Abstract
Objective: To evaluate changes in electrocardiogram (ECG) variables in healthy dogs receiving either methadone or hydromorphone IV before and during sevoflurane anesthesia.Study Design: Prospective clinical study.Animals: Forty client-owned dogs.Methods: Dogs were randomized to receive methadone 0.5 mg/kg IV or hydromorphone 0.1 mg/kg IV in each part of a two-part study. In part one, dogs received the opioid prior to sevoflurane anesthesia (groups MS, n = 12 and HS, n = 12). Anesthesia was induced with propofol IV, maintained with sevoflurane, and dogs were mechanically ventilated. Standard 6-lead ECG recordings were obtained before opioid administration, 2, 5, and 10 min after opioid administration prior to anesthesia, and during anesthesia 15 min after end-tidal sevoflurane stabilized at 2.4%. In part two, conscious dogs received the same opioid treatments and ECGs were obtained at equivalent time points without undergoing anesthesia (groups M, n = 8 and H, n = 8). Values for ECG variables were determined by a blinded cardiologist and included: Heart rate (HR), PR interval, QT interval, and HR corrected QT interval (QTc) using the Bazett (QTcB), Fridericia (QTcF), and Van de Water (QTcV) formulas. Differences over time and between all four groups were evaluated using ANOVA for repeated measures with significance set at p ≤ 0.05.Results: Both methadone and hydromorphone administration reduced HR and prolonged PR and QT intervals, with greater changes observed during sevoflurane anesthesia. The greatest prolongation in QT interval was observed in dogs administered methadone during sevoflurane anesthesia.Conclusions and Clinical Relevance: Methadone and hydromorphone caused disturbances in myocardial electrical activity, and the addition of sevoflurane enhanced these disturbances. Both drugs caused considerable QT interval prolongation into the proarrhythmogenic range, with methadone causing greater prolongation.
Highlights
Opioid agonists are routinely administered for perioperative analgesia in dogs
While QT interval prolongation and associated arrhythmias have predominantly been reported in people taking long term oral methadone for opioid addiction, QT prolongation has been identified after intravenous methadone administration in hospitalized cancer patients, while morphine administration was not associated with this effect [7]
PR interval was prolonged with both methadone and hydromorphone administration, even with significant differences in heart rate (HR) between groups. This suggests a discrepancy in the influence of methadone and hydromorphone on SA and AV nodal activity, which may be due to differences in expression of the funny pacemaker current in the different nodal cells [23]. These results suggest that either hydromorphone has proportionally greater suppression at the AV node compared to the SA node, or that methadone has less AV nodal influence and a stronger effect on pacemaker cells within the SA node
Summary
Opioid agonists are routinely administered for perioperative analgesia in dogs. Methadone is unique among opioids, acting as a full mu opioid agonist and an antagonist at the N-methyl-D-aspartate (NMDA) receptor, as well as inhibiting the re-uptake of norepinephrine and serotonin within the brain and spinal cord [1, 2]. In addition to the multimodal analgesic benefits of methadone, there are fewer undesirable effects, such as vomiting and excitatory behavior, compared to other full mu agonists [3, 4]. These advantages have led to the use of methadone for premedication prior to general anesthesia in dogs and cats, in patients experiencing vomiting, chronic or neuropathic pain [3, 5, 6]. While QT interval prolongation and associated arrhythmias have predominantly been reported in people taking long term oral methadone for opioid addiction, QT prolongation has been identified after intravenous methadone administration in hospitalized cancer patients, while morphine administration was not associated with this effect [7]
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