Citrate intoxication is a post—transfusion complication that occurs with massive transfusions of whole blood or plasma; a metabolic reaction of the body to media prepared using citric acid sodium salt (sodium citrate). It is clinically manifested by convulsive contractions of individual fibers of the lower leg muscles, disorders of the coronary rhythm, pain or heaviness behind the sternum. It is possible to develop respiratory failure, tonic seizures. It is diagnosed based on anamnesis, symptoms and results of electrolyte analysis. Treatment: termination of transfusion, correction of metabolic disorders.
T80.8 Other complications associated with infusion, transfusion and therapeutic injection
Citrate intoxication (CI, posttransfusion hypocalcemia) is a relatively rare complication. Occurs in patients who need rapid and voluminous replenishment of CBV due to donor media. The occurrence does not exceed 0.01% of the total number of hemotransfusions performed. It is diagnosed with the same frequency in men and women, about 60% of cases occur in patients over 50 years old suffering from chronic diseases of the kidneys, parathyroid glands. The phenomenon was described in the first third of the XX century, shortly after sodium citrate began to be massively used as an anticoagulant and preservative.
Citrate intoxication occurs with rapid transfusion of media that contain citric acid derivatives. Usually such transfusion media are plasma, whole blood or erythrocyte mass. The drop in calcium levels to critical values occurs at an infusion rate of more than 100 drops per minute (1 liter in 10-12 minutes). Transfusion with a frequency of 150 drops has been proven to reduce the free Ca content to 0.6-0.8 mmol/l with an average adult norm of 2.3-2.75 mmol. The probability of developing posttransfusion hypocalcemia increases in the following cases:
- Concomitant diseases. Utilization of sodium citrate occurs in the parenchyma of internal organs. Therefore, the complication is more common and more severe in patients suffering from cirrhosis of the liver, chronic renal failure, hepatitis in the active phase, pancreatitis. Patients with multiple organ failure and shock of any genesis require special care during hemotransfusion.
- Taking corticosteroids. Drugs such as prednisone, dexamethasone, hydrocortisone, with prolonged use, reduce the absorption of electrolytes from the gastrointestinal tract, contribute to increased excretion by the kidneys. In addition, they lead to the leaching of trace elements from the bone tissue. Cytostatic agents have a similar effect.
- Previous medical interventions. The concentration of calcium may change after therapeutic plasmapheresis with compensation of the exfused volume of plasma, prolonged hemodialysis, traumatic operations, resuscitation measures. Sometimes procedures that can affect the level of electrolytes are combined with the above diseases (hemodialysis on the background of renal failure). In such a situation, the risk of CI increases many times.
The pathogenesis is based on the ability of sodium citrate to bind Ca++ ions in blood plasma. Since this component takes part in electrophysiological processes, the lack of a trace element leads to their violation. The stability of cell membranes is lost, the work of the sympathetic and parasympathetic nervous system changes, the ability to regulate vascular tone decreases, the synthesis of neurotransmitters and hormones fails. All this leads to the formation of a characteristic clinical picture.
The severity of CI is directly proportional to the volume and rate of citrate blood infusion. After the termination of the procedure, the concentration of the electrolyte is restored due to its exit from the intraosseous depots. Citric acid itself is rapidly metabolized in the liver to inactive compounds. Minor and moderate intoxication does not require additional correction measures. The work of all body systems is restored within half an hour from the moment of stopping the blood transfusion. In severe reactions, drug correction of calcium levels is indicated.
At the initial stage, CI is manifested mainly by subjective symptoms. Patients complain of unpleasant sensations behind the sternum, the appearance of a metallic taste in the mouth. Slight shortness of breath is possible. As the concentration of Ca decreases, clinical manifestations increase. There are convulsive contractions of individual muscle fibers of the face, shins. The respiratory rate increases. There is a feeling of fear, drowsiness. There may be headache, ringing in the ears, blurred vision, a feeling of goosebumps on the skin. There is a decrease in blood pressure.
Severe hypocalcemia is manifested by tonic, long-lasting convulsions, mainly affecting the muscles of the extremities. Vascular tone is noticeably reduced, which leads to severe hypotension. Shortness of breath increases, episodes of apnea appear. The heart rate drops, in the most severe cases, asystole and clinical death develop. The CVP and pressure in the pulmonary artery increases. The latter leads to the appearance of swelling of the legs, accumulation of free fluid in the abdomen (ascites).
The most dangerous complication of CI is the prolongation of the QT interval on the electrocardiogram. This phenomenon is considered a predictor of fatal rhythm disturbances and often ends in cardiac arrest or ventricular fibrillation. It occurs in almost all cases of excessive intake of citrate into the bloodstream. In the absence of other provoking factors, it disappears soon after the restoration of calcium levels. With a high risk of asystole, it is eliminated by intravenous administration of calcium-containing drugs. It lends itself well to correction.
Another complication that occurs mainly in children’s patients is bronchospasm and laryngospasm. A pattern similar to that of bronchial asthma is determined: expiratory dyspnea (with laryngospasm — inspiratory or mixed), a feeling of suffocation, lack of air, a decrease in the saturation index, generalized cyanosis. If the patient is able to sit, he takes a forced position, leaning forward and resting on his hands. A barking cough appears.
Citrate intoxication is detected by characteristic clinical manifestations. In the patient’s anamnesis, there is necessarily a recent transfusion of a large volume of transfusion media. Taking into account the fact that such procedures are most often carried out in the ICU or operating rooms, the patient is examined by an anesthesiologist-resuscitator. If necessary, a cardiologist or a transfusiologist is consulted. To differentiate the condition with shock, allergic reactions, the following types of examination are indicated:
- Physical: blood pressure is reduced by 20 or more units from the “working” indicators, the patient is scared, complains of heaviness in the chest, discomfort in the heart, dizziness. The skin is pale or has a bluish tinge, the respiratory rate is 22-25 per minute. With severe hypocalcemia, BDD decreases to 5-10 times /min. There are data indicating hypertonicity of skeletal muscles, convulsive readiness. Visible contractions of individual fibers, twitching of facial tissues. The pulse against the background of hypotension increases to 100-120 beats / min, however, with a significant change in the salt balance, it can decrease to 40-50 beats /min.
- Instrumental: an ECG shows an expansion of ventricular complexes, an increase in the QT interval to 0.44 seconds or more. The RR interval increases to 1.2-1.3 seconds. at a recording speed of 25 mm/sec (bradycardia). The EEG shows changes in focal and asymmetric slow waves, indicating the presence of pathological brain activity. Measurement of the central venous pressure through the subclavian catheter detects its increase to 15-16 mm of water column.
- Laboratory: the main method of examination is analysis for the content of electrolytes. At the same time, the total Ca concentration decreases to the level of potassium content can increase to 5.3 mmol/L and higher. pH
The elimination of hypocalcemia symptoms is based on the immediate cessation of transfusion. If there are no pronounced violations of hemodynamics and the work of the muscular apparatus, correction with the help of drugs is not indicated. The patient’s condition returns to normal in a few minutes. With a significant change in the electrolyte balance and the presence of a bright clinical picture, the patient is intravenously injected with calcium chloride or gluconate in an amount of 10-20 ml of a 10% solution. Antidote therapy is not required because sodium citrate is rapidly utilized in the body.
Citrate intoxication, occurring in an extremely severe variant, requires resuscitation. The patient is placed in the intensive care unit or intensive care unit, connected to an anesthesiological monitor for constant monitoring of the respiratory system and hemodynamics. With a sharp bradycardia, atropine and cardiotonics are administered. Generalized seizures are stopped with the help of relanium, magnesium sulfate, barbiturates. If a person is on artificial ventilation, muscle relaxants in combination with hypnotics can be used for this purpose. The administration of calcium preparations under the control of the electrolyte composition of the blood is shown.
Prognosis and prevention
Citrate intoxication has a favorable prognosis if it was diagnosed in a timely manner. Termination of transfusion or a significant decrease in its rate allows to normalize the patient’s condition even without the use of medications. Severe hypocalcemia can provoke fatal complications, including ventricular fibrillation or asystole, convulsive seizures, respiratory failure up to its stop. The course of the disease worsens at the same time. There is a danger of developing posthypoxic encephalopathy and other conditions associated with post-resuscitation changes.
Prevention consists in limiting the rate of transfusion of citrate-containing media. The infusion should be carried out at a frequency of about 50 ml / minute. People predisposed to the development of hypocalcemia are recommended to transfuse washed erythrocytes that do not contain citric acid. If it is necessary to use citrate components for each liter of transfused blood, the patient should receive 10 ml of 10% Ca-gluconate. If the procedure must be carried out at a high speed (critical conditions, acute blood loss), then the drugs are administered every 0.5 liters of transfusion medium.