Citrate Toxicity During Massive Blood Transfusion

Dzik, Walter H.; Kirkley, Scott A.

doi:10.1016/s0887-7963(88)70035-8

Cited by 133 publications

(67 citation statements)

References 72 publications

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“…However, WBCT did not significantly change at 3 and 4 mmol/kg/hr of citrate despite the appearance of clinical signs that are considered to be related to ionized hypocalcemia (Kishimoto et al, 2002;Fukuda et al, 2002). In addition, electrocardiographic changes such as prolonged Q-T intervals and T wave alternans or depressions in arterial pressure and systemic vascular resistance are induced at above similar blood Ca 2+ levels in studies with pigs, dogs or humans (Dzik and Kirkley, 1988;Scheidegger et al, 1980;Liu et al, 1992;Olson et al, 1977;Howland et al, 1977;Bunker et al, 1962;Drop and Scheidegger, 1979). Thus, the effect on WBCT caused by a decrease in serum Ca 2+ is considered minimal compared with cardiovascular and hemodynamic effects as well as clinical signs.…”

Section: Discussionmentioning

confidence: 99%

“…These include the activation of factor IX, the activation of factor X by IXa, VIIIa and phospholipid, the activation of factor X by tissue factor and VIIa, the cleavage of prothrombin to thrombin by prothrombinase and the crosslinking of fibrin by factor XIIIa (Dzik and Kirkley, 1988). However, whether blood coagulation is affected by a decrease in the Ca 2+ level resulting from citrate infusion has not yet been confirmed.…”

Section: On the Other Hand Camentioning

confidence: 99%

“…The toxic effects of citrate, including tetany, a reduction in blood pressure and prolonged electrocardiographic Q-T intervals, result from a decrease in blood ionized calcium (Ca 2+ ) levels caused by its chelating action (Dzik and Kirkley, 1988;Scheidegger et al, 1980;Corbascio and Smith, 1967;Davis et al, 1995;Nakasone et al, 1954). The decreased blood Ca 2+ level is thought to be related to the citrate infusion rate (Kahn et al, 1979), and significant changes in clinical signs, cardiovascular system and hemodynamic functions are induced at blood Ca 2+ levels below 0.8 mmol/l in swine and humans (Liu et al, 1992;Martin et al, 1990;Olson et al, 1977).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Whole Blood Clotting Time in Rats With Ionized Hypocalcemia Induced by Rapid Intravenous Citrate Infusion

et al. 2006

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-Although the toxic effects of citrate including hemodynamic and cardiovascular changes result from a decrease in ionized calcium levels in serum due to chelating action, these effects of citrate on blood coagulation have not yet been fully clarified. The present study examines whether serum citrate and ionized calcium levels affect whole blood clotting time in rats using the test tube method in which citrate is administered by rapid intravenous infusion. Citrate was infused via the tail vein into 10 rats at 3, 4 or 5 mmol/kg/hr for 1 hr, and then whole blood clotting time, serum citrate and ionized calcium levels were determined. Whole blood clotting time did not significantly change at citrate infusion rates of 3 and 4 mmol/kg/hr. However, at 5 mmol/kg/hr, whole blood clotting time was significantly prolonged by a factor of 2.1 relative to the untreated group, when the serum citrate level was 10.03 ± 1.39 mmol/l (59.0-fold higher than that in the untreated group) and the serum-ionized calcium level was 0.29 ± 0.02 mmol/ l (0.2-fold lower than that in the untreated group). These results suggest that whole blood clotting time is significantly prolonged in rats with severe ionized hypocalcemia.

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Section: Discussionmentioning

confidence: 99%

Section: On the Other Hand Camentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Whole Blood Clotting Time in Rats With Ionized Hypocalcemia Induced by Rapid Intravenous Citrate Infusion

et al. 2006

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“…These changes, however, are immediately reversible in such short periods of transfusion. The administration of 4 FFP/h over a period of 8 h leads to no hemodynamic impairment [88] and only to a small extent of hypocalcemia of 0.76 mmol [63]. Kinetic studies with infusions of citrate to dogs and men, in a dose corresponding to 3 FFP/5 min over a period of 20 min, led to a 10-20-fold increasing concentration of citrate and a decrease of both cardiac work and the systolic blood pressure.…”

Section: Effects Of Hypocalcemiamentioning

confidence: 96%

“…Metabolism happens above all in mitochondrias so that tissues with a high density of mitochondrias show a high content of aconitase, the enzyme responsible for the metabolism of citric acid; these tissues are liver, skeletal muscle and kidneys. Citrate itself is not a toxic substance [63]. Citrate possess 3 negatively charged carboxyl groups at a pH of about 7.0.…”

Section: Hypocalcemiamentioning

confidence: 99%

Massive Transfusion and Its Influence on Oxygen Transport and Electrolyte Balance

Schmitt¹,

Lackes²

2000

Transfus Med Hemother

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During the process of storing erythrocyte-containing blood products, components of the preservatives and modifications of the erythrocyte function cause disorders of the electrolyte and acid-base balance as well as a deficiency of 2,3-diphosphoglycerate (2,3-DPG). Thereby transitory hyperkalemias may occur in the course of a massive transfusion, if the patient has a shock or another disturbance of the regulating mechanisms caused by diabetes mellitus or a treatment with β-blockers or ACE inhibitors. During the treatment with blood components, hypocalcemia and hypomagnesemia may develop after a dose of more than 12 fresh frozen plasms (FFP) per hour, if the metabolism of citrate, which binds bivalent cations as a chelate, is disturbed by hypothermia, shock or during the anhepatic stage of a liver transplantation. As a consequence, a low-output syndrome as well as tachyarrhythmias and torsades de pointes may develop. Whether the decrease of the 2,3-DPG level with the accompanying leftward shift of the oxyhemoglobin dissociation curve brings about a deficiency of the oxygen supply of the organs, has not yet been verified by experiment. The studies presented rather point at morphological changes of the erythrocytes due to the storage as the cause of the disturbances of capillary perfusion. For this reason patients with impending organ failure or marked disturbances of the coronary or cerebral perfusion should be transfused with packed red blood cells (RBCs) not older than 14 days.

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Mechanisms of adverse effects during hemapheresis

Strauss

1996

J. Clin. Apheresis

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Citrate Toxicity During Massive Blood Transfusion

Cited by 133 publications

References 72 publications

Effect of Whole Blood Clotting Time in Rats With Ionized Hypocalcemia Induced by Rapid Intravenous Citrate Infusion

Effect of Whole Blood Clotting Time in Rats With Ionized Hypocalcemia Induced by Rapid Intravenous Citrate Infusion

Massive Transfusion and Its Influence on Oxygen Transport and Electrolyte Balance

Mechanisms of adverse effects during hemapheresis

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