An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose

D. Perichon, S. Turfus, D. Gerostamoulos, A. Graudins

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background. Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning. Method. Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20% intravenous lipid emulsion (ILE), 8.4% sodium bicarbonate or Hartmann's solution was infused to anaesthetized and ventilated rodents (n = 10 per group). Heart rate, blood pressure, cutaneous ECG-QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA. Results. ILE infusion significantly decreased the survival compared to other treatments (10% ILE vs 70% bicarbonate vs 70% Hartmann's solution, p = 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann's solution treatments. This was associated with significantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p < 0.02). Conclusion. Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.

LanguageEnglish
Pages208-215
Number of pages8
JournalClinical Toxicology
Volume51
Issue number4
DOIs
Publication statusPublished - 1 May 2013
Externally publishedYes

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Intravenous Fat Emulsions
Amitriptyline
Hemodynamics
Stomach
Blood
Pharmaceutical Preparations
Poisoning
Blood pressure
Blood Pressure
Gastrointestinal Agents
Sodium Bicarbonate
Bicarbonates
Analysis of variance (ANOVA)
Electrocardiography
Gastrointestinal Tract
Rodentia
Analysis of Variance

Cite this

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title = "An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose",
abstract = "Background. Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning. Method. Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20{\%} intravenous lipid emulsion (ILE), 8.4{\%} sodium bicarbonate or Hartmann's solution was infused to anaesthetized and ventilated rodents (n = 10 per group). Heart rate, blood pressure, cutaneous ECG-QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA. Results. ILE infusion significantly decreased the survival compared to other treatments (10{\%} ILE vs 70{\%} bicarbonate vs 70{\%} Hartmann's solution, p = 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann's solution treatments. This was associated with significantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p < 0.02). Conclusion. Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.",
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author = "D. Perichon and S. Turfus and D. Gerostamoulos and A. Graudins",
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An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose. / Perichon, D.; Turfus, S.; Gerostamoulos, D.; Graudins, A.

In: Clinical Toxicology, Vol. 51, No. 4, 01.05.2013, p. 208-215.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose

AU - Perichon, D.

AU - Turfus, S.

AU - Gerostamoulos, D.

AU - Graudins, A.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - Background. Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning. Method. Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20% intravenous lipid emulsion (ILE), 8.4% sodium bicarbonate or Hartmann's solution was infused to anaesthetized and ventilated rodents (n = 10 per group). Heart rate, blood pressure, cutaneous ECG-QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA. Results. ILE infusion significantly decreased the survival compared to other treatments (10% ILE vs 70% bicarbonate vs 70% Hartmann's solution, p = 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann's solution treatments. This was associated with significantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p < 0.02). Conclusion. Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.

AB - Background. Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning. Method. Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20% intravenous lipid emulsion (ILE), 8.4% sodium bicarbonate or Hartmann's solution was infused to anaesthetized and ventilated rodents (n = 10 per group). Heart rate, blood pressure, cutaneous ECG-QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA. Results. ILE infusion significantly decreased the survival compared to other treatments (10% ILE vs 70% bicarbonate vs 70% Hartmann's solution, p = 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann's solution treatments. This was associated with significantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p < 0.02). Conclusion. Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.

KW - Amitriptyline

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KW - Overdose

KW - Poisoning

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