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Pharmacokinetics of remifentanil sedation in paediatric intensive care

 Ann E Rigby-Jones¹, Melanie J Priston¹, J Robert Sneyd¹, Andrew R Wolf ²

 ¹ Peninsula Medical School, Universities of Exeter & Plymouth

² University Department of Anaesthesia, University of Bristol

Introduction

Remifentanil is a potentially useful agent for sedation of critically ill children.  This study determined remifentanil pharmacokinetics in post-cardiac surgery children.

Methods

We studied 26 children (1 month to 9.25 years, 3.1 to 39.8kg) receiving remifentanil (0.8mcg kg^-1 min^-1) and midazolam (50mcg kg^-1 min^-1) for sedation during mechanical ventilation following elective cardiac surgery.  A stepped wake-up procedure was performed in which the remifentanil infusion rate was decreased by 0.1mcg kg^-1 min^-1 every 20 minutes until the patient awoke.  Arterial blood samples (1mL) were collected for remifentanil quantification.  Pharmacokinetic models were constructed using NONMEM software.

Results

The combination of remifentanil and midazolam provided satisfactory sedation for these ventilated patients.  Remifentanil pharmacokinetics were best described using a 2-compartment model with all structural parameters allometrically scaled to body weight.  Age and cardiopulmonary bypass were not supported as model covariates.  Typical parameter values were:  clearance (CL) = 68.3mL kg^-1 min^-1, intercompartmental clearance (Q) = 80mL kg^-1 min^-1, volume of the central compartment (V1) = 91.7mL kg^-1, volume of the peripheral compartment (V2) = 141mL kg^-1 for a child of 10.5kg.

Discussion

When adjusted to account for body weight, our values for CL, V1 and the volume of distribution at steady state (V1+V2) are within 15% of those reported by Davis et al ¹ who studied a similar post-cardiac surgery paediatric population.  The allometric relationship between CL and body weight results in CL values that are proportionally higher in smaller children, in agreement with the study conducted by Ross et al².  Due to enhanced clearance rates, smaller (younger) children will require higher remifentanil infusion rates than larger (older) children and adults to achieve equivalent blood concentrations (Figure 1).

Figure 1  Simulations of a 60 minute infusion of remifentanil at 0.8mcg kg^-1 min^-1 were produced using our model and the models developed by Davis et al from a similar paediatric population², and by Minto et al  from an adult population^3.

Acknowledgements  The authors thanks research nurses Adrienne McCabe and Gerald Davies for their contribution to this study.

References

1.  Ross AK, Davis PJ, del Dear GL et al. Anesth Analg 2001; 93: 1393-401

2.  Davis PJ, Wilson AS, Siewers RD et al.Anesth Analg 1999; 89: 904-8

3.  Minto CF, Schnider TW, Egan TD et al. Anesthesiology. 1997; 86: 10-23