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Biomedical subjects

D M Null

Publications and source records attributed to D M Null.

At least 19 recordsLinked to original sources
PubMed1995

Predictors of failure of high-frequency oscillatory ventilation in term infants with severe respiratory failure.

OBJECTIVE: To identify clinical factors in term neonates with severe respiratory failure that predict which neonates are unlikely to respond to high-frequency oscillatory ventilation (HFOV). DESIGN: This was a retrospective review of patient charts and medical records. PATIENTS: We studied 190 newborns treated with HFOV between July 1985 and December 1992. All patients were at least 35 weeks' estimated gestational age and had severe respiratory failure, defined as arterial to alveolar oxygen ratio (a/A ratio) of less than 0.2 or the need for peak inspiratory pressure greater than 35 cm H2O on conventional ventilation. RESULTS: Of the 190 patients, 111 (58%) responded to HFOV (HFOV responders), and 79 (42%) were placed on extracorporeal membrane oxygenation (ECMO) after HFOV failed to improve gas exchange (nonresponders). The two groups were similar in gender and birth weight. Factors associated with failure of HFOV to produce a sustained improvement in gas exchange were a diagnosis of congenital diaphragmatic hernia and more severe respiratory compromise as assessed by admission blood gas. Stepwise logistic regression analysis showed that a diagnosis of congenital diaphragmatic hernia/lung hypoplasia (CDH/LH) and the a/A ratio at initiation of and after 6 hours of HFOV were the only significant independent predictors of the need for ECMO. Among all the patients, the presence of CDH/LH or an initial a/A ratio of 0.05 or lower yielded a sensitivity of 74% and specificity of 77% in correctly identifying neonates in whom HFOV failed to produce a sustained improvement in oxygenation. When neonates with CDH/LH were excluded from analysis, the most significant predictor of failure of HFOV was the a/A ratio after 6 hours of HFOV. In neonates without CHD/LH, a 6-hour a/A ratio of 0.08 or lower discriminated responders from nonresponders (ie, treatment with ECMO) with a sensitivity of 77% and specificity of 92%. CONCLUSIONS: In our patients, the presence of CDH/LH, severe respiratory failure (a/A ratio 0.05 or lower) at initiation of HFOV, and lack of improvement in oxygenation (a/A ratio 0.08 or lower after 6 hours of HFOV) were associated with failure of HFOV and treatment with ECMO. This information should help other centers to identify neonates who are at the greatest risk for requiring ECMO support and thus allow prompt transfer to an ECMO center.

Acute Disease↗
PubMed1994

Failure of acute perinatal asphyxia or meconium aspiration to produce persistent pulmonary hypertension in a neonatal baboon model.

OBJECTIVE: Our purpose was to determine whether perinatal asphyxia or meconium aspiration, or both, can produce the physiologic and histologic pulmonary vascular changes associated with the meconium aspiration syndrome. STUDY DESIGN: Twenty neonatal baboons were studied in four groups: 1, control; 2, meconium aspiration; 3, asphyxia (intermittent cord compression); and 4, asphyxia with meconium aspiration. Animals were ventilated for 24 hours under ketamine, diazepam, and pancuronium. Data were analyzed by means of mixed model analysis of measures. RESULTS: Meconium significantly impaired oxygenation (p < 0.001), whereas concurrent asphyxia moderated this effect (p < 0.034). Meconium also increased the need for ventilatory support (p < 0.002). No animal had persistent pulmonary hypertension; neither systemic nor pulmonary systolic pressures differed statistically between the groups. No animal showed evidence of abnormal pulmonary arteriolar muscularization. CONCLUSION: Sublethal perinatal asphyxia or meconium aspiration were insufficient to produce either the physiologic or histologic changes of severe meconium aspiration syndrome. It is unlikely that intrapartum fetal distress alone can produce this syndrome in human neonates.

Acute Disease↗
PubMed1994

Selective heparinization of the extracorporeal membrane oxygenation circuit using continuous infusions of protamine and heparin in a short-term pig model.

Systemic heparinization is required for both neonatal and paediatric extracorporeal membrane oxygenation (ECMO). However, it places the patient at risk of serious haemorrhage. We report an alternative: 'selective' heparinization of the ECMO circuit using a continuous infusion of heparin near the venous catheter as blood enters the circuit, and a simultaneous protamine infusion near the arterial catheter as blood enters the patient. Theoretically, the circuit remains heparinized while the patient maintains near-normal clotting activity. Three healthy piglets were placed on venoarterial ECMO in standard fashion. When the animal and its extracorporeal circuit flow were stable, a protamine infusion was begun: 1 mg of protamine to neutralize each 100 units of infused heparin. No haemodynamic instability was noted during the five hours of each study. Mean activated clotting times (ACT) were significantly lower in all three piglets than in their respective circuits (p < 0.001). We conclude that 'selective' heparinization of the ECMO circuit is possible using continuous infusions of protamine and heparin in a short-term piglet model.

Animals↗
PubMed1994

Long-term partial liquid ventilation (PLV) with perflubron in the near-term baboon neonate.

PURPOSE: The feasibility and safety of continuous long-term (4-5 day) partial liquid ventilation (PLV) using perflubron was demonstrated in newborn baboons. PLV, a potential therapy for adult and neonatal respiratory distress syndrome (RDS), is conventional mechanical ventilation (CMV) with the lung filled to about functional residual capacity with perfluorochemical liquid. PROTOCOL: As a pilot trial for a larger preclinical study focused on the safety of extended duration PLV, three near term baboons were studied. The animals were delivered by cesarean section, anesthetized, intubated and placed on CMV. The animals were given intratracheal perflubron (30 ml/kg) and maintained on PLV for 96 hours. The transition back to gas ventilation occurred, after draining, over the fifth day (hrs 96-120). RESULTS: Two of the animals were born with normal pulmonary function, while the third developed respiratory distress prior to PLV. All the animals were adequately supported with PLV using moderate ventilator settings and low concentrations of oxygen. Perflubron distribution was enhanced by periodic rotation of the animals. Preliminary histology show vacuolated alveolar macrophages and no evidence of edema or other significant changes in the lungs. Pulmonary function in the RDS animal, after PLV treatment, showed normal gas exchange and lung mechanics. CONCLUSIONS: Three near term baboons, one with clinical RDS, tolerated 4 days of PLV followed by 1 day of CMV without complications using practical clinical management methods.

Animals↗
PubMed1993

Effect of maternal race on outcome of preterm infants in the military.

Previous studies suggest that low birth weight black infants have less morbidity and birth-weight-specific mortality during the perinatal period than low birth weight white infants. We studied the effect of maternal race on outcome in preterm infants born at a military hospital that offers free access to obstetric and neonatal care. Between January 1, 1986, and December 31, 1991, data were prospectively collected on all 667 infants delivered at Wilford Hall USAF Medical Center with an estimated gestational age of less than 35 weeks. Three hundred ninety-two white infants and 165 black infants were included in the data analysis. The mean (+/- SD) birth weight was 1701 +/- 65 g for white infants and 1462 +/- 66 g for black infants. The mean estimated gestational age was 31.0 +/- 3.2 weeks for white infants and 29.9 +/- 3.8 weeks for black infants. Preeclampsia was more frequent in black mothers than in white mothers for the entire study population (21% vs 14%), but the birth weight differential between races remained after correction for preeclampsia. There were no significant differences between races in stillbirths, gender, maternal age, maternal transfer status, number of prenatal visits, or percentages of mothers with small-for-gestational-age infants, multiple-gestation infants, prolonged rupture of membranes, or initial prenatal visit during the first trimester. Intraventricular hemorrhage was more frequent in white infants at 27 through 29 weeks estimated gestational age (50% vs 13%). There were no significant differences between the two groups in survival or in the occurrence of severe intraventricular hemorrhage or bronchopulmonary dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1992

Cardiac performance in ECMO candidates: echocardiographic predictors for ECMO.

Twenty-one neonates with severe respiratory failure, who met criteria in this center for extracorporeal membrane oxygenation (ECMO), underwent echocardiographic examinations to assess the role of cardiac dysfunction in determining the need for ECMO. The echocardiographic indexes of function included peak aortic and pulmonary flow velocity, aortic and pulmonary acceleration, shortening fraction, velocity of circumferential fiber shortening, right ventricular output, and left ventricular output. Patients were offered a staged treatment protocol using high-frequency oscillatory ventilation (HFOV), followed by ECMO if failing HFOV rescue. Nine patients demonstrated progressive deterioration and required ECMO (group 1); 12 patients recovered without ECMO (group 2). There were no significant intergroup differences in AaDO2, age, weight, gestational age, inotropic support, mean airway pressure, systemic blood pressure, or arterial blood gas parameters. Group 1 had significantly lower pulmonary and aortic peak flow velocities, lower pulmonary acceleration, lower shortening fraction, and lower velocity of circumferential fiber shortening (P less than .05). We found that values for peak pulmonary velocity less than 0.70 m/s with pulmonary acceleration less than 14 m/s2 would predict the need for ECMO in 7 of 9 group 1 patients and recovery without ECMO in 11 of 12 group 2 patients (P less than .01, Fisher's Exact test). We conclude that on initial echocardiographic evaluation, cardiac performance was impaired in those patients who subsequently required ECMO compared with a group of patients with similar severity in gas exchange who recovered without ECMO. We speculate that echocardiographic assessment of cardiac performance in ECMO candidates may prove useful in prediction of the subsequent need for ECMO or expedient transfer to an ECMO center.

Carbon Dioxide↗
PubMed1992

Frequency of chronic lung disease in infants with severe respiratory failure treated with high-frequency ventilation and/or extracorporeal membrane oxygenation.

OBJECTIVE: To assess the frequency of chronic lung disease and factors associated with its development in term infants with severe respiratory failure who receive high-frequency oscillatory ventilation, or high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective review of pulmonary outcome of all ECMO candidates admitted to Wilford Hall USAF Medical Center between July 1985 and September 1989. SETTING: A tertiary, level III, neonatal ICU accepting regional referrals for high-frequency ventilation and ECMO. PATIENTS: Ninety-four patients who were candidates for ECMO were studied. High-frequency oscillatory ventilation alone was used in 48 infants. Forty-six infants were treated with high-frequency oscillatory ventilation and ECMO. MAIN RESULTS: Twenty (24%) of 84 survivors developed chronic lung disease. There were no differences in gestational age, birth weight, or gender between those infants who developed chronic lung disease and those infants who did not. Arterial blood gas and ventilatory settings at initiation of high-frequency oscillatory ventilation were similar between those infants who did and those who did not develop chronic disease. Patients who developed chronic lung disease more often had lung hypoplasia (40% vs. 5%) and more often required ECMO (75% vs. 39%) than those patients who did not. In patients without lung hypoplasia, those patients who developed chronic lung disease were older at initiation of high-frequency oscillatory ventilation rescue than those patients who did not develop chronic lung disease (median 91 vs. 46 hrs). CONCLUSIONS: The frequency of chronic lung disease in ECMO candidates is clinically important. Factors associated with chronic lung disease in ECMO candidates are: the presence of lung hypoplasia, delayed referral, and the need for ECMO to support gas exchange.

Birth Weight↗
PubMed1992

Prospective randomized comparison of high-frequency oscillatory and conventional ventilation in respiratory distress syndrome.

A prospective randomized trial with a crossover design was conducted to compare the efficacy and safety of two distinct strategies of high-frequency oscillatory ventilation (HFOV) to conventional intermittent mandatory ventilation (CV) in the management of respiratory distress syndrome. Only premature neonates with a birth weight less than 1.751 kg were eligible for enrollment into the study. Of 83 patients studied, 26 patients were assigned to CV-only, 27 to HFOV for 72 hours followed by CV (HFOV/CV), and 30 to HFOV-only until extubation. There was no difference among the three groups with respect to the incidence of pulmonary airleak, intraventricular hemorrhage, or death. The highest incidence of chronic lung disease was in the CV-only group. Although both HFOV groups had a lower incidence of chronic lung disease assessed at 30 days and 36 weeks postconception age, the difference was statistically significant only between the CV-only and HFOV-only groups (65% vs 30% at 30 days; P = .008; 38% vs 10% at 36 weeks postconception age, P = .013). These results suggest that use of HFOV as the predominant mode of ventilation in the management of respiratory distress syndrome is as safe as CV and can contribute to a decreased incidence of chronic lung disease. Furthermore, a short (72-hour) period of HFOV support does not provide the same advantage as continuous HFOV.

Analysis of Variance↗
PubMed1991

Ureaplasma urealyticum demonstrated by open lung biopsy in newborns with chronic lung disease.

Lung biopsy tissue from eight infants with chronic lung disease was evaluated for the presence of Ureaplasma urealyticum. Specimens from four infants grew the organism. Pleural fluid cultures matched lung tissue but tracheal cultures were negative in two babies with positive lung tissue. There were no distinguishing pathologic findings in the four culture-positive infants which could be used to identify them vs. the culture-negative infants. Three culture-positive infants improved clinically after therapy directed at Ureaplasma even though two remained culture-positive. Ureaplasma grows in lung tissue of infants with chronic lung disease, it does not demonstrate any specific standard pathologic findings and tissue cultures do not match endotracheal cultures.

Biopsy↗
PubMed1991

Allopurinol-induced effects in premature baboons with respiratory distress syndrome.

To test the hypothesis that administration of allopurinol could modify the response to prolonged hyperoxia in premature baboons (140 days gestation) with respiratory distress syndrome, we evaluated physiological, pathological, and lung biochemical parameters in groups of premature baboons treated with mechanical ventilation and exposed to various amounts of oxygen for 6 days. Three groups of experimental animals were studied, including animals that received oxygen as needed to maintain arterial oxygen between 60 and 80 Torr [inspiratory O2 concentration- (FIO2) PRN], animals that received 100% oxygen continuously but also received allopurinol intravenously at a dose of 10 mg.kg-1.day-1 (FIO2-1.0 + allopurinol), and animals that received 100% oxygen continuously and the vehicle for allopurinol administration (FIO2-1.0). Pathological examinations of the experimental animals showed evidence of lung injury in both 100% oxygen-exposed groups, but the allopurinol-treated animals had findings more compatible with the FIO2-PRN group, with relatively few macrophages or polymorphonuclear lymphocytes being present in lung tissue. Lungs of animals treated with allopurinol were also more distensible and had a trend toward decreased lung water compared with the FIO2-1.0 group. Allopurinol-treated animals were able to induce lung glutathione concentrations and glutathione-related and antioxidant enzyme activities compared with the normoxic control (FIO2-PRN) group. Ventilator pressure requirements were also decreased in the allopurinol-treated animals compared with the FIO2-1.0 controls after 42 h. These data suggest that treatment of hyperoxia-exposed premature baboons with allopurinol for the first 6 days of life results in significant changes in lung responses and antioxidant defenses compared with vehicle-treated baboons exposed to 100% oxygen for the same time period.

Allopurinol↗
PubMed1991

High-frequency oscillatory ventilation versus intermittent mandatory ventilation: early hemodynamic effects in the premature baboon with hyaline membrane disease.

We studied the hemodynamic consequences during the first 24 h of life in premature baboons (140 d) with hyaline membrane disease that were treated with high-frequency oscillatory ventilation (HFOV) or conventional intermittent mandatory ventilation (IMV). Cardiac output and organ blood flow were measured at three time-points using the radiolabeled microsphere technique. Seven of seven HFOV and six of eight IMV animals survived the 24-h period. By design, initial mean airway pressure (Paw) was higher in the HFOV group (p less than 0.01). HFOV Paw was progressively reduced during the study period because of improving oxygenation as measured by the arterial to alveolar oxygen ratio. In contrast, it was necessary to increase Paw in the IMV animals to maintain the arterial to alveolar oxygen ratio. By 23 h, the IMV group required higher Paw than the HFOV group (p less than 0.05) and had a lower arterial to alveolar oxygen ratio (p less than 0.05). We found no significant differences in left ventricular output, effective systemic flow, organ blood flow, or central venous pressure between the two groups at 3, 8, or 23 h. The HFOV strategy used in our study resulted in significant improvement in oxygenation during the initial 24 h of treatment without adverse effect on left ventricular output, cerebral blood flow, or central venous pressure. We conclude that when appropriate changes in Paw are made during HFOV in response to improvement in arterial oxygenation and changes in lung inflation as assessed by chest radiographs HFOV can be achieved without depressing cardiovascular dynamics more than during conventional therapy with IMV.

Animals↗
PubMed1990

Toxic effects associated with the administration of deferoxamine in the premature baboon with hyaline membrane disease.

We hypothesized that administration of the iron chelator deferoxamine would inhibit iron-catalyzed free radical generation and lessen the severity of oxygen-induced pulmonary injury. To evaluate its efficacy and safety in premature infants, we administered deferoxamine by intravenous infusion to five premature baboons with hyaline membrane disease supported with conventional ventilation and 100% oxygen for 6 days. Seven animals served as controls. Deferoxamine treatment was initiated at 10 mg/kg per hour but, after the precipitous death of the first animal, was progressively reduced to 1.25 mg/kg per hour in the other animals. Four of five deferoxamine-treated baboons developed cardiovascular collapse and all five died by 42 hours. Five of the seven control animals survived the 6-day experimental period. Since cardiovascular toxic effects have not previously been reported, these findings suggest unique vulnerability of the immature cardiovascular system to iron chelation.

Animals↗
PubMed1990

High-frequency oscillatory ventilation and extracorporeal membrane oxygenation for the treatment of acute neonatal respiratory failure.

Forty-six (92%) outborn and four (8%) inborn term or near-term neonates were admitted for extracorporeal membrane oxygenation (ECMO) treatment to a neonatal intensive care unit between July 1, 1985, and November 1, 1987. All infants had PAO2-PaO2 greater than or equal to 600 mm Hg in spite of aggressive conventional ventilatory and pharmacologic therapy. All patients were offered rescue treatment with high-frequency oscillatory ventilation (HFOV), and only if there was no improvement in PAO2-PaO2 with HFOV were infants treated using ECMO. Four patients died before receiving an adequate trial of HFOV and before emergency ECMO support could be initiated; 21 patients, all of whom survived to hospital discharge, responded to HFOV; 25 patients ultimately required ECMO therapy for cardiopulmonary support, with 22 (88%) surviving to discharge. Neonates responding to HFOV were of slightly younger gestational age (38 +/- 2 weeks vs 40 +/- 2 weeks, mean +/- SD; P less than .001) and more frequently had clinical evidence of pneumonia (11 of 21 vs 2 of 25; P less than .002). There was no statistically significant difference in outcome with respect to the number of ventilator days, hospital days, or survival between patients responding to HFOV and patients who required ECMO. Morbidity was increased in ECMO patients, with bleeding abnormalities, seizures, and renal failure occurring more frequently than in HFOV-treated infants. Overall, 92% (46 of 50) of the patients were treated with a staged protocol using HFOV before ECMO. A total of 46% (21 of 46) responded to HFOV treatment alone and did not require ECMO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal Membrane Oxygenation↗
PubMed1989

Neonatal pneumopericardium with high-frequency ventilation.

Pneumopericardium is an uncommon condition in the neonate and has not, to our knowledge, previously been reported in patients treated with high-frequency ventilation. The results of such treatment in 8 neonates seen in the Neonatal Intensive Care Unit, Wilford Hall USAF Medical Center, San Antonio, Texas, are presented. The mean gestational age was 35 weeks, and birth weight averaged 2.7 kg. The pneumopericardium developed while the patients were on high-frequency ventilation, and the diagnosis was confirmed with a chest radiogram. Treatment included pericardiocentesis with a needle catheter followed by placement of a 10F to 14F chest tube into the pericardial space. The pneumopericardium resolved in all 8 patients. Three of the newborns died of underlying disease; 5 survived and were discharged from the hospital. Pneumopericardium in the neonate is a life-threatening complication, and appropriate therapy includes drainage with a pericardial tube placed under direct vision.

Drainage↗
PubMed1989

A comparison of ventilation strategies for the use of high-frequency oscillatory ventilation in the treatment of hyaline membrane disease.

To assess the efficacy of high frequency oscillatory ventilation (HFOV) in the management of infants with hyaline membrane disease (HMD), we compared two HFOV strategies with conventional positive pressure ventilation with positive end expiratory pressure (PPV) for 24 h in premature baboons (140 d gestation). Three out of 14 PPV, five out of five HFOV-E (begun at birth; 15 Hz; I:E 1:2), and none of 10 HFOV-L (begun after 3 h PPV; 10 Hz; I:E 1:2) were killed at 24 h for morphologic examination. Physiologic (Paw, Pa/AO2, IO2, B.P., pulse, blood gases) data on all animals in each group were assessed at each 3 h interval and over time. Intergroup differences in radiographs at 0 and 24 h and in morphology were quantitatively assessed by comparison with a panel of standards. All animals had radiographic HMD. Initial Paw was set higher with HFOV-E (16.8) than PPV or HFOV-L (14.1, 14.1). PPV baboons required increasing Paw to maintain constant Pa/AO2. Six out of 14 PPV animals developed airleak and three out of three had morphologic HMD. In contrast Pa/AO2 was higher in both HFOV groups at lower Paw by 24 h. None of 15 HFOV animals developed airleak. HFOV-E lungs had dramatic differences in morphology with uniform saccular opening and decreased edema and hyaline membranes compared to PPV. HFOV-L had less dramatic effects because of lower Paw and delayed application. Early use of HFOV at a high Paw favorably alters the course of HMD. Unless closely monitored, this strategy results in lung overinflation which may adversely affect venous return and cardiac output.

Animals↗
PubMed1989

Oxygen delivery rate and sufficiency of oxygenation during ECMO in newborn baboons.

Minimum acceptable O2 delivery (DO2) during extracorporeal membrane oxygenation (ECMO) remains to be defined in a newborn primate model. The right atrium, carotid artery, and femoral artery were cannulated, and the ductus arteriosus, aorta, and pulmonary artery ligated in neonatal baboons (Papio cynocephalus) under a combination of ketamine, diazepam, and pancuronium. The internal jugular vein was also cannulated retrograde to the level of the occipital ridge. We measured hemoglobin, pH, arterial and venous PO2 (both from the pump circuit and from the cerebral venous site), serum lactate and bicarbonate concentrations, and pump flow, and we calculated hemoglobin saturations, (DO2), O2 consumption (VO2), systemic O2 extraction, and cerebral O2 extraction. Six baboons were studied during each of two phases of the experiment. In the first, flow rates were varied sequentially from 200 to 50 ml.kg-1.min-1 with saturation maximized. In the second, flow was maintained at 200 ml.kg-1.min-1 and saturation was reduced sequentially from 100 to 38%. VO2 fell significantly below baseline at a flow rate of 50 ml.kg-1.min-1 and a DO2 of 8 +/- 2 (SE) ml.kg-1.min-1 in phase 1 and at DO2 of 12 +/- 5 in phase 2. Both systemic and cerebral O2 extraction rose significantly at a flow of 100 ml.kg-1.min-1 and DO2 of 17 +/- 4 ml.kg-1.min-1 in phase 1, whereas neither rose with decreasing DO2 in phase 2. In fact, cerebral extraction fell significantly DO2 of 16 +/- 6 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗