Hypo PO4 (< 0.8)


The Call

Overview

  • Definition
    • Mild 2.5-2.8 mg/dL
    • Moderate 1.0-2.5 mg/dL
    • Severe < 1.0 mg/dL
       
  • Synopsis
    • Rare due to ready amount of phosphate in diet, severe hypophosphatemia even rarer
      • Most common in hospitalized or ICU patients
      • Rare in isolation, usually triggered by a precipitating event or comorbidity
    • Symptoms usually not present until severe < 1.0 mg/dL
      • Severe hypophosphatemia can be life threatening
    • Repletion is generally PO unless levels are < 1.0 mg/dL
      • Then IV repletion with K-Phos, Na-Phos or a mixture
      • Caution when treating patients with renal failure
        • Risk for developing hyperphosphatemia

Etiology

  • Redistribution
    • Increased insulin secretion/administration (eg., refeeding syndrome, DKA/HHS treatment)
      • Refeeding syndrome (increased need + poor diet)
    • Extreme hyperventilation (CO2 levels < 20)
      • Including aspirin toxicity, heatstroke, NMS, hepatic encephalopathy, alcohol withdrawal
    • Hyperglycemia
    • Diabetic Ketoacidosis (DKA)
      • Acidosis and insulin administration mobilize intracellular phosphate stores
      • Serum levels may appear normal, despite a severe deficit worsened by concurrent osmotic diuresis
         
  • Malabsorption
    • Vitamin D deficiency
    • Severe, prolonged starvation
      • Often triggered by a second event like diarrhea (alcoholics predisposed)
    • Steatorrhea or chronic diarrhea
    • Hyperalimentation (most common cause in hospitalized patients)
    • Phosphate binding antacids (aluminum or magnesium containing)
       
  • Increased urinary Excretion
    • DKA, HHS
    • Hyperparathyroidism
    • Diuretics (eg., loops, thiazides, acetazolamide)
    • Vitamin D deficiency
    • Hypophosphatemic rickets
    • Tumor induced osteomalacia
    • Renal transplant (tertiary hyperparathyroidism)
    • Renal tubular acidosis
    • Fanconi syndrome (multiple myeloma, tenofivir use, Wilson's disease)
    • IV iron
    • Excessive saline diuresis
       
  • Gram negative sepsis

History/Symptoms

  • History of or current predisposing factors
  • Symptoms don't occur until levels < 2mg/dL
    • Severe hypophosphatemia: phosphorus levels in serum < 1.0 mg/dL [< 0.32 mmol/L]
  • Most common symptoms: weakness
  • CNS symptoms
    • Paresthesias, seizures, delirium
    • Ascending motor paralysis
    • Coma
  • Cardiopulmonary
    • Impaired myocardial contractility
    • Increase risk of ventricular arrhythmias
  • Musculoskeletal
    • Ophthalmoplegia, respiratory distress
    • Dysphagia, ileus, proximal myopathy
    • Ileus
  • Hematologic
    • Increased hemolysis, decreased 2,3-diphosphoglycerate (2,3-DPG) and resultant decreased O2 delivery to tissues
    • Decreased extravasation of WBCs, thrombocytopenia
    • Poor wound healing
  • Complications include hemolysis, rhabdomyolysis, CHF

Physical Exam/Signs

  • General appearance, vitals
    • Hypotensive
    • Altered mental status (eg., irritability/confusion to coma)
  • HEENT
    • Conjunctival pallor (due to hemolytic anemia)
  • Cardiovascular
    • Dysrhythmias
    • Decreased contractility
  • Pulmonary/Chest
    • Respiratory failure due to diaphragmatic weakness (decreased rate and tidal volume)
    • May have increased respiratory rate if due to respiratory alkalosis
  • Abd/GI/GU
    • Renal failure due to rhabdomyolysis
  • Musculoskeletal/Nervous System
    • Muscular weakness (most common finding)
    • Decreased deep tendon reflexes (DTRs)
    • Seizures
  • Skin/Extremities
    • Increased bleeding due to platelet dysfunction
       
  • Labs/Tests
    • Electrolytes, K+
    • Serum Phosphate, Ca2+, Mg2+
    • CPK
       
  • Other Tests/Criteria
    • EKG if indicated
       
  • Differential Diagnosis
    • Other electrolyte abnormalities
    • Diabetic Ketoacidosis
    • Hyperparathyroidism
    • Alcoholic ketoacidosis
    • Guillain-Barré syndrome
    • Botulism

Treatment

  1. Initial/Prep/Goals
    • ABCs , IV access as needed, O2, monitor
    • Respiratory failure may require mechanical ventilation
    • Treat the underlying cause
       
  2. Medical/Pharmaceutical
    • Severe Hypophosphatemia (<1.0 mg/dL):
      • Potassium phosphate (3 mmol/mL phosphate) 0.25 - 0.5 mmol/kg IV x 1, (max 80 mmol over 8 - 12h) as phosphate replacement OR
      • Sodium phosphate (3 mmol/mL phosphate) 0.25 - 0.5 mmol/kg IV x 1, (max 80 mmol over 8 - 12h) as phosphate replacement.
      • Add potassium phosphate to IV solution in place of maintenance KCL; max IV dose 7.5 mg phosphorus/kg/6h
      • To be adjusted with creatinine clearance
      • Monitor PO4, Ca q6h, switch to PO formulation when PO4 > 0.6 mmol/L
         
    • Mild to Moderate Hypophosphatemia (1.0-2.2 mg/dL):
      • Will often correct itself; treat underlying cause.
      • Hold Mg, Ca or aluminum-containing antacids (binds phosphate).
      • Sodium phosphate oral solution 4 mmol/ml (Fleet Oral Phosphosoda) 4 mL PO (16 mmol of phosphate) bid to qid. Diarrhea is the main side effect.
      • Sodium or potassium phosphate 0.25 mMoles/kg in 150-250 mL of NS or D5W at 10 mMoles/h.
      • Neutral phosphate (Nutra-Phos), 2 tab PO bid (250 mg elemental phosphorus/tab) OR
      • Phospho-Soda 5 mL (129 mg phosphorus) PO bid-tid
         
    • Acute, symptomatic
      • > 1.3 mg/dL: NaPhos or K-Phos IV at 0.08 – 0.24 mmol/kg over 6 hours (max dose 30 mmol)
      • < 1.3 mg/dL: 0.25-0.50 mmol/kg over 8-12 hours (max 80 mmol)
      • Continue IV repletion until level > 1.5 then replete PO
         
    • Asymptomatic
      • Oral phosphate: Neutra-Phos 2 capsules PO bid or Phospho-Soda 5 mL PO bid (may cause diarrhea)
      • Milk also contains 1g per liter
      • Continue repletion until level is > 2.0 mg/dL
    • Give ½ dose for reduced GFR, and give over longer period
    • Give smaller doses if patient is hypercalcemic
    • Check serum phosphate 6 hours after repletion
    • Repletion in DKA
      • Routine repletion is not recommended, as excessive repletion may lead to severe hypocalcemia and soft tissue metastatic calcification
      • It is recommended to use potassium phosphate as part of the potassium repletion in DKA: 1/3 potassium phosphate and 2/3 potassium chloride

Complications

  • Hyperphosphatemia
  • Hypocalcemia (watch for development of tetany)
  • Hypercalcemia plus IV phosphate repletion can lead to calcium phosphate deposition in tissues
     

Prevention

  • Vaccines
  • Preventative measures

Disposition

  1. Admission criteria
    • Symptomatic, or other severe underlying disorder
    • Check phosphate every 6 hours for 2 days as the serum phosphate will equilibrate with cellular stores
       
  2. Consults
    • Appropriate service based on precipitating cause
       
  3. Discharge/Follow-up instructions
    • Patient's with symptomatic hypophosphatemia will have a comorbid reason that will likely require admission
 

 

ITE 2013, Q#133. An elderly alcoholic male is brought to the hospital by his grandson, who found him in poor condition. The grandson reports that his family has not seen the patient in months. The patient says he has no health complaints, but he is obviously malnourished, dirty and unkempt, and mildly intoxicated. You admit the patient to the hospital and begin providing supportive care, including intravenous fluids with dextrose, a regular diet, and physical therapy evaluation. On the evening of the second day he becomes weak and more confused. His blood pressure is 88/56 mm Hg, and he has a seizure. Your evaluation includes the following laboratory findings:
Glucose 60 mg/dL (N 70–110)
BUN 9 mg/dL (N 6–20)
Creatinine 2.6 mg/dL (N 0.8–1.3)
Creatine kinase 480 U/L (N 38–174)
Troponin I <0.1 ng/mL (N<0.6)
Albumin 2.7 g/dL (N 3.4–4.8)
Calcium 8.2 mg/dL (N 8.6–10.0)
Phosphate 0.7 mg/dL (N 2.7–4.5)
ALT (SGPT) 68 U/L (N 10–40)
AST (SGOT) 88 U/L (N 10–30)

This episode is most likely related to abnormal levels of which one of the following?

A) Glucose
B) Creatinine
C) Creatine kinase
D) Calcium
E) Phosphate

ANSWER: E

  • Severe hypophosphatemia is a medical emergency. In poorly nourished patients, refeeding syndrome can occur. Symptoms usually develop by the second or third day of improved nutrition, and are often
    multisystemic. Findings may include weakness, confusion, dysrhythmias, respiratory failure, heart failure, hypotension, ileus, metabolic acidosis, seizures, coma, and sudden death. This constellation of problems
    results from decreased insulin secretion as stores of intracellular phosphate become depleted. Providing carbohydrates through intravenous fluids or refeeding increases insulin secretion, which stimulates cells
    to take up phosphate, causing severe hypophosphatemia. In this setting cells are unable to produce enough 2,3 diphosphoglycerate and adenosine triphosphate to meet metabolic demands.
  • While hypoglycemia is also a medical emergency, this patient’s glucose level is not low enough to cause these symptoms. Similarly, renal failure of some type is present, as is an elevated creatine kinase msuggesting rhabdomyolysis; however, neither of these problems would be expected to cause this patient’s symptoms. Hypocalcemia can cause multisystemic problems, including weakness and seizures, but the patient’s calcium level is not critically low and hypocalcemia is not associated with hypotension.