Biomedical subjects

B L Short

Publications and source records attributed to B L Short.

At least 19 recordsLinked to original sources

PubMed2006

Validation of a noninvasive neonatal optical cerebral oximeter in veno-venous ECMO patients with a cephalad catheter.

INTRODUCTION: Cerebral Oximetry is an optical technique that allows for noninvasive and continuous monitoring of brain oxygenation by determining tissue oxygen saturation (SctO2). In conjunction with pulse oximetry, cerebral oximetry offers a promising method to estimate cerebral venous oxygen saturation (SvO2). OBJECTIVE: The aim of this study was to validate the cerebral oximetry measurements with the cerebral oxygen saturation measured from blood drawn in neonates on veno-venous ECMO with existing cephalad catheter with a prototype neonatal cerebral oximeter developed by CAS Medical Systems (Branford, CT, USA). STUDY DESIGN: After obtaining informed consent, neonates undergoing VV-ECMO with cephalad catheterization were monitored by the CAS cerebral oximeter. Cephalad blood samples were periodically obtained to validate the monitor's accuracy. RESULTS: Seventeen neonates were studied with 1718 h of cerebral oximetry data collected. Compared to the reference values, the bias+/-precision for cerebral oximetry SctO2 was 0.4+/-5.1% and derived SvO2 was 0.6+/-7.3%. CONCLUSION: We recommend the use of this noninvasive method as an alternative to blood draws for cerebral venous saturation measurements in neonates requiring extracorporeal life support.

Brain Chemistry↗

PubMed2001

Outcome of perforated necrotizing enterocolitis in the very low-birth weight neonate may be independent of the type of surgical treatment.

Perforated necrotizing enterocolitis (NEC) in the low-birth weight infant is now one of the most common surgical problems encountered in contemporary neonatal intensive care units. However, morbidity and mortality from NEC remain high, and the optimal surgical management of these infants remains controversial. Currently few data exist comparing the factors influencing outcome in very low-birth weight infants with perforated NEC treated by either local drainage or exploration. We hypothesize that survival of very low-birth weight neonates with perforated NEC may be more dependent on clinical status than on treatment modality. We present our experience treating a large cohort of infants weighing less than 1000 g with perforated NEC. A retrospective cohort study describes our experience with perforated NEC in very low-birth weight infants in a Level III neonatal intensive care unit. Between January 1991 and May 1998 a total of 70 newbo infants weighing less than 1000 g were evaluated and managed for perforated NEC. Comorbid factors were identified and calculated for each infant. Primary treatment was either local drainage or laparotomy. Statistical analysis was performed by Student's t test and multiple logistic regression. A multiple logistic regression model examined factors (comorbidities, number of comorbidities, and mode intervention) influencing outcome. A Kaplan-Meier survival analysis comparing survival versus number of comorbidities was performed. Twenty-two infants with an average weight of 679 g were treated by local drainage. Forty-eight infants with an average weight of 756 g were treated with exploratory laparotomy. Infants treated by local drainage had a higher cumulative number of comorbid factors (5.2+/-0.50 vs 3.7+/-0.29; P < 0.05) than those managed by operative exploration. Fourteen infants (63%) initially undergoing local drainage for perforated NEC survived. Of the 48 infants 36 operated on survived (75%). No single factor or combination of any comorbid factors was predictive of outcome. The total number of comorbidities for each neonate did reach statistical significance (P < 0.05). A greater likelihood of death was associated with a higher number of comorbidities. Survival with four or fewer comorbidities was 84 per cent, whereas survival with greater than six comorbidities was 30 per cent. The mean number of comorbidities was greater for drainage than for surgery, and for the same number of comorbidities the probability of survival tended to be greater for those treated with drainage than for those undergoing surgery. Multiple logistic regression analysis identified the total number of comorbidities as affecting outcome rather than treatment choice. This suggests therefore that selection of therapeutic options for the patient requires evaluating all factors that may impact survival rather than applying a single treatment strategy for all patients.

Comorbidity↗

PubMed2000

Citrobacter sepsis and severe newborn respiratory failure supported with extracorporeal membrane oxygenation.

An infant with fulminant Citrobacter sepsis and respiratory failure is presented. The severity of respiratory failure and the need for systemic heparinization on extracorporeal membrane oxygenation delayed the opportunity of initial lumbar puncture to rule out meningitis. The infant was successfully treated with extracorporeal membrane oxygenation and long-term antibiotics. Repeated cranial computed tomography scans remained negative for intracerebral abscesses, and the infant is within normal limits for growth, neurologic status, and developmental status.

Anti-Bacterial Agents↗

PubMed2000

The current status of neonatal extracorporeal membrane oxygenation.

Marked changes have occurred in the practice of neonatal extracorporeal membrane oxygenation (ECMO) since the first survivor in 1975. Coagulation management has been markedly refined, new catheters allow ECMO to be done either in a venoarterial or venovenous (VV) mode, depending on cardiac function in the infant. A new design of the VV catheter will allow this technique to be used in more infants in the future. New therapies for respiratory failure have changed the complexion of the population being treated with ECMO. The 34 to 36 week gestation infant with respiratory distress syndrome and/or pulmonary hypertension rarely needs ECMO therapy due to the effectiveness of surfactant and high frequency oscillation. Present day survival for infants treated with ECMO for many diagnostic categories ranges between 90% to 100%. The effects of new interventions must be evaluated with regard to their effect on morbidity when being considered prior to ECMO. Neuro-developmental outcome is encouraging, but does indicate that ECMO and the near-miss ECMO patients need to be followed closely into school age. The number of patients being treated per ECMO center has dropped significantly over the last 10 years from 18 to 9. This brings forward the question about regional needs for ECMO Centers and how to assure that centers have enough patients to maintain their clinical competencies. The challenge for the future is where to place ECMO as a therapy. Should it remain a rescue therapy? Or should there now be a trial comparing ECMO to conventional therapies, with morbidity and cost of care as the outcome variables?

Catheterization↗

PubMed2000

A comparison of intratracheal pulmonary ventilation to conventional ventilation in a surfactant deficient animal model.

OBJECTIVE: To compare intratracheal pulmonary ventilation (ITPV) with conventional ventilation in a rabbit model of surfactant deficiency. DESIGN: A prospective randomized animal study. SETTING: The Children's National Medical Center Research Animal Facility in Washington, DC. SUBJECTS: Adult male New Zealand white rabbits (n = 20), weighing 1.4-4.2 kg. INTERVENTIONS: After anesthesia and catheter placement, rabbits were tracheotomized, paralyzed, and placed on the conventional ventilator. We determined pulmonary functions at baseline. We washed surfactant out of the lungs by using serial bronchoalveolar lavages. Pulmonary function studies were determined after completion of the bronchoalveolar lavages and were used as an indication of severity of lung injury. Animals were randomized into two groups: We placed ten animals on ITPV, using the ITPV reverse thruster catheter designed by Kolobow and a prototype ITPV ventilator designed at Children's National Medical Center; we placed ten animals on conventional ventilation using the Sechrist iv-100 ventilator. Arterial blood gases were drawn every 15 mins, and the ventilator settings were adjusted to the minimal level that would maintain arterial blood gases in the following ranges: pH 7.35-7.45, PaCO2 30-40 torr (3.995.33 kPa), PaO2 50-70 torr (6.66-9.33 kPa). Animals were ventilated with the randomized ventilation techniques for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Peak inspiratory pressure, mean airway pressure, and positive end-expiratory pressure were measured at the distal end of the endotracheal tube. We recorded these variables plus respiratory rate at baseline and every 30 mins for a total of 4 hrs of ventilation. Lung compliance did not differ between groups at the postlavage study period (ITPV, 0.56+/-0.13 mL/cm H2O/kg; conventional 0.49+/-0.15 mL/cm H2O/kg). At the end of the 4 hr study period, peak inspiratory pressure (ITPV, 26.2+/-4.6 cm H2O; conventional, 32.4+/-5.04 cm H2O, p = .007) and positive end-expiratory pressure (ITPV, 3.9+/-1.96 cm H2O; conventional, 6.3+/-1.42 cm H2O, p = .005) were lower in the ITPV ventilation group. Peak inspiratory pressure was significantly lower in the ITPV group by 2 hrs into the study. CONCLUSION: In this model of surfactant deficiency lung injury, ventilation and oxygenation were achieved at significantly lower ventilator settings using ITPV compared with conventional ventilation. Long-term studies are needed to determine whether this reduction in ventilation is maintained, and if so, if lung injury is reduced.

Animals↗

PubMed2000

Cerebral blood flow and metabolism during and after prolonged hypercapnia in newborn lambs.

OBJECTIVE: To study the effects of prolonged (6 hrs) hypercapnia on cerebral blood flow and cerebral metabolism in newborn lambs and to evaluate the effects on cerebral blood flow and cerebral metabolism on return to normocapnia after prolonged hypercapnia. DESIGN: Animal studies, using the newborn lamb, with comparison to control group. SUBJECTS: Newborn lambs of mixed breed, 1-7 days of age, were used for the study. Two groups of animals were studied: a hypercapnic group (n = 10) and a normocapnic control group (n = 5). SETTING: Work was conducted in the research laboratories at Children's National Medical Center, Washington, DC. INTERVENTIONS: Animals were anesthetized with pentobarbital, intubated, paralyzed, and mechanically ventilated. After baseline measurements were made, CO2 was blended into the ventilator gas until a PaCO2 of 75-80 torr (10-10.6 kPa) was obtained. Measurements were made 1 hr after the desired PaCO2 was achieved and after 6 hrs of hypercapnia. After 6 hrs of hypercapnia, the ventilator gas was returned to the baseline value, that is, normocapnia. Measurements were made 30, 60, and 90 mins after PaCO2 returned to baseline. MEASUREMENTS: Six measurements were made during the study. For each measurement, blood samples were drawn from the sagittal sinus and brachiocephalic artery catheters and were analyzed for pH, hemoglobin concentration, oxygen saturation, and blood gas values. Cerebral blood flow (CBF) was measured by using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period. MAIN RESULTS: Increasing PaCO2 from 37 +/- 3 torr to 78 +/- 6 torr (4.9 +/- 0.4 kPa to 10.3 +/- 0.8 kPa) for 1 hr increased CBF by 355%. After 6 hrs of PaCO2 at 78 +/- 3 torr (10.3 +/- 0.4 kPa), CBF remained 195% above baseline. At 30 mins of normocapnia, CBF had returned to baseline and remained at baseline until the conclusion of the study, a total of 90 mins of normocapnia. Cerebral oxygen consumption did not change during hypercapnia or with return to normocapnia. Oxygen transport increased 331% above baseline after 1 hr of hypercapnia and stayed 180% above baseline after 6 hrs of hypercapnia. Fractional oxygen extraction decreased by 55% at 1 hr of hypercapnia and stayed 39% below baseline at 6 hrs of hypercapnia. CONCLUSIONS: Healthy lambs seem to tolerate undergoing hypercapnia for 6 hrs with a return to normocapnia. The return to baseline of CBF and cerebral metabolism at normocapnia seen in our study with lambs may explain why prolonged hypercapnia appears to be well tolerated in mechanically ventilated patients. If these results can be extrapolated to human subjects, our study in lambs supports evidence that patients who have undergone permissive hypercapnia seem to be neurologically unaffected.

Age Factors↗

PubMed2000

Venoarterial extracorporeal membrane oxygenation impairs basal nitric oxide production in cerebral arteries of newborn lambs.

OBJECTIVE: Based on previous studies in our laboratory showing that exposure of newborn lambs to venoarterial extracorporeal membrane oxygenation (ECMO) alters cerebral blood flow autoregulation, we postulated that this altered vascular reactivity is mediated through changes in endothelial function caused by the pumping systems used in venoarterial ECMO. We tested that hypothesis in this study. DESIGN: Prospective, controlled, laboratory trial. SETTING: Animal research laboratory. SUBJECTS: Two groups of newborn lambs. INTERVENTIONS: One group of animals was exposed to venoarterial ECMO (n = 6) and another group of control animals (n = 5) was maintained under similar conditions for 2 hrs on the ventilator without ECMO. MEASUREMENTS AND MAIN RESULTS: Third-order branches of the middle cerebral arteries (140-300 microm diameter) were isolated from animals at the end of the experiment, mounted on glass cannulae in an arteriograph, and superfused with Krebs-Ringer buffer. Decrease in the diameter of the arteries induced by exposure of the vessels to nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (200 micromol/L) for 30 mins was significantly less (p <.05) in arteries from lambs exposed to ECMO compared with control animals. There were no significant differences between the two groups in myogenic response or in the contractile activity of the arteries to increasing concentrations of serotonin. CONCLUSIONS: These results demonstrate that 2 hrs of exposure of newborn lambs to venoarterial ECMO leads to a decrease in basal production of nitric oxide in cerebral arteries, and suggest that venoarterial ECMO selectively impairs cerebral arterial endothelial function.

Journal Article↗

PubMed2000

Effect of nitric oxide and high-frequency oscillatory ventilation in meconium aspiration syndrome.

OBJECTIVE: To test the hypothesis that inhaled nitric oxide, when combined with high-frequency oscillatory ventilation, is an effective therapeutic agent in meconium aspiration syndrome. DESIGN: Prospective, interventional study. SETTING: The animal research laboratory at The Children's National Medical Center. SUBJECTS: Five newborn piglets, 1-2 wks old, weighing 3.6 +/- 0.2 kg. INTERVENTION: Animals were anesthetized, paralyzed, intubated, and ventilated. Catheters were placed in the femoral vein and artery and the pulmonary artery. After 1 hr of recovery, 10 mL/kg of 20% meconium in normal saline solution was insufflated into the lungs. Animals were ventilated with a SensorMedics oscillator to maintain arterial blood gases in a normal range (pH, 7.35-7.45; Paco2, 40-45 mm Hg [5.3-6.0 kPa]; Pao2, 70-90 mm Hg [9.3-12.0 kPa]). Ventilator settings were increased as needed until maximum settings as follows: Fio2, 1.00; proximal oscillatory pressure amplitude, 36 cm H2O; mean airway pressure, 25 cm H2O; frequency, 10 Hz. After a short period of stabilization, inhaled nitric oxide was administered. Concentrations of 40, 20, and 10 ppm were given and measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. To assure that there was no additive effect of inhaled nitric oxide, each dose was given for 20 mins followed by a 15-min normalization period at 0 ppm. MEASUREMENTS AND MAIN RESULTS: Physiologic measurements, ventilatory settings, arterial blood gases, and methemoglobin were recorded at each study period. Measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. Arterial saturation and partial pressure of arterial oxygen (Pao2) were significantly lower after meconium aspiration when compared with baseline. Administration of inhaled nitric oxide improved oxygenation without a significant decrease in pulmonary artery pressure. CONCLUSION: In this model of meconium aspiration syndrome, short-term exposure to inhaled nitric oxide when combined with high-frequency oscillatory ventilation improved oxygenation secondary to better distribution of inhaled nitric oxide. The increase in oxygenation may be secondary to improved ventilation perfusion mismatch, as the primary etiology of hypoxia in this model may be a combination of parenchymal lung disease and pulmonary hypertension.

Journal Article↗

PubMed2000

Neurodevelopmental outcome in ECMO vs near-miss ECMO patients at 5 years of age.

The objective of this study was to compare the outcome of children at 5 years of age who were treated with extracorporeal membrane oxygenation (ECMO) and those who were critically ill but did not meet ECMO criteria, identified as near-miss ECMO. In one of the longest studies of its kind, we compared the neurodevelopmental outcome of 76 5-year-old ECMO-treated children with 20 5-year-old near-miss ECMO patients with similar primary diagnoses. The two groups were compared for demographic data, level of ventilatory support, and degree of hyperventilation. The comprehensive assessment protocol included an assessment of intelligence (IQ), attainment of preacademic and early academic skills, and parents' report of adaptive behavior. Both groups had similar demographic data and primary diagnosis. The near-miss ECMO patients required increased ventilatory support but not significantly more than the ECMO patients. The cognitive outcome was similar in both groups with mean estimated Full-Scale IQ in the normal range for near-miss and ECMO groups (89 and 97, respectively). Rates of severe mental handicap (FSIQ < 70) (near-miss = 11%, ECMO = 12%) and risk for school failure (near-miss = 38%, ECMO = 37%) were also similar. More parents of near-miss ECMO patients reported immature adaptive skills than did parents of ECMO patients, although the numbers were small in each group. Rates of parent-reported child behavior problems were similar in both groups. ECMO and near-miss ECMO patients have similar cognitive and adaptive outcomes at 5 years of age. A significant number in each group are at risk of school failure and should be closely followed up.

Central Nervous System Diseases↗

PubMed2000

Morbid hypocalcemia associated with phosphate enema in a six-week-old infant.

A 6-week-old premature infant who was born at 29 weeks of gestation presented to the emergency department with a several-hour history of stiffness and increased alarms on his apnea monitor at home. On arrival he was noted to have generalized seizures, apnea, and bradycardia. He was intubated and required cardiopulmonary resuscitation including chest compressions and medications. After stabilization he was transferred to the neonatal intensive care unit for further management. His initial laboratory tests revealed a serum calcium level of 2.4 mg/dL (normal range: 8.4-10.2 mg/dL) and a serum phosphorus level of 28.5 mg/dL (normal range: 2.4-4.5 mg/dL). During the first week of admission, the infant's mother reported that she had administered a full pediatric Fleets enema (CB Fleet Company Inc, Lynchburg, VA) to him. The infant was discharged after 12 days of hospitalization. Anticipatory guidance on the stool patterns and behavior of infants can prevent misconceptions about constipation that are especially prevalent in new parents. Proper management of constipation, should it arise, should be addressed with all parents at early well-child visits to avoid hazardous complications of treatments. hypocalcemia, seizures, premature infants, enema.

Apnea↗

PubMed1998

Use of nitric oxide in meconium aspiration syndrome: lack of response.

PURPOSE: To test the hypothesis that inhaled nitric oxide (INO) may not be an effective therapeutic agent in meconium aspiration syndrome (MAS). DESIGN: Prospective, interventional study. SETTING: The animal research laboratory at The Children's National Medical Center. SUBJECTS: Seven newborn pigs, 2-7 days old, weighing 2.8 +/- 0.17 kg were used for the study. MATERIALS AND METHODS: Animals were anaesthetized, paralysed, intubated and ventilated. Catheters were placed in the jugular vein, carotid artery, and pulmonary artery. After 1 h of recovery 10 ml/kg of 20% meconium in normal saline solution was insufflated into the lungs. Animals were ventilated to maintain ABGs in a normal range, i.e. pH = 7.35-7.45, PaCO2 = 40-45, and PaO2 = 70-90 torr. Ventilator settings were increased as needed until maximum settings of: FiO2 = 1.00, PIP = 40, IMV = 60. After 2 h of conventional ventilation or demonstration of significant lung disease by failure to maintain desired blood gases on maximum ventilator settings, INO was administered for 20 min in concentrations of 10, 20 and 40 ppm. To ensure that there was no additive effect of INO, a 15-min normalization period at 0 ppm was allowed between each dose of INO. Physiologic measurements, ventilatory settings, arterial blood gases, and methemoglobin were recorded at each study period. Measurements were taken after each exposure to INO and after its discontinuation. RESULTS: Arterial saturation (SaO2) and PaO2 were significantly lower ([81 +/- 18] and [54 +/- 14], respectively) and PAP was significantly higher [24 +/- 3] after MAS when compared with baseline. Administration of INO did not improve oxygenation nor decrease PAP at any of the study doses. CONCLUSION: In this model of MAS, short-term exposure to INO did not decrease PAP nor improve oxygenation. It may be postulated that poor distribution of INO caused by the obstructive nature of this disease may be responsible for the lack of response in this disease state, or that the primary etiology for hypoxia is parenchymal lung disease and not pulmonary hypertension.

Administration, Inhalation↗

PubMed1998

Cardiovascular complications adversely affect survival during extracorporeal membrane oxygenation.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used in the management of infants with cardiorespiratory failure. ECMO causes a decrease in load-dependent measures of cardiac performance that have not been demonstrated to affect patient outcome, while other cardiovascular complications occur which may affect outcome. The purpose of this study was to describe the cardiovascular complications associated with ECMO, and to determine their relationship to survival. DESIGN: Data were obtained, retrospectively, from the medical records of 500 consecutive newborns treated with ECMO at our institution since 1984. RESULTS: Hypertension (mean arterial pressure of >65 mm Hg) was the most common complication, requiring medical intervention in 192 infants. Myocardial stun, the near-total absence of systolic function during ECMO, occurred in 59 infants. Rhythm abnormalities, including noncannulation-related bradycardia, occurred in 43 infants, cardiac arrest, and pericardial effusion in 17 infants, and noninfective thrombosis in 9 infants. Only one infant required ligation of a patent ductus arteriosus during ECMO. Infants with at least one cardiovascular complication had a lower survival rate, compared with those infants without a complication. Survival rates were decreased in infants with myocardial stun, arrhythmia, and cardiac arrest. Hypertension and pericardial effusion were not associated with decreased survival. CONCLUSION: These findings suggest that some cardiovascular complications during ECMO are more common than previously thought, and cardiovascular complications may adversely impact outcome.

Cardiovascular Diseases↗

PubMed1998

Congenital diaphragmatic hernia survival and use of extracorporeal life support at selected level III nurseries with multimodality support.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.

Extracorporeal Circulation↗

PubMed1997

Reduced airway resistance and work of breathing during mechanical ventilation with an ultra-thin, two-stage polyurethane endotracheal tube (the Kolobow tube).

OBJECTIVES: To compare dynamic pulmonary function studies using the ultrathin walled Kolobow endotracheal tube, with conventional endotracheal tubes of similar external diameter on rabbits during mechanical ventilation. To test the hypothesis that the increased internal diameter of the Kolobow tube will result in decreased airway resistance and work of breathing. DESIGN: Controlled animal study. SETTING: Institutional animal research facility. SUBJECTS: Adult female Dutch Belted rabbits (n = 6), weighing 1.4 to 1.6 kg. INTERVENTIONS: The animals were initially intubated with a conventional endotracheal tube (2.5-mm internal diameter; 3.6-mm outer diameter); they were paralyzed and placed on a mechanical ventilator. Ventilatory settings were adjusted to obtain standard arterial blood gases: pH of 7.35 to 7.45; PaCO2 of 35 to 40 torr (4.7 to 5.3 kPa), and PaO2 of 90 to 100 torr (12.0 to 13.3 kPa). After the stabilization period, pulmonary function tests (PFTs) were measured (period 1), the conventional endotracheal tube was replaced with a Kolobow tube, and PFTs were measured again and recorded (period 2). While continuously monitoring tidal volume, the peak inspiratory pressure was decreased to match the tidal volume measured during ventilation with the conventional endotracheal tube. Once the desired tidal volume was reached, PFTs were recorded (period 3). Flows were unchanged during the experiment and the length of the endotracheal tubes was the same for both the conventional and the Kolobow tube. MEASUREMENTS AND MAIN RESULTS: Mean values of the airway resistance and work of breathing from periods 1 and 3 were compared using the Student's t-test. There was a 59% decrease in total airway resistance (p = .001) and 45% decrease in the work of breathing (p = .0006). CONCLUSIONS: The use of the ultrathin walled Kolobow endotracheal tube resulted in significant decreases in airway resistance and work of breathing, which has the potential for improving the ventilatory mechanics in very small premature newborns.

Airway Resistance↗

PubMed1997

Extracorporeal membrane oxygenation exposes infants to the plasticizer, di(2-ethylhexyl)phthalate.

OBJECTIVES: To determine the exposure to, and evaluate the potential toxicity from, the plasticizer, di(2-ethylhexyl)phthalate (DEHP) during extracorporeal membrane oxygenation (ECMO) therapy. DESIGN: Protocol 1 consisted of a prospective comparison of three ECMO circuit designs in vitro. Protocol 2 consisted of a prospective, comparative clinical study evaluating DEHP plasma concentrations in ECMO vs. non-ECMO patients with respiratory failure. SETTING: Neonatal intensive care unit at The Children's National Medical Center, Washington, DC. PATIENTS: In protocol 2, 28 consecutive term infants were referred for ECMO therapy. Eighteen infants required ECMO; ten control patients received conventional ventilation and improved without ECMO. INTERVENTIONS: In protocol 1, three ECMO circuit designs were primed in vitro with normal saline, albumin, and human blood, which was maintained at 37 degrees C and recirculated at 400 mL/min for 48 hrs. Plasma samples were obtained at time 0, 1 hr, and every 6 hrs. In protocol 2, ventilatory and cardiovascular management of the patients in the study was conducted by the attending physician. Patients were placed on ECMO when they met the institutional criteria for ECMO therapy. Daily plasma concentrations for DEHP were collected until 3 days after decannulation from bypass in the ECMO group. Control patients were sampled daily until extubation. Evidence of cardiac, liver, or lung toxicity was evaluated by Chest Radiographic Scores, liver function studies, and echocardiograms obtained on day 1, day 3, and the day of decannulation in the ECMO group, or at the time of extubation in the control group. Sedation, blood product transfusions as indicated, antibiotics, and hyperalimentation were administered to all patients. MEASUREMENTS AND MAIN RESULTS: All DEHP plasma concentrations were measured by gas chromatography. In protocol 1, three circuits were studied: circuit A (small surface area); circuit B (larger surface area); and circuit C (surface area of A but with heparin-bonded tubing in the circuit). DEHP leached from circuit A at 0.32 +/- 0.12 microgram/ mL/hr, compared with 0.57 +/- 0.14 microgram/mL/hr from circuit B (p < .05). This amount of DEHP extrapolates in the ECMO patient to a potential exposure of 20 to 70 times that exposure from other medical devices or procedures, such as transfusions, dialysis, or short-term cardiopulmonary bypass. Circuit C showed almost no leaching from the circuit; DEHP concentrations decreased at a rate of 0.2 +/- 0.04 microgram/mL/ hr. In protocol 2, DEHP was undetected in the control patients. DEHP concentrations in ECMO patients were greater in the early course of ECMO. However, most patients cleared this compound from the plasma before decannulation. In contrast to the in vitro results in protocol 1, the average highest concentration at any time on bypass was 8.3 +/- 5.7 micrograms/mL or 2 mg/kg. CONCLUSIONS: DEHP leaches from ECMO circuits, with potential exposure concentrations related to the surface area of the tubing in the ECMO circuit. Heparin bonding of the tubing eliminates this risk. Although significant concentrations of DEHP leach from the nonheparin-bonded circuits over time, our in vivo studies showed that the DEHP plasma concentrations were less than the previously reported values and do not correlate with any observable short-term toxicity. This compound may be either efficiently metabolized by the newborn, or redistributed into various tissues. Although signs of toxicity were not found in this study, long-term complications from chronic exposure to DEHP have not been determined.

Diethylhexyl Phthalate↗

PubMed1997

Effect of nitric oxide in meconium aspiration syndrome after treatment with surfactant.

OBJECTIVE: To test the hypothesis that inhaled nitric oxide may be an effective therapeutic agent in meconium aspiration syndrome and may improve oxygenation after pretreatment with surfactant. DESIGN: Prospective, interventional study. SETTING: The animal research laboratory at The Children's National Medical Center. SUBJECTS: Eight newborn pigs, 1 to 2 wks of age, 4.1 +/- 0.4 kg, were used for the study. INTERVENTIONS: Animals were anesthetized, paralyzed, intubated, and mechanically ventilated. Catheters were placed in the femoral vein and artery, and in the pulmonary artery. After 1 hr of recovery, 10 mL/kg of 20% meconium in normal saline solution was insufflated into the lungs. Animals were ventilated to maintain arterial blood gases in a normal range (i.e., pH of 7.35 to 7.45, Paco2 of 40 to 45 torr [5.3 to 6.0 kPa], and Pao2 of 70 to 90 torr [9.3 to 12.0 kPa]). Ventilatory settings were increased, as needed, until the following maximum settings were reached: FIO2 of 1.0; peak inspiratory pressure of 40 cm H2O; and intermittent mandatory ventilation of 60 breaths/min. After 2 hrs of conventional ventilation or demonstration of clinically important lung disease by failure to maintain desired blood gases on the maximum ventilatory settings, 4 mL/kg of beractant was given intratracheally. After a short period of stabilization following surfactant therapy, inhaled nitric oxide was administered. Concentrations of 40, 20, and 10 parts per million were given. To assure that there was no additive effect of inhaled nitric oxide, each dose was given for 20 mins, followed by a 15-min normalization period at 0 parts per million. MEASUREMENTS AND MAIN RESULTS: Physiologic measurements, ventilatory settings, arterial blood gases, and methemoglobin were recorded at each study period. Measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. Arterial oxygen saturation and Pao2 were significantly lower after meconium aspiration when compared with baseline values. After treatment with surfactant, administration of inhaled nitric oxide improved oxygenation without a significant decrease in pulmonary arterial pressure. CONCLUSIONS: In this model of meconium aspiration syndrome, short-term exposure to inhaled nitric oxide after treatment with surfactant improved oxygenation secondary to better distribution of inhaled nitric oxide. The increase in oxygenation may be secondary to an improved ventilation/perfusion mismatch, since the primary etiology of hypoxia in this model may be a combination of parenchymal lung disease and pulmonary hypertension.

Administration, Inhalation↗

PubMed1997

Use of intratracheal pulmonary ventilation versus conventional ventilation in meconium aspiration syndrome in a newborn pig model.

OBJECTIVE: To determine whether intratracheal pulmonary ventilation (ITPV) allows for effective oxygenation and ventilation at lower mean airway pressures and peak inspiratory pressures than conventional ventilation in a piglet model of meconium aspiration syndrome. DESIGN: Prospective, interventional study. SETTING: The animal research laboratory at Children's National Medical Center, Washington, DC. SUBJECTS: Twenty newborn piglets, 2 to 7 days of age, weighing 1.8 to 2.8 kg. INTERVENTION: Animals were anesthetized, paralyzed, intubated, and ventilated. Femoral arterial and venous catheters were inserted; 5 mL/kg of 20% meconium in normal saline was instilled into the endotracheal tube. Animals were randomized to either ITPV or conventional ventilation, and settings were adjusted to maintain ideal blood gases, i.e., pH 7.35 to 7.45, PCO2 40 to 45 torr (5.3 to 6 kPa), PO2 80 to 100 torr (10.7 to 13.3 kPa), and SaO2 > or = 90%. Ventilatory settings were adjusted as needed to a maximum of: FIO2 1.0, peak inspiratory pressure 40 cm H2O, positive end-expiratory pressure 5 cm H2O, and respiratory rate 80 breaths/min. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases were taken every 30 mins for 4 hrs and ventilatory settings were adjusted to maintain optimal blood gases. Heart rate, mean arterial blood pressure, and arterial saturation were monitored continuously. The animals in the ITPV group had significantly lower peak inspiratory pressure at 1, 2, 3, and 4 hrs after meconium instillation (p < .018) and significantly lower mean airway pressure at 2, 3, and 4 hrs after meconium instillation (p < .03). The mean peak inspiratory pressure in the ITPV animals ranged from 17 +/- 2.7 cm H2O at baseline to 16.6 +/- 5.7 cm H2O at 4 hrs compared with 16.5 +/- 2.7 cm H2O at baseline to 31.8 +/- 9.1 cm H2O at 4 hrs in the conventionally ventilated animals (p < .04). The mean airway pressure ranged from 6.3 +/- 1.1 mm Hg at baseline to 6.8 +/- 2.5 mm Hg at 4 hrs in the ITPV group compared with 5.5 +/- 1.2 mm Hg at baseline to 10.7 +/- 3.4 mm Hg at 4 hrs in the conventional ventilation group (p < .03). The lungs of the ITPV animals were less hemorrhagic and had less pathologic evidence of injury than the lungs of the conventionally ventilated animals. CONCLUSIONS: These results indicate that ITPV can be used to effectively ventilate and oxygenate piglets with meconium aspiration syndrome at lower mean airway pressures and peak inspiratory pressures than conventional ventilation. This lower pressure causes less injury to the lungs of the animals.

Animals↗

PubMed1997

Severity of brain injury following neonatal extracorporeal membrane oxygenation and outcome at age 5 years.

Neurodevelopmental evaluation in childhood provides an opportunity to study complex neurological compensation following documented neonatal brain injury, and furnishes important clinical information which may have an impact on patient care. We studied 152 term children treated with extracorporeal membrane oxygenation (ECMO) as neonates and who received routine neonatal neuroimaging and comprehensive neurodevelopmental evaluation at age 5 years. The cohort was divided into four groups based on an independent neuroimaging score: No lesion, N=88; Mild lesion, N=38; Moderate lesion, N=12; and Severe lesion, N=14. Standardized testing at age 5 included complete neuropsychological assessment, neurological evaluation, and assessment of motor function. All testing was conducted without knowledge of the neuroimaging score. The occurrence of disability by severity of neuroimaging was: No lesion=10%; Mild=13%; Moderate=33%; Severe=57%. The relative risk within the ECMO population for disability at age 5 after moderate or severe neonatal lesion was 4.3 (CI=1.0 to 17.5) and 11.7 (CI=3.3 to 41.3), respectively. The remaining non-disabled children who had moderate to severe lesions functioned within normal limits. Severity of neonatal neuroimaging was inversely associated with IQ scores, pre-academic skills, and neuromotor function. The effect size was small but the rank order was predictable. Our data identify in 5-year-old children an impact of brain lesion severity demonstrated on routine neonatal neuroimaging. The results indicate potential compensation following moderate and severe lesions, and suggest a subtle but consistent influence of even mild neonatal brain injury.

Central Nervous System Diseases↗