Development of PK/PD Model for Individualized Propofol Dosing

Completed

Conditions studied: Obesity, Elective Surgery

In brief

The U.S. National Health and Nutrition Examination Survey of 1994 indicated that 59% of American men and 49% of women have body mass indexes (BMIs) over 25. Extreme obesity, defined as a BMI of 40 or more, was found in 2% of the men and 4% of the women \[http://www.cdc.gov/nchs/nhanes.htm\]. The newest survey in 2007 indicates an alarming increase in BMI; 63% of Americans are overweight, with 26% now in the obese category. With extreme obesity as high as 26-30% in adults, obesity percentages in children are also sharply on the rise. These alarming numbers pose a major clinical problem in terms of the safe and effective use of drugs in children. Obesity may alter the disposition and/or clearance of drugs in the body as well as the response, which should be considered when using anesthetics in these patients. Total intravenous anesthesia (TIVA) with propofol is widely used in children, adolescents and adults undergoing surgery, because of rapid onset of action, ease of titration and rapid offset of action. While extensive research on optimal propofol dosing has been performed in non-obese adults, including in critically ill mechanically ventilated adult patients by the investigators' collaborators, there is no evidence on required dosages in morbidly obese adult or pediatric patients of this highly lipophilic agent. As a consequence, serious problems do arise due to under- and overdosing, increasing the risk of inadequate effects and adverse events, respectively. Crucial additional information is needed on the pharmacokinetics of drugs used in morbidly obese children to improve safety and efficacy. This proposal will test a novel approach by identifying pharmacokinetic/pharmacodynamic (PK/PD) factors that are associated with response to therapy and adverse events. If successful, this study will provide proof of concept data for PK/PD model-based dosing strategy that can be implemented into daily clinical care to allow tailoring of dose to individual needs. Propofol is a versatile anesthetic agent which if dosed to individual needs based on a patient's characteristics and specific PK/PD parameters, will allow individualized dosing, thereby greatly reducing related toxicities. The prospective identification of predictive factors in these morbidly obese high-risk patients represents a new approach to an increasingly common clinical problem. The investigators expect that this study will generate the PK/PD data necessary to continue with a well powered prospective clinical trial.

Key facts

Study ID

NCT00948597

Run by

Children's Hospital Medical Center, Cincinnati

People needed

26

Starts

2009-07-01

Expected to finish

2013-12-01

Last updated by the study team

2014-01-09

Who can join

Age: 5 and older, up to 18. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age 5 to 18 years of age;
• Have a Body Mass Index (BMI) greater than 30;
• Be scheduled for bariatric or other elective surgical procedure;
• Will be administered propofol anesthesia as part of procedure and standard of care and subject is expected to be under anesthesia for at least 60 minutes;
• Signed and dated IRB-approved Informed Consent or Parental Permission and Assent form, as applicable.

You may not qualify if…

• Patients receiving investigational agent as part of another clinical study;
• Patients with severe developmental delay, known neurological disorders;
• Conditions where the placement of the sensor or process of assessment could interfere with the BIS monitoring;
• Allergy to propofol / anaphylaxis to egg protein;
• History of severe sleep apnea;
• Anticipated difficult airway access;
• Significant allergies and sensitivities to tape and/or adhesives.

Where it is running

• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States

Full record on ClinicalTrials.gov

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