Characteristics of the relationship between plasma ketamine concentration and its effect on the minimum alveolar concentration of isoflurane in dogs

Bruno H Pypendop, Adrian Solano, Pedro Boscan, Jan Ilkiw

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11 Citations (Scopus)

Abstract

Objective To characterize the shape of the relationship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs. Study design Retrospective analysis of previous data. Animals Four healthy adult dogs. Methods The MAC of isoflurane was determined at five to six different plasma ketamine concentrations. Arterial blood samples were collected at the time of MAC determination for measurement of plasma ketamine concentration. Plasma concentration/effect data from each dog were fitted to a sigmoid inhibitory maximum effect model in which MACc = MAC 0 - (MAC0-MACmin)×Cγ/ EC50 γ+Cγ, where C is the plasma ketamine concentration, MACc is the MAC of isoflurane at plasma ketamine concentration C, MAC0 is the MAC of isoflurane without ketamine, MACmin is the lowest MAC predicted during ketamine administration, EC50 is the plasma ketamine concentration producing 50% of the maximal MAC reduction, and γ is a sigmoidicity factor. Nonlinear regression was used to estimate MACmin, EC50, and γ. Results Mean ± SEM MACmin, EC50 and γ were estimated to be 0.11 ± 0.01%, 2945 ± 710 ng mL -1 and 3.01 ± 0.84, respectively. Mean ± SEM maximal MAC reduction predicted by the model was 92.20 ± 1.05%. Conclusions The relationship between plasma ketamine concentration and its effect on isoflurane MAC has a classical sigmoid shape. Maximal MAC reduction predicted by the model is less than 100%, implying that high plasma ketamine concentrations may not totally abolish gross purposeful movement in response to noxious stimulation in the absence of inhalant anesthetics. Clinical relevance The parameter estimates reported in this study will allow clinicians to predict the expected isoflurane MAC reduction from various plasma ketamine concentrations in an average dog.

Original languageEnglish (US)
Pages (from-to)209-212
Number of pages4
JournalVeterinary Anaesthesia and Analgesia
Volume34
Issue number3
DOIs
StatePublished - May 2007

Fingerprint

Isoflurane
isoflurane
Ketamine
ketamine
Dogs
dogs
Sigmoid Colon
anesthetics
Anesthetics
data analysis
Retrospective Studies
experimental design

Keywords

  • Dog
  • Dose-effect relationship
  • Isoflurane
  • Ketamine
  • Minimum alveolar concentration
  • Pharmacodynamics

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{2bd68e5063d944a9861d2a0e518148fa,
title = "Characteristics of the relationship between plasma ketamine concentration and its effect on the minimum alveolar concentration of isoflurane in dogs",
abstract = "Objective To characterize the shape of the relationship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs. Study design Retrospective analysis of previous data. Animals Four healthy adult dogs. Methods The MAC of isoflurane was determined at five to six different plasma ketamine concentrations. Arterial blood samples were collected at the time of MAC determination for measurement of plasma ketamine concentration. Plasma concentration/effect data from each dog were fitted to a sigmoid inhibitory maximum effect model in which MACc = MAC 0 - (MAC0-MACmin)×Cγ/ EC50 γ+Cγ, where C is the plasma ketamine concentration, MACc is the MAC of isoflurane at plasma ketamine concentration C, MAC0 is the MAC of isoflurane without ketamine, MACmin is the lowest MAC predicted during ketamine administration, EC50 is the plasma ketamine concentration producing 50{\%} of the maximal MAC reduction, and γ is a sigmoidicity factor. Nonlinear regression was used to estimate MACmin, EC50, and γ. Results Mean ± SEM MACmin, EC50 and γ were estimated to be 0.11 ± 0.01{\%}, 2945 ± 710 ng mL -1 and 3.01 ± 0.84, respectively. Mean ± SEM maximal MAC reduction predicted by the model was 92.20 ± 1.05{\%}. Conclusions The relationship between plasma ketamine concentration and its effect on isoflurane MAC has a classical sigmoid shape. Maximal MAC reduction predicted by the model is less than 100{\%}, implying that high plasma ketamine concentrations may not totally abolish gross purposeful movement in response to noxious stimulation in the absence of inhalant anesthetics. Clinical relevance The parameter estimates reported in this study will allow clinicians to predict the expected isoflurane MAC reduction from various plasma ketamine concentrations in an average dog.",
keywords = "Dog, Dose-effect relationship, Isoflurane, Ketamine, Minimum alveolar concentration, Pharmacodynamics",
author = "Pypendop, {Bruno H} and Adrian Solano and Pedro Boscan and Jan Ilkiw",
year = "2007",
month = "5",
doi = "10.1111/j.1467-2995.2006.00324.x",
language = "English (US)",
volume = "34",
pages = "209--212",
journal = "Veterinary Anaesthesia and Analgesia",
issn = "1467-2987",
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TY - JOUR

T1 - Characteristics of the relationship between plasma ketamine concentration and its effect on the minimum alveolar concentration of isoflurane in dogs

AU - Pypendop, Bruno H

AU - Solano, Adrian

AU - Boscan, Pedro

AU - Ilkiw, Jan

PY - 2007/5

Y1 - 2007/5

N2 - Objective To characterize the shape of the relationship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs. Study design Retrospective analysis of previous data. Animals Four healthy adult dogs. Methods The MAC of isoflurane was determined at five to six different plasma ketamine concentrations. Arterial blood samples were collected at the time of MAC determination for measurement of plasma ketamine concentration. Plasma concentration/effect data from each dog were fitted to a sigmoid inhibitory maximum effect model in which MACc = MAC 0 - (MAC0-MACmin)×Cγ/ EC50 γ+Cγ, where C is the plasma ketamine concentration, MACc is the MAC of isoflurane at plasma ketamine concentration C, MAC0 is the MAC of isoflurane without ketamine, MACmin is the lowest MAC predicted during ketamine administration, EC50 is the plasma ketamine concentration producing 50% of the maximal MAC reduction, and γ is a sigmoidicity factor. Nonlinear regression was used to estimate MACmin, EC50, and γ. Results Mean ± SEM MACmin, EC50 and γ were estimated to be 0.11 ± 0.01%, 2945 ± 710 ng mL -1 and 3.01 ± 0.84, respectively. Mean ± SEM maximal MAC reduction predicted by the model was 92.20 ± 1.05%. Conclusions The relationship between plasma ketamine concentration and its effect on isoflurane MAC has a classical sigmoid shape. Maximal MAC reduction predicted by the model is less than 100%, implying that high plasma ketamine concentrations may not totally abolish gross purposeful movement in response to noxious stimulation in the absence of inhalant anesthetics. Clinical relevance The parameter estimates reported in this study will allow clinicians to predict the expected isoflurane MAC reduction from various plasma ketamine concentrations in an average dog.

AB - Objective To characterize the shape of the relationship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs. Study design Retrospective analysis of previous data. Animals Four healthy adult dogs. Methods The MAC of isoflurane was determined at five to six different plasma ketamine concentrations. Arterial blood samples were collected at the time of MAC determination for measurement of plasma ketamine concentration. Plasma concentration/effect data from each dog were fitted to a sigmoid inhibitory maximum effect model in which MACc = MAC 0 - (MAC0-MACmin)×Cγ/ EC50 γ+Cγ, where C is the plasma ketamine concentration, MACc is the MAC of isoflurane at plasma ketamine concentration C, MAC0 is the MAC of isoflurane without ketamine, MACmin is the lowest MAC predicted during ketamine administration, EC50 is the plasma ketamine concentration producing 50% of the maximal MAC reduction, and γ is a sigmoidicity factor. Nonlinear regression was used to estimate MACmin, EC50, and γ. Results Mean ± SEM MACmin, EC50 and γ were estimated to be 0.11 ± 0.01%, 2945 ± 710 ng mL -1 and 3.01 ± 0.84, respectively. Mean ± SEM maximal MAC reduction predicted by the model was 92.20 ± 1.05%. Conclusions The relationship between plasma ketamine concentration and its effect on isoflurane MAC has a classical sigmoid shape. Maximal MAC reduction predicted by the model is less than 100%, implying that high plasma ketamine concentrations may not totally abolish gross purposeful movement in response to noxious stimulation in the absence of inhalant anesthetics. Clinical relevance The parameter estimates reported in this study will allow clinicians to predict the expected isoflurane MAC reduction from various plasma ketamine concentrations in an average dog.

KW - Dog

KW - Dose-effect relationship

KW - Isoflurane

KW - Ketamine

KW - Minimum alveolar concentration

KW - Pharmacodynamics

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