Comparing Post-Operative Analgesic Effects of PCAM With Dexmedetomidine 1 mcg/ml vs PCAM With Dexmedetomidine 2 mcg/ml
Condition: Post-Operative Analgesia; Opioid Use, Unspecified; Laparotomy Surgery
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Dexmedetomidine 1 mcg/ml; Dexmedetomidine 2 mcg/ml
Intervention type(s): Drug; Drug
Intervention description(s): 34 patients received PCA morphine 1 mg/ml with combination of dexmedetomidine 1 mcg/ml; 34 patients received PCA morphine 1 mg/ml with combination of dexmedetomidine 2 mcg/ml
Other intervention name(s): Precedex; Precedex
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Supportive Care
Keywords: PCA Morphine; Dexmedetomidine; Morphine-dexmedetomidine; PCA-adjunct