Research Papers
The relationship of muscle perfusion and metabolism with cardiovascular variables before and after detomidine injection during propofol–ketamine anaesthesia in horses

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Abstract

Objectives

To study in horses (1) the relationship between cardiovascular variables and muscle perfusion during propofol–ketamine anaesthesia, (2) the physiological effects of a single intravenous (IV) detomidine injection, (3) the metabolic response of muscle to anaesthesia, and (4) the effects of propofol–ketamine infusion on respiratory function.

Study design

Prospective experimental study.

Animals

Seven standardbred trotters, 5–12 years old, 416–581 kg.

Methods

Anaesthesia was induced with intravenous (IV) guaifenesin and propofol (2 mg kg−1) and maintained with a continuous IV infusion of propofol (0.15 mg kg−1 minute−1) and ketamine (0.05 mg kg−1 minute−1) with horses positioned in left lateral recumbency. After 1 hour, detomidine (0.01 mg kg−1) was administered IV and 40–50 minutes later anaesthesia was discontinued. Cardiovascular and respiratory variables (heart rate, cardiac output, systemic and pulmonary artery blood pressures, respiratory rate, tidal volume, and inspiratory and expiratory O2 and CO2) and muscle temperature were measured at pre-determined times. Peripheral perfusion was measured continuously in the gluteal muscles and skin using laser Doppler flowmetry (LDF). Muscle biopsy samples from the left and right gluteal muscles were analysed for glycogen, creatine phosphate, creatine, adenine nucleotides, inosine monophosphate and lactate. Arterial blood was analysed for PO2, PCO2, pH, oxygen saturation and HCO3. Mixed venous blood was analysed for PO2, PCO2, pH, oxygen saturation, HCO3, cortisol, lactate, uric acid, hypoxanthine, xanthine, creatine kinase, creatinine, aspartate aminotransferase, electrolytes, total protein, haemoglobin, haematocrit and white blood cell count.

Results

Circulatory function was preserved during propofol–ketamine anaesthesia. Detomidine caused profound hypertension and bradycardia and decreased cardiac output and muscle perfusion. Ten minutes after detomidine injection muscle perfusion had recovered to pre-injection levels, although heart rate and cardiac output had not. No difference in indices of muscle metabolism was found between dependent and independent muscles. Anaerobic muscle metabolism, indicated by decreased muscle and creatine phosphate levels was evident after anaesthesia.

Conclusion

Muscle perfusion was closely related to cardiac output but not arterial blood pressure. Total intravenous anaesthesia with propofol–ketamine deserves further study despite its respiratory depression effects, as the combination preserves cardiovascular function. Decreases in high-energy phosphate stores during recovery show that muscle is vulnerable after anaesthesia. Continued research is required to clarify the course of muscle metabolic events during recovery.

Introduction

Post-anaesthetic myopathy in horses may be related to reduced muscle perfusion caused by a combination of factors including hypotension, the mass of the horse, poor padding, duration of anaesthesia, and re-perfusion of muscles during recovery (Lindsay et al. 1989; Richey et al. 1990; Serteyn et al. 1990; Steffey et al. 1993a; Trim & Mason 1973; Waldron-Mease 1977). Myopathy and fractures have been reported to account for 30.4% of the deaths that occur in relation to equine anaesthesia (Johnston 2000). Signs of muscle injury, indicated by increases in muscle enzymes in blood samples (Johnson et al. 1978), changes on ultrasound (Smith et al. 1996), histopathology (Friend 1981; Dodman et al. 1988) and electron microscopy (White 1982), have been reported after inhalation anaesthesia in the horse.

The chemical energy status of muscle may depend on the anaesthetic protocol. In dogs, little or no muscle damage was observed after propofol anaesthesia, whereas creatinine kinase (CK) was significantly elevated after halothane (Aktas et al. 1997). Halothane anaesthesia in rats results in a lower intramusclular (IM) concentration of CP and double the muscle lactate content compared to ketamine anaesthesia (McLoughlin et al. 1987). To our knowledge, there are no reports on muscle metabolism during or after propofol–ketamine anaesthesia in horses.

Muscle perfusion has been studied during inhalation anaesthesia and different techniques such as laser Doppler flowmetry (LDF) (Serteyn et al. 1986; Serteyn et al. 1988; Norman et al. 1992; Still et al. 1996; Lee et al. 1998b; Raisis et al. 2000), 133Xe clearance (Weaver & Lunn 1984) and microspheres (Manohar et al. 1987; Goetz et al. 1989) have been used. LDF is a sensitive and valuable method for estimating peripheral perfusion. It has been used to measure the perfusion in skin-flap surgery (Svensson et al. 1985) and to diagnose nerve diseases (Wollersheim et al. 1991).

Propofol alone or combined with ketamine has been found to preserve cardiovascular function in anaesthetised horses (Taylor 1989; Mama et al. 1996; Flaherty et al. 1997; Mama et al. 1998; Matthews et al. 1999). The advantages of the propofol–ketamine combination are that it provides perioperative analgesia (Guit et al. 1991) and less respiratory depression compared with propofol alone (Flaherty et al. 1997).

α2-agonists are often used for pre-anaesthetic medication before induction of propofol anaesthesia; they have been reported to reduce muscle perfusion measured with LDF both in the standing (Hennig et al. 1995) and anaesthetised horse (Lee et al. 1993).

The present study aimed to investigate the link between muscle perfusion and cardiovascular variables in conscious horses and those anaesthetised with propofol–ketamine, and also to evaluate the effect of intravenous (IV) detomidine given during anaesthesia. In addition, muscular metabolism was studied before, during and after anaesthesia. Another objective was to evaluate the effects of propofol–ketamine anaesthesia on respiratory function.

Section snippets

Horses

The study involved seven healthy standardbred trotters (three females and four geldings) with a mean body mass of 492 kg (range 416–581 kg) and a mean age of 7 years (range 5–12 years). Food was withheld for 12 hours prior to anaesthesia, but water was available until instrumentation began. The local ethical committee on animal experiments in Uppsala, Sweden approved the experimental protocol.

Anaesthetic protocol

Anaesthesia was induced with IV guaifenesin (Myolaxin Vet. diluted to 7.5%, Chassot & Cie AG,

Anaesthesia

The values for induction and maintenance doses, fluid supplementation rates, and times to extubation, sternal recumbency and standing are presented in Table 1. The mean total anaesthesia time (time of continuous infusion of propofol) was 2 hours.

Induction with guaifenesin and propofol was smooth in all horses except one, where the induction dose was insufficient and a supplemental dose of propofol (0.7 mg kg−1) was required. Endotracheal intubation was performed easily in all horses. The

Discussion

In the present study, total intravenous anaesthesia with propofol and ketamine maintained cardiovascular variables but depressed ventilation; injection of detomidine induced a marked but transient decrease in muscle and skin perfusion as measured with laser Doppler flowmetry, in spite of a simultaneous increase in systemic arterial pressure. An anaerobic muscle metabolic response was observed at the end of and during recovery from anaesthesia.

Acknowledgements

This project was supported by grants from the Swedish Medical Research Council. The authors thank Karin Thulin, Kristina Karlström, Yvette Hedström, Robert Jonasson and Anna Bergh for technical assistance and Schering Plough and VetPharma in Sweden for supplying propofol and ketamine. Warm and grateful thoughts go to the late Bertil Gazelius and others at Perimed, Sweden, for valuable help with the laser Doppler equipment and interpretation of results.

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