Safe Administration of Propofol for Sedation in Children
|First Submitted Date ICMJE||January 27, 2009|
|First Posted Date ICMJE||January 29, 2009|
|Last Update Posted Date||August 18, 2009|
|Start Date ICMJE||June 2008|
|Primary Completion Date||March 2009 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Positive result: Spontaneous ventilation continues following administration of the full loading dose of propofol by infusion. [ Time Frame: Before and during surgery ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00832013 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Negative result: Apnoea occurs (no breath for 20 seconds or oxygen saturation less than 90%) before the complete dose is administered or within 4 minutes of the end of the dose. [ Time Frame: Before and during surgery ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Safe Administration of Propofol for Sedation in Children|
|Official Title ICMJE||Safe Administration of Propofol for Sedation in Children|
Advances in health care require that more children are given sedation to allow doctors to perform investigations or minor procedures. Sedation drugs have traditionally been given orally (swallowed) by children. However, oral sedation drugs have unpredictable characteristics, such as duration of sedation, which may result in difficulties performing the planned procedure.
Anesthetic drugs are now invariably used for sedation in children. These are given through an IV (skinny plastic tube inserted in to a vein). Propofol (white liquid) is the anesthetic drug most commonly used for sedation at BC Children's Hospital for sedation. Propofol has several advantages, including an accurately controllable depth of sedation (how deeply asleep), minimal effect on the heart and circulation and control of reflexes (e,g coughing) during the procedure. Propofol also promotes rapid recovery with less sickness and an earlier return to normal functioning following the procedure.
While propofol has many advantages it can cause respiratory depression (reduced breathing rate). This reduction in breathing is more common if propofol is given quickly. When your child is given propofol for their proposed procedure this is performed by a pediatric anesthesiologist who is skilled in supporting breathing should this be required. If your child does not participate in this study they will still receive propofol administered by the anesthesiologist as this is our usual practice. It would be routine to administer the propofol rapidly and then support breathing for a few minutes. This is very safe in the hands of an expert anesthesiologist but can be sometimes more risky in other settings where extensive monitoring and anesthesiologists are not available. This is the setting that propofol is used in many institutions.
Our goal is to determine how quickly propofol can be given without reducing breathing to the point that help with breathing is required.
Purpose Advances in minimally invasive radiological and surgical techniques demand that increasing numbers of children are given sedation or anesthesia to facilitate these procedures, frequently performed on an out-patient or day-care basis. Most are performed outside the operating room environment, with intensivists and emergency physicians administering over 55 % of sedation episodes, and only 19% being performed by anesthesiologists in North America. It is well documented that risks of complications during sedation exceed those experienced during the much more controlled environment of general anesthesia, with a twelve-fold increased risk of mortality when sedation is administered outside the operating room.
Sedative agents have traditionally been administered orally to children. However, characteristics of oral sedation drugs, such as unpredictable depth and duration of sedation resulting from variable drug absorption and prolonged duration of drug effect, have resulted in both high failure and complication rates. Recently, intravenous (IV) anesthetic drugs with more accurately titratable and predictable characteristics have gained popularity for a variety of sedation procedures. Propofol is the most commonly used intravenous agent for these procedures in North America.
Hypothesis The maximum safe infusion rate for an induction dose of propofol administered to children for sedation can be reliably predicted. Safety will be optimized by preventing apnoea whilst minimizing the time for induction of sedation and ensuring an adequate depth of sedation is achieved.
Justification Propofol is an intravenous (IV) anesthetic agent used for induction and maintenance of anesthesia in both adults and children. Propofol has several characteristics favouring its use, including an accurately titratable depth of anesthesia, cardiovascular stability, suppression of upper airway reflexes, rapid recovery with reduced post-operative nausea and vomiting and overall earlier return to pre-anesthetic functional state. At lower doses, propofol may also be used to maintain a level of sedation for radiological imaging or endoscopic investigations.
While propofol provides many advantages it does cause significant respiratory depression. Adverse respiratory events have been reported to be similar in both adults and children. Propofol induced respiratory depression may lead to hypoxemia requiring the provision of supplemental oxygen by mask and/or manual positive pressure ventilation.8 Artificial ventilation requires significant expertise and if poorly managed may result in gastric insufflation, pulmonary aspiration or hypoxia, all of which can lead to devastating complications such as permanent brain injury or death. The maximum dose or rate of administration of propofol that causes respiratory depression in children has yet to be accurately defined. Age specific effects have also not been reported.
•Develop a safe dosing schedule for propofol administration in children that will ensure spontaneous ventilation is maintained in at least 95% of subjects.
•Model the effects of propofol induction administered by intravenous infusion to facilitate the prediction of dosing schedules for different doses, different end-points in different clinical scenarios.
Research Method Prospective randomized study. Subjects will be randomly assigned to receive a predetermined infusion rate for propofol during induction of sedation.
Statistical Analysis A graphical representation of each data point with crossovers will be produced. Data will be analysed on a per protocol basis using the pooled-adjacent-violators algorithm to estimate the maximal infusion rate whilst preserving spontaneous ventilation. We will apply the boot-strap methods implemented by Pace to compute 95 % confidence limits. The effect of age, will be assessed by performing separate analyses in the age-strata.
To model the ventilatory effects of propofol, we will develop a mathematical model of human respiratory control. We will base this on the respiratory model proposed by Ursino (Ursino Model)19-21 which is a three compartment model comprising the lung, brain and tissues for gas exchange. We will enhance the model to include ventilatory regulation, along with pharmacokinetic and pharmacodynamic models of propofol including a respiratory effect site. The identification of suitable parameters for the model will include non-linear fitting of the clinical data (age, weight, BSA, ventilatory volumes, CO2 excretion, respiratory rate, and entropy).
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Propofol
See detailed description
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Estimated Enrollment ICMJE||120|
|Completion Date||August 2009|
|Primary Completion Date||March 2009 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
All ASA category 1 and 2 children aged 6-15y for elective upper or lower gastrointestinal endoscopic investigations to be performed under sedation. Stratification by age (<9y, 9-12y, >12y) will be performed to ensure balanced allocation of age groups and allow for identification of age and weight specific effects.
|Ages||6 Years to 15 Years (Child)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Canada|
|Removed Location Countries|
|NCT Number ICMJE||NCT00832013|
|Other Study ID Numbers ICMJE||H07-02846|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Dr. Mark Ansermino, University of British Columbia|
|Study Sponsor ICMJE||University of British Columbia|
|Collaborators ICMJE||Canadian Anesthesiologists' Society|
|PRS Account||University of British Columbia|
|Verification Date||August 2009|
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