Resuscitating preterm infants with 100% oxygen is associated with higher oxidative stress than room air.

AIM: The starting fraction of inspired oxygen for preterm resuscitation is a matter of debate, and the use of room air in full-term asphyxiated infants reduces oxidative stress. This study compared oxidative stress in preterm infants randomised for resuscitation with either 100% oxygen or room air titrated to internationally recommended levels of preductal oxygen saturations. METHODS: Blood was collected at birth, two and 12 hours of age from 119 infants <32 weeks of gestation randomised to resuscitation with either 100% oxygen (n = 60) or room air (n = 59). Oxidative stress markers, including advanced oxidative protein products (AOPP) and isoprostanes (IsoP), were measured with high-performance liquid chromatography and mass spectrometry. RESULTS: Significantly higher levels of AOPP were found at 12 hours in the 100% oxygen group (p < 0.05). Increases between two- and 12-hour AOPP (p = 0.004) and IsoP (p = 0.032) concentrations were significantly higher in the 100% oxygen group. CONCLUSION: Initial resuscitation with room air versus 100% oxygen was associated with lower protein oxidation at 12 hour and a lower magnitude of increase in AOPP and IsoP levels between two and 12 hours of life. Correlations with clinical outcomes will be vital to optimise the use of oxygen in preterm resuscitation.

Relationship between probable nosocomial bacteraemia and organisational and structural factors in UK neonatal intensive care units.

OBJECTIVES: To assess the relationship between organisational and structural factors of UK neonatal intensive care units (NICUs) with risk adjusted probable nosocomial bacteraemia. DESIGN OF STUDY: A prospective observational study of infants concurrently admitted to 54 randomly selected UK NICUs between March 1998 and April 1999. RESULTS: Of the 13 334 infants admitted, 402 (2.97%) had probable nosocomial bacteraemia. The median unit level percentage of infants with probable nosocomial bacteraemia was 2.48% (minimum 0%, maximum 9%). The risk adjusted odds of probable nosocomial bacteraemia were increased by 1.13 (95% CI 1.07 to 1.20) for each additional level 1 cot per hand washbasin and decreased by 0.53 (95% CI 0.35 to 0.79) in infants admitted to units with an NICU infection control nurse compared with units without. There was no relation with an increase in the floor space of the unit per cot (odds ratio 0.99 (95% CI 0.98 to 1.00) per m(2)) or with the quality of hand washing signs (odds ratio 1.04 (95% CI 0.93 to 1.16) per increase in quality score). CONCLUSIONS: There is widespread variation in rates of probable nosocomial bacteraemia in UK NICUs. Probable nosocomial bacteraemia is reduced in units with a dedicated infection control nurse and with the presence of more hand washbasins. Further research is required to identify methods to eliminate nosocomial bacteraemia.

ORACLE--antibiotics for preterm prelabour rupture of the membranes: short-term and long-term outcomes.

UNLABELLED: Preterm prelabour rupture of the foetal membranes (pPROM) is the most common antecedent of preterm birth and can lead to death, neonatal disease and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. A large, randomized, multicentre trial was undertaken to try to resolve this issue. In total, 4826 women with pPROM were randomized to one of four treatments: 325 mg co-amoxiclav plus 250 mg erythromycin, co-amoxiclav plus erythromycin placebo, erythromycin plus co-amoxiclav placebo, or co-amoxiclav placebo plus erythromycin placebo, four times daily for 10 d or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease or major cerebral abnormality on ultrasonography before discharge from hospital. The analysis was undertaken by intention to treat. Indications of short-term respiratory function, chronic lung disease and major neonatal cerebral abnormality were reduced with the prescription of erythromycin. In contrast, the use of co-amoxiclav was associated with a significant increase in the occurrence of neonatal necrotizing enterocolitis. CONCLUSION: Prophylactic antibiotics can play a role in preterm prelabour rupture of the membranes in reducing infant morbidity.

Hospital mortality in relation to staff workload: a 4-year study in an adult intensive-care unit.

BACKGROUND: Few studies have examined mortality rates in relation to the workload of hospital staff. We investigated this issue in one adult intensive-care unit (ICU) in the UK. METHODS: We measured ICU workload per shift during each patient's stay for all admissions between 1992 and 1995 that met criteria for adjustment of mortality risk by the APACHE II equation (n=1050). APACHE II data were validated by one observer. Measures of workload in each patient's stay included occupancy, total ICU nursing requirement as defined by the UK Intensive Care Society, and the ratio of occupied to appropriately staffed beds. Over the period, staffing was appropriate for between 4.1 and 5.3 occupied beds (1.3 nurses per patient). FINDINGS: There were 337 deaths, 49 more (95% CI 34-65) than predicted by the APACHE II equation. Median occupancy was 5.8 beds, and median nursing requirement was 1.6 per patient. On multiple logistic regression analysis, adjusted mortality was more than two times higher (odds ratio 3.1 [1.9-5.0]) in patients exposed to high than in those exposed to low ICU workload, defined by average nursing requirement per occupied bed and peak occupancy; the unadjusted odds ratio for this comparison was 4.0 (2.6-6.2). After exclusion of measures of nursing requirement, adjusted mortality increased with the ratio of occupied to appropriately staffed beds during each patient's stay. All logistic regression models fitted the data satisfactorily. INTERPRETATION: Variations in mortality may be partly explained by excess ICU workload. This methodology may have implications for planning and clinical governance.

A cost analysis of neonatal care in the UK: results from a multicentre study. ECSURF Study Group.

BACKGROUND: A number of papers have recently been published examining the magnitude of scale economies in neonatal care and the level of activity at which these become attainable. Although these agree there is scope for economies in the production of neonatal care, they debate the extent to which such economies are attainable and how they might best be detected. A major multicentre study of neonatal units in the United Kingdom has produced costing and activity data allowing these issues to be explored afresh. METHODS: A postal questionnaire was used to determine neonatal cost and activity levels in 57 UK neonatal units. Costs for the financial year 1990-1991 related to clinical staffing, support (such as pathology) and overheads (such as heat, light, power and administrative overheads). Activity related to the total number of care days provided and the number of these that were intensive in nature. All data were scrutinized to ensure consistent definitions. A multivariate regression analysis was used to investigate the relationship between costs and activity. RESULTS: A double-log function relating variations in total costs to total days, case-mix and an interaction term provided the best fit to the data. The analysis suggests that significant economies of scale are possible within the observed range of provision of intensive care. CONCLUSIONS: Significant economies of scale may be attainable. Nevertheless, these results should be carefully interpreted. In particular, the costs of neonatal care should not be examined in isolation but in relation to outcomes. In certain instances, units of inefficient scale but acceptable outcome may be defensible on grounds of ease of access.

Risk adjustment for quality improvement.

We can learn what is achievable with current technologies by comparing our neonatal intensive care unit outcomes with others. Because neonatal intensive care units may vary with respect to their case-mix, risk adjustment is essential to making fair comparisons in any research that does not equalize risks through randomization. Risk adjustment first requires strict definition of each specific outcome. Then each risk factor is measured and weighted accordingly. Severity of illness scores are a special form of risk adjustment. The leading newborn illness severity scores rely on physiology-based items from bedside vital signs and laboratory tests. The mechanics of score development are discussed including item selection, definition, collection, and potential biases. The process of weighting risk factors usually involves building multivariate models. Issues of derivation, validation, discrimination, calibration, and reliability affect the utility of all scores. Once a comparison is appropriately risk-adjusted, there are important cautions about interpretation, including the source of the reference (benchmark) population, sample size, and biases from incomplete risk adjustment. Nonetheless, these findings can spur quality improvement efforts that can lead to dramatic, system-wide improvements in outcomes.

Neonatal risk scoring systems. Can they predict mortality and morbidity?

Physiology-based illness severity scores are proving their value through a wide variety of practical applications. The theoretical disadvantages noted in Table 1 have not turned out to be major problems, whereas the advantages have been quite real. Numerous studies have reported insightful comparisons between treatment groups, between NICUs, between countries, between eras, and over the course of care. Many institutions have implemented routine collection of physiology-based newborn scores. The answer to the question posed in the title is yes; neonatal risk scoring systems can predict some mortality and some morbidity. However, it is clear that this function is much less important than their application as a means of improving quality and cost. Future development will depend on commercially viable applications.

Predicting outcome in very low birthweight infants using an objective measure of illness severity and cranial ultrasound scanning.

AIM: To investigate the feasibility of developing an objective tool for predicting death and severe disability using routinely available data, including an objective measure of illness severity, in very low birthweight babies. METHOD: A cohort study of 297 premature babies surviving the first three days of life was made. Predictive variables considered included birthweight, gestation, 3 day cranial ultrasound appearances and 3 day CRIB (clinical risk index for babies) score. Models were developed using regression techniques and positive predictive values (PPV) and likelihood ratios (LR) were calculated. RESULTS: On univariate analysis, birthweight, gestation, 3 day CRIB score and 3 day cranial ultrasound appearances were each associated with death. On multivariate analysis, 3 day CRIB score and 3 day cranial ultrasound appearances remained independently associated. A 3 day CRIB score > 4 along with intraventricular haemorrhage (IVH) grade 3 or 4 was associated with a PPV of 64% and an LR of 9.8 (95% confidence limits 3.5, 27.9). Only 3 day CRIB score and 3 day cranial ultrasound appearances were associated with severe disability on univariate analysis. Both remained independently associated on multivariate analysis. A 3 day CRIB score > 4 along with an IVH grade of 3 or 4 was associated with a PPV of 60% and an LR of 24.2 (95% CI 4.4, 133.3). CONCLUSION: Incorporating objective measures of illness severity may improve current prediction of death and disability in premature infants.

Annual league tables of mortality in neonatal intensive care units: longitudinal study. International Neonatal Network and the Scottish Neonatal Consultants and Nurses Collaborative Study Group.

OBJECTIVE: To assess whether crude league tables of mortality and league tables of risk adjusted mortality accurately reflect the performance of hospitals. DESIGN: Longitudinal study of mortality occurring in hospital. SETTING: 9 neonatal intensive care units in the United Kingdom. SUBJECTS: 2671 very low birth weight or preterm infants admitted to neonatal intensive care units between 1988 and 1994. MAIN OUTCOME MEASURES: Crude hospital mortality and hospital mortality adjusted using the clinical risk index for babies (CRIB) score. RESULTS: Hospitals had wide and overlapping confidence intervals when ranked by mortality in annual league tables; this made it impossible to discriminate between hospitals reliably. In most years there was no significant difference between hospitals, only random variation. The apparent performance of individual hospitals fluctuated substantially from year to year. CONCLUSIONS: Annual league tables are not reliable indicators of performance or best practice; they do not reflect consistent differences between hospitals. Any action prompted by the annual league tables would have been equally likely to have been beneficial, detrimental, or irrelevant. Mortality should be compared between groups of hospitals using specific criteria-such as differences in the volume of patients, staffing policy, training of staff, or aspects of clinical practice-after adjusting for risk. This will produce more reliable estimates with narrower confidence intervals, and more reliable and rapid conclusions.

Randomised controlled trial of respiratory system compliance measurements in mechanically ventilated neonates.

AIM: To determine whether outcomes of neonatal mechanical ventilation could be improved by regular pulmonary function testing. METHODS: Two hundred and forty five neonates, without immediately life threatening congenital malformations, were mechanically ventilated in the newborn period. Infants were randomly allocated to conventional clinical management (control group) or conventional management supplemented by regular measurements of static respiratory system compliance, using the single breath technique, with standardised management advice based on the results. RESULTS: Fifty five (45%) infants in each group experienced one or more adverse outcomes. The median (quartile) durations of ventilation and oxygen supplementation were 5 (2-12) and 6 (2-34) days for the control group, and 4 (2-9) and 6 (3-36) days for the experimental group (not significant). On post-hoc secondary analysis, control group survivors were ventilated for 1269 days with a median (quartile) of 5 (2-13) days, and experimental group survivors were ventilated for 775 days with a median (quartile) duration of 3 (2-8) days (p = 0.03). CONCLUSIONS: Although primary analysis did not show any substantial benefit associated with regular measurement of static respiratory system compliance, this may reflect a type II error, and a moderate benefit has not been excluded. Larger studies are required to establish the value of on-line monitoring techniques now available with neonatal ventilators.

What do doctors record in the medical notes following discussion with the parents of sick premature infants?

UNLABELLED: In a retrospective review of medical notes we determined: (1) how often doctors record discussions with the parents of very low birth weight (VLBW) infants during the neonatal period; (2) what details of any discussion they actually record and; (3) if they are more likely to record discussion with the parents of sicker infants. A random sample (30%) of all VLBW infants admitted between 1989 and 1993 to a regional NICU was reviewed, n = 87. No discussion was documented in 47 cases, one of whom died, 24 had a single episode of discussion recorded and 16 had two or more episodes recorded. Specific discussion about prognosis was only recorded in the notes of 27 babies. Discussion was more likely to be documented in sicker infants as measured by CRIB (clinical risk index for babies) score, t = -3.9, P < 0.001. CONCLUSION: A record of discussion between medical staff and parents is found in the medical notes of less than half of all VLBW infants. These findings may have practical, ethical and legal implications.

Measurement properties of the Clinical Risk Index for Babies--reliabilty, validity beyond the first 12 hours, and responsiveness over 7 days.

OBJECTIVES: Clinical Risk Index for Babies (CRIB) is a simple instrument used to measure clinical risk and illness severity in very low birth-weight infants. We assessed its reliability, validity beyond the first 12 hrs after birth, and responsiveness to individual change in condition after 7 days. DESIGN: Cohort study. SETTING: Three tertiary and three nontertiary UK hospitals. PATIENTS: Three hundred ninety-eight infants whose birth weight was <1501 g or who were born before a 31-wk gestation period. INTERVENTIONS: Inter- and intrarater reliability of data extraction were assessed by Pearson and intraclass correlation. To validate CRIB, we tested the correlation between clinical risk and illness severity with the risk of: a) death; b) prolonged treatment with supplemental oxygen; and c) disability at 2 yrs. Logistic regression models were fitted to assess validity and responsiveness. MEASUREMENTS AND MAIN RESULTS: Reliability coefficients ranged from 0.76 (95% confidence interval, 0.71 to 0.81) to 0.97 (0.94 to 1.00). Throughout the first week, CRIB correlated with the risk of death (p < .001), prolonged treatment with oxygen (p < .001), and disability (p < .001 to p = .033). Improved condition, represented by a reduction in CRIB within the first week, was independently associated with lower risks of each adverse outcome, p < .05. CONCLUSIONS: During the first week, CRIB was reliable, valid, and responsive. These properties support the use of CRIB in the stratification of infants by risk and illness severity in cohort studies, and they also indicate that CRIB may have the potential to be used in other ways in the future.

CRIB (clinical risk index for babies) in relation to nosocomial bacteraemia in very low birthweight or preterm infants.

Positive blood cultures in very low birthweight or preterm infants usually reflect bacteraemia, septicaemia, or failure of asepsis during sampling and lead to increased costs and length of stay. Rates of nosocomial, or hospital acquired, bacteraemia may therefore be important indicators of neonatal unit performance, if comparisons are adjusted for differences in initial risk. In a preliminary study the risk of nosocomial bacteraemia was related to initial clinical risk and illness severity measured by the clinical risk index for babies (CRIB). Nosocomial bacteraemia was defined as clinically suspected infection with culture of bacteria in blood more than 48 hours after birth. One or more episodes of nosocomial bacteraemia were identified retrospectively in 36 of 143 (25%) infants in a regional neonatal unit between 1992 and 1994. Biologically plausible models were developed using regression analysis techniques. After correcting for period at risk, nosocomial bacteraemia was independently associated with gestation at birth and CRIB. Death was independently associated with CRIB, but not with nosocomial bacteraemia. CRIB may contribute, with other explanatory variables, to more comprehensive predictive models of death and nosocomial infection. These may facilitate future risk adjusted comparative studies between groups of neonatal units.

Phagocyte chemiluminescence in pre-term infants.

Intact phagocyte function is a pre-requisite for successful defence against infection, but paradoxically, these cells may also play a major role in the pathogenesis of the infant respiratory distress syndrome. Phagocyte function is known to be deficient in pre-term infants, who are at risk of infection as a result, but these infants are also at risk of respiratory distress syndrome as a result of surfactant deficiency. Despite this, few longitudinal studies of phagocyte function have been performed in pre-term infants. We have used lucigenin-enhanced chemiluminescence to examine the respiratory burst of mixed samples containing polymorphonuclear leucocytes and monocytes of 100 pre-term infants at 48- to 72-h intervals during their admission to a neonatal care unit. Increased polymorphonuclear leucocyte chemiluminescence was associated with respiratory distress syndrome and the use of intermittent positive pressure ventilation. Multiple linear regression analysis revealed a slight, but significant depression of chemiluminescence in association with the use of gentamicin and penicillin when stronger influencing factors such as the presence of respiratory distress syndrome were taken into consideration. Measurement of phagocyte function by sensitive luminescence assays requires very little blood and may be useful in pre-term infants to follow the severity of respiratory distress syndrome. However, it is probable that other factors such as antioxidant capacity also have an important influence on the degree of tissue damage.

Life-threatening inadvertent positive end-expiratory pressure.

Inadvertent positive end-expiratory pressure (PEEP) is a potential cause of lung overdistension and impaired gas exchange in ventilated infants. It can be extremely difficult to diagnose clinically and if unrecognized can be life-threatening. Measurement of lung function can lead to the recognition of inadvertent PEEP, allowing appropriate ventilator adjustment with immediate substantial improvement in clinical state. Lung function measurements can help to optimize ventilation and may improve clinical outcome.

Reliability of clinical assessments of respiratory system compliance (Crs) made by junior doctors.

OBJECTIVE: To assess the reliability of estimates of static respiratory system compliance (Crs) made by junior hospital doctors caring for ventilated newborn infants. DESIGN: A prospective comparison of junior doctors' estimates of Crs to the Crs measured immediately afterwards. SETTING: A regional neonatal intensive care nursery in Edinburgh, Scotland. PATIENTS: 46 ventilated newborn infants. MEASUREMENTS AND RESULTS: Crs was estimated by three grades of junior doctor (Senior House Officer, Registrar and Research Fellow) using two different methods, (i) based on visual assessment of tidal volume in relation to inflation pressure (optical Crs) and (ii) directly using a visual analogue scale (analogue Crs). The Crs was then measured immediately afterwards using the single breath passive expiratory flow technique. The differences between the estimates and the measurements were calculated for each grade of observer and plotted against the corresponding measurements. The relationship between estimates and measurements was also expressed in terms of the coefficients of determination r2 calculated by least squares regression. With both methods of estimation observers tended to overestimate the Crs of infants with lower measured Crs and underestimate that of infants with higher measured Crs with many estimates differing from the measurements by more than 50%. Values of r2 ranged from 0.086 to 0.481 indicating a weak relationship between the estimates and the measurements. CONCLUSIONS: Junior doctors' estimates of Crs were unreliable and did not represent a useful method of assessing respiratory function. The clinical use of compliance measurements merits wider evaluation.

Antibiotic effects on phagocyte chemiluminescence in vitro.

Phagocytes are an essential defence against infection. Since drugs which affect their function may alter the outcome of infections, we have studied the effect of nine antibiotics on phagocyte function in vitro. The effects of antibiotics on the respiratory burst function of phagocytes from healthy adult donors were investigated using lucigenin-enhanced chemiluminescence in response to serum-opsonised zymosan. Aminoglycosides showed dose-dependent suppression of polymorphonuclear leucocyte chemiluminescence, except streptomycin which caused enhancement. Erythromycin caused profound suppression of chemiluminescence from both polymorphonuclear leucocytes and monocytes. Benzylpenicillin and the cephalosporins caused variable suppression of phagocyte chemiluminescence: cefotaxime increased monocyte chemiluminescence in some experiments. None of the drugs produced suppression at clinically relevant plasma concentrations, but erythromycin and some other drugs are preferentially concentrated in phagocytes to levels which suppress their oxidative metabolism in vitro. It is therefore possible that some antibiotics alter phagocyte function: ex vivo studies of phagocyte function in patients taking antibiotics would be valuable.