Atlas of Procedures in Neonatology, 4th Edition



Exchange Transfusions

Jayashree Ramasethu

The frequency with which postnatal exchange transfusions (ET) were performed decreased in the 1990s, resulting in significantly less experience among personnel performing the procedure (1, 2, 3). However, the re-emergence of kernicterus as a public health problem underscores the importance of ET as a treatment modality that could potentially prevent devastating neurodevelopmental complications (4,5).

  1. Definitions
  2. Exchange transfusion: Replacing an infant's blood with donor blood by repeatedly removing and replacing small aliquots of blood over a short time period
  3. Indications
  4. Significant unconjugated hyperbilirubinemia in the newborn due to any cause, when intensive phototherapy fails or there is risk of kernicterus. Immediate ET is recommended if there are early signs of acute bilirubin encephalopathy (6). Figure 42.1 shows the total serum bilirubin levels at which ET is recommended for infants of 35 or more weeks' gestation.
  5. Indications for ET in more immature infants are variable and individualized (see Table 46.1). When performed for low bilirubin levels, ET is less effective than phototherapy in achieving prolonged reductions in total serum bilirubin in neonates with nonhemolytic jaundice (7).
  6. Alloimmune hemolytic disease of the newborn (HDN) (1)
  7. For correction of severe anemia and hyperbilirubinemia
  8. In addition, in infants with alloimmune HDN, ET replaces antibody-coated neonatal red cells with antigen-negative red cells that should have normal in vivo survival and also removes free maternal antibody in plasma.
  9. Severe anemia with congestive cardiac failure or hypervolemia (1, 8)
  10. Polycythemia

Although partial exchange transfusion with crystalloid or colloid reduces the packed cell volume and hyperviscosity in neonates with polycythemia, there appears to be no evidence of long-term benefit from the procedure (9).

  1. Disseminated intravascular coagulation (2)
  2. Congenital leukemia (10)
  3. Metabolic toxins
  4. Hyperammonemia (11)
  5. Organic acidemia (12)
  6. Lead poisoning (13)
  7. Drug overdose or toxicity (14, 15)
  8. Removal of antibodies and abnormal proteins (16, 17)
  9. Neonatal sepsis or malaria (18, 19)
  10. Contraindications
  11. When alternatives such as simple transfusion or phototherapy would be just as effective with less risk (7)
  12. When patient is unstable and the risk of the procedure outweighs the possible benefit

In infants with severe anemia, with cardiac failure or hypervolemia, partial ET may be useful to stabilize the patient's condition before a complete or double-volume ET is performed.

  1. When a contraindication to placement of necessary lines outweighs indication for ET. Alternative access should be sought if ET is imperative (20).
  2. Equipment
  3. Infant care center (see Chapter 2)
  4. Automatic and manually controlled heat source
  5. Temperature monitor
  6. Cardiorespiratory monitor
  7. Pulse oximeter for oxygen saturation monitoring
  8. Resuscitation equipment and medication (immediately available)
  9. Infant restraints
  10. Orogastric tube
  11. Suctioning equipment
  12. Equipment for central and peripheral vascular access
  13. Blood warmer and appropriate coils (see Precautions)



FIG. 42.1. Guidelines for exchange transfusion in infants 35 or more weeks gestation. (From 

American Academy of Pediatrics. Subcommittee on Hyperbilirubinemia. Clinical Practice Guideline. Management of hyperbilirubinemia in the newborn infant 35 or more weeks gestation. Pediatrics. 2004;114:297–316


  1. Sterile exchange transfusion equipment
  2. Pre-assembled disposable set with special stopcock (Pharmaseal, Allegiance Healthcare Corporation, McGaw Park, IL, USA) or
  3. Nonassembled
  4. 10- or 20-mL syringes Use a smaller syringe if aliquot per pass is smaller.
  5. Two three-way stopcocks with locking connections
  6. Waste receptacle (empty IV bottle or bag)
  7. IV connecting tubing
  8. Appropriate blood product
  9. Syringes and tubes for pre- and postexchange blood tests
  10. Precautions
  11. Stabilize infant before initiating exchange procedure.
  12. Do not start exchange procedure until personnel are available for monitoring and as backup for other emergencies.
  13. Use blood product appropriate to clinical indication. Use freshest blood available, preferably <5 to 7 days.
  14. Check potassium level of donor blood if patient has hyperkalemia or renal compromise.
  15. Monitor infant closely during and after procedure.
  16. Do not rush procedure.
  17. May necessitate repeat ET if efficacy is decreased by haste.
  18. Stop or slow procedure if patient becomes unstable.
  19. Use only thermostatically controlled blood-warming device that has passed quality control for temperature and alarms. Be sure to review operating and safety procedures for specific blood warmer. Do not overheat blood, i.e., beyond 38°C.
  20. Do not apply excessive suction if it becomes difficult to draw blood from line. Reposition line or replace syringes, stopcocks, and any adapters connected to line.
  21. Leave anticoagulated, banked blood in line or clear line with heparinized saline if the procedure is interrupted.



  1. Clear line with heparinized saline if administering calcium.
  2. Preparation for Total or Partial Exchange Transfusion
  3. Blood product and volume Blood Product
  4. Communicate with blood bank or transfusion medicine specialist to determine most appropriate blood product for transfusion.
  5. Plasma-reduced whole blood or packed red cells reconstituted with plasma, with a packed cell volume adjusted to 0.5 to 0.60, is suitable for ET to correct anemia and hyperbilirubinemia (1, 21, 22 and 23).
  6. Blood may be anticoagulated with citrate phosphate dextrose (CPD or CPDA1) or heparin. Additive anticoagulant solutions are generally avoided (21, 22, 23 and 24). If only RBCs stored in additive solutions are available, the additive solution may be removed by washing or by centrifugation and removal of the supernatant solution, prior to reconstitution of the red cells with plasma.
  7. Blood should be as fresh as possible (<7 days).
  8. Irradiated blood is recommended for all ET, to prevent graft-versus-host disease. There is a significant increase in potassium concentration in stored irradiated units, so irradiation should be performed as close to the transfusion as possible (<24 hours).
  9. Standard blood-bank screening is particularly important, including sickle-cell preparation, HIV, hepatitis B, and cytomegalovirus (CMV) (see Chapter 41).
  10. Donor blood should be screened for G-6-PD deficiency and HbS in populations endemic for these conditions (25).
  11. In presence of alloimmunization, e.g., Rh, ABO, special attention to compatibility testing is necessary (1).
  12. If delivery of an infant with severe HDN is anticipated, O Rh-negative blood cross-matched against the mother may be prepared before the baby is born.
  13. Donor blood prepared after the infant's birth should be negative for the antigen responsible for the hemolytic disease, and should be cross-matched against the infant.
  14. In ABO HDN, the blood must be type O and either Rh-negative or Rh-compatible with the mother and the infant. The blood should be washed free of plasma or have a low titer of anti-A or anti-B antibodies. Type O cells with AB plasma may be more effective, but this results in two donor exposures per ET (26).
  15. In Rh HDN, the blood should be Rh-negative, and may be O group or the same group as the infant.
  16. In infants with polycythemia, the optimal dilutional fluid for a partial ET is isotonic saline rather than plasma or albumin (27).

Volume of Donor Blood Required

  1. Whenever possible, use no more than equivalent of one whole unit of blood for each procedure, to decrease donor exposure.
  2. Quantity needed for total procedure = volume for the actual ET plus volume for tubing dead space and blood warmer (usually 25 to 30 mL)
  3. Double-volume ET for removal of bilirubin, antibodies, etc.:

2 × infant's blood volume = 2 × 80 - 120 mL/kg

  1. Infant's blood volume in preterm infant < 100 to 120 mL/kg, in term infant < 80 to 85 mL/kg
  2. Exchanges approximately 85% of infant's blood volume (Fig. 42.2)
  3. Single volume ET: Exchanges approximately 60% of infant's blood volume (Fig. 42.2)
  4. Partial ET for correction of severe anemia:
  5. Single-volume or partial ET for correction of polycythemia:
  6. Preparation of infant
  7. Place infant on warmer with total accessibility and controlled environment. ET on small preterm infants may be performed in warm incubators, provided a sterile field can be maintained and lines are easily accessible.
  8. Restrain infant suitably. Sedation and pain relief are not usually required. Conscious infants may suck on a pacifier during the procedure.




FIG. 42.2. Graph depicting the effectiveness of exchange transfusion against the fraction of blood volume exchanged. The formula permits the calculation of the final hemoglobin.

  1. Connect physiologic monitors and establish baseline values (temperature, respiratory and heart rates, oxygenation)
  2. Empty infant's stomach.
  3. Do not feed for 4 hours prior to procedure, if possible.
  4. Place orogastric tube and remove gastric contents; and leave on open drainage.
  5. Start IV line for glucose and medication infusion:
  6. If exchange procedure interrupts previous essential infusion rate
  7. If prolonged lack of oral or parenteral glucose will lead to hypoglycemia
  8. Extra IV line may be necessary for emergency medications.
  9. Stabilize infant prior to starting exchange procedure; e.g., give packed-cell transfusion when severe hypovolemia and anemia are present, or modify ventilator or ambient oxygen when there is respiratory decompensation.
  10. Establish access for ET
  11. Push–pull technique: Central access—usually through umbilical venous catheter.
  12. Isovolumetric exchange with simultaneous infusion of donor blood through venous line and removal of baby's blood through arterial line. This technique may be better tolerated in sick or unstable neonates because there is less fluctuation of blood pressure and cerebral hemodynamics. The technique is also favored when only peripheral vascular access is available or preferred for various reasons (28, 29 and 30).
  13. Infusion of donor blood may be through umbilical venous catheter or peripheral intravenous catheter.
  14. Removal of baby's blood may be from umbilical arterial or venous catheter, or peripheral arterial catheter, usually a radial arterial line.
  15. Laboratory tests on infant's blood pre-exchange Tests are based on clinical indications.
  16. Pre-exchange diagnostic studies. Note that diagnostic serologic tests on the infant, such as studies to evaluate unexplained hemolysis, antiviral antibody titers, metabolic screening, or genetic tests should be drawn prior to the ET.
  17. Hemoglobin, hematocrit, platelets
  18. Electrolytes, calcium, blood gas
  19. Glucose
  20. Bilirubin
  21. Coagulation profile
  22. Prepare blood.
  23. Verify identification of blood product (see Chapter 41).
  24. Type and cross-match data
  25. Expiration date
  26. Donor and recipient identities
  27. Attach blood administration set to blood-warmer tubing and to blood bag.
  28. Allow blood to run through blood warmer.
  29. Technique (See DVD for Animation of this Procedure)

Exchange Transfusion by Push–Pull Technique through Special Stopcock with Preassembled Tray



  1. Read instructions provided by manufacturer carefully.
  2. Scrub as for major procedure. Wear mask, head cover, sterile gown, and gloves.
  3. Open preassembled equipment tray, using aseptic technique.
  4. Identify positions on special stopcock in clockwise rotation (Figs. 42.3 and 42.4). The direction that the handle is pointing indicates the port that is open to the syringe. The special stopcock allows clockwise rotation in the order used: (a) withdraw from patient; (b) clear to waste bag; (c) draw new blood; (d) inject into patient. Always rotate the handle in clockwise direction to follow the proper sequence, and keep connections tight.
  5. Male adapter to umbilical or peripheral line
  6. Female adapter to the extension tubing to which waste bag will be attached
  7. Connect to blood tubing for attachment to blood-warmer coil.
  8. Neutral “off” position in which additives may be administered through rubber stopper (180 degrees from waste-receptacle port)

FIG. 42.3. Special four-way stopcock. A, male adapter to infant line; B, female adapter to waste container; C, attachment to blood tubing; D, “off” position (180 degrees from adapter to waste container), allowing injection through rubber-stoppered port “below” syringe. The stopcock is used in clockwise rotation when correctly assembled.

  1. Follow steps as provided by manufacturer to make all connections to blood and waste bags.
  2. With stopcock open to blood source, clear all air into syringe. Turn in clockwise direction 270 degrees and evacuate into waste.
  3. Turn stopcock to “off” and replace onto sterile field.
  4. Use pre-existing umbilical venous line or insert umbilical venous catheter, using sterile technique as described in Chapter 29 and attach spinal stopcock.
  5. Consider CVP measurement, using pressure transducer, in unstable baby.
  6. Place catheter in IVC and verify position by radiograph.
  7. If catheter cannot be positioned in IVC, it may still be used cautiously in an emergency, when placed in the umbilical vein, if adequate blood return is obtained.

Fig. 42.4. A, B: ET using special four-way stopcock.

  1. P.334
  2. Have an assistant document all vital signs, volumes, and other data on the exchange record.
  3. Check peripheral glucose levels every 30 to 60 minutes. Monitor cardiorespiratory status, continuous pulse oximetry. Determine blood gases as often as indicated by pre-existing clinical condition and stability.
  4. Draw blood for diagnostic studies
  5. Usual rate of removal and replacement of blood during the ET is aliquots of approximately 5 mL/kg over a 2- to 4-minute cycle.
  6. If infant is hypovolemic or has low CVP, start exchange with transfusion of aliquot (5 mL/kg) into catheter. If infant is hypervolemic or has high CVP, start by withdrawing precalculated aliquot.
  7. Remeasure CVP if indicated. Expect rise as plasma oncotic pressure increases, if CVP is low at start.
  8. Ensure that the stages of drawing and infusing blood from and into the infant are done slowly, taking at least a minute each to avoid fluctuations in blood pressure. Rapid fluctuations in arterial pressure in the push–pull technique may be accompanied by changes in intracranial pressure (28, 31). Rapid withdrawal from the umbilical vein induces a negative pressure that may be transmitted to the mesenteric veins and contribute to the high incidence of ischemic bowel complications (32).
  9. Gently agitate the blood bag every 10 to 15 minutes to prevent red cell sedimentation, which may lead to exchange with relatively anemic blood towards the end of the exchange.
  10. Consider giving calcium supplement:
  11. When hypocalcemia is documented
  12. With symptoms or signs of hypocalcemia
  13. Change in Q–Tc interval
  14. Agitation and tachycardia—these symptoms are not reliably correlated with ionized calcium levels.

It is rarely necessary or advantageous to give calcium during an exchange if the infant is normocalcemic. When calcium is administered, the effect may last only a few minutes. Calcium will reverse the effect of the anticoagulant in the donor blood and may cause clotting of the line, so administration through a peripheral intravenous line is preferred. If calcium is given through an umbilical venous catheter, clear the line of donor blood prior to calcium administration with 0.9% NaCl. Give 1 mL of 10% calcium gluconate per kilogram body weight. Administer slowly, with careful observation of heart rate and rhythm. Clear line again with 0.9% NaCl.

  1. Perform calculated number of passes, until desired volume has been exchanged.
  2. Be sure there is adequate volume of donor blood remaining to infuse after last withdrawal, if a positive intravascular balance is desired.
  3. Clear umbilical line of banked blood and withdraw amount of infant's blood needed for laboratory testing, including re-cross-matching.
  4. Infuse IV fluids with 0.5 to 1 U heparin/mL of fluid through UVC if further ET are anticipated.
  5. Total duration for double-volume ET: 90 to 120 minutes.
  6. Document procedure in patient's hospital record.

Exchange Transfusion Using a Single Umbilical Line and Two Three-Way Stopcocks in Tandem

The principles and techniques for using either the special stopcock or two three-way stopcocks in tandem are the same. It is important to ensure that all junctions are tight to produce a closed, sterile system. It is also essential to understand the working positions of the stopcocks before starting the exchange.

  1. Scrub as for major procedure. Wear sterile gown and gloves.
  2. Attach stopcock and tubing in sequence (Fig. 42.5).
  3. Proximal stopcock
  4. Umbilical catheter
  5. IV extension tubing to sterile waste container
  6. Distal stopcock
  7. Tubing from blood-warming coil
  8. 10- or 20-mL syringe
  9. Clear lines of air bubbles.
  10. Start exchange record.

Follow steps of push–pull technique until exchange is completed.

Exchange Transfusion by Isovolumetric Technique (Central or Peripheral Line)

  1. Scrub as for major procedure.
  2. Select two sites for line placement, and insert as per Section 5, Vascular Access.
  3. Venous for infusion
  4. Umbilical venous catheter (preferred)
  5. Peripheral IV cannula that is at least 23 gauge
  6. Arterial for removal
  7. Umbilical artery catheter (preferred)
  8. Peripheral, usually radial if infant's size permits
  9. Connect arterial line to three-way stopcock.
  10. Use short, connecting IV tubing to extend peripheral line.
  11. Attach additional connecting tubing to stopcock and place into sterile waste container.




FIG. 42.5. Three-way stopcocks in tandem. Step 1: Stopcocks positioned for withdrawing blood from infant. Step 2: Stopcocks positioned for emptying withdrawn blood to waste container. Step 3: Stopcocks positioned for filling syringe from blood bag. Step 4: Stopcocks positioned for injecting blood into infant line.

  1. Attach empty 3- to 10-mL syringe to stopcock, for withdrawal of blood.

An additional stopcock may also be placed on this port so that a syringe of heparinized saline (5 U/mL) may be attached for use as needed. Be cautious about total volume infused.

  1. Connect venous line to single, three-way stopcock, which in turn connects to empty 5- to 10-mL syringe and to blood-warming coil.
  2. Start exchange transfusion record.
  3. Withdraw and discard blood from arterial side at rate of 2 to 3 mL/kg/min, and infuse at same rate into venous side. Keep flow as steady as possible, and volumetrically equal for infusion and removal.
  4. Intermittently, flush arterial line with heparinized saline to clear.

The heparin solution remaining in tubing will be removed with next withdrawal, thus reducing significantly the total heparin dose actually received by the patient.

  1. Follow steps as for push–pull technique until exchange is complete.
  2. Total duration for isovolumetric ET: 45 to 60 minutes; may be longer in sick, unstable infants
  3. Postexchange for All Techniques
  4. Continue to monitor vital signs closely for at least 4 to 6 hours.
  5. Rewrite orders; adjust any drug dosages as needed to compensate for removal by exchange (Table 42.1) (33, 34, 35).
  6. Keep infant NPO for at least 4 hours. Restart feeds cautiously if clinically stable. Monitor abdominal girth and bowel sounds every 3 to 4 hours for next 24 hours if exchange has been performed using umbilical vascular lines. Observe for signs of feeding intolerance.
  7. Monitor serum glucose levels every 2 to 4 hours for 24 hours.
  8. Repeat blood gases as often as clinically indicated.



TABLE 42.1 Hypothetical Drug Loss by Exchange Transfusion Calculated by First-Order Elimination from a Single Compartment (1 — e -V/Vd)


Percent Loss

One Volume

Two Volume





































Penicillin G (crystalline)



Penicillin G (procaine)


















V, plasma volume exchanged in liters; Vd, apparent volume of distribution.
aWhole-blood volume used in calculation.
Source: From Lackner TE. Drug replacement following exchange transfusion. J Pediatr. 1982;100:813, with permission

  1. Measure serum ionized calcium levels and platelet counts in sick infants immediately after the ET and then as indicated.
  2. Repeat hemoglobin, hematocrit, and bilirubin measurements approximately 4 hours after exchange, and further as clinically indicated. A double-volume ET replaces 85% of the infant's blood volume, but eliminates only about 50% of the intravascular bilirubin. Equilibration of intra- and extravascular bilirubin, and continued breakdown of sensitized and newly formed red cells by persisting maternal antibody, results in a rebound of bilirubin levels following initial ET, and may necessitate repeated ET in severe HDN.
  3. Complications
  4. Risk of death or permanent serious sequelae is estimated to be less than 1% in healthy infants, but as high as 12% in sick infants. There may be some uncertainty in ascribing adverse events to the ET procedure in infants who are already critically ill (36, 37, 38).
  5. Many of the adverse events are hematologic and biochemical laboratory abnormalities, which may be asymptomatic. The most common adverse effects noted during or soon after the ET, usually in infants who are preterm and/or sick include:
  6. Apnea and/or bradycardia
  7. Hypocalcemia
  8. Thrombocytopenia (<50,000 in 10% of healthy infants, up to 67% of infants <32 weeks' gestational age)
  9. Metabolic acidosis
  10. Vascular spasm
  11. Complications reported from ET are related to the blood transfusion and to complications of vascular access (see Chapters 28, 29, 41).
  12. Potential complications include:
  13. Metabolic:Hypocalcemia, hypo- or hyperglycemia, hyperkalemia
  14. Cardiorespiratory:Apnea, bradycardia, hypotension, hypertension
  15. Hematologic:Thrombocytopenia, dilutional coagulopathy, neutropenia, disseminated intravascular coagulation
  16. Vascular catheter-related:Vasospasm, thrombosis, embolization (see Chapter 28 and 29)
  17. Gastrointestinal:Feeding intolerance, ischemic injury, necrotizing enterocolitis
  18. Infection:Omphalitis, septicemia




The author gratefully acknowledges the work of Dr. Maureen Edwards and Dr. Mary Ann Fletcher, who wrote this chapter for the second edition of the Atlas. The actual procedure described remains virtually unchanged.


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