Research Paper
Effects of meloxicam on renal function in dogs with hypotension during anaesthesia

https://doi.org/10.1111/j.1467-2995.2005.00208.xGet rights and content

Abstract

Objective

To evaluate the effects of meloxicam on renal function in dogs anaesthetized and rendered hypotensive with acepromazine-thiopental-isoflurane.

Animals

Eight healthy beagles, four males and four females, 25.6 ± 19.3 months old and weighing 12.8 ± 2.0 kg.

Materials and methods

Either meloxicam suspension at a dose of 0.133 mL kg−1 (0.2 mg kg−1) or 0.133 mL kg−1 saline solution (control), were given by mouth (PO) in a randomized, cross-over fashion. The treatment or control was given 3 hours before anaesthesia. Dogs were sedated with intramuscular acepromazine 0.1 mg kg−1. Anaesthesia was induced with intravenous thiopental, followed by tracheal intubation and maintenance with isoflurane in oxygen and air, delivered using a semi-closed breathing system. Renal function was quantified using serum biochemistry, urinalysis and glomerular filtration rate measured by scintigraphy. Analysis of variance or Friedman anova were used for statistical analysis.

Results

Values (mean ± SD) for mean arterial blood pressure did not differ significantly between treatments but was low (54 ± 7 mmHg) during anaesthesia. Glomerular filtration rate did not differ significantly between treatments or over time, and results of urine and serum analysis were within reference ranges after meloxicam treatment.

Conclusions and Clinical relevance

Meloxicam caused no adverse effects on renal function when given to healthy dogs anaesthetized and rendered hypotensive with acepromazine, thiopental and isoflurane.

Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesic and anti-inflammatory agents that act in damaged tissue as well as at central nervous sites. They have little or no effect on respiration or blood pressure (Rang et al. 1999) and are being increasingly used in dogs for the long-term management of arthritic pain (Vasseur et al. 1995; Doig et al. 2000) and for the provision of peri-operative analgesia (Lobetti & Joubert 2000; Mathews et al. 2001).

Non-steroidal anti-inflammatory drugs act mainly by inhibiting cyclo-oxygenase (COX) activity in the biochemical cascade that leads to prostaglandin synthesis (Mitchell et al. 1994; Smith & DeWitt 1995). Prostaglandins generated by COX-2 participate in the inflammatory process, while those engendered by COX-1 are important in some homeostatic mechanisms, e.g. preservation of gastric mucosal integrity, and maintaining renal blood flow during hypotension and hypovolaemia (Seibert et al. 1994; Smith & DeWitt 1995; Vane et al. 1998). In healthy, normovolaemic conscious animals, renal blood flow is not impaired by NSAID-induced reduction of prostaglandin synthesis (Black et al. 1998). However, anaesthetics and other medication may impair blood pressure regulation. During surgery, hypovolaemia may aggravate this impairment. Under these conditions, NSAID suppression of prostaglandin synthesis may lead to renal ischaemia and damage (Elwood et al. 1992; McNeil 1992).

Meloxicam is reported to have a favourably high IC50 ratio (concentration at which 50% enzyme inhibition is detected) for COX-2 versus COX-1 inhibition in different in vitro and in vivo models (Engelhardt et al. 1996; Pairet et al. 1998) although the extent of its COX-2 selectivity in canine cell lines has varied (Ricketts et al. 1998; Kay-Mugford et al. 2000; Brideau et al. 2001). In two studies, meloxicam was found to be a more effective inhibitor of COX-2 than COX-1 (Kay-Mugford et al. 2000; Brideau et al. 2001) while in another, very little COX-2 selectivity was detected (Ricketts et al. 1998). The hypothesis tested in the current study was that meloxicam was COX-2 selective and, therefore, would have little effect on renal function in hypotensive dogs.

The aim of this study was to evaluate the effects of meloxicam on renal function in anaesthetized healthy dogs in which hypotension was induced with acepromazine, thiopental and isoflurane.

Section snippets

Materials and methods

Eight healthy beagle dogs were included in the study, four of each sex. Their mean age was 25.6 months (range 8–68 months) and their mean body mass was 12.8 kg (range 10.0–16.1 kg). The dogs were housed by the Department of Small Animal Clinical Sciences at the Veterinary Faculty, Uppsala. They were fed a standard diet and water was available ad libitum. Approval of the study was obtained from the local ethical committee on animal experiments.

A cross-over study was conducted with treatments

Results

Plasma meloxicam levels measured in four dogs were 0.6 ± 0.1 μg mL−1 at the induction of anaesthesia and 0.5 ± 0.1 μg mL−1 after 2 hours of anaesthesia (Fig. 1). These values exceeded those previously determined after oral administration in dogs (0.46 μg mL−1) by Busch et al. (1998).

There was no difference in the mean arterial blood pressure between the treatments but there was a significant change over time (p < 0.001). Values (mean ± SD) for mean arterial blood pressure were 110 ± 12 mmHg

Discussion

Oral drug administration produces unpredictable plasma levels because of inter- and intra-individual differences in gastric emptying, drug absorption and first-pass hepatic metabolism. However, when this study began, only the oral – not the injectable preparation of meloxicam – was available in Sweden. To ensure effective plasma levels with oral administration, meloxicam was given 3 hours before the induction of anaesthesia in fasted dogs. Plasma analysed in four dogs showed that meloxicam

Acknowledgements

The authors thank Mieth Berger, Ann-Marie Löfgren and Pia Funkquist for their technical assistance in this study, and Elisabeth Berg for statistical advice and assistance. We also thank the Department of Pharmacokinetics, Boehringer Ingelheim Pharma KG, Germany, for help with the determination of plasma meloxicam concentrations.

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