Oxygen consumption in apneic premature infants after low-dose theophylline.

The effects of 2 mg/kg/day theophylline (serum concentrations, 2.9 to 4.7 micrograms/ml) on metabolic rate were observed in 11 premature infants with severe idiopathic apnea of prematurity. Oxygen consumption (VO2/kg) increased 25% from 6.5 +/- 0.4 (SEM) to 8.1 +/- 0.6 cc/min/kg after 24 to 48 hr of therapy. Respiratory quotient did not change. Apnea and bradycardia decreased from 8.6 +/- 1.4 to 1.6 +/- 0.5 episodes/hr and 4.4 +/- 1.1 to 1.2 +/- 0.4 episodes/hr, respectively. This dose of theophylline is effective in idiopathic apnea of prematurity and acts as a metabolic stimulant. In the premature infant, theophylline-induced increases in VO2 may be a result of changes in the sleep state.

Alterations in state in apneic pre-term infants receiving theophylline.

The present study is a report on 9 premature infants treated with aminophylline for relief of apnea. With serum theophylline levels of 2 to 10 microgram/ml, all infants experienced significant decrease of apneic episodes in association with increased wakefulness and increased amounts of active (REM) sleep. These effects may occur independently, but it is possible that the alteration of sleep states may be partially responsible for the decrease in apneic episodes in these infants.

Pharmacokinetics of betamethasone in twin and singleton pregnancy.

OBJECTIVE: The aims of the study were to compare the pharmacokinetics of betamethasone in singleton pregnancy with the pharmacokinetics in twin pregnancy and to assess the adrenal suppression produced by betamethasone. STUDY DESIGN: We measured serial betamethasone and cortisol levels in 30 singleton and 21 twin pregnancies after the first dose of betamethasone and calculated the pharmacokinetic parameters for betamethasone including volume of distribution, half-life, and clearance. We also measured cord and maternal blood levels of betamethasone at the birth of infants of 13 singleton and 9 twin pregnancies. RESULTS: The half-life of betamethasone in mothers with twin pregnancies was significantly shorter than that in mothers with singleton pregnancies (7.2 +/-2.4 versus 9.0 +/- 2.7 hours; P <.017). Clearance of betamethasone in the twin pregnancies appeared greater than in singleton pregnancies (8.4 +/- 6.4 versus 5.7+/- 3.1 L/h; P =.06) but did not reach statistical significance. Volume of distribution was similar in the two groups. Because the time between the last dose of betamethasone and birth varied widely (range, 2-158 hours), mothers with a longer interval after treatment tended to have a higher cord-to-maternal betamethasone ratio than did mothers with a shorter interval in both twin and singleton pregnancies. This finding indicated delayed fetal clearance, but the correlation was weak (R (2) = 0.29 for twins and 0.08 for singletons). CONCLUSION: The shorter half-life of betamethasone in twin pregnancy than in singleton pregnancy may cause the level of betamethasone to be subtherapeutic for lung maturation in twin pregnancy.

Chronic pulmonary insufficiency of prematurity (CPIP).

This report describes a syndrome of delayed respiratory distress occurring in premature infants usually under 1,250 gm at birth. Unlike hyaline membrane disease, this syndrome occurs after four to seven days in a previously healthy infant; also unlike hyaline membrane disease, it persists for two to four weeks. Chronic pulmonary insufficiency of prematurity (CPIP) carries a 10% to 20% mortality rate. The infants are frequently apneic, require supplemental oxygen, but lack the radiologic findings of hyaline membrane disease or bronchopulmonary dysplasia. When compared with nondistressed infants of similar birthweight, infants with CPIP demonstrate slowly progressive atelectasis, hypoxemia, and hypercapnia. Recovery is usually complete by 60 days of age. The importance of CPIP is that an awareness of its existence can eliminate a false sense of security, often communicated to anxious parents, during the four-to-seven-day grace period before its appearance is clinically obvious. The physiologic similarities between CPIP and hyaline membrane disease suggest that lack of surfactant may play a role in the pathogenesis of CPIP.

Voiding after neonatal circumcision.

OBJECTIVE: To determine whether it is necessary to delay discharge of newly circumcised male neonates to observe voiding. SUBJECTS AND METHODS: A prospective study was conducted in 1992 and 1993 of 51 healthy male, newly circumcised neonates between 0 and 10 days of age. The neonates were observed for the time of first voiding after circumcision was performed. RESULTS: All neonates voided after circumcision at a mean age of 5.3 +/- 2.5 hours, and there were no complications noted in the study population. CONCLUSION: Healthy male infants who are circumcised without obvious complications can be expected to void, and it is unnecessary to delay hospital discharge to make this observation.

Nosocomial ringworm in a neonatal intensive care unit: a nurse and her cat.

An outbreak of nosocomial ringworm involved five infants in a neonatal intensive care unit. The index case was a nurse infected with Microsporum canis by her cat. After standard infection control measures were initiated, the outbreak was resolved successfully by an interdisciplinary professional collaboration of physician and veterinary dermatologists and infection control personnel.

Ventilation-perfusion relationships in preterm infants after surfactant treatment.

Arterial-alveolar partial pressure differences for oxygen, carbon dioxide, and nitrogen were measured before and after surfactant replacement therapy on 15 occasions in 14 ventilator-dependent preterm infants with hyaline membrane disease (HMD). Eight treatments resulted in a significant improvement in arterial partial pressure of oxygen (PaO2) 2 hr after treatment; 7 did not. Neither group showed any significant change in arterial-alveolar partial pressure differences for oxygen, nitrogen, and carbon dioxide. This observation suggests that if surfactant replacement therapy produces an improvement in PaO2 it does so by recruitment of atelectatic alveoli with a balanced ventilation/perfusion ratio rather than by redistribution of ventilation within already ventilated alveoli.

Ventilation-perfusion abnormalities in the preterm infant with hyaline membrane disease: a two-compartment model of the neonatal lung.

Arterial-alveolar differences for oxygen, carbon dioxide, and nitrogen were measured in 7 non-distressed preterm infants and 21 ventilator-dependent preterm infants with hyaline membrane disease. The preterm infants with hyaline membrane disease had a significantly lower average arterial pH (7.34 vs. 7.44; P less than 0.001), and significantly higher arterial-alveolar differences for oxygen (286 mm Hg vs. 34 mm Hg; P less than 0.005) and nitrogen (118 mm Hg vs. 7 mm Hg; P less than 0.005). Both groups had elevated arterial-alveolar differences for PCO2 (9 mm Hg in infants with hyaline membrane disease, 5 mm Hg in nondistressed infants; P less than 0.2). When acute changes in mean airway pressure were produced in 14 distressed infants, arterial-alveolar CO2 and N2 differences moved in opposite directions in 11 infants. This observation suggests that changes in mean airway pressure do not acutely recruit atelectatic alveoli, but cause redistribution of ventilation within alveoli already ventilated.

Effect of endotracheal continuous positive airway pressure on sensitivity to carbon dioxide and on respiratory timing in preterm infants.

To determine the effects of continuous positive airway pressure (CPAP) on ventilatory response to CO2 and inspiratory and expiratory duration in preterm infants, 24 preterm infants with an average birth weight of 1220 g were studied at a mean age of 10.6 days. CPAP was applied via an uncuffed endotracheal tube. Testings were performed between ambient pressure and a positive airway pressure of 10 cm H2O. Approximately 2/3 of the applied pressure was transmitted to the esophagus. All infants demonstrated a ventilatory response to carbon dioxide of less than 50 ml/min per mm Hg Pco2 at ambient pressure, and no infant showed significant improvement at increasing levels of CPAP. Drive to breathe, as reflected in the inspiratory flow rate (Vt/Ti) also failed to change significantly. It may be concluded that in the apparent absence of significant changes in lung volume, CPAP fails to increase sensitivity to CO2 in preterm infants recovering from hyaline membrane disease.

Doctors and the health industry: a case study of transcutaneous oxygen monitoring in neonatal intensive care.

This case study presents an industry perspective on medical innovation. Introduced as a scientific breakthrough in the late 1970s, transcutaneous oxygen monitoring was rapidly adopted for routine use in neonatal intensive care. But plagued by technical problems, it was within a decade being replaced by pulse oximetry, a still more recent technology. Its use in efforts to prevent retinopathy of prematurity, an eye disease of preterm newborns often leading to blindness, proved disappointing. The project included interviews with executives and design engineers of companies marketing the device, with investigators who had pioneered the technology, and with senior practicing neonatologists. The findings, reflecting complexity and uncertainty, are relevant to issues concerning health care in the United States and other developed nations. They centre on the key role and ultimate responsibility of the medical profession, with a need for greater attention to the scientific training of health care workers, as perceived by members of the medical device industry. The views of senior investigators are integrated into the picture, with discussion of major challenges faced by the medical community.

Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids.

AIMS: To study a longitudinal change in the expression of adhesion molecules CD11b, CD18, and CD62L on neutrophils and monocytes in very low birth weight babies who develop respiratory distress syndrome, to compare these levels between bronchopulmonary dysplasia (BPD) and non-BPD infants, and to assess the effect of corticosteroid treatment on these adhesion molecules. METHODS: Of 40 eligible neonates, 11 neonates were oxygen dependent at 36 weeks (BPD 36 weeks), 16 infants were oxygen dependent at 28 days, but not at 36 weeks (BPD d28), and 13 infants did not develop BPD. Seventeen neonates received a six day course of steroid treatment. Expression of CD11b, CD18, and CD62L was measured on neutrophils and monocytes in arterial blood on days 1, 3, 7, 14, 21, and 28, and before and 2-3 days after initiation of dexamethasone treatment by flow cytometry. RESULTS: CD18 expression on neutrophils and monocytes and CD62L on neutrophils, measured as mean fluorescent intensity, was significantly decreased in BPD neonates compared to non-BPD neonates on days 1-28. Dexamethasone treatment significantly decreased CD11b, CD18, and CD62L expression on neutrophils, and CD11b and CD18L expression on monocytes. CONCLUSIONS: Decreased CD18 expression on neutrophils and monocytes, and decreased CD62L expression on neutrophils, measured as mean fluorescent intensity during the first four weeks of life in micropremies may be risk factors and early predictors of BPD. Dexamethasone use was associated with decreased expression of CD11b, CD18, and CD62L.

A program to reduce discharge delays in a neonatal intensive care unit.

Our hypothesis was that a program designed to identify the causes of discharge delays would reduce the length of stay in our neonatal intensive care unit. We reviewed every admission from January, 1994, to December, 1995. A discharge delay was defined as any delay not related to illness after the infant was cleared for release. Discharge delays were divided into the following categories: primary healthcare team, organizational, discharge planning, family, monitor related, and other. Potential discharge delays were identified daily according to established criteria. Actual discharge delays were reviewed monthly at a staff meeting attended by representatives of a multidisciplinary team. We identified 116 discharge delays, which accounted for 480 patient days. Eighty-three discharge delays accounted for 302 patient days in 1994, and 33 discharge delays for 178 patient days in 1995. Discharge delays ranged from 1 to 34 days, with an average of 4.1 days added per patient. Infants with discharge delays had a case mix index of 9.32. The average case mix index for the neonatal intensive care unit was 6.25 during 1994 and 5.18 during 1995, an average of 5.71 for the review period. Forty-four percent of infants who had discharge delays had private insurance, 55% had Medicaid, and 1% had self-payment arrangements. Eighty-eight of 116 discharge delays were caused by circumstances beyond the control of the primary care team. An additional 25 of 116 discharge delays were the result of our policy requiring 48 hours free of apnea-bradycardia alarms before discharge. Discharge delays for 1994 cost $226,298 ($749/day). For 1995, discharge delays cost $41,553 ($233/day) for a total cost of $262,431. Total savings in 1995 versus 1994 was $184,745 ($516/day). Despite the low birth weight and relatively severe illnesses of the infants, we believe that a focused team approach and monitoring for potential discharge delays can result in considerable reduction in hospital stay and cost.

Assisted ventilation: a critical review.

Assisted ventilation is a complex technique that has been responsible for much of the improvement in neonatal morbidity and mortality during the last 10 to 15 years. In unskilled hands, however, it can be dangerous. Complications run as high as 30% in some series. Assisted ventilation requires a constantly available medical and nursing team that can supervise the care of a critically ill infant around the clock. It cannot be done from a remote office, but must be carried out by intensivists on the spot. A large investment in time, labor, and skill is needed to reap the benefits without paying an excessive price in terms of morbidity among surviving infants. While the community-based pediatrician must become expert at recognizing the signs of neonatal respiratory distress and initiating the first steps to diagnose and stabilize sick infants, it is not to be expected that the definitive care of such infants can take place in every locality. Therefore local hospitals must recognize their limitations of staff and financial commitment to the care of these infants and form close clinical and educational links with tertiary hospitals capable of long-term care of infants with respiratory distress who require assisted ventilation.

Responsibility for clinical innovation. A case study in neonatal medicine.

Proper evaluation of clinical innovations and of the process of their diffusion is essential for the development of sound health care policy. This case study examines transcutaneous oxygen monitoring in neonatal intensive care, a procedure that was rapidly adopted in the late 1970s as a scientific breakthrough of great promise, then all but abandoned within a decade in favor of pulse oximetry, a still more recent technology. The study incorporates the results of interviews with representatives of industry as well as biomedical researchers and clinicians involved with these devices. Factors in technology diffusion are analyzed, with special attention to those susceptible to change by policy makers. Participants in the diffusion process also include nurses, hospital administrators, the legal profession, the news media, and the public, but the pivotal role--and hence ultimate responsibility--is seen to be that of the physician. The discussion is presented in the context of a proposed "ethics of evidence" pertinent to medical decision making.

Recent advances in hyaline membrane disease.

Survival of infants with HMD has improved remarkably in the last decade. This has resulted from improved methods of diagnosis, which enables clinicians to recognize infection, the patent ductus, and the presence of pulmonary hypertension complicating HMD; from improved methods of ventilation, which result in a lower incidence of acute and chronic complications; and from a reduced incidence of pulmonary and extrapulmonary complications, such as bronchopulmonary dysplasia and retrolental fibroplasia. These advances arise from a deep understanding of pulmonary and metabolic physiology of the newborn infant with respiratory distress. Only an approach firmly rooted in an understanding of physiology, pharmacology, and biochemistry can be completely successful in the therapy of these infants.

Premature rupture of the membranes (PROM): a neonatal approach.

The risks to the infant following prolonged premature rupture of the amniotic membranes are those of prematurity and infection. After the 36th week of pregnancy, healthy infants of healthy mothers may be treated as uninfected neonates, as their risk of infection does not appear to be significant. Before this gestational age, infants should receive a complete laboratory evaluation for infection, including blood culture and spinal fluid examination, and antibiotic therapy should not be withheld until these laboratory tests are reported to the clinician. While the indiscriminate use of antibiotic treatment should be avoided, sepsis in the newborn can be a rapidly progressive disease, with minimal physical and laboratory findings at its onset. Therefore, until some method of laboratory evaluation that will detect all cases of neonatal sepsis rapidly, and leave no infected infant unidentified, the clinician must be alerted to the presence of an infant delivered after PROM and institute the appropriate evaluation and treatment as soon as possible.