What are the causes and symptoms of acute hypocalcemia?

Acute Hypocalcemia Causes

Acute hypocalcemia most commonly results from massive blood transfusion with citrate-induced calcium chelation, post-thyroid/parathyroid surgery, and critical illness with sepsis or trauma. 1

Primary Causes of Acute Hypocalcemia

Transfusion-Related Hypocalcemia

• Citrate toxicity during massive transfusion is the leading cause in trauma and critically ill patients, as each unit of packed red blood cells or fresh frozen plasma contains approximately 3 grams of citrate that chelates serum calcium 1
• In hemorrhagic shock requiring massive transfusion, liver hypoperfusion impairs citrate metabolism, preventing the normal conversion to bicarbonate and exacerbating hypocalcemia 1
• This mechanism is particularly problematic because laboratory coagulation tests don't accurately reflect the detrimental effect on the coagulation cascade, as samples are citrated then recalcified before analysis 1

Post-Surgical Hypocalcemia

• Thyroid or parathyroid surgery is the most frequent cause of acute symptomatic hypocalcemia outside the critical care setting 2, 3
• Surgical hypoparathyroidism results in impaired PTH secretion, disrupting the key regulatory hormone for calcium homeostasis 4, 3

Critical Illness-Associated Hypocalcemia

• Hypocalcemia occurs in up to 88% of critically ill patients across all ICU settings (medical, surgical, trauma, neurosurgical, burn, respiratory, and coronary care units), regardless of sepsis presence 5
• The severity correlates with APACHE II scores and mortality (hazard ratio 1.65 for each 0.1 mmol/L calcium decrease), but does not depend on specific illness type 5
• Biological stress from surgery, fractures, injuries, childbirth, or infection increases calcium demand and decreases PTH secretion 6, 7

Intravascular Calcium Binding

• Rapid phosphate administration can acutely bind ionized calcium 2
• Medications including foscarnet and bisphosphonates can cause acute intravascular calcium chelation 2

Hypomagnesemia-Induced Hypocalcemia

• Magnesium deficiency must be identified and corrected first, as hypocalcemia will not respond to calcium administration alone when hypomagnesemia is present 8
• Hypomagnesemia impairs PTH secretion and end-organ PTH responsiveness 6, 8
• Calcium normalization requires approximately 4 days after initiating magnesium therapy, even though PTH levels normalize within 24 hours 8
• Less than 1% of total body magnesium is extracellular, so patients can have significant deficiency despite normal serum magnesium concentrations 8

Clinical Manifestations Requiring Recognition

Neuromuscular Symptoms

• Tetany is the hallmark of acute hypocalcemia (ionized calcium <0.75 mmol/L), characterized by neuromuscular irritability 2
• Mild symptoms include circumoral numbness, paresthesias of hands and feet, and muscle cramps 6, 2
• Severe manifestations include laryngospasm, focal or generalized tonic muscle cramps, and seizures 6, 2

Cardiovascular Manifestations

• QT interval prolongation occurs commonly and ionized calcium levels below 0.8 mmol/L are associated with cardiac dysrhythmias including ventricular tachycardia and fibrillation 1, 7
• Cardiac contractility and systemic vascular resistance are impaired with reduced ionized calcium 1, 7
• Myocardial dysfunction can occur acutely 2

Hematologic Effects

• Calcium is essential for fibrin polymerization and platelet function; hypocalcemia causes decreased clot strength and impaired platelet adhesion 1, 7
• Calcium acts as a cofactor for activation of factors II, VII, IX, and X, as well as proteins C and S 1
• Hypocalcemia within the first 24 hours of critical bleeding predicts mortality and transfusion needs with greater accuracy than fibrinogen, acidosis, or platelet count 1

Risk Factors and Precipitating Events

High-Risk Clinical Scenarios

• Perioperative periods, particularly thyroid/parathyroid surgery 6, 7
• Acute illness, puberty, and pregnancy 6
• Severe sepsis and pancreatitis (though magnesium/calcium substitution's impact on outcomes remains unproven in these conditions) 2

Contributing Factors

• Hypomagnesemia from any cause 6, 8, 5
• Acute renal failure 5
• Number of blood transfusions received 5
• Decreased oral calcium intake 6
• Alcohol consumption and carbonated beverage intake (especially colas) increase urinary calcium excretion 6, 7
• Loop diuretics increase urinary calcium excretion 6

Diagnostic Approach

Laboratory Assessment

• Measure pH-corrected ionized calcium (most accurate), as normal range is 1.1-1.3 mmol/L and is pH-dependent (0.1 unit pH increase decreases ionized calcium by approximately 0.05 mmol/L) 1, 7
• Check magnesium levels in all hypocalcemic patients, as hypomagnesemia must be corrected first 8
• Measure PTH levels to determine if hypoparathyroidism is present 6
• Assess renal function (creatinine) 6
• Monitor phosphorus levels 6

Critical Thresholds

• Ionized calcium <0.9 mmol/L or total corrected calcium ≤7.5 mg/dL requires prompt correction 1
• Ionized calcium <0.8 mmol/L is associated with cardiac dysrhythmias and requires urgent treatment 1, 7
• Ionized calcium <0.75 mmol/L typically manifests as tetany 2

Important Clinical Pitfalls

• Laboratory coagulation tests do not accurately reflect hypocalcemia's detrimental effect on the coagulation cascade because samples are citrated then recalcified before analysis 1
• Hypocalcemia symptoms may be confused with psychiatric conditions such as depression or anxiety 6, 7
• Administering calcium without first correcting magnesium deficiency will be ineffective 8
• While hypocalcemia associates with increased mortality, blood transfusion, and coagulopathy, no data demonstrate that prevention or treatment reduces mortality in patients with critical bleeding requiring massive transfusion 1, 7
• Patients with genetic disorders like 22q11.2 deletion syndrome have 80% lifetime prevalence of hypocalcemia 6