John B. Das

Total parenteral nutrition-associated cholestasis: Clinical and histopathologic correlation*

Cholestatic jaundice is the major complication of total parenteral nutrition (TPN) in infants and children. The pathogenesis of this syndrome is poorly understood. The aims of this study were: (1) to define the histologic liver injury in relation to the clinical course of infants on TPN and (2) to determine whether enteral feeding will reverse or halt these changes. We identified 31 infants treated for severe gastrointestinal disease for whom liver histology was available from 1987 to 1991. Clinical records and liver biopsy (23) or autopsy specimens (13) were reviewed. Five patients had biopsies at two subsequent operations. The clinical diagnosis was necrotizing enterocolitis (24), atresia or stenosis (3), midgut volvulus (2), Hirschsprungs disease (1), and sepsis (1). Twenty-one of 31 infants were premature and had a mean birth weight of 1,868 g. Twenty-five of 31 were on TPN and 28 of 31 had received some enteral feeding by the time of the biopsy. Enteral feeding was begun as early as possible in all infants even if continued TPN was necessary for full support. Cholestasis occurred in 71% of premature infants versus 22% of full-term babies. Infants with cholestasis had been on TPN for a longer time (37 days v 18) with a correspondingly shorter period of enteral feeding (17 days v 27). Mean total bilirubin level was 14 in patients with cholestasis and 5 in those without, but the bilirubin level did not correlate with the extent of histological injury and was frequently normal despite marked histological damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous dextrose-amino-acid feeding: The metabolic response in the surgical neonate

Abstract Extensive metabolic balance studies were undertaken in three neonates whose nutrition was maintained parenterally with a 20 per cent dextrose, five per cent fibrin hydrolysate mixture during staged repair of complicated omphalocele. All three showed, besides a satisfactory weight gain, positive nitrogen balance in the complete absence of oral feedings. The dextrose administered was adequately utilized; and significant glycosuria, osmotic diuresis or other adverse side effects were not detected.

Muscle surface pH as a monitor of tissue perfusion and acid-base status

Abstract Muscle pH, arterial pH, and blood gases were measured in 21 anesthetized dogs. After an initial control period, the animals were subjected to one of the following: major arterial occlusion in the limb being monitored, sever hemorrhage, hypoxia, or hypothermia (28°C). Muscle pH fell rapidly with a decrease in muscle perfusion caused by arterial occlusion or by hemorrhage, without any significant change in arterial pH. In hypoxia, muscle pH varied directly with arterial pH. Hypothermia under anesthesia did not affect muscle pH. Since muscle surface pH appears to be a reliable index of tissue perfusion and acid-base status, continuous muscle pH monitoring should prove valuable in the management of the critically ill infant. Early clinical trials have justified this impression.

Amino acid utilization during total parenteral nutrition in the surgical neonate

Abstract Amino acids, urea nitrogen, and creatinine in plasma and urine, and total urinary nitrogen were determined in five neonates during prolonged parenteral feeding. A fibrin hydrolysate-dextrose or a crystalline amino acid-dextrose solution was infused for periods as long as 33 days. These solutions supplied essential amino acids and total nitrogen (mostly as glycine) in excess of that available to infants on oral diets. Despite weight gain, positive nitrogen balance, and the absence of excessive amino aciduria, several biochemical abnormalities were detected. Plasma lysine, leucine, and glycine were consistently elevated and in one low birth weight infant, plasma phenylalanine and valine were also markedly raised. The excessive supply of glycine and nitrogen resulted in elevated urea levels in the blood and urine. The capacity to transform phenylalanine to tyrosine and methionine to cystine required by infants fed the tyrosine-cystine-free crystalline amino acid solution may be deficient in low birth weight premature infants and others with impaired liver function. These findings suggest that a more precise tailoring of the amino acid content of infusates for parenteral feeding is indicated. Such individually tailored solutions would decrease the metabolic and excretory load on the liver and kidneys.

Early hepatobiliary dysfunction during total parenteral nutrition: An experimental study

The etiology and pathophysiology of the liver disease associated with total parenteral nutrition (TPN) are unknown. In this study, we have attempted to define the early changes in hepatobiliary function during TPN in young rabbits nourished totally by the intravenous route for 3, 5, and 15 days, with age-matched rabbits on lab chow serving as controls. A decrease in basal bile flow along with elevations of serum bile acids and cholesterol was seen. The capacity for biliary secretion of sulfobromophthalein and of ursodeoxycholic acid was measured at the end of each diet regimen. Early impairment of biliary sulfobromophthalein (BSP) secretion was seen after 5 days of TPN, with no further deterioration after 15 days. Maximal bile acid secretory rate and bile flow, in response to the ursodeoxycholic acid load, were decreased after 15 days of TPN. Furthermore, after 15 days of TPN, both the volume of gallbladder bile and its bile acid content increased. The combined effects of the enteral fast and the intravenous administration of all nutrients were bile acid sequestration in an adynamic gallbladder with interruption of the enterohepatic circulation. In the parenterally fed rabbit, we have demonstrated bile secretory failure and gallbladder sludge, the two common complications of clinical TPN. These may be the early events that subsequently lead to cholestasis and liver damage in neonates maintained on prolonged TPN.

Parenteral nutritional support in children with cancer.

Acute and chronic starvation is often associated with childhood cancer. Total parenteral nutrition (TPN) with 20% glucose and 3.0% amino acids, and minerals and vitamins was instituted to treat or prevent malnutrition in 41 children with cancer, ages three months to 18 years. TPN was required for anorexia, vomiting and diarrhea associated with anti‐cancer therapy in 33 patients for intestinal complications or surgery in nine, and for preoperative correction of malnutrition in two. During TPN, general nutrition and appearance improved in all patients. Weight gain was noted in most. Despite gastrointestinal complications which usually require the interruption of chemotherapy and irradiation, in 21 children treatment could be continued at full dose with nutritional support by TPN. TPN was discontinued in six patients when blood cultures became positive. Sepsis was treated successfully by removal of the central venous catheter in all six and administration of antibiotics in three. No metabolic complications were noted. TPN appears to be a safe and effective means of combating the malnutrition which may occur with cancer and its therapy.

Continuous monitoring of pH in the tissue mode: evaluation of a miniature sensor during acidosis and tissue hypoperfusion.

The in vivo performance of a 20G copolymer pH sensor, needlelike in configuration, was studied in the normal dog, and dogs made acidotic by the constant infusion of lactic acid, or by the induction of tissue perfusion defects. Sensors were placed at two extravascular sites in the leg, deep subcutaneous (pHe/sc), and intramuscular in the adductor (pHe/im). This pH sensor is a silver wire capped by a H+-specific polymer; it has a built-in reference system. Its electrochemical characteristics and in vivo performance are similar to those of glass pH electrodes. The continuously monitored values were compared with discrete arterial blood gas analyses at 10 to 20 minute intervals. The baseline values in 15 dogs under general anesthesia were: pH/art 7.331 +/- .042, pHe/sc 7.291 +/- .076, and pHe/im 7.265 +/- .102 (mean +/- SD; n = 45 observations each). During metabolic acidosis (lactic acid infusion), the direction and rates of change were similar in pHe/sc and pHe/im. Tissue perfusion defects were induced by moderate-to-severe hemorrhage (single or repeated bleeds) or operative shock (splenectomy and exteriorization of bowel). Both pHe/sc and pHe/im fell sharply, with a more gradual drop in pH/art. In those who survived after infusion of shed blood or dextran-40, pHe recovered rapidly. In the moribund, pHe continued to deteriorate. This pH sensor is a sensitive prognosticator of acid-base changes in the tissue. The in vivo drift is small: 0.008 pH per hour. The placement of the sensor via an intracath cannula in the subcutaneous tissue of the thigh is recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle pH, pO2, pCO2 monitoring: a review of laboratory and clinical evaluations.

The vital physiologic data necessary for the care of the critically ill are currently obtained from clinical observation, pulse, arterial and central venous pressures, electrocardiogram and blood gas determinations. In the infant, these parameters are often inaccurate (clinical observation), difficult to obtain because of the infant’s size (blood pressure), potentially hazardous (in-dwelling arterial line), and fail to provide minute-to-minute information (blood gas determination). In addition, these parameters may not necessarily reflect the physiologic state of the peripheral tissues. In our search for better and safer methods to assess vital functions in the very young, we have been evaluating the feasibility of continuous tissue monitoring of pH and more recently PCO2 and PO2.

Depression of glucose utilization by intralipid in the post-traumatic period: An experimental study

We investigated the accelerated clearance of Intralipid (IL) in the immediate post-traumatic period and the influence of the concomitant rise in fatty acid ((FFA) metabolism on carbohydrate tolerance. As a result we postulate that intermediary products of fatty acid oxidation inhibit key enzymes in the glycolytic pathway. The fatty acidemia and its metabolic sequlae can be avoided by intermittent Intralipid supplementation (at low rates) during TPN. It will assure (1) a larger carbohydrate-to-fat caloric ratio during infusion and (2) cyclical regeneration of the enzyme systems involved in lipid metabolism.

Serum ionic calcium: Changes with large volume blood transfusions in the infant☆

Abstract The serial changes in serum ionic calcium and serum citrate concentrations during extensive surgery with massive blood transfusions were studied in eight infants under 2 years of age, including three infants undergoing right hepatic lobectomy. High serum citrate levels (above 50 mg/100 ml) were seen only during hepatic lobe resection and were accompanied by precipitous falls in serum ionic calcium levels to levels below 0.50 mM/liter. The current practice of administering 1 ml of 10% calcium gluconate per 200 ml of citrated blood infused was found to be inadequate in overcoming the calcium-chelating effect of citrate during rapid transfusion. Direct monitoring of the serum ionic calcium with the calcium activity flow-through system will measure the fall in the ionic fraction of serum total calcium, and provide a guide to calcium replacement during massive transfusions of citrated blood in the young infant.