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Hypophosphataemia

  • See also 

    Electrolyte abnormalities
    Hyperphosphataemia
    Intravenous fluids

    Key points

    1. Oral/enteral is the preferred route of phosphate administration
    2. Hypophosphataemia may be asymptomatic. Phosphate levels should be monitored in high-risk clinical scenarios
    3. Acute severe hypophosphataemia can be a life-threatening medical emergency
    4. Assess for other electrolyte abnormalities and renal function

    Background

    • Approximately 85% of body phosphate is located in bones and teeth, 14% in cells and <1% in extracellular fluid
    • Phosphate requirements depend on bone formation and growth rate. They are higher in childhood, especially in premature infants
    • Phosphate balance is closely related to calcium homeostasis
    • The terms serum phosphate and serum phosphorus are often used interchangeably, it is the phosphorus content of anionic plasma phosphate PO4(3-) that is measured

    Definition

    • The lower limit of normal for serum phosphate changes over childhood, from around 1.5mmol/L in early infancy to 0.8mmol/L by late adolescence
    • Reference ranges vary substantially by age and assay
    • Severe acute hypophosphataemia ( <0.5 mmol/L) may be associated with weakness, lethargy and paraesthesia
    • Serum phosphate below 0.3mmol/L represents a life-threatening medical emergency

    Causes of hypophosphataemia

    Gastrointestinal

    Renal

    Other

    Inadequate dietary intake

    • malnutrition

    Decreased intestinal absorption

    • vitamin D deficiency
    • phosphate binding agents eg calcium carbonate, antacids
    • malabsorption disorders eg Crohns disease
    • diarrhoea
    • vomiting or excessive gastric suctioning
    • post-op from intestinal surgery

     

    Decreased renal phosphate reabsorption

    • IV iron infusion
    • renal tubulopathy
    • hyperparathyroidism

    Increased renal phosphate excretion

    • metabolic acidosis
    • medication* (eg loop diuretics, corticosteroids)
    • acute tubular necrosis (diuretic phase)
    • volume expansion
    • hypomagnesemia, hypokalaemia
    • Fanconi’s syndrome

    Renal replacement therapy

    Internal redistribution between body compartments

    • refeeding syndrome
    • diabetic ketoacidosis
    • insulin/glucose therapy
    • sepsis
    • respiratory alkalosis
    • hungry bone syndrome

    *For advice about implicated medicines, discuss with a pharmacist or check adverse reactions in a drug prescribing resource

    Assessment

    • Assess renal function (urine output, serum urea, electrolytes and creatinine).
    • Check baseline serum calcium and albumin levels. Severe hypophosphataemia may cause hypercalcemia
    • Identify underlying cause and correct where possible
      • hypophosphataemia may be asymptomatic
      • lethargy may be the only symptom present
      • if underlying cause not evident, consider checking parathyroid hormone level, urine phosphate excretion and creatine kinase (for severe hypophosphataemia)
    • Assess for signs/symptoms of hypophosphataemia
      • Gastrointestinal: anorexia
      • Respiratory: respiratory muscle dysfunction, decreased oxygen delivery
      • Cardiac: arrhythmias, chest pain
      • Neuromuscular: muscle weakness, bone pain, altered mental status, seizure, arthralgia, coma
      • Haematological: haemolytic anaemia, impaired leukocyte and platelet function
      • Endocrine: rickets eg limb bowing or radiological finding

    Management

    Investigations

    Serum phosphate levels should be monitored, with frequency depending on the degree of the abnormality and whether the child is symptomatic

    Treatment

    Treatment should be directed at the underlying cause with an aim to return serum phosphate levels to the normal range

    • Reduce the dose in children with renal impairment. Seek specialist advice
    • Adjust dose as needed for response and tolerance

    Oral/enteral dosing

    Consider for mild to moderate asymptomatic hypophosphataemia

    Dose

    • Neonate: 1mmol/kg/day in 2-4 divided doses
      • higher doses (up to 3mmol/kg/day) are used for osteopenia of prematurity
    • Child: 2-3mmol/kg/day in 2-4 divided doses
      • Usual maximum dose 
        • Age <5 years: 3 tablets daily 
        • Age >5 years: 6 tablets daily
    • Adolescent/adult: 1-2 tablets 2-3 times per day

    Medication Forms

    Preparation

    Phosphate content

    Notes

    Phosphate effervescent tablets
    (500mg elemental phosphorus)

    16.1mmol

    Also contains:
    Sodium 469mg (20.4mmol)
    Potassium 123mg (3.1mmol)

    Administration
    For doses less than a whole tablet: disperse one tablet in 20mL of water to make a concentration of 0.8mmol/mL (25mg/mL) of phosphate. Mix until an even dispersion is formed and measure the required dose immediately 

    Monitoring
    Adverse effects may include:

    • abdominal pain, diarrhoea, nausea and vomiting
    • hyperphosphatemia (over-correction), hypocalcaemia, hypernatraemia
    • renal nephrocalcinosis (acute phosphate nephropathy) leading to acute renal failure

    Intravenous Dosing

    Indications

    • Intravenous phosphate replacement should be considered for
      • Symptomatic or severe hypophosphataemia
      • Contraindication to oral dosing (eg severe malabsorption or nil by mouth)

    Precautions

    • Seek specialist advice for intravenous phosphate replacement
      • Cardiac monitoring should be considered due to potassium content, rapid intravenous administration or overdose has risk of arrhythmia/cardiac arrest  
      • Check serum phosphate and potassium before infusion and approximately 2 hours after completion
      • Do not infuse via same IV access point or lumen as magnesium or calcium-containing intravenous fluids including parenteral nutrition 

    Dose
    0.36mmol/kg as slow infusion

    • Doses greater than 10mmol must be approved by a senior clinician
    • The dose may be repeated, if required, up to a maximum of 2mmol/kg/day (maximum 70mmol/day)
    • Consider the potassium content of intravenous phosphate preparation (see table below)
      • For patients with potassium levels near upper end of normal range or above, use phosphate formulation without potassium where available
      • Reserve potassium dihydrogen for patients requiring intravenous potassium replacement  

    Medication Forms

    Preparation

    Phosphate content

    Notes

    Potassium Dihydrogen Phosphate (10mL vial)

    1mmol/mL

    Also contains:
    Potassium 1mmol/mL

    Sodium Phosphate and Potassium Phosphate Concentrated Injection (20mL vial)

    0.67mmol/mL

    Also contains:
    Potassium 0.13mmol/mL
    Sodium 1.07mmol/mL

    Sodium Dihydrogen Phosphate
    Injection (10mL vial)

    1mmol/mL

    Also contains:
    Sodium 1mmol/mL

    Administration

    • Dilute before use
      • Peripheral line: dilute to 0.05mmol/mL or weaker
      • Central line: dilute to 0.12mmol/mL or weaker
    • Give via slow infusion over 6 hours
    • The rate of administration must not exceed 0.2mmol/kg/hour or 10mmol/hour
    • Careful and thorough mixing after dilution is essential to prevent pooling of phosphate solutions
    • Refer to local guidelines for more detailed administration information

    Monitoring
    Monitor for risk of hyperphosphataemia (due to over-correction)
    Adverse effects may include:

    • Bradycardia, hypotension, arrhythmias
    • Hyperkalaemia, hypocalcemia
    • Acute kidney injury
    • Dyspnoea, oedema
    • Extravasation injury

    Consider consultation with local paediatric team when

    The child is symptomatic or there is a significant abnormality

    Consider consultation with renal team when

    Renal dysfunction is present

    Consider transfer when

    The child is symptomatic or requires close monitoring not available in your centre

    Consider discharge when

    • The child is clinically stable with an appropriate management plan in place
    • Any acute abnormality has resolved 
  • Reference list

    1. Canada. TW et al. ASPEN Fluids, Electrolytes, and Acid-Base Disorders Handbook. 2015. American Society for Parenteral and Enteral Nutrition. U.S.A.
    2. Sydney Children’s Hospital Electrolyte Replacement Prescribing – SCH. Guideline no. 2018-036 v1. 27 March 2018. https://www.schn.health.nsw.gov.au/_policies/pdf/2018-036.pdf (viewed 28 April 2022)
    3. Lexicomp Online, Pediatric and Neonatal Lexi-Drugs Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information https://online.lexi.com/lco/action/home (viewed 28 April 2022)
    4. British National BNF for Children online https://www.medicinescomplete.com (viewed 28 April 2022)
    5. Martindale The Complete Drug Reference https://about.medicinescomplete.com/publication/martindale-the-complete-drug-reference (viewed 28 April 2022)
    6. Plover C, Porrello E. Paediatric Injectable Guidelines. 2021 Ed Flemington, Vic: The Royal Children’s Hospital Online https://pig.rch.org.au/monographs/ (viewed 28 April 2022]
    7. MIMS online https://www.mimsonline.com.au (viewed 28 April 2022) 
    8. Neonatal Formulary https://academic.oup.com/book/35484/chapter/304148569 (viewed 28 April 2022)