Propofol in Obese Children
Condition: Pharmacodynamics; Obesity
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 3

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).
    

Intervention name(s): Propofol; Propofol
Intervention type(s): Drug; Drug
Intervention description(s): 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); 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)
Other intervention name(s): Diprivan; Diprivan
Intervention MeSH terms: Propofol
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Propofol; Childhood obesity; Pharmacodynamics