Dose Escalation of Dexamethasone to Increase Duration of Transversus Abdominal Plane Block Following Cesarean Section

Preoperatively: informed consent will be obtained by a member of this study. The patients will be screened for inclusion/exclusion criteria on day of procedure, and then the participants will be randomized to one of three groups.

Intraoperatively: The anesthesia team involved with care of patient in the operating room will provide routine anesthesia care during the cesarean section including neuraxial anesthesia with intrathecal bupivacaine and morphine.

After completion of the procedure, the patients will receive bilateral TAP block procedure while still in OR. All blocks will include 20mL of 0.5% ropivacaine, and the patients will be randomly assigned a specific dose of dexamethasone at 0mg (given normal saline as control), 2mg, or 4mg. The resident or attending physician supervising the block will be investigators of the study, and they along with the residents performing the blocks will be blinded to the amount of dexamethasone in the injectate.

Postoperatively: The patients will then be monitored in the PACU for approximately 30-60 minutes and then subsequently monitored on an inpatient floor. Pain scores, time until first opioid dose, total opioid requirement will be assessed and recorded. In PACU, these will be recorded every 15-30 minutes. On the inpatient floor, these will be recorded every 6 hours.

Pain scores, average pain scores in first 48 hours, total opioid consumption, time until first opioid use, and PONV medication requirement will also be recorded. These will be recorded by review of the electronic medical record.

Satisfaction scores and estimation of TAP block duration will be assessed and recorded by anesthesia personnel approximately 48 hours post-operatively; these will be subjective evaluations recorded between 24-38 hours postoperatively. The patients will be asked to estimate how long they felt the block lasted. For satisfaction scores, patients will rate their satisfaction subjectively on a scale of 1-10.

Statistical Analysis: all demographic and clinical variables with continuous measures will be expressed as means and standard deviations; categorical factors will be expressed as proportions. For non-normal data, the medians and inter quartile ranges will be displayed. The distribution of the continuous factors will be examined using the Kolmogorov-Smirnov test. For data that are normally distributed, one-way ANOVA will be used to compare groups of data. For data that are not normally distributed, the Kruskal-Wallis test will be used for comparisons. Chi-square and Fisher's exact tests will be used to analyze categorical data. For all comparisons, a value of p < 0.05 will be considered statistically significant.

Statistical analyses will be performed using SAS for Windows, version 9.2. One-way ANOVA (or the Kruskal-Wallis test, as appropriate) will be used to compare duration of TAP block for the three groups. Linear regression will also be used to test the relationship between duration of block and dexamethasone dose, while controlling for relevant clinical and demographic variables.

One-way ANOVA (or the Kruskal-Wallis test) will be used to compare the groups on post-operative pain scores, opioid requirements, and patient satisfaction scores.

Statistical Power and Sample Size Estimates: Approximately 69 subjects (23 per group) are expected to be enrolled in this study. Given this sample size and assuming that the average duration of TAP block is 18 hours for the control group, 22 hours for the 2 mg of dexamethasone group, and 24 hours for the 4 mg of dexamethasone group, this study will have approximately 80.9% power to detect a difference in block duration, assuming a common standard deviation of 6 hours. If the variability in block time is smaller than 6 hours, this study will have greater power.

• 2mg Dexamethasone (Drug), also known as Baycadron, Maxidex, Decadron: 0.5 mL (2mg) of dexamethasone and 0.5 ml of normal saline
• 4mg Dexamethasone (Drug), also known as Baycadron, Maxidex, Decadron: 1 mL (4mg) of dexamethasone
• Ropivacaine (TAP blocks) (Drug): 20mL of 0% ropivacaine with 20mL of 0.5% ropivacaine
• Morphine (Drug)
• Bupivacaine Hydrochloride (Drug)
• Normal saline 1ml (Drug): 1.0 ml of normal saline split between 2 sites with standard intrathecal bupivacaine and morphine
• Normal saline 0.5ml (Drug): 0.5 ml of normal saline split between 2 sites with standard intrathecal bupivacaine and morphine

Primary outcomes

• Average Pain Score [48 hours postoperatively]: Average pain score (VAS) 48 hrs postoperatively between the study group and the control. The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. 0 represents no pain, whereas 10 represents unbearable pain.

Secondary outcomes

• First Post-Operative Opioid Administration [baseline to 48 hrs postoperatively]: Time until first dose post-operative opioid administration between the study group and the control
• Average Opioid Consumption [from the time of delivery to 48hrs postoperatively]: Average opioid consumption 48 hrs postoperatively between the study group and the control

Sex: Female, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

1. Women undergoing cesarean section delivery.
2. Patients classified as American Society of Anesthesiology (ASA) class II or III.

   1. ASA II: mild systemic disease, pregnancy
   2. ASA III: severe systemic disease
3. Women ≥ 18 years old
4. Neuraxial anesthesia (spinal) to be used as anesthetic technique intraoperatively for cesarean section (this is the UAB Anesthesiology standard of care).

Exclusion Criteria:

1. Any patient not classified as an ASA I or II.
2. General Anesthesia or neuraxial anesthesia with epidural used as anesthetic techniques for cesarean section.
3. Allergy/intolerance to local anesthetic or steroids.
4. Pre-existing neurological and/or anatomical deficit that would preclude regional block.
5. Coexisting coagulopathy such as hemophilia or von Willebrand Disease
6. BMI > 40.
7. Emergency Cesarean Sections

Participant flow

Outcome results

• Average Pain Score (Primary), Mean, units on a scale: Control Group 1.49 +/- 0.25; 2mg Dexamethasone 1.40 +/- 0.40; 4mg Dexamethasone 1.62 +/- 0.35
• First Post-Operative Opioid Administration (Secondary), Mean, Hours: Control Group 22.43 +/- 4.87; 2mg Dexamethasone 12.56 +/- 3.58; 4mg Dexamethasone 18.25 +/- 4.23
• Average Opioid Consumption (Secondary), Mean, mg of morphine equivalents: Control Group 37.93 +/- 13.50; 2mg Dexamethasone 47.11 +/- 12.44; 4mg Dexamethasone 42.38 +/- 9.17

Adverse events

Time frame: 1 year

Limitations and caveats: Early termination leading to small numbers of subjects analyzed, due to recruitment challenges related to competing studies in the women and infants center

• Study Protocol and Statistical Analysis Plan (PDF, 2016-07-22)

• Joel Feinstein, MD, Principal investigator, Anesthesiology ad Perioperative Medicine