Neonatologists less frequently discuss long term complications: A simulation-based study of prenatal consults beyond the threshold of viability.

BACKGROUND: Guidelines exist for counseling expectant families of infants at periviable gestational ages (22-25 weeks), but it is much more common for neonatologists to counsel families at gestational ages beyond the threshold of viability when several aspects of these guidelines do not apply. We aimed to develop an understanding of what information is shared with mothers at risk of preterm delivery beyond periviability and to evaluate communication skills of our participants. METHODS: We developed a checklist of elements to include in counseling based on a comprehensive literature review. The checklist was divided into an information sharing section and a connect score. The information sharing list was sub-divided into general information and specific complications. Neonatologists engaged in a simulated prenatal counseling session with a standardized patient. Videotaped encounters were then analyzed for checklist elements. RESULTS: Neonatologists all scored well in communication using our tool and two other validated communication tools - the SEGUE and the analytic global OSCE. There was no difference in scoring based on years of experience or level of training. Information sharing from neonatologists more often discussed general information over specific. Neonatologists also focused more on early outcomes over long-term outcomes. Only 12% of neonatologists quoted the correct survival rate for the case. CONCLUSIONS: Neonatologists generally communicate well but share less information specific to prematurity and the long-term sequelae of prematurity. Our tool may be used to test if other interventions improve information sharing or communication.

Impact of a dedicated neonatal stabilization room and process changes on stabilization time.

OBJECTIVE: Our objective was to evaluate the impact of a dedicated resuscitation and stabilization (RAS) room and process changes on infant stabilization time. STUDY DESIGN: A prospective quality improvement study was conducted on preterm infants in a tertiary care center. A dedicated RAS room, preresuscitation huddle, infant-isolette-ventilator pairing and improved documentation were implemented. The primary outcome was median time to stabilization and secondary outcomes were illness severity on day 1 and morbidity at discharge. RESULTS: A sustained reduction in median time to stabilization from 90 min in the preimplementation phase to 72 min in the sustainability phase was observed. All planned and iterative process changes were integrated into the RAS team's daily routine. Time to completion of procedures decreased, illness severity and morbidity remained unchanged. CONCLUSION: A dedicated RAS room adjacent to the delivery suite in conjunction with process changes improves efficiency of care.

Should we still use vitamin A to prevent bronchopulmonary dysplasia?

Bronchopulmonary dysplasia (BPD) is associated with significant short- and long-term morbidity in preterm infants, and it can be prevented in some infants with vitamin A prophylaxis. Vitamin A, once widely used in neonatal intensive care, was scarce for the last few years, but has become available again at a much higher price, leading to dilemmas about its routine use. In this review we discuss experimental, clinical and socioeconomic evidence related to BPD, and provide a framework for clinicians and policy-makers to evaluate the value of vitamin A treatment and make decisions about its use for prevention of BPD.

Oxygen targeting in preterm infants: a physiological interpretation.

Randomized controlled trials evaluating low-target oxygen saturation (SpO2:85% to 89%) vs high-target SpO2 (91% to 95%) have shown variable results regarding mortality and morbidity in extremely preterm infants. Because of the variation inherent to the accuracy of pulse oximeters, the unspecified location of probe placement, the intrinsic relationship between SpO2 and arterial oxygen saturation (SaO2) and between SaO2 and partial pressure of oxygen (PaO2) (differences in oxygen dissociation curves for fetal and adult hemoglobin), the two comparison groups could have been more similar than dissimilar. The SpO2 values were in the target range for a shorter period of time than intended due to practical and methodological constraints. So the studies did not truly compare 'target SpO2 ranges'. In spite of this overlap, some of the studies did find significant differences in mortality prior to discharge, necrotizing enterocolitis and severe retinopathy of prematurity. These differences could potentially be secondary to time spent beyond the target range (SpO2 <85 or >95%) and could be avoided with an intermediate but wider target SpO2 range (87% to 93%). In conclusion, significant uncertainty persists about the desired target range of SpO2 in extremely preterm infants. Further studies should focus on studying newer methods of assessing oxygenation and strategies to limit hypoxemia (<85% SpO2) and hyperoxemia (>95% SpO2).

CoMFA and CoMSIA studies on 5-hydroxyindole-3-carboxylate derivatives as 5-lipoxygenase inhibitors: generation of homology model and docking studies.

In this study, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of 2-substituted 5-hydroxyindole-3-carboxylate derivatives as potent 5-LOX inhibitors with IC(50) values ranging from 0.031 to 13.4 µM. Two datasets of same molecules were prepared with two different partial atomic charges; one with Gasteiger-Huckel and another with the ESPFIT charges obtained from the gaussian package. CoMFA and CoMSIA models were generated for both the datasets and the results were analysed. With regard to the non-cross validated r(2) values (r(ncv)(2)) and cross-validated q(2) values (q(cv)(2)) of the resulting QSAR models, the dataset with ESPFIT charges yielded higher values; hence it was further used in the study. The CoMFA and CoMSIA models have been further validated for their stability and robustness using group validation and bootstrapping techniques and for their predictive abilities using an external test set of ten compounds. The predictive power of the CoMSIA model was higher than the CoMFA model, the high predictive r(2) values of the test set reveals that the models prove to be useful tools for activity prediction of newly designed 5-LOX inhibitors. The ESPFIT-derived charges yielded better models than those based on charges calculated from Gasteiger-Huckel charges. We generated a homology model for human 5-LOX and identified the key residues at the binding site. The 3D-QSAR models were compared with the interactions at the active site to further elucidate the accuracy of the models. The data generated from 3D-QSAR study was used to design potential 5-LOX inhibitors.

Real time patient safety audits: improving safety every day.

BACKGROUND: Timely error detection including feedback to clinical staff is a prerequisite for focused improvement in patient safety. Real time auditing, the efficacy of which has been repeatedly demonstrated in industry, has not been used previously to evaluate patient safety. Methods successful at improving quality and safety in industry may provide avenues for improvement in patient safety. OBJECTIVE: Pilot study to determine the feasibility and utility of real time safety auditing during routine clinical work in an intensive care unit (ICU). METHODS: A 36 item patient safety checklist was developed via a modified Delphi technique. The checklist focused on errors associated with delays in care, equipment failure, diagnostic studies, information transfer and non-compliance with hospital policy. Safety audits were performed using the checklist during and after morning work rounds thrice weekly during the 5 week study period from January to March 2003. RESULTS: A total of 338 errors were detected; 27 (75%) of the 36 items on the checklist detected >or=1 error. Diverse error types were found including unlabeled medication at the bedside (n = 31), ID band missing or in an inappropriate location (n = 70), inappropriate pulse oximeter alarm setting (n = 22), and delay in communication/information transfer that led to a delay in appropriate care (n = 4). CONCLUSIONS: Real time safety audits performed during routine work can detect a broad range of errors. Significant safety problems were detected promptly, leading to rapid changes in policy and practice. Staff acceptance was facilitated by fostering a blame free "culture of patient safety" involving clinical personnel in detection of remediable gaps in performance, and limiting the burden of data collection.

Exogenous surfactant therapy in newborn infants.

Exogenous surfactant therapy has an established role in the management of neonatal respiratory distress syndrome (RDS). This article summarises the current evidence on surfactant therapy. The use of surfactant for the treatment or prophylaxis of neonatal RDS results in a 30% to 65% relative reduction in the risk of pneumothorax and up to a 40% relative reduction in the risk of mortality. Adverse effects, of which pulmonary haemorrhage is of most concern, are infrequent and long-term follow-up studies of treated patients are reassuring. Natural surfactants have advantages over synthetic surfactants, including a lower frequency of pneumothorax and a lower mortality. Prophylactic administration of surfactant is preferred over 'rescue' administration, especially in infants of < 30 weeks' gestation, as it decreases the risk of pneumothorax, pulmonary interstitial emphysema and neonatal mortality. Prophylaxis can be administered after initial resuscitation and stabilisation. In preterm infants who do not receive prophylactic surfactant, the first dose of surfactant should be administered as early as possible--early selective treatment decreases the risk of pneumothorax, pulmonary interstitial emphysema, chronic lung disease and neonatal mortality. A regimen of using multiple doses of surfactant if required has advantages over a single dose regimen. Exogenous surfactant therapy has also been used in neonatal respiratory disorders other than RDS. In trials in severe meconium aspiration syndrome, surfactant therapy reduced the need for extracorporeal membrane oxygenation. Its role in other disorders requires testing. The development and testing of newer surfactants is in progress.

Metalloporphyrins for treatment of unconjugated hyperbilirubinemia in neonates.

BACKGROUND: Metalloporphyrins are heme analogues that inhibit heme oxygenase, the rate-limiting enzyme in the catabolism of heme to bilirubin. By preventing the formation of bilirubin, they have the potential to reduce the level of unconjugated bilirubin in neonates and thereby reduce the risk of neonatal encephalopathy and long term neurodevelopmental impairment from bilirubin toxicity to the nervous system. OBJECTIVES: 1. To determine the efficacy of metalloporphyrins in reducing bilirubin levels, reducing the need for phototherapy or exchange transfusion and reducing the incidence of bilirubin encephalopathy in neonates with unconjugated hyperbilirubinemia when compared to placebo, phototherapy or exchange transfusion. 2. To determine the nature and frequency of side effects of metalloporphyrins when used to treat unconjugated hyperbilirubinemia in neonates. SEARCH STRATEGY: We searched Medline (1966 - January 2003) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (2003, issue 1). We hand-searched the articles cited in each publication obtained. We hand searched the abstracts of the Society for Pediatric Research (USA) (published in Pediatric Research) for the years 1985 - 2002. SELECTION CRITERIA: We included only randomized controlled studies, in which preterm or term neonates (age 28 days of life or less) with unconjugated hyperbilirubinemia due to any cause were randomly allocated to receive a metalloporphyrin in the treatment arm(s), and to receive a placebo or a conventional treatment (phototherapy or exchange transfusion) or no treatment for hyperbilirubinemia in the comparison arm(s). Any preparation of metalloporphyrin could be used, in any form, by any route, at any dose. DATA COLLECTION AND ANALYSIS: Two authors extracted data independently. Data were entered into Revman by one author and checked by a second author. Prespecified subgroup analyses were planned in term versus preterm infants, hemolytic versus non-hemolytic causes of jaundice and according to the type of metalloporphyrin used. MAIN RESULTS: Three small studies, enrolling a total of 170 infants, were eligible for inclusion in this review. None blinded intervention or outcome assessment. In all three studies some patients were excluded after randomization. Metalloporphyrin-treated infants appeared to have short-term benefits compared to controls, including a lower maximum plasma bilirubin level in one study, a lower frequency of severe hyperbilirubinemia in one study, a decreased need for phototherapy, fewer plasma bilirubin measurements and a shorter duration of hospitalization. None of the enrolled infants required an exchange transfusion in the two studies that described this outcome. None of the studies reported on neonatal kernicterus, death, long-term neurodevelopmental outcomes or iron deficiency anemia. Though a small number of metalloporphyrin-treated as well as control infants developed a photosensitivity rash, the trials were too small to rule out an increase in the risk of photosensitivity or other adverse effects from metalloporphyrin treatment. No subgroup analyses were possible due to the small number of included trials. REVIEWER'S CONCLUSIONS: Treatment of neonatal unconjugated hyperbilirubinemia with metalloporphyrins may reduce neonatal bilirubin levels and decrease the need for phototherapy and hospitalization. There is no evidence to support or refute the possibility that treatment with a metalloporphyrin decreases the risk of neonatal kernicterus or of long-term neurodevelopmental impairment due to bilirubin encephalopathy. There is no evidence to support or refute the possibility that cutaneous photosensitivity is increased with metalloporphyrin treatment. Routine treatment of neonatal unconjugated hyperbilirubinemia with a metalloporphyrin cannot be recommended at present.

Superoxide dismutase for preventing chronic lung disease in mechanically ventilated preterm infants.

BACKGROUND: Free oxygen radicals have been implicated in the pathogenesis of chronic lung disease in preterm infants. Superoxide dismutase is a naturally occurring enzyme which provides a defence against such oxidant injury. Exogenously administered superoxide dismutase has been tested in clinical trials to prevent chronic lung disease in preterm infants. OBJECTIVES: To determine if exogenously administered superoxide dismutase is efficacious in the prevention of chronic lung disease in preterm infants who are mechanically ventilated, and efficacious in decreasing the following outcomes: bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus and mortality. To determine the frequency and nature of adverse effects of superoxide dismutase. SEARCH STRATEGY: We searched Medline (1966 - 2000) and the Cochrane Controlled Trials Register (CCTR) using the following keywords: [bronchopulmonary dysplasia OR chronic lung disease] AND superoxide dismutase, limited to human studies in newborn infants (infant, newborn). We hand searched the reference lists of articles located and the abstracts of the Society for Pediatric Research (USA) (published in Pediatric Research) from 1980 - 2000. SELECTION CRITERIA: Randomized controlled trials where subjects were preterm infants who had developed or were at risk of developing respiratory distress syndrome requiring assisted ventilation and who were randomly allocated to receive either superoxide dismutase (in any form, by any route) or placebo or no treatment. We included studies which reported any of the following outcomes: chronic lung disease, bronchopulmonary dysplasia, any intraventricular hemorrhage, intraventricular hemorrhage grades III/IV, patent ductus arteriosus, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, neonatal mortality, death prior to discharge and neurodevelopmental outcome. DATA COLLECTION AND ANALYSIS: We extracted and assessed separately all data for each study and entered final data into RevMan. We did not perform subgroup analyses (which were originally planned) because only two studies were eligible for inclusion. We assessed the methodological quality of the studies by assessing the risk for bias. We pooled the outcomes of infants who had developed bronchopulmonary dysplasia at 28 days with those who had died at 28 days to derive the combined outcome of bronchopulmonary dysplasia or death at 28 days. Similarly we pooled the outcomes of infants who had respiratory problems after discharge with those who had died prior to discharge to derive the combined outcome of respiratory problems after discharge or death. We used the standard method of the Cochrane Neonatal Review Group for statistical analysis, using a fixed effect model. MAIN RESULTS: Two randomized controlled trials were included for analysis. No differences were found in either study or in the pooled data in death prior to discharge, oxygen dependency at 36 weeks corrected age, oxygen dependency at 28 days of life or in other outcomes. In one study (Rosenfeld 1984), survivors who had been treated with superoxide dismutase had a shorter duration of continuous positive airway pressure (4.9 vs 9.7 days), a lower frequency of respiratory problems after discharge (relative risk 0.33, 95% confidence limits 0.11, 0.96) and a lower frequency of chest radiograph abnormalities (relative risk 0.30, 95% confidence limits 0.11, 0.87) compared to survivors who received placebo. A third study was available only in abstract form and will be evaluated for inclusion after publication. REVIEWER'S CONCLUSIONS: Based on currently available published trials, there is insufficient evidence to draw firm conclusions about the efficacy of superoxide dismutase in preventing chronic lung disease of prematurity. Data from a small number of treated infants suggest that it is well tolerated and has no serious adverse effects.

Current surfactant use in premature infants.

Exogenous surfactant therapy has been a significant advance in the management of preterm infants with RDS. It has become established as a standard part of the management of such infants. Both natural and synthetic surfactants lead to clinical improvement and decreased mortality, with natural surfactants having additional advantages over currently available synthetic surfactants. The use of prophylactic surfactant administered after initial stabilization at birth to infants at risk for RDS has benefits compared with rescue surfactant given to treat infants with established RDS. In infants who do not receive prophylaxis, earlier treatment (before 2 hours) has benefits over later treatment. The use of multiple doses of surfactant is a superior strategy to the use of a single dose, whereas the use of a higher threshold for retreatment seems to be as effective as a low threshold. Adverse effects of surfactant therapy are infrequent and usually not serious. Long-term follow-up of infants treated with surfactant in the neonatal period is reassuring. In the future we are likely to see the development of new types of surfactants. Further research is required to determine the optimal use of surfactant in conjunction with other respiratory interventions.

Major birth defects in very low birth weight infants in the Vermont Oxford Network.

OBJECTIVE: To study the frequency and types of major birth defects in very low birth weight (VLBW) infants and their impact on mortality and resource use. STUDY DESIGN: Analysis of data from the Vermont Oxford Network Database from 1994 and 1995 on infants with birth weights of 501 to 1500 g. Major birth defects were reported from a list of 40 defined major defects or if they were considered lethal or life-threatening. Mortality and length of stay were determined. RESULTS: Major birth defects were present in 823 (4.3%) of 19,228 VLBW infants from 147 hospitals. The most common categories were chromosomal anomalies (20%); named syndromes, sequences, and associations (19%); and gastrointestinal (14%), cardiovascular (11%), and nervous system (10%) anomalies. Infants with major birth defects had a higher mortality rate (58% vs 13%, P <.001) and a higher rate of major surgery (29% vs 5%, P <.001) than infants without such defects. Infants with major birth defects accounted for 16.3% of deaths and 18.9% of major surgical procedures but only for 2.9% of total hospital days. CONCLUSIONS: Major birth defects accounted for 16% of all deaths in VLBW infants. However, they accounted for a low proportion of total hospital days.

Delivery room management of infants born through thin meconium stained liquor.

A total of 3472 deliveries were studied over a year to evaluate (i) the importance of thin meconium stained liquor (MSL) in the causation of meconium aspiration syndrome (MAS), and (ii) the efficacy of intrapartum plus endotracheal suction at birth in the prevention of MAS due to thin meconium. Two hundred and ninety four (8.5%) of deliveries had meconium stained liquor of which thin MSL was present in 101. MAS occurred in 98 babies. Thin MSL was responsible for 19.4% of cases of MAS. Inspite of intrapartum suction, a high proportion (55-78%) of infants had meconium in the trachea, though thin meconium was found in the trachea significantly less often than thick meconium. Combined intrapartum and endotracheal suction reduced the incidence of MAS due to thin meconium from 26% to 16%. MAS due to thin meconium occurred in asphyxiated as well as vigorous babies inspite of combined suction. Thin meconium accounts for a significant proportion of deliveries with MSL and causes a considerable number of cases of MAS. To prevent meconium aspiration syndrome caused by thin meconium, all neonates born through thin MSL, whether they are asphyxiated or not should undergo intrapartum suction followed by immediate endotracheal suction at birth.