30: Exchange Transfusion

1. Hyperbilirubinemia. Exchange transfusion (ET) is most commonly done for infants with hyperbilirubinemia of any origin when the serum bilirubin level reaches or exceeds a level that puts the infant at risk for central nervous system toxicity (see Chapters 58 and 100). Serum levels of bilirubin for which to begin an ET are under considerable debate. Double-volume ETs taking 50–70 minutes are used for removal and reduction of serum bilirubin. Efficiency of bilirubin removal is increased in slower paced exchanges to allow for time of extravascular and intravascular bilirubin equilibration.

2. Hemolytic disease of the newborn. Results from destruction of fetal red blood cells (RBCs) by passively acquired maternal antibodies. ET aids in removing antibody-coated RBCs and replaces them with uncoated donor RBCs that lack sensitizing antigen, thereby prolonging intravascular RBC survival. It also reduces a potentially toxic bilirubin concentration, the result of the antibody destruction of RBCs. Intravenous immunoglobulin (IVIG) is now used to reduce the need for ET in hemolytic disease of the newborn. American Academy of Pediatrics guidelines recommend IVIG if the total serum bilirubin (TSB) is rising despite intensive phototherapy or the TSB level is within 2–3 mg/dL of the exchange level.

3. Sepsis. May be associated with shock caused by bacterial endotoxins. ET may help remove bacteria, toxins, fibrin split products, and accumulated lactic acid. It may also provide immunoglobulins, complement, and coagulating factors.

4. Disseminated intravascular coagulation (DIC). ET may provide necessary coagulation factors and help reduce the underlying cause of the abnormal coagulation. Repletion of clotting factors by transfusion of fresh-frozen plasma (10–15 mL/kg) may be all that is necessary in less severe cases of DIC.

5. Metabolic disorders causing severe acidosis. Partial exchanges are usually acceptable and beneficial; however, peritoneal dialysis may also be needed to treat severely acidotic disorders of metabolism.

6. Severe fluid or electrolyte imbalance. Isovolumetric partial exchanges can be used to modulate electrolyte fluctuations with each aliquot of blood exchanged. The process allows for a gradual correction of electrolyte imbalances.

7. Polycythemia. This can be managed by partial ET using normal saline. Normal saline is preferred because it reduces both the polycythemia and the hyperviscosity of the infant's circulating blood volume. (See also Chapter 71 and 122.)

8. Severe anemia. Normovolemic or hypervolemic anemia causing cardiac failure, as in hydrops fetalis, is best treated with a partial ET using packed RBCs.

9. Any disorder requiring complement, opsonins, or gamma globulin. Infants with these conditions may require frequent exchanges, and their fluid status must be carefully managed. Partial exchanges are recommended.

1. Single-volume exchange blood transfusion. Refers to 1 times the estimated blood volume at ∽60% of infant's blood volume.

2. Double-volume exchange blood transfusion. Refers to 2 times the estimated blood volume at ∽85% of infant's blood volume. This is indicated for severe hyperbilirubinemia (to remove bilirubin), for alloimmune hemolytic disease of newborns, to remove antibodies and abnormal proteins, and for idiopathic severe hypermagnesemia, DIC, congenital leukemia, neonatal sepsis, malaria, malignant pertussis, drug overdose, and metabolic toxin removal (hyperammonemia, organic academia, lead poisoning). Cochrane review states that there are insufficient data to support or refute the use of single-volume ET as opposed to double-volume ET in newborns with jaundice. Double-volume ET is still recommended for infants with severe jaundice and Rh hemolytic disease.

3. Isovolumetric double-volume exchange blood transfusion. Exchange is done simultaneously pulling blood out of the umbilical artery and pushing blood into the umbilical vein. Indicated in sick and unstable neonates because of less fluctuation of blood pressure and cerebral hemodynamics (eg, hydrops fetalis).

4. Partial-volume exchange (<2 volumes) transfusion. This type of exchange is indicated in neonates with polycythemia (to decrease the hematocrit and whole blood viscosity) or to correct severe anemia (usually associated with congestive cardiac failure or hypervolemia).

An assistant needed to help maintain a sterile field, monitor and assess the infant, and record the procedure and exchanged volumes. Also needed are radiant warming bed or hybrid incubator, equipment for cardiorespiratory monitoring, support and resuscitation, immediate access to blood gas determinations, equipment for umbilical artery and umbilical vein catheterization (see Chapters 24 and 44), disposable ET tray, and nasogastric tube for evacuating the stomach before beginning the transfusion. Temperature-controlled device must be used for warming of the blood before and during the transfusion (should have an internal disposable coil and connectors to the donor blood bag and the ET circuit. The blood should be warmed to 37°C. Use of makeshift water baths or heaters is not advised because blood that is too warm may hemolyze).

1. Blood collection

   1. Homologous blood. Blood donated by an anonymous donor with a compatible blood type is most commonly used. Donor-directed blood (blood donated by a selected blood type–compatible person) is another option.

   2. Cytomegalovirus (CMV). Seronegative donor blood is preferred. White blood cells harboring CMV can be removed using leukodepletion filters during blood preparation. The use of frozen deglycerolized RBCs, reconstituted with fresh-frozen plasma, is another means of using seropositive blood free of viable CMV.

   3. Hemoglobin S (sickle cell trait). Precautions should be taken to avoid ET with donor blood from a carrier. If the donor blood with sickle trait becomes acidic, sickling can occur, with expected complications to the patient.

   4. Graft-versus-host disease. Consideration should be given for using irradiated donor blood to avoid graft-versus-host disease in known immune-compromised infants and low birthweight infants. Preterm infants who have been transfused in utero or who have received >50 mL of transfused blood are candidates for irradiated blood.

2. Blood typing and cross-matching

   1. Infants with Rh incompatibility. The blood must be type O, Rh-negative, low titer anti-A, anti-B blood. It must be cross-matched with the mother's plasma and RBCs.

   2. Infants with ABO incompatibility. The blood must be type O, Rh-compatible (with the mother and the infant) or Rh-negative, low-titer anti-A, anti-B blood. It must be cross-matched with both the infant's and mother's blood.

   3. Other blood group incompatibilities. For other hemolytic diseases (eg, anti-Rhc, anti-Kell, anti-Duffy), blood must be cross-matched to the mother's blood to avoid offending antigens.

   4. Hyperbilirubinemia, metabolic imbalance, or hemolysis not caused by isoimmune disorders. The blood must be cross-matched against the infant's plasma and RBCs.

3. Freshness and preservation of blood. In newborn infants, it is preferable to use blood or plasma that has been collected in citrate phosphate dextrose (CPD). The blood should be <72 hours old. These 2 factors ensure that the blood pH is >7.0. For disorders associated with hydrops fetalis or fetal asphyxia, it is best to use blood that is <24 hours old. Use of irradiated blood less than 24 hours before the ET is recommended for all ETs to decrease the potassium in the blood and to decrease graft-versus-host disease.

4. Hematocrit (Hct). Most blood banks can reconstitute a unit of blood to a desired Hct of 50–70%. The blood should be agitated periodically during the transfusion to maintain a constant Hct.

5. Potassium levels in donor blood. Should be determined if the infant is asphyxiated or in shock, and renal impairment is suspected. If potassium levels are >7 mEq/L, consider using a unit of blood that has been collected more recently or a unit of washed RBCs.

6. Temperature of the blood. Warming of blood is especially important in low birthweight and sick newborn infants.

1. Simple 2-volume exchange transfusion is used for uncomplicated hyperbilirubinemia

   1. The normal blood volume in a full-term newborn infant is 80 mL/kg. In an infant weighing 2 kg, the volume would be 160 mL, and twice the volume of blood is exchanged in a 2-volume transfusion. Therefore, the amount of blood needed for a 2-kg infant would be 320 mL. Blood volume of low birthweight and extremely low birthweight newborns, which may be up to 95 mL/kg, should be taken into account when calculating exchange volumes.

   2. Allow adequate time for blood typing and cross-matching at the blood bank. The infant's bilirubin level increases during this time, and this increase must be taken into account when ordering the blood.

   3. Perform the transfusion in an intensive care setting. Place the infant in the supine position. Restraints must be snug but not tight. A nasogastric tube should be passed to evacuate the stomach and should be left in place to maintain gastric decompression and prevent regurgitation and aspiration of gastric juices.

   4. Scrub and put on a sterile gown and gloves.

   5. Perform umbilical vein catheterization and confirm the position by radiograph. (See Figure 11–10.) If an isovolumetric exchange is to be performed, then an umbilical artery catheter (high position preferred) must also be placed and confirmed by radiograph (see Figure 11–11 for correct positioning of a high umbilical artery catheter and Figure 11–12 for correct positioning of a low umbilical artery catheter).

   6. Have the unit of blood prepared

      1. Check the blood types of the donor and the infant.

      2. Check the temperature of the blood and warming procedures.

      3. Check the Hct. The blood should be agitated regularly to maintain a constant Hct.

   7. Attach the bag of blood to the tubing and stopcocks according to the directions on the transfusion tray. The orientation of the stopcocks for infusion and withdrawal must also be checked by the assistant (ie, a procedure “time out”).

   8. Establish the volume of each aliquot. (Table 30–1)

2. Isovolumetric double-volume exchange transfusion. Performed using a double setup, with infusion via the umbilical vein and withdrawal via the umbilical artery. This method is preferred when volume shifts during simple exchange might cause or aggravate myocardial insufficiency (eg, hydrops fetalis). Two operators are needed; one to perform the infusion and the other to handle the withdrawal.

   1. Perform steps 1–6 as in double-volume ET. In addition, perform umbilical artery catheterization.

   2. Attach the unit of blood to the tubing and stopcocks attached to the umbilical vein catheter. The catheter may be left in place after the ET to monitor central venous pressure. It should be placed above the diaphragm with placement confirmed by chest radiograph.

   3. The tubing and the stopcocks of the second setup are attached to the umbilical artery catheter and to a sterile plastic bag for discarding the exchanged blood.

   4. If isovolumetric exchange is being performed because of cardiac failure, the central venous pressure can be determined via the umbilical vein catheter. It should be placed above the diaphragm in the inferior vena cava.

3. Partial exchange transfusion (PET). Performed in the same manner as double-volume ET. If a partial exchange is for polycythemia (using normal saline) or for anemia (using packed RBCs), the following formula can be used to determine the volume of the transfusion.

   1. To calculate volume to exchange for polycythemia:

      

   2. To calculate volume to exchange for anemia:

      

4. Isovolumetric partial exchange transfusion with packed RBCs. Best procedure if the diagnosis is severe hydrops fetalis.

5. Ancillary procedures

   1. Laboratory studies. Blood should be obtained for laboratory studies before and after ET.

      1. Blood chemistry. Total calcium, sodium, potassium, chloride, pH, Paco₂, acid-base status, bicarbonate, and serum glucose.

      2. Hematologic studies. Hemoglobin Hct, platelet count, white blood cell count, and differential count. Blood for retyping and cross-matching after exchange is often requested by the blood bank to verify typing and re–cross-matching and for study of transfusion reaction, if needed.

      3. Blood culture. Recommended after ET (controversial).

   2. Administration of calcium gluconate. The CPD buffer in stored blood binds calcium and transiently lowers ionized calcium levels. Treatment of suspected hypocalcemia in patients receiving transfusions is controversial. Some physicians routinely administer 1–2 mL of 10% calcium gluconate by slow infusion after 100–200 mL of exchange donor blood. Others maintain that this treatment has no therapeutic effect unless hypocalcemia is documented by electrocardiogram showing a change in the QT interval.

   3. Phototherapy. Begin or resume phototherapy after ET for disorders involving a high bilirubin level (for phototherapy guidance, see Chapters 58 and 100).

   4. Monitor serum bilirubin levels after transfusion at 2, 4, and 6 hours and then at 6-hour intervals. A rebound of bilirubin levels is to be expected 2–4 hours after the transfusion.

   5. Remedication. Patients receiving antibiotics or anticonvulsants need to be remedicated. Patients receiving digoxin should not be remedicated, unless the cardiac status is deteriorating or serum digoxin levels are known to be low. The percentage of lost medications is extremely variable. As little as 2.4% of digoxin is lost, but up to 32.4% of theophylline may be lost during a 2-volume ET. Determination of drug levels after ET is advisable

   6. Antibiotic prophylaxis after the transfusion should be considered on an individual basis. Infection is uncommon but is the most frequent complication.

See also complications related to umbilical vein catheterization, Chapter 44.

1. Infection. Bacteremia (usually a Staphylococcus organism), hepatitis, CMV, malaria, and HIV have been reported.

2. Vascular complications. Clot or air embolism, vasospasm of the lower limbs, thrombosis, and infarction of major organs may occur. Perforation of vessels can occur.

3. Cardiac. Arrhythmias, cardiac arrest, and volume overload can occur.

4. Bleeding/coagulopathies. Coagulopathies may result from thrombocytopenia or diminished coagulation factors. Platelets may decrease by >50% after a 2-volume ET.

5. Electrolyte abnormalities. Hyperkalemia, hypernatremia, hyperglycemia, hypercalcemia, hypomagnesemia, and hypocalcemia can occur.

6. Hypoglycemia. Especially likely in infants of diabetic mothers and in those with erythroblastosis fetalis because of islet cell hyperplasia and hyperinsulinism. Rebound hypoglycemia may result in these infants in response to the concentrated glucose (300 mg/dL) contained in CPD donor blood.

7. Metabolic acidosis. Metabolic acidosis from stored donor blood (secondary to the acid load) occurs less often in CPD blood.

8. Metabolic alkalosis. Metabolic alkalosis may occur as a result of delayed clearing of citrate preservative from the donated blood by the liver.

9. Necrotizing enterocolitis. An increased incidence of NEC after ET has been suggested. For this reason, the umbilical vein catheter should be removed after the procedure unless central venous pressure monitoring is required. Also, it is recommended that feedings be delayed for at least 24 hours to observe the infant for the possibility of a post-ET ileus.

10. Miscellaneous. Feeding intolerance, hypothermia, hyperthermia, graft-versus-host disease, apnea, bradycardia.