The effect of age on spontaneous breathing using propofol and remifentanil in children
Authors: Barker N. , Malherbe S. , Ansermino J.M. 
Published: May 2007

Introduction:  Maintaining spontaneous ventilation in children, using total intravenous anaesthesia, is often desirable, particularly for invasive airway procedures such as diagnostic airway endoscopy and removal of inhaled foreign bodies. The maximum tolerated infusion rate of remifentanil during spontaneous ventilation in combination with a volatile anaesthetic (sevoflurane) has been studied in children (1), where a large dose variation was found. This also seemed to vary widely compared to adults, who tolerated significantly less (2). Contrary to expectations however, younger children appeared to be more resistant to the respiratory depressant effect of the opioid. The aim of this study was therefore to determine what the effect of age is on spontaneous respiration when anaesthesia is maintained using infusions of propofol and remifentanil.

Methods:  After institutional ethics review board approval, 45 ASA I–II children, aged 6 months to 8 years and scheduled for strabismus surgery, were stratified by age into three equal groups (see Figure 1). After induction with propofol and remifentanil, a laryngeal mask was inserted. A propofol infusion was commenced at 300 μg·kg−1·min−1 and titrated to achieve a state entropy (GE Healthcare) value between 40 and 45. A remifentanil infusion was commenced after spontaneous respiration was restored and titrated using a modified up and down method, and using respiratory rate depression as a pharmacodynamic end point. Once the patient was breathing at a rate of just greater than 10, and was stable at this end point for 10 min, the rate of the remifentanil infusion was recorded. This method was used to estimate the group mean for final remifentanil infusion rate tolerated (RD50). The inter‐group comparisons were performed using one‐way ANOVA with subsequent pairwise comparisons using a Bonferroni correction.

 Final tolerated remifentanil infusion (μg·kg‐1·min‐1) for each patient in relation to their age (months).

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Results:  The plot of age against the final tolerated remifentanil dose is shown in the figure. Mean and (standard deviation) for the RD50 of groups 1 to 3 are 0.19 (0.08), 0.10 (0.04) and 0.08 (0.03) μg·kg‐1·min‐1 respectively. Pairwise comparisons between the groups for the rate of remifentanil tolerated revealed a statistically significant increase in the RD50 in children less than 3 years of age compared with older children in groups 2 and 3 (P < 0.001).

Conclusions:  The results suggest that younger children, especially those aged less than 3 years, are more tolerant to the respiratory rate depressant effect of remifentanil. This difference may be partly due to the larger volume of distribution compared with weight observed in younger children. However other pharmacokinetic and pharmacodynamic differences may exist in this population.

These findings confirm our clinical experience that maintaining spontaneous ventilation using total intravenous anaesthesia in younger children and infants is a feasible and attractive technique in situations where spontaneous ventilation is advantageous.