Severe hypernatremia in a dog following activated charcoal treatment for chocolate ingestion

Abstract

A 7-year-old spayed female Corgi dog was presented for care 1.5 h after ingestion of chocolate brownies (theobromine dosage: 88.3 mg/kg, BW). Physical examination revealed mild tachycardia and hyperthermia. Vomiting was induced, and the dog was treated with maropitant and activated charcoal with sorbitol (1.9 g/kg, BW, PO) prior to ER transfer. Tremors and seizures were noted 4.5 h following ingestion. Despite rehydration, treatment with activated charcoal containing no sorbitol (0.9 g/kg, BW, PO) resulted in the dog’s serum sodium concentration quickly elevating [Na: 174 mmol/L; reference range (RR): 144 to 160 mmol/L]. The dog developed neurologic signs and azotemia. Treatment included customized fluid therapy, anticonvulsant medications, positive pressure ventilation, and administration of emergency drugs related to a near-arrest event. With continued care, the dog was discharged 57 h following admission. One month following discharge, the dog had mild vestibular signs remaining that resolved 10 mo after discharge. To the authors’ knowledge, this is the first reported case that documents a dog developing severe hypernatremia following activated charcoal therapy related to chocolate toxicosis. The case details may be helpful to clinicians treating similar complex toxicity, those interested in potential neurologic recovery following severe hypernatremia, and those who are seeking insights into risk factors for developing hypernatremia with activated charcoal therapy.

Key clinical message:

A case of chocolate toxicity and severe hypernatremia following activated charcoal therapy highlights that patients which have ingested an osmotically active toxin, such as chocolate, especially those at risk of dehydration, may be at increased risk for hypernatremia following activated charcoal therapy. If activated charcoal is used in such complex cases, frequent monitoring of patient’s electrolytes and neurologic status is recommended to minimize the risk of development of life-threatening hypernatremia.

Chocolate (theobromine) toxicosis is a common toxicosis of small animal patients (1). Activated charcoal is an often used adjunct to gastrointestinal decontamination following toxin ingestion (2). This case describes the management of a theobromine case and highlights the adverse effects and challenges that can be encountered in cases of substantial theobromine ingestion. This case also highlights the importance of monitoring serum sodium concentration to direct the decision to use activated charcoal therapy and continued monitoring following treatment to minimize potential hypernatremia-induced neurologic clinical signs. The follow-up associated with this case provides insights into the potential for neurologic improvement following a severe case of hypernatremia.

CASE DESCRIPTION

A 7-year-old spayed female Corgi was referred to a 24-hour emergency and referral center for continued care related to chocolate toxicosis (theobromine dosage: 88.3 mg/kg, BW). The dog had ingested chocolate brownies and failed to vomit at home following hydrogen peroxide administration (2.4 mL/kg, BW, PO). Upon initial arrival at the primary veterinarian’s clinic approximately 1.5 h following the chocolate ingestion, the dog was noted to be mildly hyper-thermic (temperature: 39.6°C/103.3°F) and tachycardic (pulse rate: 160 beats/minute) with normal mentation.

A complete blood (cell) count/chemistry was completed at the primary veterinarian’s clinic. Serum sodium concentrations were within the normal range at presentation [Na: 156 mmol/L; reference range (RR): 144 to 160 mmol/L], and the dog was noted to be non-azotemic (creatinine: 0.9 mg/dL; RR: 0.5 to 1.8 mg/dL) (blood urea nitrogen: 20 mg/dL; RR: 7 to 27 mg/dL). A mild hyperglycemia (blood glucose: 167 mg/dL; RR: 74 to 143 mg/dL) and eosinopenia (eosinophils: 0.08 K/mL; RR: 0.10 to 1.40 K/mL) was suspected to relate to an underlying stress response. The dog had received subconjunctival (SCH) apomorphine with successful emesis induction (0.24 mg/kg BW, SCH), maropitant (1 mg/kg BW, IV), and activated charcoal with sorbitol (1.9 g/kg BW, PO) before referral.

On initial physical examination upon arrival at the emergency clinic approximately 4.5 h after chocolate ingestion, the dog was quiet but appropriately alert with a normal body temperature and continued mild tachycardia (heart rate: 160 beats/min). At this time, the dog was also noted to have generalized muscle tremors and had a grand mal seizure during initial triage care.

Upon arrival at the emergency service, the dog was started on IV fluids (Normosol-R 4.2 mL/kg BW per hour). For the tremors and seizure, the dog was treated with methocarbamol (50 mg/kg BW, IV) and midazolam (0.2 mg/kg BW, IV). The dog had a transient loss of gag reflex following the seizure and administration of methocarbamol and midazolam. Intubation was attempted but not completed due to the dog regaining gag reflex during attempted intubation. The dog was then started on flow-by oxygen. Two additional doses of methocarbamol (30 mg/kg BW, IV) were given once the dog had a return of tremoring following normalization of mentation. The dog was normally responsive and able to ingest activated charcoal without sorbitol (0.9 g/kg BW, PO) approximately 6 h after arrival at the hospital. The dog was then treated for approximately 4 h with a methocarbamol continuous rate infusion (CRI) (10 to 20 mg/kg BW, per hour) before transitioning to a midazolam CRI for 7.5 h (0.25 to 0.5 mL/kg BW, per hour) due to lack of tremor improvement with methocarbamol. In addition, IV antibiotic therapy (ampicillin-sulbactam: 30 mg/kg BW, IV) was started to treat for potential aspiration pneumonia. With the support of gastrointestinal (GI) medications (maropitant: 1 mg/kg BW, IV, pantoprazole: 1 mg/kg BW, IV, q12h) and when the dog had appropriate mentation, the dog was eating intermittently.

Thoracic radiographs were taken the morning following the dog’s initial admission, due to concern for crackles on auscultation. The Board-certified radiologist reported a mild caudo-dorsal bronchial pattern consistent with age or due to chronic underlying lower airway disease.

Initial electrolyte monitoring through the emergency service revealed that mild hypernatremia (Na: 164 mmol/L; RR: 144 to 160 mmol/L) had developed over approximately 4.5 h since initial sodium evaluation (initial Na: 156 mmol/L; RR: 144 to 160 mmol/L) and following initial activated charcoal with sorbitol (Table 1). The sodium rate of change at that time was calculated to be 1.8 mEQ Na/h. Despite rehydration with crystalloid therapy, a second reduced dose of activated charcoal without sorbitol (0.9 g/kg BW, PO) resulted in progressive hypernatremia (Na: 174 mmol/L; RR: 144 to 160 mmol/L) within 3 h. At this time, the rate of sodium change from the initial value was calculated to be 1.7 mEQ Na/h. Despite being started on 5% dextrose in water (D5W 2.5 mL/kg BW per hour), the dog experienced progression of hypernatremia (Na: > 180 mmol/L; RR: 144 to 160 mmol/L) approximately 15 h after the initial sodium evaluation and 8 h after the last dose of activated charcoal without sorbitol. Considering the hemoconcentration (PCV/TS: 60/8.1) and creatinine elevation noted concurrently (creatinine: 2.85 mg/dL; RR: 0.4 to 1.5 mg/dL) as well as the timing of the elevations in relation to activated charcoal treatment, the hypernatremia was suspected to have been related to a combination of activated charcoal treatment and dehydration. This hemoconcentration was suspected to be the result of fluid loss of induced emesis, suspected polyuria [the dog had frequently urinated during the first 12 h in hospital, possibly secondary to caffeine-induced increased urinary sodium excretion (1)], fluid loss secondary to the dog’s initial tremors/seizure and hyperthermia, and possible non-observed fluid pooling within the GI tract.

TABLE 1.

Changes in serum sodium concentrations over time in a dog after ingestion of theobromine with notation of pertinent treatments in relation to serum sodium concentration.

Interval post-ingestion of theobromine (h)	Sodium concentration (mmol/L)	Treatment given
1.5	156	Activated charcoal with sorbitol
6	164	Normosol-R fluid therapy initiated
9	—a	Activated charcoal without sorbitol
12	174	D5W started concurrent with Normosol-R
16.5	> 180	Two warm water enemas; D5W rate increased; Transitioned off Normosol-R to Lactated Ringer’s solution (LRS)
25.3	157	No significant change
25.8b	174	Two crystalloid boluses 7.2% hypertonic saline boluses Positive pressure ventilation D5W paused before restarting at a reduced rate LRS continued with increased KCl supplementation
40.3	158	D5W continued at a reduced rate; LRS fluid rate reduced
44.8	149	D5W discontinued; LRS fluid rate further decreased

^aNo sodium value measured during this period.

^bTime of near-arrest.

Due to the concurrent hypernatremia and hemoconcentration, the dog was transitioned to LRS fluids (5 mL/kg BW per hour) and increasing rates of 5% dextrose in water (D5W) (12.7 mL/kg BW per hour) as guided by the free water deficit calculation:

$$[\text{water\hspace{0.17em}deficit\hspace{0.17em}}(\text{L})=\text{weight\hspace{0.17em}in\hspace{0.17em}kilograms}\times [(\text{Na\hspace{0.17em}measured}/\text{Na\hspace{0.17em}desired})-1)]$$

Electrolytes and hydration status (PCV/TS, blood urea nitrogen, creatinine) were monitored every 4 h (3). The dog’s free water deficit at the time of most marked hypernatremia (Na > 180 mmol/L) was calculated to be approximately 1.82 L with the utilization of an approximated measured serum sodium concentration of 180 mmol/L. Two warm-water enemas (8.5 mL/kg BW warm water) were done to treat hypernatremia. This resulted in the dog defecating a large volume of stool containing charcoal and walnut material, consistent with the brownies ingested by the dog ~21 h prior, as well as unidentifiable foreign material.

Within 21 h following presentation to the ER clinic (25.3 h after chocolate ingestion), the dog had a markedly improved serum sodium concentration (Na: 157 mmol/L; RR: 140 to 151 mmol/L) and a resolve of creatinine elevation (creatinine: 1.47 mg/dL; RR: 0.4 to 1.5 mg/dL) and hemoconcentration (PCV/TP: 50/5.1). At this time, the estimated calculated rate of hypernatremia correction was 2.6 mmol/h (based on an estimated serum sodium concentration of 180 mmol/L for the dog’s highest sodium concentration that was measured above the analyzer’s highest range). In addition to the serum sodium concentration improvement, 21 h following presentation to the ER, the other electrolytes evaluated for the dog were within or near the reference range (K: 3.5 mmol/L; RR: 3.5 to 5.0 mmol/L; Cl: 130 mmol/L; RR: 106 to 127 mmol/L).

Despite this blood value improvement, the dog experienced a near-arrest episode ~30 min following peripheral phlebotomy. The near-arrest episode involved the dog appearing mentally dull before developing apnea, profound bradycardia, and hypotension (HR: 40 bpm; BP: 60 mmHg). The dog was intubated and required positive pressure ventilation for 1.5 h before being extubated and transitioned to nasal prong oxygen therapy; this oxygen supplementation was discontinued 12 h after initiation. In addition, the dog was administered atropine therapy (0.02 mg/kg BW, IV), 2 crystalloid boluses (10 mL/kg BW, LRS each), and 2 boluses of 7.2% hypertonic saline (3 and 2 mL/kg BW, IV, respectively) because of the hypotension and inappropriate mentation. Accordingly, serum sodium concentration transiently increased (Na: 174 mmol/L; RR: 140 to 151 mmol/L). The dog also required 7 h of potassium chloride supplementation at the near-maximum rate (0.46 mEQ KCl/kg BW, per hour) because of the severe hypokalemia (K: 2.3 mmol/L; RR: 3.5 to 5.0 mmol/L) noted following the near-arrest. The dog remained nonazotemic but had developed profound acidosis (pH: 6.939; RR: 7.360 to 7.460) and hypercapnia (PCO₂: 97.1 mmHg; RR: 30 to 47 mmHg) at the time of near-arrest.

Despite the improving blood values just before the near arrest, it is possible that the dog’s recent acute development of hypernatremia potentially resulted in intracranial pathology (e.g., intracranial hemorrhage) or primary cardiac pathology (e.g., intra-cardiac hemorrhage) to cause the near-arrest and subsequent hypercapnia and suspected catecholamine release resulting in the observed hypotension and hypokalemia (4–9). The dog’s acidosis, hypercapnia, and blood potassium normalized after a 1.5-hour period of positive pressure ventilation and continued resuscitative efforts with custom IV fluid therapy.

With continued care, the dog’s serum sodium concentration was back near the initial value (Na: 158 mmol/L; RR: 140 to 151 mmol/L) within 14.5 h following the near-arrest and within the reference range (Na: 149 mmol/L) within 19 h following the near-arrest episode. On the dog’s 4th day of hospitalization and following weaning of fluid support prior to discharge, the dog’s serum sodium concentration remained normal (Na: 149 mmol/L). The dog remained appropriately hydrated (PCV/TP: 49/6.2) and non-azotemic (creatinine: 0.8 mg/dL; RR: 0.4 to 1.5 mg/dL) (BUN: 11 mg/dL; RR: 15 to 32 mg/dL). The dog’s liver enzymes had mildly elevated within 20 h after the near arrest (ALT: 165 U/L; RR: 10 to 125 U/L) (ALP: 269 U/L; RR: 23 to 212 U/L).

The dog regained normal mentation within 16 h following the near-arrest episode, and, within 20 h, the dog had a resolve of nystagmus and regained ambulation abilities but was walking with ataxia and demonstrated ptyalism. The dog’s ataxia appeared to be resolved by time of discharge (36 h after the near-arrest episode), and the dog’s ptyalism resolved through using ondansetron therapy (0.5 mg/kg BW, IV, q12h). Despite the dog’s eyes being lubricated every 4 h when mentation was impaired, the dog was diagnosed with a corneal ulcer in the right eye and was started on ofloxacin 0.3% topical therapy prior to discharge.

The dog was discharged 57 h following admission to the hospital (62.5 h after chocolate ingestion). The discharge medication plan included amoxicillin/clavulanic acid (21.2 mg/kg BW, PO, q12h), omeprazole (0.85 mg/kg BW, PO, q12h), maropitant (2.1 mg/kg BW, PO, q24h), ondansetron (0.5 mg/kg BW, PO, q12h), and ofloxacin 0.3% topical ophthalmic solution (1 drop, OD, q8h).

The dog was brought to the primary veterinarian approximately 8 h following initial ER discharge due to ptyalism and being restless. The dog’s temperature was mildly elevated at the time of recheck (39.5°C/103.1°F). Recheck radiographs showed no obvious aspiration pneumonia. The dog remained non-azotemic (creatinine: 0.9 mg/dL; BUN: 17 mg/dL) and continued to have a normal sodium concentration (Na: 158 mmol/L). The dog’s liver enzymes had increased since discharge (ALT: 341 U/L; RR: 10 to 125 U/L, ALP: 274 U/L; RR: 23 to 212 U/L) such that the dog was started on Denamarin (19.1 mg/kg BW, PO, q24h). Ptyalism improved with the dog restarting maropitant therapy. In relation to the dog’s restlessness, the dog was discharged with trazodone (2.1 mg/kg BW, PO, q8h).

Within 48 h following initial discharge from the hospital, the dog was noted to remain restless and not wanting to sleep at home such that the trazodone dose was increased (4.2 mg/kg BW, PO, q8h). Methocarbamol (21.2 mg/kg BW) was prescribed to aid in twitching that the client noted at night but was discontinued due to excessive sedation. By 72 h following initial ER discharge, the dog was only having rare shakes/tremors at home. Within 96 h following initial discharge, the dog was being weaned off trazodone, and navigation ability had improved. Within 32 d following ER discharge, the dog was rechecked by the primary veterinarian and was noted to have returned to normal barking behavior. At that time, the dog was still having mild daily vestibular episodes. Recheck of liver enzymes 71 d following ER discharge revealed normalization of liver enzymes (ALT: 19 U/L; RR: 18 to 121 U/L) (ALP: 33 U/L; RR: 5 to 160 U/L). Approximately 10 mo (304 d) following ER discharge, the owner reported that the dog was acting normally with a good quality of life and had no further neurological signs.

DISCUSSION

This report describes a case of chocolate toxicosis that was further complicated by severe hypernatremia following activated charcoal treatment. Previous case studies describe concurrent salt toxicity and chocolate toxicity; however, to the authors’ knowledge, this is the first case study that documents a dog developing hypernatremia following activated charcoal therapy related to chocolate toxicosis (4,5). Considering the common need to treat chocolate toxicosis in small animal patients and the high frequency of using activated charcoal as an adjunct to gastrointestinal decontamination, our case report can provide insight into treatment strategies and identifying risk factors for developing hypernatremia secondary to chocolate toxicity and treatment (1,2). The report also provides an example for potential neurologic recovery following severe hypernatremia.

The dog in the current case study had multiple risk factors that may have contributed to development of severe hypernatremia. Large chocolate volume ingestions, such as that ingested by the dog in the current case study, result in an osmotic pull of fluid toward the GI tract and consequential risk for hemoconcentration and hypernatremia (10). The chocolate ingested likely also resulted in caffeine-induced increased urinary sodium excretion to cause polyuria and a further increased risk for hemoconcentration.

The dog’s subsequent development of hyperthermia, tremors, seizures, and need for sedating anti-convulsant medications were most likely also the result of chocolate intoxication (1) rather than the result of the mild increase in sodium concentration following the initial activated charcoal with sorbitol therapy. It is suspected that the resulting hyperthermia, tremors, seizures, and impaired mentation (the dog first demonstrated depressed mentation following apomorphine treatment and progressed to be sedate following anti-convulsant treatment) resulted in inability to intake oral fluids and risks for increased fluid loss that contributed to the dog’s risk for hypernatremia.

The dog’s initial vomiting following apomorphine administration likely also contributed to the dog being at risk for hypernatremia from fluid loss (11,12). Additional free water loss for the dog potentially occurred secondary to osmotic pull of fluid into the GI tract following treatment with activated charcoal (13). A retrospective review of dogs treated with 1 g/kg BW activated charcoal and which had fluid access in relation to toxin treatment did not reveal substantial risk for hypernatremia. The risk for sodium elevation, however, was noted in healthy dogs treated with 2 g/kg BW activated charcoal with sorbitol and which had water withheld for 12 h after administration (2,14). Although further veterinary studies are needed to fully understand the effects of dosing and cathartics on risk for development of hypernatremia, based upon the current literature, the dog herein may have had a heightened risk for hypernatremia. This dog had multiple risk factors for free water loss and lack of water intake (vomiting, inappropriate mentation preventing oral water intake, polyuria, hyperthermia, tremors/seizures) as well as having received 2 doses of activated charcoal, with 1 of those doses being a larger volume (1.9 g/kg BW) and containing sorbitol.

In this case, the dog developed further neurologic signs, near arrest, and azotemia following development of hypernatremia; knowledge of the effects of hypernatremia on body systems can help explain the clinical course. The neurological changes noted were suspected to most likely be secondary to a combination of brain pathology secondary to acute severe hypernatremia (e.g., intracranial hemorrhage) and secondary to the post near-arrest episode (6). Brain injury secondary to the dog’s tremors/seizure events could be another differential for the dog in the case report having inappropriate neurological status (15). On the histopathologic level, perhaps these neurologic signs resulted from vascular congestion, perivascular hemorrhage, and axonal sheath dilation and degeneration in the cerebrum and cerebellum, as is present at necropsy of patients with salt toxicity (4). Such changes within the cerebellum could also be the reason the dog had vestibular signs after discharge. The near arrest of the dog could relate to these neurological changes but could also relate, at least in part, to cardiac changes associated with hypernatremia. These could include intra-cardiac hemorrhage, myocardial dysfunction, and secondary arrhythmias, as such cardiac changes were noted on necropsy of dogs with dual chocolate and salt toxicity (4,5). The azotemia of the dog in the current case report was suspected to be primarily pre-renal, considering the concurrent hemoconcentration; however, based on case reports of salt and chocolate toxicosis, the azotemia could also have been related to renal tubular necrosis secondary to hypernatremia (5,16,17).

In conclusion, the current case study describes the unique clinical challenges experienced when treating concurrent chocolate toxicosis and hypernatremia potentially secondary to activated charcoal and cathartic treatment. Such challenges likely arose secondary to the effects of high sodium concentrations at the level of the central nervous system, cardiopulmonary system, renal system, and secondary effects of dehydration from osmotic-induced colonic fluid loss associated with chocolate and activated charcoal (4–6,10,13,16,17). The dog in our case demonstrated the potential increased risk for development of hypernatremia in patients treated with multiple doses and larger volumes of activated charcoal. Also, the patient had the risks that are present in patients which have ingested an osmotically active toxin, such as chocolate, and which have risk factors for lack of water intake and increased water loss (vomiting, inappropriate mentation, hyperthermia, tremors/seizures) (10–12). Although the mortality rate associated with hospital management of chocolate toxicosis cases is reported as low (3%), concurrent severe hypernatremia substantially increases morbidity and mortality risk (1,11). Although severe hypernatremia can be life-threatening, the current case exhibited the ability for neurologic improvements with initial aggressive critical care management. Therefore, the current case study highlighted the importance of close electrolyte monitoring in all cases involving the need for activated charcoal therapy. The case also demonstrates the need for consideration if activate charcoal therapy should be avoided when planning treatment of a patient which has ingested an osmotically active toxin (e.g., chocolate), especially in patients with concurrent risks for dehydration. CVJ