- A relatively young woman with ESRD for more than 10 years, presenting awake and alert, breathing well on 2L O2 (her home dose) and a pH of 7.6
- The patient had gone for hemodialysis as per her usual schedule earlier in the day, but was noted to be behaving confused afterwards by her bus driver and was taken to the ED as a precaution
- The initial ABG looked more like Metabolic Alkalosis, but over the course of the night, her pH increased to 7.73 as her respiratory alkalosis worsened
Why it’s weird?
- We don’t typically see alkalosis in ESRD patients! Acidosis is far more common.
- Instead of compensating her Metabolic Alkalosis with her respirations, she developed a concurrent Respiratory Alkalosis overnight
- Our Nephrologist’s initial response was, “Curious” …
- Hypokalemia - not exactly the bread and butter of ESRD patients, but we initially wondered if too much potassium was dialyzed, resulting in an Intracellular Shift in hydrogen ions to compensate, but alas, her K was just over 4 on admission.
- Gastrointestinal losses - these tend to present in patients as emesis or diarrhea. The patient had not had any of these symptoms.
- Renal losses - these occur through loop and thiazide diuretic use or a variety of inheritable ion transport syndromes (Bartter, Gitelman, and Pendred). Since the patient didn’t make urine, these renal losses were not really an issue.
- => Mineralocorticoid excess - this is a subset of “renal losses” because it stimulates the mechanisms promoting proton excretion in the urine (collecting duct/tubule proton pump, ENaC channels, and the sodium-potassium pump). The patient had changed physicians and had missed getting refills of some of her medications. One of her antihypertensive medications - Minoxidil - has been shown to increase Plasma Aldosterone Clearance, so missing doses of this could theoretically cause a rebound aldosterone excess, but this was considered a low-likelihood scenario
- Contraction Alkalosis - this typically occurs with large NaCl losses without concurrent HCO3 clearance. Since the patient went to hemodialysis prior to admission, this could be a possible cause
- Post-Hypercapnia - not really a consideration as the patient had no reason to have a rapid drop in pCO2 and she doesn’t make urine (which is part of the compensatory mechanism)
- Weird ingestions - these can include Sodium Polystyrene Sulfonate (commonly known as Kayexalate), antacids, and milk, all of which she denied taking
- => As an aside on this one, the overconsumption of milk is classically part of the “Milk Alkali Syndrome” with presentation of the triad of Hypercalcemia, Metabolic Alkalosis, and Acute Kidney Injury. The colloquially named “Modern Milk Alkali Syndrome” is associated with antacid use, usually Calcium Carbonate. In renal failure patients, Secondary Hyperparathyroidism is often managed with Calcium Carbonate, to act as a Phosphate-binding agent. Our patient was used a sibling drug called Phoslo (Calcium Acetate). This diagnosis would be hard to prove because two of the classic signs were not present, i.e. the patient already had renal failure so AKI would go unnoticed and her calcium levels were normal, but the calculations were likely skewed by her use of the calcium-chelating Sensipar (Cinacalcet).
- LYTES!! - Na, K, Mg, Cl, HCO3, Ca, PO4
- Trend your ABG
- Saline challenge and Urine chloride - this is recommended as part of the initial workup from UpToDate to our friendly purple Pocket Medicine books. Unfortunately, the whole ‘not peeing’ component of her ESRD kind of threw a wrench in this plan. With the respiratory status at baseline, we did eventually give normal saline at a slow rate (50mL/hr) with the hope that the patient could replace some of the bicarbonate with chloride and compensate with some respiratory acidosis
- Screening for classic abuse and overdose (urine drug screen, urinalysis with microscopic analysis, salicylate level, acetaminophen level) - while we couldn’t test her nonexistent urine, her other medication levels were normal
- Endocrine testing - Thyroid function tests, Cortisol level
What we did:
- Slow infusion rate of 0.9% NaCl (50mL/hr) - for chloride replacement
- IV PPI (Protonix injections) - to slow
- Holding her Phoslo (Calcium Acetate)
- Ativan (Lorazepam) low dose 0.5mg Q8H scheduled to slow the respiratory rate and reduce CO2 loss through respiration
- As her alkalosis worsened, we repeated Hemodialysis with a low-bicarbonate solution and partial fluid replacement with 0.9% NaCl
What we had left in our arsenal:
- Hydrochloric Acid infusion … not a solution for the basic layman (pun intended) or the faint of heart!
- Ammonium Chloride infusion
- Continuous Renal Replacement Therapy (CRRT)
- The hemodialysis restored her pH to 7.33
- At no point, even with a pH of 7.73, did the patient show any physical signs except for slightly slowed mentation
- With no clear diagnosis, it’s possible that this will recur, but seeing as the patient is dialyzed thrice-weekly, the metabolic alkalosis, like hyperkalemia for most ESRD patients, might be managed by exogenous clearance
What we think happened/Take-home points:
- Contraction Alkalosis from hemodialysis, but the patient’s symptoms have been going on for a few days, so it’s possible her HD formulation changed recently
- Non-classic Modern Milk Alkali Syndrome with surreptitious or overuse use of her Calcium Acetate
- If this metabolic alkalosis recurs, and given her history of early-onset ESRD likely secondary to hypertension, she would be a good candidate for additional workup for Hyperaldosteronism
- Metabolic Alkalosis DDx - Hypokalemia, GI losses, Renal Losses, Mineralocorticoid Excess, and Milk Alkali Syndrome or other ingestions (e.g. Antacids + Kayexalate)
More common presentations:
- ESRD patient post-HD presenting with metabolic alkalosis and hypokalemia. Monitor for EKG changes and cardiopulmonary symptoms and delicately replace potassium
- Severe metabolic alkalosis in a patient who pees? Saline challenge, monitor Urine chlorine, replace chloride and potassium as needed, and know the diuretics potassium-sparing diuretics (Amiloride and mineralocorticoid receptor antagonists such as Spironolactone) as well as Diamox (Acetazolamide) could be used in edematous states, and that HD/CRRT or HCl might be necessary in severe or refractory cases.