Comparing Post-Operative Analgesic Effects of PCAM With Dexmedetomidine 1 mcg/ml vs PCAM With Dexmedetomidine 2 mcg/ml

Comparing Post-Operative Analgesic Effects of Patient-Controlled Analgesia Morphine (PCAM) in Combination With Dexmedetomidine 1 mcg/ml Versus PCAM With Dexmedetomidine 2 mcg/ml

PCA morphine have been a common method in providing excellent analgesia for post-operative period. However, the usage of morphine is not without any side effects such as nausea, vomiting, respiratory depression, and over sedation.

Many adjunct have been used in combination with morphine to observe the opioid sparing effects at the same time providing good analgesia.

Dexmedetomidine is a potent and selective alpha-2 receptor agonist with sedative, anxiolytic, sympatholytic, and analgesic effects. As dexmedetomidine and morphine act via different mechanism, this combination produces synergistic analgesic effects.

The objective of our study was to observe the effectiveness in pain relief between two low concentration of dexmedetomidine (2 mcg/ml versus 1 mcg/ml) as an adjunct to PCA morphine 1 mg/ml.

Study Overview

• Status: Completed
• Conditions: Opioid Use, Unspecified; Laparotomy Surgery; Post-Operative Analgesia
• Intervention / Treatment: Drug: Dexmedetomidine 1 mcg/ml; Drug: Dexmedetomidine 2 mcg/ml

Detailed Description

This was a double-blinded prospective randomised study conducted in Universiti Kebangsaan Malaysia Medical Centre from January 2020 till November 2020. This study was approved by Dissertation Committee of the Department of Anaesthesiology and Intensive Care, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and Medical Research and Ethics Committee of UKMMC.

Consent was taken during preoperative visit whereby patients were counselled on the use of PCA machine and assessment of pain score using visual analogue scale (VAS). All patients were not given sedative premedication before surgery. Induction of general anaesthesia was with IV fentanyl 2 mcg/kg, IV propofol 2 mg/kg and paralysed with IV rocuronium 0.6 mg/kg. Patients were given IV dexamethasone 0.2 mg/kg for postoperative nausea and vomiting (PONV) prophylaxis. Anaesthesia was maintained with sevoflurane to achieve MAC of 1.0 with oxygen and air in 1:1 ratio. All patients received IV morphine 0.1mg/kg intraoperatively, and surgical site infiltrated with levobupivacaine 0.5% 2 mg/kg. IV granisetron 1 mg was given to all patients at the end of the surgery and reversal was with IV neostigmine 0.05 mg/kg and IV atropine 0.02 mg/kg.

All patients were connected to the PCA morphine with test drugs after arrival in the recovery area. Patients were encouraged to self-administer the PCA whenever required. In an event of uncontrolled pain, rescue analgesia was with IV fentanyl 20 mcg boluses. All patients upon discharged to ward from recovery bay must have pain score (VAS) of less than 4, respiratory rate more than 10, MAP > 65 mmHg and HR > 60 beats/minute.

Patients were followed up at 6, 12, and 24 hours after surgery to look at the cumulative PCA morphine usage, incidence of nausea and vomiting, sedation score, respiratory depression (respiratory rate < 10 breath/min/). Side effects from dexmedetomidine namely hypotension (MAP < 65) and bradycardia (HR < 60) were also documented. The severity of nausea and vomiting was defined as mild, moderate, or severe while sedation was assessed according to five levels: 0, 1, 2, 3 and 4.

The power calculation for this study was based on a pilot study observing PCA consumption in the first 24 hours after surgery, with a mean difference, 14.67 and pooled standard deviation 20.27 in regard to dosage delivered comparing PCA morphine with dexmedetomidine 1 mcg/ml to PCA morphine with dexmedetomidine 2 mcg/ml. A group of 34 subjects each would be needed for a study with an alpha level of 0.05 (two-tailed) and a beta level of 0.2 (80% power) including 10% dropout rate.

Data were analysed using IBMR SPSSRs Statistics MacOS version 26.0 (IBM Corporation, New York, United States of America). The results were presented as frequency (percentage) and standard deviation whenever appropriate. The cumulative PCA morphine and dexmedetomidine usage pain score was analysed using the Mann-Whitney U-test. The incidence of sedation and PONV was analysed using Chi-square. Heart rate and blood pressure were analysed using independent T-test. A probability level of < 0.05 was considered to be statistically significant.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 4

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • Universiti Kebangsaan Malaysia Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA 1 & 2 patient
• going for elective or emergency laparotomy surgery

Exclusion Criteria:

• patient with known allergy to morphine or dexmedetomidine
• Creatinine clearance less then 30ml/min
• Current alcohol dependency
• Psychiatric illness on regular sedative-hypnotic drugs
• significant obstructive sleep apnoea (OSA)
• Chronic pain patient who on regular opioids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group D1; PCA morphine 1mg/ml	Drug: Dexmedetomidine 1 mcg/ml; 34 patients received PCA morphine 1 mg/ml with combination of dexmedetomidine 1 mcg/ml; Other Names: Precedex
ACTIVE_COMPARATOR: Group D2; PCA morphine 1mg/ml	Drug: Dexmedetomidine 2 mcg/ml; 34 patients received PCA morphine 1 mg/ml with combination of dexmedetomidine 2 mcg/ml; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total morphine consumption	Measure the total PCA morphine (mg) consumption post laparotomy	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine side effects	Assess the frequency and severity of morphine side effects with the use of PCA morphine post laparotomy (PONV, over sedation, respiratory depression)	at 6, 12, and 24 hours post laparotomy
Analgesic effects	Assess patient's pain score post laparotomy	at 6, 12, and 24 hours post laparotomy
Dexmedetomidine side effects	Assess frequency and severity of dexmedetomidine side effects (hypotension, bradycardia)	at 6, 12, and 24 hours post laparotomy

Collaborators and Investigators

• Sponsor: Universiti Kebangsaan Malaysia Medical Centre

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 9, 2019
• Primary Completion (ACTUAL): December 8, 2020
• Study Completion (ACTUAL): January 10, 2021

Study Registration Dates

• First Submitted: March 10, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (ACTUAL): March 21, 2022

Study Record Updates

• Last Update Posted (ACTUAL): March 21, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Dexmedetomidine; PCA Morphine; Morphine-dexmedetomidine; PCA-adjunct
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: FF-2019-543

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No