Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler-Najjar disease

Abstract

We summarize the treatment of 20 patients with Crigler-Najjar disease (CND) managed at one center from 1989 to 2005 (200 patient-years). Diagnosis was confirmed by sequencing the UGTA1A gene. Nineteen patients had a severe (type 1) phenotype. Major treatment goals were to maintain the bilirubin to albumin concentration ratio at <0.5 in neonates and <0.7 in older children and adults, to avoid drugs known to displace bilirubin from albumin, and to manage temporary exacerbations of hyperbilirubinemia caused by illness or gallstones. A variety of phototherapy systems provided high irradiance over a large body surface. Mean total bilirubin for the group was 16±5 mg/dl and increased with age by approximately 0.8 mg/dl per year. The molar ratio of bilirubin to albumin ranged from 0.17 to 0.75 (mean: 0.44). The overall non-surgical hospitalization rate was 0.12 hospitalizations per patient per year; one-half of these were for neonatal hyperbilirubinemia and the remainder were for infectious illnesses. Ten patients (50%) underwent elective laproscopic cholecystectomy for cholelithiasis. No patient required invasive bilirubin removal or developed bilirubin-induced neurological damage under our care. Visual acuity and color discrimination did not differ between CND patients and age-matched sibling controls. Four patients treated with orthotopic liver transplantation were effectively cured of CND, although one suffered significant transplant-related complications.Conclusions. While patients await liver transplantation for CND, hyperbilirubinemia can be managed safely and effectively to prevent kernicterus. Lessons learned from CND can be applied to screening and therapy of non-hemolytic jaundice in otherwise healthy newborns.

Appendix

Potential bilirubin-albumin displacing interactions (see text for references)

	SAFETY CLASS (see Note)
	1	2	3	4
ANTI-INFLAMMATORY/ANTIPYRETIC
Acetaminophen	•
Aspirin		•
Dexamethasone	•
Ibuprofen			•
Indomethacin				•
Ketorolac				•
Naproxen	•
Phenacetin	•
Prednisolone	•
Salicylate, sodium		•
ANTIMICROBIAL
Acyclovir	•
Amoxicillin			•
Amoxicillin-Clavulanate			•
Amphotericin B	•
Amphotericin, liposomal
Ampicillin			•
Ampicillin-Sulbactam				•
Azithromycin
Azlocillin				•
Aztreonam		•
Carbenicillin				•
Cefazolin			•
Cefalothin	•
Cefepime				•
Cefixime				•
Cefmetazole		•
Cefonicid		•
Cefoperazone		•
Ceforanide	•
Cefotaxime			•
Cefotetan		•
Cefoxitin				•
Cefpodoxime proxetil				•
Ceftazidime	•
Ceftizoxime	•
Ceftriaxone		•
Cefuroxime	•
Cefuroxime axetil	•
Cephalexin				•
Cephapirin	•
Cephradine	•
Ciprofloxacin	•
Clarithromycin				•
Clindamycin	•
Dicloxacillin		•
Doxycycline				•
Erythromycin	•
Erythromycin ES-sulfisoxazole		•
Fusidic acid	•
Gangcyclovir				•
Gentamicin	•
Imipenem	•
Imipenem-cilastatin	•
Isoniazid	•
Levofloxacin				•
Lincomycin	•
Linezolid				•
Meropenem				•
Methicillin			•
Metronidazole	•
Minocycline				•
Nafcillin	•
Nitrofurantoin				•
Oxacillin	•
Penicillin G	•
Penicillin V		•
Piperacillin	•
Piperacillin-Tazobactam	•
Rifampin				•
Streptomycin	•
Sulfisoxazole		•
Sulphamethoxazole		•
Sulphasalazine		•
Tobramycin	•
Trimethoprim	•
Trimethoprim-Sulfa (Bactrim)		•
Vancomycin	•
CARDIOVASCULAR DRUGS
Atropine	•
Bretylium tosylate	•
Digoxin	•
Disopyramide	•
Dobutamine	•
Dopamine	•
Edrophonium chloride	•
Enalapril	•
Epinephrine	•
Hydralazine	•
Isoproterenol	•
Lidocaine	•
Nitroprusside	•
Procainamide	•
Propanalol	•
Verapamil	•
CONTRAST AGENTS
Diatrizoate sodium				•
Iodate sodium		•
Iodipamide sodium		•
Iopanoic acid		•
Meglumin ioglycamate		•
Metrizamide	•
Metrizoate sodium				•
DIURETICS
Acetazolamide		•
Bumetanide	•
Chlorothiazide				•
Ethacrynic acid		•
Furosemide			•
Hydrochlorothiazide			•
Mannitol	•
Spironolactone	•
NEUROACTIVE DRUGS
Aminophylline		•
Amitryptyline HCl	•
Atomoxetine				•
Bupropion				•
Carbamazepine	•
Chloral hydrate	•
Clonazepam	•
Codeine	•
Desipramine HCl				•
Diazepam	•
Ethosuximide	•
Etomidate				•
Fentanyl	•
Fluoxetine/Norfluoxetine				•
Inhaled anesthetics	•
Imipramine HCl				•
Ketamine	•
Lorazepam	•
Meperidine	•
Methylphenidate				•
Midazolam	•
Morphine	•
Naloxone	•
Nortryptyline	•
Olanzapine				•
Oxazepam	•
Paroxetine				•
Phenobarbital	•
Phenytoin	•
Primidone	•
Propofol				•
Risperidone				•
Theophylline				•
Thiopental	•
Valproic acid			•
Venlafaxine				•
NEUROMUSCULAR BLOCKING AGENTS
Neostigmine	•
Pancuronium	•
Rocuronium				•
Succinylcholine				•
Vecuronium	•
PRESERVATIVES/METABOLITES [a]
N-acetyl-DL-tryptophan			•
N-acetyltyrosine				•
Benzoic acid (benzoate sodium)		•
Caprylic acid			•
Hippurate (from benzoic acid)
2-Hyroxybenzoylglycine		•
MISCELLANEOUS
Bicarbonate	•
Calcium chloride	•
Calcium gluconate	•
Carnitine	•
Clofibrate	•
Heparin	•
Intralipid/free fatty acids [b]			•
Magnesium sulfate	•
Prostaglandin E1	•
Tin mesoporphyrin				•

1. 1 Probably SAFE for clinical use
2. 2 Considered UNSAFE
3. 3 Safety variable: eg. drug dosing and combinations
4. 4 Insufficient data
5. a) acetyltryptophan (stabiliser in HSA I), acetyltyrosine (component of some TPN amino acid mixtures), caprylic acid, hexanoic acid (stabiliser in HSA I and II)
6. b) plasma free fatty acids are increased by fasting and infusions of intralipid, epinephrine or heparin.