Effects of medetomidine and ketamine on the regional cerebral blood flow in cats: A SPECT study

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Abstract

Brain perfusion can be investigated using single photon emission computed tomography (SPECT) and the intravenous injection of 99mtechnetium ethyl cysteinate dimer (99mTc-ECD). However, sedation using medetomidine, an α2-agonist, or anaesthesia using medetomidine and ketamine, an N-methyl-d-aspartate-(NMDA)-antagonist, may be required for SPECT studies in cats but can affect the regional cerebral blood flow (rCBF). The effects of medetomidine, with or without ketamine, on regional brain perfusion were therefore investigated in six cats under three conditions. Injection of tracer occurred before sedation or anaesthesia (condition A), following intramuscular (IM) sedation with medetomidine (condition M) or after IM anaesthesia with medetomidine and ketamine (condition MK).

Medetomidine and medetomidine with ketamine caused a significantly higher total tracer uptake in all brain regions. Semi-quantification of brain perfusion gave lower perfusion indices in several sub-cortical regions in conditions M and MK, compared to A. Left–right differences were observed in the temporal cortex (A), the temporal, parietal cortex and the thalamus (M) and the frontal cortex (MK). A significantly higher perfusion index in the sub-cortical regions, compared to the whole cortex, was only present in condition A. This study showed that caution is needed when quantifying brain perfusion indices when using sedative or anaesthetic agents that may affect rCBF.

Introduction

Measurements of regional cerebral blood flow (rCBF), an indirect tool for determination of neuronal functionality, can be performed by using tools based on functional magnetic resonance imaging (fMRI), positron emission tomography (PET) or single photon emission computed tomography (SPECT) (Moretti et al., 1995, Hagen et al., 1999, Feng et al., 2004).

SPECT using 99mtechnetium ethylcysteinate dimer (99mTc-ECD) is a functional neuroimaging technique that has become a routine procedure in human nuclear medicine for evaluation of rCBF (Catafau, 2001). In veterinary medicine, the tracer has been used in behaviour disorders and in epileptic dogs (Peremans et al., 2003, Martle et al., 2009, Vermeire et al., 2009). ECD is a neutral lipophilic complex which is rapidly taken up by the human brain (Vallabhajosula et al., 1989). Following intravenous (IV) injection, ECD crosses the blood brain barrier and becomes rapidly trapped in the brain in proportion to the rCBF (Ishizu et al., 1995, Ichise et al., 1997). The tracer exhibits prolonged retention in the brain due to its intracellular conversion into a hydrophilic compound. The lack of redistribution makes it possible to inject the tracer several hours before acquisition, creating an image that represents the cerebral blood flow distribution pattern at the time of injection (Leveille et al., 1992, Ichise et al., 1997, Catafau, 2001, Peremans et al., 2001).

Sedation or anaesthesia is required in veterinary nuclear medicine during image acquisition and can cause changes in the cerebral blood flow (Zornow et al., 1990, McPherson et al., 1997, Prielipp et al., 2002). This is comparable with the situation in children or in patients with severe cognitive dysfunction, dementia or behavioural disorders. In those patients it is recommended that the tracer is administered prior to sedation to avoid sedation-induced metabolism or blood flow changes (Catafau, 2001). It is generally accepted that the influence of sedatives or anaesthetics is negligible and that tracer displacement is very unlikely due to the rapid intra-neuronal trapping mechanism of the tracer (Walovitch et al., 1994).

In cats, intramuscular (IM) sedation or general anaesthesia is often required before IV catheter placement and tracer administration, and this may affect the distribution pattern of the tracer. Medetomidine, a highly selective α2-agonist, induces a reliable sedative effect following IM administration. Ketamine, a dissociative anaesthetic and N-methyl-d-aspartate (NMDA) antagonist, is frequently used in cats in combination with medetomidine (as an IM injection) for general anaesthesia (Lin, 2007).

The purpose of the present study was to investigate the influence of IM sedation with medetomidine alone or in combination with ketamine on the movement of 99mTc-ECD to the brain and on the semi-quantification of rCBF in domestic cats. Our hypothesis was that sedation or anaesthesia before tracer injection may change the uptake of this tracer within the whole brain and, more importantly, that this would also influence the semi-quantification of rCBF.

Section snippets

Subjects

Six healthy, drug naïve, domestic shorthair neutered female cats, 6 years of age, weighing 5.34 ± 0.51 kg (mean ± SD), were included in this study. The animals were used to being handled for IV catheter placement and all procedures were performed according to good animal practice in order not to provoke excitation or aggression. In every study condition, a 22G IV catheter was placed in the cephalic vein. After catheter placement, the cats were allowed to relax for 10 min in a quiet room with dimmed

Results

Comparing the total counts in the different conditions revealed that tracer uptake in conditions M and MK were significantly higher than in condition A in all brain regions (Table 1). Although significance could not be reached, tracer uptake was lower in all brain regions in the MK-condition when compared to condition M (Table 1).

Statistical analysis of the perfusion indices (Table 2) showed increased perfusion indices in the cingulate gyrus, the olfactory bulb and the right parietal cortex,

Discussion

The results of this study confirmed our hypothesis that significant differences in the uptake of 99mTc-ECD occur when tracer injection was preceded by the administration of medetomidine alone (M) or in combination with ketamine (MK). Table 1 indicates that medetomidine alone caused the highest tracer uptake in all brain regions, while the combination of medetomidine and ketamine caused a significant higher tracer uptake in all brain regions, compared to non-sedated cats.

Cardiovascular changes,

Conclusions

Sedation or anaesthesia with medetomidine or the combination of medetomidine and ketamine is sometimes required before IV tracer injection in cats. In these cases, caution is needed when rCBF is measured. Medetomidine alone or in combination with ketamine will induce an increased 99mTc-ECD supply to the brain and the semi-quantification, mainly of the sub-cortical brain regions and the cingulate gyrus, can be influenced as well. It was clear from this work that sedation or anaesthesia before

Conflict of interest statement

None of the authors of this paper has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper.

References (40)

  • A. Dobbeleir et al.

    Cat brain perfusion with a multi-pinhole SPECT imaging system

    European Journal of Nuclear Medicine and Molecular Imaging

    (2006)
  • P. Dobromylskyj

    Cardiovascular changes associated with anaesthesia induced by medetomidine combined with ketamine in cats

    Journal of Small Animal Practice

    (1996)
  • K. Engel et al.

    Neuroimaging in anxiety disorders

    Journal of Neural Transmission

    (2009)
  • A. Fale et al.

    Alpha2-adrenergic agonist effects on normocapnic and hypercapnic cerebral blood-flow in the dog are anesthetic dependent

    Anesthesia and Analgesia

    (1994)
  • T. Hagen et al.

    Correlation of regional cerebral blood flow measured by stable xenon CT and perfusion MRI

    Journal of Computer Assisted Tomography

    (1999)
  • M. Ichise et al.

    Regional differences in technetium-99m-ECD clearance on brain SPECT in healthy subjects

    Journal of Nuclear Medicine

    (1997)
  • K. Ishizu et al.

    Ultra-high resolution SPECT system using four pinhole collimators for small animal studies

    Journal of Nuclear Medicine

    (1995)
  • T. Itoh et al.

    Effects of anesthesia upon F-18-FDG uptake in rhesus monkey brains

    Annals of Nuclear Medicine

    (2005)
  • A.C. Lahti et al.

    Ketamine activates psychosis and alters limbic blood flow in schizophrenia

    NeuroReport

    (1995)
  • L.A. Lamont et al.

    Cardiopulmonary evaluation of the use of medetomidine hydrochloride in cats

    American Journal of Veterinary Research

    (2001)
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