Adjuvant Analgesic Effects of Low Dose Tramadol/Acetaminophen Combination After Open Gynaecological Surgery

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

Inclusion criteria

• ASA I to III
• Age 18 to 80 years
• Scheduled for elective lower abdominal surgery (gynecological or colorectal surgery) at Queen Mary Hospital, Hong Kong

Exclusion criteria

• Allergy to tramadol, acetaminophen, or other opioid drugs
• Patient with epilepsy or history of seizures
• Concurrent use of selective serotonin uptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors
• Impaired or retarded mental state
• Impaired renal function, defined as preoperative serum creatinine level over 120µmol/L
• Impaired hepatic function, defined as preoperative serum albumin level less than 30g/L
• Intraoperative use of clonidine or dexmedetomidine
• Patient requiring postoperative mechanical ventilation
• Difficulties in using patient-controlled analgesia
• Pregnancy
• Current or previous drug abuser
• Alcoholism
• Patient refusal