Research Paper
Cardiopulmonary effects of an infusion of remifentanil or morphine in horses anesthetized with isoflurane and dexmedetomidine

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Abstract

Objective

To examine the cardiopulmonary effects of infusions of remifentanil or morphine, and their influence on recovery of horses anesthetized with isoflurane and dexmedetomidine.

Study design

Randomized crossover study with 7-day rest periods.

Animals

Six adult horses (507 ± 61 kg).

Methods

After the horses were sedated with xylazine, anaesthesia was induced with ketamine and diazepam, and maintained with isoflurane. After approximately 60 minutes, a dexmedetomidine infusion was started (0.25 μg kg−1 then 1.0 μg−1 kg−1 hour−1) in combination with either saline (group S), morphine (0.15 mg kg−1 then 0.1 mg kg−1 hour−1; group M), or remifentanil (6.0 μg kg−1 hour−1; group R) for 60 minutes. Mean arterial pressure, heart rate, end-tidal carbon dioxide tension, and end-tidal isoflurane concentration were recorded every 5 minutes. Core body temperature, cardiac output, right ventricular and arterial blood-gas values were measured every 15 minutes. Cardiac index, systemic vascular resistance (SVR), intrapulmonary shunt fraction, alveolar dead space, oxygen delivery and extraction ratio were calculated. Recoveries were videotaped and scored by two observers blinded to the treatment. Data were analyzed using repeated measures anova followed by Dunnett’s or Bonferroni’s significant difference test. Recovery scores were analyzed using a Kruskal–Wallis test.

Results

No significant differences were found among groups. Compared to baseline, heart rate decreased and SVR increased significantly in all groups, and cardiac index significantly decreased in groups S and M. Hemoglobin concentration, oxygen content and oxygen delivery significantly decreased in all groups. The oxygen extraction ratio significantly increased in groups M and R. Lactate concentration significantly increased in group S. Recovery scores were similar among groups.

Conclusions and clinical relevance

Dexmedetomidine alone or in combination with remifentanil or morphine infusions was infused for 60 minutes without adverse effects in the 6 healthy isoflurane-anesthetized horses in this study.

Introduction

Opioids and alpha2-adrenergic agonists are used as components of partial intravenous anaesthesia (PIVA) techniques in numerous species for their analgesic and anesthetic sparing properties (Ilkiw 1999; Bettschart-Wolfensberger & Larenza 2007; Lamont 2008). However, the potential for adverse effects and species-related singularities have precluded their extensive use for PIVA in horses. Although alpha2-adrenergic agonists reduce the minimum alveolar concentration (MAC) of inhalation anesthetic agents in a dose-dependent manner (Bettschart-Wolfensberger & Larenza 2007; Gozalo-Marcilla et al. 2013), the anesthetic-sparing effect of opioids in horses is unpredictable. Morphine (Steffey et al. 2003) and fentanyl (Thomasy et al. 2006; Knych et al. 2009) administered intravenously (IV) can cause either a reduction or increase in isoflurane MAC in horses, although neither was of clinical significance.

The cardiovascular effects of opioids and alpha2-adrenergic agonists have been evaluated during inhalation anaesthesia in horses. No significant adverse effects were reported in halothane and sevoflurane-anesthetized horses given morphine or fentanyl (Clark et al. 2005; Ohta et al. 2010). Dexmedetomidine, however, has been reported to have a significant impact on hemodynamic variables when administered as an infusion to isoflurane-anesthetized ponies (Marcilla et al. 2010).

The potential post-anesthetic adverse effects of opioids and alpha2-adrenergic agonists remain a limiting factor to their use in horses. The use of morphine during surgery was associated with an increase in the risk of colic (Senior et al. 2004), and alpha2-adrenergic agonists can decrease intestinal motility (Merritt et al. 1998). Increased locomotor activity and excitement during recovery have been observed in isoflurane-anesthetized horses given fentanyl or a high dose of morphine IV (Steffey et al. 2003; Knych et al. 2009). In contrast, the quality of recovery after inhalation anaesthesia can be improved by the use of alpha2-adrenergic agonists (Santos et al. 2003; Marcilla et al. 2012).

Remifentanil is an ultrashort-acting mu-opioid agonist with similar potency to fentanyl in humans (Glass et al. 1999). Its half-life in humans is 3–5 minutes, regardless of the duration of infusion (Glass et al. 1999). This unique pharmacokinetic profile is favorable for its use for PIVA in veterinary anaesthesia. Remifentanil infusions have been successfully used in dogs and cats (Ferreira et al. 2009; Monteiro et al. 2010), but reports of its use in horses are not available. The preliminary unpublished results of the pharmacokinetic study conducted in conjunction with the present study have revealed an elimination half-life of approximately 14 minutes for remifentanil in the horse. Although dexmedetomidine has been suggested to be an ideal agent for infusion in equine anaesthesia (Marcilla et al. 2012), its effects in combination with an opioid and an inhalation anesthetic agent in horses have not been documented.

The primary objective was to evaluate the cardiopulmonary effects of a dexmedetomidine infusion with or without remifentanil or morphine infusion in isoflurane-anesthetized horses, and the secondary objective was to evaluate the effects of these drug protocols on quality of recovery from anaesthesia. It was hypothesized that a combination of remifentanil and dexmedetomidine infusions would be an equally effective option for PIVA in isoflurane-anesthetized horses, when compared to infusions of dexmedetomidine alone or dexmedetomidine in combination with morphine.

Section snippets

Materials and methods

Approval for the study was obtained from the University Animal Care and Use Committee. Animals were housed and fed according to the Institutional guidelines.

Results

Isotonic fluid was administered at a rate of 9.7 ± 3.1 mL kg−1 hour−1 (group S), 9.1 ± 2.3 mL kg−1 hour−1 (group R) and 9.3 ± 2.0 mL kg−1 hour−1 (group M). Total anaesthesia time was 138 ± 21 minutes (group S), 135 ± 11 minutes (group R) and 137 ± 11 minutes (group M). Instrumentation time was 59 ± 18 minutes (group S), 52 ± 7 minutes (group R) and 59 ± 8 minutes (group M). Pre-recovery time was 13 ± 3 minutes (group S), 13 ± 3 minutes (group R) and 13 ± 4 minutes (group M). No statistical

Discussion

The results of this study documented similar effects for all treatment groups for any of the variables examined when compared at each time point with no significant differences among groups. Administration of dexmedetomidine alone or combined with remifentanil or morphine did not cause clinically significant adverse effects on the cardiopulmonary system when compared with baseline. During the post-anesthetic period, no clinically detectable recovery problems or gastrointestinal problems were

Acknowledgement

Dr Steve Manning for use of horses from his herd and Ingrid Sproll, class of 2013.

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