Peri -and Postoperative Drug Therapy Schedules for Morbidly Obese Patients
Information source: St. Antonius Hospital
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Obese; Atracurium; Cefazolin; Morphine; Nadroparin
Intervention: Atracurium, TBW (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: St. Antonius Hospital Official(s) and/or principal investigator(s): Simone van Kralingen, MD, Principal Investigator, Affiliation: St. Antonius Hospital
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.
Clinical Details
Official title: Peri -and Postoperative Drug Therapy Schedules for Morbidly Obese Patients
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Diagnostic
Primary outcome: Time course of the pharmacodynamic effect of atracuriumPharmacokinetic parameters of cefazolin in blood Pharmacokinetic parameters of morphine and metabolites in blood Time course of anti-factor Xa levels in blood following nadroparin
Secondary outcome: Dosing of atracurium based on total or ideal body weightTo 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)
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Morbidly obese patients undergoing bariatric surgery with a BMI > 40 kg/m2, ASA I-III
Exclusion Criteria:
- Epilepsy, pregnancy, breastfeeding and known allergy allergies to cefazolin,
morphine, nadroparin, atracurium, or benzene sulphonic acid. History of coagulation
disorder or history of heparin/LMWH induced thrombocytopenia.
Locations and Contacts
St. Antonius Hospital, NIeuwegein 3435EM, Netherlands
Additional Information
Starting date: November 2009
Last updated: October 12, 2010
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