INTRODUCTION — The patient with alcohol use disorder is prone to severe hypophosphatemia, particularly when admitted to the hospital. However, the fall in the serum phosphate concentration may not become prominent until 12 to 36 hours after admission. This sequence is due to underlying chronic phosphate depletion, complicated by acute shifts of phosphate into the intracellular compartment. (See 'Etiology' below.)
The causes and treatment of hypophosphatemia in the patient with alcohol use disorder will be reviewed here. The major causes of hypophosphatemia; the clinical manifestations of hypophosphatemia, most of which are due to intracellular phosphate depletion, and the diagnosis and treatment of hypophosphatemia in the general population are discussed elsewhere:
●(See "Hypophosphatemia: Causes of hypophosphatemia".)
●(See "Hypophosphatemia: Clinical manifestations of phosphate depletion".)
●(See "Hypophosphatemia: Evaluation and treatment".)
ETIOLOGY — Hypophosphatemia can result from reduced intestinal phosphate absorption and/or increased phosphate excretion (table 1) [1]. Both mechanisms may be operative in patients with alcohol use disorder:
●Decreased intestinal phosphate absorption can result from poor dietary intake of both phosphate and vitamin D, binding of dietary phosphate by antacids given to treat recurring gastritis (eg, calcium carbonate), and/or reduced net intestinal phosphate absorption, which may be induced by chronic diarrhea. (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Decreased intestinal absorption'.)
●Increased urinary phosphate excretion due to reduced proximal phosphate reabsorption can result from secondary hyperparathyroidism induced by vitamin D deficiency; therefore, 25(OH)D levels should be measured in patients with alcohol use disorder exhibiting hypophosphatemia. Alternatively, alcohol may directly promote urinary phosphate wasting by causing generalized proximal tubule dysfunction, which results in reduced phosphate reabsorptive capacity in the nephron. This proximal tubule dysfunction typically improves within days of abstinence from alcohol [2]. The physiology of phosphate handling within the nephron is discussed elsewhere. (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Increased urinary excretion'.)
In addition, chronic alcohol use disorder can induce cellular phosphate depletion [3]. This is clinically important since the clinical manifestations of hypophosphatemia are thought to be largely due to cellular phosphate depletion. (See "Hypophosphatemia: Clinical manifestations of phosphate depletion", section on 'Extraskeletal effects of phosphate depletion'.)
After hospital admission — Although phosphate depletion is common in patients with alcohol use disorder admitted to the hospital, the fall in the serum phosphate concentration, occasionally to less than 1 mg/dL (0.32 mmol/L), may not become prominent until 12 to 36 hours after admission, due to movement of extracellular phosphate into the cells [4,5]. (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Internal redistribution'.)
Two factors may contribute to this shift:
●Patients with alcohol use disorder usually receive intravenous therapy with dextrose-containing solutions. Glucose stimulates insulin release, which promotes phosphate uptake by the cells as phosphorylated glucose intermediates [5]. If dextrose-containing infusions are avoided or discontinued, a shift of extracellular phosphate into cells may still occur due to refeeding-induced insulin release.
●Acute respiratory alkalosis may result from alcohol withdrawal or other causes of hyperventilation. The elevation in extracellular pH produces a similar pH change within the cells since carbon dioxide can rapidly diffuse across cell membranes. The ensuing intracellular alkalosis stimulates intracellular phosphofructokinase, leading to an increase in glycolysis and movement of phosphate into cells.
Thus, serial monitoring of the serum phosphate concentration is warranted when patients with alcohol use disorder are admitted to the hospital.
Hypophosphatemic patients with alcohol use disorder may have a myopathy due to both phosphate depletion and alcohol and are at risk for clinically significant rhabdomyolysis [6]. The release of intracellular phosphate from damaged muscle cells may be one reason why two potentially fatal sequelae of hypophosphatemia—respiratory failure and severe central nervous system dysfunction—are rarely seen in patients with alcohol use disorder. (See "Hypophosphatemia: Clinical manifestations of phosphate depletion" and "Rhabdomyolysis: Clinical manifestations and diagnosis".)
TREATMENT — The approach to phosphate repletion takes into account the serum phosphate concentration, the presence or absence of overt symptoms of hypophosphatemia, and whether the patient can take oral therapy. If possible, we prefer oral rather than intravenous phosphate therapy since intravenous repletion can lead to hyperphosphatemia that may result in serious complications such as hypocalcemia, acute kidney injury, and arrhythmias. (See "Hypophosphatemia: Evaluation and treatment", section on 'Intravenous dosing'.)
We suggest the following approach:
●In asymptomatic patients with a serum phosphate less than 2 mg/dL (0.64 mmol/L), we give oral phosphate therapy since many of these patients have myopathy and weakness that are not clinically apparent.
●The treatment of symptomatic patients varies with the severity of the hypophosphatemia:
•We treat with oral phosphate if the serum phosphate is 1 to 1.9 mg/dL (0.32 to 0.63 mmol/L).
•We treat with intravenous phosphate if the serum phosphate is less than 1 mg/dL (0.32 mmol/L) and switch to oral replacement when the serum phosphate exceeds 1.5 mg/dL (0.48 mmol/L).
●We stop phosphate repletion when the serum phosphate is greater than or equal to 2 mg/dL (0.64 mmol/L) unless there is an indication for chronic therapy such as persistent urinary phosphate wasting.
Phosphate repletion can be achieved with sodium and/or potassium phosphate. Oral repletion is most often achieved with a combined preparation of sodium and potassium phosphate, while sodium phosphate is preferred for intravenous therapy.
Oral phosphate therapy — Although there are no available data on oral phosphate repletion in patients with alcohol use disorder, we use a dose of 15 to 20 mg/kg (0.48 to 0.64 mmol/kg) per day. This dose is lower than that given to patients with hypophosphatemia due to renal phosphate wasting in whom raising the serum phosphate will increase phosphate excretion, thereby limiting the increase in serum phosphate. If present, a defect in proximal tubular phosphate reabsorption is usually mild in patients with alcohol use disorder and begins to reverse soon after admission to the hospital [2]. (See "Hypophosphatemia: Evaluation and treatment", section on 'Treatment'.)
Intravenous phosphate therapy — There are two main indications for intravenous phosphate therapy in patients with alcohol use disorder: an inability to take or tolerate oral phosphate supplementation, or a serum phosphate concentration below 1 mg/dL (0.32 mmol/L) in patients who have overt symptoms of hypophosphatemia.
The dose of intravenous phosphate is the same in patients with and without alcohol use disorder. Because of the potential adverse effects of inducing hyperphosphatemia, the serum phosphate concentration should be measured every six hours. Intravenous phosphate supplementation should be discontinued when the serum phosphate is above 1.5 mg/dL (0.48 mmol/L). Intravenous phosphate repletion is discussed in detail elsewhere. (See "Hypophosphatemia: Evaluation and treatment", section on 'Treatment'.)
Avoidance of dextrose-containing fluids — As mentioned above, hypophosphatemia in patients with alcohol use disorder often occurs or is exacerbated after admission to the hospital due to phosphate movement from the extracellular fluid into the cells. This may be driven in part by the release of insulin following the administration of dextrose-containing intravenous fluids. Thus, dextrose-containing fluids should not be given in patients who are hypophosphatemic at presentation and who do not have an indication for dextrose therapy (eg, hypoglycemia, alcoholic ketoacidosis). (See 'After hospital admission' above and "Fasting ketosis and alcoholic ketoacidosis".)
Vitamin D — Vitamin D deficiency may contribute to hypophosphatemia in patients with alcohol use disorder and should be corrected if present. (See 'Etiology' above and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Fluid and electrolyte disorders in adults".)
SUMMARY AND RECOMMENDATIONS
●The patient with alcohol use disorder often has chronic phosphate depletion and, after admission to the hospital, is prone to severe hypophosphatemia resulting from redistribution of extracellular phosphate into the cells. This intracellular shift can be mediated by one or both of two mechanisms: the release of insulin induced by the administration of dextrose-containing fluid and/or refeeding, and acute respiratory alkalosis. (See 'Introduction' above and 'After hospital admission' above.)
●The major causes of chronic phosphate depletion in the patient with alcohol use disorder include poor dietary intake of both phosphate and vitamin D, binding of dietary phosphate by antacids used to treat recurring gastritis, chronic diarrhea, and increased urinary phosphate excretion, which can result from secondary hyperparathyroidism induced by vitamin D deficiency and/or a proximal tubular defect associated with alcohol use disorder. (See 'Etiology' above.)
●After admission to the hospital, the acute shift of phosphate into cells is primarily caused by increased insulin release due to intravenous solutions containing dextrose, but this may also result from acute respiratory alkalosis. (See 'After hospital admission' above.)
●In patients with alcohol use disorder who have hypophosphatemia and a serum phosphate less than 2 mg/dL (0.64 mmol/L), we suggest phosphate repletion (Grade 2C). Even if these patients are not overtly symptomatic, they may have myopathy and weakness that are not clinically apparent. We suggest the following approach (see 'Treatment' above):
•In asymptomatic patients with a serum phosphate less than 2 mg/dL (0.64 mmol/L), we give oral phosphate therapy.
•The treatment of symptomatic patients varies with the severity of the hypophosphatemia: oral phosphate if the serum phosphate is 1 to 1.9 mg/dL (0.32 to 0.63 mmol/L) and intravenous phosphate if the serum phosphate is less than 1 mg/dL (0.32 mmol/L), with a switch to oral replacement when the serum phosphate exceeds 1.5 mg/dL (0.48 mmol/L).
•We stop phosphate repletion when the serum phosphate is greater than or equal to 2 mg/dL (0.64 mmol/L) unless there is an indication for chronic therapy such as persistent urinary phosphate wasting.
●When using oral therapy in patients with alcohol use disorder who have hypophosphatemia, we usually treat with 15 to 20 mg/kg (0.48 to 0.64 mmol/kg) per day. (See 'Oral phosphate therapy' above.)
●The dose of intravenous phosphate is the same in patients with or without alcohol use disorder. Because of the potential adverse effects of inducing hyperphosphatemia, the serum phosphate concentration should be measured every six hours. (See 'Intravenous phosphate therapy' above and "Hypophosphatemia: Evaluation and treatment", section on 'Intravenous dosing'.)
●Dextrose-containing intravenous fluids should be avoided in patients with alcohol use disorder who are hypophosphatemic at presentation and who do not have an indication for dextrose therapy (eg, hypoglycemia, alcoholic ketoacidosis). (See 'Avoidance of dextrose-containing fluids' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Zalman S Agus, MD, who contributed to an earlier version of this topic review.
