BY GREGORY TAYLOR, DO, & CHRISTOPHER COOLEY, DO
A 66-year-old woman with a history of type 1 diabetes, hypertension, and end-stage renal disease (ESRD) on hemodialysis presented via EMS to the emergency department with altered mental status. She lived with her family, and they noted that she refused to go to dialysis for her past four sessions and had increasing lethargy for two days.
She was afebrile, and her other vital signs were blood pressure 136/92 mmHg, heart rate 77 bpm, respiratory rate 20 bpm, and oxygen saturation 96% on room air. She was agitated and reaching for objects in the sky. Her cardiopulmonary exam was notable for a regular rate and rhythm with coarse breath sounds bilaterally, and she was alert and oriented x 1 (baseline of AOx3). Her speech was slurred, and her exam was limited due to little patient cooperation and altered mental status.
She was also experiencing asterixis to her arms, and she had 2+ pitting edema bilaterally to her legs, extending to distal knees. An ECG revealed a normal sinus rhythm of 82 and peaked T-waves, with a prolonged PR interval and QT interval concerning for hyperkalemia.
Chest radiography revealed bilateral pulmonary vascular congestion and bilateral pleural effusions. (Images A and B.) A CT of the head without IV contrast was negative for any acute process. Pertinent laboratory evaluation was notable for a white blood cell count of 11.2, hemoglobin of 6.8 g/dL, hematocrit of 21.3, and a platelet level of 370. Basic metabolic panel revealed a hyponatremia of 129, hyperkalemia of 7.8 (non-hemolyzed), blood/urea/nitrogen (BUN) of 81, creatinine of 8.3, glomerular filtration rate (GFR) of 4.5, and blood glucose of 99. Arterial blood gas was notable for a pH of 7.51, pCO2 28, p02 54, HCO3 22, and a lactic acid of 1.6. Other relevant laboratory abnormalities included an ammonia level of 45, brain natriuretic peptide (BNP) of 2572, and troponin of 0.05.
Nephrology was consulted immediately for emergent dialysis for her hyperkalemia and altered mental status secondary to uremic encephalopathy and medical noncompliance with hemodialysis. The patient received 10 mg albuterol breathing treatment, 10 units of regular insulin intravenous with an amp of d50, and 3 gm of calcium gluconate while preparing for dialysis. Lasix was held because the patient was not making urine. Her acute hypoxic respiratory failure and hypervolemic hyponatremia was likely secondary to volume overload and missed hemodialysis. Her anemia was secondary to renal failure, and she was transfused 1 unit of pRBCs in dialysis. She continued to improve clinically over her hospital course, and was dialyzed three times. Repeat chest radiography showing significant improvement in pulmonary vascular congestion and bilateral pleural effusions.
Uremia is a clinical condition associated with declining renal function and end-stage renal disease. It is associated with electrolyte imbalances, fluid imbalances, and metabolic abnormalities, and is most often seen in patients with ESRD and also may occur in acute kidney injury. (StatPearls, June 15, 2017; http://bit.ly/2PvHUFe.)
Dysfunction occurs at multiple levels when the kidneys are not functioning effectively, which affects acid-base homeostasis, hormone production/secretion, fluid regulation, electrolyte regulation, and waste elimination. The result can be severe metabolic disturbances and conditions like hypertension, acidosis, hyperkalemia, anemia, and hypothyroidism, and the increased anion-gap metabolic acidosis can lead to lethargy, muscle weakness, hyperventilation, and congestive heart failure. A buildup of uremic toxins contributes to the development of coagulopathy secondary to diminished platelet adhesion, increased platelet turnover, and reduction in the number of platelets, ultimately resulting in a bleeding diathesis. These toxins also contribute to the development of uremic pericarditis, pericardial effusions, and may further worsen valvular function with resulting suppression of myocardial contractility.
Uremia can result in numerous clinical presentations (WikEM, February 2017; https://wikem.org/wiki/Uremia), including but not limited to:
- Cerebrovascular accident (as a result of hypertension, bleeding dyscrasias, and trauma)
- Peripheral neuropathy (parasthesias, weakness, dizziness, impaired proprioception in 60-100% of dialysis patients)
- Subdural hematoma (10 times more likely than the general population to develop this as a result of platelet dysfunction)
- Uremic pericarditis (seen in about 75% of cases, blood urea and nitrogen >60, and a loud friction rub)
- Tamponade (patients present with hypotension, dyspnea, and altered mental status and seldom present with the classic Beck's triad)
- Pulmonary edema and congestive heart failure
- Hematologic abnormalities (anemia and bleeding diathesis with an increased risk of spontaneous intracranial hemorrhage, hematoma of the liver, and gastrointestinal hemorrhage secondary to an impairment in platelet function)
- Dermatologic abnormalities (crystallized nitrogenous waste from sweat results in uremic frost, often seen with BUN >200)
- Renal bone disease (amyloidosis, hyperparathyroidism, and metastatic calcification)
- Increased anion gap metabolic acidosis
- Uremic encephalopathy
Our patient presented with uremic encephalopathy, a toxic metabolic encephalopathy, which is considered a rare and life-threatening disease in patients with acute or chronic renal failure. Early symptoms include anorexia, irritability, drowsiness, nausea, and delayed cognitive function. As the encephalopathy progresses, patients become confused and disoriented, and may present with emotional instability and bizarre behavior, with eventual coma and death. (StatPearls, June 15, 2017; http://bit.ly/2PvHUFe.) Asterixis, clonus, hyperreflexia, and tremor have been shown to parallel the degree of mental status changes. (UpToDate, Sept. 1, 2016; http://bit.ly/2o77tA1.)
Clinical research has shown that uremic encephalopathy is uncommon when the BUN level is <35. (Clinical Gate, February 2, 2015; http://bit.ly/2LhckHL.) It has also been shown that the severity and onset of uremic encephalopathy is associated with the degree of azotemia. (UpToDate, Sept. 1, 2016; http://bit.ly/2o77tA1.) Patients presenting with a true uremic emergency with hyperkalemia refractory to medical treatment, lactic acidosis, uremic encephalopathy, and symptomatic pericardial effusion, require emergent dialysis. (StatPearls, June 15, 2017; http://bit.ly/2PvHUFe.) Signs and symptoms of uremia don't often develop until the GFR is 10-15 mL/min, and no minimum GFR indicates an absolute indication for dialysis without symptoms. (UpToDate, March 5, 2018; http://bit.ly/2whuOm0.) “A-E-I-O-U” is a mnemonic for clinicians commonly used for dialysis indications. (First Aid Team, April 7, 2014; http://bit.ly/2nY6hi9.)
A: Acidosis: increased anion gap metabolic acidosis with a pH <7.1
E: Electrolyte abnormalities: rapidly-rising potassium levels or refractory hyperkalemia
I: Intoxications: lithium, isopropanol, methanol, salicylates, and ethylene glycol
O: Overload: patients presenting with volume overload refractory to diuresis
U: Uremia: elevated BUN with signs and symptoms of uremia, including uremic encephalopathy.
Improvement in uremic encephalopathy can take several months, with some patients never returning to baseline. By day four, our patient was alert and oriented x 3, had no complaints, and her mental status was back to baseline and her potassium was within normal limits at discharge.
Dr. Taylor is a captain in the United States Air Force and an emergency medicine resident at Beaumont Hospital in Farmington Hills, MI, a teaching hospital of Michigan State University, where Dr. Cooley is also an emergency physician.