Upper Airway Obstruction Secondary to Anticoagulant Rodenticide Toxicosis in Five Dogs
ABSTRACT
Five dogs were presented with clinical signs compatible with upper airway obstruction, including stridor, stertor, coughing, gagging, and varying degrees of respiratory distress. All dogs had radiographic findings of soft tissue opacity in the area of the pharynx, larynx, or trachea, and several had narrowing of the tracheal lumen. Coagulation abnormalities (prolonged prothrombin time, activated partial thromboplastin time) were present in the four dogs that underwent testing. Four of five dogs were treated for the coagulopathy, presumably due to anticoagulant rodenticide toxicosis, and survived to discharge.Upper airway obstruction is an unusual presentation for anticoagulant rodenticide toxicosis in dogs. Raising the index of suspicion for this treatable condition may help clinicians to identify this sooner.
Introduction
Anticoagulant rodenticide ingestion and associated coagulopathy is one of the most common presentations to small animal emergency hospitals.1 The American Society for the Prevention of Cruelty to Animals Animal Poison Control Center has repeatedly reported that rodenticides are in the top 10 intoxications in dogs and cats.2 Rodenticides were the fourth most common reported toxin ingested in dogs according to a report published in 2006.1 Anticoagulant rodenticides are currently the most common of these reported intoxications.2
A retrospective study published in 2013 found that brodifacoum was the most common anticoagulant rodenticide identified when screening was performed to evaluate for brodifacoum, diphacinone, and chlorophacinone. In addition, 28% of the patients that tested positive for anticoagulant rodenticide had no known exposure.3 Anticoagulant rodenticides cause life-threatening hemorrhage by inhibiting vitamin K epoxide reductase in the liver, and the pathophysiology has been reviewed elsewhere.4–9
The clinical signs of anticoagulant rodenticide toxicosis are numerous and quite variable, depending on the site of hemorrhage. These include lethargy, inappetence, vomiting, respiratory distress, and cough. There may or may not be external signs of hemorrhage, including gingival bleeding, epistaxis, hematemesis, melena, or hematuria. Internal hemorrhage generally occurs within body cavities, including the retro-peritoneum, pleural space, pulmonary parenchyma, and occasionally the pericardial space.10,11 Patients may also hemorrhage into the mediastinum, brain, joints, and eyes.12 Diagnosing coagulopathy from presumed anticoagulant rodenticide toxicosis is generally straightforward when the patient has overt signs of hemorrhage and a history of exposure. The challenge lies in diagnosing patients that present with unrecognized hemorrhage.
Upper airway obstruction is frequently seen in small animal emergency rooms, and there is a long list of differential diagnoses, including laryngeal paralysis, foreign body obstruction, and brachycephalic airway syndrome.7,13,14 In a review of four reference texts commonly available in small animal emergency hospitals, there was no mention of anticoagulant rodenticide toxicosis as a differential for upper airway obstruction, and clinicians may not have an increased index of suspicion for anticoagulant rodenticide toxicosis when presented with a dog with upper airway obstruction.7,13–15
This case series describes five dogs with anticoagulant rodenticide toxicosis that were treated through the Emergency Service (ES) within a 2-yr period at the Veterinary Teaching Hospital, University of Illinois.
Materials and Methods
Case 1
A 1 yr 10 mo old intact female Maltese (2.82 kg) was presented to the ES for difficulty breathing and possible esophageal foreign body. The patient presented for acute respiratory distress and was evaluated previously in the day by the primary care veterinarian. Lateral cervical radiographs revealed a soft tissue opacity within the laryngeal region.
Upon arrival to the ES, the patient had labored breathing with significant stridor. A physical examination with limited handling revealed a mass in the cranioventral cervical region, and palpation induced worsening respiratory distress. There were no visible ecchymoses or other masses found on brief physical examination. The patient was placed in an oxygen cage (40% fraction of inspired oxygen [FiO2]), butorphanol (0.2 mg/kg intramuscular) was administered, and the patient was handled as little as possible to minimize stress. Approximately 5 hr after arrival, the patient vomited a brown fluid multiple times, collapsed, and experienced cardiopulmonary arrest. Multiple doctors attempted intubation but were unsuccessful due to a soft tissue obstruction in the caudal pharyngeal region. An emergency tracheostomy was performed to obtain an airway, but there was no return of spontaneous circulation after 15 min of cardiopulmonary resuscitation. The surgeon that performed the tracheostomy noted hemorrhage in the fascial planes surrounding the tracheal region.
The body was submitted for necropsy, and the patient was found to have significant hemorrhage and edema in the region of the pharynx and larynx. There was locally extensive elevation of the tracheal submucosa with hemorrhage and edema in the laryngeal region and mild hemorrhage in the mediastinum, lungs, and renal interstitium. The cause of death was airway obstruction secondary to hemorrhage. A coagulation abnormality was suspected, and the owners stated that there was anticoagulant rodenticide on the property. Two other dogs in the home had increased prothrombin time (PT) when screened. They were treated with Vitamin K1a by the referring veterinarian (RDVM) and lacked any clinical signs of hemorrhage.
Case 2
A 9 yr old female spayed Labrador retriever (30.7 kg) was presented to the ES for a 3-day history of increased respiratory rate (RR) and a several hr history of increased respiratory effort. The dog lived outside and had a history of eating rabbits and rodents. The dog had ingested a rabbit and vomited shortly thereafter, 3 days before presentation. A dog living in the household had acutely died 1 wk previously. It is unknown whether there was rodenticide in the dog's environment.
The patient was evaluated by the RDVM when her respiratory effort had increased and she was coughing and gagging. Lateral tracheal and cranial thoracic radiographs revealed a narrowing of the tracheal lumen, predominantly at the thoracic inlet. Dexamethasone sodium phosphate and butorphanol were administered in hospital, and cephalexin, prednisone, and butorphanol were prescribed for home administration (dosages unknown). The patient was referred to the ES when no improvement was noted at home.
On arrival to the ES, the patient was quiet, alert, and responsive, blood oxygen saturation (SpO2) was 100% (unknown if supplemental oxygen provided at this time), the RR was elevated at 44 breaths per min, and the patient had significantly increased inspiratory effort and stridor. There were no auscultable crackles in the lung fields. A mild soft tissue swelling was palpated caudal to the larynx.
Due to progressive respiratory distress, the patient was administered butorphanol [0.33 mg/kg IV] and propofole (IV) was titrated to effect to allow intubation. Given the patient's body weight, an abnormally small endotracheal tube was necessary for intubation, and the tube had to be inserted beyond the thoracic inlet to provide an adequate airway. The patient was heavily sedated with propofol, midazolam, and hydromorphone constant rate infusions (doses unknown). Based on prolonged PT and activated partial thromboplastin time (aPTT) (Table 1), fresh frozen plasma (FFP) (13.8 ml/kg) was administered over 3 hr, and Vitamin K1 (5 mg/kg) was given subcutaneously (SC). The patient was extubated after 4 hr because of suspected occlusion of the endotracheal tube but was not reintubated based on the patient's ability to breathe and oxygenate appropriately at that time (SpO2 100% at FiO2 of 40%). The patient was kept sedate with propofol (1.95–2.6 mg/kg/hr), midazolam (0.2 mg/kg/hr), and hydromorphone (0.05–0.1 mg/kg/hr) constant rate infusions for approximately 12 hr, and supplemental oxygen was administered for 24 hr.
The patient was diagnosed with probable anticoagulant rodenticide toxicosis, resulting in the narrowing of the tracheal lumen from extra-luminal hemorrhage. The dog was hospitalized for 48 hr and discharged with Vitamin K1 (2.5 mg/kg per os [PO]) every 12 hr for 30 days. The medications prescribed by the referring veterinarian were discontinued. The patient made a full recovery.
Case 3
A 6 yr 10 mo old castrated male shih tzu (6.07 kg) was referred to the ES for suspected esophageal foreign body. The dog had a 1-day history of stertorous, labored breathing with progressive coughing and lameness of the left pelvic limb and a previous history of a similar cough that was associated with excitement or pulling on a leash. Lateral thoracic radiographs performed by the RDVM revealed a narrowed tracheal lumen. There was no mention in the record of whether the narrowing was intrathoracic or extrathoracic or both.
On arrival the RR was 16 bpm. There was obvious stertor and significantly increased inspiratory effort, but thoracic auscultation was normal. The dog's mucous membranes were pale on arrival, and the heart rate was elevated at 240 beats per minute on auscultation. The left pelvic limb was noted to have considerable edema and moderate ecchymosis. A coagulation panel [PT, aPTT), fibrinogen] and complete blood count were submitted (Table 1). Cervical and thoracic radiographs confirmed significant narrowing of the tracheal lumen, particularly in the extrathoracic portion (Figure 1). No esophageal foreign body was identified on radiographs, but there were changes consistent with mediastinal widening. There was no evidence of pulmonary infiltrates or pleural effusion. No peritoneal fluid was present on limited abdominal ultrasound. The patient developed mild scleral hemorrhage in the left eye while hospitalized.
Citation: Journal of the American Animal Hospital Association 53, 4; 10.5326/JAAHA-MS-6658
Based on clinical signs and coagulation abnormalities, despite no known exposure, the patient was diagnosed with probable anticoagulant rodenticide toxicosis. The dog was sedated with butorphanol (0.4 mg/kg IV) as needed during hospitalization. FFP (10 ml/kg) was administered over 2 hr. Vitamin K1 (5 mg/kg) was administered SC initially and then 2.5 mg/kg PO every 12 hr for 30 days. The patient was placed in an oxygen cage (40% Fi02) for 24 hr. The patient was discharged with mild increased inspiratory effort, which had improved significantly from presentation. The patient did well for the first mo after discharge and then was lost to follow up.
Case 4
A 1 yr 8 mo old spayed female cocker spaniel (12 kg) was referred to the ES for labored breathing and a history of mild anemia and thrombocytopenia. The patient had been evaluated by a local veterinarian for lethargy and inappetence 2 days before presentation, and abdominal radiographs revealed a moderate sized mineral opacity (consistent with a rock) in the stomach. Blood work revealed anemia (hematocrit 25.1%; 37.4–61.7%) and thrombocytopenia (58,000/uL; 148,000–484,000/uL), and the patient developed gingival bleeding during the RDVM's exam. Surgery to remove the rock was not performed because of presumed immune-mediated hemolytic anemia and thrombocytopenia. The patient was treated with immunosuppressive doses of prednisone and doxycycline (doses unknown) by the RDVM. Within 2 days of evaluation by the RDVM, the patient had developed labored breathing and was referred to the ES for further diagnostics and treatment. There was no known exposure to anticoagulant rodenticide.
Upon arrival to the ES, the patient was bright, alert, and responsive. There were auscultable harsh sounds over the trachea. The patient was panting, but there was no significant respiratory distress. There were mild ecchymoses on the buccal mucosa, a large ecchymosis in the left axillary region, and a 3 to 4 cm palpable mass in the ventral proximal neck. Based on initial examination, there was concern for coagulopathy rather than an immune-mediated disease, and a coagulation panel was performed (Table 1). The clinician on this case had been present for two of the previous cases (case 2 and 3) and had developed an index of suspicion for upper airway obstruction from anticoagulant rodenticide toxicoses. Tracheal and thoracic radiographs were performed, and there was no evidence of pulmonary infiltrates, pleural effusion, or tracheal narrowing, but there was increased soft tissue swelling in the pharyngeal region and mild ventral deviation of the larynx (Figure 2). Limited abdominal ultrasound revealed no free peritoneal fluid.
Citation: Journal of the American Animal Hospital Association 53, 4; 10.5326/JAAHA-MS-6658
Despite reported lack of exposure, the patient was diagnosed with presumed anticoagulant rodenticide toxicosis. Treatment was initiated with FFP (10 ml/kg), Vitamin K1 (5 mg/kg) SC, and aminocaproic acidj (48 mg/kg IV) as an antifibrinolytic. The patient had an episode of coughing and mild respiratory distress five hr after arrival. Butorphanol was administered (0.2 mg/kg IV), and the patient was placed in an oxygen cage (40% FiO2) for 24 hr. Repeat of PT and aPTT were normal 36 hr after hospitalization (Table 1), and gastroscopy was performed approximately 48 hr after hospitalization to remove a rock from the patient's stomach. The patient was discharged receiving Vitamin K1 (3 mg/kg PO) every 12 hr for a total of 30 days. By the time of discharge the soft tissue swelling in the neck region was still present, but it was significantly improved and was no longer causing respiratory distress. The patient made a full recovery.
Case 5
A 6 yr old spayed female Pomeranian (5.2 kg) was referred to the ES for acute onset of respiratory distress. The patient had developed a voice change and significant trouble breathing after becoming excited when her owner returned home from work. Radiographs performed by the RDVM revealed a narrowed tracheal lumen and increased soft tissue opacity in the cranial lung fields. The dog was given furosemide (2 mg/kg), enrofloxacin (5 mg/kg), dexamethasone sodium phosphate (0.5 mg/kg), and penicillin (62,500 U/kg IV), presumably to address possible heart failure, pneumonia, and/or inflammation. The dog developed very mild serosanguinous nasal discharge upon arrival to the ES.
On presentation, the dog was panting, with an increased inspiratory effort and a SpO2 of 98%. There was significant referred upper airway noise but no sensitivity or cough on tracheal palpation. The patient was placed in an oxygen chamber at 40% FiO2 shortly after arrival. There was no history of previous coughing episodes or difficulty breathing. The patient was hospitalized with the preliminary diagnosis of severe collapsing trachea causing respiratory distress. Within the first few hr of hospitalization, the nasal discharge became more hemorrhagic, and she developed mild scleral hemorrhage. Although the owner initially thought there was no potential rodenticide exposure, searching of their yard revealed a bait box with a hole chewed through the lid. A coagulation panel and complete blood count were performed to confirm the suspicion for coagulopathy (Table 1).
Treatment for probable anticoagulant rodenticide toxicosis was initiated. The dog was given FFP (10 ml/kg IV) over 2 hr, Vitamin K1 (5 mg/kg) SC, and butorphanol (0.2 mg/kg IV) as necessary for anxiety. Within 6 hr of receiving the plasma transfusion, the epistaxis resolved, and no additional external bleeding was appreciated. Vitamin K1 was administered (2.5 mg/kg) SC until the patient started eating, at which time she was switched to oral dosing. The dog remained in an oxygen chamber at 40% FiO2 for approximately 36 hr and at the time of discharge was much more comfortable, had mild inspiratory effort, and a resting RR of 20 breaths per minute. Vitamin K1 was prescribed (2.5 mg/kg PO) every 12 hr for 30 days. The patient made a full recovery.
Results
This case series demonstrated patients can present with clinical signs of upper airway disease due to anticoagulant rodenticide-induced hemorrhage. Hemorrhage can be focal or diffuse and swelling can quickly lead to airway obstruction. As Case 1 demonstrates, this can become an acute life-threatening situation soon after the onset of clinical signs if not treated promptly.
Although tracheal or laryngeal obstruction is a rare complication from anticoagulant rodenticide toxicosis, it has been previously reported in the veterinary literature.16–19 The last published case report was 10 yr ago, and, to the authors' knowledge, this is the first case series describing patients presenting for upper airway obstruction from anticoagulant rodenticide toxicity.18 A retrospective study evaluating thoracic radiographic changes with anticoagulant rodenticide toxicity revealed that four of 14 patients had tracheal narrowing, but none of them presented with signs of upper airway obstruction.19
There are rare case reports in the human literature of upper airway obstruction from hematoma formation localized to the larynx, trachea, and retropharyngeal and cervico-mediastinal regions.20–24 The etiology in human medicine is variable and includes trauma and infection, but a study published in 1991 found that five of 29 reported cases of upper airway obstruction from hematoma were associated with anticoagulants.25 The most common sites for bleeding from Coumadinb overdose in humans are the urinary tract (hematuria), skin, nose, and mucous membranes.20,21 Bleeding from Coumadin could be caused by ingestion of either normal doses of prescribed medications or intentional ingestion of anticoagulant rodenticides as a means of self-harm.20,21 To the authors' knowledge, there are no reports in the veterinary literature of upper airway obstruction from therapeutic anticoagulant administration.
A potential weakness of this case series is the lack of laboratory testing confirming anticoagulant rodenticide ingestion. With the exception of the first case, patients were diagnosed with presumed anticoagulant rodenticide toxicosis based on physical examination findings, prolonged PT, and positive response to treatment with FFP and Vitamin K1. Due to the nature of a retrospective case series, some details (time sequence between procedures, etc.) were not possible to glean from the records. A follow up PT was only done for case 4. A recheck PT in our institution is >$100 (recheck exam $70 + PT $60), and many cases do not get follow up PT due to financial constraints.
Discussion
Analysis of the five cases highlighted some factors that may help an astute clinician identify which upper airway obstruction patients could be suffering from anticoagulant rodenticide toxicosis. Case 1 and 3 were referred for suspected esophageal foreign bodies based on tracheal and thoracic radiographs showing severe tracheal narrowing. Foreign bodies were considered unlikely based on no history of recent food or foreign body ingestion. Cases 1, 3, and 5 were small breed dogs that could have collapsing trachea, and the observed tracheal narrowing on radiographs would support this diagnosis. Interestingly, however, the tracheal narrowing was static through a series of several radiographs, rather than dynamic, as would be expected in patients with collapsing trachea. Case 3 had a history of suspected collapsing trachea with coughing when pulling against a collar, but none of the cases had a history of previous respiratory distress episodes. The acute nature of respiratory distress, the lack of history of distress episodes, and the potential exposure to rodenticide in the environment made upper airway obstruction from hemorrhage more likely.
Lack of external signs of hemorrhage made diagnosis of anticoagulant rodenticide toxicosis difficult in three out of the five cases (cases 1, 2, and 4) presented in this series. Cases 3 and 5 had minor signs of hemorrhage, including mild serosanguinous nasal discharge and hind limb edema with ecchymosis, that helped to raise the suspicion for coagulopathy.
Intoxications tend to be associated with young animals, but cases 2, 3, and 5 demonstrate that dogs of all ages and sizes can and will ingest anticoagulant rodenticides.2 Case 2 was a 9 yr old female spayed Labrador retriever, the oldest patient in this series. Labrador retrievers are a common breed presenting for toxicosis in our hospital, and they are the most commonly registered American Kennel Club breed.2 Case 1 was a 1 yr 10 mo old Maltese, the smallest and the second youngest patient in this case series. Anticoagulant rodenticide toxicosis should not be excluded from a list of differentials simply based on the signalment of the patient.
Conclusion
As this case series demonstrates, it is important to consider anticoagulant rodenticide toxicosis as a cause of upper airway obstruction. The death of the first case in this series led to awareness within the hospital and among clinicians and ultimately led to timely diagnosis in the remaining cases. By publishing this case series, the authors hope to raise awareness of this treatable toxicosis as a possible differential diagnosis for dogs presenting for upper airway obstruction.
Lateral cervical radiograph of case 3, showing severe narrowing of the tracheal lumen, presumably from submucosal bleeding secondary to anticoagulant rodenticide ingestion.
Lateral cervical radiograph of case 4, showing severe soft tissue opacity in the pharyngeal region, presumably from bleeding secondary to anticoagulant rodenticide ingestion.
Contributor Notes
