Extracorporeal membrane oxygenation.
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Biomedical subjects
Publications and source records attributed to A R Wilkinson.
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Comparisons of mortality and rates of cerebral palsy in different populations can be confusing. This is illustrated by comparing two populations of very low birthweight infants born in the 1980s, one from the Netherlands, the other from the UK (Oxford region). Although a number of biases were controlled for while comparing two large geographically defined populations, by assessing the survivors at similar ages and describing their health status in a standard way, some problems in interpretation of outcome remained. Differences in registration practice of live births at early gestational ages, as well as differences in withholding or withdrawing treatment, which occurred in about half of the cases of neonatal death in the Netherlands and in about one third of those in the Oxford region, may have influenced the incidence of registered live births, neonatal mortality, and the rate of cerebral palsy.
OBJECTIVES: To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN: Cohort study of a geographically defined population of babies. SETTING: Oxford Regional Health Authority. SUBJECTS: All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES: Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS: Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS: With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.
Between 1 October 1988 and 30 September 1991 the results of all 896 cerebrospinal fluid examinations from 736 neonates were correlated with clinical diagnosis, treatment, and outcome. The prevalence of fungal or bacterial meningitis in babies requiring lumbar puncture was only 0.95%. Gram staining had a sensitivity of 68% and a positive predictive value of only 46% for the diagnosis of meningitis. Primary cultures directly onto agar plates had a sensitivity of 81% and positive predictive value of 46%. Broth enrichment cultures did not improve sensitivity and were frequently found to be false positive. Empirical treatment should not be altered unless more than a few organisms are seen on Gram staining. Primary cultures are adequate for the diagnosis of fungal and bacterial meningitis. Enrichment cultures should be performed only when the Gram stain and/or cell count suggests meningitis is likely. Clinicians should be aware that diagnostic tests performed in populations with a low prevalence of disease are likely to generate many false positive results and have a low positive predictive value.
Data on infection in a neonatal unit were collected prospectively for seven years. After the first four years, the number of surface cultures obtained from neonates with suspected sepsis and for surveillance was reduced. Rates of systemic infection (sepsis and meningitis) were not significantly different in the four years before and the three years after this change. Reduction in surface culture information made no observable difference to detection of colonisation in neonates with early onset sepsis (within first 48 hours of life) nor to antibiotic choice in late onset sepsis. Decisions concerning the length of antibiotic course in suspected infection were not adversely affected. Reduction in the number of surface cultures led to considerable saving of time, effort, and cost while appearing safe in terms of clinical practice and outcome.
Auditory evoked potentials were measured in 10 newborn babies who had hydrocephalus of different etiologies. Eight showed abnormal results in the initial study with the most frequent anomaly being an absence of all waves that was unrelated to the postconceptional age. The results changed with time in one case who, after 10 weeks, showed the appearance of waves. Furthermore, in two cases the insertion of a ventriculo-peritoneal shunt provoked striking changes consisting of the appearance and normalization of the waves I, III and V latencies.
OBJECTIVES: To investigate (a) which clinical variables and physiological measures of disease severity best predict death in very low birthweight infants and (b) their use in comparing mortality between two neonatal units. DESIGN: Retrospective study of two cohorts of very low birthweight infants from overlapping time periods who received mechanical ventilation. SETTING: Two neonatal intensive care units (hospitals A and B). SUBJECTS: 262 Very low birthweight infants, 130 in hospital A, 132 in hospital B. MAIN OUTCOME MEASURE: Death in hospital. RESULTS: In hospital A the mean level of oxygenation in the first 12 hours of life, whether measured as inspired oxygen requirement (FIO2), arterial/alveolar oxygen (a/AO2) ratio, or alveolar-arterial oxygen difference (A-aDO2), was more closely associated with death than any of four "traditional" risk factors: low birth weight, short gestation, the diagnosis of respiratory distress syndrome, and male sex. Mean pH in the first 12 hours was as strongly associated with death as birth weight. Multiple logistic regression models were derived in infants from hospital A using the four traditional risk factors with measures of oxygenation and pH. The validity of each model was then tested in infants from hospital B. The model based on the four traditional risk factors alone predicted death in hospital B with only 31% sensitivity. Adding mean a/AO2 ratio and mean pH increased its sensitivity to 75%, and when mean a/AO2 ratio was replaced by mean FIO2 its sensitivity increased further to 81%. Based on crude mortality rates alone, the odds of death in hospital A versus hospital B were 0.67 (95% confidence interval 0.37 to 1.23). After correcting for traditional risk factors and mean FIO2 and mean pH, however, the odds of death in hospital A increased to 3.27 (1.35 to 7.92; p less than 0.01). This increased risk persisted after adjusting for the time difference between each cohort. CONCLUSIONS: Crude comparisons of hospital mortality can be highly misleading. Reliable assessment of neonatal outcome is impossible without correcting for major risk factors, particularly initial disease severity. International agreement on a minimum core dataset of clinical and physiological information could improve neonatal audit and help to identify effective treatments and policies.
A preliminary study showed that placental histology was abnormal for babies who subsequently had rickets. The findings--low plasma phosphate concentration; maximum percentage tubular reabsorption of phosphate; and high urinary calcium loss--are those of renal conservation of phosphate in the presence of phosphate deficiency. In a controlled trial no baby receiving phosphate supplements (50 mg per day) had radiological evidence of rickets whereas bone changes were apparent in 42% of the control group. Prenatal deficiency of phosphate, due to placental insufficiency, can be corrected by phosphate supplementation thereby preventing rickets of prematurity.
Cerebral electrical impedance (dZ) and intra-arterial blood pressure were measured continuously during the first 48 h after birth in 26 sick ventilated preterm infants with a birth weight less than 1500 g. The aim was to establish whether any patterns of dZp or the variability of either blood pressure or dZp would allow identification of those infants who developed intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL) or a poor neurological outcome. IVH and PVL were diagnosed by ultrasound image obtained every 6 h. Cerebral electrical impedance recordings were unsuitable for analysis in three patients and a further three died within 14 h of birth. In the remaining 20 patients, no step changes that may have been related to the onset of IVH or PVL were evident and whilst three patterns of dZp were identified, they were not useful in distinguishing between normal infants or those who developed IVH, PVL or had a poor neurological outcome. Using multiple linear regression, the coefficient of variation of dZp was significantly associated with both IVH and outcome, as was the coefficient of variation of blood pressure. Continuous measurement of cerebral electrical impedance, whilst technically feasible in sick preterm infants, was not found useful as a method of identifying those who developed IVH, PVL or had a poor neurological outcome.
Ninety-five patients, who underwent fine catheter peripheral angiography as outpatients, were followed up and assessed to determine the safety of this procedure. No patients reported any major side effects and in particular no patients experienced a rebleed from the arterial puncture site. This procedure could be safely adopted in any radiology department.
All babies admitted to the neonatal unit during a period of 41 months were prospectively studied to find out the incidence, aetiology, and outcome of neonatal pneumonia, and the value of routine cultures of endotracheal tubes. Pneumonia of early onset (before age 48 hours) occurred in 35 babies (incidence 1.79/1000 live births). In 20 (57%) it was caused by group B streptococci. Blood cultures showed the presence of organisms in 16 of the 35 (46%). There were 41 episodes of pneumonia of late onset in 39 babies. Thirty six of the 39 were preterm, and 34 were artificially ventilated (10% of all ventilated babies). Endotracheal tube colonisation had occurred in 94% of these, most commonly by Gram negative organisms and Staphylococcus epidermidis. In only one of seven cases with simultaneous bacteraemia was the same organism grown from cultures of the blood. After controlling for gestational age and duration of artificial ventilation there was no difference in the incidence or timing of endotracheal tube colonisation between babies who did and did not have pneumonia of late onset. Ten babies with pneumonia of early onset (29%) died; all were preterm infants. Only one death (2%) was associated with an episode of pneumonia of late onset. Routine surveillance cultures were not helpful in predicting and managing pneumonia of late onset.
Two babies in a neonatal unit presented on the same day with meningitis due to echovirus 11, which was thought to have been introduced by staff. At this time echovirus 11 was also isolated from the stools of eight other babies; five of them did not have signs of infection. No intervention was made except to emphasise the importance of handwashing. There was evidence of secondary spread to two babies who were both clinically well. The attack rate was twelve (29%) of forty-one babies exposed. Seven of the twelve infected babies were born before 30 weeks' gestation and would have had little or no maternal antibody, yet only two of the seven babies had signs of infection. Despite lack of special measures, all babies recovered. Most cases of horizontally acquired neonatal echovirus infection are mild: extreme measures in the management of outbreaks are unnecessary.
Apnoeic oxygenation (AO) combined with extracorporeal CO2 removal (ECCO2R), using venovenous perfusion across a membrane area of 0.1 m2 has been shown to be feasible in six healthy anaesthetized rabbits. In a further twelve rabbits, ECCO2R has been randomly compared with conventional mechanical ventilation (CMV) following saline lavage to induce respiratory failure. Blood gases were maintained for up to 6 h within the same range (PaO2 = 8-20 kPa, PaCO2 = 4-6 kPa) in two groups of six by varying airway pressures and the oxygen fraction delivered either to the membrane lung (ECCO2R group) or to the ventilator (CMV group). The influence of single hourly sustained inflations (SI) on oxygenation was studied. ECCO2R subjects remained stable and survived. CMV subjects deteriorated and had 80% mortality. Hyaline membranes were absent from ECCO2R subjects and present in all CMV subjects. The response to SI suggests that a lung volume recruitment is maintained during AO for up to 1 h but is ineffective during CMV.
We analyzed 3705 measurements of inspired gas temperature in the first 96 hours of life, with concurrent measurements of ventilator variables and arterial oxygen tension, to determine any relationship to respiratory sequelae in 149 infants assisted by artificial ventilation. All management was with one type of ventilator (model IV100B, Sechrist Industries Inc., Anaheim, Calif.) and one type of humidifier (model MR 500, Fisher and Paykel, Auckland, New Zealand), and infants were placed under radiant heaters. Outcome for infants weighing greater than or equal to 1500 gm at birth was no different at low (less than or equal to 36.5 degrees C) versus high (greater than 36.5 degrees C) values of mean inspired gas temperature during the first 96 hours. However, infants weighing less than 1500 gm at birth had less respiratory morbidity at the higher temperatures; there was a reduction in the incidence of pneumothorax from 43% at low to 13% at high temperatures (p = 0.006) and a reduction in the severity of chronic lung disease, measured as mean Fio2 at 29 days in survivors, from 37.2% at low to 27.5% at high temperatures (p = 0.001). Clinical evaluation of the humidifier, as it was used in this study, suggested that temperature settings less than 36.5 degrees C were associated with inspired gas humidity between 28 and 36 mg H2O/L. For any humidifier, there may be a critical threshold for inspired gas humidity below which the risk of respiratory complications in very low birth weight babies is increased. This hypothesis requires rigorous scrutiny by controlled trial. In future studies, direct measurements of inspired gas humidity are needed to make a precise estimate of the optimal level.
We present the first report of two preterm infants who died from respiratory failure secondary to cystic fibrosis which presented in the early neonatal period.
Cerebrovascular responses were studied in preterm infants by Doppler ultrasound and cerebral electrical impedance for one hour after intravenous indomethacin infusion for patent ductus arteriosus. Indomethacin in a dose of 0.2 mg/kg body weight was infused over five minutes in one group of infants (20 doses) and over 20 minutes in a second group of infants (16 doses). There were no significant differences between the two groups in birth weight (mean = 1068 g, range 569-1950), gestational age (mean 28.4 weeks, range 25-31), or postnatal age (mean 18.1 days, range 6-42). There was a significant reduction in both the Doppler mean flow velocity in the anterior cerebral artery (mean (SE) -20 (4.2)%) and peak amplitude of cerebral electrical impedance (-26 (3.9)%) within two minutes of starting the indomethacin infusion over five minutes. There was no significant change after the infusion over 20 minutes. There were no significant changes in blood pressure or carbon dioxide tensions after infusion at either rate. The results suggest that infusion of indomethacin over five minutes caused a potentially deleterious reduction in cerebral blood flow. No such reduction occurred when it was infused over 20 minutes.
In a randomised, double-blind study, a transdermal patch containing either hyoscine or placebo was applied post-auricularly in 190 adult patients under 65 year old, seven to twelve hours prior to their undergoing minor orthopaedic or plastic surgery under thiopentone/nitrous oxide/halothane general anaesthesia. In the first 24 hours after surgery 34% of patients vomited. The incidence of nausea (31% vs 54%; P less than 0.01) and the number of episodes of vomiting (66 vs 125; P less than 0.05) during the first 24 hours were significantly less with hyoscine than with placebo. The hyoscine group required fewer doses of antiemetic than the placebo group (12 vs 27; P less than 0.05). Side-effects were mild, the only difference between the two groups being the frequency of dry mouth immediately preoperatively. No differences were seen in the second 24 hours after surgery. We conclude that transdermal hyoscine is moderately effective in reducing the occurrence of postoperative nausea and vomiting following minor surgery.
Auditory evoked potentials were recorded in 25 babies with postconceptional age between 32 and 37 weeks without any risk factors for brainstem dysfunction. Waves I, III and V were constant while waves II and IV appeared more frequently with increasing gestation. The latency of waves I and III did not vary significantly in the period investigated while waves V significantly decreased its latency from 7.69 m in week 32 to 7.06 m in week 37 (p less than 0.01). I-V interwave interval or brainstem conduction time decreased from 5.59 m to 4.96 m over this period (p less than 0.01).