A 40-year-old woman presented with general weakness, nausea, vomiting, numbness, and weight loss of 8 kg over the previous two months. The patient was 154 cm tall and weighed 57 kg. Her blood pressure was 100/60 mmHg and pulse was 110 beats/min. She was on no diuretics or other medications. She did not have a medical history or diarrhea upon presentation. On admission, she had weakness in both limbs (Medical Research Council Grade 2), but her deep-tendon reflexes were intact. Babinski’s sign and ankle clonus were absent.
Upon initial laboratory analysis, her sodium was 142.8 mEq/L; potassium, 2.3 mEq/L; chloride, 125.5 mEq/L; calcium, 7.7 mg/dL; phosphorus, 1.1 mg/dL; magnesium, 2.6 mg/dL; blood urea nitrogen, 17.7 mg/dL; creatinine, 1.0 mg/dL; and albumin, 4.2 g/dL. Her spot urine potassium was 16.9 mEq/L, and the transtubular potassium gradient (TTKG) was 7%, suggesting renal loss. Blood gas analysis revealed a pH of 7.194, PCO2 of 19.5 mmHg, PO2 of 67.8 mmHg, HCO3 of 7.6 mEq/L, SpO2 of 90.2%, and a serum anion gap of 9.7, suggesting normal anion gap metabolic acidosis. Urinalysis revealed a pH of 6.5 and a urine anion gap of 6.1.
Due to the patient’s hypotension and altered mental status, she was admitted to the intensive care unit. She required mechanical ventilatory support with supplemental oxygen due to lethargy, somnolence, and respiratory failure (PCO2 45.3 mmHg). She was treated with intravenous potassium chloride and an oral potassium chloride tablet via nasogastric tube.
In addition to ventilatory support, she also required treatment for her severe acidemia with sodium bicarbonate. Her desired bicarbonate level was 24 mEq, and her bicarbonate deficit was calculated to be 365 mEq from the following formula: bicarbonate deficit = (0.5 × lean body weight) × (24- serum bicarbonate) [6]. Her lean body weight was calculated to be 44.5 kg from the following formula: lean body weight [kg] = 9270 × body weight [kg]/6680 + (216 x BMI [kg/m2]). We treated her with an overdose of 480 mEq of intravenous sodium bicarbonate in 5% dextrose and water solution because her mental status and severe metabolic acidosis did not improve. The next day, her potassium was corrected to normal levels (4.2 mEq/L). However, we found acute hypernatremia with her sodium levels rising from 142.8 mEq/L to 172.8 mEq/L. We began treating her with half-normal saline and 5% dextrose in water, and her serum sodium level gradually decreased from 172.8 mEq/L to 148.0 mEq/L over the course of six days (Figure 1). As her hypernatremia was corrected, she became more alert and her weakness was greatly improved.
Six days after the development of hypernatremia, several other symptoms became evident including dysarthria, drooling, difficulty swallowing, and tetraparesis. Because of these symptoms, we suspected ODS associated with acute hypernatremia. Consistent with our clinical suspicion, a brain MRI revealed symmetric, high-intensity signal in the central pons with sparing of the peripheral portion, suggesting CPM (Figure 2). Soon after this diagnostic confirmation of CPM, two consecutive therapeutic plasma exchange sessions for two days were started with a total of 4394 mL plasma exchanged with albumin 5%, crystalloids, and fresh frozen plasma. The day following the plasma exchange, she regained speech and became oriented. Her neurological symptoms, which included dysarthria, difficulty swallowing, and tetraparesis, were markedly improved, but mild diplopia was present.
After the patient was stabilized, we were able to work her up to explore the primary cause of her presenting symptoms. We suspected distal renal tubular acidosis (RTA) due to the normal anion gap metabolic acidosis, a serum bicarbonate level < 10, hypokalemia, and urine pH of 6.5 (> 5.5), and due to the presence of a calyceal stone in her left kidney. We performed a sodium bicarbonate (NaHCO3) loading test to confirm distal RTA [7]. In NaHCO3 loading test, 8.4% NaHCO3 solution was infused intravenously at a rate of 57 mEq/hour (1 mEq/kg/hour). Urine and blood samples were taken at 1-hour intervals and urine and blood PCO2 were measured using a blood gas analyzer. When the urine pH was raised to 7.6, urine PCO2, blood PCO2, urine HCO3, blood HCO3, urine creatinine and serum creatinine were 44.5 mmHg, 34.8 mmHg, 40.1 mEq/L, 25.8 mEq/L, 64.5 mg/dL, and 0.7 mg/dL, respectively. The results of NaHCO3 loading test revealed a fractionated excretion of HCO3 of 1.68% and the urine-to-blood carbon dioxide tension gradient (U-B PCO2) of 9.7, suggesting distal RTA. In addition to the distal RTA, we also found that she had Sjögren’s syndrome after the results of Schirmer’s test and after she screened positive for anti-Lo and anti-Ra, which was confirmed by a salivary scan and lower lip biopsy. She was discharged and treated at an outpatient clinic with oral sodium bicarbonate and potassium chloride. After one year of follow-up, her neurological symptoms were improved, but mild diplopia remained.