Abstract
Purpose
Overdose with baclofen, a derivative of the inhibitory neurotransmitter γ-aminobutyric acid, may lead to severe respiratory and central nervous system depression and can be life-threatening. Prolonged half-lives of baclofen, of up to 34 h, have been reported in patients after overdose. Hemodialysis has proven to be a successful approach to improve clearance of baclofen, but the value of continuous venovenous hemofiltration (CVVH) is unclear. We applied CVVH in a patient with acute baclofen overdose.
Methods
Pharmacokinetic measurements of baclofen in serum and hemofiltrate were made at six time points after hospital admission. Baclofen concentration-time data were analyzed using non-compartmental methods, and the relative contribution of clearance by hemofiltration to total baclofen clearance was calculated.
Results
Baclofen concentrations in serum varied between 1.81 and 0.05 mg/L. Concentrations of baclofen in hemofiltrate were within the same range (between 0.74 and 0.05 mg/L), and the elimination half-life during hemofiltration was estimated at 4.8 h. Total clearance and clearance via hemofiltration were estimated at 6.6 and 2.4 L/h, indicating that clearance could be increased by approximately 57 % by applying hemofiltration.
Conclusions
The presented case demonstrates the usefulness of CVVH in the treatment of baclofen overdose and indicates that CVVH can be used as an alternative to hemodialysis in patients with overdose of baclofen.
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References
Summary of product characteristics baclofen. www.cbg-meb.nl/cbg/en. Accessed 12 Oct 2014
Weißhaar GF, Hoemberg M, Bender K et al (2012) Baclofen intoxication: a “fun drug” causing deep coma and nonconvulsive status epilepticus—a case report and review of the literature. Eur J Pediatr 171:1541–1547. doi:10.1007/s00431-012-1780-y
Fraser AD, MacNeil W, Isner AF (1991) Toxicological analysis of a fatal baclofen (Lioresal) ingestion. J Forensic Sci 36:1596–1602
Chen KS, Bullard MJ, Chien YY, Lee SY (1997) Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother 31:1315–1320
Faigle JW, Keberle H (1972) The chemistry and kinetics of Lioresal. Postgrad Med J 48(Suppl 5):9–13
Kochak GM, Rakhit A, Wagner WE et al (1985) The pharmacokinetics of baclofen derived from intestinal infusion. Clin Pharmacol Ther 38:251–257
Wuis EW, Dirks MJ, Termond EF et al (1989) Plasma and urinary excretion kinetics of oral baclofen in healthy subjects. Eur J Clin Pharmacol 37:181–184
Perry HE, Wright RO, Shannon MW et al (1998) Baclofen overdose: drug experimentation in a group of adolescents. Pediatrics 101:1045–1048. doi:10.1542/peds.101.6.1045
Sauneuf B, Totouom HK, Savary B et al (2012) Clinical and EEG features of acute intrathecal baclofen overdose. Clin Neurol Neurosurg 114:84–86. doi:10.1016/j.clineuro.2011.07.028
(2009) Martindale, The complete drug reference, 36th ed. 1888.
Ghose K, Holmes KM, Matthewson K (1980) Complications of baclofen overdosage. Postgrad Med J 56:865–867
Hsieh M-J, Chen S-C, Weng T-I et al (2012) Treating baclofen overdose by hemodialysis. Am J Emerg Med 30(1654):e5–e7. doi:10.1016/j.ajem.2011.07.013
Dias LS, Vivek G, Manthappa M, Acharya RV (2011) Role of hemodialysis in baclofen overdose with normal renal function. Indian J Pharmacol 43:722–723. doi:10.4103/0253-7613.89835
Brvar M, Vrtovec M, Kovac D et al (2007) Haemodialysis clearance of baclofen. Eur J Clin Pharmacol 63:1143–1146. doi:10.1007/s00228-007-0371-8
Wu V-C, Lin S-LS-M, Fang C-C (2005) Treatment of baclofen overdose by haemodialysis: a pharmacokinetic study. Nephrol Dial Transplant 20:441–443. doi:10.1093/ndt/gfh297
Gibaldi M, Perier D (1982) Noncompartmental analysis based on the statistical moment theory. Pharmacokinetics, 2nd ed. New York, pp 409–417
Rowland M, Tozer T (1995) Clinical pharmacokinetics: concepts and applications, 3rd ed. Williams & Wilkins
Nielsen SU, Jansen T, Johansen SS et al (2011) Venovenous hemodiafiltration for patient with baclofen intoxication. Ugeskr Laeger 173:1578–1579
Ghose K, Holmes KM, Matthewson K (1980) Complications of baclofen overdosage. Postgrad Med J 56:865–867
Lipscomb DJ, Meredith TJ (1980) Baclofen overdose. Postgrad Med J 56:108–109
Wuis EW, Dirks MJ, Termond EF et al (1989) Plasma and urinary excretion kinetics of oral baclofen in healthy subjects. Eur J Clin Pharmacol 37:181–184
Anderson P, Nohér H, Swahn CG (1984) Pharmacokinetics in baclofen overdose. J Toxicol Clin Toxicol 22:11–20
Gerkin R, Curry SC, Vance MV et al (1986) First-order elimination kinetics following baclofen overdose. Ann Emerg Med 15:843–846
Acknowledgments
We would like to thank the nurses at the intensive care unit of the Slotervaart Hospital for their contribution.
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The author (s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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The author (s) received no financial support for the research, authorship, and/or publication of this article.
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Meulendijks, D., Khan, S., Koks, C.H.W. et al. Baclofen overdose treated with continuous venovenous hemofiltration. Eur J Clin Pharmacol 71, 357–361 (2015). https://doi.org/10.1007/s00228-014-1802-y
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DOI: https://doi.org/10.1007/s00228-014-1802-y