History
An 11-week-old 5.8-kg (12.8-lb) sexually intact female Golden Retriever–Poodle crossbred dog was referred for evaluation because of progressive respiratory distress of 5 hours’ duration. Before the onset of respiratory distress, the dog was examined and vaccinated by the referring veterinarian. Vaccinations included a third booster vaccination (SC) against distemper, parvovirus, adenovirus, and coronavirus; an initial vaccination (SC) against Leptospira canicola and L icterohaemorrhagiae; and a vaccination (PO) against Bordetella bronchiseptica. Within an hour after being vaccinated, the dog became ataxic, had signs of agitation, and began wheezing. The referring veterinarian administered diphenhydramine hydrochloride (2.0 mg/kg [0.9 mg/lb], IM, twice), epinephrine hydrochloride (0.005 mg/kg [0.002 mg/lb], IM once, then IV for subsequent 3 to 4 dosages), and dexamethasone sodium phosphate (total of 1.0 to 1.7 mg/kg [0.45 to 0.77 mg/lb], unknown route); however, the dog continued to deteriorate and began vomiting blood-tinged foam. The dog was referred to our facility for further care.
On initial referral examination, the dog was alert and responsive but sluggish, tachycardic (heart rate, 188 beats/min; reference range, 100 to 130 beats/min), tachypneic (120 breaths/min; reference range, 20 to 30 breaths/min), normothermic (rectal temperature, 38.2°C [100.8°F]; reference range, 38.1° to 39.2°C [100.5° to 102.5°F]), and hyper-salivating. The dog's body condition score was a 5 on a scale from 1 to 9. In addition, oral examination and abdominal palpation elicited signs of pain. Indirect systolic blood pressure (measured with an oscillometric sphygmomanometer connected to a size 4 cuff placed around the distal aspect of a forelimb) was 147 mm Hg (reference range, 110 to 190 mm Hg), and blood oxygen saturation (measured with a pulse oximeter) was 100% (reference range, 97% to 100%). The dog was not receiving supplemental oxygen at the time that blood oxygen saturation was measured. Electrocardiography revealed a normal sinus rhythm, and results of a CBC and serum biochemical analyses indicated a stress leukogram (moderate mature neutrophilia [21.9 × 103 neutrophils/μL; reference range, 3.5 × 103 neutrophils/μL to 14.2 × 103 neutrophils/μL] and absolute eosinopenia [0 × 103 eosinophils/μL; reference range, 0.1 × 103 eosinophils/μL to 1.3 × 103 eosinophils/μL]) and high serum concentrations of glucose (251 mg/dL; reference range, 75 to 125 mg/dL), creatine kinase (11,890 U/L; reference range, 50 to 300 U/L), and lactate (2.1 mmol/L; reference range, 0.42 to 3.58 mmol/L). Results of venous blood gas analysis, a coagulation profile, and abdominal radiography were unremarkable. Orthogonal thoracic radiographs were obtained (Figure 1).
Ventrodorsal (A) and left lateral (B) radiographic images of an 11-week-old 5.8-kg (12.8-lb) sexually intact female Golden Retriever–Poodle crossbred dog evaluated because of acute respiratory distress after receiving routine vaccinations.
Citation: Journal of the American Veterinary Medical Association 254, 12; 10.2460/javma.254.12.1393
Determine whether additional imaging studies are required, or make your diagnosis from Figure 1—then turn the page →
Image Findings and Interpretation
Thoracic radiography revealed a severe, diffuse alveolar pulmonary pattern in all lung lobes, but most severe in the perihilar region and caudodorsal lung fields (Figure 2). The alveolar pulmonary pattern was characterized by air bronchograms and border effacement of the cardiac silhouette and diaphragm. The visible margins of the cardiac silhouette and pulmonary lobar arteries and veins appeared normal. Multiple, thin pleural fissure lines were present between the right cranial, right middle, and right caudal lung lobes as well as between the cranial and caudal subsegments of the left cranial lung lobe. Low serosal detail in the visible portion of the abdomen was consistent with the dog's young age. The moderate amount of gas evident in the stomach was thought to have been secondary to the dog's aerophagia from respiratory distress.
The same radiographic images as in Figure 1. An alveolar pulmonary pattern, characterized by air bronchograms (arrows; A and B) and border effacement with the cardiac silhouette and diaphragm, is evident. A moderate amount of gas is present in the stomach (arrowhead; A and B). The thymus (asterisk; A) is a clinically normal finding in such a young dog and should not be mistaken for pleural effusion.
Citation: Journal of the American Veterinary Medical Association 254, 12; 10.2460/javma.254.12.1393
A primary differential diagnosis for the dog's severe, diffuse alveolar pulmonary pattern was noncardiogenic pulmonary edema (NCPE), particularly secondary to an anaphylactic reaction, and lesser consideration was given to hemorrhage and cardiogenic pulmonary edema as potential causes of the dog's condition. Radiographic evidence of pleural fissures was attributed to a small volume of pleural effusion or tangential beam artifact.
Treatment and Outcome
The dog's abnormal clinicopathologic results were attributed to acute respiratory distress (causing a stress leukogram and mild stress-induced hyperglycemia), decreased oxygenation and perfusion (causing high serum lactate concentration), and IM injections (causing high serum creatine kinase activity). Methadone hydrochloride (0.2 mg/kg [0.09 mg/lb], IV, q 6 h) and acepromazine (0.01 mg/kg [0.0045 mg/lb], IV, once) were administered, and fluid therapy with lactated Ringer solution (15 mL/kg [6.8 mL/lb], IV bolus over 30 minutes) was initiated. The dog was hospitalized and placed in an oxygen cage set at 50% saturation.
Because the dog did not improve, fluid therapy was discontinued, and furosemide (2.0 mg/kg, IV, q 2 h for 3 dosages) was administered; however, still, no clinical signs of improvement occurred. Therefore, treatment with albuterol (90 μg by inhalation, q 4 h), maropitant citrate (1.0 mg/kg, IV, q 24 h), ondansetron hydrochloride (0.5 mg/kg [0.23 mg/lb], IV, q 12 h), diphenhydramine (2 mg/kg, IM, once, 6 hours after initial referral examination), and pantoprazole (1.0 mg/kg, IV, q 24 h) was added.
The following day, thoracic radiography was repeated and revealed a persistent but slightly improved pulmonary pattern and resolution of the pleural fissures. Hospitalization and supportive care continued. The dog's heart rate and respiratory rate progressively decreased to 148 beats/min and 48 breaths/min, respectively. Ondansetron and diphenhydramine were discontinued, and famotidine (0.5 mg/kg, IV, q 12 h) was initiated. Hematologic assessment was repeated, and results indicated substantial improvement.
The next day, the dog continued to improve and was weaned from oxygen support. Thoracic radiography was repeated and revealed marked improvement, with near resolution of the dog's pulmonary edema, with only a mild unstructured interstitial pulmonary pattern remaining and resolution of the alveolar pattern component (Figure 3). Further, the visible portion of the stomach was no longer gas filled.
Ventrodorsal (A) and left lateral (B) radiographic images of the same dog in Figures 1 and 2 obtained 3 days after the initial physical and radiographic examinations. Compared with the earlier radiographic findings, the alveolar component has resolved, and only a mild, unstructured interstitial pulmonary pattern remains, most notably in the right caudal lung lobe (arrows; A and B). The thymus (asterisk; A) is also evident.
Citation: Journal of the American Veterinary Medical Association 254, 12; 10.2460/javma.254.12.1393
On the following day (4 days after the initial referral examination), the dog was discharged with a prescription of omeprazole (0.86 mg/kg [0.39 mg/lb], PO, q 12 h, for 7 days). After discharge, the owner reported that the dog continued to improve and returned to normal activity without evidence of respiratory issues.
Comments
Noncardiogenic pulmonary edema occurs relatively infrequently in veterinary patients. Complications associated with NCPE can develop rapidly and be fatal. For example, neurogenic pulmonary edema, a form of NCPE, can develop within minutes of the inciting injury.1 The pathophysiologic processes of NCPE vary depending on the underlying cause; however, the condition is attributed to alterations in Starling forces, with increased pulmonary vascular permeability implicated as a key component in NCPE.2 Potential causes of NCPE include anaphylactic shock, acute respiratory distress syndrome, brain injury, upper airway obstruction, adverse drug reactions, electric shock, and near-drowning.3 Practitioners should consider NCPE in patients with clinical signs of respiratory distress and a history of 1 of the aforementioned causes. Thoracic radiography of affected patients would reveal an unstructured interstitial pulmonary pattern coalescing to an alveolar pulmonary pattern, typically in the caudodorsal lung fields. In the absence of a heart murmur or radiographic evidence of cardiovascular disease, cardiogenic pulmonary edema may be considered less likely. In addition, results of ECG and echocardiography can facilitate the determination of whether cardiac disfunction is an underlying cause of a patient's pulmonary edema.
Treatment for NCPE is primarily supportive care with oxygen therapy; however, sedation may be needed in patients with signs of anxiety. With NCPE, vascular permeability increases and allows for proteins in the blood to leak into the interstitium, leading to an oncotic gradient that results in interstitial edema. The differentiation of cardiogenic pulmonary edema and NCPE may be difficult but will alter treatments. In NCPE, fluid therapy should be used with caution because the increased vascular permeability associated with NCPE may lead to worsening pulmonary edema.2
In the dog of the present report, type 1 hypersensitivity anaphylaxis was the likely underlying cause for NCPE, given the dog's history of recent vaccination and sudden onset of respiratory difficulties afterward. This type of anaphylactic reaction is IgE mediated and causes a release of histamine, prostaglandins, and leukotrienes.4,5 Most anaphylactic reactions may cause mild clinical signs such as erythema, hives, or scratching4,6; however, severe, life-threatening consequences (eg, upper airway constriction, cardiovascular collapse, and NCPE) may develop. Typical treatment for noncomplicated anaphylactic reactions includes administration of antihistamines and potentially glucocorticoids. In the event of anaphylactic induced cardiovascular collapse, administration of epinephrine and fluid resuscitation may also be needed.7 Care must be taken when administering epinephrine because high dosages may induce NCPE. For instance, a study8 shows that epinephrine at a dose of 1 mg/kg IV is enough to cause pulmonary edema and death in mice. Treatment of patients with NCPE is geared toward supportive measures and can have favorable outcomes, as was evident with the dog of the present report.
Acknowledgments
The authors declare that there were no conflicts of interest.
References
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