Propofol in Obese Children

NCT ID: NCT01242241

Last Updated: 2020-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-01
• Study Completion Date: 2011-12-31

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).

Conditions

Pharmacodynamics; Obesity

Keywords

Propofol; Childhood obesity; Pharmacodynamics

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Non-obese

Non-obese children categorized as those with a body mass index(BMI)between 25-84th percentile

Group Type: OTHER

Propofol

Intervention Type: DRUG

This arm of patients(non-obese)will act as the control group for the obese children. Each non-obese child/subject will receive a predetermined dose of propofol from a range of 1.0mg/kg to 4.25mg/kg depending on the response of the previous patient to their assigned dose( biased coin design)

Obese children

Obese children are categorized as those with a body mass index \>95th percentile

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

Each Obese child/subject in this group will receive a predetermined dose of propofol ranging from 1.0mg/kg to 4.25mg/kg to induce loss of consciousness depending on the response (presence or absence of lash reflex) of the preceding patient to his/her assigned dose (biased coin design)

Interventions

Propofol

Each Obese child/subject in this group will receive a predetermined dose of propofol ranging from 1.0mg/kg to 4.25mg/kg to induce loss of consciousness depending on the response (presence or absence of lash reflex) of the preceding patient to his/her assigned dose (biased coin design)

Intervention Type: DRUG

Propofol

This arm of patients(non-obese)will act as the control group for the obese children. Each non-obese child/subject will receive a predetermined dose of propofol from a range of 1.0mg/kg to 4.25mg/kg depending on the response of the previous patient to their assigned dose( biased coin design)

Intervention Type: DRUG

Other Intervention Names

Diprivan; Diprivan

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 -

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Olutoyin A. Olutoye

Associate Professorof Anesthesiology & Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Olutoyin A Olutoye, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Texas Children's Hospital, Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17585226 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20585055 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

H-22091

Identifier Type: -

Identifier Source: org_study_id