Peri -and Postoperative Drug Therapy Schedules for Morbidly Obese Patients
Condition: Obese; Atracurium; Cefazolin; Morphine; Nadroparin
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 4

Summary: 
      Rationale: Obesity is an increasing health risk worldwide, with the USA recording prevalence
      in adults of around 20%. The mean body weight of obese patients is also increasing. One of
      the strategies to treat extreme obesity (Body Mass Index (BMI) > 40 kg/m2) is weight-reducing
      surgery like laparoscopic gastric banding or gastric bypass. During anaesthesia, morbidly
      obese patients are exposed to an increased risk at developing postoperative wound infections,
      apnoea and thrombotic events and may be more difficult to intubate. Routinely, amongst
      others, cefazolin, morphine, nadroparin and atracurium are administered in standard dosages.
      However, it is not known to what extend the pharmacokinetics and/or -dynamics of these drugs
      are affected in morbidly obese patients. Therefore, evidence-based dosing schedules for these
      drugs in morbidly obese patients should be developed.

      Objective: The study is performed in order to develop population pharmacokinetic and/or
      pharmacodynamic models of the routinely used drug therapies during bariatric surgery in
      morbidly obese patients (BMI > 40 kg/m2): cefazolin, morphine, nadroparin and atracurium.

      A covariate analysis will be performed in order to account for variability in pharmacokinetic
      and/or pharmacodynamic parameters. This covariate analysis will take into account procedure
      and patient bound covariates, with specific interest for body weight as a covariate. Whenever
      possible, non-obese patients will be included in the covariate analysis.

      The results will be used to develop individualised dosing schemes for routinely used drugs
      peri-operatively in morbidly obese patients.

      Study design: A randomised, prospective, observational, therapeutic and invasive study.

      Study population: Morbidly obese patients with a Body Mass Index > 40 kg/m2 undergoing
      laparoscopic banding or gastric bypass surgery, 18-60 years old. A total of 20 patients will
      be included in the study.

      Intervention (if applicable): All measurements and data collection will take place around
      administration of drugs that are given according to routine clinical practice (cefazolin 2
      grams for prophylaxis of infections, morphine 10 mg intravenously at the end of surgery, a
      patient-controlled analgesia (PCA) pump with morphine for postoperative pain relief and
      nadroparin 0,6 ml for trombo-embolic prophylaxis). For muscle relaxation, patients are
      randomised to receive one of two generally accepted dosing regimen of atracurium (0.5 mg/kg
      based on ideal body weight or 0.5 mg/kg based on total body weight). Peri- and
      postoperatively, a maximum amount of 70 ml of blood will be collected from an indwelling
      arterial line for measurement of concentrations of cefazolin, morphine, and anti-Xa
      (nadroparin). One week after surgery the patient will be checked for thrombosis using
      ultrasonography.

      Main study parameters/endpoints:

      Primary endpoints to evaluate in morbidly obese patients are;

        -  pharmacokinetic parameters of cefazolin in blood;

        -  pharmacokinetic parameters of morphine and metabolites in blood;

        -  time course of anti-factor Xa levels in blood following nadroparin;

        -  time course of the pharmacodynamic effect of atracurium.

      Secondary endpoints to evaluate in morbidly obese patients are:

        -  to compare primary endpoints (obtained in morbidly obese patients) with data of
           non-obese patients

        -  the occurrence of postoperative wound infections;

        -  postoperative pain scores, sedation scores and nausea scores;

        -  the occurrence of bleedings or thrombotic events ;

        -  required amounts of morphine (PCA);

        -  to compare the time course of the pharmacodynamic effect of two different doses of
           atracurium.
    


Intervention name(s): Atracurium, TBW
Intervention type(s): Drug
Intervention description(s): Dose atracurium 0.5 mg/kg based on total body weight
Intervention MeSH terms: Atracurium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Diagnostic
Keywords: Obese; Atracurium; Cefazolin; Morfine; Nadroparin