Pharmacokinetic data on high dose baclofen administration in unhealthy alcohol user in the ICU

Abstract

In the intensive care unit, alcohol intake above the NIAAA recommendations regardless of the existence of an Alcohol Use Disorder (AUD), was associated with an increased risk of death and longer time on ventilator. This rises the hypothesis that unhealthy alcohol use may lead to specific issues when weaning the mechanical ventilation (i.e. agitation or its related complications) regardless of AUD or withdrawal syndrome. Thus, we proposed to use baclofen off-label to avoid agitation. The data presented in this article is related to the research article entitled: "Pharmacokinetics and toxicity of high-dose baclofen in ICU patients" Vourc'h et al., 2019 Data provided in this submission includes 1) the detailed methods for baclofen assay by mass spectrometric detection, 2) the supplementary population pharmacokinetic analysis presenting observed concentration vs. population or individual predicted concentration (raw data of the latter is also available), and 3) the algorithm for the adaptation of baclofen daily doses according of the renal clearance to assess the risk of toxicity in critically ill patients.

Keywords: Agitation; Alcohol use disorder; Baclofen; Intensive care unit; Pharmacokinetic.

Fig. 1

Chromatograms of a patient (A) plasma sample (0,17 mg/L) and the internal standard (B). These chromatograms with a high intensity signal for a low baclofen plasma concentration show the specificity and the high sensitivity of the assay. This assay is specific because no interfering chromatographic peak was found with a retention time close to the retention time of the baclofen peak (3.07 min). This assay is sensitive because the peak intensity (about 5.0 × 10⁴ cps) is highly superior to the background noise of the baseline although the baclofen plasma concentration (0,17 mg/l) is low.

Fig. 2

Population pharmacokinetic analysis of baclofen (color). Diagnostic plots for population pharmacokinetic analysis of baclofen: observed concentration [DV (mg/L)] versus population predicted concentration [PRED (mg/L)], weighted residuals (WRES) versus PRED in the final model (Figs. 2-1 and 2-2) and the base model (Figs. 2-3 and 2-4).