Adjuvant Analgesic Effects of Low Dose Tramadol/Acetaminophen Combination After Open Gynaecological Surgery
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      Patient experience moderate to severe pain after abdominal surgery. This post-operative pain
      can also contribute to complications such as respiratory impairment, cardiovascular events,
      ileus, sleep deprivation and mood disturbance. Opioid based patient-controlled analgesia
      (PCA) is commonly employed but opioids have the side effects such as respiratory depression,
      nausea and vomiting, sedation, pruritus and urinary retention. Bowel motility can also be
      affected. Consequently alternative or adjunct analgesic medications without these
      side-effects have been investigated in order to reduce opioid consumption.

      Multimodal analgesia is a technique whereby a combination of analgesic drugs with different
      modes of action can be used to improve analgesia and decrease adverse effects by virtue of
      synergism. Postoperatively, with adjunctive analgesia, PCA morphine consumption as well as
      the side effects may be reduced. Non-steroidal anti-inflammatory drugs (NSAIDs) have been
      shown to be opioid sparing and decrease the adverse effects of PCA morphine. A recent review
      showed that acetaminophen combined with PCA could induce a significant opioid-sparing effect
      but the incidence of PCA morphine related side effects were not reduced.

      It is common nowadays to give oral analgesic supplements to post-operative patients on PCA
      morphine. Tramadol, an analogue of codeine, is one of the choices. However, some of the
      patients cannot tolerate the side effects such as nausea, drowsiness, sweating, postural
      hypotension and dry mouth. Combination of tramadol 37.5 mg and acetaminophen 375 mg, which
      has been used successfully to treat post-operative pain, may improve analgesic response with
      better tolerability.

      This study is to assess tramadol 37.5 mg and acetaminophen 375 mg combination on the efficacy
      of pain control, down stepping of morphine consumption and related adverse events with PCA
      use after open colorectal surgeries.

      Objectives:

      This study aims to compare and evaluate:

        -  The efficacy of tramadol/acetaminophen combination on postoperative pain relief after
           lower abdominal surgeries

        -  The effects of tramadol/acetaminophen combination on the consumption and the duration of
           PCA morphine use

        -  The adverse effects related to this regimen

        -  The effects on postoperative bowel function, tolerability of fluid and diet, ambulatory
           function, sleep, and duration of hospital stay

        -  The overall satisfaction of the patients
    

Detailed description: 
      This is a randomized, double-blinded, placebo-controlled study.

      Study site Patients will be recruited and studied at Queen Mary Hospital, Hong Kong.

      Anaesthesia for operation No premedication will be prescribed. Patients will be induced with
      fentanyl 1 to1.5µg/kg, thiopentone 2-4mg/kg or propofol 2-3mg/kg and rocuronium 1mg/kg.
      Anaesthesia will be maintained with cisatracurium and isoflurane with air and oxygen.
      Intravenous morphine will be used for pain relief intraoperatively.

      Postoperative PCA settings

      After the operation, at the recovery area, patients will be given boluses of intravenous
      morphine until satisfactory pain control, i.e. numerical rating scale (NRS) less than 4. PCA
      machine will then be connected and patient will learn the technique of using PCA. The PCA
      pump will be programmed as follow:

      Each bolus: 1 to 1.5mg Lockout interval: 5 minutes Maximum hourly dose limit: 0.1mg/kg for
      patients up to 65 years old and 0.075mg/kg for patients over 65 No background morphine
      infusion will be given. Intramuscular pethidine 0.5mg/kg four-hourly will be prescribed as
      rescue pain medications. Patients will be assessed everyday by the pain team of the hospital.

      Randomisation and blinding

      Patients will be randomised to one of the following 2 groups:

      Group T: Tramadol 37.5mg / acetaminophen 325mg: 1 tablet 3 times daily orally Group P:
      Acetaminophen 500mg 3 times daily A computer-generated random sequence will decide the
      allocation order. The appearance of acetaminophen looks similar to the tramadol/acetaminophen
      combination. Both pain team members and patients will be blinded to the study medications.
      The study medications will be used for 48 hours after operation.

      Follow-up and assessments Patients will be assessed each morning by the pain team. The daily
      average pain score at rest and during cough will be recorded in numerical rating scale (NRS).
      Average daily pain intensity (0=none, 1=mild, 2=moderate, 3=severe) and average daily relief
      (4=complete relief, 3=a lot, 2=moderate, 1=slight, 0=no, -1=worse pain) will be assessed. The
      tries/good ratio shown on PCA machine and the total amount of morphine used, daily rescue
      pain drug consumption will be charted. The adverse effects (nausea, vomiting, pruritus,
      dizziness, and others) will be recorded with their frequencies and severity graded. Sedation
      will be assessed based on the scale shown.

      The ambulatory function, tolerability of fluid and diet and bowel function will also be
      assessed. Sleeping quality will be evaluated using NRS and reason for it asked.

      The PCA machine will be off if the NRS pain score on cough is less than 4. Patients will then
      grade their overall satisfaction of pain relief at postoperative day 3.

      Data Collection

      Efficacy

        -  Resting and coughing NRS pain scores,

        -  Average daily pain intensity and average daily relief

        -  Tries/good ratio, cumulative morphine consumption,

        -  Rescue pain drug consumption every day until 2 days after stopping PCA

        -  Overall patient's satisfaction using NRS

      Safety

      - Adverse effects and their severity, sedation, ambulatory function, tolerability of fluid
      and diet, bowel function, and sleeping quality every day until off PCA

      Demographics

        -  Age

        -  Sex

        -  Body weight

        -  ASA grading

        -  Operation duration

        -  Intraoperative opioids

        -  Morphine consumption at recovery room
    

Intervention name(s): tramadol/acetaminophen; acetaminophen
Intervention type(s): Drug; Drug
Intervention MeSH terms: Acetaminophen; Tramadol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Open gynecological surgery