Richard L. Schreiner

Indomethacin therapy on the first day of life in infants with very low birth weight

To investigate the optimal timing for treatment of small premature infants, we performed a double-blind, controlled trial of indomethacin therapy on the first day of life in 104 infants weighing between 700 and 1300 gm. Infants were given indomethacin or placebo at a mean age of 15 hours. Eleven of the 56 infants given placebo developed large left-to-right shunts through a patent ductus arteriosus. In contrast, only two of the 51 infants given indomethacin developed large shunts (P less than 0.025). There were no significant differences in incidence of surgical ligation, duration of oxygen therapy, duration of endotracheal intubation, days required to regain birth weight, or incidence of complications. However, the power of the tests of significance was low because of the small number of patients. Thus, although the incidence of large left-to-right ductus shunts was decreased in the indomethacin group, morbidity was not otherwise altered for the entire group of patients, possibly because of the relatively low incidence (21%) of large shunts in the placebo group. We conclude that although treatment with indomethacin on the first day of life appears to be safe, there is little advantage to its use in centers where the incidence of large shunts through a patent ductus arteriosus is relatively low.

Hepatic failure in infants on total parenteral nutrition (TPN): Clinical and histopathologic observations*

Total parenteral nutrition (TPN) is an important adjunct in the care of neonates with surgical disorders. Although cholestasis complicates TPN in 30% of cases, it is usually transient in nature. This report, however, describes 9 instances (8 fatal) of progressive liver failure in surgical neonates who were maintained on prolonged TPN (6 wk-15 mo) and demonstrated distinct hepatic pathologic changes. Diagnosis included complicated gastroschisis, (2) bowel atresia with peritonitis (1), NEC (4), prune belly and antenatal peritonitis (1), and total colonic and ileal aganglionosis (1). Mean gestational age was 35 wk with sexes equally affected. The 8 fatal cases had persistant cholestasis that failed to respond to changes in parenteral protein or glucose concentrations. Enteral feedings were not tolerated. Clinical deterioration was manifested by increasing serum bilirubin (22–35 mg%), clotting dysfunction, enzyme elevations (SGOT), and hepatomegaly. Histologic examination of the liver showed significant distortion of hepatic architecture with hepatocytes arranged in pseudoacini rather than cords and trapped by fibrous tissue. Bile duct proliferation was noted, but ducts contained no bile. Bile plugs were seen in canaliculi only. Hepatocytes showed diffuse vacuolization (+for fat) and contained brown pigment (+for iron). Portal triads were free of inflammation. Ultrastructural examination showed hepatocytes in an acinar array surrounded by collagen. Cystic changes in the endoplasmic reticulum, osmophilic cytoplasmic pigment, lipid droplets, and severe glycogen depletion consisten with acytotoxic insult were seen. Prematurity, immature liver function, and amino acid imbalance with formation of a toxic bile salt are implicated in these findings. Peritonitis, sepsis and inability to tolerate enteral feedings may also play a role. These observations indicate a need to modify TPN application in selected prematures requiring long-term nutritional support.

An evaluation of methods to monitor infants receiving intravenous lipids.

Nephelometric measurement of light-scattering index and visual estimates of turbidity have been advocated to monitor serum Intralipid levels. This study describes a simple modified fluorometric method for accurately measuring lipid particles in serum and examines the reliability of such estimates compared with other chemical measurements. Ten percent IL was diluted with either saline or serum to various concentrations (0 to 250 mg/dl). The LSI showed an excellent correlation with known IL standard solutions in saline or serum (R = 0.99) and with triglyceride concentrations (R= 0.98). One hundred nine blood samples were obtained from 35 patients (28 neonates) receiving IL. An elevated TG, free fatty acid, or cholesterol level could not be reliably predicted from the LSI. The ability of clinical personnel to visually grade the degree of turbidity was evaluated by having them assign a turbidity score of 0 to 4+ to 39 hematocrit tubes which contained clear, hemolyzed, or icteric serum, each of which had IL concentrations varying from 0 to 292 mg/dl. The 15 tubes of identical IL concentration of 99 mg/dl were graded from 0 to 4+ by two of the observers, from 1 to 4+ by three of the observers, and 0 to 3+, 1 to 3+, and 2 or 3+ by one each of the observers. This study shows that (1) in vitro fluorometric LSI correlates well with IL concentrations; (2) in vivo correlations of LSI with FFA, cholesterol, and TG are poor; and (3) personnel are unable to reliably grade turbidity by visual examination of hematocrit tubes. Infants on IL should be monitored by TG and FFA levels.

An Analysis of Tolazoline Therapy in the Critically-Ill Neonate

There were 47 seriously-ill neonates with medical causes of respiratory distress and 10 infants with severe respiratory distress secondary to a congenital diaphragmatic hernia treated with tolazoline according to a strict protocol designed to manage persistent fetal circulation (PFC). Of the 47 infants, 28 (60%) had a positive response defined as an increase in the pO2 greater than or equal to 24 mm Hg within 4 hr of beginning the drug. Of 7 infants, 4 with congenital diaphragmatic hernia had a positive response. The mean increase in the pO2 for the 47 infants was statistically significant (p less than .05). Of the 47 infants with medical disorders, 27 survived (survival 57%), whereas only 2 of the 10 infants with congenital diaphragmatic hernia and severe persistent fetal circulation survived (survival 28%). Erythema (60%), hematest positive gastric aspirates (55%), thrombocytopenia (45%), hyponatremia (40%) and increased gastric aspirates (36%) were the most common adverse effects occurring during tolazoline infusion. Hypotension occurred in nine cases, but was transient. Of the 27 survivors, 20 with medical causes of persistent fetal circulation were evaluated at age 1 yr. Eighty percent of these infants studied were considered normal as defined by an MDI and PI of the Bayley Scales of greater than or equal to 70. These data suggest that tolazoline is a useful adjunct in the management of neonates with PFC. In addition, tolazoline was more effective in mechanically ventilated neonates treated with respiratory paralytic agents. Although tolazoline resulted in a significant improvement in the paO2 in 4 infants with congenital diaphragmatic hernia, it did not appear to improve mortality in these infants.

Changes in clinical presentation of term infants with intracranial hemorrhage.

The clinical course and outcome of eight term infants with intracranial hemorrhage are reported. Before computerized tomography became available, term infants with intracranial hemorrhage were usually diagnosed only at autopsy and the hemorrhage was associated with a traumatic birth or severe asphyxia. In contrast, since the availability of computerized tomography, term infants with a diagnosis of intracranial hemorrhage have a non‐traumatic delivery, present with seizures, and survive.

The relative efficacy of four methods of human milk expression

In view of the current trend toward increased breast-feeding, both of normal term infants as well as sick or premature infants, a successful means for milk expression in order to establish and maintain lactation is of major importance to the mother. The present study was designed to evaluate four methods of milk expression, measuring the amount as well s the fat content of milk expressed by each method during a 10-min period. The four methods included the Egnell electric pump, the Loyd B pump, the Evenflo system, and manual expression. The electric pump enabled mothers to express significantly more milk with adequate fat content during the expression period than any of the other methods tested. No significant differences were found between the other three methods. The Egnell or similar electric pump may be a preferred method for milk expression for some mothers, particularly those anticipating a prolonged need for pumping.

Incidence and Effect of Traumatic Lumbar Puncture in the Neonate

The incidence of non‐traumatic, traumatic and unsuccessful lumbar punctures in 181 neonates was similar whether a needle with a stylet, a butterfly needle without stylet, or a standard venipuncture needle without stylet was used. Comparison of 20 lumbar puncture pairs in 17 patients showed that traumatic lumbar puncture does not result in a cerebrospinal fluid pleocytosis between two and 13 days after initial traumatic lumbar puncture.

Long-term follow-up after surgical management of necrotizing enterocolitis: Sixty-three cases

One hundred twenty-five infants underwent surgical intervention for necrotizing enterocolitis between 1972 and 1984. Sixty-three infants, who survived more than 30 days postoperatively, were evaluated for long-term complications. There were 28 girls and 35 boys (mean birth weight 1,725 +/- 890 g; gestational age 32 +/- 4 weeks). Associated problems included hyaline membrane disease (43), cardiac anomalies (25), and trisomy 21(2). Thirty-six survivors required long-term ventilatory support. Fifty-nine infants underwent bowel resection and enterostomy, 3 decompressing enterostomies without resection, and 1, exploratory laparotomy only. Enterostomies were closed at four months. Twenty four had short bowel syndrome. Fifteen infants subsequently died for a late mortality rate of 23%. Mortality was related to sepsis (3), respiratory failure (5), cardiac anomalies (3), cardio-respiratory arrest (2), and TPN related liver failure (2), and was common with gestational age less than 31 weeks and birth weight less than 1,000 g. Medical problems included cholestasis (17), TPN induced cirrhosis (3), meningitis (3), seizures (8), and nutritional rickets (6). Significant developmental and intellectual delays were observed.

Respiratory paralysis to improve oxygenation and mortality in large newborn infants with respiratory distress

The nonsynchronous respiratory efforts of neonates with surgically correctable disorders may inhibit effective mechanical ventilation. The records of 25 infants treated with metocurine for muscular paralysis to improve mechanical ventilation were reviewed. All patients were greater than 35 (37.6 +/- 2.1) weeks gestation and 2.27 (2.98 +/- .47) kg. All required ventilatory support with an FiO2 of 100%. The mortality rate of this group of infants was 20% as compared with 73% (p < .001) in a similar group of 26 infants managed without paralysis. In 10 of the 25 infants treated with metocurine, pre- and 1 hr postparalysis paO2 values were available. The mean paO2 prior to paralysis was 62 (45--111) mm Hg and the mean post-paralysis paO2 was 144 (75--227) mm Hg, representing at 132% increase in paO2 (p < .001). The mean dosage for metocurine was 3.5 (1.45--6.79) mg/kg/day; however, those requiring paralysis for greater than 7 days showed a dramatically increasing requirement. These preliminary data suggest that respiratory paralysis reduces right-to-left shunting, improves paO2 and decreases mortality in large infants with severe respiratory distress requiring ventilatory support.

Significance of portal vein air in necrotizing entercolitis: Analysis of 53 cases*

Fifty-three of 177 infants with necrotizing enterocolitis (NEC) developed portal vein air (PVA). These infants were evaluated for prenatal, perinatal, therapeutic, clinical, laboratory, radiographic, and operative factors as they related to infants with and without PVA. A significantly higher incidence of PVA was seen in infants with NEC who weighed less than 2400 g (P less than 0.025). The use of Vitamin E (P less than 0.01), aminophylline, and high-density premature formula (P less than 0.001) was associated with an increased incidence of PVA. NEC totalis was seen in 55% of the infants with NEC and PVA (P less than 0.001). The presence of PVA was associated with a 58% mortality rate (P less than 0.05). Infants with NEC and PVA operated on prior to 1983 had a 71% mortality. Since 1983, seven of nine infants with NEC and PVA survived early operation using PVA as an indication for surgical intervention. In infants at risk for this highly lethal form of NEC, the avoidance of enteral feedings or altered dietary intake, cautious placement of arterial catheters and the judicious application of pharmacologic agents (eg, Vitamin E, aminophylline) is of importance in regard to prevention. These observations suggest that PVA is a sign of advanced disease and that these high-risk patients should be considered candidates for early surgical intervention.