Clinical trial NCT04539249: Opioid-free Analgesia for the Management of Acute Post-operative Pain Following Caesarean Section
Official title: Single-centre, Randomized, Clinical Trial of Opioid-free Analgesia Versus Routine Opioid-based Analgesia Regimen for the Management of Acute Post-operative Pain Following Caesarean Section
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Post-operative Pain Following Caesarean Section
Lead sponsor: Federal Medical Centre, Yenagoa
Sponsor class: OTHER_GOV
First posted: 2020-09-04
Enrollment: 324
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Post-operative Pain Scores Following Caesarean Section at 4 Hours Post-operative
timeFrame: 4 hours post-operative
measure: Post-operative Pain Scores Following Caesarean Section at 8 Hours Post-operative
timeFrame: 8 hours post-operative
measure: Post-operative Pain Scores Following Caesarean Section at 24 Hours Post-operative
timeFrame: 24 hours post-operative
measure: Post-operative Pentazocine Use
timeFrame: 24 hours post-operative
measure: Pentazocine Use as Rescue Analgesia
timeFrame: 24 hours post-operative
measure: Frequency and Nature of Pentazocine Use
timeFrame: 24 hours post-operative
measure: Mean Dose of Pentazocine Used
timeFrame: 24 hours post-operative
Secondary outcomes:
measure: Number of Participants With Peri-operative Adverse Events
timeFrame: Time of first administration of peri-operative analgesia to 2 hours postoperative
measure: Number of Participants With Post-operative Adverse Events
timeFrame: First 24 hours post-operative
measure: Apgar Scores of the Neonates
timeFrame: At first and fifth minutes after birth
Other outcomes:
Locations:
city: Yenagoa
country: Nigeria
facility: Federal Medical Centre, Yenagoa
state: Bayelsa State
Study officials:
affiliation: Federal Medical Centre, Yenagoa
name: Olakunle I Makinde, MBChB, MWACS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Kim M. An opioid success story: efforts to minimize painkillers after surgery appear to be working. Johannesburg, South Africa: The Conversation Africa, Inc.; 2019.
citation: Johnson SR. Hospitals look to cut opioids from surgery and beyond. Detroit, Michigan: Crain communications, Inc.; 2019.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.