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You are here: Home / IBCC / Hypophosphatemia


Hypophosphatemia

May 9, 2019 by Josh Farkas

CONTENTS

  • Phosphate physiology
  • Symptoms 
  • Phosphate level
  • Causes of hypophosphatemia
  • Investigation of etiology
  • Treatment
  • Algorithm
  • Podcast
  • Questions & discussion
  • Pitfalls
  • PDF of this chapter (or create customized PDF)

phosphate physiology

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phosphate basics
  • 99% of phosphate is present within cells.
  • Symptoms from phosphate deficiency result from intracellular phosphate deficiency.   Unfortunately, we can measure only extracellular phosphate levels.   This creates some variability among patients with hypophosphatemia:
    • Symptoms tend to occur in patients with chronic hypophosphatemia and total-body deficiency (e.g. alcoholism, chronic antacid ingestion, chronic malnutrition with re-feeding syndrome).
    • Symptoms are uncommon in patients with acute shifts of phosphate out of the blood (e.g. diabetic ketoacidosis).
  • In practice, it is often difficult to tell whether hypophosphatemia represents a total-body deficiency or a transient phosphate shift.  Given the potential consequences of true phosphate deficiency, it is generally better to err on the side of phosphate repletion.
endocrine physiology
  • The most common endocrine causes of hypophosphatemia are as follows:
  • (1a) Hyperparathyroidism – as shown above, this may cause hypophosphatemia and hypercalcemia.
  • (1b) Hungry Bone Syndrome
    • Occurs immediately following resection of a parathyroid adenoma which was causing hyperparathyroidism.
    • Bone mineralization occurs, which pulls phosphate and calcium into the bone.
    • Clinically this should be easy to recognize because it occurs in the immediate postoperative period following parathyroid surgery.
  • (2) Vitamin D deficiency – this causes impaired phosphate absorption in the gut and increased phosphate excretion.
  • (3) Oncogenic osteomalacia
    • Extremely rare paraneoplastic disorder which usually occurs with small, benign tumors.
    • Tumor secretes phosphaturic hormones that reduce renal phosphate absorption and synthesis of 1,25-OH-vitamin D.
    • Clinical presentation:  hypophosphatemia with paradoxically low 1,25-OH-vitamin D levels (this is paradoxical, because normally hypophosphatemia would stimulate elevation of 1,25-OH-vitamin D).

symptoms

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neurologic
  • Seizures, paresthesias, tremor
  • Confusion, dysarthria, stupor, coma
  • May promote the development of central pontine myelinolysis
cardiac
  • Impaired contractility, heart failure
  • Arrhythmia (supraventricular and ventricular tachycardia)
muscular
  • Rhabdomyolysis
    • Rare; May mask diagnosis of hypophosphatemia by release of phosphate from muscle!
  • Muscle weakness, including diaphragm
    • May sometimes contribute to difficult weaning
other rare manifestations
  • Insulin resistance
  • Hemolysis

phosphate level

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When checking a phosphate level, consider obtaining a complete electrolyte panel (including Ca/Mg/Phos).  Electrolyte disorders tend to occur in pairs and triplets (“electrolytic disarray”).  

when should phosphate be checked ?
  • When initiating nutrition in patients at-risk for refeeding syndrome.
  • Patients with diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome (HHNS).
  • Patients on continuous renal replacement therapy (CRRT).
  • Possibly once, upon admission for all patients entering the ICU?
  • If there is clinical concern of symptoms due to hypophosphatemia.
    • In patients with difficulty weaning from ventilation (some evidence shows that hypophosphatemia may be a contributory factor by causing diaphragmatic weakness).
spurious hypophosphatemia (pseudohypophosphatemia)
  • Uncommon
  • Potential causes:  hyperbilirubinemia, mannitol, paraproteins, acute leukemia

causes of hypophosphatemia

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shifting phosphate into cells
  • Insulin
    • Diabetic ketoacidosis
    • Re-feeding syndrome
  • Acute respiratory alkalosis
  • Hungry bone syndrome (s/p surgery for hyperparathyroidism)
reduced gastrointestinal uptake
  • Inadequate oral intake
  • Chronic diarrhea
  • Drugs
    • Chronic use of antacids containing calcium, magnesium, or aluminum
increased renal loss
  • Diuresis or Dialysis
    • Diuretics (loop diuretics, acetazolamide, thiazides)
    • Osmotic diuresis (hyperosmolar hyperglycemic nonketotic syndrome, i.e. HHNS)
    • Auto-diuresis following iatrogenic volume overload
    • Post-ATN or post-obstructive polyuria
    • Hypothermia (“cold diuresis”)
    • Continuous renal replacement therapy (CRRT) – especially prolonged high-intensity runs for intoxication
  • Proximal tubule dysfunction (Type II RTA, a.k.a. Fanconi Syndrome)
  • Hyperparathyroidism
  • Medications
    • Aminoglycosides
    • IV iron
    • Tenofovir
    • Chemotherapeutic agents (especially imatinib, VEGF inhibitors, and target of rapamycin inhibitors such as temsirolimus)
  • Oncogenic osteomalacia
multifactorial
  • Alcoholism
  • Vitamin D deficiency
  • Critical illness of most types:
    • Sepsis, systemic inflammation
    • Trauma (especially head trauma)
    • Major surgery (especially cardiothoracic, aortic, or hepatic)
    • Burns

investigation of etiology

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Generally, the cause of hypophosphatemia can be determined by a history and review of labs and medications.   In rare situations where hypophosphatemia persists and the cause is unclear, a fractional excretion of phosphate might be helpful (Fe-Phos).

fractional excretion of phosphate
  • Calculated in the same fashion as fractional excretion of sodium (FeNa)
    • You can use any calculator for FeNa (just insert phosphate in place of sodium).
    • Or you can use this online calculator for fractional excretion of phosphate.
  • Fe-Phos should be <5% as a normal response to hypophosphatemia.  Thus:
    • Fe-Phos <5%:  Gastrointestinal problem, shifting into cells
    • Fe-Phos >5%:  Renal phosphate wasting
    • Multifactorial etiologies should be considered regardless of the Fe-Phos.

treatment

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cautions
  • Significant hypophosphatemia (e.g. phosphate <2 mg/dL or <0.65 mM) should generally be repleted, with the following potential exceptions:
  • (1) Renal insufficiency
    • Phosphate should be given only if truly necessary, since these patients tend to develop hyperphosphatemia over time.
  • (2) Hypercalcemia
    • Increasing phosphate may risk precipitation of calcium-phosphate in tissues (calciphylaxis).
    • Try to keep the calcium-phosphate product <70 (calcium multiplied by phosphate, both in mg/dL).
  • (3) Hypocalcemia
    • Rapid infusion of IV phosphate may reduce calcium level.
    • If hypotension occurs during infusion of IV phosphate, consider possibility of hypocalcemia.
intravenous phosphate
  • Indications:
    • Severe hypophosphatemia (<1 mg/dL or <0.32 mM)
    • Symptoms
    • Lack of enteral access
    • Malabsorption
  • Either potassium phosphate or sodium phosphate may be used, depending on the potassium level.
  • Typical dose:
    • Phosphate <1.5 mg/dL (<0.48 mM) ==> Initial dose of 30 mM phosphate infused over 4 hours
    • Phosphate >1.5 mg/dL (<0.48 mM) ==> Initial dose of 15 mM phosphate infused over 2 hours
  • Repeat electrolytes and provide more as needed.  Patients with severe hypophosphatemia often require several doses (e.g. 60-90 mM total).
  • Should probably be infused slowly:
    • Sources disagree about the safe rate of infusion.1
    • Rapid infusion may cause transient hyperphosphatemia (which leads to hypocalcemia).  However, studies suggest that infusion at rates up to 20 mM/hour are safe.  A rate of 7.5 mM/h is definitely safe (as recommended in the algorithms here):2
oral phosphate
  • Used if there isn't an indication for IV phosphate (listed above).
  • High bioavailability, but tends to cause diarrhea.
  • Available in increments of 8 mM phosphate.  One of the following options may be chosen, depending on the patient's potassium level:
    • (a) PHOS-NAK packet (8 mM phosphate, 7 mEq potassium, 7 mEq sodium)
    • (b) Oral sodium phosphate liquid
    • (c) Oral potassium phosphate liquid
  • Dosing depends roughly on patient's phosphate level, for example:
    • Phosphate <1.5 mg/dL (<0.48 mM) ==> 16 mM q6hr
    • Phosphate >1.5 mg/dL (<0.48 mM) ==> 8 mM q8hr
  • For patients with active refeeding syndrome, consider using higher doses than would otherwise be indicated based solely on the phosphate level.

algorithm

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podcast

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

  • Patients with alcoholism, diabetes, or malnutrition may initially have a normal phosphate level, but develop hypophosphatemia later on during their hospital course (following administration of carbohydrate and/or insulin).
  • Don't overlook the possibility of refeeding syndrome in patients with hypophosphatemia after initiation of nutrition.  In this situation, other electrolytes and thiamine may be needed.
  • In severe hypophosphatemia treated with IV repletion, several doses may be required.  Don't assume that a single dose will be effective.
Going further: 
  • Hypophosphatemia (Chris Nickson, LITFL)

References

1.
Felsenfeld A, Levine B. Approach to treatment of hypophosphatemia. Am J Kidney Dis. 2012;60(4):655-661. https://www.ncbi.nlm.nih.gov/pubmed/22863286.
2.
Geerse D, Bindels A, Kuiper M, Roos A, Spronk P, Schultz M. Treatment of hypophosphatemia in the intensive care unit: a review. Crit Care. 2010;14(4):R147. https://www.ncbi.nlm.nih.gov/pubmed/20682049.

The Internet Book of Critical Care is an online textbook written by Josh Farkas (@PulmCrit), an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont.


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