What is the most adverse effect that can occur after a massive blood transfusion of cold blood, such as Hypocalcemia (low calcium levels) and Alkalosis (elevated blood pH) due to citrate chelation of serum Calcium (Ca)?

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From the Guidelines

The most adverse effect that can occur after massive blood transfusion of cold blood is hypocalcemia and alkalosis due to citrate chelating of serum calcium (option A). When large volumes of cold blood are rapidly transfused, the citrate preservative in stored blood binds to calcium in the recipient's bloodstream, leading to a decrease in ionised calcium concentration, which is essential for the formation and stabilisation of fibrin polymerisation sites and many platelet-related functions 1. This chelation of calcium can lead to symptomatic hypocalcemia, which may manifest as cardiac arrhythmias, hypotension, muscle cramps, and tetany. Additionally, the metabolism of citrate in the liver produces bicarbonate, which can cause metabolic alkalosis. Some key points to consider include:

  • The normal range of ionised calcium (Ca2+) is 1.1–1.3 mmol/L and is pH-dependent, with a 0.1 unit increase in pH decreasing ionised calcium concentration by approximately 0.05 mmol/L 1.
  • Ionised calcium levels are easily monitored, as they are included as a standard part of a blood gas analysis by the majority of blood gas analysers available on the market 1.
  • Transfusion-induced hypocalcaemia, with ionised Ca2+ levels below 0.9 mmol/L or serum total corrected calcium levels of 7.5 mg/dL or lower, should be corrected promptly, as ionised Ca2+ levels below 0.8 mmol/L are associated with cardiac dysrhythmias 1. While febrile non-hemolytic reactions and hemolytic reactions are potential complications of blood transfusions, they are not specifically related to the temperature of the blood or the massive volume being transfused, making hypocalcemia and alkalosis the most significant adverse effect in this scenario.

From the FDA Drug Label

The safety of Calcium Gluconate Injection for long term use has not been established. Calcium Gluconate Injection is a form of calcium indicated for pediatric and adult patients for the treatment of acute symptomatic hypocalcemia. The most common adverse events with Calcium Gluconate Injection are local soft tissue inflammation and necrosis, calcinosis cutis and calcification that are related to extravasation.

The most adverse effect that can occur after massive blood transfusion of cold blood is Hypocalcaemia due to citrate chelating of serum calcium, as calcium gluconate is used to treat acute symptomatic hypocalcemia 2.

  • Key points:
    • Hypocalcaemia is a condition where the blood calcium levels are low.
    • Citrate, a preservative in blood products, can chelate calcium, leading to hypocalcaemia.
    • Calcium gluconate is used to treat hypocalcaemia.
    • Massive blood transfusion of cold blood can lead to hypocalcaemia due to citrate chelation of serum calcium.

From the Research

Adverse Effects of Massive Blood Transfusion

The most adverse effect that can occur after massive blood transfusion of cold blood is:

  • Hypocalcaemia and alkalosis, which is caused by citrate chelating of serum calcium 3, 4

Causes of Hypocalcaemia and Alkalosis

Hypocalcaemia and alkalosis can occur due to:

  • Citrate toxicity, which can lead to electrolyte abnormalities, including hypocalcemia 3
  • The citrate preservative in blood products, which binds to the patient's endogenous calcium, rendering it inactive 4

Comparison with Other Options

Other options, such as:

  • Febrile non-haemolytic reaction, are possible complications of blood transfusion, but are not directly related to the use of cold blood 5
  • Haemolytic reaction, is a possible complication of blood transfusion, but is not the most adverse effect associated with massive blood transfusion of cold blood 5, 6

Importance of Monitoring and Education

Monitoring and education are crucial in preventing and managing hypocalcemia and alkalosis, as:

  • Lack of knowledge and national standards may be root causes for hypocalcemia 4
  • Educational interventions, such as innovative videos, can be effective for enhancing staff members' knowledge and improving patient care 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hypocalcemia and Massive Blood Transfusions: A Pilot Study in a Level I Trauma Center.

Journal of trauma nursing : the official journal of the Society of Trauma Nurses, 2019

Research

Risks and side effects of therapy with plasma and plasma fractions.

Best practice & research. Clinical haematology, 2006

Research

Massive blood transfusion.

Anaesthesia and intensive care, 1980

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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