Evaluation of propofol anesthesia in morbidly obese children and adolescents

Abstract

Background: Poor characterization of propofol pharmacokinetics and pharmacodynamics in the morbidly obese (MO) pediatric population poses dosing challenges. This study was conducted to evaluate propofol total intravenous anesthesia (TIVA) in this population.

Methods: After IRB approval, a prospective study was conducted in 20 MO children and adolescents undergoing laparoscopic surgery under clinically titrated propofol TIVA. Propofol doses/infusion rates, hemodynamic variables, times to induction and emergence, and postoperative occurrence of respiratory adverse events (RAE) were recorded, along with intraoperative blinded Bispectral Index/BIS and postoperative Ramsay sedation scores (RSS). Study subjects completed awareness questionnaires on postoperative days 1 and 3. Propofol concentrations were obtained at predetermined intra- and post-operative time points.

Results: Study subjects ranged 9 - 18 years (age) and 97 - 99.9% (BMI for age percentiles). Average percentage variability of hemodynamic parameters from baseline was ≈ 20%. Patients had consistently below target BIS values (BIS < 40 for >90% of maintenance phase), delayed emergence (25.8 ± 22 minutes), increased somnolence (RSS ≥ 4) in the first 30 minutes of recovery from anesthesia and 30% incidence of postoperative RAE, the odds for which increased by 14% per unit increase in BMI (p ≤ 0.05). Mean propofol concentration was 6.2 mg/L during maintenance and 1.8 mg/L during emergence from anesthesia.

Conclusions: Our findings indicate clinical overestimation of propofol requirements and highlight the challenges of clinically titrated propofol TIVA in MO adolescents. In this setting, it may be advantageous to titrate propofol to targeted BIS levels until more accurate weight-appropriate dosing regimens are developed, to minimize relative overdosing and its consequences.

Keywords: Adolescents; Anesthetic depth; Bariatric; Bispectral index; Morbidly obese; Pediatric; Propofol; Total intravenous anesthesia.

Figure 1

Linear regression of propofol induction dose to weight scalars. Linear regression trendlines for correlation of posthoc calculated induction dose of propofol (titrated to loss of verbal contact) with weight scalars are shown. The correlation coefficients, Root Mean Square Errors (Root MSE) and p-values for the correlations were found to be R² = 0.58, Root MSE = 45.92, p = 0.0068 for Lean Body Mass (LBM), R² = 0.54, Root MSE = 47.82, p = 0.01 for Adjusted Body Weight (ABW) and R² = 0.5, Root MSE = 49.61, p = 0.0143 for Total Body Weight (TBW).

Figure 2

Maintenance propofol infusion rates. Data analysis of propofol infusion rates used during the maintenance phase (in μg kg^-1 h^-1 on the left Y-axis and mg kg^-1 h^-1 on the right Y-axis) based on total body weight (TBW) and adjusted body weight (ABW) are depicted in (A) and (B) respectively. The red solid circles and the grey shaded area within the error bands (red dotted lines) represent the means and SD of actual administered infusion rates over time, while the green dots and vertical lines represent the means and SD of infusion rates corresponding to BIS values of 40-60.

Figure 3

Variability of hemodynamic parameters over time during propofol anesthesia. In this figure, time profiles of variability of heart rate (A), diastolic blood pressure (DBP) (B), systolic blood pressure (SBP) (C) and mean blood pressure (MAP) (D) are presented as the mean (black solid circles) and standard deviation (SD) {grey shaded area between error bands (black dotted lines)} of the % change from baseline for the stated parameter, plotted every 5 minutes during 200 minutes of propofol anesthesia. The first dot on the timeline represents the start of propofol induction (baseline) and hence % variability is 0%.

Figure 4

Summary of propofol concentrations during different phases of propofol anesthesia and BIS values over time. (A) represents the means (black solid circles for induction phase, squares for maintenance and inverted triangles for emergence phase) and standard deviations (SD) (black vertical lines) of propofol concentrations during different phases of anesthesia; The propofol concentration during the induction phase (first 15 minutes) was 7.0 ± 4.1 mg.l^-1 (n = 16). The mean (SD)(number of samples) for propofol concentrations collected during 15-30, 30-60, 60-90, 90-120 and >120 minute time intervals of maintenance anesthesia were 6.8(1.8)(26), 6.9(2.5)(41), 5.8(2.2)(36), 5.4(2.7)(15) and 6.1(3.2)(29) mg.l^-1 respectively. (B) shows the means (black solid circles) and SD (black vertical lines) of blinded BIS values during 10-200 minutes of maintenance phase of propofol anesthesia. Grey shaded areas depict range of propofol concentrations reported to be associated with BIS 50 in children (A) (3.2-5.4 mg.l-1: Riguozzo et. al, 2010) and BIS values generally considered to infer adequate depth of anesthesia (B) (46-60) for this population.