David E. Woodrum

Early Postnatal Dexamethasone Increases the Risk of Focal Small Bowel Perforation in Extremely Low Birth Weight Infants

OBJECTIVE:We observed two clusters of spontaneous pneumoperitoneums in extremely low birth weight infants during the use of a protocol for early dexamethasone prophylaxis (EDP) for bronchopulmonary dysplasia from 1996 to 1997. During surgery, focal small bowel perforation (FSBP) was found in eight of nine cases. A retrospective study was designed to identify risk factors for FSBP in these extremely low birth weight infants.METHODS:A case-controlled analysis was performed using all infants born weighing <1001 gm and admitted to the University of Washington Medical Center Neonatal Intensive Care Unit during a 13-month period. A total of 51 infants were identified and divided into groups based on treatment or not with dexamethasone and indomethacin. These cohorts were homogeneous for gestational age, birth weight, and perinatal stability. Relative risk and confidence intervals were calculated for each of the comparisons. Routine pathology was performed on all surgical specimens and additional sections were cut and stained for further study.RESULTS:Infants who received EDP had a relative risk of perforation that was 12.3 times that of untreated infants. Those treated with indomethacin had a risk that was comparable with that for infants who did not receive indomethacin. Infants who received both EDP and indomethacin tended to have higher rates of pneumoperitoneum than infants who received EDP alone but comprised a cohort too small for valid analysis. The pathology of surgical specimens revealed FSBP with segmental loss of the muscularis externa. There was no evidence of fungal or bacterial infection in any of the surgical specimens.CONCLUSION: These findings implicate EDP, but not indomethacin, as a significant risk factor for FSBP.

The OHRP and SUPPORT

A group of medical ethicists and pediatricians asks for reconsideration of the recent Office for Human Research Protections decision about informed consent in SUPPORT.

HYPOXIC VENTILATORY RESPONSE IN THE NEWBORN MONKEY

Summary: The hypoxic ventilatory response was determined in twelve unanesthetized newborn monkeys, Macaca nemestrina, Measurements of blood gases and ventilation were made during normoxia and hypoxia at the postnatal ages of 2, 7, and 21 days, Data were collected during quiet sleep. The infant monkey demonstrated a definite but transient hyperventilatory response following exposure to a Fi02 of 0.12 or 0.14 on the second day of life. Baseline ventilation increased 15% (Fi02 = 0.14) and 28% (Fi02 0.12) after 1 minute of hypoxia; p. 0.05 in both instanes. Return to baseline ventilation occurred between 3 and 5 minutes after hypoxic stimulus onset. This biphasic response to hypoxia converted to an adult-like, sustained hyperventilation during the ensuing three weeks of postnatal maturation. Episodes of periodic breathing and/or apnea were noted to occur during the induced hypoxemia. These data demonstrate that the infant subhuman primate has a ventilatory response to hypoxia that is similar to that of the human infant and is an excellent model for the study of the maturation of the respiratory control system.Speculation: The mechanisnis involved i n the unique neonatal response to hypoxia have not been elucidated. In light of current evidence, direct suppression of respiratory center output by an inhibitor seems the most likely possibility.However, adverse alterations in pulmonary mechanics brought on by the hypoxia itself or fatigue of the carotid body remain viable alternatives.

Attitudes toward limitation of support in a pediatric intensive care unit.

Objective: To prospectively determine opinions of members of a pediatric intensive care unit (PICU) team regarding the appropriateness of aggressive care. The types of support that caregivers sought to limit and their reasons for wanting these limits were collected over time. Design: Prospective survey of caregiver opinions. Setting: PICU in an academic tertiary care childrens hospital. Subjects: A total of 68 intensive care nurses, 11 physicians attending in the PICU, 10 critical care and anesthesia fellows, and 24 anesthesia and pediatric residents. Interventions: None. Measurements and Main Results: During a 6‐month period, 503 patients were admitted to the PICU. Within this time period, 52.4% of all deaths were preceded by limitation of support, with 100% of noncardiac surgical deaths preceded by limitation of medical interventions. At least one caregiver wished to limit care for 63 of these patients (12.5%). When caregivers wished to limit support they most frequently wished to limit invasive modes of support such as cardiopulmonary resuscitation (94%) and hemodialysis (83%). The ethical rationales identified most often for wishing to limit support were burden vs. benefit (88%) and qualitative futility (83%). Preadmission quality of life was cited less frequently (50%). Caregivers were less likely to limit care on the basis of quality of life. Nurses and physicians in the PICU were very similar to each other in the types of support they thought should be limited and their ethical rationales. Conclusions: When making decisions about whether or not to limit care for a patient, caregivers were more likely to rely on the perceived benefit to the patient than preadmission quality of life.

Bronchopulmonary dysplasia: The need for epidemiologic studies

IT IS COMMONLY STATED that there is an increasing incidence of chronic pulmonary disease occurring in newborn infants within neonata l intensive care units. Substantive information on incidence, either past or present, is difficult to obtain since there has been no agreement on terminology, clinical definition, nor on an appropriate denominator for comparative studies. There is general agreement that bronehopulmonary dysplasia is a major contributor to prolot~ged hospitalization with high economic and emotional costs.

Postnatal Changes in Transdiaphragmatic Pressure in Piglets

ABSTRACT. We examined diaphragmatic force output in 25 anesthetized piglets ranging in postnatal age from 4 to 21 days (weight 1.3–4.0 kg) in order to determine whether the diaphragm produces greater force output with maturation for a given level of neural input. Transdiaphragmatic pressure (Pdi) served as our index of diaphragmatic force output and was measured during “supramaximal‘’ transvenous phrenic nerve stimulation at 100 Hz in order to control neural drive. Mean Pdi was 53 ± 17 cm H2O and ranged from a minimum of 29 cm H2O to a maximum of 83 cm H2O. A significant positive correlation between Pdi and postnatal age was observed (r = 0.79, p < 0.001). In addition, positive correlations were noted between Pdi and total body weight (r = 0.73, p < 0.001) and Pdi and diaphragmatic wet weight (r = 0.77, p < 0.001). The voltage needed to stimulate the phrenic nerves “supramaximally‘’ did not correlate with postnatal age (r = 0.02, p = 0.16). We conclude that a developmental pattern of increasing Pdi with increasing postnatal age, total body weight, and diaphragmatic wet weight exists in piglets and occurs within the context of a controlled level of neural drive.

Unchanged incidence of bronchopulmonarydysplasia in survivors of hyaline membrane disease

To test the hypothesis that decreased mortality from severe HMD will result in increased morbidity fromBPD, chest films of 30-day survivors of severe HMD were reviewed for evidence of Northways Stage IV BPD. During July, 1970 to June, 1971, 20 survivors of severe HMD were identified; one case of Stage IV BPD was found in this group. During July 1974–June 1975, 80 survivors of severe HMD were identified; five infants had BPD. In spite of more survivors of severe HMD, no increase in the incidence of BPD could be demonstrated.

Response to resistive loading in the newborn piglet

ABSTRACT: The diaphragmatic force generation and electromyographic response to long-term (1 h) inspiratory resistive loading was examined in the newborn piglet during the 3rd postnatal wk of life. Minute ventilation decreased to approximately 50% of baseline level within 5 min of imposition of a severe resistive load and remained at this level for the duration of loading. The decrease in ventilation was secondary to a fall in tidal volume at a constant frequency. There was a significant increase in central nervous system output to the diaphragm as manifested by integrated diaphragmatic electromyogram. Progressive augmentation of this index of central drive continued throughout the period of loading. Functional residual capacity fell significantly by 60 min of inspiratory resistive loading. This strategy should allow greater force generation by placing the diaphragm at a more optimal length-tension relationship. However, the force generating capability of the diaphragm was compromised as assessed by force frequency curve analysis. These results suggest that the diaphragm of the neonatal piglet fatigues during prolonged inspiratory resistive loading.

Effects of PEEP and tolazoline infusion on respiratory and inert gas exchange in experimental meconium aspiration

Meconium aspiration syndrome often produces respiratory failure in the neonate. We utilized the multiple inert gas elimination technique to study the effects on respiratory and inert gas exchange of the application of positive end expiratory pressure or continuous infusion of tolazoline HCl. The application of PEEP, with the optimal level of PEEP defined for each animal, produced a decrease in AaDO2 and pulmonary shunt, without an increase in blood flow to low VA/Q areas, or an increase in dead space. Tolazoline infusion, at 2 mg/kg/hour, had no apparent effect on AaDO2 or shunt, or magnitude of low VA/Q regions. Tolazoline therapy was associated with an increase in heart rate and a decrease in systemic blood pressure. We conclude that immediate postaspiration application of PEEP, but not of tolazoline, will diminish pulmonary shunt without creating low VA/Q areas, and therefore will improve gas exchange in MAS.

Lung development in the fetal primate Macaca nemestrina. I. Growth and compositional changes.

Summary: This report relates lung growth and composition to body growth in 23 fetal and 2 newborn Macaca nemestrina (pigtail monkey) during the last third of gestation.There was a linear relationship (r = 0.883) between gestational age and crown-rump length over the age range studied, and length increased by 1.18 mm/day. The average increment in body weight was 5.1 g/day.Total lung weight increased in a manner similar to total body weight (wet lung weight = 1.91 ± 0.44% of total body weight). Lung weight increased by 109 mg/day until term. A correlation of 0.849 was observed between lung weight and gestational age. There was a linear increase in lung dry mass with increasing gestational age (9 mg/day, r = 0.701) and with increasing body weight (1.38 mg/g body weight, r = 0.691). The dry weight of fetal lung accounted for 10.8 ± 2.9% of total lung weight throughout the gestational period studied. Dry weight increased to 22–23% after birth.There was a decrease in protein and DNA per g wet weight of lung with advancing gestational age. Increases in total protein, DNA, and hemoglobin reflected the increasing size of the lung. Because gestational age is correlated with body size, body weight, and lung weight, total lung protein and total lung DNA should not provide any great advantage over total lung weight as a denominator for quantitative estimates of changing cell constituents with growth. Protein and DNA do not increase with gestational age when plotted per g dry lung. DNA per g dry lung tends to decrease with maturity, suggesting an increase in cell size.Speculation: Whereas fetal lung growth is linearly related to body growth over the last third of gestation, both lung and body size show wide variance at any given age. Constituents of lung increase in a manner which varies from general lung or body growth and are best compared when expressed in relation to a common denominator such as a unit of lung dry weight.