If both the albumin and total plasma calcium levels are below normal, the low calcium level may be clinically unimportant i. One formula to determine the significance of a low total calcium is to correct the calcium upward by. One limitation of this value is that the total plasma calcium and the ionized calcium do not rise and fall proportionately. The corrected calcium is an estimate of the true ionized calcium.
A retrospective study of serum calcium levels in a hospital population in Malaysia. Med J Malaysia ; 50 —9. Prevalence and predictive value of ionized hypocalcemia among critically ill patients. Acta Anaesthesiol Scand ; 47 —9. Baird GS. Ionized calcium. Clin Chim Acta ; — Orrell DH. Albumin as an aid to the interpretation of serum calcium. Clin Chim Acta ; 35 —9. Interpretation of serum calcium in patients with abnormal serum proteins.
Br Med J ; 4 —6. Correcting the calcium. Br Med J ; 1 Variation in plasma calcium with induced changes in plasma specific gravity, total protein, and albumin. Br Med J ; 4 —3. Investigating hypocalcaemia. BMJ ; :f Failure of total calcium corrected for protein, albumin, and pH to correctly assess free calcium status. J Clin Endocrinol Metab ; 46 — Albumin-corrected calcium and ionized calcium in stable haemodialysis patients.
Nephrol Dial Transplant ; 15 —6. Nephrol Dial Transplant ; 24 —8. The nordic reference interval project recommended reference intervals for 25 common biochemical properties. Scand J Clin Lab Invest ; 64 — Bruunhuus I, Magdal U. Kompendium - Kompendium i Laboratoriemedicin online [Edited ].
Creatininium reference intervals for corrected methods. Reference intervals for serum creatinine concentrations: assessment of available data for global application. Clin Chem ; 54 — A formula to predict corrected calcium in haemodialysis patients.
Nephrol Dial Transplant ; 23 —8. An estimated glomerular filtration rate equation for the full age spectrum. Nephrol Dial Transplant ; 31 — Prevalence of chronic kidney disease in the United States. JAMA ; — Comparison of serum total calcium, albumin-corrected total calcium, and ionized calcium in patients with suspected calcium disorders.
Scand J Clin Lab Invest ; 49 — Derivation and internal validation of an equation for albumin-adjusted calcium. BMC Clin Pathol ; 8 Newson RB. Interpretation of Somers' D under four simple models [Edited ].
Metz CE. Basic principles of ROC analysis. Semin Nucl Med ; 8 — Reference intervals and age and gender dependency for arterial blood gases and electrolytes in adults. Clin Chem Lab Med ; 49 — Like PTH, it increases plasma calcium by resorbing bone and decreasing calcium excretion. The uncontrolled action of PTHrP inevitably results in abnormal loss of calcium from bone and consequent hypercalcemia.
Direct destruction of bone tissue osteolysis by tumor cells that have metastasized to bone can also result in hypercalcemia; this is the principal mechanism of the hypercalcemia associated with multiple myeloma. Generally speaking, hypercalcemia develops late in malignant disease and is a poor prognostic sign [24]. It is still important to detect because treatment aimed at normalizing calcium provides relief from symptoms of hypercalcemia, which in turn materially improves the quality of life of affected cancer patients [25].
Rare causes of hypercalcemia [26] include chronic renal failure, hyperthyroidism, sarcoidosis and tuberculosis. Some drugs, including thiazide diuretics and lithium, can precipitate hypercalcemia, as can ingestion of excessive vitamin D. Hypocalcemia is much less common than hypercalcemia [27] except in two patient groups: the critically ill and neonates.
The conditions most frequently associated with hypocalcemia in this patient group are sepsis, acute pancreatitis, acute renal failure, severe burns, trauma with rhabdomyolysis, alkalosis and massive blood transfusion. Hypocalcemia is relatively common in the neonatal intensive care unit. The normal transition from an intrauterine environment to physiological independence at birth includes a rapid reduction in plasma calcium concentration. In some babies, most notably the premature, those with low birth weight and those born to diabetic mothers, this physiological reduction is exaggerated and transient hypocalcemia develops due to inadequate PTH response of immature parathyroid glands [29].
In general, the range and severity of symptoms associated with hypercalcemia reflect the severity of the increase. Mild hypercalcemia, roughly defined as ionized calcium in the range 1. These may include gastrointestinal nausea, vomiting, constipation and neuropsychiatric lethargy, depression, confusion ; psychosis, seizures and coma may ensue. Cardiac arrest can occur if hypercalcemia is particularly severe. The effect of hypercalcemia on renal function is manifest acutely as polyuria and resulting polydipsia thirst.
Long-standing chronic hypercalcemia, even if mild, predisposes to urine-stone formation and calcium-induced damage to renal tubule cells that can progress to renal failure. Mild hypocalcemia, roughly defined as ionized calcium in the range 0. Most common signs and symptoms associated with more severe hypocalcemia are manifestations of neuromuscular irritability, including paresthesia of peripheral extremities, muscle cramps, tetany and seizures.
Laryngeal spasm may restrict normal respiration and the effect on cardiac contractility may be evident as arrhythmias; ECG changes include prolonged QT interval and T-wave inversion. Markedly severe hypocalcemia can cause cardiac arrest.
Long-standing hypocalcemia is associated with risk of cataracts. Measurement of ionized calcium is made using calcium ion-selective electrode ISE direct potentiometry. A reference method [30] has been described that is the basis of all routine methods available in blood gas and electrolyte analyzers. All that is required of the operator is introduction of sample whole blood, serum or plasma into the analyzer; results are available within a minute or two.
Despite the consensus that ionized calcium, rather than total calcium, is the preferred measure of calcium status and that ionized calcium measurement is simpler and faster, total calcium continues to be measured in clinical laboratories.
Ionized calcium measurement has in general been confined to point-of-care settings such as recovery room, intensive care, emergency rooms and operating theaters.
One of the reasons for the slow adoption of ionized calcium is that blood collection and preservation requirements are far more exacting than those required for measurement of total calcium. It is vital that the pH of a blood sample for ionized calcium estimation is preserved because calcium binding and therefore ionized calcium concentration is pH dependant. For this reason, blood must be collected anaerobically to minimize the in vitro decrease in pH that would result from aerobic metabolism.
At this temperature whole-blood samples can be stored for up to 4 hours. For whole-blood estimation, the most suitable if results are required urgently, the sample must be collected into a syringe containing the anticoagulant heparin in a lyophilized dried state. The use of standard lithium heparin is associated with significant potential error because heparin binds calcium, leading to artefactually reduced ionized calcium concentration. The magnitude of this error is dependant on heparin concentration.
Whatever the heparin formulation used, it is essential for accurate results that the correct volume of blood is sampled to achieve correct heparin concentration and that blood and anticoagulant are well mixed immediately after sampling. Blood collected for serum estimation must be processed anaerobically. Samples should ideally be centrifuged at low temperature and the cap should not be removed prior to analysis.
Full recommendations for collection, transport and storage of specimens for ionized calcium are published [31].
The maintenance of plasma ionized calcium concentration within well-defined limits is essential for the many life-preserving physiological and cellular pathways that depend on ionized calcium. The action of two hormones, parathyroid hormone and calcitriol, is of major importance in this regard. A range of clinical conditions — some very common — are associated with disturbance in calcium metabolism and resulting abnormality in ionized calcium concentration.
If sufficiently severe, these changes in plasma ionized calcium concentration have profound adverse effect and may actually threaten survival. Before the development of a reliable means of accurately measuring ionized calcium concentration in the mid-to-late s, the only means of assessing calcium status was to measure total calcium concentration in plasma.
Because this does not accurately reflect ionized calcium concentration in some clinical situations, it is a less satisfactory alternative. For a number of mainly logistical reasons, it continues to be used, but measurement of ionized calcium rather than total calcium is widely considered mandatory for some patient groups, most notably the critically ill. May contain information that is not supported by performance and intended use claims of Radiometer's products.
Janet Simons on June 26, By Dr. Janet Simons biography, no disclosures What gap I have noticed Calcium levels are commonly ordered in both primary and acute care in patients with a variety of signs and symptoms.
What data addresses this gap There is considerable evidence that application of the Payne formula tends to misclassify the calcium status of patients and performs less well than simply evaluating uncorrected total calcium. What I recommend practice tips Formulae to adjust total calcium for the albumin concentration should be abandoned. Measurement of ionized calcium is recommended over total calcium when calcium homeostasis is in question.
If this level is abnormal, confirmation with ionized calcium may be sought prior to further workup or therapy. Where ionized calcium is not available, total calcium should be assessed without the application of any correction formula.
Order serum albumin only if clinically indicated for reasons other than adjusting total calcium. Interpretation of serum calcium in patient with abnormal serum proteins. Br Med J. DOI: Corrected calcium formula in routine clinical use does not accurately reflect ionized calcium in hospital patients.
Canad J Gen Int Med. Misclassification of calcium status based on albumin-adjusted calcium studies in a tertiary hospital setting. Clin Chem. Albumin-adjusted calcium is not suitable for diagnosis of hyper- and hypocalcemia in the critically ill. Crit Care Med. A comparison of corrected serum calcium levels to ionized calcium levels among critically ill surgical patients.
Am J Surg. Arch Geron Geri. Albumin-corrected calcium and ionized calcium in stable haemodialysis patients. Nephrol Dial Transplant. A comparison of corrected serum calcium levels to ionized calcium levels in haemodialysis patients. Ann Biol Clin Paris. Derivation and internal validation of an equation for albumin-adjusted calcium. BMC Clin Pathol. View Antonio JM. New predictive equations for serum ionized calcium in hospitalized patients. Med Princ Pract. Should total calcium be adjusted for albumin?
A retrospective observational study of laboratory data from central Norway. BMJ Open. Albumin-adjusted calcium and ionized calcium for assessing calcium status in hospitalized patients. Carbamylation of albumin is a cause for discrepancies between albumin assays. Clinica Chimica Acta. Increased absolute calcium binding to albumin in hypoalbuminaemia. J Clin Pathol. View Glendenning P. It is time to start ordering ionized calcium more frequently: preanalytical factors can be controlled and postanalytical data justify measurement.
Ann Clin Biochem. A practical approach to hypercalcemia. Am Fam Physician. Margaret Smith June 26, at pm Permalink. Duncan Etches June 26, at pm Permalink.
Vahid Salimpour July 11, at am Permalink. Philip Goldwasser December 14, at pm Permalink. Leave a Reply Click here to cancel reply. This communication reflects the opinion of the author and does not necessarily mirror the perspective and policy of UBC CPD. Comments are moderated according to our guidelines. Visit ubccpd. Previous Next. Click here to print this article.
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