NEODOSE

INDICATIONS

• Cardiopulmonary bypass, adjunct to priming fluids: The agents of choice for the priming solution for cardiopulmonary bypass pumps are crystalloid solutions (for example, lactated Ringer’s solution and NS). Nonprotein colloids in addition to crystalloids may be preferred when pulmonary shunting is a concern. For postoperative volume expansion, the preferred order of choice is crystalloids, nonprotein colloids (for example hetastarch, dextran, and synthetic colloids), and lastly albumin . In cardiopulmonary bypass performed in neonates, human albumin has been added to the priming solution . In addition to other components, 5% albumin 200 mL replaced fresh frozen plasma or 20% albumin 100 mL replaced a portion of the fresh frozen plasma in the priming solution.
• Hemolytic disease of the newborn: Albumin may be used to bind free serum bilirubin in infants with severe hemolytic disease prior to exchange transfusion; it should not be administered in conjunction with phototherapy. Immunoglobulin, not albumin, is recommended in infants with isoimmune hemolytic disease and an increasing total serum bilirubin despite intensive phototherapy or when bilirubin is within 2-3 mg/dL of exchange level.
• Hyperbilirubinemia, adjunct to exchange transfusion: Hyperbilirubinemia, adjunct to exchange transfusion: Adjunctive albumin is not included in the American Academy of Pediatrics recommendations for management of hyperbilirubinemia,. however, guidelines from the University HealthSystem Consortium state albumin may be considered as an adjunct to exchange transfusion if administered concurrently, and not before, transfusion. At one institution, albumin is considered before exchange transfusion, especially if serum albumin is less than 3.4 mg/dL. Two studies of infants with intensive phototherapy failure (n=92; 32 weeks or more gestation; weighing more than 1000 g) demonstrated lower bilirubin levels at 6 and 12 hours post-exchange, shorter duration of phototherapy after exchange, and need for second exchange transfusion in albumin-treated neonates compared with the control group. The dosing regimen was 1 g/kg IV of 5% or 20% albumin administered 1 to 2 hours prior to exchange.
• Hyperbilirubinemia, adjunct to phototherapy: Adjunctive albumin is not included in the American Academy of Pediatrics recommendations for management of hyperbilirubinemia . In addition, the University HealthSystem Consortium states that albumin should not be administered as an adjunct to phototherapy. Human 25% albumin 1 g/kg IV during the first 2 hours of intensive phototherapy rapidly reduced (by 2 hours) unbound bilirubin values compared with no albumin in a retrospective study (n=58; gestational age 39.4 weeks; birthweight 3245 g) of Japanese infants with hyperbilirubinemia. However, there was no difference in total bilirubin values. A followup study identified abnormalities of auditory brainstem responses at 6 months in 3 of 38 albumin-treated infants and 6 of 20 infants in the control group. At 2 years of age, abnormal development, including hearing loss, was not identified in either group .
• Hypoalbuminemia: Albumin is not considered appropriate for treatment of hypoalbuminemia according to the University HealthSystem Consortium. There is not enough evidence from randomized trials to determine if routine use of albumin (1 g/kg/day) in preterm neonates with hypoalbuminemia (less than 3 g/dL) is beneficial or harmful.
• Hypotension: Albumin may be considered for volume expansion in neonates if 10 mL/kg of crystalloid solution is unsuccessful, however, the majority of very low birth weight (VLBW) premature infants (weighing 1500 grams or less and younger than 3 postnatal days) with hypotension are not hypovolemic . When hypovolemia is present, albumin is generally not recommended for use; isotonic saline is preferred when a volume expander is needed . Dopamine increased blood pressure better than albumin in preterm hypotensive neonates (weighing 1500 grams or less) younger than 24 hours (n=39). Albumin was superior to normal saline in neonates with hypotension in the first 24 hours of life in a randomized, double-blind study (n=101; mean birthweight 1528 to 1617 g; mean gestational age 30.1 to 30.8 weeks). Over 70% of neonates weighing less than 1500 g failed bolus therapy with either albumin or normal saline and required dopamine infusion. The rate for intraventricular hemorrhage was higher than the norm for both treatments; however, these hemorrhages were less common and less severe in the albumin treated grou. In contrast, 2 studies (n=104) did not demonstrate a difference between albumin and isotonic saline in normalizing mean arterial pressure
• Nephrotic syndrome, adjunct for edema: Diuretics alone are first line therapy, however, short-term use of 25% albumin may be considered in conjunction with a diuretic in patients with acute several peripheral or pulmonary edema having failure with diuretic therapy alone. In pediatric patients with severe edema secondary to nephrotic syndrome, diuretics (eg, loop and thiazide) and 25% albumin infusions may be required in addition to a low-sodium diet and fluid restriction . The benefit of albumin and a diuretic is transient and furthermore, albumin may lead to hypertension, pulmonary edema, and congestive heart failure. Studies are lacking in neonates. In one case-series (n=7) of full-term infants diagnosed with congenital nephrotic syndrome, the regimen was 20% albumin 1 g/kg IV (based upon ideal body weight) over 4 hours followed by IV furosemide (0.5 to 1 mg/kg) when needed
• Perioperative hemodynamic support: No differences in hemodynamics, fluid input, or fluid output were observed between perioperatively administered human 5% albumin and 6% hydroxyethyl starch 130/0.4 (Voluven®) in newborns (at 30 weeks gestation) and infants younger than 24 months of age undergoing non-cardiac surgery in a randomized, open-label trial (n=82). Infusion volume and rate were adjusted to maintain stable hemodynamics.
• Polycythemia, adjunct to dilutional exchange transfusion: Crystalloid solutions, such as normal saline or Ringers solution, are considered the solutions of choice for exchange transfusion in neonates with polycythemia. Albumin is more expensive, frequently in short supply, and has a potential risk of infection.
• Resuscitation: Albumin is not used during neonatal resuscitation. Isotonic crystalloid solution or blood is recommended for volume expansion during resuscitation
• Severe Sepsis and Septic Shock:

FDA APPROVED INDICATION

• AlbuRx®-25 and Flexbumin® 25%: Indicated for hemolytic disease of the newborn to attempt to bind and detoxify unconjugated bilirubin in infants with severe hemolytic disease prior to exchange transfusion.
• Kedbumin™: In patients 12 to 16 years of age, indicated for hypovolemia, hypoalbuminemia, burns (after 24 hours post burn in patients experiencing severe albumin depletion in order to favor edema reabsorption), ovarian hyperstimulation syndrome, and adult respiratory distress syndrome, and in cardiopulmonary bypass (as part of the priming fluids), hemodialysis, and to prevent central volume depletion after paracentesis due to cirrhotic ascites. Safety of albumin solutions has been demonstrated in children provided the dose is appropriate for body weight; however, the safety of Flexbumin® 25% has not been evaluated in sponsor conducted pediatric studi. No clinical studies using Albuminar®-5 have been conducted in pediatric patients. Safety and effectiveness in pediatric patients have not been established. However, extensive experience in patients suggests that children respond to Albuminar®-5 in the same manner as adults.

PRECAUTIONS

• Severe anemia or cardiac failure with normal or increased intravascular volume
• History of hypersensitivity reaction to albumin preparations or to any component of the product (eg, N-acetyltryptophan, sodium caprylate).

PRECAUTIONS

• Administration:
  • Conditions where hypervolemia and/or hemodilution may occur may require dose and infusion rate adjustment; increased risk with heart failure, hypertension, esophageal varices, pulmonary edema, hemorrhagic diathesis, severe anemia, and renal failure; monitoring recommended
  • Circulatory overload or cardiac overload (eg, headache, dyspnea, jugular venous distention, rales and abnormal elevations in systemic or central venous blood pressure) may occur; monitoring recommended ; discontinue use at first clinical signs of cardiovascular overload
  • Rapid rise in blood pressure may occur; monitoring recommended.
  • Do not dilute product with Sterile Water for Injection as there is risk of hemolysis, including potentially fatal cases, and acute renal failure in recipients.
• Hematologic:
  • Re-bleeding secondary to clot disruption can occur in trama and postoperative surgery patients; monitoring recommended.
• Immunologic:
  • Hypersensitivity reactions, including anaphylactic reactions, have been observed; discontinue use for suspected hypersensitivity reaction; implement standard treatment for anaphylactic shock.
  • Infectious agent transmission may occur, including a risk of exposure to viruses, Creutzfeldt-Jakob disease or variant Creutzfeldt-Jakob disease, and other pathogens.

ADVERSE EFFECTS

Common: flushing, urticaria, fever, chills, nausea, vomiting, tachycardia, and hypotension. These reactions usually subside when the infusion rate is slowed or stopped . Lid edema occurred in 19.5% and 29.3% of newborns (at 30 weeks gestation) and infants younger than 24 months of age undergoing non-cardiac surgery receiving albumin 5% and hydroxyethyl starch 130/0.4, respectively.

ADMINISTRATION

• Administer slow enough to avoid too-rapid plasma volume expansion. The 5% and 25% may be administered without dilution or diluted with normal saline or D5W. Adequately hydrate patients during or after infusion of albumin 25% solutions.
• In patients with normal blood volume, avoid circulatory overload and pulmonary edema by administering albumin no faster than 1 mL/min.
• In the presence of hypertension, infuse at a slower rate.
• Do not administer more than 4 hours after vial has been entered. Ensure substitution of other blood constituents (coagulation factors, electrolytes, platelets, and erythrocytes) is adequate when replacing comparatively large volumes of albumin or if blood loss is severe.
• Warm to room temperature if infusing large volumes. In plasma exchange, adjust infusion rate to the rate of removal.

MONITORING

Closely monitor infusion rates and the patient’s clinical state during infusion. Observe injured patients after restoration of blood pressure for bleeding points that may have failed to bleed at lower blood pressure . Closely monitor for circulatory overload during administration. Regularly monitor hemodynamic performance, including arterial blood pressure and pulse rate, central venous pressure, pulmonary artery occlusion pressure, urine output, electrolyte levels, and HCT/Hb. Closely monitor hemodynamic parameters after administering for evidence of cardiac or respiratory failure, renal failure or increasing intracranial pressure . For a full-term newborn, the target heart rate and perfusion pressure (mean arterial pressure minus central venous pressure) are 110 to 160 beats/min and 55 mmHg, respectively.