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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Post-operative Pain Following Caesarean Section

Intervention / Treatment
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* Drug: Magnesium sulphate
* Drug: Pentazocine


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Magnesium sulphate<br>Combination of intravenous magnesium sulphate, intravenous paracetamol and rectal diclofenac | Drug: Magnesium sulphate<br>* 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.<br>* Other names: MgSO4;|
| Active Comparator: Pentazocine<br>Combination of intramuscular pentazocine, intravenous paracetamol and rectal diclofenac | Drug: Pentazocine<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Peri-operative Adverse Events | Number of participants with peri-operative adverse events including hypersensitivity reaction, respiratory depression, bradycardia, hypotension, nausea and vomiting, lightheadedness, presyncope, and any other adverse event recorded from the time of first administration of peri-operative analgesia to 2 hours postoperative | Time of first administration of peri-operative analgesia to 2 hours postoperative | 
| Number of Participants With Post-operative Adverse Events | Number of participants with post-operative adverse events including respiratory depression constipation, ileus, pruritus, urinary retention and any other adverse event recorded during the first 24 hours post-operative. | First 24 hours post-operative | 
| Apgar Scores of the Neonates | Apgar scores of the neonates delivered by the women who had caesarean section under the study, taken at first and fifth minutes after birth. Apgar score has a minimum score of 0, a maximum score of 10 and a range of 0-10, where higher scores mean a better outcome (0-3= low Apgar score, 4-6= moderately abnormal Apgar score and 7-10= reassuring Apgar score | At first and fifth minutes after birth |