primigravidas, aged 20 ‐ 35 years
Exclusion: complications of pregnancy, regular use of drugs and chronic disease

Interventions

Epidural: preload unknown
6 mL 0.5% bupivacaine initially. Intermittent top‐ups with 4 mL (only 1st stage)
IV narcotic: fentanyl 50 mg initially. PCA delivered. 20 mg boluses (only 1st stage)

Outcomes

Maternal: VAS pain score, side effects, length of labour after analgesia, mode of delivery, heart rate, oxygen saturation
Fetal/neonatal: CTG variability, Apgar score, cord pH arterial and venous, Amiel‐Tison's neurological score, birthweight

Notes

Finland
4 (40%) women randomised to fentanyl received epidural as well

Dates: Not stated

Funding: "supported by funds from Instrumentarium Research Foundation, Finland and funds from Turku University Hospital, Finland"

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomised

Allocation concealment (selection bias)

Unclear risk

Randomised

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

3 of 10 participants in fentanyl group received epidural because of unsatisfactory pain relief and 1 because fentanyl prolonged delivery.

Selective reporting (reporting bias)

Low risk

All outcomes in the Methods section have been reported on in the Results.

Other bias

Low risk

Methods

"Randomly assigned by random numbers, contained in sealed, consecutively opened envelopes."
1 woman in non‐epidural group lost to follow‐up. Intention‐to‐treat analysis used

Participants

112 women recruited (epidural N = 57, pethidine N = 55)
Eligibility: 37 ‐ 42 weeks' gestation, no medical/obstetric abnormality, in early spontaneous labour, no scars on uterus, 104/112 primiparous

Interventions

Epidural method: preload given. Bupivacaine 0.375% (1 mL per 10 kg) by intermittent top‐up. T10 ‐ L1 block.
2nd stage: epidural use discontinued
Control method: pethidine 75 mg IM (x 1 ‐ 2)

All women offered nitrous oxide/oxygen inhalation on demand, and pudendal block (20 mL mepivacaine) in 2nd stage

Outcomes

Maternal: pain, hypotension, nausea and vomiting, urinary retention, sleepiness, motor blockade, length of 1st stage of labour, duration of 2nd stage of labour, position of fetal head at delivery, mode of delivery, maternal memory of labour
Fetal/neonatal: fetal heart rate abnormality, Apgar score at 5 minutes, cord venous pH, neurobehavioural abnormalities

Notes

Denmark
9 (16%) women randomised epidural and 29 (53%) women randomised pethidine had entonox also.

Dates: Year trial carried out not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomly assigned

Allocation concealment (selection bias)

Unclear risk

Sealed, consecutively opened envelopes.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No participant loss

Selective reporting (reporting bias)

High risk

Additional outcomes reported in tables not specified in the Methods section.

Other bias

High risk

9 participants in the epidural group and 29 in the pethidine group used nitrous oxide. The participants' pain scores in stage 2 were found equal in the 2 groups, 86% in the pethidine versus 85% in the epidural group had a pudendal block.

Methods

RCT

Parallel design

Single centre

Riyadh, Saudi Arabia

Participants

30 pregnant women were randomised to Group EP (N = 15) ‐ epidural or Group R ‐ (N = 15).

Eligibility: ASA I or II with no obstetric complications or contraindication to remifentanil or epidural analgesia
Exclusion: not reported

Interventions

Group EP (N = 15) ‐ epidural analgesia ‐ epidural infusion of bupivacaine 1% plus 2 µg/mL of fentanyl

Group R (N = 15) ‐ PCA remifentanil ‐ with a bolus of 0.4 µg kg‐1 over 20 s and a lockout period of 1 min as an analgesia for labour

Outcomes

1. Pain intensity (pain relief ‐ VAS)

2. Arterial blood pressure, heart rate, oxygen saturation

3. Satisfaction with childbirth experience (overall parturient's satisfaction)

4. Side effects (for mother and baby: nausea, bradycardia, hypotension, desaturation, sedation scores, fetal heart rate change)

5. Apgar scores at 1 and 5 mins

6. Umbilical cord gases

7. Lactate levels

Notes

Abstract only, so data limited

Dates: Not stated

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not reported

Selective reporting (reporting bias)

Unclear risk

Not reported

Other bias

Unclear risk

Not reported

Methods

RCT

Parallel design

Single centre

University of Texas Southwestern Medical Center, Dallas

Participants

1330 women with uncomplicated term pregnancies were randomised to be offered epidural (N = 664) or IV analgesia (N = 666) ‐ 65% of each randomisation group accepted the allocated treatment ‐ epidural group (N = 432), IV group (N = 437).

Eligibility: women with normal pregnancies presenting in spontaneous labour
Exclusion: women with an identified pregnancy complication, cervical dilatation > 5 cm, or other than singleton cephalic gestations were excluded.

Interventions

Epidural analgesia ‐ epidural bupivacaine‐fentanyl ‐ at participant's 1st request for pain relief, a 3 mL test dose of 0.25% bupivacaine was given, followed by further 3‐mL increments to achieve a bilateral T‐10‐ sensory level. This was followed by a continuous epidural infusion of 0.125% bupivacaine with 2 µg/mL fentanyl at 8 ‐ 10 mL/hr. The infusion was titrated to achieve a maximum T‐8 sensory level. Additional boluses of fentanyl or bupivacaine or both were injected to overcome inadequate analgesia.

IV analgesia ‐ IV meperidine ‐ 50 mg with 25 mg of promethazine hydrochloride IV at 1st request for pain relief. Additional 50 mg doses of meperidine were given on request, to a maximum of 200 mg in 4 hrs. When pain relief was inadequate, epidural analgesia was administered on patient request.

Outcomes

1. Pain intensity (10 cm visual analogue pain scale score ‐ repeated hrly until delivery from 1st request of analgesia)

2. Satisfaction with pain relief (24 hrs after delivery ‐ 5‐point descriptive scale ‐ excellent, very good, good, fair or poor)

3. Duration of labour

4. Amniotomy

5. Augmentation of labour using oxytocin

6. Spontaneous delivery

7. Assisted vaginal birth (forceps)

8. Caesarean section

9. Side effects (for mother and baby; chorioamnionitis, hypotension, uterine infection, meconium‐stained amniotic fluid, infant seizure within 24 hrs birth, intubation in delivery room, Group B streptococcal sepsis)

10. Apgar score < 3 at 1 min and 5 mins and < 6 at 5 mins

11. Umbilical artery blood pH

12. Birthweight

Notes

Single centre, Dallas, USA

2680 offered participation, 1330 (51%) accepted. 1279 who did not consent to participate were demographically similar to those accepting of 1330 ‐ 664 randomised to epidural ‐ but 232 (35%) never received allocated treatment ‐ half had refused offer of epidural and the remainder progressed to delivery before epidural analgesia could be initiated. 666 women randomised to meperidine IV, but 229 (34%) were not treated ‐ 103 of this group requested epidural after finding meperidine to be inadequate.

Dates: Trial carried out November 1 1993 ‐ April 30 1994

Funding: Not stated

Declarations of Interest: Not stated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"The randomisation sequence was computer‐derived in blocks of 20."

Allocation concealment (selection bias)

Low risk

Women were randomly assigned using numbered, sealed opaque envelopes.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not reported

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

There was a substantial loss of participants from both groups due to them not following the allocated protocol (35% loss in epidural group, 34% loss in the IV group). All but 1 set of results are therefore based on the available data ‐ operative delivery for dystocia was only outcome analysed on an intention‐to‐treat basis "when comparing the two groups on an intention‐to‐treat basis".

However, they do say that a "multivariate analysis of the entire cohort was performed to control for confounding effects of other variables, particularly parity." The results of this cohort analysis are consistent with the labour outcome difference observed between the 2 allocation‐compliant treatment groups for the outcomes of caesarean section and operative delivery for dystocia.

Selective reporting (reporting bias)

High risk

Hypotension ‐ described as an outcome in Methods ‐ but not within the Results. All other prespecified outcomes reported within the Methods section are available within the Results.

Other bias

Low risk

None evident

Methods

Randomised controlled trial (prospective parallel single‐blind) with individual randomisation

Set in hospital in Egypt.

Participants

60 women randomised to receive combined spinal epidural or epidural with bupivacaine or lidocaine (10 women received each method), or IV pethidine (20 women).

Full‐term nulliparous women in active labour with cervical dilatation of 5 cm and cephalic‐presenting fetus.

Exclusion criteria: women who had diabetes, neurological disease, pre‐eclampsia, or those who received parenteral analgesics or those with contraindication to epidural or spinal analgesia, or sensitivity to local anaesthetics or opioids were excluded

Interventions

Group 1 (CSE1) – CSE, bupivacaine, (n = 10): CSE analgesia, 25 µg fentanyl were injected intrathecally and a bolus dose of 10 mL of 0.5% lidocaine injected epidurally. Top‐ups of 5 ‐ 10 mL of 0.5 ‐ 0.8% of lidocaine injected epidurally upon request

Group 2 (CSE2) – CSE, lidocaine (n = 10): received CSE analgesia, 25 µg fentanyl were injected intrathecally and a bolus dose of 10 mL of 0.0625% bupivacaine injected epidurally. Top‐ups of 5 ‐ 10 mL of 0.0625 ‐ 0.8% of lidocaine injected epidurally upon request

Group 3 (E1) – Epidural, bupivacaine (n = 10): received epidural analgesia, 50 µg fentanyl were injected epidurally together with a bolus dose of 10 mL of 0.5% lidocaine. Top‐ups of 5 ‐ 10 mL of 0.5 ‐ 0.8% of lidocaine injected epidurally upon request

Group 4 (E2) – Epidural, lidocaine (n = 10): received epidural analgesia, 50 µg fentanyl were injected epidurally together with a bolus dose of 10 mL of 0.125 – 0.25% bupivacaine injected epidurally upon request

Group 5 (IV) (n = 20): 50 mg of IV pethidine administered as a loading dose, followed by 0.5 mg/kg, with a maximum limit of 130 mg

4 epidural groups were combined in data and analysis, and compared with IV pethidine.

Outcomes

SD for VAS pain score, number of top‐ups, degree of motor block

Notes

Dates of trial: January 2008 – January 2009

Funding: self‐funded

Conflicts of interest: none

Maternal hypotension EA: 9/40; IV 0/20

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described