Dexamethasone for Post-cesarean Delivery Pain

• ClinicalTrials.gov Identifier: NCT01812057
• Recruitment Status: Completed
• First Posted: March 15, 2013
• Results First Posted: July 25, 2017
• Last Update Posted: July 25, 2017
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

The purpose of this study is to compare post-cesarean section consumption of pain medication between two groups of patients undergoing scheduled cesarean section at term gestation who receive a single-dose of intraoperative steroid (dexamethasone 8 milligrams) versus placebo at 24 hours after surgery. The hypothesis is that a single perioperative dose of dexamethasone 8 mg will significantly reduce postoperative opioid consumption at 24 h in women having cesarean delivery under spinal anesthesia.

Condition or disease	Intervention/treatment	Phase
Pain, Postoperative; Postoperative Nausea and Vomiting	Drug: Dexamethasone; Drug: Placebo	Phase 4

Detailed Description:

Steroids have been used to reduce inflammation and tissue damage in a variety of conditions, have potent immunomodulatory effects, and are a mainstay in the treatment of acute allograft rejection. Dexamethasone has been shown to be a safe and effective anti-emetic therapy for patients undergoing cesarean section surgery with spinal anesthesia containing morphine.

However, recent evidence suggests that dexamethasone may also play a role in reducing post-operative pain and opioid consumption. Early studies in patients undergoing dental procedures showed that glucocorticoids were effective in reducing postoperative pain and edema. Multiple recent studies have also investigated the potential analgesic benefit of a single perioperative dose of dexamethasone, but the results have been inconsistent. The effect of single-dose, intraoperative, intravenous dexamethasone therapy on post-operative pain and opioid consumption has not yet been studied in patients undergoing cesarean section.

Pain is a significant source of morbidity for many women following cesarean section, and has serious consequences beyond the immediate post-operative period. Patients with poorly-controlled pain may have difficulty with ambulation that can lead to atelectasis, pneumonia, and venous thromboembolism.

Poor maternal pain control may also affect the infant by interfering with bonding and breastfeeding. Reduction of post-operative opioid consumption is desirable because it may also reduce the incidence of opioid-induced side effects such as sedation, constipation, nausea, vomiting and pruritus. Some evidence suggests that the severity of post-operative pain following cesarean section may predict progression to chronic pain, and postpartum depression.

Although 10 to 18% of women who undergo cesarean section will experience chronic pain following surgery, it is difficult to predict those patients who will experience this complication. Recent investigations have shown that patient responses to standardized painful stimuli prior to surgery help predict severity of post-operative pain and possibly progression to chronic pain. This type of information could potentially help to tailor the clinical management of patients at risk for severe and/or chronic post-operative pain to improve outcomes for these patients. Landau and colleagues have described a simple and minimally-invasive method of assessing response to noxious stimuli using a von-Frey filament to obtain a mechanical temporal summation score.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Dexamethasone as an Analgesic Adjunct for Post-cesarean Delivery Pain Relief
• Study Start Date: December 2012
• Actual Primary Completion Date: May 27, 2016
• Actual Study Completion Date: September 21, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dexamethasone; Dexamethasone 8 mg IV given intraoperatively as a one-time dose.	Drug: Dexamethasone; Dexamethasone 8 mg IV (as a one time dose)
Placebo Comparator: Placebo; Sodium chloride 0.9% (5 ml) given IV intraoperatively as a one time dose.	Drug: Placebo; Sodium Chloride 0.9% -5 ml; Other Name: Sodium Chloride 0.9%

Outcome Measures

Primary Outcome Measures :

1. Morphine Consumption at 24 Hours Post-op [ Time Frame: 24 hours from admission to Postanesthesia care unit (PACU) ]
   The primary outcome will be the cumulative morphine consumption at 24 h in the two study groups. All postoperative opioids were converted to IV morphine equivalents using the following conversion factors: 100 micrograms IV = 10 mg IV morphine, 20 mg oxycodone po = 10 mg IV Morphine

Secondary Outcome Measures :

1. Pain Scores Between the Groups at 2 Hours. [ Time Frame: 2 hours from admission to postanesthesia care unit (PACU) ]
   Pain scores were measured using a numeric rating scale with a range from 0 to 10, with 0 meaning no pain and 10 indicating the most severe pain.
2. Time to Administration of First Rescue Analgesic Request Between the Groups. [ Time Frame: PACU admission to discharge from PACU an average of 2 hours ]
   Time in minutes from admission to PACU to the first request by the patient for oral oxycodone (analgesia) administration for pain
3. Cumulative Opioid Consumption at 48 Hours Between the Groups [ Time Frame: Admission to PACU through 48 hours ]
   The secondary outcome was the cumulative morphine consumption at 48 h in the two study groups. All postoperative opioids were converted to IV morphine equivalents using the following conversion factors: 100 micrograms IV = 10 mg IV morphine, 20 mg oxycodone po = 10 mg IV Morphine
4. Pain Scores Between the Groups at 24 Hours. [ Time Frame: 24 hours from PACU admission ]
   Pain scores were measured using a numeric rating scale with a range from 0 to 10, with 0 meaning no pain and 10 indicating the most severe pain.
5. Pain Scores Between the Groups at 48 Hours. [ Time Frame: 48 hours from PACU Admission ]
   Pain scores were measured using a numeric rating scale with a range from 0 to 10, with 0 meaning no pain and 10 indicating the most severe pain.
6. Cumulative Opioid Consumption at 24 Hours Between MTS Groups [ Time Frame: 24 hours from admission to Postanesthesia care unit (PACU) ]
   Mechanical temporal summation (MTS) was assessed using A 180 g Von Frey Filament was applied to the volar aspect of the dominant forearm, and subjects were asked to rate pain scores (NRS 0-100, 0 = no pain and 100= worst pain possible) after the 1st and 11th tap. A difference < 1 was recorded as MTS negative, and a difference > or = 1 was recorded as MTS positive.
7. Incidence of Chronic Persistent Pain at 8 Weeks [ Time Frame: 8 weeks from the day of surgery ]
   Patients answered a questionnaire at 8 weeks to determine whether they still had persistent surgical site pain 8 weeks following surgery
8. Incidence of Chronic Persistent Pain at 6 Months [ Time Frame: 6 months from the day of surgery ]
   Patients answered a questionnaire at 6 months to determine whether they still had persistent surgical site pain 6 months following surgery
9. Pain Scores Between MTS Groups [ Time Frame: 24 hours after PACU admission ]
   Mechanical temporal summation (MTS) was assessed using A 180 g Von Frey Filament was applied to the volar aspect of the dominant forearm, and subjects were asked to rate pain scores (NRS 0-100, 0=no pain and 100=worst pain possible) after the 1st and 11th tap. A difference < 1 was recorded as MTS negative, and a difference > or = 1 was recorded as MTS positive.
10. Incidence of Intraoperative Nausea and Vomiting (IONV) and Need for Rescue Antiemetics. [ Time Frame: From spinal anesthesia placement to end of surgery, approximately 70 minutes ]
    Incidence of intraoperative nausea and vomiting and need for rescue antiemetics were recorded during surgery. Patient who reported a nausea score on a 11 point NRS where 0=no nausea and 10 = the worse nausea possible. Patients who retched or vomited were reported to have vomited. Patients receiving any antiemetic during surgery were recorded as those requesting ( needing) rescue antiemetic.
11. Incidence of Intraoperative Pruritus [ Time Frame: From spinal anesthesia placement to end of surgery, approximately 70 minutes ]
    pruritus was defined as patients reporting a pruritus score of greater than o on a numerical rating scale with o=no pruritus and 10= worst pruritus
12. Incidence of Postoperative Pruritus [ Time Frame: 48 hours from admission to PACU ]

    Incidence of postoperative pruritus was calculated based on their postoperative pruritus scores measured at 2 hours, 24 hours and 48 hours. Median of the scores recorded at three time points was calculated.

    If median score >0 then patient experienced postoperative pruritus.

13. Need for Intraoperative Analgesic Supplementation [ Time Frame: From spinal anesthesia placement to end of surgery, approximately 70 minutes ]
    Need for intraoperative analgesic supplementation was determined by patients who required intraoperative analgesics for pain
14. Incidence of Post-operative Nausea and Vomiting (PONV) and Need for Rescue Antiemetics [ Time Frame: 2, 24 and 48 hours from PACU admission ]

    Patients who had experienced Postoperative nausea either reported postoperative nausea scores at 2, 24 and 48 hours from >0, reported an episode of vomiting or received an antiemetic were recorded as experiencing PONV.

    Patients who received at least one rescue antiemetic postoperatively were recorded as requiring a rescue antiemetic

15. Incidence of Wound Complications [ Time Frame: 24 hours from PACU admission ]
    Patients were assessed for signs of surgical wound inspection by the obstetric team following surgery
16. Blood Pressure Measurements Obtained by the Standard of Care Non-invasive Blood Pressure Monitor Compared With the Continuous Noninvasive Arterial Pressure (CNAP) [ Time Frame: Intraoperatively ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• American Society of Anesthesiology (ASA) class 1, 2 and 3
• Gestational age > 37 weeks
• scheduled for elective cesarean delivery
• spinal or combined spinal epidural anesthesia
• 18 years or older
• speak English

Exclusion Criteria:

• BMI > 45 kg/m2
• Diabetes Mellitus (Type 1, 2 and gestational)
• mild or severe preeclampsia
• history of intravenous drug or opioid abuse
• previous history of chronic pain syndrome
• history of opioid use in the past week
• receipt of an antiemetic within 24 h prior to surgery
• Non-English speaking

Contacts and Locations

Locations

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27705

Sponsors and Collaborators

Duke University

Investigators

• Principal Investigator: Terrence Allen, MD; Duke University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Griffiths JD, Gyte GM, Popham PA, Williams K, Paranjothy S, Broughton HK, Brown HC, Thomas J. Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. Cochrane Database Syst Rev. 2021 May 18;5(5):CD007579. doi: 10.1002/14651858.CD007579.pub3.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01812057
• Other Study ID Numbers: Pro00041334
• First Posted: March 15, 2013
• Results First Posted: July 25, 2017
• Last Update Posted: July 25, 2017
• Last Verified: June 2017

Keywords provided by Duke University:

Anesthesia; Cesarean Section; Pain, Postoperative; Postoperative Nausea and Vomiting; Dexamethasone; Injections, Spinal; morphine

Additional relevant MeSH terms:

Nausea; Vomiting; Pain, Postoperative; Postoperative Nausea and Vomiting; Signs and Symptoms, Digestive; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Dexamethasone; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents