Vancomycin pharmacokinetics in very low birth weight neonates

The pharmacokinetics of vancomycin hydrochloride was studied in 12 very low birth weight infants. The gestational age (mean +/- SD) was 25.9 +/- 1.3 weeks and body weight was 769.2 +/- 151.5 g at the time of initiation of the study. Vancomycin was infused over a period of 60 minutes in a dosage of 14.2 +/- 3.2 mg/kg once daily in 10 patients, twice daily in 1 patient and every 36 hours in 1 patient for a mean of 10.5 +/- 4.9 days. Serial blood samples were obtained and the concentration time data were fitted to a one-compartment open model using the ADAPT computer program. A significant positive correlation was found between postconceptional age and vancomycin clearance (P less than 0.005) and between vancomycin elimination half-life and plasma creatinine (P less than 0.01). A negative correlation existed between plasma creatinine and vancomycin clearance (P less than 0.005), between postconceptional age and plasma creatinine (P less than 0.005) and between vancomycin half-life and postconceptional age (P less than 0.01). On the basis of these findings a vancomycin dosage of 15 mg/kg every 24 hours for infants less than 1000 g should yield concentrations within the accepted therapeutic range. This susceptible population requires frequent monitoring of vancomycin concentrations because of the high degree of interpatient variability and the continuous maturation of renal function.     

Cefotaxime and desacetylcefotaxime pharmacokinetics in very low birth weight neonates

The single-dose pharmacokinetics of cefotaxime (CTX) and desacetylcefotaxime (dCTX) after a 50.0 mg/kg intravenous dose were evaluated in 18 very low birth weight neonates (13 male; 1015.6 +/- 349.8 gm; 28.4 +/- 2.4 weeks gestational age) during the first week of life. Microanalytic high-performance liquid chromatography was used to quantitate both CTX and dCTX from serum. A two-compartment open model best characterized the disposition of CTX during a 24-hour post-dose period. The disposition of dCTX was adequately characterized by a one-compartment model. The elimination half-life, apparent steady-state volume of distribution, and total body clearance of CTX (mean +/- SEM) were 4.44 hours, 0.461 +/- 0.027 L/kg, and 0.074 +/- 0.003 L/hr/kg, respectively. Peak concentrations (mean +/- SD) of dCTX (17.96 +/- 5.54 mg/L) occurred at 0.6 to 8.3 hours (5.9 +/- 1.9 hours) after CTX administration, and the apparent elimination half-life of dCTX was 9.36 hours. Comparison of CTX and dCTX pharmacokinetic parameters between very low birth weight neonates who weighed less than 1000 gm (n = 9; 703.3 +/- 46.6 gm; 27.0 +/- 0.8 weeks gestational age) and greater than or equal to 1000 gm (n = 9; 1328.8 +/- 48.6 gm; 29.8 +/- 0.5 weeks gestational age) revealed no significant differences, but significant linear correlations were found between gestational age and weight versus CTX half-life and total body clearance. Because of the prolonged clearance of both CTX and dCTX in the very low birth weight neonate, a CTX dose of 50 mg/kg every 24 hours may provide effective serum concentrations for susceptible infections outside the central nervous system.     

Pharmacokinetics of intravenous immunoglobulin in very low birth weight neonates

We studied the pharmacokinetics of single doses of intravenous immunoglobulin (IVIG) of 1000, 750 and 500 mg/kg administered to 21 neonates with birth weights from 750 to 1500 g. No adverse effects were detected. Mean pharmacokinetic values for the large, intermediate and small dose groups, respectively, were: elimination half-life, 19.6, 28.7 and 22.1 days; clearance, 5.2, 5.6 and 3.7 ml/kg/day; volume of distribution, 151, 255 and 130 ml/kg. Mean peak IgG concentrations in serum were 1826, 1476 and 1257 mg/dl for the large, intermediate and small dose groups, respectively. Mean IgG on post-infusion Days 1 to 28 were similar for the intermediate and small dose groups but were higher in the larger dose group. Both large and intermediate doses achieved larger increases in IgG over preinfusion values (delta IgG) than the small dose. The differences in delta IgG between the large and intermediate doses were less notable. The wide variability observed indicates that individualization of intravenous immunoglobulin dosage will be required in these patients.     

Thoracotomy for persistent bronchopleural fistula in the very low birth weight infant

Although conservative treatment is appropriate for most very low birth weight infants with bronchopleural fistulas, early surgical closure may improve survival in properly selected patients. We report our experience with successful surgical closure in 3 consecutive neonates weighing <800 g.     

Liver vitamin A reserves of very low birth weight neonates

This study assessed the liver vitamin A concentrations at birth in a group of very low birth weight neonates (n = 25) (less than 1500 g birth weight, less than 32 wk gestation), dying within 24 h of birth, prior to possible changes in vitamin A status induced by postnatal intervention. Serum concentrations of vitamin A and retinol-binding protein were also measured in 16 of these neonates. The mean (+/- SD) liver vitamin A concentration was 30.0 +/- 12.9 micrograms/g (range 2.0-49.0 micrograms/g). The mean (+/- SD) serum vitamin A concentration was 13.0 +/- 4.7 micrograms/dl (range 6.7-22.8 micrograms/dl). The mean (+/- SD) serum retinol-binding protein concentration was 2.2 +/- 0.8 mg/dl (range 1.5-4.8 mg/dl). Liver vitamin A, serum vitamin A, and serum retinol-binding protein concentrations did not correlate significantly with gestational age or birth weight. Linear regression analysis did not show a significant correlation between liver vitamin A, and serum vitamin A or retinol-binding protein concentrations. This study provides reference values for vitamin A concentrations at birth in very low birth weight neonates, which may be helpful in future studies designed to evaluate postnatal changes in the vitamin A status of these high-risk neonates.     

Early predictors of mortality in very low birth weight neonates.

OBJECTIVE: To evaluate early predictors of mortality in very low birth weight neonates. SETTING: Teaching hospital. DESIGN: Case control study. METHODS: Hospital born very low birth weight newborns (500-1500 g) enrolled for study and followed up till death or 28 days. Infants' birth data and data on physiologic alterations, investigation and interventions in the first 24 hours of life and CRIB score were analyzed for their ability to predict neonatal mortality. RESULTS: 115 subjects were enrolled into the study of which 47 died in the neonatal period. The factors significantly associated with early neonatal mortality included birth weight, gestation, low Apgar scores, need for assisted ventilation at birth, need for supplemental oxygen and mechanical ventilation in the first 24 hours, presence of shock, hypoxia and acidosis (p < 0.05). The factors associated with late neonatal mortality were birth weight and gestation only. Multivariate analysis of these factors showed that besides low birth weight, shock, need for mechanical ventilation, acidosis and high alveolar-arterial oxygen gradients were significant predictors of neonatal mortality. When compared with the CRIB score, birth weight <1200g proved to be an equally good predictor of mortality risk. CONCLUSION: VLBW neonates with disturbed cardio-pulmonary physiology during the first 24 hours of life, especially those in need of mechanical ventilation, are at an increased risk of early neonatal mortality.     

Small-bowel perforation in very low birth weight neonates treated with high-dose dexamethasone.

INTRODUCTION: Early postnatal treatment with high doses of corticosteroids may be effective in reducing the duration of mechanical ventilation in very low birth weight infants at risk for bronchopulmonary dysplasia. However, serious side effects may occur. MATERIAL AND METHODS: A retrospective study on 5 very low birth weight neonates, mean (+/- SEM): gestational age range 27.5 +/- 2 weeks, mean birth weight (+/- SEM): 836 g +/- 169 referred between April 1997 and October 1998 from a single academic neonatal intensive care unit to our tertiary pediatric surgical center with the diagnosis of intestinal perforation. During the same period, 60 very low birth weight infants have been treated in that unit following a standardized protocol including surfactant for respiratory distress syndrome and high-dose dexamethasone to prevent bronchopulmonary dysplasia. RESULTS: Pneumoperitoneum was diagnosed between 6 to 9 days after birth. Clinically, all babies remained surprisingly stable. An isolated ileal perforation, without sign of necrotizing enterocolitis, was found at laparotomy in each patient. A limited intestinal resection was performed, with primary end-toend anastomosis (3 cases) or with transient ileostomies (2 cases). Surgical outcome was favorable in all patients. CONCLUSION: isolated intestinal perforation may be a complication of the preventive treatment of chronic lung disease with high-dose corticosteroids in very low birth weight infants. Conversely, corticosteroids may reduce the clinical signs and the multiple organ dysfunction associated with an abdominal drama, explaining the very good surgical prognosis of these newborns. Attention must be paid to an insidious pneumoperitoneum.     

Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates

OBJECTIVE: To test the hypothesis that normalizing the intestinal flora by administration of prophylactic probiotics would provide a natural defense, thereby reducing both the incidence and severity of necrotizing enterocolitis (NEC) in preterm neonates. STUDY DESIGN: Neonates < or =1500 g birth weight were randomized to either receive a daily feeding supplementation with a probiotic mixture (Bifidobacteria infantis, Streptococcus thermophilus, and Bifidobacteria bifidus; Solgar, Israel) of 10(9) colony forming units (CFU)/day or to not receive feed supplements. NEC was graded according to Bell's criteria. RESULTS: For 72 study and 73 control infants, respectively, birth weight (1152 +/- 262 g vs 1111 +/- 278 g), gestational age (30 +/- 3 weeks vs 29 +/- 4 weeks), and time to reach full feeds (14.6 +/- 8.7 days vs 17.5 +/- 13.6 days) were not different. The incidence of NEC was reduced in the study group (4% vs 16.4%; P=.03). NEC was less severe in the probiotic-supplemented infants (Bell's criteria 2.3 +/- 0.5 vs 1.3 +/- 0.5; P=.005). Three of 15 babies who developed NEC died, and all NEC-related deaths occurred in control infants. CONCLUSION: Probiotic supplementation reduced both the incidence and severity of NEC in our premature neonatal population.     

Risk factors for early sepsis in very low birth weight neonates with respiratory distress syndrome

AIM: To identify maternal and neonatal factors that increase suspicion of early sepsis in Very Low Birth Weight neonates with respiratory distress syndrome. METHODS: The cohort included 282 neonates born at Soroka Medical Centre 1996-2000. Definitions of 'high' and 'low'-suspicion groups for early sepsis were based on comparison between neonates with early sepsis and the remaining cohort. Univariate analysis and logistic regression were used to compare between groups. RESULTS: The incidence of early sepsis in the cohort was 1.8%, and 94% received antibiotics following delivery. Comparing with the remaining cohort, the five neonates with early sepsis had increased incidence of positive maternal cultures, use of antenatal antibiotics, lower 1 min Apgar scores and tendency to leucopenia. A 'low-suspicion' group comprised 38% of the cohort and did not include any neonates with early sepsis. This group were more frequently treated with antenatal steroids and delivered by Caesarean section compared to the 'high-suspicion' group, but otherwise there were no clinical and laboratory differences. CONCLUSION: Although the incidence of early sepsis is low almost all neonates received antibiotics. A 'low-suspicion' group was defined and the role of antibiotic treatment in this group needs to be determined.     

Cardiovascular effects of low-dose dexamethasone in very low birth weight neonates with refractory hypotension

BACKGROUND: Administration of hydrocortisone and relatively high doses of dexamethasone increase blood pressure in volume- and pressor-resistant hypotensive preterm infants. However, little is known about the temporal relationship of dexamethasone administration and the improvement in blood pressure and the weaning of pressors/inotropes. Furthermore, there are no sufficient data available on whether a smaller dose of dexamethasone would also be effective in treating refractory hypotension. OBJECTIVE: To study the cardiovascular responses to low-dose dexamethasone in very low birth weight neonates with volume- and pressor-resistant hypotension. METHODS: Retrospective database review. Twenty-four preterm neonates (gestational age 26 (23-34) weeks; birth weight 801 (457-1,180) g; postnatal age 2 (1-24) days, medians (ranges)) who remained hypotensive despite volume administration and combined dopamine and dobutamine treatment at >or=30 microg/kg/min received dexamethasone 0.1 mg/kg followed by 0.05 mg/kg intravenously every 12 h for 5 additional doses if still on pressors >or=8 microg/kg/min. RESULTS: Two hours after the first dose of dexamethasone the mean blood pressure increased from 30 +/- 5 to 34 +/- 6 mm Hg (p < 0.001) and remained elevated at 4, 6, 12, and 24 h after treatment was started (p < 0.001). Six hours after the initial dose of dexamethasone the pressor/inotrope requirement decreased from 34 +/- 9 to 24 +/- 13 microg/kg/min (p = 0.001) and continued to decrease at 12 and 24 h (p < 0.001). Urine output also increased significantly during the first 6 h after dexamethasone (p < 0.001). CONCLUSIONS: Low-dose dexamethasone rapidly increases blood pressure and decreases pressor requirements in very low birth weight neonates with volume- and pressor-resistant hypotension.     

Disposition of an immunoglobulin intravenous preparation in very low birth weight neonates

To assess the disposition, tolerance, and toxicity of an intravenous preparation of immunoglobulin (IGIV) in very low birth weight (VLBW) neonates, we administered single doses of 500 or 750 mg/kg to 20 neonates with birth weights between 750 and 1500 g during the first week of life. The infusion of this product was well tolerated. Modest changes in hemoglobin, hematocrit, and total hemolytic complement occurred as expected. Hepatic toxic effects were not detected. Mean peak IgG concentrations were 1564 and 1316 mg/dL for the high-dose and low-dose groups, respectively. Mean IgG concentrations were very similar for both groups on postinfusion days 1, 4, 7, 14, 21, and 28. IgG concentrations remained above 300 mg/dL in seven of 10 infants in each group by day 21, and in six of the high-dose group and seven of the low-dose group by day 28. Mean elimination half-lives were 22.6 and 22.8 days in the high-dose and low-dose groups, respectively. These data provide a basis for assessment of potential efficacy of IGIV in the prevention of late-onset infection in VLBW neonates.     

Optimization of gentamicin therapy in very low birth weight infants

In order to optimize gentamicin (G) therapy we studied G pharmacokinetics in 48 preterm infants (gest. age 31.6 +/- 3.4, range 25-37 wk; birth weight 1.5 +/- 0.5 kg, range 0.7-2.5 kg). They received IV G twice daily (5.2 +/- 0.6 mg/kg/day). After at least 2 days of treatment trough and peak levels were measured for 2 successive doses. Trough levels were significantly higher in infants less than 1 kg receiving 5 mg/kg/day than in other infants (1-2.5 kg) who received the same dose (3.1 +/- 1.0 vs. 2.3 +/- 0.5 micrograms/ml; p less than 0.01). Mean G t 1/2 was significantly longer in infants under 1 kg than in those weighing 1-2.5 kg (7.9 +/- 1.9 and 6.5 +/- 1.6 hr, respectively; p less than 0.01). These differences could be attributed to lower G clearance in infants less than 1 kg (31 +/- 6 vs. 39 +/- 8 ml/kg/hr; p less than 0.005). There was no difference in G distribution volume between less than 1 kg and 1-2.5 kg infants (0.35 +/- 0.07 and 0.38 +/- 0.13 L/kg, respectively). A correlation was found between clearance and t 1/2 for the total group (r = 0.57, p less than 0.01). No correlation was detected between BUN and clearance or between gestational age and clearance. Our data suggest that G dose in infants less than 1 kg should be reduced to 3.5-4 mg/kg/day in order to avoid excessive levels associated with nephrotoxicity.     

Insulin pump therapy in the very low birth weight infant

Ten critically ill, very low birth weight infants less than 30 weeks' gestation were treated with exogenous insulin administered through a continuous insulin infusion pump (Betatron II, Cardiac Pacemaker, Inc). Infants were hyperglycemic to dextrose infusions greater than 6 mg/kg/min. The blood glucose concentration became normal in all infants within two to four hours, with varying requirements for continued insulin treatment. Tolerance to intravenous dextrose increased from a mean of 7.4 mg/kg/min to 11.2 mg/kg/min with glycosuria. Energy intake increased from 49.5 calories/kg/d prior to insulin pump therapy to 70.4 calories/kg/d afterward (P less than .01) with weight gain changed from -23 g/d to +13 g/d (P less than .01). One unexpected observation was the apparent normalization of blood glucose homeostasis on higher dextrose doses among some infants after only one three- to six-hour treatment with insulin. The continuous insulin infusion pump is a flexible tool that allows insulin infusion rates to be changed as dictated by blood glucose values without altering other parenteral infusions.     

Randomized low-dose indomethacin trial for prevention of intraventricular hemorrhage in very low birth weight neonates

We admitted 36 preterm neonates (600 to 1250 gm birth weight) with normal 6-hour echoencephalograms to a randomized, placebo-controlled prospective trial to determine whether a low dose of indomethacin would prevent germinal matrix or intraventricular hemorrhage and permit adequate urinary output. Between the sixth and tenth postnatal hours, indomethacin (0.1 mg/kg) or placebo was administered intravenously every 24 hours for a total of three doses. Cardiac ultrasound studies to assess the status of the ductus arteriosus were performed at 6 postnatal hours and on day 5. Urinary output, serum electrolytes, serum indomethacin levels, and renal and clotting functions were monitored. No differences in birth weight, gestational age, or Apgar scores were noted between the two groups of infants. Two indomethacin-treated infants and three infants given placebo had significant urinary output difficulties, requiring that the study medication be withheld. Of 19 infants given indomethacin, two had germinal matrix or intraventricular hemorrhage, in comparison with 8 of 17 infants given saline solution (p = 0.02). Of the infants who had a left-to-right patent ductus arteriosus shunt before treatment, 64% of the indomethacin-treated and 33% of the saline solution-treated infants no longer had a patent ductus arteriosus on day 5. Ductal status appeared unrelated to the development of germinal matrix or intraventricular hemorrhage.     

改良式雾化吸入肺表面活性物质治疗极低体重儿肺炎

目的 观察改良式雾化吸入肺表面活性物质（PS）治疗极低体重儿肺炎的疗效。方法 用固尔苏采用改良式雾化吸入治疗极低体重儿肺炎6例，观察治疗前后血气、肺泡充气程度、临床症状的变化。结果 用药1hPO2和动脉－肺泡氧分压比值（a／APO2）较用药前明显升高，用药后6h，PO2和a／APO2仍高于用药前，差异均有显著意义（P均＜0．05）。用药1hPCO2下降不明显，用药后6hPCO2显著下降，与用药前比较，差异有显著意义（P＜0．05，同时胸部X线显示肺野靛度明显改善，临床症状明显好转。结论 采用改良式雾化吸入治疗极低体重儿肺炎能有效改善肺换气和通气，提高肺泡充气程度。