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

Opioid Use, Unspecified Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05288738
• Other study ID #: FF-2019-543
• Status: Completed
• Phase: Phase 4
• Start date: December 9, 2019
• Est. completion date: January 10, 2021

Study information

• Verified date: April 2021
• Source: Universiti Kebangsaan Malaysia Medical Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: January 10, 2021
• Est. primary completion date: December 8, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Laparotomy Surgery
• Opioid Use, Unspecified
• Post-Operative Analgesia

Intervention

Drug:
• Dexmedetomidine 1 mcg/ml
34 patients received PCA morphine 1 mg/ml with combination of dexmedetomidine 1 mcg/ml
• Dexmedetomidine 2 mcg/ml
34 patients received PCA morphine 1 mg/ml with combination of dexmedetomidine 2 mcg/ml

Locations

Country	Name	City	State
Malaysia	Universiti Kebangsaan Malaysia Medical Center	Cheras	Kuala Lumpur

Sponsors (1)

Lead Sponsor	Collaborator
Universiti Kebangsaan Malaysia Medical Centre

Country where clinical trial is conducted

Malaysia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total morphine consumption	Measure the total PCA morphine (mg) consumption post laparotomy	24 hours
Secondary	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
Secondary	Analgesic effects	Assess patient's pain score post laparotomy	at 6, 12, and 24 hours post laparotomy
Secondary	Dexmedetomidine side effects	Assess frequency and severity of dexmedetomidine side effects (hypotension, bradycardia)	at 6, 12, and 24 hours post laparotomy