K. R. Vega-Villa1, K. Kaneda2, S. Yamashita3, S. Woo1* and T. H. Han4* Aulianur

Burn patients develop resistance to Non-Depolarizing Neuromuscular Blocking Agents (NDNMBAs) and require a significantly large dose to produce a desired clinical response.

20 adults (2358 year) 2781% TBSA burn. Studied at 457 post-burn days and compared with age- and sex-matched,non-burn controls

Anaesthesia Induction and maintenance consisted of propofol 2.02.5 mg kg bolus, followed by 0.10.2 mg kg min.Intermittent fentanyl 12 mg/kgnitrous oxide 50% in oxygenVecuronium 0.12 mg/kg single IV

One patient in the burn group received a second bolus of vecuronium followed by continuous infusion at 3 hour after the first bolus of the study drug.A total of 565 data were used to construct the model, whereas 13.4% (n106) and 12.6% (n89)

On the contrary, 13 out of 20 non-burn patients had their plasma concentrations above the LOQ at 4 h after the bolus, although by the end of study period, only 5 patients had measurable concentrations

Tissue distribution of vecuronium was affected by burn injury.Of the total simulated concentrations, 28% corresponded to below LOQ, which was comparable with the 26% in the observed concentrations.

The pharmacological significance of our findings can be summarized in two aspects:the altered vecuronium disposition was characterized in burns compared with that in non-burns using a population PK modelling approach.

2. Data below LOQ were analysed using a likelihood-based approach in population PK model construction.

Multiple factors may contribute to the distributional changes of the drug, for example,- physiological changes by thea. thermal trauma, b. degree and mechanism of the injury, c. site of burn

Changes in plasma protein concentrations are observed in burn patients. During the first 48 hour after burn injury, albumin concentrations decrease (acute phase) and remain low for close to 60 days (hypermetabolic phase).

In this study, vecuronium concentrations fell below the quantifiable level by 4 hour after the bolus to a greater extent in burns than in non-burns, accounting for 26% of the total data being below LOQ.

PK analysis suggests that the rate and extent of tissue distribution of vecuronium are increased in burn patients, resulting in the rapid reduction of plasma vecuronium concentrations at the distribution and terminal phases.

Thank you