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Management of Crigler-Najjar syndrome

Management of Crigler-Najjar syndrome
Principles of effective phototherapy
  • Light source: High-intensity LED, BB fluorescent tubes, or energetic equivalent (eg, TL52); maximum emission of 400 to 525 (peak 450 to 460) nm
  • Source distance from skin: 30 to 45 cm for infants, 45 to 60 cm for children and adults
  • Skin exposure: Body surface area exposure 60 to 70% for neonates, 35 to 50% for children and adults
  • Exposure duration: 15 to 20 hours per day for neonates, 7 to 13 hours per day for children and adults

  • Surroundings: White bedsheets; reflective surfaces
Treatment goals
  • Phototherapy with irradiance at skin surface: 40 to 100 microW/cm2 per nm*
  • Maintain unconjugated bilirubin (serum or plasma): <20 mg/dL (340 micromol/L)
  • Maintain unconjugated bilirubin/albumin (B/A) ratio in safe range:  
    • <0.7 mol:mol (molar ratio) 
    • <6.15 mg/g (mass ratio)
    • 1 g of albumin binds approximately 9 mg total bilirubin 

  • Avoid: Drugs and drug vehicles that displace bilirubin from the albumin-binding site
Inpatient management for severe hyperbilirubinemia
  • Reverse and/or prevent concomitant neurologic threats, such as:
    • Hypovolemia, hypotension
    • Hypercarbia, acidosis
    • Hypoglycemia, hyperglycemia
    • Hypernatremia, hyperosmolarity
    • Hyperthermia
  • Rule out concomitant conditions that exacerbate hyperbilirubinemia, such as:
    • Hemolytic disease
    • Internally sequestered or ingested bloodΔ
    • Cholelithiasis or biliary obstruction◊
    • Constipation
  • Provide continuous high-intensity phototherapy:
    • Position the light source at minimal tolerated distance from skin
    • Maximize the proportion of skin surface exposed
    • Provide light exposure for about 24 hours per day
  • Restore and maintain intravascular hydration:
    • Intravenous normal saline (10 to 20 mL/kg bolus infusions) to establish euvolemia
    • Intravenous dextrose in normal saline at 1 to 1.5 times maintenance rate◊
  • Prevent bilirubin displacement from albumin:
    • Avoid drugs and drug vehicles that displace bilirubin from the albumin-binding site
    • Avoid drug combinations when possible
    • Use special caution with intravenous bolus dosing of drugs or contrast agents
  • Optimize enterohepatic lumirubin excretion:
    • Enteral feeding: Milk-based formula in infants, lipid-rich foods in children and adults
    • Enteral calcium salts (mixture of calcium phosphate and calcium carbonate)§
    • For cholelithiasis and/or biliary sludging: Consider emergency cholecystectomy
  • Prepare for emergency measures, based on B/A ratio:
    • For B/A ≥0.7 mol:mol: Give intravenous albumin 1 to 2 g/kg per dose, every 6 to 12 hours as needed

    • For B/A ≥0.9 mol:mol: Plasmapheresis (or exchange transfusion in neonates)
LED: light-emitting diode; W: watts; B: total bilirubin; A: albumin.
* Different light meters produce variable measurements from the same source. We use the BiliBlanket Meter II (GE Healthcare, Chicago, IL).
¶ Hemolytic conditions should be sought and treated. Consider (1) immunologic/autoimmune, (2) red blood cell enzymopathies, (3) ineffective erythropoiesis, and (4) physical destruction.
Δ Internal hemorrhage, occult tissue hematoma, peripartum blood ingestion by neonates.
◊ 10% dextrose solution for infants and toddlers, 5% dextrose for older children and adults.
§ Equimolar doses of calcium carbonate and calcium phosphate are better tolerated and more effective than calcium carbonate alone. We use the following total daily doses for oral calcium salts:
  • Adults and children >40 kg body weight: 100 mmol calcium, which may be delivered as[1]:
    • Four 1250 mg calcium carbonate tablets (or 20 mLs of 1250 mg/5 mL oral suspension), providing 50 mmol (2 g) elemental calcium plus
    • Two rounded teaspoonfuls of dicalcium phosphate (4 g salt/teaspoon) bulk powder supplement[2] providing approximately 50 mmol (2 g) elemental calcium
  • Children <40 kg body weight:
    • 2.5 mmol calcium/kg body weight (up to 100 mmol per day), as equal calcium mmols as carbonate and phosphate salts.
    • The following conversions may be used[3]:
      • 1 gram calcium carbonate = 400 mg elemental calcium = 10 mmol calcium
      • 1 gram dicalcium phosphate = 233 mg elemental calcium = 5.8 mmol calcium
   The above total daily doses for adults and children are given in 3 to 4 divided doses per day (eg, with meals and at bedtime).
References:
  1. Van der Veere CN, Jansen PL, Sinaasappel M. Oral calcium phosphate: a new therapy for Crigler-Najjar disease? Gastroenterology 1997; 112:455.
  2. National Institutes of Health; Dietary Supplement Label Database: Dicalcium Phosphate (DCP) bulk powder. Available at https://dsld.od.nih.gov/dsld/prdLabel.jsp?id=23078 (accessed November 26, 2020).
  3. Lexicomp online. Copyright © 1978-2023 Lexicomp, Inc. All Rights Reserved.
From: Strauss KA, Ahlfors CE, Soltys K, et al. Crigler-Najjar Syndrome Type 1: Pathophysiology, Natural History, and Therapeutic Frontier. Hepatology 2020; 71(6):1923-1939. https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.30959. Copyright © 2019 by the American Association for the Study of Liver Diseases. Modified with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on Wiley Online Library (https://onlinelibrary.wiley.com/).
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