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.

Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates.

The authors report 2 cases of premature neonates who had enterocutaneous fistula complicating necrotizing enterocolitis. Pulmonary hypertension developed after administration of a somatostatin analogue, octreotide, to enhance resolution of the fistula. The authors discuss the mechanism of the occurrence of this complication and recommend caution of its use in high-risk premature neonates.

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.

Ethical implications of aggressive obstetric management at less than 28 weeks of gestation.

BACKGROUND: The purpose of this study is to evaluate the outcome of infants born between 23 and 28 completed weeks of gestational age for whom aggressive obstetric management was performed. METHODS: Prenatal data were collected retrospectively from medical records. Neonatal mortality, early morbidity, and the outcome at one year corrected for postconceptional age (corrected age) were determined. RESULTS: Ninety-seven infants were included in the study. Serious early morbidity decreased with increasing gestational age. All the infants born prior to 24 weeks showed serious early morbidity: only 26% of the infants born at 24 weeks or later did. There was a significant decline in mortality with increasing gestational age, as there was also in birth weight (p<0.001, p<0.001). Sixty-seven percent of the infants prior to 24 weeks showed disability at one year corrected age whereas only 13% at 24 weeks or older did. The likelihood of having a surviving child without disability was 12.5% at 23 weeks, 39% at 24 weeks, 50% at 25 weeks, 52% at 26 weeks, and 70% at 27 weeks. CONCLUSION: Viability of fetuses at 23 and 24 weeks of gestation remains ethically and clinically controversial. It cannot be reliably established at that time that there is a fair balance of clinical goods over harms for the survivor at 23 weeks. On the other hand we should continue to treat fetuses at 24 weeks as viable, because 50% of them survived and 78% of those survived without disability. Neonatal mortality and survival with disability further decreases with increasing gestational age.

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.

Functional residual capacity and pulmonary mechanics in premature infants receiving a 12-day dexamethasone course.

The objective of this paper is to determine the effects of a 12-day dexamethasone course of the pulmonary function of preterm infants. The design consisted of a consecutive sample of eligible patients, before-after trial. The Regional referral center neonatal ICU was the setting. The patients were 13 preterm infants, 545-1315 g, requiring mechanical ventilation. The following was used: Intravenous dexamethasone for a 12-day tapering course beginning at 0.5 mg/kg every 12 hr. Main outcome measures were as follows: Measurements of functional residual capacity (FRC), compliance, resistance, arterial blood gases and alveolar-arterial differences, level of ventilatory assistance, weight, length. All measures of pulmonary function demonstrated significant improvement by Day 12 of treatment. Most improvement occurred in the first 6 days of treatment, in association with increased lung volume.

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.

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.

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.

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.

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.

Neonatal extracorporeal membrane oxygenation (ECMO): clinical trials and the ethics of evidence.

Neonatal extracorporeal membrane oxygenation (ECMO), a technology for the treatment of respiratory failure in newborns, is used as a case study to examine statistical and ethical aspects of clinical trials and to illustrate a proposed 'ethics of evidence', an approach to medical uncertainty within the context of contemporary biomedical ethics. Discussion includes the twofold aim of the ethics of evidence: to clarify the role of uncertainty and scientific evidence in medical decision-making, and to call attention to the need to confront the irreducible nature of uncertainty.

Control of inspiratory timing in newborn infants.

In order to determine if inspiratory time in preterm infants was influenced by lung volume, two studies were carried out. In the first investigation, carbon dioxide was used to stimulate tidal volume to a level three to six times normal. The anticipated decrease in inspiratory time at increased tidal volumes was not found. These preterm infants behaved in a similar fashion to vagotomized animals studied in the same way by Clark and von Euler. In the second investigation, Hering-Breuer activity was measured in relation to lung volume changes occurring with growth, measured in a body plethysmograph. Although thoracic gas volume correlated well with age and weight, inspiratory slowing with airway occlusion was found to be independent of both age and lung volume. These investigations suggest that neurologic factors have a significant influence on the inspiratory time in newborn human infants.

Characteristics associated with successful weaning in ventilator-dependent preterm infants.

Eighteen ventilator-dependent preterm infants with hyaline membrane disease were studied for 24 hours before and after an attempt at extubation. All were treated with theophylline prior to weaning and achieved average levels of 8.9 +/- 1.7 micrograms/ml (49 +/- 9 mumol/liter) in 13 successfully weaned infants and 8.4 +/- 1.1 micrograms/ml (47 +/- 6 mumol/liter) in 5 infants not extubated, p > 0.05. Infants successfully weaned were significantly (p < 0.01) older, more mature (29 +/- 1 versus 26 +/- 2 weeks' gestational age) and heavier (1107 +/- 236 versus 1016 +/- 256 gm) than infants not successfully extubated. Infants successfully weaned differed only in developing a greater maximal inspiratory force (33.8 +/- 12.3 versus 23.3 +/- 15.0 cm H2O) and higher compliance (1.1 +/- 0.3 versus 0.7 +/- 0.3) during the preweaning treatment period. These results indicate that maturity and size play a significant role in the ability to wean a preterm infant from the ventilator successfully, that maximal inspiratory force and compliance are higher in preterm infants who can be successfully extubated, and that methylxanthines do not uniformly improve pulmonary function in all potentially extubatable preterm infants.

Ascorbic acid prevents oxidative stress in glutathione-deficient mice: effects on lung type 2 cell lamellar bodies, lung surfactant, and skeletal muscle.

Glutathione deficiency in adult mice leads to lung type 2 cell lamellar body and mitochondrial damage; as reported here, these effects are associated with marked decrease of the levels of phosphatidylcholine (the main component of lung surfactant) in the lung and the bronchoalveolar lining fluid. Severe mitochondrial damage was also found in skeletal muscle. Treatment with ascorbate (1-2 mmol per kg of body weight per day), which led to greatly increased (approximately 2-fold) levels of lung and muscle mitochondrial glutathione, prevented damage to lamellar bodies and mitochondria as well as the decline of phosphatidylcholine levels in lung and alveolar lining fluid. The findings indicate that glutathione deficiency leads to depletion of lung surfactant and that this can be prevented with ascorbate. Administration of ascorbate spares glutathione and prevents cellular damage. Lamellar body degeneration in glutathione deficiency appears to be associated with oxidative damage to the perilamellar membrane, which contains the enzymes required for phosphatidylcholine synthesis. It is notable that although severe glutathione deficiency is lethal to newborn rats, which apparently do not synthesize ascorbate, adult mice are better able to survive such a deficiency because they can synthesize ascorbate. The present studies, which suggest that high doses of ascorbate may be of therapeutic value, emphasize that ascorbate and glutathione have actions in common and that they function together in a physiologically significant antioxidant system.

Aortic root blood flow increases after pancuronium in neonates with hyaline membrane disease.

OBJECTIVE: To determine the effects of muscle paralysis on aortic root blood flow in preterm infants with hyaline membrane disease. DESIGN: Each patient served as his/her own control in a prospectively controlled trial. SETTING: Neonatal ICU in a university hospital. PATIENTS: Ten ventilator-dependent preterm infants weighing 800 to 2820 g, 0 to 8 days of age, with hyaline membrane disease and seven control patients. INTERVENTIONS: Noninvasive measurement of aortic root blood flow by Doppler echocardiography 30 min before and 60 min after respiratory paralysis with 0.1 to 0.5 mg/kg of iv pancuronium, or following ventilator changes in control subjects. RESULTS: Mean aortic root blood flow increased significantly (p less than .001), from 212 to 276 mL/min.kg, accompanied by significant increases in stroke volume and heart rate. CONCLUSIONS: Pancuronium bromide may have a direct beneficial effect on the circulation of preterm infants with hyaline membrane disease.

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.

Discrepancies between transcutaneous and end-tidal carbon dioxide monitoring in the critically ill neonate with respiratory distress syndrome.

PaCO2, transcutaneous PCO2 (PtcCO2), and end-tidal PCO2 (PetCO2) measurements were studied in 12 critically ill neonates. PtcCO2 was measured using a combination CO2/O2 sensor during the routine care of these patients. End-tidal sidestream sampling was performed during blood gas measurement as dictated by the patient's clinical condition. There was a linear correlation between PtcCO2 and PaCO2 (n = 51, r = .71, slope = 0.90). PetCO2 and PaCO2 did not correlate as well (n = 51, r = .52, slope = 0.42). Acidosis negatively affected the correlation between PtcCO2 and PaCO2. When pH was greater than 7.30, r = .75 and slope = 1.28 (n = 38), whereas when pH was less than 7.30, r = .62 and slope = 0.73 (n = 13). The presence or absence of a metabolic acidosis did not have a significant effect on the slopes obtained. PtcCO2 monitoring using combined sensors is a useful and practical means of monitoring in the neonatal ICU, although acidosis affects the ability to correlate transcutaneous and arterial values. End-tidal sidestream measurements are not as clinically useful because they vary due to different ventilation/perfusion relationships in the sick neonate.