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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Non-obese | Other | Non-obese children categorized as those with a body mass index(BMI)between 25-84th percentile |
|
| Obese children | Active Comparator | Obese children are categorized as those with a body mass index >95th percentile |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propofol | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Dose of Propofol That Caused Loss of Consciousness in 95% (ED95) of Obese and Non-obese Children | 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. | 20 seconds |
| Measure | Description | Time Frame |
|---|---|---|
| Depth of Sedation | 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Olutoyin A Olutoye, MD | Baylor College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Texas Children's Hospital, Baylor College of Medicine | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17585226 | Background | 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. | |
| 20585055 | Background | 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. |
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A total of 213 patients were screened for study eligibility. Eighty-two patients were excluded; 51 did not meet inclusion criteria either becasue they declined participation, did not have intravenous access, were re-scheduled due to inadequate preparation for surgery or patient illness. All patients enrolled completed the study.
Patients were recruited in the operating room setting between the period of April 2008 to December 2011
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| ID | Title | Description |
|---|---|---|
| FG000 | Obese Children | Obese children are categorized as those with a body mass index >95th percentile Propofol : Each Obese child/subject in this group received 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) |
| FG001 | Non-obese | Non-obese children categorized as those with a body mass index(BMI)between 25-84th percentile Propofol : This arm of patients(non-obese)served as the control group for the obese children. Each non-obese child/subject received 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) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Obese Children | Obese children are categorized as those with a body mass index >95th percentile Propofol : Each Obese child/subject in this group received 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) |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dose of Propofol That Caused Loss of Consciousness in 95% (ED95) of Obese and Non-obese Children | 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. | The sample size of 40 patients in each group was based on previous simulation studies which used the biased coin design in which a group size of 20-40 patients was shown to demonstrate stable estimates of the target dose for most scenarios. | Posted | Median | Full Range | mg/kg | 20 seconds |
|
From 0-120 seconds of propofol administration
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Non-obese | Non-obese children categorized as those with a body mass index(BMI)between 25-84th percentile 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) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Olutoyin A. Olutoye | Baylor College of Medicine | 832-824-5800 | oao@bcm.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 12, 2012 | Sep 1, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D063766 | Pediatric Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D015742 | Propofol |
| ID | Term |
|---|---|
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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|
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| Propofol | 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) |
|
|
| 30 seconds, 1 minute, and 2 minutes |
| BG001 | Non-obese | Non-obese children categorized as those with a body mass index(BMI)between 25-84th percentile Propofol : This arm of patients(non-obese)served as the control group for the obese children. Each non-obese child/subject received 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) |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
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| OG001 | Non-obese | Non-obese children categorized as those with a body mass index(BMI)between 25-84th percentile Propofol : This arm of patients(non-obese)served as the control group for the obese children. Each non-obese child/subject received 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) |
|
|
| Secondary | Depth of Sedation | 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). | Due to unavoidable circumstances during a clinical surgery, depth of sedation was not able to be collected on every subject at every time point. | Posted | Mean | Full Range | units on a scale | 30 seconds, 1 minute, and 2 minutes |
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| 0 |
| 40 |
| 0 |
| 40 |
| 0 |
| 40 |
| EG001 | Obese Children | Obese children are categorized as those with a body mass index >95th percentile 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) | 0 | 40 | 0 | 40 | 0 | 40 |
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| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| UMSS - 1 minute |
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| UMSS - 2 minutes |
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| Ramsay - 30 seconds |
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| Ramsay - 1 minute |
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| Ramsay - 2 minutes |
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