Effect of Different Labour Analgesics on Maternal UtA, Fetal UA and MCA Blood Flow Index Observed by Doppler Ultrasonography：a Prospective Randomized Double-blinded Controlled Trial
Conditions: Labor Pain, Analgesia, Fetus Disorder
Sponsor: First Affiliated Hospital of Jinan University

Official Title:  
Effect of different labor analgesics on maternal UtA, fetal UA and MCA 
blood flow index observed by Doppler ultrasonography: A prospective 
randomized double-blinded controlled trial 
 
Document Date:  
March 1, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
Study protocol 
1. Study design  
Pregnant women of ASA grade I to II, aged 20 to 35 years, weighing 50 to 100 kg, 
150-175 cm in height, and 37 to 41 weeks of gestation were included in the study. 
Women with contraindications of spinal anesthesia, maternal complications (such as 
pregnancy-induced hypertension, preeclampsia, cardiovascular and cerebrovascular 
diseases, etc.), abnormal uterine contractions, abnormal placental function or position, 
signs of fetal distress, and known fetal malformations were excluded. The patients who 
were failed to administer combined spinal and epidural block analgesia, those who were 
transferred from vaginal trial labor to cesarean section, those who could not cooperate 
with ultrasound detection, and those who needed to use oxytocin were excluded. The 
study was planned and implemented in accordance with the Declaration of Helsinki. 
2. Randomization and blinding  
90 parturients in the study were randomly assigned to Sufentanil group (S, n=30), 
Ropivacaine group (R, n=30) and Sufentanil added to Ropivacaine group (SR, n=30) 
by non-blind personnel according to the computer random number table, and the 
allocation was hidden. The solution was prepared by an unblinded anesthesiologist and 
packaged in a blind way and administered by another anesthesiologist. The patients, 
anesthesia providers, data recorders, ultrasound examiners, obstetrical staff, and 
nursing staff remained blinded to group assignment throughout the study.  
3. Study intervention 

At the time of request for labor analgesia, patients were randomized to receive either 
sufentanil 5 μg (Group S), ropivacaine 3mg (Group R), or sufentanil 2.5 μg added to 
ropivacaine 2.5 mg (Group SR) into the subarachnoid space. All groups received the 
standard epidural solution that contained 0.1% ropivacaine with 0.25 μg/ml sufentanil. 
Routine obstetric and anaesthetic monitoring was given after maternal entered the 
delivery room.  
An experienced the anesthesiologist select L3-4 lumbar vertebra clearance to 
puncture with standard sterile technique using loss of resistance when the puerpera 
palace has expanded to about 3 cm. After the puncture reached the epidural space, a 25-
gauge lumbar anesthesia needle was used to puncture into the subarachnoid space. 2 
mL of anesthetic drug as determined by her group randomization were administered 
into the cavity through the lumbar anesthesia needle after cerebrospinal fluid flow out. 
A 19-gauge spring-wound catheter was threaded 4-6 cm into the epidural space. All 
patients received a test dose of 3 ml of 1.5% lidocaine followed by an initial loading 
dose of 5 ml of the standard epidural solution. Epidural catheters into vessels or 
subarachnoid space were excluded. An analgesic pump (PCEA pump, 100ml) 
containing standard epidural solution was then connected to the epidural catheter at a 
background continuous infusion rate of 5 mL/h. The visual analogue score for pain 
(VAS) was performed 15 minutes after the injection dose, and if the VAS score fell 
below 3, the case was included in the study.  
An anesthesia provider assessed the adequacy of analgesia for the patients 
throughout the duration of labor. Any breakthrough pain was managed with a 
physician-administered epidural bolus. All obstetric analgesia procedures were 
performed by the same anesthesiologist to reduce errors due to technical reasons. 
4. Ultrasonic examination method 
The patients were placed in a supine position with calm breathing to perform 
doppler ultrasonography during the interval of contractions. Ultrasound probe was 

placed on fetal head area. Middle cerebral arteries (MCA) run anteriorly on both sides 
of the ring of cerebral arteries at the position of the double head diameter (see Figure 
1A). We can get waveforms of MCA examined by pulsed wave doppler (see Figure 
1B). The probe was placed at the placenta area, and we can see the fetal umbilical cord 
connecting to the center of the placenta. Umbilical artery (UA) could be identified by 
color flow, and its waveforms were examined by pulsed wave doppler (see Figure 1C 
and 1D). The probe was placed at the midpoint of the groin. The right and left uterine 
arteries (UtA) could be identified by color flow at the apparent crossover with the 
external iliac arteries, and pulsed wave doppler was used to obtain waveforms (see 
Figure 1E and 1F). 3 to 10 arterial spectrograms with clear edges and no background 
noise at baseline were selected. The above arterial blood flow indexes were measured 
three times and the average value was taken. The S/D、PI、 RI value of MCA、UA、
UtA can be measured automatically by ultrasound instrument. All doppler 
examinations were performed by the same sonographer. 
5. Primary outcomes  
The main indexes were doppler blood flow indexes (S/D, PI, RI value) of UtA, 
UA, MCA before analgesia (T0) and 30 min (T1), 60min (T2), 90 min (T3) after 
analgesia in the three groups. 
6. Secondary outcomes  
Fetal heart rate (FHR) and mean artery pressure (MAP) at T0, T1, T2 and T3, 
neonatal weight, time of each stage of labor, rate of midwifery, neonatal umbilical 
artery blood gas index and Apgar score at 1 min, 5 min, 10 min after birth of the three 
groups were included in the secondary indicators. 
7. Statistical Analysis Plan 
In this study, SPSS 13.0 was used for statistical analysis, and GraphPad Prism 8 
was used for mapping. Measurement data were expressed as mean ± standard deviation 
(x±s), and categorical data were expressed as frequency, percentage, or rate. Paired t 

test was used for intra-group comparison and independent sample t test was used for 
inter-group comparison of measurement data conforming to normal distribution. The 
measurement data with non-normal distribution were analyzed by rank sum test. Chi-
square test was used for statistical analysis of categorical data. P<0.05 indicates 
statistical significance.