Evaluation of Propofol Anesthesia in Morbidly Obese Children and Adolescents

Vidya Chidambaran; Senthilkumar Sadhasivam; Jeroen Diepstraten; Hope Esslinger; Shareen Cox; Beverly M Schnell; Paul Samuels; Thomas Inge; Alexander A Vinks; Catherijne A Knibbe


BMC Anesthesiol. 2013;13(8) 

In This Article


A prospective study was conducted in MO children and adolescents between July 2009 and July 2010. The study protocol was approved by Cincinnati Children's Hospital institutional review board and written informed assent/consent was obtained from all participants and/or their guardians as appropriate.

Study Subjects

Inclusion criteria: 1) Males and females between the ages of 5 and 18 years, 2) Body Mass Index (BMI) for age > 95th percentile {> 95th percentile (obese), >99th percentile (MO)[13]}; 3) Patients undergoing elective surgery scheduled for a duration of at least 60 minutes.

Exclusion criteria: 1) Severe developmental delay, 2) Known cardiac anomaly, neurological, renal or hepatic disorders, 3) Known allergy to propofol, 4) Skin condition which would preclude placement of BIS sensor on the forehead.

Study Protocol

The patient was brought to the operating room, electrocardiograph, non-invasive blood pressure and pulse oximeter were applied, and an intravenous catheter was established. Before or immediately after induction, an age and head-size appropriate disposable BIS sensor® XP, (Aspect Medical Systems, Norwood, MA) was placed on each patient's forehead and connected to the BIS monitor. The BIS monitor screen was covered throughout the procedure to blind the anesthesia personnel to the BIS score and trend screen. Anesthesia was induced with propofol at a standardized infusion rate of 1000 μg.kg−1.min−1 after intravenous injection of lidocaine 30 mg. Infusion rates were based on adjusted body weight (ABW) which was calculated using total body weight (TBW) and ideal bodyweight (IBW), as described by Servin et. al.,[14] substituting 22 kg/m2 as Ideal BMI (in Servin's formula) with 50th percentile BMI for age and gender, obtained from Centers for Disease Control and Prevention, National Center for Health Statistics growth charts, United States. (https://www.cdc.gov/growthcharts/ webcite. May 30, 2000).

Patients were asked to count, or called repeatedly in a normal voice until the induction end-point of loss of verbal contact; this was recorded as 'time to induction'. Succinylcholine was administered and the trachea was intubated with an appropriate cuffed endotracheal tube. Anesthesia was maintained with propofol infusion. Vecuronium was titrated to Train-of-Four response (goal: one of four twitches). The induction dose of propofol was followed by propofol infusion at a rate of 250-350 μg/kg/min for 10 minutes and titrated in 25–50 μg/kg/min steps (reduced to prevent drop in systolic arterial blood pressure and heart rate below 30% of baseline values and titrated up when greater than 30% increase in heart rate or blood pressure occurred in the absence of new painful stimuli). Propofol was infused using calibrated pumps with internal memory and downloading capability. This allowed all real-time rates and rate changes to be recorded, including start and stop time of propofol dosing, propofol infusion rates, and propofol dose adjustments. Fentanyl 50–100 μg was administered after induction and 50 μg doses were administered in case of inadequate analgesia (defined as increase in heart rate and/or blood pressure above 30% of baseline with surgical incision or manipulation). When inadequate anesthesia or analgesia was not considered to be the reason for increase in blood pressure or heart rate, medications to correct hemodynamics were administered. The propofol infusion was decreased by 50% about 15 minutes before conclusion of surgery and discontinued when skin sutures were being placed. Muscle relaxants were reversed and once the patient was breathing, morphine/hydromorphone was dosed incrementally towards the end of the surgery, titrated to respiratory rate of 14–16 breaths per minute. After clinical confirmation of reversal, the trachea was extubated awake. Patients were then transferred to the recovery area (PACU) and followed until they achieved PACU discharge criteria.


Patient demographics, age, gender, weight (TBW) and height were collected. After computing the BMI, IBW and ABW were calculated according to equations 1 and 2. Ideal BMI in Equation 2 is defined as the 50th percentile values from age and sex – specific BMI for age charts at https://www.cdc.gov webcite. A calculator available at https://www.bcm.edu/cnrc/bodycomp/bmiz2.html webcite was used to calculate BMI for age percentiles. Lean body mass (LBM) was calculated using the formula described by Peters et. al. by first estimating Extracellular Volume (ECV) from weight and height[15] according to the following equation.

Propofol and Opioid Doses

Posthoc calculation of induction dose required to achieve loss of verbal contact was performed by multipying the rate of infusion and time taken to reach the end-point. Means and SD of propofol infusion rates during maintenance were analyzed from pooled data. Propofol maintenance infusion rates were plotted against BIS values and time since start of propofol infusion. Infusion rates of eight patients corresponding to BIS values of 40–60 were then analyzed to derive mean and SD. Hourly opioid use as fentanyl equivalent doses were calculated, based on an equivalence of morphine 10 mg = 2 mg hydromorphone = 100 μg fentanyl.


Clinical data including mean, systolic, diastolic blood pressure (MAP, SBP and DBP respectively) and heart rate/HR were recorded electronically every 5 minutes intraoperatively. For each of the measured hemodynamic parameters, percentage difference from baseline (value recorded 5 minutes before propofol induction) was calculated according to the following equation.


BIS data were transferred electronically to a computerized record in one-second increments. This included the date and time of BIS data collection, minimum and maximum BIS values, average Signal Quality Index (SQI) and average electromyography (EMG). The smoothing rate of the BIS monitor was set at 15 seconds. Evaluable BIS values were defined as those with Signal Quality Index > 70.

Blood Sampling and Propofol Analysis

Blood samples (1.0 ml) were obtained from a dedicated intravenous catheter placed in the upper extremity contralateral to the propofol infusion site. Samples were obtained at baseline prior to the start of propofol, approximately 15, 30, 45, 60, 120, 180, 240 minutes after the start of the propofol infusion, at 5 and 20 minutes after dose adjustment, just before discontinuation of the propofol infusion and at 5, 10, 15, 30, 45 and 120 minutes after termination of the infusion. Whole-blood samples for propofol analysis were stored at 4°C until analysis (within 1 month) by high-performance liquid chromatography with fluorescence detection. The coefficients of variation for the intra-assay and interassay precision over the concentration range from 0.05 to 5.0 mg.l−1 were less than 4.5% and 7.1% respectively. The lower limit of quantification was 0.05 mg.l−1.[16]

Ramsay Sedation Scores

Ramsay Sedation Scores (RSS) were recorded post-operatively about every 10 minutes for the first 30 minutes and thereafter every 30 minutes while in the PACU.[17]

Other Clinical Data

'Time to eye opening', defined as the time from cessation of propofol infusion to eye opening on verbal command, was noted. Respiratory adverse events (RAE) defined as airway obstruction requiring airway manipulation, episodes of desaturation (< 90%) and/or need for oxygen for >120 minutes in the immediate postoperative period were also recorded. On postoperative day 1 and 3, patients were evaluated using the Structured Awareness Screening Interview created by Davidson et. al.[18]

Statistical Analysis

GraphPad Prism 5 software (GraphPad Software Inc., La Jolla, CA) was used to generate descriptive statistics (mean, standard deviation, median and range for continuous variables and frequencies for categorical variables). Linear, quadratic and cubic trends were tested to detect correlation of weight scalars (TBW, ABW and LBM) with induction dose, in addition to calculation of root mean square errors (MSE) and the regression lines fitted. SAS software © (SAS version 9.2, Cary, North Carolina) was used to perform logistic regression between occurrence of respiratory adverse events and explanatory variables (TBW, IBW, ABW, BMI, propofol amount and duration of propofol infusion) to detect two-tailed p values with a 95% Confidence Intervals (CI).