Brunfelsia australis (Yesterday, Today, and Tomorrow Tree) and Solanum Poisoning in a Dog

Introduction

The Solanaceae family consists of between 1,500 and 2,000 species, including the more familiar members, such as Deadly Nightshade (Atropa belladonna), tobacco (Nicotiana spp.), Jimsonweed (Datura stramonium), and Mandrake (Mandragora officinarum). The final determination of familial assignment is in flux as cladistic investigation using DNA analysis is currently refining family designation. Not all species are determined to be toxic, and although toxin distribution can be extensive (with especially high concentrations in berries and/or seeds), not all toxic plant components are dangerous. Several important cultivars are included in this family, such as the commercial potato (Solanum tuberosum), eggplant (S. melongena), domestic tomato (S. lycopersicum), and paprika peppers (Capsicum spp.), the latter of which includes the familiar bell pepper. All cultivars have worldwide consumption. In a minority of societies, Solanum spp. are used for their psychoactive substances, such as some indigenous peoples of South America who include native Brunfelsia spp. in infusion brews for their scopoletin content.¹

Collectively, species within the Solanaceae family generally contain an amalgamation of toxic alkaloids that are often in concert with various other toxic principles. These include tropanes (in Belladonna, Jimson weed, Mandrake, etc.), which function as anticholinergics and block acetylcholine in neurotransmission.^2,3 Nicotine (in Nicotiana, Horsetail, Nightshades, Jimson weed, potato, etc.) is also widely distributed among the family and is a cholinergic agonist that activates nicotinic acetylcholine receptors.^3,4 Diverse glycoalkaloids (sugar-decorated alkaloids) can also be present (in Black Nightshade, Bittersweet, wild and domestic potatoes, etc.) and have manifold mechanisms.^2,4–7 Solanine has also been shown to be an active toxin (neurotoxin) and experimentally has been shown to reduce mitochondrial membrane potential by opening potassium channels and simultaneously releasing excessive Ca to the cytosol.^8,9 Due to a variable composition, concentration, and distribution within plant parts of these toxic organic compounds, it is problematic to describe the effects of Solanaceae ingestion as a sole clinical portrait. The purpose of this report is to provide an information update for an emerging toxin source not readily accessible in the literature or data bases.

Case Report

A 2.5 yr old spayed female beagle weighing 9.5 kg presented to the local emergency facility after several hours of vomiting following the ingestion of small fragments of potato skins during an evening meal preparation. The owner stated that the few pieces with green skin fell where the dog was allowed to ingest them. The dog had no significant pre-existing medical history, but had a history of a few limited episodes of gastroenteric upset and one incident of insect hypersensitivity. The dog recovered without complication from all previous episodes. She was not on any medications, was in good body condition, and all vaccinations were current. The patient resided in the house and a fenced backyard. No additional environmental, pharmaceutical, or topical toxin exposure source could be identified by the owners.

Physical examination revealed the patient to be alert, restless, 6% dehydrated (determined by skin turgor), had moderate ptyalism, injected mucous membranes with normal capillary refill time, significant mydriasis, substantial abdominal pain on palpation, and a significant bradycardia (heart rate was 55 beats/min). Systolic blood pressure (BP) was mildly elevated at 178 mm Hg (reference range, 125–155 mm Hg). Body temperature (38.5°C), respiratory rate (36 breaths/min), and blood glucose concentration (111 mg/dL) were all normal. The dog was neurologically normal for motor function, pain, and conscious proprioception on initial presentation. On-site blood analysis revealed a mild elevation in γ-glutamyltransferase (21 U/L; reference range, 0–14 U/L), mild hyperproteinemia (8.0 mg/dL; reference range, 5.1–7.8 mg/dL), a slight hemoconcentration (packed cell volume was 56%; reference range, 37–55%), mild lactate elevation (2.7 mmol/L; reference range, 0.5–2.0 mmol/L), mild hyponatremia (143 mmol/L; reference range, 146–156 mmol/L), moderate hypokalemia (2.98 mmol/L; reference range, 3.8–5.10 mmol/L), and hypocalcemia (0.79 mmol/L; reference range, 1.12–1.40 mmol/L). All other electrolyte levels (including chloride), hematologic, and serum enzymes were normal. Pancreatic lipase testing determined by Spec cPLI^a was negative. Abdominal radiographs taken 4 hr postpresentation revealed a significant amount of diffuse material along the rugal folds of the gastric fundus, pylorus, and colon.

Following consultation with the American Society for Prevention of Cruelty to Animals (ASPCA) Poison Control Center^b, a putative diagnosis of potato (S. tuberosum) toxicity was concurred and appropriate treatment was initiated. Differential diagnoses included marijuana intoxication, oleander exposure, and other nonspecific gastroenteric irritant etiologies.

Initial therapy included a 200 mL IV bolus balanced electrolyte fluids^c followed by 45 mL/hr of the same fluid to correct secondary dehydration. For potassium replacement, 40 mEq/L of potassium chloride was added. IV ondansetron^d (1 mg or 0.1 mg/kg q 12 hr) was initiated for emesis. Atropine sulfate^e was injected as an IV bolus in response to the bradycardia. The heart rate increased from 55 beats/min to 100 beats/min. Subcutaneous famatidine^f (5 mg q 12 hr) to reduce gastritis and ameliorate vomiting was also administered. The patient was hospitalized for care overnight until she could be transferred to the dog's primary veterinarian.

During the night, vomiting persisted despite the antiemetic, and tiny fragmented pieces of green potato skins were noted. Due to the severity of signs, the owner speculated that the dog may have ingested more potato fragments than suspected, and the owner postulated the dog had consumed additional pieces from the kitchen garbage. Over the following 4 hr the dog became increasingly vocally distressed and painful on abdominal palpation. Abdominal radiographs were taken, indicating that a larger volume of materials and/or potatoes than previous postulated by the owners estimation and may have been contributing to the patient's signs. Approximately 5 hr after presentation, the dog exhibited manic-type behavior (with intense and persistent muzzle rubbing of her bedding) followed by ataxia. The dog then rapidly developed numerous neurologic deficits, including muscular weakness and muscular fasciculation, and rapidly became obtunded. The dog was offered activated charcoal in food, but either refused or was incapable of deglutition due to neuromuscular weakness. Force feeding the activated charcoal slurry was not performed due to the risk of inhalation pneumonia. Alternatively, a warm water enema was administered to induce vomiting. A significant amount of material consistent with plant root ingestion was voided. Vomiting continued intermittently throughout the remainder of the dog's overnight hospitalization. BP remained slightly elevated and the heart rate ranged from 60 beats/min to 120 beats/min.

The beagle was transferred to the primary veterinarian in the morning for continued care. The dog presented to the primary veterinarian in lateral recumbency with marked lethargy, a poor response to tactile stimulation, a body temperature of 37.6°C, moderate abdominal distension with extreme pain on palpation, and frank blood on rectal palpation. Auscultation revealed a normal heart rate (90 beats/min) but with an arrhythmia. An electrocardiogram displayed flat T waves and frequent premature ventricular contractions (Figure 1). BP was normal at 141 mm Hg.

View Figure

• Download as Powerpoint
• Download Figure

The therapeutic plan was continued from the previous night with subcutaneous maropitant^g (1.0 mg/kg) replacing the previous ondansetron for additional emetic control. Buprenorphine^h (0.012 mg/kg IV q 8 hr) was added to control visceral pain. Additionally, ampicillinⁱ was instituted at 250 mg (25 mg/kg) IV q 8 hr and 250 mg of a sucralfate^j suspension was administered orally q 8 hr as a gastrointestinal protectant. An external air-blown blanket^k was also applied, and a 2% lidocaine solution^l (60 μg/kg/min) was administered to desensitize the myocardium. Subsequent electrocardiograms over the next 11 hr showed discontinuation of any previous arrhythmias.

Subsequent discussion with the owners revealed that the root substances produced via the enema had prompted further investigation of their yard to define alternate toxins beyond the suspect potato skins. Holes dug by the dog were found to contain chewed roots matching the size and character of those collected following the enema. The holes were located at the base of a Yesterday, Today, and Tomorrow tree (Brunfelsia australis). The ingestion was estimated to be very recent due to daily inspection of the yard during oversight of family children.

Symptomatic treatment of Solanum spp. toxicity was continued, but as the nature and intensity progressed, the etiologic diagnosis was quantitatively shifted from the potato ingestion to the newly discovered B. australis source. Because of the overlap in toxic principles, this case was therefore considered a compound Solanum spp. toxicity. Brunfelsia spp. are members of the Solanaceae family and produce related glycoalkaloids in their flowers, roots, seeds, bark, leaves, and roots. The signs of toxicity mirror those of the classic Solanaceae family, which includes potatoes. The dog continued to recover in strength, coordination, and mental capability over the following 24 hr, accompanied by an increase in appetite and resolution of the diarrhea and associated hematochezia. The dog was discharged approximately 48 hr after the onset of the episode. A bland diet and sucralfate^j (0.5 gm PO q 8 hr 3 days) were prescribed for 48 hr to assist in gastrointestinal regeneration. The dog continued to improve the following day and appeared in good condition on the scheduled follow-up examination 2 wk after discharge.

Discussion

Patients affected by Solanum spp. poisoning generally exhibit early systemic signs and clinically progress from gastrointestinal to cardiovascular to neuromuscular to neurologic disease in their pathophysiology. These signs are consistent between three dogs intentionally fed Brunfelsia berries and two previous accidental case reports.^10–13 Solanine and chaconine, another frequent toxic component, both possess tissue distribution and bioelimination that parallel each other.^14,15 A general list of signs noted in Solanum and Brunfelsia clinical poisonings are noted and are generally considered to occur secondary to the anticholinergic neuro- and cardiovascular toxic effects (Table 1). For purposes of this specific case presentation, further discussion of Solanum-origin toxicity is restricted to Brunfelsia and potato species.

TABLE 1 Clinical Signs of Solanum/Brunfelsia Toxicity: General Temporal Progression

View Fullscreen

Yesterday, Today, and Tomorrow Tree Poisoning

The genus Brunfelsia includes around 40 neotropical (New World south of the Tropic of Cancer) species, including shrubs, vines, and small trees originating from South and Central America, Australia, Caribbean Islands, and southern Florida.^16–18 The common name is derived from the large, brightly star-shaped, colored flowers with five petals that change from deep blue to lavender to white over time, giving the impression that three sets of blossoms are produced independently (Figure 2). Other common names include: Morning, Noon, and Night Tree; Lady-of-the-Night; Paraguay Jasmine; Kiss-me-Quick; Cuban Raintree; and Franciscan Raintree. The United States Department of Agriculture lists nine separate American species, apart from those cultivated south of the United States and/or in Africa and Australia.¹⁸ Indigenous nomenclature used by nurserymen further complicate accurate case etiology assignment and include: Manacá, Manacán, Chiric Sanango, Chuchuwasha, Manaka, Vegetable Mercury, Managá Caa, Gambá, Jeratacaca, Bloom Of The Lent, Camgaba, Christmas Bloom, Chuchuwasha, Gerataca, Geratacaca, Good Night, Jerataca, Moka Pari, Santa Maria, Umburapuama, and White Tree.¹⁷ Alternative names used for Brunfelsia spp. are widely diverse, frequently restricted by specific locales, and often incorrectly referenced as Brunsfelsia spp., which severely convolutes case management during data searches. Case in point, B. australis was previously designated B. bonadora, B. francissia, and B. latifolia, and these prior names persist in the very limited literature.¹⁰

View Figure

• Download as Powerpoint
• Download Figure

The primary alkaloids responsible are largely unreported or under-reported in the literature as to their full actions. However, two substances are described: brunsfelsamidine, which produces central nervous system depressant actions, and scopoletin, which is a psychoactive substance and a derivative of coumarin.^2,5,19–22 Hopeanine has also been isolated, and along with brunfelsamidine, has been reported to cause neuropathology when administered to rodent test subjects.^16,19,20 The primary mechanisms involved in scopoletin toxicity in animal models include negative chronotropic and inotropic responses, plus inhibition of acetylcholine-mediated skeletal muscle contractions.²³

Clinical signs reported for veterinary patients include pain, vomiting, diarrhea, salivation, lethargy, ataxia, cough, muscular tremors progressing to rigidity (“sawhorse stance”), and seizures.^10–13,19 Nystagmus has also been reported.¹⁹ Accidental poisoning cases by ingestion parallel those of dogs intentionally fed berries or supernatants of berry mash by researchers.^10–13,19 Signs generally last 48–72 hr and either terminate in recovery with no lingering effects or progress to fatality, probably in a dose-dependent manner. Symptomatic therapies are indicated, including emetics, cathartics, activated charcoal, atropine, muscle relaxants, antiarrhythmics, and anticonvulsants (diazepam or phenobarbital), which have been used successfully for both canine patients and rodent test subjects. Definitive toxin analysis is not yet possible as it is not offered by either academic or commercial labs (oral communication with Safdar A. Khan at the ASPCA poisoning center [October 2010] and Robert H. Poppenga and Birgit Puschner at the California Animal Health & Food Safety Laboratory at UC Davis School of Veterinary Medicine [October 2010]). The toxic principle is still referred to as being “strychnine-like.” The litany and progression of clinical signs are most likely due to the mélange of various suspect and known toxic components, as seen in this case.

Conclusion and Clinical Relevance

This case report is offered as an update to intoxication via ingestion of B. australis (“Yesterday, Today, and Tomorrow”) and is one of several very limited reports available through the National Institute of Health Pubmed database. The others reported as separate, but related, species listed as B. pauciflora and B. calcyina.^12,19 The patient's signs and clinical progression were identical to those reported in the small number of other dogs with exposure to unidentified species, and one report in 1983 for B. australis.¹¹ One brief letter of a toxicity study referencing B. bonodora (in Australia in 1975) is also noted.¹⁰ Readily available information and therapeutic guidelines for practitioners for this toxicity were found to be scarce despite text reviews and numerous consultations with toxicologists and veterinary specialists. Case in point is a fairly informative review available through the ASPCA poison control website, but was located only by using the search term for the toxin “brunfelsamide.” This restricted identification terminology and alternative name variations used for this group of Brunfelsia spp. (over 25), often incorrectly referenced as Brunsfelsia, can result in case mismanagement.

This landscape tree, along with other Solanaceae family members, are becoming more widespread in their distribution in the United States in the warmer climes due to inherent drought resistance, as well as its appeal as an indoor potted plant. Undoubtedly this case presentation will confront practitioners with increasing frequency. Case in point, the author's clinic was presented with yet another Brunfelsia poisoning within 2 wk subsequent to the dismissal of this specific case. Additionally, the author was informed by his wife during manuscript development that both a Yesterday, Today and Tomorrow tree and a related Solanaceae family member, S. macranthum (Potato tree), had been purchased and were now residing in their back yard based on recommendations for hardiness.

Furthermore, this case is somewhat unique in that it is a combined Solanum poisoning, but with the majority of the toxic principle contributed by the Morning, Noon and Night Tree. While the treatment here was relatively straightforward, rational, and successful, the potential for a complex case of toxicity always exists. A traditional poisonous substance was intensely compounded by an emerging source of a related toxin, resulting in a life-threatening toxicosis. When patients inappropriately ingest one aberrant item, the probability of consuming a second toxic item is inherently statistically elevated and compels consideration.

This case is presented for practitioners to provide enhanced information and therapeutic support due to limited data for which summaries or details are largely inaccessible by name and/or completely unrecognized in many online databases and current textbooks.