A sustained metabolic alkalosis only occurs when an additional factor impairs bicarbonate excretion or enhance its reabsorption, namely an impaired kidney function (in our patient, CKD with superimposed pre‑renal AKI); hypochloremia (large amount of chloride rich gastric fluid losses); volume contraction (our patient was severely dehydrated from nasogastric tube, improper fluid administration and forced diuresis with furosemide); hypokalemia (fasting, secondary hyperaldosteronism due to volume contraction and furosemide) and increased sodium delivery to the distal nephron that led to hydrogen and potassium secretion (a loop diuretic effect, but less important in our patient).^1,3

Our patient presented all these factors, that impaired the above‑mentioned mechanisms, perpetuating alkalosis.

Hypoventilation and consequent PaCO2 elevation are a physiologic response to alkalemia, preventing life‑incompatible pH elevations.

For every 1.0 mM increase in arterial bicarbonate concentration, PaCO2 should increase 0.5 to 0.7 mm Hg.2 Mortality correlates with elevation of arterial pH: mortality rate could reach 45% in patients with arterial blood pH of 7.55 and 80% when pH is greater than 7.65. The prognosis is worse in patients with respiratory and metabolic alkalosis.⁵

The PaCO2 increase was lifesaving in our patient and it was appropriate to the degree of bicarbonate elevation (calculated respiratory compensation: PaCO2 96 mm Hg). Such a dramatic increase was allowed by an appropriate arterial PaO2 maintained by external oxygen supply, despite bradypnea - hypoxia would have limited hypercapnia.

How can we explain the electrolytic changes?

Our patient presented with severe hypochloremia, hypokalemia, hypernatremia and low ionized calcium.

The nasogastric tube was draining for several days, leading to a great loss of chloride and hydrogen rich fluid, provoking severe hypochloremia. Chloride depletion impairs chloride‑dependent bicarbonate excretion and concomitant potassium depletion in distal nephron, through activation of ROMK channel (principal cells). These mechanisms lead to low urinary chloride and elevated urinary potassium, which can be measured in a spot urine. This secondary potassium depletion plays an essential role in alkalosis perpetuation, through maintenance of chloride depletion [downregulating Na+‑K+‑2Cl‑ cotransporter (loop of Henle) and Na+‑Cl‑ cotransporter (distal tubule)] and through loss of hydrogen (stimulating distal nephron K+/H+‑ATPase in the α‑intercalated cells) in order to maintain electroneutrality. Furthermore, potassium depletion induces renal ammonia production, allowing acid excretion and sustaining metabolic alkalosis.1, 4 In our patient, chloride depletion, as well as volume depletion, was also exacerbated by furosemide. Further renal chloride losses can ensue when potassium depletion is severe and consequently much larger amounts of chloride are needed to correct alkalosis.

In this patient, hypernatremia is clearly hypovolemic, caused by severe dehydration due to nasogastric tube, poor fluid intake and forced diuresis. Hyperuricemia is also concordant with dehydration along with reduced glomerular filtration rate and furosemide use.⁶

The patient presented with hypocalcemia highlighted by low ionized calcium, despite normal corrected total calcium. This discrepancy is explained by alkalemia, which can alter the equilibrium of the albumin‑calcium complex. PH elevation enhance their binding, leading to a lower ionized calcium (but not total calcium). When major shifts in pH are present, it is prudent to directly measure the ionized calcium level in order to determine the presence of hypocalcemia, its risk of complications and need for correction. However, it is expected that ionized calcium increases with alkalosis correction.⁷

How should we manage this patient?

The priority in this patient is to correct volume depletion with chloride rich fluids (such as 0,9% NaCl), along with potassium supplementation and prevention of continuing loss of chloride.^3,8

Monitoring urinary chloride concentration can help guiding chloride replenishment and responsiveness of alkalosis to chloride administration. Calcium supplementation should be guided by possible occurrence of arrythmias or other complications, rather than trying to normalize it.⁹ Furosemide and hypotensive medication suspension is mandatory.

If nasogastric drainage must be continued, proper parenteral nutrition must be placed while correcting ongoing losses of fluids and electrolytes. Losses of chloride and hydrogen could be reduced with inhibition of gastric acid secretion.⁶ Prokinetics may have a role to treat ileus or even surgical correction of mechanical bowel obstruction, if present.

To proper care and monitorization of this life‑threatening situation, the patient should be admitted to an intensive care unit (ICU). Due to severe AKI, dialysis with low bicarbonate dialysate may be indicated if the patient fails to improve with conservative measures or if life‑threatening complications do not allow time for conservative correction of alkalosis. Hydrochloric acid infusion may have a role in severe cases in which dialysis is contra‑indicated.^3,8,10

Our patient was immediately admitted in ICU and he started on aggressive intravenous (IV) hydration with NaCl 0,9%, along with IV potassium supplementation and parenteral nutrition. Offending drugs where discontinued and a proton pump inhibitor was started. The patient evolved with respiratory failure, needing invasive mechanical ventilation. Twelve hours after ICU admission, arterial blood gas showed a pH of 7.60, PaCO2 of 60.0 mm Hg and bicarbonate of 58.9mmol/L, while maintaining reasonable urinary output. On the next day, due to persistence of ileus a new exploratory laparotomy was performed, with detection of dilation of the small intestine, but without identification of a mechanical obstruction. He was started on prokinetics and the ileus resolved after few days. The patient had a progressive improvement with supportive measures, with no needfor renal replacement therapy.

FOLLOW‑UP

He was discharged on September 19th completely recovered, with a Cr of 1.58 mg/dL, and his anti‑hypertensive medication was changed to captopril due to the etiology of the lithiasis. Three months after discharge his functional status was excellent (ECOG 1) and renal function was stable.

CONCLUSION

This is an extreme case of metabolic alkalosis, where a myriad of contributors gathered in a perfect storm to achieve a bicarbonate concentration above 100 mmol/L, thought to be incompatible with life and, to our knowledge, never reported in the literature. However, the pH value was maintained in life‑compatible values by an extreme respiratory compensation which may have saved the patient before treatment initiation. Despite the severity of the alkalosis and AKI there was no need for dialysis to adequately treat this patient. An approach correcting the cause and, at the same time, the perpetuators are the key factors to successfully treat a metabolic alkalosis.

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