Acute hypernatremia and hypocalcemia after oral sodium phosphate administration to a dog

Abstract

A 15‐year‐old male neutered mixed breed dog weighing 28 kg presented to a referral center after developing severe tremors and altered mentation. There was hypocalcemia and hypernatremia after oral administration of sodium phosphate as a bowel cleansing agent in preparation for colonoscopy. The dog was treated intravenously with low sodium fluids and calcium gluconate. Neurologic status and electrolyte derangements normalized over the next 12 hours. Oral administration of sodium phosphate appeared to cause clinical electrolyte derangements in this dog.

Abbreviations

bpm

beats per minute

BUN

blood urea nitrogen

ER

emergency room

GFR

glomerular filtration rate

GI

gastrointestinal

IRIS

International Renal Interest Society

LRS

Lactated Ringer's Solution

mmHg

millimeters of mercury

NaP

sodium phosphate

PEG

polyethylene glycol

1. INTRODUCTION

Hypocalcemia and hypernatremia are both common conditions in veterinary medicine that are generally defined for dogs as a total calcium of <8.0 mg/dL or an ionized calcium of <1.25 mmol/L and a sodium of >155 mEq/L. ¹ , ²

The characteristic findings of sodium phosphate intoxication include hypocalcemia, hypernatremia, and hyperphosphatemia with increased serum osmolality. Other reported abnormalities include hypokalemia or hyperkalemia, hyperglycemia, hypomagnesemia, and metabolic acidosis. ³ , ⁴ Tremors and tetany are the hallmark clinical signs of NaP intoxication in humans. Ataxia, somnolence, hypothermia, and GI upset were the most commonly reported signs in dogs. ³ , ⁴ , ⁵

Bowel preparation is a common practice before colonoscopy or other imaging of the lower gastrointestinal tract as it improves visualization and evaluation of the colonic mucosa and collection of biopsies. Many protocols are used including a combination of oral cleansing agents, enemas, and withholding food. There are few prospective trials comparing different methods of bowel preparation in veterinary medicine. ⁶ , ⁷ Most protocols have been extrapolated from human medicine where polyethylene glycol‐containing electrolyte solution (PEG) and sodium phosphate (NaP) are 2 of the most commonly used agents along with withholding food. ⁸

PEG is becoming more commonly utilized as an oral cleansing agent in veterinary medicine, but sodium phosphate can also be administered for pre‐imaging bowel cleansing in dogs. ⁹ , ¹⁰ , ¹¹ Sodium phosphate enemas, which are administered in large volumes at 20 to 30 mL/kg, can cause severe electrolyte abnormalities which can result in death of dogs and cats. ³ , ⁴ , ⁵ This case demonstrates that administration of oral sodium phosphate can be associated with severe clinical hypocalcemia and hypernatremia in a dog.

2. CASE SUMMARY

A 15‐year‐old male castrated mixed breed dog weighing 28 kg presented to the ER with acute, severe tremors, altered mentation, hypocalcemia, and hypernatremia. The dog had been admitted to the referral hospital that morning for a bowel cleanse in preparation for a colonoscopy the next day. The dog had a history of chronic, large bowel diarrhea unresponsive to empiric medical management with focal colonic thickening on ultrasonographic examination, IRIS stage 2 chronic kidney disease with historic proteinuria ¹² that was normal on most recent urine protein : creatinine ratio and recent vestibular events suspected to be secondary to idiopathic vestibular disease. The dog's only current medications were a probiotic (Visbiome, ExeGi Pharm LLC, Rockville, Maryland) and meclizine (0.9 mg/kg PO every 24 hours).

The dog was initially presented as a drop‐off appointment in preparation for a colonoscopy. The dog was bright and alert with no neurologic abnormalities noted. A biochemistry panel revealed mild azotemia (BUN 49 mg/dL—reference range 6‐30 mg/dL; creatinine 2.0 mg/dL—reference range 0.5‐1.5 mg/dL), mild hyperphosphatemia (7.0 mg/dL—reference range 2.5‐5.6 mg/dL), and normal sodium (151 mmol/L—reference range 145‐151 mmol/L) and total calcium (10.9 mg/dL—reference range 9.3‐11.4 mg/dL). The dog was administered lactated ringer's solution (Lactated Ringer's solution, ICU Medical Inc, San Clemente, California; LRS; 90 mL/kg/day), maropitant citrate (Cerenia, Zoetis, Parsippany‐Troy Hills, New Jersey; 1 mg/kg IV) and sodium phosphate tablets (OsmoPrep, Salix Pharmaceuticals, Ltd, Bridgewater, New Jersey; 15 g or 535 mg/kg every 4 hours for 3 doses PO) as well as warm water enemas (500 mL every 4 hours). The dog was not offered food but free choice water was available. Approximately 3 hours after the last dose of sodium phosphate, the dog was tachypneic, tachycardic and laterally recumbent with a systolic blood pressure of 120 mmHg. A 10 mL/kg intravenous bolus of LRS was administered followed by methadone (0.1 mg/kg IV) due to concern for abdominal discomfort. The tachycardia improved but blood pressure increased to 180 mmHg. There was marked hypernatremia (168.3 mmol/L) and ionized hypocalcemia (0.75 mmol/L). The dog was administered a 0.5 mL/kg dose of 10% calcium gluconate and transferred for continued care.

On presentation, the dog was laterally recumbent and minimally responsive with severe tremors that had been ongoing during transfer (~45 minutes), a core temperature of 106.1 °F, tachycardia (170 bpm), hypertension (180 mmHg) and harsh lung sounds. There was ionized hypocalcemia (0.65 mmol/L) and hypernatremia (168.6 mmol/L). ECG confirmed sinus tachycardia. The dog was treated with active cooling, an additional 10 mL/kg bolus of LRS and a 1 mL/kg bolus of 10% calcium gluconate followed by a continuous infusion at 0.5 mL/kg/h. The dog's mentation improved after these interventions. The tremor resolved and the dog was able to sit up on its own. Chest radiographs revealed signs consistent with aspiration pneumonia and atelectasis.

The dog was treated with 0.45% sodium chloride solution at 120 mL/kg/day and tepid water enemas. The calcium gluconate infusion was continued. Empiric antibiotics were administered for presumed aspiration pneumonia. Active cooling continued until the core temperature was <103 °F. The temperature remained normal throughout the remainder of hospitalization and the initial hyperthermia was attributed to the severe tremors. No arrhythmias were noted. Hypernatremia and hypocalcemia progressively improved and normalized approximately 12 hours after transfer at which point the calcium gluconate infusion was discontinued. The serum sodium concentration increased mildly throughout the day but improved without further intervention as the dog was able to consume food and water voluntarily. The dog remained neurologically normal throughout the remainder of its hospitalization and was discharged on the third day. There was resolution of hypernatremia and hypocalcemia and a mild progression in azotemia 1 week after discharge. Electrolytes remained normal for 2 months until the dog was euthanized because of progression of the GI disease.

3. DISCUSSION

It is suspected that the dog in this case developed altered mentation and tremors secondary to acute hypocalcemia given the rapid improvement when serum calcium concentration normalized. Hypocalcemia secondary to sodium phosphate is caused by a rapid absorption of phosphate resulting in severe hyperphosphatemia. Through the law of mass action, the phosphorus binds with ionized and protein‐bound calcium forming biologically inactive calcium complexes. ¹ These effects can be exacerbated when low glomerular filtration rate (GFR) reduces phosphorus excretion. Neither phosphorus nor magnesium were measured in this dog.

Hypernatremia cannot be fully excluded as a contributing factor for this dog's acute decline, but given the neurologic improvements noted when serum calcium concentration had begun to normalize while sodium remained relatively unchanged, this is thought to be less likely.

Literature supporting the oral use of sodium phosphate in veterinary species is sparse and only 1 article was found evaluating its safety profile and this was performed using healthy research dogs. This study found no significant changes in serum electrolyte concentrations after NaP administration and no adverse clinical signs apart from several episodes of vomiting. ¹¹ Studies where orally administered NaP was used as a bowel cleanser in preparation for imaging or surgical procedure did not report any adverse events secondary to the bowel cleanse, though this was not the purpose of these studies. ⁹ , ¹⁰ , ¹¹ , ¹³

Complications secondary to NaP administration in human medicine are better documented. A 2022 systemic review of 13 studies in human medicine found that between 35 and 360 patients out of 1000 patients developed serum electrolyte disturbances after bowel cleanses with NaP. ¹⁴ These electrolyte abnormalities most commonly included hypokalemia, hypernatremia, hyperphosphatemia, hypocalcemia and hypomagnesemia. Clinical signs attributed to these abnormalities ranged from mild/moderate such as muscle weakness, constipation, nausea, and vomiting to severe signs (paralysis, seizures, cardiac arrhythmias, coma, and death) in patients undergoing bowel cleansing. ¹⁴ Elderly humans (>65 years old) appear to be disproportionately at risk for electrolyte derangements likely due to a more sedentary lifestyle, altered gut motility, constipation, and systemic illness—in particular age‐related decrease in GFR. ¹⁵ Sodium phosphate is contraindicated in humans with congestive heart failure, renal failure and inflammatory bowel disease and caution is urged for patients with renal insufficiency and heart disease due to the increased risk of electrolyte abnormalities. ¹⁶ Note that these are all common co‐morbidities in veterinary patients undergoing colonoscopy. There is a paucity of literature from humans directly comparing the adverse effects of oral versus rectal administration of NaP. The 2 studies assessing the products head‐to‐head found similar efficacy as bowel cleansers but the adverse events assessed did not include electrolyte derangements. ¹⁷ , ¹⁸

The safe and effective dose of NaP in veterinary species is not reported. The 3 studies using oral administration of NaP for bowel cleanse report total doses of between 222 and 1140 mg/kg (111 mg/kg every 4 hours for 2 doses and 285 mg/kg every 8 hours for 4 doses). ⁹ , ¹⁰ , ¹¹ No citation was provided by the authors of these studies for the origin of their dosing regimen. Published dosing for humans varies between a total dose of 125 and 600 mg/kg. ¹⁹ , ²⁰ The dog in this case received a total dose of 1605 mg/kg (535 mg/kg every 4 hours for 3 doses) which is considerably higher than other published dose in human or veterinary medicine. It is suspected that the dog in this case could have been predisposed to developing electrolyte complications due to the pre‐existing renal disease and colonic disease which was then exacerbated by a higher than previously reported dose of NaP.

In conclusion, oral NaP should be used with caution in dogs with underlying chronic kidney disease or other systemic illnesses and serum electrolytes should be monitored before and after NaP administration.

CONFLICT OF INTEREST DECLARATION

Authors declare no conflict of interest.

OFF‐LABEL ANTIMICROBIAL DECLARATION

Authors declare no off‐label use of antimicrobials.

INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) OR OTHER APPROVAL DECLARATION

Authors declare no IACUC or other approval was needed.

HUMAN ETHICS APPROVAL DECLARATION

Authors declare human ethics approval was not needed for this study.

VanDerslice J, Carroll M. Acute hypernatremia and hypocalcemia after oral sodium phosphate administration to a dog. J Vet Intern Med. 2024;38(2):1157‐1159. doi: 10.1111/jvim.16989