Propofol in Obese Children

Phase 3

Completed

Conditions: Obesity
Pharmacodynamics

Interventions: Drug: Propofol

Registration Number: NCT01242241

Lead Sponsor: Baylor College of Medicine

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 80

Inclusion Criteria

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)
American Society of Anesthesiology(ASA) classification 1 or 2-

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non-obese	Propofol	Non-obese children categorized as those with a body mass index(BMI)between 25-84th percentile
Obese children	Propofol	Obese children are categorized as those with a body mass index \>95th percentile

Primary Outcome Measures

Name	Time	Method
Dose of Propofol That Caused Loss of Consciousness in 95% (ED95) of Obese and Non-obese Children	20 seconds	Propofol is administered over 10 seconds. 20 seconds after adminstration, loss of consciousness is assessed by the presence or absence of a lash reflex. The dose responsible for loss of lash reflex/consciousness in 95% of patients was determined in mg/kg.

Secondary Outcome Measures

Name	Time	Method
Depth of Sedation	30 seconds, 1 minute, and 2 minutes	After propofol administration, the patient was assessed for depth of sedation at 30 seconds, 1 minute, and 2 minutes using the University of Michigan Sedation Scale (UMSS) and Ramsay Sedation Scale. UMSS assesses the level of alertness on a five-point scale ranging from 1 (wide awake) to 5 (unarousable with deep stimulation). Ramsay Sedation Scale assesses the level of sedation on a six-point scale ranging from 1 (Patient is anxious and agitated or restless, or both) to 6 (Patient exhibits no response).