Respiratory effort with airway closure during mixed apneas.
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Biomedical subjects
Publications and source records attributed to N N Finer.
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We investigated the effects of clinically comparable doses of ibuprofen and indomethacin on renal, gastrointestinal and cerebral perfusion in newborn piglets, and hypothesized that ibuprofen would have less effect on regional circulation. Animals were randomly assigned to receive ibuprofen (20 mg/kg, n = 8), indomethacin (0.3 mg/kg, n = 7) or vehicle (n = 6). Fluorescent microspheres were injected prior to and at 20, 40, 60, 90 and 120 min after drug administration. Regional blood flow was measured and vascular resistances were calculated. Cardiovascular and respiratory variables were not significantly affected by either study drug or vehicle. Ibuprofen increased renal cortical and medullary resistance by 44 and 52% (p < 0.05). However, ibuprofen had no significant effects on gastrointestinal or cerebral resistance. Indomethacin raised renal cortical and medullary resistance by 66 and 71% at 60 min postinjection, respectively (p < 0.05). Indomethacin increased duodenojejunal, ileal and colon resistance by 97, 102 and 75% at 60 min, respectively (p < 0.05). Indomethacin increased cerebral cortical and cerebellar resistance by 92 and 86% at 90 min (p < 0. 05). While indomethacin and, to a lesser extent, ibuprofen both increase renal vascular resistance, indomethacin vasoconstricts the gastrointestinal and cerebral circulations which are unaffected by ibuprofen.
The object of this study was to determine the effects of partial liquid ventilation (PLV) with and without inhaled nitric oxide (NO) over a 4-h period on lung mechanics, gas exchange, and hemodynamics in an animal model of meconium aspiration syndrome (MAS). Twenty-four fentanyl-anesthetized piglets were instrumented and administered a slurry of human meconium to create a model with hypoxia, hypercarbia, acidosis, and pulmonary hypertension. They were then randomly assigned to conventional ventilation, conventional ventilation plus inhaled NO at 40 ppm, PLV using perfluorodecalin, or PLV plus inhaled NO. The perfluorocarbon was added until a meniscus was visible in the endotracheal tube during expiration. Hemodynamics, lung mechanics, and gas exchange were monitored for 4 h, and then the animals were killed. The conventionally ventilated animals continued to deteriorate, and three of the six died prior to 4 h. All the animals in the remaining groups survived. Oxygenation improved significantly immediately with the start of inhaled NO (from 43.8 SD 10.3 to 62.6 SD 11.7 mm Hg after 30 min) and stayed elevated compared with the control group for the remainder of the study (62.4 SD 21.8 mm Hg at 4 h compared with 44.9 SD 1.6 mm Hg for the control group, p < 0.05). Oxygenation improved more slowly in the PLV alone group, being slightly less than control at 30 min (p = NS) but increasing to 104 SD 34.9 after 4 h (p < 0.01 compared with the control group), at which time it was also greater than inhaled NO alone (p < 0.05). The combined group had an acute increase in oxygenation indistinguishable from the NO alone group and maintained this until the end of the study. Lung compliance was unaffected in the inhaled NO group. In both the liquid ventilation groups the lung compliance improved with the instillation of perfluorodecalin (from 0.46 SD 0.18 to 0.62 SD 0.09 ml/cm H(2)O/kg in the PLV alone group at 1 h, p < 0.05 compared with the control group) and remained stable for the remainder of the study. Cardiac output and pulmonary vascular resistance were not significantly affected by any of the treatments. It was concluded that in this animal model of MAS, inhaled NO led to an acute improvement in gas exchange and prolonged survival compared with conventional therapy. PLV improved lung mechanics, which was maintained over the course of the study. The combination of PLV and inhaled NO produced both effects, acutely improving both gas exchange and lung mechanics. Combined therapy with PLV and inhaled NO may have benefits in the MAS.
OBJECTIVE: The limited literature available to date suggests that the use of delivery room cardiopulmonary resuscitation (DR-CPR) is associated with very poor outcomes, especially for extremely low birth weight infants. We reviewed the cumulative experience of the Vermont Oxford Network to determine the actual utilization of DR-CPR and the neonatal outcomes of such infants. METHODS: A retrospective review of information available in the Vermont Oxford Network Database for the years 1994 to 1996. The data set was collected from 196 neonatal units who participate in the Network (data for infants 401 to 500 g were from 1996 only). Infants were eligible for study if they received DR-CPR defined as the administration of chest compressions and/or epinephrine in the delivery room as noted on the Vermont Oxford Network Database record. RESULTS: Information regarding survival was available for 27 707 newborns with birth weights from 501 to 1500 g, and 497 infants with birth weights from 401 to 500 g. There were 24 001 (86.6%) survivors. Overall DR-CPR was given to 9.3% of infants from 401 to 500 g and 6% of infants from 501 to 1500 g, 82.1% receiving chest compressions, and 66.7% receiving epinephrine. Survival of infants receiving DR-CPR was 23. 9% for infants of 401 to 500 g, and 63.3% for infants of 501 to 1500 g, compared with 16.7% and 87.9% for infants in these weight groups not receiving DR-CPR. Survival was greater for infants of 501 g or greater without DR-CPR compared with those who received this intervention within each 250-g birth weight subgroup. For infants of <1000 g, survival was 53.8% with DR-CPR compared with 74.9% without. Head ultrasounds were available for 95.5% of all surviving infants and 96.7% of infants who received DR-CPR. Overall, any grade of intraventricular hemorrhage (IVH) occurred more frequently in infants who received DR-CPR (38%) than in those who did not (21%). Grade 3 or 4 (severe) IVH was seen in 15.3% of infants who received DR-CPR compared with 4.9% of the infants who did not. Overall, survival without severe IVH occurred in 52.2% of DR-CPR infants compared with 81.3% of infants who did not require this intervention. CONCLUSION: The majority of very low birth weight and extremely low birth weight infants who receive DR-CPR survive, and at least half of such infants who survive do not have evidence of severe IVH. Further follow-up studies are required to determine the long-term neurodevelopmental outcome of such infants. The current study does not support the previously noted poor outcome in extremely low birth weight infants who receive DR-CPR.
OBJECTIVE: None of the 20 previously reported infants weighing <750 g at birth who received cardiopulmonary resuscitation (CPR) in the delivery room (DR) survived. To clarify whether such resuscitation is futile in our center, we evaluated our experience with DR-CPR over a 4-year period. STUDY DESIGN: We retrospectively reviewed the outcomes of all inborn infants with birth weights <1000 g at University of California, San Diego Medical Center from January 1993 to December 1996. Surviving infants and matched control infants were followed for </=40 months' adjusted age using standardized neurodevelopmental assessments. RESULTS: Of the infants with birth weight <1000 g born during this period, 29% (51/177) died, including 44% of those <750 g and 16% of those >/=750 g. Overall, 19 infants received DR-CPR, of whom 12 were <750 g. Of the infants who received DR-CPR, 79% (15/19) survived, including 10 of 13 infants <750 g and 5 of 6 infants >/=750 g. Of the 15 survivors, 10 were followed beyond 10 months' adjusted age (median: 28 months). At last examination, 70% were both neurologically and developmentally normal. Two infants had cerebral palsy with mild cognitive and severe motor developmental delay. Of 7 infants with birth weight <750 g, 6 had normal neurodevelopmental outcomes. The mean composite mental and motor scores of DR-CPR survivors were 93 +/- 10 and 89 +/- 25, respectively. No differences were found in neurologic or developmental outcome between DR-CPR survivors and control infants matched for gestational age, sex, and year of birth. CONCLUSIONS: Our results indicate that intact survival is possible for infants weighing <750 g at birth after DR-CPR.
BACKGROUND/PURPOSE: The purpose of this study was to evaluate the evolving outcome of newborns who have congenital diaphragmatic hernia (CDH) using a protocolized approach to management, which includes extracorporeal membrane oxygenation (ECMO) and to present the details of such a management protocol. METHODS: A retrospective chart review was conducted of the neonatal outcome of near-term (>34 weeks' gestation) newborns with CDH all referred to the Royal Alexandra Hospital either before or after delivery. A protocol was developed that included antenatal assessment, the use of antenatal steroids, planned delivery, use of prophylactic surfactant, pressure limited gentle ventilation, permissive hypercarbia and hypoxia, and venovenous ECMO, if indicated. RESULTS: Sixty-five infants with CDH were treated from February 1989 through August 1996. Twenty-three infants were inborn, 20 of whom were antenatal referrals. Overall, 51 of the 65 infants survived (78%). Thirteen of the 23 inborn infants survived with conservative management, and 10 required ECMO, of whom, eight were long-term survivors. Thirty-eight infants required ECMO, and 26 survived (68%), whereas there were only two deaths among the 27 conservatively treated infants. Eighteen of 20 inborn infants with an antenatal diagnosis survived, compared with 13 of 21 (62%) outborn infants. An antenatal diagnosis before 25 weeks' gestation was associated with a 60% survival rate. Sixty-three percent of infants whose best postductal PaO2 value before ECMO was less than 100 torr survived, and 7 of 11 infants with a best postductal PaO2 value of less than 50 torr before ECMO survived (64%). The average age at surgery progressively increased over time both for infants who did not require ECMO (1.3 days to 5.8 days; P = .01) and for infants who received ECMO (1.9 days to 8.2 days; P = .016). CONCLUSIONS: The use of a protocolized management for infants with CDH has been associated with improving outcome in a population at high risk. The components (either separately or combined) of these protocolized approaches need to be tested in prospective trials to determine their true benefit. In addition, there is a need to evaluate prospectively the outcomes of infants with CDH born in ECMO centers compared with those infants born in other tertiary care neonatal units to determine the most appropriate management of the fetus with CDH.
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Bronchopulmonary dysplasia (BPD), first described in 1966, remains an issue of both clinical and public health importance. BPD may be associated with chronic respiratory difficulties, prolonged and recurrent hospitalization, an increased incidence of neurodevelopmental disabilities, growth restriction, and death. Controversies regarding the cause of BPD are important to resolve in an attempt to develop strategies for prevention.
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Although venoarterial extracorporeal membrane oxygenation (ECMO) is an accepted form of cardiopulmonary support for critically ill neonates, carotid artery reconstruction (CAR) after decannulation remains controversial. Long-term follow-up information regarding the natural progression of the anastomosis is unavailable. From January 1990 through December 1990, 13 venoarterial neonatal ECMO survivors had CAR performed and were enrolled into this prospective study based on sonographic follow-up of CAR. A total of 34 carotid artery sonographic studies were performed (13 within 1 week after reconstruction, 8 at 6 to 9 months, and 13 at 4 years of age). A high patency rate during the neonatal period was observed (12 of 13, 92%). Among 12 children with normal neonatal sonographic studies, 5 had completely normal studies during 4 years of follow-up. Narrowing at the anastomotic site (defined as structural narrowing with velocity ratio of peak systolic velocity at the anastomosis to peak systolic velocity proximal to the anastomosis > 1.0 but < or =2.0) by 4 years of age developed in 7 children. Two of these 7 children had hemodynamically significant stenotic anastomosis (defined as structural narrowing with velocity ratio >2.0) by 4 years of age. One neonate had a narrowed anastomosis that resolved completely by the age of 4 years. The incidence of normal studies decreased from 92% to 75% to 46% during the neonatal period, at 6 to 9 months, and at 4 years follow-up, respectively (Chi-square test for trend, P < .01). Long-term follow-up information on the natural progression of carotid reanastomosis is required.
A complex vascular abnormality in the lungs, termed alveolar capillary dysplasia (ACD) and misalignment of the lung vessels, has been recently recognized in some infants with persistent pulmonary hypertension. These infants die despite maximal medical support including extracorporeal membrane oxygenation (ECMO). Inhaled nitric oxide has been reported to improve oxygenation in neonates with persistent pulmonary hypertension of the newborn, and may allow some infants to avoid the need for ECMO. We identified five infants who had received inhaled nitric oxide to treat refractory hypoxemia caused by persistent pulmonary hypertension of the newborn, and who subsequently died and had autopsy confirmation of ACD. Each infant received care at a different medical center. In each patient, inhaled NO increased the arterial partial pressure of oxygen dramatically. Despite initial clinical improvement, the response to NO was not sustained in any patient. As responsiveness was lost, each infant with ACD required inhaled NO concentrations of 80 ppm or higher to sustain oxygenation. Each infant died, four after extensive periods of ECMO support. This experience demonstrates that a short-term improvement after inhalation of nitric oxide does not lead to long-term survival in ACD. Further, in three infants the diagnosis of ACD was established by lung biopsy before death. Increasing awareness of this clinical entity may allow for the avoidance of costly, invasive procedures such as ECMO until more specific therapies become available.
Nitric oxide given as an inhalation (INO) is a novel selective pulmonary vasodilator without effects on the systemic circulation. Preliminary observations indicated that INO treatment was associated with improvements in oxygenation in near-term newborn infants with hypoxic respiratory failure and persistent pulmonary hypertension of the newborn (PPHN). Subsequently, at least eight prospective randomized controlled trials evaluating the use of INO in the near-term neonate with hypoxic respiratory failure have been presented or published. A meta-analysis of these trials has provided evidence that INO improves the PaO2 in the INO-treated infants by 52.8 mm Hg (weighted mean difference) compared with controls (95% CI, 38.2, 67.4), and significantly decreases the oxygenation index by 16.9 compared with controls (95% CI, -22.2, -11.6). The incidence of death or need for ECMO is significantly reduced by treatment with INO, relative risk 0.71 compared to control (95% CI, 0.57, 0.87), with the majority of the improvement observed in the reduction in the need for ECMO. A single study of infants with congenital diaphragmatic hernia (CDH) did not show a benefit for early INO therapy, with treated infants having a greater requirement for ECMO (P = .043). At present, there are no long-term evaluations of infants who have received INO as part of these prospective trials. INO improves oxygenation and reduces the need for ECMO in the near-term hypoxic neonate, but further research is required to evaluate the ultimate safety and benefit of this therapy.
The role of rescue high-frequency oscillatory ventilation (HFO) in treating very-low-birth-weight neonates with severe respiratory failure in relation to neurodevelopmental outcome has not been evaluated. We performed a retrospective cohort study on 21 patients (out of 52 consecutively admitted preterm neonates with gestational age < or = 30 weeks and birth weight < or = 1.250 g; mortality rate 60%) rescued with HFO between October 1988 and August 1993. Neurodevelopment, including Bayley Scales in Infant Development, was assessed at 12-61 (mean 28.5) months adjusted age. Thirteen normal (scores better than 2 SD below mean, and no sensory or motor disability) (62%) and neurodevelopmentally disabled children (38%) survived more than 1 year for developmental assessment. The mental and performance developmental indices were 94 (78-117) and 89 (68-110), and 63 (49-102) and 49 for the 13 normal and 8 disabled children, respectively (both p < 0.05). The incidence of bronchopulmonary dysplasia, intraventricular hemorrhage (IVH; grade 3 or 4), growth retardation, developmental scores and disabilities of these 21 HFO survivors were not significantly different from that of a birth-weight- and gestational-age-matched comparison group. While all HFO survivors had significant improvement in oxygenation 12 and 24 h after starting HFO, FiO2 and the alveolar-arterial oxygen gradient (A-aDO2) decreased significantly 1 h after starting HFO in survivors with normal neurodevelopmental outcome. The lack of initial response to HFO (20% decrease in A-aDO2 1 h after starting HFO) and the presence of grade 3 or 4 IVH predicted neurodevelopmental disability with a sensitivity of 63%, a specificity of 100%, and positive and negative predictive values of 100 and 81%, respectively. We concluded that HFO could be used as a rescue treatment in sick preterm neonates. The lack of early improvement in oxygenation and the presence of grade 3 or 4 IVH can predict adverse early childhood neurodevelopment in such neonates.
The response of the systemic, pulmonary, hepatic and portal circulations to infusion of dopamine and epinephrine was studied in newborn piglets 1 to 3 d of age. Anesthetized animals were instrumented to measure cardiac index (CI), hepatic arterial flow, and portal venous blood flow. Catheters were inserted for measurement of systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), and for sampling of arterial, portal venous, and mixed venous oxygen saturations and plasma lactate levels. Systemic, pulmonary and mesenteric vascular resistance indices (SVRI, PVRI, MVRI), and systemic and mesenteric oxygen extraction were calculated. Dopamine and epinephrine were infused in doses of 2, 10, 32 microg/kg/min and 0.2, 1.0, 3.2 microg/kg/min respectively, given in random order. Significant increases in SAP, PAP, and CI were demonstrated with 32 microg/kg/min of dopamine and the two higher doses (1.0 and 3.2 microg/kg/min) of epinephrine. There were no significant changes in SVRI and PVRI with dopamine infusions. Epinephrine at 3.2 microg/kg/min significantly elevated SVRI and PVRI. The SAP/PAP ratio was decreased with 32 microg/kg/min of dopamine whereas epinephrine did not affect the ratio. Dopamine had no significant effect on hepatic arterial flow, portal venous flow, or mesenteric vascular resistance. Epinephrine infusion at 3.2 microg/kg/min decreased portal venous blood flow, total hepatic blood flow, and hepatic oxygen delivery with an increase in calculated mesenteric vascular resistance. Systemic and mesenteric oxygen extraction were not affected by dopamine or epinephrine infusions. Plasma lactate levels were significantly elevated with epinephrine infusion 3.2 microg/kg/min. The differential responses of dopamine and epinephrine on pulmonary and mesenteric circulations may be significant in the pathophysiology and management of persistent fetal circulation and necrotizing enterocolitis.
From February 1989 to January 1994, nine of 63 (14.3%) survivors of neonatal extracorporeal membrane oxygenation developed bilateral sensorineural hearing loss. Seven of nine children were tested and passed initial or repeat clinical auditory brainstem response evaluation completed before discharge from neonatal intensive care. Hearing loss was suspected and confirmed between 6-36 and 10-48 months of age, respectively. We recommend regular audiologic follow-up for these high-risk infants until bilateral thresholds for hearing can be obtained.
Neonates with chronic lung disease often require oxygen in the neonatal intensive care unit. The purpose of this study was to determine (1) the actual inspired oxygen concentration (FiO2) delivered to neonates when using a low-flow flowmeter and a nasal cannula, and (2) the accuracy with which FiO2 could be estimated using a formula that we developed. We studied two groups of infants: 18 infants less than 1,500 g and 13 infants greater than 1,500 g. We measured pharyngeal oxygen levels by sampling pharyngeal gas in infants receiving 100% humidified oxygen by nasal cannula from a low range flow flowmeter. The oxygen flow was increased by 25 mL/min increments from 25 to 200 mL/min. The measured FiO2 was compared with the calculated FiO2 using the formula: [formula: see text] where minute ventilation (VE) equals the minute ventilation in mL/min (VE = VT X respiratory rate). For both groups of infants, increments of 25 mL/min of flow produced distinctive changes in FiO2 at all levels (P < 0.001). The calculated FiO2 did not significantly differ from the actual FiO2 at any flow. The calculated FiO2 was most predictive when using an assumed tidal volume of 5.5 mL/kg. We conclude that an accurate flowmeter connected to 100% humidified oxygen can produce a wide range of predictable FiO2s for neonates, especially those with birthweights of less than 1,500 g. The proposed formula allows useful estimation of the infant's FiO2 when we assume a tidal volume of 5.5 mL/kg.
Venovenous (VV) extracorporeal membrane oxygenation (ECMO) using a double lumen catheter has become an accepted method of providing ECMO support for critically ill newborn infants. In addition, use of the cephalic jugular catheter can provide augmented venous blood flow, potentially prevent increased cerebral venous pressure, maintain cerebral venous blood flow, and increase ECMO oxygen delivery. The authors compared their experience using VV double-lumen (VVDL) ECMO with a cephalic jugular catheter with their previous experience using venoarterial (VA) ECMO. They compared 15 infants who had meconium aspiration syndrome (MAS) and 12 who had congenital diaphragmatic hernia (CDH) treated with VVDL ECMO with a cephalic jugular catheter with the same number of infants with each condition treated with VA ECMO (historical controls). There were no significant differences between the groups with respect to birth weights, oxygen indexes before ECMO, of ECMO flows at 4 and 24 hours. For infants with MAS treated with VVDL ECMO, the overall duration of ECMO support was significantly shorter (63 hours VVDLv 118 hours VA; P = .001), and the average cephalic flow was 33 mL/kg for infants treated with VVDL support. For infants with CDH, there were no differences in any of the variables evaluated, including total duration (100 hours VVDLv 128 hours VA; P = .06 [NS]), and the average cephalic flow was 39 mL/kg for infants treated with VVDL support. The venous oxygen content was significantly lower in infants with MAS treated with VVDL ECMO than for historical controls treated with VA ECMO at 4 hours of ECMO support (15.8 v 16.7; P < or = .05). No other significant differences were noted for any of the calculated oxygen transport variables comparing VVDL with VA ECMO infants with CDH treated with VVDL ECMO were extubated sooner than those treated with VA ECMO (10.3 days VVDL v 15.4 days VA; P = 048). In addition, there was no significant difference in the overall incidence of complications or death. This experience suggests that VVDL ECMO using a cephalic jugular catheter results in shorter ECMO runs and provides support that is comparable to VA ECMO for infants with CDH and MAS while avoiding carotid artery cannulation and ligation.