The Effect of Low-Dose vs High-Dose Epidural Fentanyl on Gastric Emptying - A Prospective Double-Blinded Randomized Controlled Trial
Phase: NA
Conditions: Effects of; Anesthesia, Spinal and Epidural, in Pregnancy, Aspiration
Sponsor: Tel-Aviv Sourasky Medical Center

THE EFFECT OF HIGH-DOSE VS. LOW-
DOSE EPIDURAL FENTANYL ON GASTRIC 
EMPTYING IN NON-FASTED PARTURIENTS 
23.09.2019 
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THE EFFECT OF HIGH-DOSE VS. LOW-DOSE EPIDURAL FENTANYL ON 
GASTRIC EMPTYING IN NON-FASTED PARTURIENTS 
A Prospective Double-Blinded Randomized Controlled Trial 
STUDY PROTOCOL 
 
 
 
This single-center, prospective blinded randomized-controlled trial will be conducted over a twelve-
month period after receiving IRB approval (IRB request number 0040-19-TLV), at the Tel Aviv Sourasky Medical 
Center (“Lis Maternity Hospital”). Written consent will be obtained upon arrival to the delivery room and 
prior to the request for epidural analgesia.  
 
Inclusion criteria: Laboring women ⩾18 years of age, ⩾37 weeks gestation with a singleton pregnancy, 
cephalad fetus, with cervical dilatation ⩽5cm and who request epidural analgesia for labor. 
 
Exclusion criteria: Contraindications to neuraxial analgesia, chronic opioid consumption, and factors 
increasing risk of cesarean delivery and/or risk of aspiration.  These include disorders of the upper 
gastrointestinal tract (severe gastro-esophageal reﬂux, history of bariatric surgery), neurological and 
endocrine disorders associated with gastroparesis (such as multiple sclerosis, diabetes with autonomic 
neuropathy), trial of labor after cesarean delivery (TOLAC), non-reassuring fetal heart rate (NRFHR), 
dysfunctional labor, estimated fetal weight >4000g,  body mass index (BMI)⩾40kg/m2.    
 
Women who received ineffective epidural analgesia, deﬁned as verbal numerical rating scale (VNRS) 
>3, thirty minutes after placement will be withdrawn from the study and will not be followed up further. 
Their subsequent management will be according to department protocol.  
1. Epidural Analgesia Protocol 
 
Laboring women will be approached and requested to enroll upon arrival to the delivery room and 
prior to their request for epidural analgesia.  Women who consent to participate will be randomized into one 
of two groups according to high versus low dose fentanyl administered in the labor epidural solution.  
 
Upon request for labor epidural analgesia, the epidural will be performed by one of the 
anesthesiologists working in the delivery room.  The epidural will be performed in the sitting or lateral 
decubitus position with a 18G Touhy needle (Portex Epidural Minipack), and upon identiﬁcation of the 
epidural space using the loss of resistance technique, the epidural catheter will be inserted.   
 
The epidural drugs will be administered according to randomization group by the anesthesiologist 
performing the epidural: 
•
Group LF - “Low dose fentanyl” - 10ml bolus: bupivacaine 0.1% + 25mcg fentanyl, followed by a 
solution of bupivacaine 0.083% + fentanyl 1mcg/ml 
•
Group HF - “High dose fentanyl” - 10ml bolus: bupivacaine 0.1% + 100mcg fentanyl,  followed by 
a solution of bupivacaine 0.083% + fentanyl 2mcg/ml 
 
Both groups will receive an identical patient controlled epidural analgesia (PCEA) protocol 
comprising a 6 ml/hour background infusion with 5ml bolus, 10min lockout time. 
  
Breakthrough pain will be treated with physician administered “top-ups” of 10 ml bupivacaine 
0.1-0.25% or 8ml lidocaine 1% to the physician’s discretion.  Women will be blinded to group allocation. 
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2. Gastric Ultrasonography (US) 
 
The Gastric US will be performed using a portable device (Sonosite Edge II) with an abdominal 
probe by the same operator (EF) for all women.  The operator will be blinded to the woman’s oral intake and 
to her randomization group. 
 
The Cross Sectional Area (CSA) of the antrum will be measured as described by Arzola et al23 in the 
supine position with the head elevated 45 degrees.  The antrum of the stomach will be identiﬁed in the 
sagittal plane using the left lobe of the liver, aorta and inferior vena cava as anatomical landmarks.  CSA will 
be calculated using the formula (AP x CC x pi)/4, where AC is the anterio-posterior diameter and CC the 
cranio-caudal diameter.   Three consecutive measurements will be performed and the average of the three will 
be used as the ﬁnal data.  The cutoff used to deﬁne a “full stomach” will be a CSA⩾381 mm2, which has been 
validated in previous studies on laboring women 22, 24.  
 
Gastric US will be performed immediately after veriﬁcation of effective epidural analgesia (T0) and 
intrapartum, two hours after the baseline measurement (T2h), corresponding to a cumulative dose of 
37-97mcg fentanyl in Group LF and 124-240mcg fentanyl in Group HF.    
3. Oral Intake Protocol 
 
At the time of consent women will be told they may eat, in line with departmental policy,  and 
encouraged to note oral intake (drink volume, food amount and type).  
4. Data Measurements 
 
Ultrasound measures: Baseline CSA at epidural placement (T0) will be measured.  The primary data 
measurements corresponding to the study aim will be CSA measured by US two hours (T2h) after baseline 
measurement. 
 
Patient characteristics: Age, parity, gestational age, BMI and smoking.  
 
Oral intake: At the time of epidural placement (T0) oral intake within the previous 8 hours will be 
recorded.  At the time of the intrapartum ultrasound (T2h), women will be asked about oral intake during the 
previous two hours. 
 
Epidural management: Number of PCEA boluses (attempts and given) and physician administered 
“top-ups” between T0 and T2h, and pain scores at T0 and T2h (VNRS scale) will be recorded. 
 
Obstetric characteristics: Cervical dilation at T0 and T2h, use of labor induction and augmentation 
agents. 
 
Other measures:  Occurrence of vomiting and use of anti-emetics. 
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STATISTICAL ANALYSIS 
 
The primary study endpoint is the CSA at T2h according to HF versus LF.  Our sample size was 
calculated on the assumption that women who receive HF will have a signiﬁcantly slower gastric emptying 
(and thus higher mean CSA) than women who receive LF14,15,16.  Based on Porter et al.14, each group requires 
at least 14 subjects in order to detect a signiﬁcant difference with a power 80% and 0.05 two-tailed 
signiﬁcance level.  However, as opposed to Porter et al. who examined only fasted women, our subjects will 
have unknown fasting status.  Thus the change in CSA from T0  to T2h among women randomized to HF 
versus LF is a relevant variable.  In order to take this into consideration, we require enough women with both 
an empty and a full stomach at T0 to calculate the change at T2h.  Previous studies on gastric US in laboring 
women have demonstrated that approximately 60% of laboring women have a full stomach and 40% have an 
empty stomach regardless of prior fasting state22,24.  Therefore we calculated that in order to account for the 
expected differences in CSA at T0, 
80 women are required for the 
study; 48 would be expected to have 
a full stomach (CSA>381mm2) and 
24 would be expected to have an 
empty stomach (CSA<381mm2) at T0 
(epidural insertion), as presented in 
Figure 1. Data will be assessed for 
normal distribution using the 
Kolmogorov-Smirnov test and Q-Q 
plots. Continuous data will be 
summarized as mean (standard 
d e v i a t i o n ) , a n d m e d i a n 
(interquartile range) as appropriate 
for normal or non-normal data. 
Categorical variables will be tested 
using Chi-square and presented as 
counts (percentages).  Data will be 
analyzed using Microsoft Excel 
Ofﬁce 2013 and SPSS (IBM) 25.0 
(SPSS Inc. Chicago, IL).  P-value 
<0.05 will be considered signiﬁcant 
for the primary outcome. 
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