A reexamination of the role of oxygen in retrolental fibroplasia.

A critical review of the literature of retrolental fibroplasia indicates that the cause of this disease is not yet known. Oxygen is certainly a critical factor but it is still not possible to make precise recommendations as to the amount or the duration of therapy that is safe. We have overemphasized the role of oxygen in the past, and as a result of this the false impression has been created that RLF is a disease that can be prevented. This gross oversimplification of a complex disease with multiple causes has resulted in many unjustified malpractice claims. A study of the present epidemic indicates that excessive oxygen administration probably plays a minor role, in contrast to the first epidemic in which prolonged oxygen administration was clearly a major factor. A reasonable working hypothesis is that the developing retina is highly sensitive to any disturbance in its oxygen supply, either hyperoxemic or hypoxemic. The retinal circulation is subject to the same wide fluctuations as the cerebral circulation in newborn infants. The very low-birth-weight, sick premature infant suffers from a number of conditions, many of which can seriously disturb the retinal circulation, resulting in hypoperfusion and ischemia. These factors (immaturity, hyperoxia, hypoxia, blood transfusions, intraventricular hemorrhage, apnea, infection, hypercarbia, hypocarbia, patent ductus arteriosus, prostaglandin synthetase inhibitors, vitamin E deficiency, lactic acidosis, prenatal complications, genetic factors) may all be present in an infant. They may interact to produce various degrees of retinal damage. Nearly all of these factors cannot be prevented or controlled by our present methods of care. Unfortunately, this means that RLF is an extremely difficult disease to prevent, treat, or investigate. A disease of this complexity with multiple causes will require very large numbers of infants in any controlled study of a therapy. Retrolental fibroplasia should not be considered an avoidable iatrogenic disease in very low-birth-weight infants. Its cause in these infants is not known.

Effect of application force on noninvasive measurements of intracranial pressure.

Application of the Ladd fiberoptic sensor to the anterior fontanel of the human newborn has been used as a method for monitoring intracranial pressure noninvasively. This study measures the effect of varying the force with which the sensor is applied to the fontanel. The Ladd sensor readings of five preterm human infants were continuously monitored while sensor application force was increased in a stepwise manner. The Ladd sensor readings for each infant varied with the force applied. In one infant sensor application was gradually increased while direct measurements of lumbar CSF pressure were made. Ladd sensor readings in this infant increased with increasing application force, while lumbar CSF pressure remained unchanged. It is concluded that readings obtained with the Ladd sensor applied to the anterior fontanel of the human infant depend on the force with which the sensor is applied. The effect of application force must be taken into account if noninvasive measurements of intracranial pressure are to be made with the Ladd device.

Excessive handling as a cause of hypoxemia.

Continuous transcutaneous oxygen (TcPo2) monitoring was used to study low-birth-weight infants (15 control, 15 experimental) during their stay in the intensive care nursery (ICN). Twenty hours of continuous recordings were made of heart rate, respiratory rate, and TcPo2 in the first five days after birth. Personnel caring for the control infants were blind to the TcPo2 measurements. Those caring for the experimental group were instructed in the operation of the TcPo2 monitor and used the device to modify the timing and extent of procedures to minimize "undersirable time" (TcPo2 less than 40 or greater than 100 torr). Control group infants had an average of 40 min/20 hr in "undesirable time." When personnel used TcPo2 monitoring to modify care this "undesirable time" was reduced to 6 min/20 hr. This difference was statistically significant (P less than .001). Infants in the control group were handled more frequently, and experienced more hypoxemia. Of the hypoxemic time suffered by the control infants 75% was associated with handling. Only 5% of the hypoxemia or hyperoxemia was detected by blood Pao2 analysis or conventional monitors. Intermittent arterial blood gas sampling is an inadequate method for monitoring arterial oxygenation in low-birth-weight infants since hypoxemia and hyperoxemia are often missed. Continuous TcPo2 monitoring improves care by diminishing "undesirable time."

The newborn oxygram: automated processing of transcutaneous oxygen data.

Hypoxemic and hyperoxemic episodes are common in newborns with respiratory disorders. We have developed a microprocessor-based data system for use with transcutaneous oxygen (TcPO2) monitors in an attempt to quantitate these episodes. The amount of time spent by an infant in each of ten preset TcPO2 ranges can be automatically recorded. These data are referred to as the oxygram. Fourteen newborn infants were monitored for a total of 552 hours using this system. They spent a mean of 2.96% of the time with a TcPO2 less than or equal to 40 torr and 0.26% of the time with a TcPO2 greater than 100 torr. Representative oxygrams are presented. Clinical and research applications of the data system are discussed.

Ultrasound detection of changing ventricular size in posthemorrhagic hydrocephalus.

Real time ultrasonography has been used to follow sequentially the changing size of the cerebral ventricles in an infant with posthemorrhagic hydrocephalus. A method for quantitating ventricular size is presented and the rapidity with which ventricular size decreases following removal of cerebrospinal fluid is demonstrated.

Neonatal mortality risk for the eighties: the importance of birth weight/gestational age groups.

Since 1976 a computerized data base has been used to store information on babies admitted to two intensive care nurseries serving the Vermont/New Hampshire region. The data base now allows reporting "neonatal" mortality by birth weight/gestational age (BW/GA) groupings for 1976--1979. For all BW/GA groups, except the most immature infants, there has been marked improvement compared to data gathered in the sixties (ie, mortality has decreased). These data are probably applicable to most other centers providing neonatal intensive care. The use of BW/GA categories provides the most reliable way of objectively comparing statistics from one center to another. Differences between two centers were observed when birth weight specific rates were used, but were largely abolished by using BW/GA groups. Data gathered in this way will be increasingly important for comparisons between centers and across years and when evaluating the effectiveness of new therapeutic interventions.

Transcutaneous oxygen monitoring in aminophylline-treated apneic infants.

Transcutaneous PO2 (tcPO2) monitoring offers a new approach to the evaluation of drug effects. We investigated the effect of theophylline on ten premature infants with apnea. Theophylline was administered as aminophylline, 8 mg/kg per rectum every 12 hours for two doses and 4 mg/kg every 12 hours for a total of two or five days (short and long courses). The tcPO2, heart rate (beat-to-beat), and thoracic impedance were continuously monitored during each of three 4-hour study periods: 12 hours before theophylline administration, 12 hours after initiation of theophylline therapy, and 24 to 48 hours after discontinuing the drug's use. Plasma levels were measured by a radioimmunoassay developed in our laboratory. Polygraphic recordings were analyzed without knowledge of treatment for frequency of apneic spells, mean duration of apneas, total duration of hypoxemia (tcPO2 less than or equal to 40 torr), total duration of hyperoxemia (tcPO2 greater than or equal to 100 torr), basal tcPO2, heart rate, and respiratory rate. In each case during theophylline use, cardiorespiratory patterns were altered, respirations were more regular, apneic spells were reduced, PO2 was stabilized with less hypoxia and hyperoxia, and bradycardic episodes were decreased. There was considerable variation in the response of the ten infants and a significant difference in the frequency of return of symptoms between those receiving short-term therapy and those receiving the longer course.

Randomized controlled trial of exogenous surfactant for the treatment of hyaline membrane disease.

We conducted a prospective, randomized, unblinded, controlled trial of exogenous bovine surfactant (surfactant TA) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease. Forty-one low birth weight infants with severe hyaline membrane disease were randomly assigned to saline or surfactant therapy and treated within eight hours of birth. Significant improvements in oxygenation (increased arterial/alveolar PO2) and respiratory support (decreased mean airway pressure) were seen in the group receiving surfactant within four hours after treatment. These improvements were maintained in the surfactant-treated infants, who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg. No problems were associated with administration of surfactant, and no acute side effects were detected. We conclude that exogenous surfactant, administered early in the course of severe hyaline membrane disease, is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life.

Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Septicemia is a major antecedent of morbidity and mortality in very low birth weight (501- to 1500-g) infants. Our purpose was to determine prospectively the incidence, clinical presentation, laboratory features, risk factors, morbidity and mortality associated with late onset septicemia in infants 501 to 1500 g. METHODS: Clinical data were prospectively collected for 2416 infants enrolled in a multicenter trial to determine the efficacy of intravenous immunoglobulin in preventing nosocomial infections. Septicemia was confirmed by positive blood culture in 395 symptomatic infants. Multivariate analyses of factors associated with septicemia were performed. RESULTS: Sixteen percent of VLBW infants developed septicemia at a median age of 17 days. Factors associated with septicemia by logistic regression included male gender, lower gestational age and birth weight and decreased baseline serum IgG concentrations. Increasing apnea (55%), feeding intolerance, abdominal distension or guaiac-positive stools (43%), increased respiratory support (29%), lethargy and hypotonia (23%) were the dominant presenting features of septicemia. An abnormal white blood cell count (46%), unexplained metabolic acidosis (11%) and hyperglycemia (10%) were the most common laboratory indicators. Septicemic infants, compared with nonsepticemic infants, had significantly increased mortality (21% vs. 9%), longer hospital stay (98 vs. 58 days) and more serious morbidity, including severe intraventricular hemorrhage, bronchopulmonary dysplasia and increased ventilator days (P < 0.001). CONCLUSIONS: Late onset septicemia is common in very low birth weight infants, and the rate is inversely proportional to gestational age and birth weight. Septicemia is more common in males and those with low initial serum IgG values. A set of clinical signs (apnea, bradycardia, etc.) and laboratory values (leukocytosis, immature white blood cells and neutropenia) increase the probability of late onset sepsis, but they have poor positive predictive value.

Episodic abnormalities in transcutaneous oxygen (TcPO2) recorded during neonatal intensive care.

An automated TcPO2 data system was tested and used to: 1) quantitate the frequency and duration of hypoxemic and hyperoxemic events experienced during the first three days after birth by 25 very low birth weight infants, and 2) determine whether hypoxemic events were associated with the occurrence of periventricular-intraventricular hemorrhage. During the first three days after birth, infants experienced a median of 41 episodes with a TcPO2 less than 40 torr having a cumulative duration of 37 minutes, and a median of 28 episodes with a TcPO2 greater than 100 torr having a cumulative duration of 14 minutes. Most episodes were less than 30 seconds in duration, but in some infants the duration was longer. There was no association between the occurrence of periventricular-intraventricular hemorrhage and either the frequency or cumulative duration of episodes with a TcPO2 less than 40 torr. A major problem with automated TcPO2 data systems is the inability of currently available systems to recognize inaccurate TcPO2 data. Twenty-four per cent of the summary TcPO2 monitoring data collected in this study was contaminated with unreliable TcPO2 values. Before automated TcPO2 data systems can be recommended for widespread research use or for medicolegal documentation, the problem of data contamination must be resolved.

Growth and development of transcutaneous monitoring in the U.S.A.--1978-1986.

Surface blood gas monitoring is an invaluable clinical technique. It is, unfortunately, subject to many errors unless carefully carried out. This can be done by clinicians. Clinicians, however, cannot be responsible for the cumulative effects of changes in the electrodes made by manufacturers. Before a modified electrode is approved for use its accuracy under clinical conditions and at high arterial PO2 tensions has to be established. In America this has not and is not being done. The F.D.A. met in December, 1986, to consider this problem. Recommendations are expected to be published in 1987. In any new regulations similar but not identical requirements for accuracy should be demanded from pulse oximeters, as these devices have their own unique limitations under hyperoxic and hypoxic conditions.