Reduction In Serum Bilirubin Levels Research Articles

URINARY EXCRETION OF LUMIRUBIN DURING PHOTOTHERAPY

Lumirubin (LR) is a stable photoproduct of bilirubin (BR), formed by an essentially irreversible intramolecular cyclization reaction. Unlike other BR photoisomers, LR is detected in both urine and bile in infants under phototherapy (PT). Clinical studies have suggested that the production and excretion of LR may contribute to the reduction of serum BR levels produced by PT. We therefore sought to determine the urinary LR excretion. We measured urinary LR clearance (clr) rate in 9 preterm infants under PT studied at a mean age of 4 days (range 1-6). Mean birthweight was 1.8 kg (range .7-2.9); mean gestational age (GA) was 32 wks (range 25-37). Urine and a serum sample obtained during the 24 hour collection period were analyzed for BR photoproducts by HPLC. Creatinine (Cr) clr was measured on the sample. Mean LR clr was .16±.19 ml/min (mean±S.D.) which is equivalent to 8±4% of Cr clr (2.6±3.2 ml/min). LR clr increased with GA in parallel with Cr clr. The amount of LR excreted per 24 hours was 1.4±1.5 mg (range .9-4). Daily BR production far exceeds the amount of LR excreted in the urine of preterm infants, so this cannot account for the efficacy of PT. However, were the clearance rate of LR to be increased to that of Cr through pharmacologic means (i.e. by blocking tubular reabsorption), urinary clearance of LR could become quantitatively important. As the urinary excretion of LR does not account for the decrease in serum BR with PT, the bile is presumably the major site of excretion of BR photoproducts.

Percutaneous Decompression of Benign and Malignant Biliary Obstruction

Percutaneous transhepatic catheterization of the biliary tree was performed in 41 patients with obstructive jaundice. In 39 patients, the catheter was successfully advanced past the obstructing lesion into the distal common duct and duodenum to establish internal biliary drainage. The remaining two patients had the obstructed biliary tract drained externally. Chronic internal catheter drainage was instituted in five patients with stricture and ten with malignant obstruction as a means of palliating symptomatic jaundice. Twenty-two patients had marked reduction in serum bilirubin levels and pruritus, eight patients had moderate decreases in serum bilirubin levels, and six patients did not improve despite adequate catheterization due to hepatic parenchymal disease. This procedure effectively decompresses the severely obstructed biliary tree prior to surgery and can also palliate patients with unresectable malignant biliary obstruction and stent high-risk, benign strictures.

Partial exchange transfusion in sickle cell anemia. Use in children with serious complications.

Seventeen children with sickle cell anemia received 40 partial exchange transfusions for serious complications of sickle cell anemia, and preoperatively to reduce the risk of anesthesia. Each patient received two partial exchange transfusions at 24-hour intervals and all patients tolerated the exchange transfusions well. The mean hematocrit level rose from 22.9% before the exchange transfusion to 40.6% at the end of the second exchange. The mean sickle hemoglobin level decreased from 93.8% before the exchange to 28.0% after the second exchange. Patients with acute lung syndrome had remarkable improvement in clinical symptoms and PaO2 levels, and those with acute liver crisis had substantial reduction in serum bilirubin levels. All the other patients showed marked clinical improvement following the exchange transfusions.

PHENOBARBITONE ENHANCEMENT OF BROMSULPHALEIN CLEARANCE IN NEONATAL HYPERBILIRUBINEMIA

Forty jaundiced Chinese newborn infants were randomly assigned to treatment and control groups. Twenty infants in the former group were given phenobarbitone 5 mg 8-hourly; those in the control group received no drug. BSP tests were performed in all infants on admission and repeated 24 hours afterwards. The percentage disappearance of the dye at designated intervals up to 135 minutes of each test before and after drug therapy was compared with that of the controls. Rate constants for the hepatic uptake phase (K1) and the biliary excretory phase (K2) in BSP removal were calculated from the plasma dye disappearance graph. Following phenobarbitone therapy, a significant increase in BSP clearance was observed, with increases in K1 and K2 values, suggesting the corresponding enhanced hepatic uptake and excretion of the dye. These results are consistent with the hypothesis that several mechanisms together are responsible for the phenobarbitone effect on the impaired liver function of newborn infants. It is suggested that the observed reduction of serum bilirubin levels with phenobarbitone therapy results both from enhanced uptake and from increased excretion of bilirubin by the liver.

Effect of phenobarbital on hyperbilirubinemia and glucuronide formation in newborns.

Twenty full-term newborns given phenobarbital 8 mg/kg/day for the first four days of life had significantly lower concentrations of serum indirect bilirubin than a group of 20 control infants by the fourth and fifth day of life. Similarly, ten infants with elevated serum indirect bilirubin levels treated from the fifth to ninth day showed significantly lower values by day 10 than controls. In vivo glucuronidation studies using salicylamide as the substrate showed a more pronounced average increase in the glucuronide fraction between the fifth and tenth day of life in ten infants pretreated with phenobarbital as compared to a group of 14 controls, suggesting that the effect of phenobarbital in reducing serum bilirubin levels is mediated, at least in part, by enhanced glucuronide formation.

CLINICAL EXPERIENCE WITH PHENOBARBITONE IN ICTERUS NEONATORUM

To test the clinical feasibility of reducing serum-bilirubin levels in neonates by druginduced glucuronidation, 52 full term, healthy infants were given phenobarbitone orally 8 mg. per kg. bodyweight daily when icterus neonatorum first appeared after 24 hours of life. 12 similarly affected infants who were not given phenobarbitone comprised the control group. The data showed no significant reductions in serumbilirubin levels between control and treated neonates and suggested that, once unconjugated hyperbilirubinæmia exists in the neonate, it is unresponsive to phenobarbitone.

"EARLY" VERSUS "LATE" FEEDING OF LOW BIRTH WEIGHT NEONATES: EFFECT ON SERUM BILIRUBIN, BLOOD SUGAR, AND RESPONSES TO GLUCAGON AND EPINEPHRINE TOLERANCE TESTS

Effects of early (2 hours after birth) and late (24 to 36 hours after birth) feeding were studied in 42 "well born" and clinically well low birth weight infants in the 1,250 to 2,000 gm birth weight range. Twenty-one of these, selected at random, were early fed and 21 were late fed. In the early-fed infants weight loss was less (mean 4.7% of birth weight) and regained earlier (mean 7.3 days); in the late-fed infants weight loss was greater (7.4% of birth weight) and regained later (mean 12.6 days). Blood glucose was higher in the early-fed group than in the late-fed group at 24 hours of age. A higher response in blood glucose level was seen in the early-fed infants following glucagon and epinephrine administration at 24 hours. No adverse effects were observed as a result of early feeding. Such feedings may indeed have an advantage in reducing serum bilirubin levels, raising blood sugar, and increasing liver glycogen reserves.