1. Plasma calcium concentration
mg/dL meq/L mmolL % total
Free ionized
Protein-bound
Complexed
Total 

2. Serum Ca corrections
Correction of total serum Ca for serum albumin – add 0.8 meq/L for each 1 gm reduction in albumin
Ionized Ca – can obtain if do not have a serum albumin measurement
Gadolinium – certain gadolinium salts can dramatically transiently lower measured total serum Ca 

3. Hypocalcemia – effects of change in serum pH
Alkalosis – decreases ionized Ca
Acidosis – increases ionized Ca
Clinical ramifications - if patient is acidotic and hypocalcemic treatment with NaHCO3 without addressing the hypocalcemia can further lower ionized Ca

4. Hypocalcemia – signs and symptoms
Weakness
Paresthesias
Seizures
Latent tetany – Trousseau, Chvostek signs
Hypotension
Long QT

5. Tests for latent tetany
Chvostek sign - tap the skin over the facial nerve in front of the external auditory meatus, causes an ipsilateral contraction of the facial muscles, but up to 10% of population have a positive test
Trousseau sign – inflate BP cuff on arm to 20 mmHg>systolic BP for 3-5 min & watch for carpopedal spasm, insensitive test

6. Mechanisms of hypocalcemia
Reduced GI absorption – GI disease, hypoparathyroidism, vitamin D deficiency
Renal loss – low Mg, genetic disorders, drugs (e.g. cisplatinum, cyclosporine, aminoglycosides, proton pump inhibitors)
Redistribution of Ca into: bone (post parathyroidectomy) or abdominal cavity (pancreatitis)
Binding by citrate (transfusions) or PO4 load (IV or enema)

7. Hypocalcemia in critical illness
Mechanisms: low Mg renal failure blood transfusions (citrate)
multiple mechanisms in gram negative
sepsis including probable cytokine
induction of hypoparathyroidism and
vitamin D deficiency or resistance
No proof correction of Ca affects course

8. Hypocalcemia – indications for IV Ca
Patients who are severely symptomatic – tetany, carpopedal spasm, decreased cardiac function, or prolonged QT interval
Asymptomatic patients with an acute decrease if corrected total serum Ca<7.5 mg/dl
Not an indication - neuromuscular irritability such as paresthesias and corrected total serum Ca >7.5; initial treatment with oral Ca sufficient

9. Hypocalcemia treatment with bolus intravenous Ca
Calcium gluconate – 10 mL of a 10% solution is 90 mg of elemental Ca
Calcium chloride – 10 mL of a 10% solution is 270 mg of elemental Ca
Tissue necrosis with extravasation – much more common with calcium chloride
Code cart – contains Ca chloride
Formation of insoluble Ca salts – occurs when HCO3 or PO4 is added to solution containing Ca
Hyperkalemia with marked EKG changes (with no hypocalcemia) – affects conduction not serum [K+]

10. Hypocalcemia Rx with Ca infusion
Since duration of action of IV Ca bolus is just 1-3 hours to maintain the serum Ca level may need to give IV infusion
Add 11 amps of Ca gluconate to either D5W or NS to make a 1 L solution with a Ca concentration of 1 mg/ml
Usual starting rate 1 ml/minute or mg/hour of elemental Ca

11. Hypocalcemia with concurrent hypomagnesemia
Often cannot correct the Ca unless the Mg is corrected
Give 2 gm of Mg (16 meq) of MgSO4 as a 10% solution over 10 to 20 minutes
Followed by 1 gm MgSO4 (8 meq) at 100 mL/hr
Continue intravenous MgSO4 as long as Mg < 1 mg/dL
Careful monitoring if patient has impaired renal function

12. Vitamin D nomenclature
Vitamin D – cholecalciferol D3, ergocalciferol D2
25-hydroxy vitamin D - calcidiol D3, ercalcidiol D2
Vitamin D receptor agonist - calcitriol D3 (Rocaltrol), paricalcitol D2 (Zemplar) a synthetic analog, doxercalciferol D2 (Hectoral) a synthetic prohormone

13. Measurement of vitamin D deficiency or insufficiency
Vitamin D deficiency best determined by measuring 25-OH vitamin D even though the active form is 1,25 dihydroxy vitamin D
This is because 1,25 dihydroxy vitamin D levels are often normal in vitamin D insufficiency because of a compensatory increase of PTH which then stimulates conversion of 25 to 1,25 dihydroxy vit D
25-hydroxy vitamin D levels are reported as a combination of D2 and D3
Vitamin D deficiency < 20 ng/ml
Vitamin D insufficiency ng/ml

14. Sources of vitamin D
Very few foods contain vitamin D (livers of fatty fish are the exception)
Synthesis in the skin of vitamin D3 during exposure to UV rays in sunlight is a major source
This system is exceedingly efficient and brief casual exposure such as minutes of the arms and face is equivalent to ingestion of 200 IU per day
Disabled persons and elderly may have inadequate sun exposure
Skin of those >70 does not convert vitamin D effectively
At northern latitudes there is not enough radiation to convert vitamin D, particularly during the winter

15. Vitamin D deficiency
Elderly – up to 74% deficient in vitamin D even if adequate intake; suggested guidelines in elderly IU/day
NHANES study – 42% of African American women were deficient vs 4% Caucasian
Response to bisphosphonates – may be blunted if vitamin D deficient

16. Hypocalcemia – rationale for Rx with calcitriol (Rocaltrol)
PTH stimulates the conversion of 25-hydroxy vitamin D to 1-25 dihydroxy vitamin D
So if give a patient with hypoparathyroidism vitamin D it would not be converted to the active form 1-25 dihydroxy vitamin D (calcitriol)
Calcitriol must be given in this circumstance.
Onset of action – much quicker in onset than vitamin D which may take several days
Offset of action – much quicker than vitamin D, so if develop hypercalcemia of shorter duration
Dosage - start with .25 ug bid, up to 2 ug per day
Elevated urinary Ca and nephrolithiasis – can be induced by calcitriol even if no hypercalcemia

17. Ergocalciferol vs cholecalciferol
Vitamin D2 – ergocalciferol (nephrologists use since listed in their guidelines)
Vitamin D3 - cholecalciferol, longer half-life, greater activity

18. Vitamin D dosage in Rx of chronic hypocalcemia
Simple dietary deficiency - can be corrected by the use of ergocalciferol IU/day
However in conjunction with other hypocalcemic disorders (e.g., underlying impairments in vitamin D metabolism or renal insufficiency) larger doses may be needed e.g., a 6 to 8 week regimen of 50,000 units, dosed weekly
Severe malnutrition or malabsorption – may require even higher doses

19. Oral calcium supplements
Calcium carbonate - 40% elemental Ca (Oscal 250 or 500 mg Ca per tablet or Tums ES 400 mg Ca per tablet)
Calcium acetate - 25% elemental Ca (Phoslo)
Calcium Citrate 21% elemental Ca (Citracal)
Dose – 1-2 gm of elemental calcium tid
Should give apart from meals to enhance Ca absorption

20. Symptoms of severe phosphate depletion (< 1mg/dl)
In general are due to inability to form ATP as well as impaired oxygen delivery due to a decrease in RBC 2,3 DPG: ) muscle injury - rhabdomyolysis, impaired diaphragmatic function, CHF 2) neurologic - paresthesias, dysarthria, confusion, stupor, seizures, coma ) hematologic (rare) – hemolysis, thrombocytopenia

22. Hypophosphatemia treatment
Acute moderate hypophosphatemia (1-2.5 mg/dl) - is common in hospitalized patients, often due to transcellular shifts, if asymptomatic may require no treatment except correction of underlying cause
Acute severe hypophosphatemia (< 1 mg/dl) - may require intravenous P if serious clinical manifestations

23. Intravenous phosphorus treatment for hypophosphatemia
Total body P deficit – can not be easily determined but has been demonstrated that the dosage listed below can be given safely
Infuse 0.08 to 0.16 mmol/kg in 500 mL of .45% NS over 6 hours and stop when P>1.5 mg/dl (so in a 100 kg patient this is 8-16 mm - order set in Cerner is for 10 mm)
Duration of infusion – it may take hours to replenish intracellular stores
Hypocalcemia is the main risk (binding of serum Ca by the P) especially with prolonged infusions; hyperphosphatemia

24. Phosphorus preparations
Normal dietary P about 1000 mg
1 mmol P = 31 mg
Neutraphos mg elemental P, K+ 7 meq, Na+ 7 meq
Neutra-Phos potassium mg elemental P, K+ 14 meq
Fleets Phospho-Soda – 815 mg P, Na+ 33 meq/ 5 mls
Intravenous K+ phosphate – 1.5 meq KCl/mm PO4
Intravenous Na+ phosphate meq NaCl/mm PO4
Intravenous phosphate preparations recently not always available in hospital pharmacies

25. Hypomagnesemia - signs and symptoms
Nonspecific symptoms – anorexia, nausea, apathy
Hypocalcemia – tetany, seizures, positive Chvostek and Trousseau signs
Hypokalemia – weakness, arrhythmias
Increased susceptibility to ventricular arrhythmias during myocardial ischemia

26. Significance of low serum Mg in CV disease
Mild hypomagnesemia is common with diuretics
Predisposes to cardiac arrhythmias in the settings of acute ischemic event, CHF, cardiopulmonary bypass, torsades de pointes, or in ICU patients
Myocardial infarction - with low Mg is increased risk of ventricular arrhythmias especially first 24 hours - which risk may be reduced by IV Mg
Torsades de pointes – increased risk with low Mg especially if on class Ia or III antiarrhythmics

27. Plasma magnesium concentration
mg/dL meq/L mmolL
Free
Complexed
Protein-bound
Total
( ) ( ) ( )

28. Hypomagnesemia treatment
Severe symptomatic hypomagnesemia (tetany, hypocalcemia, arrhythmias): treat intravenously: e.g., 50 meq IV over 8 to 24 hours, to maintain Mg >1 mg/dl
MgSO4 vial =1 gm MgSO4=96 mg elemental Mg=8 meq
Asymptomatic hypomagnesemia: treat with oral agents

29. Oral magnesium preparations
Normal daily dietary Mg intake 360 mg
Mag-Ox mg of elemental Mg per 400 mg tablet
Uro-Mag – 84 mg per 140 mg tablet
Sustained release (Slow-Mag) - 64 mg per tablet
Typically 240 mg of elemental Mg is given for dietary deficiency, more severe deficiency may require up to 720 mg/day elemental Mg
major side effect - diarrhea

30. Hypermagnesemia
Urinary Mg excretion can increase more than fivefold in response to a Mg load thus hypermagnesemia is typically only seen in the setting of renal failure when a very large Mg load is given intravenous, oral, via enema

31. Hypermagnesemia - clinical manifestations
Mg 4-6 meq/L – lethargy, drowsiness, diminished reflexes
Mg 6-10 meq/L – somnolence, hypocalcemia, absent reflexes, low BP, bradycardia, EKG changes (with IV Mg in eclampsia usual level 5-7 meq/L)
Mg >10 meq/L – muscle paralysis, complete heart block, cardiac arrest

32. Hypermagnesemia – signs and symptoms
3 types of symptoms are seen when Mg >4 meq/L : ) neuromuscular effects (curare like) ) cardiovascular effects (Ca and K channel blockade) ) hypocalcemia (PTH suppression)

33. Hypermagnesemia – treatment of symptomatic patient
If renal function is normal cessation of Mg allows prompt restoration of normal levels
If renal function is impaired hemodialysis is effective in removing Mg
In cases with severe symptoms mg elemental Ca over 5-10 minutes is effective antagonist

34. Key points
Main risk of IV Mg is giving to azotemia patients and development of hypermagnesemia
Main risk of IV P is binding to serum Ca causing hypocalcemia, usually with prolonged infusions not adequately followed
Main risk of IV Ca - infiltration of vein and tissue necrosis, especially with calcium chloride
If hypocalcemia consider may also be low [Mg]
If hypokalemia consider may also be low [Mg]
Hypermagnesemia – inhibit effects with IV Ca