Clinical Outcomes in Patients Undergoing Cesarean Section Via the Enhanced Recovery After Surgery (ERAS) Pathway: a Retrospective Study
Conditions: Cesarean Section
Sponsor: University of Alabama at Birmingham

Implementation of an enhanced recovery after surgery 
pathway for patients undergoing cesarean section: impact on 
clinical outcomes  
 
     Study Protocol & Statistical Analysis Plan  
 
 
 
 
   
 
 
 
 
        NCT03552822 
 
 
 
 
 
 
 
 
 
 
 
        April 24, 2020 
 
 
 
 
Mark Powell, M.D., Principal Investigator 
 
 
  University of Alabama at Birmingham 
 
 
 
 
Birmingham, AL 35294 
 
 
 
 
 
 
 
 
 
 
 
 
 

STUDY SUMMARY 
 
1 ..................................................................................................................... INTRODUCTION 
2 .......................................................................................................... STUDY OBJECTIVES 
3 ..................................................................................................................... STUDY DESIGN 
4 ......................................................... SUBJECT SELECTION AND WITHDRAWAL 
5…………………………………………………………………...........STUDY PROCEDURES 
6 ............................................................................................................ STATISTICAL PLAN 
7 ............................................................................... SAFETY AND ADVERSE EVENTS 
8 .......................................................... DATA HANDLING AND RECORD KEEPING 
9……………………..…..STUDY MONITORING, AUDITING, AND INSPECTING  
10 ............................................................................................................ STUDY FINANCES 
11 ........................................................................................................PUBLICATION PLAN 
12…………………………………………………………………….………………REFERENCES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

INTRODUCTION 
Cesarean section (CS) is one of the most common surgeries performed worldwide. It is the most 
common major surgery performed in the United States, with over 1.25 million patients undergoing CS 
annually.1 As enhanced recovery programs have been shown to accelerate postoperative recovery and 
decrease dependence on postoperative opioids in other surgical specialties,2 they have begun to gain 
popularity for CS.3,4 Such a program for CS presents an opportunity to affect outcomes for patients who 
could benefit from a multidisciplinary, multimodal, and opioid-sparing approach to improving their 
recovery. The Society for Obstetric Anesthesia and Perinatology (SOAP) strongly supports this effort and 
recently released a consensus statement on an enhanced recovery protocol for CS.5 
An important aspect of many enhanced recovery protocols is a multimodal approach to opioid-
sparing pain control.2 Potential benefits of opioid-sparing pain control for women undergoing CS include 
decreased amounts of opioids transferred in breastmilk,6 as well as reduced risk of maternal opioid 
abuse after delivery.7 Opioid-naïve patients who undergo surgery are at particular risk for developing 
opioid dependence after surgery.7-8 Approximately 1 in 300 opioid-naïve women become persistent 
prescription opioid users following CS.9 
As enhanced recovery programs in obstetrics begin to gain popularity, more studies evaluating 
their impact are needed.3 We therefore sought to evaluate the impact of instituting an enhanced 
recovery program for CS. 
STUDY OBJECTIVES 
 
The purpose of this study was to determine if there are significantly improved patient outcomes 
after implementing an enhanced recovery protocol for CS. Initially, we had planned to study hospital 
length of stay as our primary outcome; however, because of Rose’s Law, we determined that length of 
stay would not be an appropriate primary outcome at our institution. Rose’s Law is a state law that 
prohibits early discharge (<96 hours) of a patient after cesarean delivery unless a waiver is signed by the 
patient to allow for discharge before 96 hours after delivery. 
The primary outcome of this study was to determine if implementation of an enhanced recovery 
program could reduce postoperative opioid consumption in patients undergoing CS. Secondary 
outcomes included determining the impact of an enhanced recovery program for CS on postoperative 
pain scores, length of stay, and 30-day complication rates. We hypothesized that implementing an 
enhanced recovery program for CS would decrease postoperative opioid consumption. 
STUDY DESIGN 
We compared a retrospective pre-enhanced recovery cohort (pre-ERC) of women delivered by 
CS to a prospective enhanced recovery cohort (ERC) exposed to the enhanced recovery program. The 
pre-ERC included patients from January 1, 2017 to June 30, 2018. The Enhanced Recovery for Cesarean 
Delivery Program was implemented July 1, 2018. The ERC included patients from July 1, 2018 to 
December 31, 2018.  
 
 

SUBJECT SELECTION 
Analysis was restricted to women undergoing scheduled, elective CS at the Women and Infants’ 
Center who were admitted to the hospital on the day of surgery. Patients excluded from analysis 
included those: (1) less than 18 years of age; (2) who had an urgent or emergent CS; (3) who had a 
diagnosis of preeclampsia, eclampsia, insulin dependent diabetes, abnormal placentation, or opioid use 
disorder. The pre-ERC group included patients from January 1, 2017 to June 30, 2018. The ERC group 
included patients from July 1, 2018 to December 31, 2018. 
STUDY PROCEDURES 
Pre-Enhanced Recovery Cohort  
The pre-ERC was identified through a query of our electronic medical records database. Only 
surgeries scheduled at least 24 hours prior to documented delivery time were considered as to exclude 
urgent or emergent surgeries. Also, patients were excluded if they had a documented International 
Classification of Diseases (ICD) diagnosis of preeclampsia, eclampsia, placenta accreta, placenta increta, 
placenta percreta, Type 1 diabetes, Type 2 insulin dependent diabetes, opioid dependence, or had 
outpatient prescriptions for insulin, methadone, buprenorphine, or buprenorphine-naloxone. Eligible 
charts were reviewed, and patients were further excluded if they were admitted for inpatient 
management prior to the day of surgery or if they had an exclusion diagnosis that was in a physician 
note but not captured as an ICD code.  
 
Enhanced Recovery Program Implementation  
The Enhanced Recovery after Cesarean Delivery Program was implemented on July 1, 2018. The 
program included the enhanced recovery protocol and a quality improvement initiative with monthly 
reports. The program was designed by a multidisciplinary committee with leadership from obstetric 
anesthesia and stakeholders including obstetricians, pediatricians, nursing leadership, pharmacy, and 
information technology.  
Patients received a written educational handout on enhanced recovery after CS in the 
preoperative obstetric clinic. Instead of the previous “nil per os (NPO) after midnight” preoperative 
instructions, these patients were instructed to consume a 20-ounce carbohydrate sports drink up to 2 
hours before arrival to the hospital. Upon admission, the ERC had an icon placed on the electronic 
tracking board signifying that they were in the enhanced recovery protocol. In preoperative holding, 
patients received the standard gastrointestinal and antibiotic prophylaxis with the addition of 1000 mg 
of oral acetaminophen. The acetaminophen would continue throughout hospitalization as a scheduled 
dose of 650 mg every six hours. A forced-air warming device was placed on the patient, and patients 
were warmed for 30 minutes prior to surgery.  
No major changes occurred in the intraoperative setting. Patients undergoing spinal or 
combined spinal-epidural anesthesia received our standard spinal dose of 12 mg hyperbaric bupivacaine 
combined with 15 µg fentanyl and 150 µg preservative-free morphine. Patients undergoing epidural 
anesthesia received our standard dose of 3 mg preservative-free morphine in combination with local 
anesthetic. A bilateral transversus abdominis plane block was performed in the post-anesthesia care 
unit (PACU) with 20 ml 0.5% ropivacaine on each side for patients who underwent general anesthesia 
and were unable to receive neuraxial preservative-free morphine. Unless contraindicated, all patients 
received 30 mg of intravenous (IV) ketorolac in the PACU. The ketorolac was given as a scheduled 
medication every 6 hours for the first 24 hours. Patients then were transitioned to scheduled ibuprofen 
600 mg every 6 hours.  

Postpartum changes included earlier postoperative oral intake, earlier urinary catheter removal, 
increased ambulation goals, and changes in standard analgesic medication orders. Patients were now 
offered a clear liquid diet immediately upon arrival to the postpartum floor and advance to solid foods 
as soon as tolerated. Prior to July 1, 2018, the urinary catheter was removed on postoperative day (POD) 
1. This meant that the catheter might have remained in place for up to 23 hours or more after delivery. 
The enhanced recovery protocol specified to remove the catheter eight hours after delivery while 
awake. Prior to the ERC, there were no clearly defined postoperative ambulation goals. In the ERC, 
specific activity goals included out of bed and to a chair three times a day and ambulating in the hallway 
once on POD 0. From POD 1 until discharge, patients were expected to ambulate in the hallway four 
times a day. Changes to the analgesic regimen included scheduled oral acetaminophen and ibuprofen 
throughout hospitalization as well as non-opioid management (heat/cold packs, distraction therapy) for 
mild pain. Pain scores were defined as: mild (1-3), moderate (4-6), and severe (7-10) and were recorded 
by nursing as part of the routine vital signs. There were as needed orders for oral oxycodone 5mg every 
4 hours for moderate pain, and oral oxycodone 10mg every 4 hours for severe pain. At the time of 
discharge, patients were written for a maximum number of 20 tablets of oxycodone 5 mg, which was a 
reduction from the 30 tablets prior to enacting the enhanced recovery protocol. 
After implementation of the protocol in July 2018, data were pulled monthly and summary 
statistics were provided to the committee. Regular feedback was solicited from providers involved in the 
enhanced recovery protocol. Adherence to the protocol was assessed by actions recorded in the 
electronic medical record including medication administration and catheter removal time, as well as 
times recorded for oral intake and first ambulation. 
 
Enhanced Recovery Cohort  
The ERC for data analysis was identified through a monthly query of the electronic medical 
record after July 1, 2018.  Charts were identified based on the presence of an order for the Enhanced 
Recovery for Cesarean Delivery Protocol and were reviewed to confirm adherence to study inclusion and 
exclusion criteria, with chart abstraction as needed for missing data. 
STATISTICAL PLAN 
Statistical Analysis  
Data were summarized using either means and standard errors (SE) for continuous outcomes or 
counts and percentages for categorical outcomes. Two-sample t-tests and chi-square tests were used to 
compare the two cohorts. Normality for continuous outcomes was assessed using probability plots and 
the Shapiro-Wilk test for normality; for any outcomes where normality could not be reasonably 
assumed, the Wilcoxon rank sum test was used in place of two-sample t-tests. For categorical outcomes, 
Fisher’s exact test was used when assumptions for the chi-square test were not met. 
Any missing observations were assumed to be missing at random. Pairwise deletion was used to 
handle missing data. That is, subjects with missing data were not excluded from all analyses, but only 
those analyses where the outcome of interest was missing. For the primary and secondary outcomes, a 
Bonferroni adjustment was used to correct for multiple comparisons. For these outcomes, a two-sided 
p-value < 0.002 (= .05/22) was considered statistically significant. For all other measures, p-value < 0.05 
was considered statistically significant. SAS version 9.4 (SAS Institute Inc., Cary, NC) was used to conduct 
all statistical analyses. 
 
 
 

Sample Size Estimate  
We assessed baseline values of our primary clinical outcome to determine appropriate sample 
size. After initial retrieval of patient charts for the pre-ERC, and prior to chart abstraction, the baseline 
total oral morphine equivalents (OME) used postoperatively from July 1, 2017 to April 30, 2018 was an 
average of 126 (5.93) mg. Based on these values, a sample size of 138 patients would give us 80% power 
at the 0.05 significance level to detect a 15% decrease in morphine equivalents from baseline using a 
two-sample t-test. We analyzed patients in the ERC from July 1, 2018 through December 31, 2018. This 
was based on the monthly review of data that were part of the enhanced recovery program. Given the 
pattern of opioid decrease seen in these monthly reviews, we decided to finalize analysis at the end of 
2018. 
SAFETY AND ADVERSE EVENTS 
For the study, breach of confidentiality is a rare but potential adverse event. Any adverse event 
will be documented and immediately reported to the departmental human studies research committee 
and institutional review board.  
DATA HANDLING AND RECORD KEEPING 
All data collected are stored electronically in the HIPAA-compliant, password-protected research 
drive maintained by our department. Only study personnel on the study protocol have access to the 
data stored in this system.  
STUDY MONITORING, AUDITING, AND INSPECTING 
The PI of the study is responsible for oversight of the study and all co-investigators. The research 
division within the department tracks and ensures all investigators of the study maintain appropriate 
credentialing to participate in research. The research division within the department also reviews and 
approves all protocols. The IRB requires a yearly progress report be submitted and includes all patients 
screened and enrolled, study update, and any adverse events. The study is also subject to audit by the 
IRB at any point during the time it is open. 
STUDY FINANCES 
No external funding was received for this study. All resources for this study were provided by 
the department. 
PUBLICATION PLAN 
 
The completed manuscript was submitted for publication and accepted in the International 
Journal of Obstetric Anesthesia. Citation for this article: 
 
 Lester SA, Kim B, Tubinis MD, Morgan CJ, Powell MF. Impact of an enhanced recovery program 
for cesarean delivery on postoperative opioid use. Int J Obstet Anesth 2020; 43:47-55. 
 
 

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