Little information is published regarding the pathologic effects of nonsteroidal anti-inflammatories in avian species. Injectable carprofen was administered intramuscularly to pigeons (Columba livia) at 2 mg/kg, 5 mg/kg, and 10 mg/kg for 7 days. Blood samples were obtained prior to administration of the drug, and again immediately prior to euthanasia for complete blood counts and plasma chemistry analysis. Randomly selected birds were euthanatized 24 hours after treatment days 1, 3, 5, and 7, and necropsies and histopathology were performed. Clinically significant pathologic effects were not found in these birds. Although an elevation of some plasma biochemical values occurred (specifically liver enzymes), the dose and length of treatment did not have a significant histopathologic effect on organ systems as a whole.
Carprofen is a nonsteroidal anti-inflammatory (NSAID) used therapeutically in veterinary medicine, to alleviate pain and decrease inflammation. Carprofen is a specific cyclooxygenase-2 (COX-2) inhibitor in the propionic acid class of NSAIDs.6 This class is used for their analgesic, anti-inflammatory, and antipyretic properties, and presumably does not cause as many side effects as cyclooxygenase-1 (COX-1) inhibitors.6 The introduction of parenteral carprofen (Pfizer Animal Health, Exton, PA, USA) in the United States presents another analgesic option to avian veterinarians. Although carprofen has been recommended in avian species for pain relief, few reports are available on the pathologic effects of NSAIDs, and specifically carprofen.1,3-5 The purpose of this study was to evaluate the pathologic and biochemical effects of parenteral carprofen in avian species, with pigeons (Columba livia) as a model.
Fifty-two apparently healthy pigeons were purchased from a private breeder. Eight birds were housed in six enclosures with four control birds in a separate enclosure. All birds were fed a commercial diet and water ad libitum. Baseline estimated white blood cell counts, plasma biochemical profiles, and cursory physical exams were performed prior to administration of the drug to determine overall health. All birds were weighed (mean 554 g, range 382–713 g) and were randomly assigned to one of three treatments groups, each containing 16 birds: carprofen at 2 mg/kg (group 1), 5 mg/kg (group 2), and 10 mg/kg (group 3). The medication was administered once a day for 7 days to all birds in alternating pectoral muscles. The four control animals were treated with saline injections in corresponding volumes in alternating pectoral muscles. Four carprofen-treated birds randomly selected from each group were humanely euthanatized at 24 hours after treatment days 1, 3, 5, and 7, along with one randomly selected control bird. Hematologic and plasma biochemical samples were obtained on all animals prior to euthanasia. All birds were necropsied with sections of ingluvia, proventriculus, ventriculus, small intestine, liver, kidney, and pectoral muscles submitted for histologic evaluation. Following fixation in 10% neutral buffered formalin, collected tissues were embedded in paraffin, sectioned to 10 µm, and stained with hematoxylin and eosin for histopathologic examination by an observer blinded to the treatments. Histologic changes were ranked by the pathologist (CAS) as: N—tissue within normal limits, 0—no lesion/not present, 1—minimal, 2—mild, 3—mild to moderate, 4—moderate, 5—moderate to marked, and 6—marked.
No statistically significant differences in hematologic parameters were measured between dosage groups, the control group, or within the groups over time. A statistically significant effect of treatment duration on total solids was detected. There was a trend of decreasing total solids on days 5 and 7 for each dose, while values were decreased on all days for the highest dose.
No significant difference in plasma creatine, potassium, albumin, total bilirubin, and blood urea nitrogen was measured between dosage groups or within the groups over time. Treatment duration had a statistically significant effect on sodium, chloride, calcium, total protein, globulin, alkaline phosphatase, and uric acid levels. The dosage of carprofen had a significant effect on the mean values of sodium, chloride, calcium, globulins, total protein, alkaline phosphatase, uric acid, glucose, aspartate aminotransferase (AST), and alanine aminotransferase (ALT).
The pectoral musculature had focally extensive pale areas that occasionally extended between the fascial planes in 33% of the birds in group 1, 50% of the birds in group 2, and 50% of the birds in group 3. No birds euthanatized 24 hours after treatment on day 1 had pale areas, but this lesion was present on half of the birds every euthanasia day thereafter. Mottled yellow livers were seen in 10 birds total with three in each carprofen treatment group and one control bird. Five of the birds with mottled livers were among those euthanatized 24 hours after the day one treatment. In the gastrointestinal tract, congested, erythematous small intestines were seen in seven birds, with representatives in all carprofen treatment groups. Of these birds, lesions were present 24 hours following treatment days 5 and 7. All other systems and organs were grossly normal.
Significant histopathologic changes were noted in the liver, kidney, and musculature. In the liver, acute lymphoid necrosis was significant, although by the ranking scale was considered only minimal (average 1). In the kidney, reactive diffuse lymphoid tissue and acute diffuse congestion were significant lesions. The pectoral muscle lesions consisted of myodegeneration. Histopathologic changes present in the ingluvia, proventriculus, ventriculus, and small intestine were not significant.
Clinical pathology results revealed significant changes compared to documented acceptable avian liver, muscle and kidney plasma biochemical parameters. Clinical evaluation of the mean concentrations of glucose, sodium, calcium, and alkaline phosphatase were within normal limits compared to International Species Information System (ISIS) normal reference ranges for domestic pigeons.2 Uric acid values were within normal reference limits for all mean plasma values except for the 2 mg/kg dose on day 7. Chloride control values were higher than ISIS reference ranges; however, all response values were within reference ranges. The most significant mean response value results were for AST and ALT, which were considerably higher than the clinical reference ranges. The mean values increased as the dose administered increased. Both values were statistically significant due to the effect of dose, and there was no effect of the length of treatment on the mean values of AST or ALT. This finding would suggest liver damage rather than muscle damage from multiple injections. Plasma creatine phosphokinase levels were not measured in this study; therefore, elevations in serum AST or ALT due to muscle damage cannot be entirely ruled out.
Grossly pale areas were observed in the pectoral musculature indicating muscle damage; however, significant necrosis of the muscles was not seen histopathologically. Acute, diffuse congestion of the kidney was observed in all animals (even controls), minimally or mildly. As clinically significant changes to the kidney values were not observed and this finding was present in the control animals, it would appear that the carprofen doses utilized in this study did not adversely affect renal tissue. The histopathologic changes to the liver were also mild, suggesting that the AST and ALT elevations were transient and are not due to significant damage to the liver due to the medication.
The use of injectable carprofen at 2 mg/kg, 5 mg/kg, or 10 mg/kg did not cause clinically significant pathologic effects in these birds. Although an elevation of some plasma biochemical values (specifically liver or muscle enzymes) was likely due to the dose administered, the dose did not have a significant histopathologic effect on organ systems as a whole. Injectable carprofen can be used at each of the stated doses for a treatment length of up to 1 week without significant clinicopathologic or histopathologic effects. Further research will be necessary, however, to determine efficacy and dosage for injectable carprofen in control of painful stimuli.
1. Carpenter, J.W., T.Y. Mashima, and D.J. Rupiper. 2001. Exotic Animal Formulary. 2nd ed. W.B. Saunders Co., Philadelphia, PA. Pp. 165.
2. International Species Inventory System. 1999. Physiologic data reference values. 12101 Johnny Cake Ridge Road, Apple Valley, MN.
3. McGeown, D., T.C. Danbury, A.E. Waterman-Pearson, and S.C. Kestin. 1999. Effect of carprofen on lameness in broiler chickens. Vet. Rec. 144: 668–671.
4. Paul-Murphy, J., and J.W. Ludders. 2001. Avian analgesia. Vet. Clin. North Am. Exot. Anim. Pract. 4: 35–45.
5. Pollock, C. 2002. Postoperative management of the exotic animal patient. Vet. Clin. North. Am. Exot. Anim. Pract. 5: 183–212.
6. Ricketts, A.P., K.M. Lundy, and S.B. Seibel. 1998. Evaluation of selective inhibition of canine cyclooxygenase 1 and 2 by carprofen and other nonsteroidal anti-inflammatory drugs. Am. J. Vet. Res. 59: 1441–1446.