Sustained reductions in neonatal nosocomial infection rates following a comprehensive infection control intervention.

OBJECTIVE: Nosocomial infections (NI) are a frequent and important cause of morbidity and mortality in newborn infants who receive intensive care. We sought to determine if comprehensive infection control (CIC) measures decrease rates in a large neonatal intensive care nursery. METHODS: Single center interventional study. The CIC intervention consisted of increasing nursing and physician education and awareness of infection rates, establishing common improvement goals, training in hand and environment care, and implementing a specialty nursing team for central venous and arterial catheter care. Demographic and microbiology information for all infants admitted to the NICU from January 1, 1999 to December 31, 2000 established baseline data. The intervention period was during January and February 2001. The postintervention period was March 1, 2001 to February 29, 2004. The main outcome measure was the rate of blood, cerebrospinal and/or urinary tract bacterial infections per 1000 hospital days. RESULTS: Baseline infection rate was 8.5 per 1000 hospital days. The NI rate fell 26% (P=0.002) from baseline in the first year and 29% (P<0.001) in the second and third years after the CIC intervention. The reduction in total NI was due mostly to a 46% fall in coagulase-negative Staphylococcus infection rate (P<0.001); however, rates of all other organisms also fell by 21% (P=0.05). CONCLUSIONS: CIC measures can reduce bacterial and fungal NI rates. This effect has been sustained for 3 years following the intervention.

Meconium diseases in infants with very low birth weight.

Retained meconium resulting in intestinal obstruction in infants with very low birth weight (VLBW) may cause significant morbidity and even mortality. Immature intestinal neuromuscular function, abnormal meconium composition, and maternal magnesium sulfate therapy results in delay of first meconium passage. This "normal" passage of first meconium may not occur until 1 week of life or later. A spectrum of conditions results from this delayed passage. At the most serious end of this continuum is intestinal obstruction. These patients present with abdominal distension, emesis, and reduced stool frequency. Early diagnosis of this condition using plain abdominal radiographs and contrast enemas where appropriate is imperative. Contrast enemas may be both diagnostic and therapeutic. Most patients do not need surgical intervention. Operation is indicated when enemas fail to relieve the obstruction or perforation occurs. Prompt diagnosis and appropriate management results in a good outcome. Meconium obstruction in VLBW infants does not appear to be associated with cystic fibrosis or Hirschsprung's disease.

The role of prospective randomized clinical trials in pediatric surgery: state of the art?

PURPOSE: This study sought to determine the role of randomized controlled trials (RCT) in the evolution of pediatric surgical practice. METHODS: The authors used a computer-assisted literature search to identify all clinical trials related to pediatric surgery published in the English-language literature from 1966 through 1999. Each article was reviewed in detail for purpose, content, conduct, and quality of the trial. The authors assessed quality with a previously validated instrument (Chalmers Qualitative Assessment). RESULTS: The authors identified 134 RCTs related to pediatric surgery over the past 33 years. This accounts for 0.17% of 80,377 articles published in the field. The areas of surgery studied were analgesia 65 (49%), antibiotics 17 (13%), extracorporeal membrane oxygenation (ECMO) 9 (7%), gastrointestinal, burns, oncology, minimally invasive surgery, vascular access, congenital anomalies, and trauma (each <5%). Only 16 (12%) trials compared 2 surgical therapies, 9 (7%) compared a medical versus a surgical therapy, and 109 (81%) compared 2 medical therapies in surgical patients. Fourteen (10%) RCTs were funded by peer-reviewed agencies. Only 17 (13%) RCTs included a biostatistician as an author or a consultant. Trial design included calculation of sample size and statistical power in 21 (16%) RCTs. Method of randomization was reported in only 51 (38%). The test statistic and observed probability value was reported in 15 (11%). CONCLUSIONS: Clinical trials are used infrequently to answer questions related to pediatric surgery. When RCTs are utilized, they often suffer from poor trial design, inadequate statistical analysis, and incomplete reporting. Pediatric surgery could benefit from increased expertise, funding, and participation in clinical trials.

A meta-analysis of peritoneal drainage versus laparotomy for perforated necrotizing enterocolitis.

BACKGROUND/PURPOSE: Both primary peritoneal drainage (PPD) and laparotomy (LAP) are used widely for treatment of perforated necrotizing enterocolitis (NEC). Published reports include only anecdotes and small series. The authors used techniques of meta-analysis to determine which treatment is most effective. METHODS: The authors identified published studies reporting surgical treatment of NEC from January 1, 1978 to December 31, 1999; there were 10 studies (n = 475). The authors were contacted and all available raw patient data for use in meta-analysis (n = 190) were obtained. The authors used logistic regression to determine the relative survival rate after PPD and LAP, controlling for the effect of gestational age and institution. RESULTS: The combined probability of survival in the 10 published studies did not show an advantage for PPD (55%) or LAP (67%; P =.27). When the authors corrected for the effect of birth weight on survival rate, they still did not observe a difference (P =.67). A marked bias in treatment assignment was found with smaller babies undergoing PPD than LAP (931 g versus 1,615 g, respectively; P =.0004). Analysis of raw data showed an even greater bias in treatment assignment. The authors found increased survival rate for LAP versus PPD (62.3% v 35.6%; P =.0009). However, a logistic regression model could not overcome the bias in assignment of patients with a much higher expected mortality rate to PPD. CONCLUSIONS: Using currently available data, it is not possible to determine whether PPD or LAP is superior. Bias in treatment assignment precludes conclusions regarding comparative survival. Only a randomized trial will determine which operation is best for the treatment of perforated NEC.

Salvage laparotomy for failure of peritoneal drainage in necrotizing enterocolitis in infants with extremely low birth weight.

BACKGROUND/PURPOSE: Peritoneal drainage is a temporizing procedure for infants with extremely low birth weight (ELBW) who have perforated necrotizing enterocolitis (NEC). "Salvage" laparotomy is advocated when patients worsen after drainage. Some patients have survived with intact gastrointestinal functional after drainage alone. The purpose of this study is to determine if these salvage laparotomies are beneficial. METHODS: The authors reviewed the records of ELBW infants treated at Stanford University with perforated NEC from 1993 through 1998. Data collected included demographic makeup, type of operation, survival rate, postoperative complications, length of stay (LOS), and cost. RESULTS: The authors treated 26 patients, 9 with laparotomy and 17 with peritoneal drainage. The peritoneal drainage group had lower birth weight and more comorbid conditions. Survival rate was similar between laparotomy and drainage: 55.6% versus 41.2%. Four patients in the drainage group underwent salvage laparotomy for perceived clinical deterioration. All of these patients died. The clinical status of patients who had salvage laparotomy and died was similar to those who did not and lived. Seven of 13 patients treated with drainage followed only by supportive care and antibiotics survived. Cost and LOS for patients undergoing salvage laparotomy were much greater than for nonsurviving patients undergoing only peritoneal drainage: 84 +/- 20 days and $660,000 compared with 34 +/- 11 days and $306,000. CONCLUSIONS: Both primary peritoneal drainage and laparotomy should be considered primary therapy for perforated NEC. Patients undergoing peritoneal drainage typically experience clinical deterioration after operation. In this limited experience, salvage laparotomy did not appear beneficial.

Venoarterial versus venovenous extracorporeal membrane oxygenation in congenital diaphragmatic hernia: the Extracorporeal Life Support Organization Registry, 1990-1999.

BACKGROUND/PURPOSE: Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) traditionally has been the mode of support used in congenital diaphragmatic hernia (CDH). A few studies report success using venovenous (VV) ECMO. The purpose of this study is to compare outcomes in CDH patients treated with VA and VV. METHODS: The authors queried the Extracorporeal Life Support Organization Registry for newborns with CDH treated with ECMO from January 1, 1990 through December 31, 1999. They analyzed the pre-ECMO data, ECMO course, and complications. RESULTS: VA was utilized in 2,257 (86%) and VV in 371 (14%) patients. The pre-ECMO status was similar, with greater use of nitric oxide, surfactant, and pressors in VV. Survival rate was similar (58.4% for VV and 52.2% for VA, P =.057). VA was associated with more seizures (12.3% v 6.7%, P =.0024) and cerebral infarction (10.5% v 6.7%, P =.03). Sixty-four treatments were converted from VV to VA (VV-->VA). Survival rate in VV-->VA was not significantly different than VA (43.8% v 52.2%, respectively; P =.23). VV-->VA and VA patients had similar neurologic complications. CONCLUSIONS: CDH patients treated with VV and VA have similar survival rates. VA had more neurologic complications. The authors identified no disadvantage to the use of VV as an initial mode of ECMO for CDH, although some infants may need conversion to VA.

Intrauterine tobacco smoke exposure and hyaline membrane disease amongst triplets.

We assessed the association between prenatal smoking and respiratory distress syndrome (RDS) among triplets using a population-based retrospective cohort of 12,169 triplet live births in the United States between 1995 and 1997. Analysis was conducted using the generalised estimating equation framework to adjust for intra-cluster correlations. A total of 938 cases of RDS were reported comprising 35 among smoking (7.2%) and 903 among non-smoking gravidas (7.7%). The likelihood of RDS was comparable in both smoking categories [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.65-1.32]. The risk for RDS due to smoking diminished with declining birth weight albeit non-significantly: low birth weight (OR = 0.99; 95% CI = 0.40-2.42), very low birth weight (OR = 0.85; 95% CI = 0.39-1.86), and extremely low birth weight (OR = 0.69; 95% CI = 0.30-1.58). In conclusion, among triplet neonates, smoking during pregnancy was not associated with respiratory distress syndrome.

Fetal therapy with rhIGF-1 in a rabbit model of intrauterine growth retardation.

BACKGROUND: Intrauterine growth retardation (IUGR) may, in part, be due to a deficiency of insulin-like growth factor-1 (IGF-1). The objectives of this study were to determine the relationship between fetal serum IGF-1 levels and fetal and placental size in a rabbit model of IUGR and to compare two techniques of selective, exogenous IGF-1 administration (transamniotic and branch uterine arterial catheter infusion) to growth-retarded fetuses in utero. MATERIALS AND METHODS: Pregnant rabbits (n = 6) had their fetuses harvested near term (31 days) for fetal and placental weighing and serum collection. Growth-retarded fetuses were selectively infused for 7 days with recombinant human IGF-1 (rhIGF-1; 1,440 ng/day) either through a transamniotic catheter (n = 8) or via an adjacent uterine arterial branch catheter (n = 6). Opposite horn runts were sham catheterized, but not infused. At term, the fetal runt pairs and their placentas were harvested and weighed, and their serum was collected. The correlation between fetal and placental weight and endogenous serum IGF-1 was calculated (Pearson coefficient, r), while paired t-tests were used to compare the means between the IGF-1-infused and control groups. RESULTS: There was a significant correlation between fetal (r = 0.4230; P = 0.022) and placental weight (r = 0.4166; P = 0.025) and endogenous serum levels of IGF-1. Transamniotic infusion of rhIGF-1 was associated with an increase in serum IGF-1 level (254 +/- 79 vs 351 +/- 101 ng/ml, P = 0.04) and placental weight (5.4 +/- 2.3 vs 7.1 +/- 3.2 g, P = 0.005), and with a trend toward increased fetal weight between matched fetal runt pairs. Fetal mortality in the uterine arterial catheterized group was 76%, and there was no significant difference in fetal or placental weight or IGF-1 levels between infused and noninfused survivors. CONCLUSIONS: Endogenous fetal serum levels correlate with fetal and placental size in the rabbit IUGR model. Transamniotic administration of rhIGF-1 significantly increases serum IGF-1 levels and placental weight of fetal runts, while uterine vessel catheterization results in prohibitive fetal mortality and does not increase fetal or placental growth or IGF-1 levels.

Inhibition of nitric oxide synthesis results in a selective increase in arterial resistance in rabbit lungs.

Endogenous nitric oxide (NO) opposes the vasoconstriction that occurs when lungs are ventilated with a hypoxic gas mixture. However, the contribution of NO to pulmonary vascular resistance when alveolar gas tension is not reduced remains to be defined. Here, we investigated the hypothesis that endogenous NO is a determinant of pulmonary vascular resistance in isolated perfused rabbit lungs ventilated with a normoxic gas mixture. Moreover, we wished to establish that, as flow rate increases, the contribution of NO to vascular resistance increases. In addition, we examined the contribution of NO to the longitudinal distribution of pulmonary vascular resistance. Pressure-flow curves were generated in isolated blood perfused rabbit lungs by varying flow rate from 50 ml/min to 300 ml/min in the presence and absence of the cyclooxygenase inhibitor, indomethacin (100 microM) and the inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). Indomethacin did not alter total pulmonary vascular resistance or the longitudinal distribution of resistance. In contrast, L-NAME administration resulted in significant, flow-related increases in total vascular resistance, i.e., after L-NAME, as flow rate increased, the increment in resistance increased. L-NAME-induced increases in total pulmonary vascular resistance were the result of flow-related increases in the arterial component of vascular resistance. These results provide support for the hypothesis that NO is an important determinant of pulmonary vascular resistance in the rabbit and that the major site of NO activity resides in the arterial side of that circulation.

Effect of L-NAME on pressure-flow relationships in isolated rabbit lungs: role of red blood cells.

Nitric oxide (NO) is produced by and relaxes pulmonary arteries and veins; however, a role for NO as a participant in the control of pulmonary vascular resistance (PVR) remains to be defined. Here we investigated the hypothesis that for NO to serve as a determinant of PVR in the rabbit requires the presence of blood. In isolated blood-perfused rabbit lungs, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) increased PVR and the slope of the pressure-flow relationship. These effects of L-NAME were prevented by pretreatment with L-arginine. In contrast, in lungs perfused with a physiological salt solution, L-NAME had no effect on PVR or the pressure-flow relationship. The addition of washed red blood cells (RBCs) to physiological salt solution, but not the addition of plasma and platelets, restored the response to L-NAME. This effect of RBCs was not reproduced by increasing perfusate viscosity with dextran. These results suggest that, in the rabbit lung, NO is a determinant of PVR in the presence of blood. Moreover, that aspect of blood that permits the generation of NO appears to be related to the RBC and not to perfusate viscosity.