Spectroscopic detection of brain propylene glycol in neonates: Effects of different pharmaceutical formulations of phenobarbital

Petra J W Pouwels, Monique van de Lagemaat, Laura A van de Pol, Bregje C M Witjes, Inge A Zonnenberg

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: The first choice for treatment of neonatal convulsions is intravenous phenobarbital, which contains propylene glycol (PG) as a solvent. Although PG is generally considered safe, the dosage can exceed safety thresholds in neonates. High PG levels can cause lactic acidosis.

PURPOSE/HYPOTHESIS: To investigate a relationship between brain PG concentration and medication administered to neonates, and to study if a correlation between spectroscopically detected PG and lactate was present.

STUDY TYPE: Retrospective.

POPULATION: Forty-one neonates who underwent MRI/MRS.

FIELD STRENGTH/SEQUENCE: Short echo time single voxel MRS at 1.5T.

ASSESSMENT: Spectra were quantified. Concentrations of PG were correlated with medication administered, because intravenously administered phenobarbital solutions contained 10, 25, or 50 mg phenobarbital per ml, all containing 350 mg PG per ml. The interval between medication and MRI/MRS was determined.

STATISTICAL TESTS: Chi-square test, Student's t-test, Mann-Whitney U-test and Spearman correlation.

RESULTS: Eighteen neonates had brain PG >1 mM (median 3.4 mM, maximum 9.5 mM). All 18 neonates with high brain PG and 14 neonates with low brain PG (<1 mM) received phenobarbital as the only source of PG. Nine neonates did not receive any phenobarbital/PG-containing medication. Neonates with high brain PG more often received 10 mg/ml phenobarbital, resulting in higher PG dose (high vs. low brain PG (median [interquartile range]: 1400 [595] vs. 350 [595] mg/kg, respectively, P < 0.01). In addition, the interval between the last phenobarbital dose and MRI was shorter in the high brain PG group (high vs. low brain PG: 16 [21] vs. 95 [83] hours, respectively, P < 0.001). Within neonates that received phenobarbital, there was no conclusive correlation between spectroscopically detected PG and lactate (Spearman's rho = 0.23, P = 0.10).

DATA CONCLUSION: These MRS findings may increase awareness of potentially toxic PG concentrations in the neonatal brain due to intravenous phenobarbital administration and its dependence on the phenobarbital formulation used.

LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.

Original languageEnglish
Pages (from-to)1062-1068
JournalJournal of magnetic resonance imaging : JMRI
Volume49
Issue number4
DOIs
Publication statusPublished - 2019

Cite this

@article{410ee9f967cd46ceba6a950446988e48,
title = "Spectroscopic detection of brain propylene glycol in neonates: Effects of different pharmaceutical formulations of phenobarbital",
abstract = "BACKGROUND: The first choice for treatment of neonatal convulsions is intravenous phenobarbital, which contains propylene glycol (PG) as a solvent. Although PG is generally considered safe, the dosage can exceed safety thresholds in neonates. High PG levels can cause lactic acidosis.PURPOSE/HYPOTHESIS: To investigate a relationship between brain PG concentration and medication administered to neonates, and to study if a correlation between spectroscopically detected PG and lactate was present.STUDY TYPE: Retrospective.POPULATION: Forty-one neonates who underwent MRI/MRS.FIELD STRENGTH/SEQUENCE: Short echo time single voxel MRS at 1.5T.ASSESSMENT: Spectra were quantified. Concentrations of PG were correlated with medication administered, because intravenously administered phenobarbital solutions contained 10, 25, or 50 mg phenobarbital per ml, all containing 350 mg PG per ml. The interval between medication and MRI/MRS was determined.STATISTICAL TESTS: Chi-square test, Student's t-test, Mann-Whitney U-test and Spearman correlation.RESULTS: Eighteen neonates had brain PG >1 mM (median 3.4 mM, maximum 9.5 mM). All 18 neonates with high brain PG and 14 neonates with low brain PG (<1 mM) received phenobarbital as the only source of PG. Nine neonates did not receive any phenobarbital/PG-containing medication. Neonates with high brain PG more often received 10 mg/ml phenobarbital, resulting in higher PG dose (high vs. low brain PG (median [interquartile range]: 1400 [595] vs. 350 [595] mg/kg, respectively, P < 0.01). In addition, the interval between the last phenobarbital dose and MRI was shorter in the high brain PG group (high vs. low brain PG: 16 [21] vs. 95 [83] hours, respectively, P < 0.001). Within neonates that received phenobarbital, there was no conclusive correlation between spectroscopically detected PG and lactate (Spearman's rho = 0.23, P = 0.10).DATA CONCLUSION: These MRS findings may increase awareness of potentially toxic PG concentrations in the neonatal brain due to intravenous phenobarbital administration and its dependence on the phenobarbital formulation used.LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.",
keywords = "MR spectroscopy, lactate, newborns, phenobarbital, propane-1,2-diol, propylene glycol",
author = "Pouwels, {Petra J W} and {van de Lagemaat}, Monique and {van de Pol}, {Laura A} and Witjes, {Bregje C M} and Zonnenberg, {Inge A}",
note = "{\circledC} 2018 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.",
year = "2019",
doi = "10.1002/jmri.26344",
language = "English",
volume = "49",
pages = "1062--1068",
journal = "Journal of magnetic resonance imaging : JMRI",
issn = "1053-1807",
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}

Spectroscopic detection of brain propylene glycol in neonates : Effects of different pharmaceutical formulations of phenobarbital. / Pouwels, Petra J W; van de Lagemaat, Monique; van de Pol, Laura A; Witjes, Bregje C M; Zonnenberg, Inge A.

In: Journal of magnetic resonance imaging : JMRI, Vol. 49, No. 4, 2019, p. 1062-1068.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Spectroscopic detection of brain propylene glycol in neonates

T2 - Effects of different pharmaceutical formulations of phenobarbital

AU - Pouwels, Petra J W

AU - van de Lagemaat, Monique

AU - van de Pol, Laura A

AU - Witjes, Bregje C M

AU - Zonnenberg, Inge A

N1 - © 2018 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

PY - 2019

Y1 - 2019

N2 - BACKGROUND: The first choice for treatment of neonatal convulsions is intravenous phenobarbital, which contains propylene glycol (PG) as a solvent. Although PG is generally considered safe, the dosage can exceed safety thresholds in neonates. High PG levels can cause lactic acidosis.PURPOSE/HYPOTHESIS: To investigate a relationship between brain PG concentration and medication administered to neonates, and to study if a correlation between spectroscopically detected PG and lactate was present.STUDY TYPE: Retrospective.POPULATION: Forty-one neonates who underwent MRI/MRS.FIELD STRENGTH/SEQUENCE: Short echo time single voxel MRS at 1.5T.ASSESSMENT: Spectra were quantified. Concentrations of PG were correlated with medication administered, because intravenously administered phenobarbital solutions contained 10, 25, or 50 mg phenobarbital per ml, all containing 350 mg PG per ml. The interval between medication and MRI/MRS was determined.STATISTICAL TESTS: Chi-square test, Student's t-test, Mann-Whitney U-test and Spearman correlation.RESULTS: Eighteen neonates had brain PG >1 mM (median 3.4 mM, maximum 9.5 mM). All 18 neonates with high brain PG and 14 neonates with low brain PG (<1 mM) received phenobarbital as the only source of PG. Nine neonates did not receive any phenobarbital/PG-containing medication. Neonates with high brain PG more often received 10 mg/ml phenobarbital, resulting in higher PG dose (high vs. low brain PG (median [interquartile range]: 1400 [595] vs. 350 [595] mg/kg, respectively, P < 0.01). In addition, the interval between the last phenobarbital dose and MRI was shorter in the high brain PG group (high vs. low brain PG: 16 [21] vs. 95 [83] hours, respectively, P < 0.001). Within neonates that received phenobarbital, there was no conclusive correlation between spectroscopically detected PG and lactate (Spearman's rho = 0.23, P = 0.10).DATA CONCLUSION: These MRS findings may increase awareness of potentially toxic PG concentrations in the neonatal brain due to intravenous phenobarbital administration and its dependence on the phenobarbital formulation used.LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.

AB - BACKGROUND: The first choice for treatment of neonatal convulsions is intravenous phenobarbital, which contains propylene glycol (PG) as a solvent. Although PG is generally considered safe, the dosage can exceed safety thresholds in neonates. High PG levels can cause lactic acidosis.PURPOSE/HYPOTHESIS: To investigate a relationship between brain PG concentration and medication administered to neonates, and to study if a correlation between spectroscopically detected PG and lactate was present.STUDY TYPE: Retrospective.POPULATION: Forty-one neonates who underwent MRI/MRS.FIELD STRENGTH/SEQUENCE: Short echo time single voxel MRS at 1.5T.ASSESSMENT: Spectra were quantified. Concentrations of PG were correlated with medication administered, because intravenously administered phenobarbital solutions contained 10, 25, or 50 mg phenobarbital per ml, all containing 350 mg PG per ml. The interval between medication and MRI/MRS was determined.STATISTICAL TESTS: Chi-square test, Student's t-test, Mann-Whitney U-test and Spearman correlation.RESULTS: Eighteen neonates had brain PG >1 mM (median 3.4 mM, maximum 9.5 mM). All 18 neonates with high brain PG and 14 neonates with low brain PG (<1 mM) received phenobarbital as the only source of PG. Nine neonates did not receive any phenobarbital/PG-containing medication. Neonates with high brain PG more often received 10 mg/ml phenobarbital, resulting in higher PG dose (high vs. low brain PG (median [interquartile range]: 1400 [595] vs. 350 [595] mg/kg, respectively, P < 0.01). In addition, the interval between the last phenobarbital dose and MRI was shorter in the high brain PG group (high vs. low brain PG: 16 [21] vs. 95 [83] hours, respectively, P < 0.001). Within neonates that received phenobarbital, there was no conclusive correlation between spectroscopically detected PG and lactate (Spearman's rho = 0.23, P = 0.10).DATA CONCLUSION: These MRS findings may increase awareness of potentially toxic PG concentrations in the neonatal brain due to intravenous phenobarbital administration and its dependence on the phenobarbital formulation used.LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.

KW - MR spectroscopy

KW - lactate

KW - newborns

KW - phenobarbital

KW - propane-1,2-diol

KW - propylene glycol

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U2 - 10.1002/jmri.26344

DO - 10.1002/jmri.26344

M3 - Article

VL - 49

SP - 1062

EP - 1068

JO - Journal of magnetic resonance imaging : JMRI

JF - Journal of magnetic resonance imaging : JMRI

SN - 1053-1807

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