Second-generation anticoagulant rodenticide poisoning in a captive andean condor (Vultur gryphus).
Key words: brodifacoum, secondary anticoagulant rodenticide toxicosis, blood transfusion, second-generation anticoagulant rodenticide, SGAR, vitamin [K.sub.1], raptor, avian, Andean condor, Vultur gryphus
A 28-year-old female Andean condor (Vultur gryphus) housed in an outdoor exhibit at the National Aviary in Pittsburgh, PA, began showing signs of weakness. Toxicosis with an anticoagulant rodenticide was suspected because its mate had died 1 day before from possible brodifacoum poisoning. The female condor was thought to have ingested rodenticide as a result of the male feeding it, since this behavior was historically observed between the pair.
The female condor had a pre-existing grade 3/5 heart murmur and an estimated weight of 10 kg. Findings on physical examination were otherwise normal. A blood sample was collected for a complete blood count (CBC), a plasma biochemical panel, a bile acid level, and toxin screening, including lead, zinc, (Avian and Exotic Animal Clin Path Labs, Wilmington, OH, USA), and anticoagulant rodenticides (Michigan State University, Diagnostic Center for Population and Animal Health, East Lansing, MI, USA). Given the history and pending blood test results, a preventative treatment plan of vitamin [K.sub.1] (0.2 mg/kg q12h IM), single-dose vitamin B complex (0.06 mg/kg IM), enrofloxacin (10 mg/kg IM q12h; Baytril, Bayer HealthCare, Indianola, PA, USA), and single-dose selenium/vitamin E (0.06 mg/kg IM) was prescribed. Blood test results revealed total solids (TS) of 3.8 g/dL (reference interval, 2.9-5.5 g/dL) (1) and a packed cell volume (PCV) of 56% (reference interval, 39%-48%) (2) with slight to moderate degranulation of heterophils. Table 1 summarizes the PCV and TS values throughout the initial 9 days of treatment. Figure 1 demonstrates these values in relation to the transfusion date on day 4. Results of lead and zinc tests were within normal reference intervals.
On day 2, the results of the deceased mate's blood anticoagulant rodenticide screen confirmed the presence of brodifacoum at 0.005 ppm. With this knowledge, the vitamin [K.sub.1] dosage for the female condor was increased to 5 mg/kg IM q12h. Additionally, the weakness worsened and vomiting developed after restraint on the previous day, supporting continued treatment for brodifacoum toxicosis.
On day 3, the condor was restrained for blood collection to assess for changes in values of PCV and TS that would indicate internal hemorrhage. The results revealed the PCV value had decreased to 37% and the TS value had decreased to 3.4 g/dL. After restraint, 3 episodes of vomiting and prolonged marked weakness were observed, with trace amounts of blood present in the vomitus. The bird appeared quiet and depressed. Because it would not ingest the medication if hidden in food, the condor had to be caught and restrained twice daily for treatment. The concern was that with repeated capture and restraint, the stress and energy expenditure would weaken it further. Additionally, the natural defense mechanism of vomiting complicated restraint efforts and resulted in consumption of insufficient calories for maintenance (3) During restraint on day 3 of subcutaneous fluids (800 mL), 2.5% dextrose and 0.45% sodium chloride were administered in addition to other medications.
On day 4, the bird's PCV value dropped to 33% and the TS value to 3.0 g/dL, and blood clotting time was measured at 15 minutes. Despite twice daily vitamin K| administration, trace blood was observed in vomit and feces. Vomiting persisted at rest, and the bird was anorectic and appeared nauseous even when not being handled. With the rapid decline in PCV paired with the clotting time of 15 minutes, blood transfusion was considered necessary.
The goal of the transfusion was to provide 10% blood volume replacement, which was estimated at 50 mL. Donor birds were 1 bald eagle (Haliaeetus leucocephalus; 18 mL whole blood collected with 1.8 mL of acid citrate dextrose (ACD) and 2 Steller's sea eagles (Haliaeetus pelagicus; 1 donating 27 mL of whole blood with 2.7 mL of ACD, the second donating 30 mL of whole blood with 3.0 mL of ACD), which, combined, provided a total of 41.5 mL of whole blood (0.415% of the recipient bird's body weight) collected into ACD. Donor birds were manually restrained and placed on their backs with a wing extended. Blood was collected from the ulnar wing vein at 0.3% of donor body weight with a 22-gauge butterfly needle into a syringe prefilled with ACD solution. The volume of ACD was predetermined by selecting a target volume to collect from the donor without compromising it and matching the ACD for a 1:10 ratio. The syringe was rocked to mix the blood and ACD as the blood was pulled into the syringe. Donors received subcutaneous fluids, calcium glubionate, and supplemental oxygen after blood collection. No Andean condors were available to serve as donors; although homologous transfusion is ideal, due to erythrocyte longevity, heterologous blood transfusions across species have been successful. (4)
The procedure was performed without anesthesia due to the bird's debilitated state and the risk of anesthesia. Single-dose preprocedure medications administered were vitamin [K.sub.1] (10 mg/kg IM), diphenhydramine (2 mg/kg IM) to prevent reaction to the donor blood, and dexamethasone (4 mg/kg IM). Lidocaine 2% gel was applied at the catheter site. Fresh unfiltered donor blood (41.5 mL) was transfused into the medial metatarsal vein through a 25-gauge catheter at a rate of 2 mL/min. Six minutes after the transfusion, the bird regurgitated, followed by intermittent vomiting for the next 24 hours. Posttransfusion supportive therapy consisted of vitamin [K.sub.1] (5 mg/kg IM q12h), enrofloxacin (15 mg/kg IM q24h), vitamin B complex (0.06 mg/ kg IM 1 time), selenium and vitamin E (0.06 mg/kg IM 1 time), and supplemental fluids as needed (180 mL q24h; 2.5% dextrose with 0.45% NaCl).
On day 5, 1 day after transfusion, the bird appeared weak, quiet, and responsive and was exhibiting abnormal posture, resting on its hocks with its head drooped. Its appetite was also decreased, and as a result, medications for that day were administered intramuscularly, when the bird did not eat medication offered in food. Famotidine (1 mg/kg IM q12h) was added to the treatment plan.
Vomiting was resolved by day 6, and the condor appeared stronger. Medications were then offered in food. Both the bird's PCV and TS values had increased (44% and 3.7 g/dL, respectively), and the bird was now considered stable, rather than critical. A calcium supplement (5 mg/kg PO q12h; calcium glubionate syrup, 1.8 g/5 mL) was added to the treatment plan on the basis of a literature review suggesting that calcium supports several steps of the avian clotting cascade. (5)
On day 7, the bird was restrained for physical examination, after which it was quiet with openmouth breathing. The treatment plan was revised to increase the vitamin [K.sub.1] to 15 mg/kg IM q24h for 3 days, followed by a tapered dose of 10 mg/kg q24h every other day for 4 weeks.
On day 9, although the bird's PCV and TS values were stable at 46% and 3.8 g/dL, respectively, it showed slight to moderate clinical signs of weakness, vomiting with no trace blood, and hyporexia for 6 days after transfusion. Overall, on day 9, the bird appeared bright, alert, and responsive, and although slightly weak during the subsequent 5 weeks, it continued to gain strength.
During a 39-day course of treatment, 21 days had 100% treatment success in administration of vitamin [K.sub.1] in the food. Handling of the bird was minimized to decrease stress. On day 39, the plan was to decrease the vitamin [K.sub.1] dosage, at that time being given as tablets PO q12h in food, to 5 mg/kg q24h starting at week 10 of treatment, and then decreased further to 2.5 mg/kg q24h at week 14. At week 17, vitamin [K.sub.1] was discontinued. Table 2 summarizes the vitamin [K.sub.1] regimen until it was discontinued on day 119 after onset of illness.
Approximately 4 months after the onset of illness and 2 weeks after discontinuing vitamin K], the bird exhibited hyporexia, weakness, and trembling legs. Concerned about a relapse, vitamin [K.sub.1], was again prescribed at a dosage of 5.5 mg/kg q24h PO in food for 4 weeks. The next day, the bird was depressed and shivering and presented with decreased mentation, drooped wings, and poor posture. The bird was admitted to the hospital, and fecal testing revealed abundant Clostridium. Although Clostridium is found as normal flora in condors, the bird was treated with metronidazole (10 mg/kg PO q12h) for 10 days as a precautionary measure due to its compromised state. Treatment with vitamin K, (5.5 mg/kg PO q24h) continued for 4 months on a tapering dosage.
During an environmental investigation of the bird's enclosure, fur from a wild rat was found. As a result, it was suspected that the bird suffered from secondary brodifacoum toxicosis after consuming a poisoned rat from a neighboring park that had been recently baited with brodifacoum rodenticide. Brodifacoum was not used within the aviary itself; thus, exposure likely was from an outside source, such as a poisoned rat entering the enclosure. The rat fur tested positive for brodifacoum, and the liver brodifacoum level of the deceased male condor was positive at 0.038 ppm, further supporting exposure.
This case study demonstrates the diagnosis of a captive Andean condor with brodifacoum toxicosis and successful treatment with a blood transfusion and vitamin K] therapy. Brodifacoum is a second-generation anticoagulant rodenticide (SGAR) suspected to be the etiologic agent in this case. Given the necessity for pest control in zoo and wildlife facilities, along with the ease of accessibility of exhibits to wildlife, secondary SGAR toxicosis poses a threat to captive birds of prey and mammalian carnivores.
Brodifacoum demonstrates a similar mechanism of action as that of warfarin, but with greater toxicity potential because of its accumulation in the liver, pancreas, and kidneys, where it is stored for a minimum of 6 months. (6-9) Brodifacoum functions by inhibiting vitamin K epoxide reductase, an enzyme critical for the production of useable vitamin [K.sub.1] in the body. The product of the vitamin K epoxide reductase reaction serves as a cofactor in the activation of clotting factors II (prothrombin), VII, IX, and X. (10) Because clotting factors are in reserve, brodifacoum toxicosis does not typically exhibit clinically in exposed animals until 3-5 days after ingestion, with changes in prothrombin time and activated partial thromboplastin time times being unapparent for 36-48 hours. (11)
In companion animals, brodifacoum poisoning is associated with clinical signs of hematuria, bruising, generalized internal hemorrhaging, and melena, sometimes with epistaxis and gingival and prepuce bleeding. (12,13) In cats, common clinical signs are petechia, bleeding from the conjunctiva, lethargy, respiratory distress, and hematomas. (14)
Second-generation anticoagulant rodenticides are a common form of pest control in zoos and other animal facilities throughout the United States; however, as this report highlights, these rodenticides pose a risk of secondary toxicosis, also called relay toxicosis, to carnivorous birds and mammals that consume poisoned rodents. Cockroaches and woodlice that consume brodifacoum have been found to maintain a detectable amount in their systems for 6 weeks; however, a bird would need to consume at least its own body weight in cockroaches to reach the median lethal dose. (15) Nevertheless, since little information is available regarding toxic levels and treatment in Andean condors, the idea of secondary exposure via insects should not be entirely dismissed.
One study has reported the successful treatment of a white-winged wood duck (Cairina scutulata) that presented with anemia and bilateral epistaxis. The duck received vitamin K] injections at 0.2 mg/ kg IM q24h, then switched to oral administration on day 5 after presentation. A transfusion was performed after the bird again presented for epistaxis on day 9. (16)
Similar to signs seen in domestic animals, avian species have reportedly exhibited subcutaneous hematomas in addition to weakness and anemia when exposed to toxic levels of brodifacoum. (17) However, the condor we describe did not present with unusual bleeding, despite intramuscular treatment injections and venipuncture for blood collection. It was initially bright, alert, and responsive, but its condition quickly declined as it began vomiting and regurgitating, even when unprovoked by handling. Vomiting continued until 6 days after transfusion. Weakness, hyporexia, and lethargy were also apparent at the initial onset of clinical symptoms and in the several days after the transfusion. Overt hemorrhaging, subcutaneous hematomas, epistaxis, and petechiae of mucosal membranes were not observed.
Treatment efforts were hindered by several factors. The turnaround time for a rodenticide toxicosis panel ranges from 5 to 7 days. In this case, liver brodifacoum values from the deceased mate did not return until day 2 of the case, and this female condor's own test results for brodifacoum were not confirmed until day 4. However, the bird was in a critical condition within 12 hours after the onset of clinical signs. As with any test, there are also challenges with sensitivity. Although the bird's blood brodifacoum concentration was low (<0.002 ppm), studies have confirmed that accumulation of anticoagulant rodenticide in the liver is sufficient to cause clinical signs and death, even while blood assays do not confirm its presence. (18)
Because test results were pending, a preliminary treatment regimen of vitamin [K.sub.1] enrofloxacin, dexamethasone, subcutaneous fluids, selenium/ vitamin E, and vitamin B complex was prescribed. Enrofloxacin was chosen as a prophylaxis against possible secondary infection, and dexamethasone was given for initial shock and for its anti-inflammatory effect. Subcutaneous fluids were given supportively to counter dehydration, and selenium/vitamin E complex was provided to minimize capture myopathy. On day 6, calcium glubionate was incorporated to help facilitate clotting.
For Andean condors and other raptors that are more likely to suffer from secondary brodifacoum toxicosis, lack of known species clotting times, species size, need for restraint, and exertion during restraint are additional factors that complicate treatment. All of these factors limit testing, treatment, and monitoring. Unfortunately, canine and feline prothrombin time/partial thromboplastin time tests and values are not appropriate for birds. Thus, the best assessment for clotting ability is observed clotting times in a red-topped tube. In the condor we describe, the blood sample was initially clotting at 15 minutes. Normal clotting times are between 2 to 10 minutes but vary between species and individuals. (13) The vomiting and lack of appetite compromised the success rate of orally administered vitamin [K.sub.1], yet catching and restraining the condor for intramuscular injections elicited the behavioral response of vomiting. (1) Ultimately, oral administration was successful and may have aided in the bird's recovery, in that orally administered vitamin [K.sub.1] has greater bioavailability. (4)
Success with oral medications is challenging in condors because of their stress reflex of vomiting when restrained for examination, tests, and treatments. Treatment success increases when initial treatments are administered by intramuscular injections when the bird is critical. Once stabilized, the bird can be handled less and transitioned to medications hidden in food items. While mice, rats, and chicks were used for oral administration of medications in this condor, fatty meals, such as egg yolks, have been suggested, which may potentially increase intestinal absorption of vitamin [K.sub.1]. (13)
Overall, the features of success in this case are attributed to a higher than recommended dose and longer treatment duration of vitamin [K.sub.1], along with a blood transfusion. Because of the time delay between signs and laboratory confirmation of brodifacoum toxicosis, vitamin [K.sub.1] should be administered if there is a remote possibility of anticoagulant rodenticide toxicosis, because it is safe, inexpensive, and essential for treatment. (19)
A recommended dosage of vitamin K in birds is 0.2-2.2 mg/kg IM every 4-8 hours until the animal is determined stable, and then the dosage decreases to once a day for 2 weeks. (20) In a retrospective study of raptors presenting to a wildlife center, a vitamin K| dosage of 0.2-2.5 mg/kg IM every 4-8 hours was effective in 8 out of 9 of raptors with suspect anticoagulant poisoning. (21) Successful treatment of a red-tailed hawk (Buteo jamaicensis) was reported with a 4-week treatment regimen of 2.5 mg/kg q24h. (2) Distinction was not made in the former study as to whether or not the anticoagulants were first or second generation, which would affect the extent and duration of coagulopathy. However, in the case we describe, the traditional dose of vitamin [K.sub.1] was found to be inadequate, and it was not until the dose was increased to 15 mg/kg that clinical response was observed. This dose is much higher than the current avian recommendation of 0.2-2.5 mg/kg as needed for hemorrhagic disorders. (19) Furthermore, the bird in this case required an extended treatment of vitamin [K.sub.1] for a total of 17 weeks, followed by a 4-month tapering dosage after suspected relapse. Such treatment duration is likely because of the lengthy persistence of brodifacoum in the body, particularly in the liver. (6,22) In this case, a tapering dosage of vitamin [K.sub.1] was used as a safeguard in monitoring for relapse without full debilitation, as the persistence of brodifacoum in condors is unknown.
In companion animals, either whole blood or plasma transfusions are often necessary to support patients while they recuperate their proper vitamin [K.sub.1] levels. (23) The decision to transfuse must be made in a timely fashion, as evidenced by this bird's rapid progression from stable to critical within 12 hours and declining PCV values. The normal PCV ranges for Andean condors are reported to be between 39% and 48% with a mean of 42%.2 Although transfusions have been recommended in raptors with a PCV less than 20%, the decrease in the bird's PCV from 56% on day 1 to 33% on day 4, with a corresponding increase in clotting times and decrease in plasma protein, marked a wide enough margin to warrant transfusion. (24) Whole blood is preferred in cases of excessive blood loss, but fresh or fresh-frozen plasma may be transfused in cases where the animal has not yet become anemic. (10) In this case study, whole blood was chosen to replace lost cells and replenish clotting factors. Although a transfusion of 1% body weight has been proven safe, the bird in this case received 0.415% of its body weight in whole blood. (25)
Currently, the condor is doing well and is stable. It is still housed at the National Aviary along with a new mate that was introduced in January 2014. Aside from the potential relapse, there has been no evidence of sequelae from the toxicosis or subsequent treatment procedures.
Acknowledgments: We thank the doctors and staff of the Pittsburgh Veterinary Specialty and Emergency Clinic for their provision of blood collection bags, the Pittsburgh Zoo and PPG Aquarium for their assistance during the transfusion, and Dr Robert Van Saun of the Pennsylvania State University for his assistance in editing this manuscript.
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Kira L. Hydock, BS, BA, Camille DeClementi, VMD, Dipl ABT, Dipl ABVT, and Pilar H. Fish, DVM
From The University of Pennsylvania School of Veterinary Medicine. 331 Thistle Court, Pittsburgh, PA 15239, USA (Hydock); the ASPCA Animal Poison Control Center, 1717 South Philo Road. Suite 36, Urbana, IL 61802. USA (DeClementi); and The National Aviary, 700 Arch Street, Pittsburgh, PA 15212, USA (Fish).
Caption: Figure 1. Serial packed cell volume (PCV) and total solids (TS) by day in a captive Andean condor with brodifacoum rodenticide toxicosis. Case day indicates day of transfusion; values from that day were collected before transfusion.
Table 1. Packed cell volume (PCV) and total solids (TS) values in a captive Andean condor with brodifacoum toxicosis by case day after presentation. Day PCV (%) TS (g/dL) 1 56 3.8 3 37 3.4 4 (a) 33 3.0 6 44 3.7 9 46 3.8 (a) Values before transfusion on day 4. Table 2. Vitamin K, dosages used for treatment of a captive Andean condor with brodifacoum toxicosis. Days after onset of clinical signs Dosage 1 0.2 mg/kg q12h 2-6 5 mg/kg q 12h 7-9 15 mg/kg q24h 10-39 10 mg/kg q24h 40-70 5 mg/kg q24h 71-98 2.5 mg/kg q24h 99-118 2.5 mg/kg q48h 119 Discontinued
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|Title Annotation:||Clinical Report|
|Author:||Hydock, Kira L.; DeClementi, Camille; Fish, Pilar H.|
|Publication:||Journal of Avian Medicine and Surgery|
|Date:||Sep 1, 2017|
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