Metabolites of Tramadol in the Postoperative Surgical Patients
Condition: Abdominal Surgery; Respiratory Failure; Renal Failure; Liver Dysfunction; Multiorgan Failure
MeSH terms: Liver Diseases; Respiratory Insufficiency; Multiple Organ Failure
Study type: Observational

Summary: 
      Tramadol is opioid analgesic widely used to treat moderate to severe pain. It is metabolized
      by cytochrome CYP2D6 into two major metabolites: pharmacologically active metabolite
      O-desmethyltramadol (M1) and inactive N-desmethyltramadol (M2), respectively. Tramadol
      kinetics in a population of patients undergoing major abdominal surgical procedures, and in
      patients with a greater or lesser degree of organic failure, is still not well researched.
      The investigators will measure plasma concentrations of tramadol and its metabolites after
      usual tramadol doses in ICU patients after major abdominal surgery. Also analgesic affect and
      side effect of tramadol will be recorded.
    

Detailed description: 
      The blood samples for the CYP2D6 gene polymorphism analysis will be taken from all patients
      included in the study. The patients will be categorized as slow (PM), normal (NM) or
      ultra-fast metabolizers (UM) of tramadol using analysis of the CYP2D6 phenotype. Standard
      laboratory findings including red blood cells, urea, creatinine, and cholinesterase will be
      done before surgery.

      The patients will receive 500 mg of tramadol intravenously divided into 5 doses during the
      first 24 postoperative hours in the ICU. The plasma concentrations of tramadol,
      O-desmethyltramadol and N-desmethyltramadol will be measured 1, 2 and 4 hours after the first
      dose, and immediately before the 2nd, 3rd and 5th dose. There will therefore be 6
      measurements of tramadol and its metabolites.

      The analgesic effect of tramadol will be measured in awake patients with Numeric Rating Scale
      - NRS (0 - without pain, 10 - strong pain) 30 minutes before and 30 minutes after tramadol
      administration. The NRS value of 3 or less will be considered as adequate analgesia. In case
      of inadequate analgesia rescue analgesic (morphine) will be used according to the local
      protocol.

      In unconscious patients the analgesic effect of tramadol will be tested by Critical Care Pain
      Observation Tool (CPOT). The CPOT value of less than 2 will be considered as adequate
      analgesia. In case of inadequate analgesia rescue analgesic (morphine) will be used according
      to the local protocol. During the first 24 hours side effect of tramadol, such as nausea,
      vomiting and new respiratory depression will be recorded.
    

Intervention name(s): Postoperative analgesia using tramadol
Intervention type(s): Drug
Intervention description(s): Tramadol 100 mg will be given to the patients in the postoperative period.
Other intervention name(s): Morphine for rescue analgesia
Intervention MeSH terms: Morphine; Tramadol
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The patients undergoing major open abdominal cancer surgery in Osijek University Hospital
        who are admitted in the ICU after surgery, age between 18 and 90 years, BMI >18 and <35,
        who signed the informed consent will be included in the study.
      
Biospecimen description: 
      CYP2D6 polymorphism will be done from DNA isolated from white cells.
    
Keywords: Tramadol; CYP2D6 polymorphism; analgesia; intensive care; organ failure