A Comparison Study Between Ketamine Versus Tramadol for Pain Management After Major Upper Abdominal Surgery
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional

Summary: 
      The purpose of the study is the comparison between ketamine and tramadol, regarding the
      analgesia quality and efficiency, in patients receiving Patient Controlled Analgesia (PCA)
      morphine, after major upper abdominal surgeries such as hepatectomies, gastrectomies, Whipple
      procedures and peripheral pancreatectomies. The goal is to bring out an improved analgesia
      scheme, which can be applied to the clinical work and refine the analgesia provided for major
      procedures which require increased postoperative opioids doses. In the study, half of
      patients will receive continuous intravenous infusion of tramadol and Patient Controlled
      Analgesia morphine and the other half will receive continuous intravenous infusion of
      ketamine and Patient Controlled Analgesia morphine postoperatively after major upper
      abdominal surgery. The successful combination of different drugs targets at the improvement
      of the analgesia provided, the reduction of complications and the exploitation of the
      pharmacodynamic properties of each drug.
    

Detailed description: 
      This is a single blind, prospective, randomized controlled trial. Forty two adults patients
      of American Society of Anesthesiologists (ASA) physical status I-II, aged 18-70yr, scheduled
      for elective upper abdominal surgery under general anaesthesia are recruited. Signed informed
      consent is obtained from all patients. Patients are randomized into two groups.

        1. Ketamine group: thirty minutes before the expected end of surgery, ketamine is
           administered IV at a load dose of 0.5mg/kg followed by a continuous infusion of ketamine
           (0.12mg•kg-¹•h-¹) for up to 48 h.

        2. Tramadol group: thirty minutes before the expected end of surgery, tramadol is
           administered IV at a load dose of 1mg/kg followed by a continuous infusion of tramadol
           (0.2mg•kg-¹•h-¹) for up to 48 h.

      The evening before the elective surgery, all patients are premedicated with 150 mg ranitidine
      and 100mg hydroxyzine orally and provided with instructions on how to use the PCA device.
      They are also explained the Visual Analogue Scale (VAS: 0-10).

      All participants received the same protocol of general anaesthesia. Before the induction of
      anaesthesia all patients received metoclopramide 10 mg, ranitidine 50 mg and dimethindene 4
      mg intravenously. Anaesthesia was induced with propofol 2 mg/kg, and fentanyl 2 mcg/kg, while
      the administration of rocuronium facilitates the trachea intubation. The anaesthesia
      maintenance is attained through continuous infusion of propofol 1%. After the induction of
      anaesthesia and before the surgical incision, patients receive 3 mcg/kg fentanyl and 0.1mg/kg
      morphine intravenously, while repetitive doses of morphine 0.05 mg/kg are administered in
      order to keep intraoperative systolic arterial pressure and heart rate within the range of
      20% of the baseline values. The total morphine consumption is recorded.

      Thirty minutes before the expected end of surgery, paracetamol 1gr is administered
      intravenously. Consequently, patients receive either ketamine or tramadol according to the
      study group, at the aforementioned bolus and continuous infusions doses. The pump remained
      attached to the intravenous line for 48 hours.

      After the anaesthesia recovery patients are transferred to the Postanaesthesia Care Unit,
      where pain is assessed using the VAS (0-10) and treated with morphine bolus doses of 2 mg IV
      to achieve VAS scores <4. When VAS score <4 is attained, a PCA morphine pump is connected to
      a peripheral intravenous line and set to deliver morphine at a bolus dose of 1 mg with a
      lockout period of 8 minutes.

      When patients are full recovered and stabilized, are transferred to the wards. Postoperative
      analgesia consisted of PCA morphine and continuous infusion of either ketamine in the
      ketamine-group or tramadol in the tramadol-group, respectively. If analgesia is not adequate
      and VAS >5, morphine rescue doses of 2 mg are given intravenously. If the repetitive morphine
      doses are not efficient, the interval time of the PCA morphine pump is set at 6 minutes.
      Metoclopramide 10 mg is prescribed to be given intravenously twice a day. Postoperative
      nausea and vomiting (PONV) is assessed with a 5-points scale (0-4). If PONV is >2,
      dexamethasone 8 mg is given as first line treatment, while ondansetron 4 mg is the second
      line treatment. Itching is treated with propofol 10 mg IV. If the symptom continues, the
      patient is removed from the study.

      The study period is 48 hours (1, 2, 4, 6, 12, 18, 24, 36 and 48 hours) considering as zero
      time, the time of the connection of the PCA morphine pump to the patient. At these time
      points, morphine consumption, VAS scores, oxygen saturation, respiratory rate, bradycardia,
      hypotension, postoperative day of patient's mobilization, complications, drugs' side effects
      (itching, seizures, illusions, confusion, disorientation, sense of dry mouth, urinary
      retention, sedation, quality of sleep, PONV,) ability to cough are assessed. Additionally,
      patient's overall satisfaction at 48 hours is assessed and the postoperative total
      intrahospital stay is also recorded.
    

Intervention name(s): Tramadol; Ketamine
Intervention type(s): Drug; Drug
Intervention description(s): Tramadol administered intravenously (1mg/kg) thirty minutes before the expected end of surgery, followed by a continuous infusion of tramadol (0.2mg•kg-¹•h-¹) for up to 48 h after major upper abdominal surgery, in patients receiving PCA morphine postoperatively at a bolus dose of 1 mg with a lockout period of 8 minutes.; Ketamine administered intravenously (0.5mg/kg) thirty minutes before the expected end of surgery, followed by a continuous infusion of ketamine (0.12mg•kg-¹•h-¹) for up to 48 h after major upper abdominal surgery, in patients receiving PCA morphine postoperatively at a bolus dose of 1 mg with a lockout period of 8 minutes.
Other intervention name(s): Tramal; Ketalar
Intervention MeSH terms: Ketamine; Tramadol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Tramadol; Ketamine; Morphine