Stocki 2014.

Methods	Randomised, controlled trial. Not blinded. Randomisation after onset of labour. The purpose of this trial was to compare the analgesia efficacy and maternal satisfaction of remifentanil labour analgesia with standard treatment (epidural analgesia). The study was conducted in a Jerusalem tertiary hospital labour and delivery suite from February 2010 to August 2010. Trial Identifier: NCT00801047
Participants	Participant flow: Number assessed for eligibility: 144 Number randomised: 40 (20/20) Number receiving treatment: 39 (19/20) Number analysed: 39 (19/20) Inclusion criteria: Healthy, ASA I or II, age 18 to 40 years, body weight < 110 kg, gestational age > 36 completed weeks, with singleton pregnancy and vertex presentation Exclusion criteria: Contraindication to epidural analgesia, opioid administration in the previous 2 h, previous uterine surgery, pre‐eclampsia, inability to understand the consent form, nasal obstruction for any reason, medical indication for epidural analgesia (e.g. cardiac disease, suspected difficult airway), or non‐reassuring FHR tracing Baseline details: Remifentanil group (n = 19): Age (years, mean (SD)): 31 (5) Weight (kg, mean (SD)): 72 (10) ASA I/II (n/n): NA Type of delivery (n): spontaneous (NA), vacuum delivery (2), CS (0) Week of gestation: NA Singleton, twin, multiple pregnancy: NA Parity (median (IQR) or n): 1 (1‐1), Nulliparous (4) Duration of labour: ‐ First stage of labour (min, mean (SD)): 329 (215) ‐ Second stage of labour (min, mean (SD)): 35 (41) Epidural group (n = 20): Age (years, mean (SD)): 30 (6) Weight (kg, mean (SD)): 73 (13) ASA I/II (n/n): NA Type of delivery (n): spontaneous (NA), vacuum delivery (1), CS (4) Week of gestation: NA Singleton, twin, multiple pregnancy: NA Parity (median (IQR) or n): 1 (0‐1), Nulliparous (6) Duration of labour: ‐ First stage of labour (min, mean (SD)): 404 (259) ‐ Second stage of labour (min, mean (SD)): 69 (81)
Interventions	Remifentanil group (n = 19): PCA: The bolus dose was titrated to effect from 20 µg up to a maximum of 60 µg as required; the lockout interval was initially set at 2 min, without a background infusion. The PCIA bolus/lockout interval was titrated to an endpoint of either woman's comfort or a maximal bolus dose of 60 µg/minimal lockout interval of 1 min by the recruiting anaesthesiologist at any time during labour. The PCIA pump tubing was “piggybacked” into the distal most port of the mainline IV fluid tubing. The mainline tubing contained an antireflux valve designed to prevent remifentanil inadvertently backing up in the IV line during administration. Epidural group (n = 20): A 17‐gauge Tuohy needle was inserted by the midline approach using loss of resistance to air at intervertebral space L3‐4 or L2‐3. An incremental initial loading dose of 15 mL of 0.1% bupivacaine with 50 µg fentanyl was administered followed by patient‐controlled epidural analgesia infusion of 0.1% bupivacaine with 2 µg/mL fentanyl: basal infusion of 5 mL/h, patient‐controlled bolus 10 mL, and lockout interval 20 min. Additional epidural bolus doses (either 0.1% bupivacaine 10 mL during the first stage of labour or 1% lidocaine 8 mL during the second stage of labour) were administered by the anaesthesiologist to treat breakthrough pain. If epidural analgesia failed, the epidural catheter was reinserted.
Outcomes	The primary endpoint of the study was to demonstrate non‐inferiority of remifentanil labour analgesia compared with epidural analgesia in labouring women, measured by hourly assessment of NRS for pain throughout the duration of labour and maternal satisfaction. Continuous: ‐ satisfaction with pain relief (NRS 0 to 10, at 10 min and postpartum) ‐ pain intensity (NRS 0 to 10, at 0, 30 min, 1, 2, 3, 4, 5, 6 h) ‐ newborns: Apgar score at 1 and 5 min (median + IQR + range (symmetric), data for Apgar score at 5 min dichotomised: all newborn had an Apgar score of 10 at 5 min) Dichotomous: ‐ additional analgesia after 1 h (rescue), additional analgesia (cross‐over to the other treatment arm) ‐ rate of CS, rate for assisted birth (vacuum) ‐ need for neonatal resuscitation ‐ umbilical cord BE (artery), umbilical cord pH (artery) ‐ oxytocin use ‐ sedation score (observer, awake or easily arousable at 1 h) ‐ women: apnoea (> 20 s of zero respiratory rate), respiratory depression (< 8 breaths/min), oxygen desaturation (< 94%), nausea (at 1 h and postpartum), pruritus (at 1 h and postpartum)
Notes	‐ Small trial sample size (< 200 participants) ‐ Power analysis performed (NRS pain, n = 17 per group) Concomitant medication: Women were informed before study enrolment that conversion to the other treatment would be possible at any time during labour beginning 30 min after analgesia initiation with the study technique. All women received continuous supplementary oxygen (2 L/min) through an oral‐nasal cannula. Funding: Hadassah Medical Organisation Contact to the authors: We contacted Dr. Weiniger via e‐mail (16 March 2016) to inquire the number of women who reported 'pain intensity at 30 min, 1, and 2 hours'. We received the missing data.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Randomization and group allocation were determined: cards were divided into groups of 8 cards. Each group contained 4 allocation cards for remifentanil and 4 allocation cards for epidural analgesia (ratio 1:1), and 8 opaque envelopes numbered in groups from 1 – 8, 9 – 16, etc. were assigned to each group of cards. The cards were placed face down, manually shuffled, randomly selected, and then inserted into the numbered, opaque envelopes by a person not involved in the study. These envelopes were then sealed. Treatment assignment was revealed by breaking the seal of an envelope in consecutive order from number 1.”
Allocation concealment (selection bias)	Low risk	Quote: “…inserted into the numbered, opaque envelopes by a person not involved in the study. These envelopes were then sealed. Treatment assignment was revealed by breaking the seal of an envelope in consecutive order from number 1.”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: “This randomized nonblinded controlled noninferiority study […].” The study was not blinded due to technical reasons and at least the subjective1 outcomes or outcome measurements are likely to be influenced by lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: “The investigator inquired whether opioid side effects (i.e., pruritus and/or nausea and vomiting) were present or absent.”, “After delivery, face‐to‐face follow‐up was performed on the first postpartum day for both mother and child by one of the investigators”, “Hence, the mathematician was not blinded to group allocation. However, she was blinded to our study hypothesis that remifentanil was noninferior to epidural analgesia and that remifentanil may have respiratory effects different from those seen with epidural analgesia.” The study did not adequately report on blinding of outcome assessors. Therefore, we assume that the study was not blinded due to technical reasons and at least the subjective1 outcomes or outcome measurements are likely to be influenced by lack of blinding.
Incomplete outcome data (attrition bias) All outcomes	Low risk	‐ Dropout rate: 5%/0% One woman was excluded after enrolment but before analgesia due to obstetrician request. Reasons for missing outcome data unlikely to be related to true outcome. ‐ Rate of escape (other pain relief after 1 h): 0%/17% (may influence data on AE, satisfaction and pain) ‐ Rate of cross‐over: 16%/5% ‐ Data‐analysis: Partial‐ITT ‐ Study design: non‐inferiority study (per‐protocol analysis recommended)
Selective reporting (reporting bias)	High risk	A registered protocol (NCT00801047) is available and there are several deviations. The VAS pain score was defined as primary outcome and no other primary or secondary outcomes were defined in the protocol. In the published report, however, the authors defined maternal satisfaction as another primary endpoint, and incidence of apnoea was defined as secondary outcome. The primary outcome pain score was reported on a 11‐point NRS scale in the final report. The authors further reported on SpO2, sedation, pruritus, nausea, and adverse effects on the newborn. The protocol was prospectively registered: Protocol registration: 12/2008 First enrolment: 02/2010
Other bias	Low risk	The study appears to be free of other sources of bias.