Clinical trial NCT01242241: Propofol in Obese Children
Official title: Propofol in Obese Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pharmacodynamics
Obesity
Keywords: Propofol
Childhood obesity
Pharmacodynamics
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2010-11-16
Enrollment: 80
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Obesity in children,as in adults,has rapidly become a public health concern. Studies in adults have shown that obesity, now considered to be a disease state, is a modifier of the effect of drugs on the body as well as how the body handles the drug.The anesthetic management of obese children poses a variety of significant challenges which include determination of the appropriate dose of anesthetic intravenous agents. Dosing of most drugs is calculated based on the effective dose in 50% of patients but the more practical and required information is the effective dose in 95%(ED95%)of patients. The aim of this study is to determine the effective dose in 95% of patients(children). The hypothesis is the ED95 of propofol in obese children will be higher than that of non-obese children.

Detailed description: All subjects were fasted in keeping with our institutional NPO guidelines and had IV access established in the upper extremity in the pre-anesthesia area. No pre-induction sedative drugs were administered. Routine ASA monitors were applied and in cooperative children, a bispectral index (BIS) monitor pad (Aspect Medical Systems, Inc., Shattuck, MA) was applied over the forehead. Each child was given a water-filled syringe to hold tightly in the hand contralateral to the IV site. Lidocaine 1 mg/kg IV (maximum of 60 mg) was administered to decrease pain with propofol injection. A predetermined sequential dose of propofol (Diprivan, APP Pharmaceuticals, LLC, Schaumburg, IL) was administered IV rapidly over 10 seconds, followed by a normal saline flush.

Biased Coin Design An independent observer blinded to the propofol dose tested for lash reflex at 20 seconds, and also recorded the vital signs; level of sedation, using the University of Michigan sedation scale (UMSS)10; and the BIS values at 20, 60, and 120 seconds after propofol administration, along with the time the patient dropped the handheld syringe. The study was terminated after 120 seconds and additional propofol administered if needed.

Both nonobese and obese patients were studied in parallel using the biased coin design (BCD), in which a certain number of dose levels (k levels) are chosen with a fixed constant interval. In the absence of dose-ranging data in obese children, we chose a low starting dose of 1.0 mg/kg for the first patient in both groups to avoid missing a desired response in this patient population. If the desired effect (loss of lash reflex at 20 seconds) was not observed, the next patient in the assigned group received the next higher dose of propofol in predetermined increments (0.25 mg/kg) from the previous dose. If the desired effect was observed, the next patient in the same assigned group was randomized with a 0.95 probability to receive the same dose or a 0.05 probability to receive the next lower dose (also in 0.25 mg/kg decrements).

Eligibility criteria: Inclusion Criteria:

1. Children between the ages of 3 and 17 years who fall into the categories of non-obese(BMI percentile between 25-84th percentile) or obese(\>95th percentile)
2. American Society of Anesthesiology(ASA) classification 1 or 2-

Exclusion Criteria:

1. Patients classified as ASA (American Society of Anesthesiology) Class 3 or greater.
2. Patients with documented kidney or liver disease or those presenting for open surgery on the liver or kidney.
3. Patients who will NOT be receiving propofol for induction as part of their anesthetic regimen.
4. Patients who are currently on anti-convulsant medication or receiving drugs with sedative effects.
5. Patients currently being treated for attention deficit disorder.
6. Patients who are diagnosed with failure to thrive or those with a BMI less than 25th percentile.
7. Patients who are hemodynamically unstable.
8. Patients with egg allergy.
9. Patients with low levels of albumin -

Primary outcomes:
measure: Dose of Propofol That Caused Loss of Consciousness in 95% (ED95) of Obese and Non-obese Children
timeFrame: 20 seconds
Secondary outcomes:
measure: Depth of Sedation
timeFrame: 30 seconds, 1 minute, and 2 minutes
Other outcomes:
Locations:
city: Houston
country: United States
facility: Texas Children's Hospital, Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Olutoyin A Olutoye, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a precis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology. 2007 Jul;107(1):144-52. doi: 10.1097/01.anes.0000267514.42592.2a.
citation: Mulla H, Johnson TN. Dosing dilemmas in obese children. Arch Dis Child Educ Pract Ed. 2010 Aug;95(4):112-7. doi: 10.1136/adc.2009.163055. Epub 2010 Jun 28.