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

Disclosures

BMC Anesthesiol. 2013;13(8) 

In This Article

Discussion

TIVA with propofol in MO pediatric patients can be challenging in the absence of weight and dosing guidelines.We evaluated the clinical response to propofol anesthesia in this population.

While hemodynamic parameters during propofol TIVA were largely unchanged, BIS values for MO adolescents were below 40 for 93% of the maintenance phase. We believe that the increased anesthetic depth was a result of clinical overestimation of propofol requirements. Although our study did not have a BIS control group, our findings that MO adolescents undergoing clinically titrated propofol TIVA received high propofol doses, is in accordance with what has been reported in obese adults. Gaszynski et. al. demonstrated that obese adults undergoing clinically titrated propofol TIVA without BIS monitoring received higher propofol infusions (10 vs. 5.8 mg.kg-1/h), consumed more total propofol (2012 ± 310 mg vs. 1210 ± 370 mg) and had longer awakening times,[19] compared to those who were BIS monitored.

There are two other findings of significance. Firstly, prolonged emergence from anesthesia was observed in our study patients, with an average 'time to eye opening' of 25.9 ± 22.6 min, compared to 10.3 ± 5.4 minutes reported in non-obese children after clinically titrated propofol TIVA.[19,20] This was also reflected by deeper levels of sedation (RSS > 4) during the first 30 minutes in the PACU. Although there is some evidence for propofol accumulation and slow washout after continuous propofol infusions in MO adults,[21] this has not been supported by clinical data in adults.[14] We believe the prolonged emergence is due to the high propofol doses our study subjects received (mean = 3244 mg or 11.5 mg kg−1 h−1), which positively correlated with the 'time to eye-opening' (p = 0.03). Secondly, we note a 30% incidence of RAE in the immediate postoperative period with a 14% increased risk of RAE for every unit increase in BMI. Increased risk of RAE after propofol TIVA in obese patients, is supported by Zoremba et. al.'s finding of excessive impairment of pulmonary function in obese adults, two hours after propofol anesthesia.[22]

Despite the fact that in clinical settings, propofol is generally administered as a bolus for induction, we chose to use a standardized infusion method for induction. This allowed us to calculate an induction dose based on a clinical endpoint rather than an arbitrary weight-based dose. We noted a high correlation for induction dose to LBM (similar to findings of Ingrande et. al.)[23] and ABW which suggests that the dosing for induction be based on these scalars and not TBW. These findings need to be confirmed with large prospective studies and a formal pharmacokinetic-pharmacodynamic analysis. Pharmacokinetic analysis following this study has been completed and results have been published in an earlier report wherin TBW proved to be the most significant determinant for clearance, while no predictive covariates for volume of distribution were identified.[24] Our infusion regimen was based on ABW as Servin et. al. had used this weight in morbidly obese adults without evidence of propofol accumulation.[14] Our finding that an average infusion rate of 7 mg kg−1 h−1 TBW during 20–90 minutes of propofol maintenance phase correlates with a BIS of 40–60 (Figure 2A), is higher than the recommended rate of 4.6 to 6 mg kg−1 h−1 TBW to maintain BIS of 50 in obese adults during the same time period.[14,25] Considering that concentrations of 4.3 ± 1.1 mg.l−1 in non-obese children[11] and 3–4 mg.l−1 in obese adults, have been reported to correlate with a BIS of 50,[26] our findings of higher propofol concentrations during maintenance of anesthesia and corresponding lower BIS values suggests that clinical titration of propofol anesthesia in MO adolescents is not optimal.

Ramsay sedation scores were used to assess sedation in the postoperative period. We used a single non-anesthesia observer to rate RSS in all study subjects to limit inter-observer variance. However, caution is required in interpreting correlation of propofol concentrations with RSS as these sedation scores reflect the combination of propofol and opioid effects. We also note that the observational study design allowing clinical titration of propofol doses prevented standardization of dosages. Although dosing of propofol could be affected by differences in opioid doses, it has been reported to not affect the relation between propofol concentrations and BIS.[27] Hence, the lack of standardization of opioid doses would likely not affect our conclusions. Finally, our premise that BIS values below 40 represent very 'deep' anesthesia is debatable, but there is no evidence to the contrary, as none of our patients suffered any awareness. The other dilemma concerning the risks associated with excessive anesthesia dosing is still unresolved.[28]

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