Opioid-free Analgesia for the Management of Acute Post-operative Pain Following Caesarean Section

NCT04539249 | Completed Results

• 1 other identifier: FMCY/O&G/OFAAPPCS/2020
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Multimodal analgesia; a combination of opioid and non-opioid analgesics, for management of acute post-operative pain significantly reduces the incidence of adverse effects associated with liberal post-operative opioid use including sedation, respiratory depression, constipation, ileus, urinary retention, delayed recovery, addiction etc. However, opioid addiction remains a worsening public health problem and have followed administration of opioid analgesics for post-operative pain and subsequent chronic use in many addicts; especially the opioid naive. Caesarean section is a commonly performed surgery and is a common source of first exposure to opioids in women. Trend in post-operative analgesia is moving towards opioid-free (multimodal) analgesia; a combination of non-opioid and adjuvant analgesics. Magnesium sulphate is an adjuvant analgesic. When administered peri-operatively, it has been reported to prolong the duration of spinal anaesthesia, decrease post-operative pain and opioid use without adverse effect. Aim: To determine the effectiveness and safety of a combination of peri-operative intravenous magnesium sulphate, intravenous paracetamol, and post-operative rectal diclofenac as opioid-free, multimodal analgesia for management of acute post-operative pain after a caesarean section. Null Hypothesis: Combination of intravenous magnesium sulphate, intravenous paracetamol, and rectal diclofenac as analgesia regimen for acute post-operative pain after a caesarean section is not as effective and safe as a routine opioid-based multimodal analgesia regimen used in the study setting. Alternate Hypothesis: Combination of intravenous magnesium sulphate, intravenous paracetamol, and rectal diclofenac as analgesia regimen for acute post-operative pain after a caesarean section is as effective and safe as a routine opioid-based multimodal analgesia regimen used in the study setting. Materials and Methods: A randomized clinical trial, comparing a combination of peri-operative intravenous magnesium sulphate, intravenous paracetamol, and post-operative rectal diclofenac with an opioid-based multimodal regimen as control. Eligible patients will be consecutively selected from among women booked for caesarean section at the Federal Medical Centre, Yenagoa. Control group will receive a combination of post-operative intramuscular pentazocine, intravenous paracetamol and rectal diclofenac. Pain intensity will be determined in both groups and compared. Need for rescue opioid analgesic will be determined in both groups and compared. Incidence of any adverse event in both groups will be determined.

Conditions

Acute Post-operative Pain Following Caesarean Section

Outcome Measures

Primary Outcomes (7)

• Post-operative Pain Scores Following Caesarean Section at 4 Hours Post-operative

  Post-operative pain scores following caesarean section at 4 hours post-operative using the Numerical Rating Scale for pain. The Numerical Rating Scale for pain has a minimum score of 0, a maximum score of 10 and a range of 0-10, where higher scores mean a worse outcome (0= No pain at all, 5= Moderate pain and 10= Worst pain imaginable)

  4 hours post-operative

• Post-operative Pain Scores Following Caesarean Section at 8 Hours Post-operative

  Post-operative pain scores following caesarean section at 8 hours post-operative using the Numerical Rating Scale for pain. The Numerical Rating Scale for pain has a minimum score of 0, a maximum score of 10 and a range of 0-10, where higher scores mean a worse outcome (0= No pain at all, 5= Moderate pain and 10= Worst pain imaginable)

  8 hours post-operative

• Post-operative Pain Scores Following Caesarean Section at 24 Hours Post-operative

  Post-operative pain scores following caesarean section at 24 hours post-operative using the Numerical Rating Scale for pain. The Numerical Rating Scale for pain has a minimum score of 0, a maximum score of 10 and a range of 0-10, where higher scores mean a worse outcome (0= No pain at all, 5= Moderate pain and 10= Worst pain imaginable)

  24 hours post-operative

• Post-operative Pentazocine Use

  Whether or not Pentazocine was used post-operatively

  24 hours post-operative

• Pentazocine Use as Rescue Analgesia

  Whether or not pentazocine was used as rescue analgesia

  24 hours post-operative

• Frequency and Nature of Pentazocine Use

  Frequency of Pentazocine use per participant in each arm of the study and whether it was used as indicated in the protocol and/or for rescue analgesia

  24 hours post-operative

• Mean Dose of Pentazocine Used

  Mean dose of Pentazocine used in each arm of the study

  24 hours post-operative

Secondary Outcomes (3)

• Number of Participants With Peri-operative Adverse Events

  Time of first administration of peri-operative analgesia to 2 hours postoperative

• Number of Participants With Post-operative Adverse Events

  First 24 hours post-operative

• Apgar Scores of the Neonates

  At first and fifth minutes after birth

Study Arms (2)

Magnesium sulphate

EXPERIMENTAL

Combination of intravenous magnesium sulphate, intravenous paracetamol and rectal diclofenac

Drug: Magnesium sulphate

Pentazocine

ACTIVE COMPARATOR

Combination of intramuscular pentazocine, intravenous paracetamol and rectal diclofenac

Drug: Pentazocine

Interventions

Magnesium sulphate DRUG

1g of paracetamol as an I.V infusion and 4g of magnesium sulphate as an I.V. bolus preoperatively. Continuous infusion of 1g/hr of magnesium sulphate intraoperatively and for the first 2 hours post-operatively. Further post-operatively, 100 mg of suppository diclofenac 12 hourly, intravenous paracetamol 1g 6 hourly, both over 24 hours. N.B: Intramuscular pentazocine 30 mg (45 mg if patient is \> 70 kg) will be used as rescue analgesia as needed (that is, only on patients' request for further analgesia or following an assessment of moderate to severe pain despite the planned analgesic regimen) at least 4 hourly during the first 24 hours after caesarean section.

Also known as: MgSO4

Magnesium sulphate

Pentazocine DRUG

Post-operatively, suppository diclofenac 100mg 12 hourly, intramuscular pentazocine 30 mg (45 mg if patient is \> 70 kg) 6 hourly, intravenous paracetamol 1g 6 hourly, all for 24 hours. N.B: Intramuscular pentazocine 30 mg (45 mg if patient is \> 70 kg) will be used as rescue analgesia as needed (that is, only on patients' request for further analgesia or following an assessment of moderate to severe pain despite the planned analgesic regimen) at least 4 hourly during the first 24 hours after caesarean section.

Pentazocine

Eligibility Criteria

• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Pregnant women booked for elective, scheduled and urgent caesarean section at the Federal Medical Centre, Yenagoa, Bayelsa State during the study period,
• Pregnant women who give consent to participate in the study.

You may not qualify if:

• Pregnant women with active peptic ulcer disease, active liver disease, hepatic failure, and renal failure,
• Pregnant women with previous history of ischaemic heart disease/myocardial infarction, heart failure, venous thrombosis and stroke,
• Hypersensitivity to pentazocine, paracetamol, diclofenac or magnesium sulphate,
• Pregnant women with history of non-medical use (abuse) of opioids,
• Pregnant women on magnesium sulphate or have a clinical indication to receive magnesium sulphate,
• Pregnant women booked for emergency caesarean section (because the urgency may not allow time for adequate patient counseling before recruitment)
• Pregnant women booked for caesarean section under general anaesthesia or epidural anaesthesia,
• Pregnant women who can neither communicate in english nor colloquial english.

Sponsors & Collaborators

• Olakunle Ifeoluwa Makinde: lead

Study Sites (1)

Federal Medical Centre, Yenagoa

Yenagoa, Bayelsa State, 560231, Nigeria

Location

Related Publications (14)

• Vadivelu N, Mitra S, Schermer E, Kodumudi V, Kaye AD, Urman RD. Preventive analgesia for postoperative pain control: a broader concept. Local Reg Anesth. 2014 May 29;7:17-22. doi: 10.2147/LRA.S62160. eCollection 2014.

  PMID: 24872720 BACKGROUND

• Kim M. An opioid success story: efforts to minimize painkillers after surgery appear to be working. Johannesburg, South Africa: The Conversation Africa, Inc.; 2019.

  BACKGROUND

• Johnson SR. Hospitals look to cut opioids from surgery and beyond. Detroit, Michigan: Crain communications, Inc.; 2019.

  BACKGROUND

• Dinis J, Soto E, Pedroza C, Chauhan SP, Blackwell S, Sibai B. Nonopioid versus opioid analgesia after hospital discharge following cesarean delivery: a randomized equivalence trial. Am J Obstet Gynecol. 2020 May;222(5):488.e1-488.e8. doi: 10.1016/j.ajog.2019.12.001. Epub 2019 Dec 6.

  PMID: 31816306 BACKGROUND

• Kahraman F, Eroglu A. The effect of intravenous magnesium sulfate infusion on sensory spinal block and postoperative pain score in abdominal hysterectomy. Biomed Res Int. 2014;2014:236024. doi: 10.1155/2014/236024. Epub 2014 Mar 19.

  PMID: 24772415 BACKGROUND

• McKeown A, Seppi V, Hodgson R. Intravenous Magnesium Sulphate for Analgesia after Caesarean Section: A Systematic Review. Anesthesiol Res Pract. 2017;2017:9186374. doi: 10.1155/2017/9186374. Epub 2017 Dec 3.

  PMID: 29333156 BACKGROUND

• Shin HJ, Kim EY, Na HS, Kim TK, Kim MH, Do SH. Magnesium sulphate attenuates acute postoperative pain and increased pain intensity after surgical injury in staged bilateral total knee arthroplasty: a randomized, double-blinded, placebo-controlled trial. Br J Anaesth. 2016 Oct;117(4):497-503. doi: 10.1093/bja/aew227. Epub 2016 Oct 17.

  PMID: 28077538 BACKGROUND

• Kalani N, Sanie MS, Zabetian H, Radmehr M, Sahraei R, Kargar Jahromi H, Zare Marzouni H. Comparison of the Analgesic Effect of Paracetamol and Magnesium Sulfate during Surgeries. World J Plast Surg. 2016 Sep;5(3):280-286.

  PMID: 27853692 BACKGROUND

• Murphy JD, Paskaradevan J, Eisler LL, Ouanes JP, Tomas VA, Freck EA, Wu CL. Analgesic efficacy of continuous intravenous magnesium infusion as an adjuvant to morphine for postoperative analgesia: a systematic review and meta-analysis. Middle East J Anaesthesiol. 2013 Feb;22(1):11-20.

  PMID: 23833845 BACKGROUND

• Albrecht E, Kirkham KR, Liu SS, Brull R. Peri-operative intravenous administration of magnesium sulphate and postoperative pain: a meta-analysis. Anaesthesia. 2013 Jan;68(1):79-90. doi: 10.1111/j.1365-2044.2012.07335.x. Epub 2012 Nov 1.

  PMID: 23121612 BACKGROUND

• Hwang JY, Na HS, Jeon YT, Ro YJ, Kim CS, Do SH. I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia. Br J Anaesth. 2010 Jan;104(1):89-93. doi: 10.1093/bja/aep334.

  PMID: 19933175 BACKGROUND

• Apan A, Buyukkocak U, Ozcan S, Sari E, Basar H. Postoperative magnesium sulphate infusion reduces analgesic requirements in spinal anaesthesia. Eur J Anaesthesiol. 2004 Oct;21(10):766-9. doi: 10.1017/s026502150400002x.

  PMID: 15678729 BACKGROUND

• Helmy N, Badawy AA, Hussein M, Reda H. Comparison of the preemptive analgesia of low dose ketamine versus magnesium sulphate on parturient undergoing caesarean section under general anaesthesia. Egypt. J. Anaesth. 2015;31(1):53-58.

  BACKGROUND

• Paech MJ, Magann EF, Doherty DA, Verity LJ, Newnham JP. Does magnesium sulfate reduce the short- and long-term requirements for pain relief after caesarean delivery? A double-blind placebo-controlled trial. Am J Obstet Gynecol. 2006 Jun;194(6):1596-602; discussion 1602-3. doi: 10.1016/j.ajog.2006.01.009. Epub 2006 Apr 17.

  PMID: 16615926 BACKGROUND

MeSH Terms

Interventions

Magnesium Sulfate; Pentazocine

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Benzomorphans; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

1. The subjectivity of the perception, expression and assessment of pain was a limitation to this study. The intensity of pain cannot be perfectly compared between one person and the other, neither can it be objectively measured. 2. This study was done only among pregnant women undergoing a caesarean section at the Federal Medical Centre Yenagoa, Bayelsa State, which limits the generalizability of the findings to other populations.

Results Point of Contact

• Title: Dr. Olakunle I. Makinde
• Organization: Federal Medical Centre, Yenagoa

olakunleife@gmail.com

08032136315

Study Officials

• Olakunle I Makinde, MBChB, MWACS

  Federal Medical Centre, Yenagoa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Registrar

Study Record Dates

• First Submitted: August 30, 2020
• First Posted: September 4, 2020
• Study Start: November 4, 2020
• Primary Completion: March 30, 2021
• Study Completion: March 31, 2021
• Last Updated: July 20, 2023
• Results First Posted: July 20, 2023

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting 3 months after publication
• Access Criteria: Open access

Locations

NG (1)