Effect of heart rate on the pharmacokinetics of fentanyl in dogs anesthetized with isoflurane and hydromorphone

Marcela L. Machado, Joao HN Soares, Bruno H Pypendop, Natalia Henao-Guerrero, Noah D. Pavlisko, Juliet Ross

Research output: Contribution to journalArticle

Abstract

Objective: To compare the pharmacokinetics of fentanyl at lower (LHR) or higher heart rate (HHR) in dogs anesthetized with isoflurane. Study design: Prospective, randomized, crossover controlled trial. Animals: A group of six healthy 13-month-old male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation). Methods: Dogs were allocated to two treatments: LHR (HR: 45–75 beats minute−1) and HHR (HR: 100–130 beats minute−1). Anesthesia was maintained with isoflurane and hydromorphone (0.1 mg kg−1 followed by 0.02–0.10 mg kg−1 hour−1) for both treatments. Glycopyrrolate was administered in HHR to maintain HR within the desired range. Afterwards, fentanyl (20 μg kg−1) was intravenously administered over 5 minutes. Arterial blood samples were collected for plasma fentanyl concentration measurement by liquid chromatography/mass spectrometry. The pharmacokinetics of fentanyl were compared between treatments and the differences were considered significant at p < 0.05. Results: A three-compartment model best fitted the changes in plasma fentanyl concentration. Clearance (CL; mL minute−1 kg−1) was 33.2 (24.0–48.0) and 61.3 (44.5–72.7), maximum concentration (ng mL−1) 33.6 (23.4–36.6) and 20.0 (16.7–28.0), apparent volume of the rapid peripheral compartment (mL kg−1) 436 (352–723) and 925 (499–1887), apparent volume at steady state (mL kg−1) 4064 (3453–6546) and 7195 (5077–8601), cardiac index (CI; mL minute−1 m−2) 2.83 (1.98–3.67) and 4.91 (3.22–6.09) and HR (beats minute−1) 68 (49–72) and 120 (102–129) for LHR and HHR, respectively, with significant differences between treatments. Significant correlations (0.92 and 0.90) were found between CI and CL, and between HR and CL, respectively. Conclusions and clinical relevance: The increase in HR and the resultant improvement in cardiac output increased fentanyl CL and volume of distribution, which resulted in a decrease in plasma fentanyl concentration in isoflurane-anesthetized dogs.

Original languageEnglish (US)
JournalVeterinary Anaesthesia and Analgesia
DOIs
StateAccepted/In press - Jan 1 2019

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Hydromorphone
fentanyl
Isoflurane
isoflurane
Fentanyl
pharmacokinetics
heart rate
Pharmacokinetics
Heart Rate
Dogs
dogs
Glycopyrrolate
cardiac output
Beagle
Liquid Chromatography
Cardiac Output
Cross-Over Studies
liquid chromatography
Mass Spectrometry
anesthesia

Keywords

  • cardiac output
  • dog
  • fentanyl
  • heart rate
  • isoflurane
  • pharmacokinetics

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Effect of heart rate on the pharmacokinetics of fentanyl in dogs anesthetized with isoflurane and hydromorphone. / Machado, Marcela L.; Soares, Joao HN; Pypendop, Bruno H; Henao-Guerrero, Natalia; Pavlisko, Noah D.; Ross, Juliet.

In: Veterinary Anaesthesia and Analgesia, 01.01.2019.

Research output: Contribution to journalArticle

Machado, Marcela L. ; Soares, Joao HN ; Pypendop, Bruno H ; Henao-Guerrero, Natalia ; Pavlisko, Noah D. ; Ross, Juliet. / Effect of heart rate on the pharmacokinetics of fentanyl in dogs anesthetized with isoflurane and hydromorphone. In: Veterinary Anaesthesia and Analgesia. 2019.
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abstract = "Objective: To compare the pharmacokinetics of fentanyl at lower (LHR) or higher heart rate (HHR) in dogs anesthetized with isoflurane. Study design: Prospective, randomized, crossover controlled trial. Animals: A group of six healthy 13-month-old male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation). Methods: Dogs were allocated to two treatments: LHR (HR: 45–75 beats minute−1) and HHR (HR: 100–130 beats minute−1). Anesthesia was maintained with isoflurane and hydromorphone (0.1 mg kg−1 followed by 0.02–0.10 mg kg−1 hour−1) for both treatments. Glycopyrrolate was administered in HHR to maintain HR within the desired range. Afterwards, fentanyl (20 μg kg−1) was intravenously administered over 5 minutes. Arterial blood samples were collected for plasma fentanyl concentration measurement by liquid chromatography/mass spectrometry. The pharmacokinetics of fentanyl were compared between treatments and the differences were considered significant at p < 0.05. Results: A three-compartment model best fitted the changes in plasma fentanyl concentration. Clearance (CL; mL minute−1 kg−1) was 33.2 (24.0–48.0) and 61.3 (44.5–72.7), maximum concentration (ng mL−1) 33.6 (23.4–36.6) and 20.0 (16.7–28.0), apparent volume of the rapid peripheral compartment (mL kg−1) 436 (352–723) and 925 (499–1887), apparent volume at steady state (mL kg−1) 4064 (3453–6546) and 7195 (5077–8601), cardiac index (CI; mL minute−1 m−2) 2.83 (1.98–3.67) and 4.91 (3.22–6.09) and HR (beats minute−1) 68 (49–72) and 120 (102–129) for LHR and HHR, respectively, with significant differences between treatments. Significant correlations (0.92 and 0.90) were found between CI and CL, and between HR and CL, respectively. Conclusions and clinical relevance: The increase in HR and the resultant improvement in cardiac output increased fentanyl CL and volume of distribution, which resulted in a decrease in plasma fentanyl concentration in isoflurane-anesthetized dogs.",
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T1 - Effect of heart rate on the pharmacokinetics of fentanyl in dogs anesthetized with isoflurane and hydromorphone

AU - Machado, Marcela L.

AU - Soares, Joao HN

AU - Pypendop, Bruno H

AU - Henao-Guerrero, Natalia

AU - Pavlisko, Noah D.

AU - Ross, Juliet

PY - 2019/1/1

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N2 - Objective: To compare the pharmacokinetics of fentanyl at lower (LHR) or higher heart rate (HHR) in dogs anesthetized with isoflurane. Study design: Prospective, randomized, crossover controlled trial. Animals: A group of six healthy 13-month-old male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation). Methods: Dogs were allocated to two treatments: LHR (HR: 45–75 beats minute−1) and HHR (HR: 100–130 beats minute−1). Anesthesia was maintained with isoflurane and hydromorphone (0.1 mg kg−1 followed by 0.02–0.10 mg kg−1 hour−1) for both treatments. Glycopyrrolate was administered in HHR to maintain HR within the desired range. Afterwards, fentanyl (20 μg kg−1) was intravenously administered over 5 minutes. Arterial blood samples were collected for plasma fentanyl concentration measurement by liquid chromatography/mass spectrometry. The pharmacokinetics of fentanyl were compared between treatments and the differences were considered significant at p < 0.05. Results: A three-compartment model best fitted the changes in plasma fentanyl concentration. Clearance (CL; mL minute−1 kg−1) was 33.2 (24.0–48.0) and 61.3 (44.5–72.7), maximum concentration (ng mL−1) 33.6 (23.4–36.6) and 20.0 (16.7–28.0), apparent volume of the rapid peripheral compartment (mL kg−1) 436 (352–723) and 925 (499–1887), apparent volume at steady state (mL kg−1) 4064 (3453–6546) and 7195 (5077–8601), cardiac index (CI; mL minute−1 m−2) 2.83 (1.98–3.67) and 4.91 (3.22–6.09) and HR (beats minute−1) 68 (49–72) and 120 (102–129) for LHR and HHR, respectively, with significant differences between treatments. Significant correlations (0.92 and 0.90) were found between CI and CL, and between HR and CL, respectively. Conclusions and clinical relevance: The increase in HR and the resultant improvement in cardiac output increased fentanyl CL and volume of distribution, which resulted in a decrease in plasma fentanyl concentration in isoflurane-anesthetized dogs.

AB - Objective: To compare the pharmacokinetics of fentanyl at lower (LHR) or higher heart rate (HHR) in dogs anesthetized with isoflurane. Study design: Prospective, randomized, crossover controlled trial. Animals: A group of six healthy 13-month-old male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation). Methods: Dogs were allocated to two treatments: LHR (HR: 45–75 beats minute−1) and HHR (HR: 100–130 beats minute−1). Anesthesia was maintained with isoflurane and hydromorphone (0.1 mg kg−1 followed by 0.02–0.10 mg kg−1 hour−1) for both treatments. Glycopyrrolate was administered in HHR to maintain HR within the desired range. Afterwards, fentanyl (20 μg kg−1) was intravenously administered over 5 minutes. Arterial blood samples were collected for plasma fentanyl concentration measurement by liquid chromatography/mass spectrometry. The pharmacokinetics of fentanyl were compared between treatments and the differences were considered significant at p < 0.05. Results: A three-compartment model best fitted the changes in plasma fentanyl concentration. Clearance (CL; mL minute−1 kg−1) was 33.2 (24.0–48.0) and 61.3 (44.5–72.7), maximum concentration (ng mL−1) 33.6 (23.4–36.6) and 20.0 (16.7–28.0), apparent volume of the rapid peripheral compartment (mL kg−1) 436 (352–723) and 925 (499–1887), apparent volume at steady state (mL kg−1) 4064 (3453–6546) and 7195 (5077–8601), cardiac index (CI; mL minute−1 m−2) 2.83 (1.98–3.67) and 4.91 (3.22–6.09) and HR (beats minute−1) 68 (49–72) and 120 (102–129) for LHR and HHR, respectively, with significant differences between treatments. Significant correlations (0.92 and 0.90) were found between CI and CL, and between HR and CL, respectively. Conclusions and clinical relevance: The increase in HR and the resultant improvement in cardiac output increased fentanyl CL and volume of distribution, which resulted in a decrease in plasma fentanyl concentration in isoflurane-anesthetized dogs.

KW - cardiac output

KW - dog

KW - fentanyl

KW - heart rate

KW - isoflurane

KW - pharmacokinetics

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