Acute Salt Toxicity Caused by Whey Ingestion in Mixed-breed 6-months-old Puppy: A case study

This case report aims to emphasize the acute management of a dog with suspected salt intoxication, which consists of a treatment protocol with hematological and Modified Glasgow Coma Scale (MGCS) changes and electrocardiographic (ECG) evaluation. A 6-month-old male mixed-breed dog was admitted to the emergency clinic with complaints of weakness, hypersalivation, vomiting, diarrhea and gait disturbance. It was learned from the owner that the dog was fed on whey for the first time on the morning of the admission day. Salt toxication was suspected based on history and clinical symptoms. The diagnosis was confirmed by laboratory analysis (pH: 7.185, Na: 178 mmol./L, Cl: 155 mmol./L, K: 8.3 mmol./L, HCO3: 16.1 mmol./L, BE: -8.8 mmol./L, BUN: 105.7 mg/dl, creatinine: 5.4 mg/dl, AST: 513 U/L, amylase: 2324 U/L, LDH: 794 U/L, calcium: 11.8 mg/dl, phosphorus: 13.9 mg/dl, cholesterol: 515 mg/dl, magnesium: 3.6 mg/dl, GGT: 62 U/L CPK: 450 U/L and CK-MB: 324.5 U/L), ECG (sinus tachycardia (180 bpm) and mild ST depression) and MGCS evaluation (pre-treatment score; 7, grave). A treatment protocol including fluid therapy, antiemetic, diuretic, anticonvulsant, beta-blocker to prevent sodium retention and oxygen therapy was administrated to the dog during the hospitalization period. It was observed that the clinical findings and MGCS score improved and some blood parameters returned to their reference range on Day 2. Since the dog died on Day 3 after the hospitalization period, which was terminated at the owner's request, it was concluded that an adequate hospitalization period is important. The presented treatment protocol with MGCS evaluation in salt toxicity was successful enough only in acute management. ـــــــــــــــــــــــــــــــــــــــــ


INTRODUCTION
The key factors for the development of hypertension, renal failure and coronary heart disease are considered to be medical conditions such as severe water loss and intake of iatrogenic sodium (Arambewela et al., 2016) or excessive consumption of processed food which meets more than 75% of daily salt need (Titze and Ritz 2009). While the recommended daily sodium consumption in humans is 1500-2400 mg/day (Kim et al., 2012), the sodium requirement in adult dogs is reported as 5 mg/kg/day or 0.2 g / 1000 kcal (metabolisable energy) (Morris et al., 1976, Smith et al., 2016. The clinical signs of salt toxicity are lethargy, depression, dehydration, vomiting and diarrhea (Angelos et al., 1999), followed by neurologic findings such as muscle stiffness, opistotonus, tremors, convulsions, seizures, and loss of consciousness (Hardy, 1989). Laboratory findings of salt toxicity are metabolic acidosis, hypernatremia, hypoglycemia, and serum biochemistry abnormalities such as azotemia, increasing some liver enzyme levels due to tissue hypoperfusion resulting from dehydration (Kazanji et al., 2015, Arambewela et al., 2016. The most prominent findings on ECG are QT prolongation, PR shortening, ST depression, decrease in P and QRS amplitudes and sinus tachycardia (Fisher et al., 2006).
Clinical findings of salt toxicity are associated with pathological changes in the brain and the level of consciousness depends on the severity of the hypernatremia (Braun et al., 2015). In cases that affect the level of consciousness such as hypoglycemia, hypotension, hypernatremia and trauma (Bowins, 2018), the Modified Glasgow Coma Scale (MGCS) is useful in observing the progression of neurological disorders and the effects of therapeutic interventions (Platt et al., 2001).
In this case report, based on historical information of the dog such as iatrogenic whey consumption (0.7-1.7 M NaCl; maximum 99.34 g per 1 liter) and clinical signs, salt toxicity was suspected and confirmed by laboratory analyzes. Acute management and changes in hematochemical parameters, ECG and MCGS score findings during the hospitalization period are presented.

Case Description:
A 6-month-old male mixed-breed dog weighing 20 kg was brought to Selcuk University Faculty of Veterinary Medicine Animal Hospital Emergency Clinic with complaints of sudden weakness, respiratory distress, hypersalivation, vomiting, diarrhea and gait disturbance (Fig. 1). It was learned from the owner that the dog had two seizures lasting less than 1 minute at 15-minute intervals at home and one seizure on the road before admitting to the hospital. The dog was vaccinated, had no history of the disease, was fed commercial dry dog food, and was fed on whey for the first time as a supplement on the morning of the admission day (Day 0, approximately 3 hours before admission). Clinical and laboratory tests were performed for further diagnosis.
Physical examinations including palpation of lymph nodes, measurement of heart and respiratory rate and temperature, auscultation of lung and heart, evaluation of color of mucous membranes, capillary refill time, degree of dehydration, ECG (Biocare ECG 300G, China) and MGCS assessment to determine the level of consciousness were performed. Laboratory analysis included blood gases (ABL80 Flex, Denmark), complete blood count (CBC) (MS4 Autoanalyzer, France) and serum biochemistry (BT3000 Autoanalyzer, Italy) measurements.

RESULTS
During a physical examination, a considerable loss of skin turgor and severe dehydration (~10%) with enophthalmos, pale mucous membranes, prolonged capillary refill time (> 4 sec), high rectal temperature (39.8 °C), weak femoral pulse, mildly depressed respiratory sounds and normal palpable lymph nodes were detected. ECG measurement revealed sinus tachycardia (180 bpm) and mild ST depression (Fig 2). Blood pressure was measured as 220 mmHg (systolic) and 130 mmHg (diastolic) and urine specific gravity as 1.040 (URIT-31, China). The MGCS score at the bedside was determined to be seven and evaluated as severe (Table 1).

Treatment and Outcome:
Following diagnostic tests immediate fluid therapy (0.9% NaCl, 154 mEq / L Na content to reduce serum sodium more slowly), antiemetic (metoclopramide 0.4 mg / kg IV), diuretic (furosemide 6 mg / kg IV), anticonvulsant (diazepam 1 mg / kg IV), beta-blockers (atenolol 1 mg / kg sublingual) to prevent sodium retention and heart rate control and oxygen therapy (50 milliliters / kg / minute) with nasal tube was initiated and the dog was hospitalized for continuous cardiac monitoring. Idwelling urinary catheter was inserted. After 24 hours of hospitalization. It was observed that convulsions disappeared and urine output was started. MGCS score was reevaluated at the bedside (Day 2) and was determined as 12 (guarded). In the second blood analysis (Day 2), the sodium concentration was measured as 158 mmol / L ( Table 3). As a result of the significant clinical improvement observed in the dog, the owner did not accept the longer hospitalization period and the patient was discharged on Day 2. It was learned that the dog was standing but vomiting and diarrhea continued in the evening of Day 2, after discharge. The next day, it was learned that the dog died on the morning of Day 3 (considering the first admission as Day 0).

DISCUSSION
The sodium content of a regular commercial dry dog food is 0.5 -2.5 g / 1000 kcal equal to 2-10 g / kg dry matter (Beynen, 2017). Therefore, extra salt, especially sodium, originated from milk, milk permeate, or whey consumption causes excessive salt intake (Smith et al., 2016). In this case report, the cause of salt toxicity was evaluated as iatrogenic whey use.
The majority of clinical signs recorded in salt toxicity cases were gastrointestinal and neurological disorders (Bagley et al., 1993, Pouzot et al., 2007). In this case report, neurological findings such as seizures and gait disturbances, hypersalivation, vomiting and diarrhea due to mucosal irritation of salt were the most prominent clinical symptoms.
Hypernatremia is a common electrolyte abnormality caused by salt intoxication, diabetes insipidus or heat stroke, or hypotonic fluid loss such as vomiting, diarrhea, osmotic diuresis (Pouzot et al., 2007). Extracellular volume abnormalities and hypernatremia, hyperchloremia and metabolic acidosis resulting from endocrine changes such as reninangiotensin-aldosterone system and sympathetic nervous system due to excessive sodium intake have been reported as hematological changes (Dibartola, 2006). The hematochemical abnormalities detected in our case were consistent with previous reports (Pouzot  et al., 2007, Arambewela et al., 2016).
The actual pathophysiology of hypernatremia on cardiac dysfunction is unknown. It is, however, hypothesized that increased extracellular sodium causes more calcium to exit the cell via a sodium-calcium exchanger on the sarcolemma. Therefore, ECG findings such as QT prolongation, PR shortening, ST depression, decreased P and QRS amplitudes and sinus tachycardia have been reported (Arambewela et al., 2016). In our case, sinus tachycardia and mild ST depression were remarkable.
Changes in the brain and the level of consciousness have been reported in cases of salt toxicity, and the severity depends on the level of hypernatremia (Bowins, 2018). Observing the progression of neurological disorders and general prognosis, MGCS is useful and is important in evaluating the patient's motor activity, brainstem reflexes and level of consciousness (Platt et al., 2001). In our case, the MGCS score assessment was useful in evaluating general prognosis (7 at first admission, 12 before discharge) along with blood analysis .
The main goal of salt toxicity treatment is to correct the hypernatremia to a maximum of 2 mEq / L / hour of sodium (Pouzot et al., 2007). The amount of fluid required to correct the sodium concentration in the case of hypernatremia (178 mmol / L) detected in our case was calculated as 24.72 liters using the formulation [Free water deficit = 0.6 x bodyweight x (Na Measured / Na desired -1) 9]. It was given intravenously as a slow infusion during hospitalization (24 hours). Although a rate of 10-12 mmol / 24 hours is recommended for correction of hypernatremia by several authors (Al-Absi et al., 2012, Braun et al., 2015, Arambewela et al., 2016, it has been reported that slow correction is associated with high mortality (Alshayeb et al., 2011). In our case, the correction of hypernatremia was performed at a rate of 23 mmol / 24 hours. A decrease in sodium concentration (Table 3) was obtained and improvement in clinical findings and in MGCS (Table 1) score was observed on Day 2, the end of the hospitalization period.
The prognosis of salt toxicity in dogs depends on the amount of salt ingested, blood sodium concentration, the severity of neurological findings determined at the clinic admission, and the presence of any comorbid disease (Pouzot et al., 2007). The salt content of a typical whey ranges from 0.7-1.7 M and this corresponds to 99.34 g salt per 1 liter (Blaschek et al., 2007). Since the dog in the presented case is 20 kg, 80 grams of salt is sufficient for the occurrence of severe salt toxicity findings.
The origin (type of cheese) of whey given by the owner was unknown. Therefore, it was thought that it contained a maximum of 99.34 gr salt in 1 liter and it was confirmed that salt toxicity was related to iatrogenic whey consumption.
In this case, the duration of hospitalization could not be extended to the recommended period (Fisher et al., 2006, Pouzot et al., 2007, Arambewela et al., 2016 as it was against the will of the owner. It was determined that the pre-discharge blood sodium level was decreased (178 mmol / L at first admission, 158 mmol / L before discharge) and the MGCS score (7 at first admission, 12 before discharge) was found to be increased, but the ECG could not be evaluated. Therefore, blood analyzes, including blood gases and electrolyte measurements with MGCS assessment, were determined to be useful to gain insight into prognosis in the acute management of salt intoxication.
The limitation of this case report is that because of insufficient hospitalization period, the treatment protocol could not be completed and the cause of death could not be determined due to the lack of necropsy examination.

CONCLUSION
It is reported in the previous studies that the management of hypernatremia due to excessive sodium intake is difficult to treat. There is only one dog reported to have survived in cases of salt intoxication with neurological findings. Considering the difficulty of managing salt toxicity and the lack of literature data, this case report focuses on the clinical findings and acute management of salt toxicity. The most prominent findings in salt toxicity are ECG findings such as tachycardia and ST depression, low MGCS score and laboratory findings such as hypernatremia, hyperchloremia and metabolic acidosis. It was concluded that the treatment and management protocol, including fluid therapy, antiemetic, diuretic, anticonvulsant, beta-blocker and oxygen therapy administrations and evaluation of MGCS scoring with appropriate hospitalization period are beneficial.

Declaration of competing interest
On behalf of all authors, I hereby declare that no conflict of interest may interfere with the publication of the manuscript.