Hemodynamic Effects of Intravenous, High-Dose Lipid Emulsion With and Without Metoprolol Infusion in Healthy Volunteers: A Randomized Clinical Trial

Kasper Meidahl Petersen; Søren Bøgevig; Tonny Studsgaard Petersen; Thomas Bo Jensen; Kim Peder Dalhoff; Trine Henriksen; Henrik Enghusen Poulsen; Mikkel Bring Christensen

doi:10.1002/cpt.1281

Hemodynamic Effects of Intravenous, High-Dose Lipid Emulsion With and Without Metoprolol Infusion in Healthy Volunteers: A Randomized Clinical Trial

Kasper Meidahl Petersen, Søren Bøgevig, Tonny Studsgaard Petersen, Thomas Bo Jensen, Kim Peder Dalhoff, Trine Henriksen, Henrik Enghusen Poulsen, Mikkel Bring Christensen^*

^*Corresponding author for this work

Department of Clinical Medicine

Abstract

In a double-blinded, randomized, crossover trial, we investigated the hemodynamic effects of high-dose intravenous lipid emulsion (ILE) with/without metoprolol. Ten healthy volunteers each completed 4 trial days (placebo + ILE; metoprolol + placebo; metoprolol + ILE; placebo + placebo) in random order. Metoprolol was administered as an initial bolus (10 mg), followed by an infusion (50 mg) from 5 to 30 minutes. ILE was administered as a bolus at 12.5 minutes (2.5 mL/kg), followed by a 15-minute infusion (0.25 mL/kg per minute). On metoprolol + ILE days (compared with metoprolol + placebo) after 120 minutes, mean heart rates were significantly higher (difference, 5.5 beats per minute (bpm); 95% confidence interval (CI), 3.0–8.1 bpm; P < 0.001), and average relative cardiac output was higher (difference, 10 percentage points; 95% CI, 5–15 percentage points; P < 0.001). The hemodynamic effect of ILE developed gradually. ILE had no effect on plasma metoprolol or major adverse events. In conclusion, high-dose ILE has relatively marginal and delayed hemodynamic effects that may have limited clinical relevance in the short-term clinical toxicological setting.

Original language	English
Journal	Clinical Pharmacology and Therapeutics
Pages (from-to)	1009-1017
ISSN	0009-9236
DOIs	https://doi.org/10.1002/cpt.1281
Publication status	Published - Apr 2019

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Petersen, K. M., Bøgevig, S., Petersen, T. S., Jensen, T. B., Dalhoff, K. P., Henriksen, T., Poulsen, H. E., & Christensen, M. B. (2019). Hemodynamic Effects of Intravenous, High-Dose Lipid Emulsion With and Without Metoprolol Infusion in Healthy Volunteers: A Randomized Clinical Trial. Clinical Pharmacology and Therapeutics, 1009-1017. https://doi.org/10.1002/cpt.1281

Hemodynamic Effects of Intravenous, High-Dose Lipid Emulsion With and Without Metoprolol Infusion in Healthy Volunteers: A Randomized Clinical Trial. / Petersen, Kasper Meidahl; Bøgevig, Søren; Petersen, Tonny Studsgaard et al.
In: Clinical Pharmacology and Therapeutics, 04.2019, p. 1009-1017.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Hemodynamic Effects of Intravenous, High-Dose Lipid Emulsion With and Without Metoprolol Infusion in Healthy Volunteers: A Randomized Clinical Trial",

abstract = "In a double-blinded, randomized, crossover trial, we investigated the hemodynamic effects of high-dose intravenous lipid emulsion (ILE) with/without metoprolol. Ten healthy volunteers each completed 4 trial days (placebo + ILE; metoprolol + placebo; metoprolol + ILE; placebo + placebo) in random order. Metoprolol was administered as an initial bolus (10 mg), followed by an infusion (50 mg) from 5 to 30 minutes. ILE was administered as a bolus at 12.5 minutes (2.5 mL/kg), followed by a 15-minute infusion (0.25 mL/kg per minute). On metoprolol + ILE days (compared with metoprolol + placebo) after 120 minutes, mean heart rates were significantly higher (difference, 5.5 beats per minute (bpm); 95% confidence interval (CI), 3.0–8.1 bpm; P < 0.001), and average relative cardiac output was higher (difference, 10 percentage points; 95% CI, 5–15 percentage points; P < 0.001). The hemodynamic effect of ILE developed gradually. ILE had no effect on plasma metoprolol or major adverse events. In conclusion, high-dose ILE has relatively marginal and delayed hemodynamic effects that may have limited clinical relevance in the short-term clinical toxicological setting.",

author = "Petersen, {Kasper Meidahl} and S{\o}ren B{\o}gevig and Petersen, {Tonny Studsgaard} and Jensen, {Thomas Bo} and Dalhoff, {Kim Peder} and Trine Henriksen and Poulsen, {Henrik Enghusen} and Christensen, {Mikkel Bring}",

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AU - Petersen, Kasper Meidahl

AU - Bøgevig, Søren

AU - Petersen, Tonny Studsgaard

AU - Jensen, Thomas Bo

AU - Dalhoff, Kim Peder

AU - Henriksen, Trine

AU - Poulsen, Henrik Enghusen

AU - Christensen, Mikkel Bring

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N2 - In a double-blinded, randomized, crossover trial, we investigated the hemodynamic effects of high-dose intravenous lipid emulsion (ILE) with/without metoprolol. Ten healthy volunteers each completed 4 trial days (placebo + ILE; metoprolol + placebo; metoprolol + ILE; placebo + placebo) in random order. Metoprolol was administered as an initial bolus (10 mg), followed by an infusion (50 mg) from 5 to 30 minutes. ILE was administered as a bolus at 12.5 minutes (2.5 mL/kg), followed by a 15-minute infusion (0.25 mL/kg per minute). On metoprolol + ILE days (compared with metoprolol + placebo) after 120 minutes, mean heart rates were significantly higher (difference, 5.5 beats per minute (bpm); 95% confidence interval (CI), 3.0–8.1 bpm; P < 0.001), and average relative cardiac output was higher (difference, 10 percentage points; 95% CI, 5–15 percentage points; P < 0.001). The hemodynamic effect of ILE developed gradually. ILE had no effect on plasma metoprolol or major adverse events. In conclusion, high-dose ILE has relatively marginal and delayed hemodynamic effects that may have limited clinical relevance in the short-term clinical toxicological setting.

AB - In a double-blinded, randomized, crossover trial, we investigated the hemodynamic effects of high-dose intravenous lipid emulsion (ILE) with/without metoprolol. Ten healthy volunteers each completed 4 trial days (placebo + ILE; metoprolol + placebo; metoprolol + ILE; placebo + placebo) in random order. Metoprolol was administered as an initial bolus (10 mg), followed by an infusion (50 mg) from 5 to 30 minutes. ILE was administered as a bolus at 12.5 minutes (2.5 mL/kg), followed by a 15-minute infusion (0.25 mL/kg per minute). On metoprolol + ILE days (compared with metoprolol + placebo) after 120 minutes, mean heart rates were significantly higher (difference, 5.5 beats per minute (bpm); 95% confidence interval (CI), 3.0–8.1 bpm; P < 0.001), and average relative cardiac output was higher (difference, 10 percentage points; 95% CI, 5–15 percentage points; P < 0.001). The hemodynamic effect of ILE developed gradually. ILE had no effect on plasma metoprolol or major adverse events. In conclusion, high-dose ILE has relatively marginal and delayed hemodynamic effects that may have limited clinical relevance in the short-term clinical toxicological setting.

U2 - 10.1002/cpt.1281

DO - 10.1002/cpt.1281

M3 - Journal article

C2 - 30412277

AN - SCOPUS:85059097126

SN - 0009-9236

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EP - 1017

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

ER -

Hemodynamic Effects of Intravenous, High-Dose Lipid Emulsion With and Without Metoprolol Infusion in Healthy Volunteers: A Randomized Clinical Trial

Abstract

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