Neil McIntosh

Cutaneous hypersensitivity following peripheral tissue damage in newborn infants and its reversal with topical anaesthesia.

&NA; The flexion reflex threshold has been used as a measure of sensation in a group of premature infants born at 27–32 weeks postmenstrual age. The threshold in an area of local tissue damage created by routine heel lances was half the threshold on the intact heel on the other side. This indicated a hypersensitivity to tissue damage analogous to tenderness or hyperalgesia reported in adults. In a double‐blind study, treatment of the damaged area with the topical anaesthetic cream, EMLA, was found to reverse this hypersensitivity or in other words increase the flexion reflex threshold. Treatment with placebo had no effect. The results show that the newborn infant central nervous system is capable of mounting a chronic pain response to local injury which can be reduced by local anaesthetic.

Intra-arterial blood pressure reference ranges, death and morbidity in very low birthweight infants during the first seven days of life.

OBJECTIVES We aimed to: (1) assess the association of average, low, high and variable mean blood pressure (mbp) on death and the common morbidities of very low birthweight infants, and in doing so, (2) to derive representative reference ranges for mbp in very low birthweight infants. STUDY DESIGN This five year retrospective study assessed 1 min computer recordings of intra-arterial mbp in 232 very low birthweight infants over the first 7 days of life in a tertiary NICU. Four measures of mbp were assessed: average, variability, maximum (per time period), and percentage of time with a mean blood pressure less than the infants gestation. Correlation was made with death and the development of intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL) and retinopathy of prematurity (ROP). RESULTS The mbp increased with increasing birthweight and postnatal age (though with a slight decrease on days 6 and 7). Birthweight, gestation and colloid support (adjusted for birthweight and gestation) were the only factors significantly associated with mbp. IVH was predominantly associated with a low and variable mbp on the day IVH was noted or the day before. PVL and ROP were not associated with blood pressure. CONCLUSIONS These reference ranges include more infants and data than previously published and relate mbp in this cohort to morbidity and mortality. They could assist clinicians in judging appropriate mbp for birthweight.

Knowledge-Based Event Detection in Complex Time Series Data

This paper describes an approach to the detection of events in complex, multi-channel, high frequency data. The example used is that of detecting the re-siting of a transcutaneous O2/CO2 probe on a baby in a neonatal intensive care unit (ICU) from the available monitor data. A software workbench has been developed which enables the expert clinician to display the data and to mark up features of interest. This knowledge is then used to define the parameters for a pattern matcher which runs over a set of intervals derived from the raw data by a new iterative interval merging algorithm. The approach has been tested on a set of 45 probe changes; the preliminary results are encouraging, with an accuracy of identification of 89%.

The pain of heel prick and its measurement in preterm infants

&NA; Variability of physiological parameters was used as a measure of stress in the newborn infant. There was a significant increase in variability of the heart rate (P < 0.01) when the stab of the heel prick occurred in addition to the other elements of the procedure (positioning, warming, alcohol swab cleansing and squeezing). This dummy procedure itself caused some increase in variability although this was not significant at the 5% level. There were similar significant increases in variability of the respiratory rate and O2 and CO2 tensions in the blood (P < 0.05) during the stab procedure.

Randomised trial of erythromycin on the development of chronic lung disease in preterm infants

AIMS To determine if erythromycin given from birth reduces the inflammatory response and the incidence and severity of chronic lung disease. METHODS Seventy five infants less than 30 weeks of gestation and ventilated from birth for lung disease were randomly assigned to receive erythromycin intravenously for 7 days or to no treatment. Ureaplasma urealyticum was detected in tracheal secretions by culture and polymerase chain reaction. Differential cell counts were obtained from bronchoalveolar lavage fluid collected daily for 5 days and concentrations of the cytokines interluekins IL-1β and IL-8, and tumour necrosis factor α (TNF-α) were measured. Chronic lung disease (CLD) was defined as oxygen dependency at 36 weeks of gestation. RESULTS Nine infants (13%) were positive forU urealyticum. The inflammatory cytokines in the lungs increased over the first 5 days of life in all babies, but no association was found between their concentrations and the development of CLD. Those treated with erythromycin showed no significant differences from the non- treated group in the differential cell counts or concentrations of the cytokines. The two groups had a similar incidence of CLD. Babies infected with U urealyticum did not have a more pronounced cytokine response than those without infection. Chorioamnionitis was associated with significantly higher concentrations of IL-1β and IL-8 on admission: these babies had less severe acute lung disease and developed significantly less CLD. CONCLUSIONS U urealyticum in the trachea was not associated with an increased inflammatory response in preterm infants. Erythromycin did not reduce the incidence or severity of CLD.

Neonatal research: the parental perspective

Objectives: To investigate the recollections of parents consenting for their infants to be research subjects and determine their views about the need for consent. Subjects: Parents of 154 sick newborn infants enrolled in a randomised trial in the early neonatal period. All parents had given written consent and received printed information. Methods: A questionnaire and accompanying letter was sent to the parental home 18 months later. Non-responders were sent a further questionnaire and letter. Results: Response rate was 64% (99/154). Some respondents (12%) did not remember being asked to consent to their baby joining a study, and a further 6% were unsure. Most of the respondents (79%) were happy, 13% neutral, and 8% unhappy with their decision to give consent. None felt heavy pressure to agree. Entering the trial caused 24% of respondents to feel more anxious, 56% neutral, and 20% less anxious about their baby. Most of the respondents (83%) would be unhappy to forgo the consent process for trials passed by the institutional ethics committee. Conclusions: A significant proportion of parents who give written consent for a trial in the early neonatal period do not later remember having done so. Parents who have had experience of neonatal research would be unhappy for their baby to be enrolled in a study that had ethics committee approval without their consent being obtained.

Factorial Switching Linear Dynamical Systems Applied to Physiological Condition Monitoring

Condition monitoring often involves the analysis of systems with hidden factors that switch between different modes of operation in some way. Given a sequence of observations, the task is to infer the filtering distribution of the switch setting at each time step. In this paper, we present factorial switching linear dynamical systems as a general framework for handling such problems. We show how domain knowledge and learning can be successfully combined in this framework, and introduce a new factor (the ldquoX-factorrdquo) for dealing with unmodeled variation. We demonstrate the flexibility of this type of model by applying it to the problem of monitoring the condition of a premature baby receiving intensive care. The state of health of a baby cannot be observed directly, but different underlying factors are associated with particular patterns of physiological measurements and artifacts. We have explicit knowledge of common factors and use the X-factor to model novel patterns which are clinically significant but have unknown cause. Experimental results are given which show the developed methods to be effective on typical intensive care unit monitoring data.

Temperature control in very low birthweight infants during first five days of life

AIM To determine ranges for skin temperatures in infants weighing under 1000 g in the first five days of life. METHOD Abdominal skin and foot temperatures were automatically collected each second, averaged over 1 minute and stored on computer. A computer program analysed the data in 83 babies weighing under 1000 g at birth over the first five days of life and expressed the temperatures as means and standard deviation. The temperature patterns seen in these babies were also visually analysed. The relation between an increasing abdominal skin-foot temperature difference and other signs of hypovolaemia was also studied. RESULTS These babies all had similar temperature patterns. Just after birth there was little ability to vasoconstrict in the presence of cold stress and the babies behaved more like poikilothermic animals. Vasomotor tone developed in the first three days, resulting in a stabilisation of the abdominal skin temperature to a mean of 36.90C and a widening of the central-peripheral temperature difference (Td) to a mean of 1.00 C. A Td of > 20 C was associated with other evidence of hypovolaemia for only 11% of the time. CONCLUSIONS Infants weighing under 1000 g have poor vasomotor control at birth and are at increased risk from cold stress. After the first two to three days of life, monitoring the central-peripheral temperature difference gives an early indication of cold stress.

Clinical Diagnosis of Pneumothorax Is Late: Use of Trend Data and Decision Support Might Allow Preclinical Detection

Pneumothorax in the newborn has a significant mortality and morbidity. Early diagnosis would be likely to improve the outlook. Forty-two consecutive cases of pneumothorax that developed after admission to a tertiary referral neonatal medical intensive care unit over 4 y from 1993 to 1996 were reviewed. The time of onset of the pneumothorax was determined by retrospective evaluation of the computerized trend of transcutaneous carbon dioxide (tcpCO2) and oxygen tensions. The timing of the occurrence in the notes and x-rays determined the time of clinical diagnosis noted at the time. The difference was the time the condition was undiagnosed. The overall mortality before discharge was 45% (19cases), four patients succumbing within 2 h. The median time (range) between onset of pneumothorax and clinical diagnosis was 127 min (45–660 min). In most cases, the endotracheal tube was aspirated and the transcutaneous blood gas sensor was repositioned, and in at least 40% of the cases, the baby was reintubated before the diagnosis was made. Reference centiles were constructed for level of tcpCO2 and slope of the trended tcpCO2 over various time intervals (in minutes) from 729 infants from 23 to 42 wk gestation who needed intensive care during the first 7 d of life from the same time period. The 5-min tcpCO2 trend slopes were compared in index and matched control infants. The presence of five consecutive and overlapping 5-min slopes greater than the 90th centile showed good discrimination for a pneumothorax (area under the receiver operating characteristic curve, 89%). We concluded that 1) the clinical diagnosis of pneumothorax was late, occurring when infants decompensate;2) trend monitoring of tcpCO2 might allow the diagnosis to be made earlier if used properly; and 3) use of reference centiles of the trended slopes of tcpCO2 might be used for automatic decision support in the future.

Sucrose and non-nutritive sucking for the relief of pain in screening for retinopathy of prematurity: a randomised controlled trial

Background: Screening is necessary for infants at risk of retinopathy of prematurity. Despite local anaesthetic drops, infants find eye examinations distressing, displaying behavioural and physiological changes indicating acute pain. Oral sucrose and non-nutritive sucking reduce pain responses associated with invasive procedures. Objective: To evaluate the use of oral sucrose and/or pacifier for reducing pain responses during eye examinations. Methods: Forty infants <32 weeks gestation or <1500 g birth weight, in two neonatal units, were randomised to one of four interventions administered two minutes before their first screening examination: 1 ml sterile water as placebo (group 1, n  =  10), 1 ml 33% sucrose solution (group 2, n  =  10), 1 ml sterile water with pacifier (group 3, n  =  9), or 1 ml 33% sucrose solution with pacifier (group 4, n  =  11). Examinations were videotaped. Two observers, blind to the intervention, assessed recordings. Pain responses were scored using the premature infant pain profile (PIPP). Results: The groups were similar in gestation, birth weight, and age at examination. Mean PIPP scores were 15.3, 14.3, 12.3, and 12.1 for groups 1, 2, 3, and 4 respectively. Analysis of variance showed a significant difference in PIPP score between groups (p  =  0.023). Infants randomised to pacifiers scored lower than those without pacifiers (p  =  0.003). There was no difference between groups receiving sucrose and those receiving water (p  =  0.321). Conclusions: Non-nutritive sucking reduced distress responses in infants undergoing screening for retinopathy of prematurity. The difference in response was large enough to be detected by a validated assessment tool. No synergistic effect of sucrose and pacifier was apparent in this group.