A survey of fetal care centers in the United States.

OBJECTIVE: Fetal care centers have recently emerged in affiliation with children's hospitals throughout the United States. Few studies have evaluated this new multidisciplinary model of care. STUDY DESIGN: We conducted a survey of multidisciplinary fetal care centers in the United States; survey data was analyzed using descriptive statistics. RESULTS: 59 centers were identified; 29 centers (49%) returned completed surveys. Most centers are located in a children's hospital (54%), and the majority of centers (76%) opened in the past 10 years. The majority of centers (62%) are administered by a specialist in Maternal Fetal Medicine or Obstetrics and Gynecology. A specialist in MFM or Ob/Gyn evaluates every patient at 90% of centers; a neonatologist evaluates every patient at 52% of centers. All responding centers have the capability to perform ultrasounds although fewer centers perform fetoscopic surgery (38%) or open fetal surgery (31%). Many centers (41%) conduct research protocols in fetal medicine. Most centers (61%) considered the provision of information to families as their most important goal. CONCLUSIONS: This is the first study to describe multidisciplinary fetal centers in the United States. It demonstrates variability between centers. More research is needed in order to evaluate the impact of this variability.

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 children's 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.

Ventilatory failure during resistive loaded breathing in the newborn primate.

Previous investigations have shown that ventilatory failure during severe inspiratory resistive loading (IRL) in the 21-day-old infant primate occurs secondary to a decrease in respiratory frequency, that is, central failure. To examine the response of the more immature newborn to IRL, minute ventilation (V'E), arterial blood gases and pH, minute diaphragmatic electromyogram (EMG) activity, peak inspiratory airway pressure, and the centroid frequency (Fc) of the diaphragmatic EMG power spectrum were measured in four unanesthetized tracheotomized 2-day-old monkeys during various levels of IRL, until either 1) ventilatory failure occurred (ventilatory failure run) or 2) normocapnia was sustained for 1 hr (successful trial). During successful trials, minute ventilation, breathing frequency, tidal volume, Fc, and PaCO2 were sustained at baseline levels and an increase in minute EMG activity and peak inspiratory airway pressure were observed. In contrast, during ventilatory failure runs, minute ventilation and tidal volume fell and PaCO2 rose compared to their respective baseline values. Respiratory frequency did not change. The decline in tidal volume occurred despite significant increases in minute diaphragmatic EMG activity and peak inspiratory airway pressure. No shifts in Fc were noted, suggesting that peripheral diaphragmatic fatigue did not occur. We conclude that ventilatory failure during IRL in the 2-day-old monkey is due to the animal's inability to defend tidal volume as opposed to central failure.

Diaphragmatic failure during group B streptococcal sepsis in piglets: the role of thromboxane A2.

Group B Streptococcus (GBS) causes an impairment of diaphragmatic pressure generation (Pdi) in 2-wk-old piglets, whereas 4-wk-old piglets are unaffected. In this study, we examined the effect on 4-wk-old piglets of a higher dose of GBS than previously utilized. We sought to determine whether an eicosanoid product of arachidonic acid metabolism accounted for the decrease in Pdi during GBS infusion and whether thromboxane A2 (TxA2) is the putative eicosanoid mediator of decreased Pdi during GBS infusion. Measuring Pdi during phrenic nerve stimulation, we studied four groups of anesthetized spontaneously breathing 4-wk-old piglets. Group 1 (GBS) was infused with live GBS, which caused a decrease in Pdi by 1 h at 20-, 30-, 50-, and 100-Hz stimulation frequencies. Group 2 [GBS + indomethacin (Indo)] was pretreated with Indo before GBS infusion. In the GBS + Indo group, Pdi did not decrease throughout 4 h of GBS infusion. Because Indo proved to be protective of Pdi during GBS infusion, we examined the role of TxA2, the only eicosanoid present at 1 h in the serum of GBS-infused piglets. Group 3 was infused with the TxA2 analogue U-46619 only for 1 h. Group 4 was treated with the TxA2-receptor antagonist SQ-29548 before and concomitant with GBS infusion for 1 h; the SQ-29548 was then discontinued, and GBS was continued for 1 h more. In the U-46619-infused group, Pdi decreased at 1 h, and in the SQ-29548-treated group, Pdi did not decrease during GBS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of group B streptococcal sepsis on diaphragmatic function in young piglets.

Recent studies indicate that diaphragmatic pressure generation (Pdi) is impaired by bacterial infection. However, group B streptococcus (GBS) had no effect on Pdi when infused into 4-wk-old piglets. As responsiveness to GBS is age-dependent, we therefore studied the acute effect of GBS infusion on Pdi, using a younger, 2-wk-old piglet model. Using trans-Pdi with phrenic nerve stimulation, we studied the effect of continuous GBS infusion in seven anesthetized, spontaneously breathing 2-wk-old piglets. Pdi was measured under baseline conditions (50% O2/50% N2) and at 1, 2, and 4 h of GBS infusion. GBS was infused at a rate which caused a doubling of the pulmonary artery pressure but which avoided hypotension or acidosis--both of which can decrease Pdi. In addition, the piglets were kept hyperoxic [PaO2 > 13.3 kPa (100 torr)], and no piglet with hypercapnia [PaCO2 > 8.7 kPa (65 torr)] was included, as hypoxia and hypercapnia can also cause respiratory muscle dysfunction. For the GBS group, diaphragmatic contractility declined significantly by 1 h at 30-, 50-, and 100-Hz stimulation frequency and, by 2 h, was significantly decreased at all frequencies. We conclude that 2-wk-old piglets, in contrast to 4-wk-old piglets, demonstrate a decline in Pdi during GBS infusion. These data demonstrate an age-related response to GBS in the piglet.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of methylxanthines on diaphragmatic fatigue in the piglet.

Studies in adult animal and human subjects have suggested that the methylxanthine drugs can delay the onset or attenuate the severity of diaphragmatic fatigue. We have investigated the effect of aminophylline and caffeine on the pressure-generating capacity of the fatigued diaphragm in 1-mo-old piglets. Measurements of ventilation, transdiaphragmatic pressure, blood gases and pH, diaphragmatic electromyogram, diaphragmatic pressure-frequency curve (PdiFC), diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 90 min of inspiratory resistive loaded breathing (IRL), and again 30 min after methylxanthine infusion while still on IRL. IRL resulted in a significant decrease in minute ventilation secondary to a fall in tidal volume. Spontaneously generated transdiaphragmatic pressure increased 7-fold from baseline. EMG activity increased to both segments of the diaphragm. Abdominal expiratory muscle activity was noted after the onset of IRL and was accompanied by a fall in end-expiratory lung volume. The PdiFC was significantly decreased from baseline after 90 min of IRL, demonstrating diaphragmatic fatigue. Aminophylline did not alter the PdiFC of the diaphragm. Diaphragmatic electromyogram and tidal volume increased. No change in diaphragmatic blood flow was demonstrated after infusion of aminophylline. Serum theophylline levels averaged 117 +/- 11 mumol/L (21 +/- 2 micrograms/mL). Caffeine administration did not alter the PdiFC or the diaphragmatic electromyogram during IRL. Blood flow to both segments of the diaphragm decreased after caffeine infusion. Serum caffeine levels averaged 86 +/- 30 mumol/L (16.6 +/- 5.9 micrograms/mL).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of inspiratory resistive loaded breathing and hypoxemia on diaphragmatic function in the piglet.

The combined effects of inspiratory resistive loaded breathing (IRL) and hypoxemia on transdiaphragmatic pressure (Pdi) in nine 1-mo-old Yorkshire piglets were studied. IRL was adjusted to increase spontaneously generated Pdi five to six times above baseline but maintain arterial PCO2 < 70 Torr to prevent hypercapnic depression of diaphragmatic contractility. Measurements of ventilation, blood gases and pH, Pdi, diaphragmatic electromyogram, Pdi during phrenic nerve stimulation, diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 2 h of IRL, and then after 1 h of hypoxemia (arterial PO2 approximately 40 Torr) combined with IRL. Diaphragmatic muscle samples were obtained after study completion and immediately frozen in liquid nitrogen for determination of tissue ATP, phosphocreatine, lactate, and glycogen levels. Ten 1-mo-old piglets were subjected to IRL alone and served as controls. IRL alone resulted in significant impairment of Pdi generation. The addition of hypoxemia for 1 h did not further compromise Pdi in comparison to control animals who were subjected to IRL alone. Blood flow to both the costal and crural segments of the diaphragm increased significantly during IRL; the addition of the hypoxemic stress resulted in further significant augmentation of blood flow to both segments of the diaphragm. No differences were noted in diaphragmatic muscle tissue ATP, phosphocreatine, or glycogen between control and IRL animals or between control and IRL plus hypoxemia animals. Muscle lactate levels increased significantly in the IRL plus hypoxemia animals only. The data from this study suggest that moderate hypoxemia during resistive-loaded breathing in the piglet does not accentuate diaphragmatic fatigue.

Group B streptococcus has no effect on piglet diaphragmatic force generation.

Recent studies indicate that diaphragmatic contractility is adversely affected by bacterial infection. Using transdiaphragmatic pressure (Pdi) with phrenic nerve stimulation, the effect of continuous Group B Streptococcus (GBS) infusion on diaphragmatic force output was studied in seven anesthetized, spontaneously breathing 1-month old piglets. Pdi was measured under baseline condition (50% O2/50% N2) and at 1, 2, and 4 h of GBS infusion. The GBS was infused at a level that caused a doubling of the pulmonary artery pressure and a 32% decrease in cardiac output but which avoided hypotension or acidosis--both of which can decrease diaphragmatic contractility. In addition, the piglets were kept hyperoxic (PaO2 greater than 100) and no piglet with hypercapnia (PaCO2 greater than 65) was studied, as hypoxia and hypercapnia also can cause respiratory muscle dysfunction. Pdi in response to phrenic nerve stimulation did not change during GBS infusion. We conclude that GBS infusion, in the absence of hypotension, hypercapnia, hypoxia, or acidosis, has no effect on diaphragmatic force generation in the piglet.

Diaphragmatic force and substrate response to resistive loaded breathing in the piglet.

Inspiratory resistive loaded (IRL) breathing results in hypoventilation and diaphragmatic fatigue in the piglet. We studied the effects of 6 h of IRL on ten 1-mo-old piglets. The load was adjusted to increase spontaneously generated transdiaphragmatic pressure five to six times baseline. Six 1-mo-old piglets acted as controls and were identically instrumented but were not subjected to IRL. Measurements of ventilation, blood gases and pH, diaphragmatic electromyogram, force-frequency curve, blood flow, and end-expiratory lung volume were obtained hourly. Diaphragmatic muscle samples were obtained after 6 h for determination of ATP, phosphocreatine, lactate, and glycogen levels. No changes occurred in the control animals. IRL resulted in a significant decrease in ventilation, an increase in diaphragmatic EMG, onset of abdominal expiratory muscle activity, and a fall in end-expiratory lung volume by 1 h. The force-frequency curve adjusted for lung volume change fell by 20% at all frequencies of stimulation at 1 h and by 40% at 6 h. Blood flow to the costal and crural diaphragm increased by 51 and 141%, respectively. No differences were noted in ATP, phosphocreatine, lactate, or glycogen between control and IRL animals. It is concluded that submaximal spontaneous contractions of the piglet diaphragm over a 6-h period cause a substantial decrease in its maximal force-generating capacity that is not related to substrate depletion.

Respiratory mechanics of the piglet during the first month of life.

Piglets at 3, 14, and 30 days of age were studied to assess the postnatal changes in lung, chestwall, and total respiratory system compliance associated with normal growth. Static deflation compliance of the lung and total respiratory system increased significantly with age; there was no change in chestwall compliance. When normalized for body weight or lung volume, all measures of compliance tended to decrease with postnatal age. Measures of lung and chestwall compliance obtained with an end-inspiratory occlusion technique were less than the static compliance measures, but demonstrated the same relative changes with postnatal maturation. Chestwall compliance at 3 days of age was only 1.3 times greater than lung compliance and there was no significant change in this ratio with postnatal age. In contrast to the trend for the human infant, the piglet's chestwall at 3 days of age is stiff relative to the lung and does not become stiffer with age over the first 4 weeks of life.

The ventilatory pump: neonatal and developmental issues.

This review documents the current knowledge with regard to the structure and function of the developing ventilatory pump. We note that while the neonate's compliant rib cage and diaphragmatic configuration may predispose the newborn to pump failure, its diaphragmatic endurance properties and ability to recruit accessory muscles of respiration may protect against such impairment. We also share evidence that central neural failure can lead to an inability to defend minute ventilation during periods of heightened respiratory effort. Nevertheless, our fund of knowledge remains limited and at this juncture it is unclear which factors or interplay of factors contribute to the development of ventilatory failure in the human neonate and infant. The ventilatory pump is a vital component of the respiratory system. As such, our understanding of the pathogenesis and reversal of ventilatory pump impairment is crucial to improving our management of respiratory failure. We are only beginning to develop such an understanding within a neonatal and developmental context. Future research endeavors will enlarge our fund of knowledge regarding the thorax, the respiratory muscles, and the central neural respiratory-related neurons that control them. From such an understanding will emerge clinically relevant information that has therapeutic implications for the care of newborns and infants with respiratory disease.

Effect of aminophylline on diaphragmatic contractility in the piglet.

Minute ventilation, arterial blood gases, arterial pH, cardiac output, and transdiaphragmatic force generation, both during spontaneous ventilation and in response to phrenic nerve stimulation during airway occlusion at end expiration, were measured in nine anesthetized, tracheostomized piglets before and 30 min after parenteral infusion of 20 mg/kg aminophylline. Serum theophylline levels averaged 109 +/- 21 mumol/L (19.7 +/- 3.7 micrograms/mL) at 30 min postinfusion. No significant changes were noted in pH, blood gases, blood pressure, or ventilatory measures after aminophylline. Aminophylline infusion also had no effect on transdiaphragmatic force generation at any frequency of phrenic nerve stimulation studied. It is concluded that aminophylline has no effect on diaphragmatic contractility in the quietly breathing, nonfatigued piglet.

Developmental changes in the response of the newborn to sustained ventilatory elastic loads.

Postnatal development of the steady-state response to inspiratory elastic loading was studied in eight 48-h-old and eight 24-day-old unanesthetized, tracheostomized monkeys. Both age groups exhibited a fall in minute ventilation (VE) with loads of two to five times baseline respiratory elastance. There was no statistical difference in the ventilatory response between age groups. The response patterns of both groups were characterized by a fall in both tidal volume (VT) and mean inspiratory flow (VT/TI) associated with a prolongation of TI and TI/Ttot. All subjects demonstrated a significant load compensatory response both in terms of neural drive (diaphragmatic EMG output) and force output (inspiratory work production). Arterial CO2 increased significantly during loading in the older subjects in linear correlation with the decline in VE, but the newborns did not exhibit a statistically significant alteration in PaCO2 throughout the range of elastic loads. These data indicate that normal newborns are capable of responding to an external elastic load and that the newborn response is comparable to that of more mature subjects.

Estimation of intrapleural pressure in the newborn.

We examined the changes in esophageal (Pes), proximal airway (Paw), and direct intrapleural (Ppl) pressure measurements following end-expiratory airway occlusion in anesthetized spontaneously breathing newborn piglets. Simultaneous occluded pressure measurements were obtained during resting ventilation, inspiratory resistive loaded (IRL) breathing, and bilateral transvenous phrenic nerve stimulation. During spontaneous resting ventilation, occluded Paw/Ppl averaged 104 +/- 4% and occluded Pes/Ppl averaged 89 +/- 3%. Similar values were found for occluded spontaneous breaths with IRL. During phrenic nerve stimulation at end-expiratory lung volume, occluded Paw/Ppl averaged 104 +/- 6% while occluded Pes/Ppl decreased to 70 +/- 22%. We conclude that proximal airway pressure more accurately reflects intrapleural pressure than esophageal pressure with occlusion in newborn swine. During phrenic nerve stimulation, esophageal pressure measures are grossly inaccurate estimates of intrapleural pressure with occlusion.

The effect of aminophylline on diaphragm blood flow in the piglet.

The effect of aminophylline on diaphragmatic blood flow was investigated in two groups of newborn piglets. Six animals were studied during spontaneous breathing and seven additional animals were paralyzed and ventilated to assess the effect of aminophylline on blood flow to the nonworking diaphragm. Arterial blood gases and pH, cardiac output, and diaphragmatic blood flow were measured before and 20 min after infusion of 20 mg/kg aminophylline. Blood theophylline concentrations averaged 117 mumols/L (21 micrograms/mL) in both groups of animals. Heart rate increased significantly in all animals. Cardiac output increased significantly only in spontaneously breathing animals. Aminophylline had no effect on blood flow to the costal or crural portions of the diaphragm in either the paralyzed or spontaneously breathing animals.

Increased survival of low birth weight infants: impact on the incidence of retinopathy of prematurity.

Retinopathy of prematurity is a retinal vascular disease that occurs only in premature infants. Because of concern that the occurrence of this potentially blinding disease is increasing, a retrospective chart review was undertaken to compare the incidence of retinopathy of prematurity at the University of Washington during the years 1981 to 1984 with previously published data collected at the same institution during the years 1968 to 1980. During 1981 to 1984, there was an increase in the annual numbers of admissions and survivors weighing 1750 g at birth; the survival rate increased significantly (P less than .000001). A trend toward an increased risk for proliferative retinopathy of prematurity (P = .057) during 1981 to 1984 period was noted, but the number of "excess cases" was calculated to be only 6 per year. The remainder of the additional cases, 19 annually, were due to increased survival of infants at risk. Thus, the "second epidemic" of retinopathy of prematurity is largely due to improved survival of low birth weight infants rather than to new iatrogenic factors. In infants with proliferative retinopathy of prematurity, there was a previously unreported association between increased severity of disease and lower birth weight (P = .015). There were four children with severe bilateral visual loss due to retinopathy of prematurity identified during the 1981 to 1984 period, whereas only one bilaterally blind infant was noted during the preceding 12.7 years.

Effects of digoxin on diaphragmatic contractility in the piglet.

Minute ventilation, arterial blood gases and pH, cardiac output, and transdiaphragmatic force generation were measured in eight anesthetized, tracheostomized piglets before and after administration of 40 micrograms/kg body wt of digoxin. No changes were noted in cardiac output, heart rate, tidal vol, respiratory rate, or minute ventilation. Blood pressure decreased from baseline to 60 min postinfusion. No change was noted in the force frequency curves at 30 and 60 min postinfusion. Serum digoxin levels averaged 10.4 ng/mL at 30 min and 5.6 ng/mL at 60 min. In seven control animals, no changes were noted in any ventilatory or hemodynamic parameter from baseline to 60 min. In contrast to the reported effects of digoxin on the diaphragm of adult humans and animals, digoxin did not augment diaphragmatic contractility in normal infant swine.

Ventilatory failure during loaded breathing: the role of central neural drive.

Minute ventilation (VE), arterial blood gases, diaphragmatic electromyogram (EMG) activity, centroid frequency (Fc) and peak inspiratory airway pressures (Paw) were measured in five unanesthetized tracheostomized infant monkeys during various intensities of inspiratory resistive loaded breathing (IRL) until either 1) ventilatory failure occurred (failed trial) or 2) normocapnia was sustained for 1 h (successful trial). During successful trials VE and arterial PCO2 (PaCO2) were sustained at base-line levels, and an increase in peak integrated diaphragmatic EMG activity and peak inspiratory Paw occurred. In contrast, during ventilatory failure runs, VE decreased and PaCO2 rose compared with their respective base-line values. The fall in VE occurred secondary to a significant decline in breathing frequency. Tidal volume was sustained at base-line levels during all trials (both successful and failed groups). Inspiratory Paw's and peak moving time average EMG were sustained at elevated levels during ventilatory failure runs, suggesting that the respiratory muscles did not fail as pressure generators. Furthermore, the EMG Fc did not change from base line during either successful or failed trials. These data suggest that peripheral muscle fatigue did not occur, although in the absence of a more direct test of muscle performance, i.e., a force-frequency curve, we cannot rule out the possibility that a component of peripheral failure contributed to our results. Ventilatory failure during severe IRL in the infant monkey was most clearly associated with an alteration in the respiratory center timing mechanism, i.e., such failure was a function of a decline in respiratory frequency.

Effect of hypercapnia and hypoxia on costal and crural diaphragm electromyograms in piglets.

We examined the separate effects of acute hypercapnia and acute hypoxia, on the electromyographic activity (EMG) of the costal and crural diaphragm in 6 anesthetized spontaneously breathing piglets (age 12-23 days, weight 3.00-4.37 kg). Bipolar wire electrodes were inserted into the anterior paratendinous costal diaphragm and the midportion of the crural diaphragm. EMG activity was quantified in arbitrary units (au) of peak moving time average while the animals breathed 50% O2/50% N2 (base-line) and after 30 min of either hypercapnia (12% CO2) or hypoxia (12% O2) exposure. After 30 min of hypercapnia, the peak moving time average EMG increased in both parts of the diaphragm with the increase in crural diaphragm EMG activity (from baseline: 20 +/- 2 au to 30 min 12% CO2: 83 +/- 20 au) not being significantly different from that observed in the costal diaphragm (from baseline: 21 +/- 2 au to 30 min 12% CO2: 72 +/- 20 au, p = 0.17). Similarly, the peak moving time average EMG increased in both parts of the diaphragm after 30 min of hypoxia with the increase in the crural diaphragm EMG activity (from baseline: 21 +/- 2 au to 30 min 12% O2: 28 +/- 6 au) not being significantly different from that observed in the costal diaphragm (from baseline: 21 +/- 1 au to 30 min 12% O2: 26 +/- 7 au, p = 0.51). These data indicate that the inspiratory EMG activity of the diaphragm is not differentially distributed between its costal and crural components during chemically stimulated breathing in piglets.

Developmental changes in the ventilatory response of the newborn to added airway resistance.

Postnatal development of the steady-state response to inspiratory resistive loading was studied in eight 48-hour-old and seven 24-day-old tracheostomized monkeys. The newborn subjects did not maintain minute ventilation (Vl) with increasing loads of from 2 to 6 times baseline respiratory resistance, whereas the older subjects kept Vl constant when challenged by the same added resistances. The response patterns in both groups were characterized by a prolongation of Tl and Tl/Ttot, a reduction of respiratory frequency, and increases in airway occlusion pressure and respiratory work output. Apart from Vl, tidal volume (VT) was the only other ventilatory variable that differed significantly between age groups during loading. Arterial CO2 and O2 did not change from baseline in either group during loading, indicating that both age groups defended blood gas values equally well. The increases in occlusion pressures, inspiratory work output, and the maintenance of PaCO2 in the newborns indicated the presence of load compensatory mechanisms despite the fact that Vl was not strictly defended.