What is the role of calcium gluconate in cardiac arrest management?

Calcium Gluconate in Cardiac Arrest

Routine administration of calcium gluconate during cardiac arrest is not recommended and may cause harm, based on the most recent high-quality evidence showing no benefit for return of spontaneous circulation and worse neurological outcomes at 90 days. 1

General Cardiac Arrest Management

Primary Recommendation

• The 2023 International Consensus strongly recommends against routine calcium administration for out-of-hospital cardiac arrest (OHCA) in adults and suggests against its use for in-hospital cardiac arrest (IHCA). 1
• Multiple randomized controlled trials and observational studies demonstrate no improvement in survival to hospital discharge when calcium is given during cardiac arrest. 1
• The most recent large trial (Vallentin et al.) was stopped early due to concerns for harm, showing statistically worse survival with favorable neurological outcomes at both 90 days and 1 year in the calcium group. 1

Evidence Against Routine Use

• In ventricular fibrillation (VF), calcium does not restore spontaneous circulation. 1
• In asystole, calcium administration fails to improve return of spontaneous circulation (ROSC) or survival to hospital discharge. 1
• Two studies found calcium administration was associated with decreased survival to hospital discharge and reduced rates of ROSC. 1
• A 2022 systematic review concluded calcium shows no benefit and can cause harm, recommending against further studies on routine use. 2

Specific Indications Where Calcium May Be Considered

Despite the recommendation against routine use, calcium may have a role in specific cardiac arrest scenarios:

Hyperkalemia with Cardiac Arrest

• When cardiac arrest occurs secondary to hyperkalemia, calcium administration may be reasonable as adjuvant therapy in addition to standard ACLS protocols. 1
• The American Heart Association recommends calcium chloride 10% (5-10 mL) or calcium gluconate 10% (15-30 mL) IV over 2-5 minutes for severe hyperkalemia with ECG changes. 3, 4
• Calcium acts as a cardioprotector by stabilizing the myocardial membrane but does not reduce potassium levels; it must be combined with therapies that shift potassium intracellularly (insulin/glucose, bicarbonate, albuterol) and promote excretion. 4
• One study of PEA arrests showed calcium improved ROSC in a subgroup with wide QRS complexes, though long-term survival was not reported. 1
• Hyperkalemia during cardiac arrest is not uncommon, with some patients developing interstitial hyperkalemia that may contribute to wide complex electromechanical dissociation (EMD). 5

Hypermagnesemia-Associated Cardiac Arrest

• Administration of calcium (calcium chloride 10% 5-10 mL or calcium gluconate 10% 15-30 mL IV over 2-5 minutes) may be considered during cardiac arrest associated with hypermagnesemia. 1, 4
• Calcium directly antagonizes the effects of magnesium on the myocardium. 3

Calcium Channel Blocker Overdose

• Administration of calcium in patients with shock refractory to other measures may be considered (Class IIb, LOE C). 1
• For calcium channel blocker toxicity, administer 0.3 mEq/kg of calcium (0.6 mL/kg of 10% calcium gluconate or 0.2 mL/kg of 10% calcium chloride) IV over 5-10 minutes, followed by an infusion of 0.3 mEq/kg per hour. 1
• Limited evidence supports calcium use in hemodynamically unstable calcium channel blocker overdose refractory to other treatments. 1, 3
• Serum ionized calcium levels should be monitored, and severe hypercalcemia (ionized calcium greater than twice the upper limits of normal) should be avoided. 1

Documented Hypocalcemia

• Calcium is indicated for symptomatic hypocalcemia or when ionized calcium levels fall below normal range, particularly in massive transfusion protocols where citrate chelates calcium. 3
• Severe hypocalcemia may occur during cardiac arrest, and in these patients calcium may augment myocardial contractility, decrease intracardiac filling pressures, and increase mean arterial pressure. 6

Beta-Blocker Overdose

• Administration of calcium in patients with shock refractory to other measures may be considered based on case reports and animal studies. 1

Dosing and Administration

Standard Dosing

• Calcium chloride 10%: 5-10 mL (500-1000 mg) IV over 2-5 minutes 3, 4
• Calcium gluconate 10%: 15-30 mL (1500-3000 mg) IV over 2-5 minutes 3, 4
• Calcium chloride provides approximately three times more elemental calcium than an equivalent volume of calcium gluconate and results in more rapid increases in ionized calcium concentration; it is preferred for critically ill patients. 3

Pediatric Dosing

• For hypocalcemia: 20 mg/kg (0.2 mL/kg of 10% calcium chloride) IV/IO by slow push for cardiac arrest or infusion over 30-60 minutes for other indications. 3
• For hyperkalemia: 100-200 mg/kg/dose via slow infusion with ECG monitoring for bradycardia. 4

Rate of Administration

• Rapid injection can cause vasodilation, decreased blood pressure, bradycardia, cardiac arrhythmias, syncope, and cardiac arrest. 7
• The rate should not exceed 200 mg/minute in adults and 100 mg/minute in pediatric patients. 7
• ECG monitoring during administration is recommended, especially in patients receiving cardiac glycosides. 7

Critical Safety Considerations

Cardiac Glycoside Interactions

• Avoid calcium administration in patients receiving digoxin or other cardiac glycosides. 7
• Hypercalcemia increases the risk of digoxin toxicity, and synergistic arrhythmias may occur if calcium and cardiac glycosides are administered together. 1, 7
• If concomitant therapy is necessary, administer calcium slowly in small amounts with close ECG monitoring. 1, 7

Administration Route and Extravasation Risk

• Administer through a central venous catheter when possible; peripheral IV extravasation can cause severe skin and soft tissue injury, tissue necrosis, and calcinosis cutis. 3, 4, 7
• If extravasation occurs or clinical manifestations of calcinosis cutis are noted, immediately discontinue administration at that site. 7
• Sustained infusions of IV calcium require central venous access. 1

Drug Incompatibilities

• Never administer sodium bicarbonate and calcium through the same line due to risk of precipitation. 4
• In patients older than 28 days, ceftriaxone and calcium may be administered sequentially only if infusion lines are thoroughly flushed between infusions. 7
• Do not administer ceftriaxone simultaneously with calcium via Y-site in any age group. 7

Monitoring Requirements

• Continuous ECG monitoring during administration is essential. 4, 7
• Stop infusion immediately if symptomatic bradycardia occurs or heart rate decreases by 10 beats per minute. 4
• Monitor serum ionized calcium levels during continuous infusions to prevent hypercalcemia. 1, 3

Common Pitfalls and How to Avoid Them

Pitfall 1: Using Calcium Routinely

• The evidence is clear that routine calcium administration during cardiac arrest provides no benefit and may worsen neurological outcomes. 1, 2
• Reserve calcium only for the specific indications outlined above (hyperkalemia, hypermagnesemia, calcium channel blocker overdose, documented hypocalcemia). 1

Pitfall 2: Confusing Calcium Chloride and Calcium Gluconate Dosing

• Calcium chloride contains approximately three times more elemental calcium per mL than calcium gluconate. 3
• When switching between formulations, adjust doses accordingly: 10 mL of 10% calcium chloride ≈ 30 mL of 10% calcium gluconate. 3, 4

Pitfall 3: Administering Too Rapidly

• Rapid bolus administration can cause life-threatening hypotension, bradycardia, and cardiac arrest. 7
• Always dilute with 5% dextrose or normal saline and infuse slowly unless treating life-threatening hyperkalemia with ECG changes. 7

Pitfall 4: Ignoring Contraindications

• Calcium is contraindicated in hypercalcemia and in neonates (≤28 days) receiving ceftriaxone due to fatal ceftriaxone-calcium precipitates. 7
• In tumor lysis syndrome with hyperphosphatemia, calcium can increase risk of calcium phosphate precipitation. 4

Pitfall 5: Expecting Calcium to Lower Potassium

• Calcium stabilizes the myocardial membrane but does not reduce serum potassium levels. 4
• Always combine with definitive potassium-lowering therapies (insulin/glucose, albuterol, diuretics, dialysis). 4

Knowledge Gaps

The evidence base has significant limitations:

• The effect of calcium remains unknown for specific subgroups such as patients with wide QRS complexes, documented hypocalcemia, or hemorrhagic shock during cardiac arrest. 1
• No high-quality studies exist specifically evaluating calcium in IHCA settings. 1
• The optimal timing and dosing of calcium for special circumstances requires further investigation. 1
• Limited data exist on the effectiveness of calcium gluconate specifically for ECG changes in hyperkalemia, with one study showing benefit only for main rhythm disorders, not non-rhythm ECG abnormalities. 8