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Biomedical subjects

D M Null

Publications and source records attributed to D M Null.

At least 37 records · Page 2Linked to original sources

Influence of ventilatory technique on pulmonary baroinjury in baboons with hyaline membrane disease.

To assess the influence of ventilatory technique on pulmonary baroinjury in experimental hyaline membrane disease, we randomized 24 premature baboons to six treatment groups according to ventilator (PPV, positive pressure ventilator; HFO, high frequency oscillator; HFI, high frequency flow interrupter) and O2 therapy FIO2 as clinically indicated, or FIO2 1.0). PaCO2 was adjusted by varying pressure amplitude, and for PPV, also by rate (less than 60/min). HFO and HFI were set at a frequency of 10 Hz. Animals were cared for with standard NICU techniques until death or sacrifice at 11 days. One animal died at delivery and was excluded from data analysis. There were no intergroup differences in Paw, Pa/AO2, PaCO2 or oxygenation index (IO2 = [Pa/AO2]/Paw) prior to death of the first study animal at 13 h. Animals who subsequently developed airleak had higher Paw, lower Pa/AO2 and lower IO2 during this period. The degree of airleak was significantly less with HFO compared to PPV or HFI. The effect of O2 exposure did not appear different with respect to the degree of airleak or the frequency of severe tracheal injury, although survival was shortened. Severe tracheal injury was more frequent with HFI compared to PPV or HFO. BPD was found only in 100% O2 exposed animals surviving greater than 1 wk. Management of premature baboons with HFO and appropriate O2 resulted in less severe airleak, 100% survival, and no evidence of severe tracheal injury or BPD. These outcomes were not achieved with clinically similar strategies using PPV or HFI.

Animals↗

Tracheal and bronchial injury in high-frequency oscillatory ventilation and high-frequency flow interruption compared with conventional positive-pressure ventilation.

We compared the histopathologic changes in the airways of premature baboons treated with conventional positive-pressure ventilation (PPV) with those seen after high-frequency oscillatory ventilation (HFOV) and high-frequency flow interruption (HFFI). Twenty-six animals were treated with ventilation for 24 hours (five PPV, 10 HFOV, 11 HFFI), and 18 were treated with ventilation for 96 hours (six PPV, six HFOV, six HFFI). A semiquantitative scoring system was used to grade tissue changes in the trachea, carina, and both main-stem bronchi. Alterations were produced by all forms of mechanical ventilation. The degree of injury was similar and relatively mild for the PPV- and HFOV-treated animals at both 24 and 96 hours. Eleven of 17 baboons treated with HFFI ventilation (8/11 at 24 hours; 3/6 at 96 hours) had severe airway damage characterized by diffuse submucosal necrosis, extensive hemorrhage, dense polymorphonuclear leukocyte infiltration, sloughed epithelium, focal basophilia, and intraluminal debris. HFOV resulted in no greater degree of airway damage than did PPV. The use of HFFI, with the particular strategy we employed, resulted in a far greater degree of damage than either PPV (P less than 0.01) or HFOV.

Animals↗

High-frequency ventilation: its various techniques and clinical applications.

High-frequency ventilation can be considered to be ventilation with a tidal volume close to or less than the anatomical dead space. The various techniques of high-frequency ventilation will be discussed including high-frequency positive pressure ventilation, high-frequency jet ventilation or high-frequency flow interruption, and high-frequency oscillatory ventilation. The clinical application of the various types of high-frequency ventilation will be discussed including their use during surgical procedures, their use for various kinds of barotrauma, their usefulness in respiratory failure, their use in newborns with hyaline membrane disease, and their usefulness for respiratory support in emergency situations involving cardiopulmonary resuscitation. The potential use for high-frequency ventilation in the management of battlefield casualties and air evacuation of critically ill patients will also be discussed.

Barotrauma↗

Tracheal and bronchial injury in high-frequency oscillatory ventilation compared with conventional positive pressure ventilation.

We compared airway histopathologic findings in premature baboons given standard positive pressure ventilation with those seen after high-frequency oscillatory ventilation. Six animals received standard frequency conventional ventilation for a mean of 9.2 days; seven received high-frequency oscillatory ventilation at 10 Hz using a piston oscillator for a mean of 10.2 days; five baboons served as controls, and were killed immediately after birth. A semiquantitative histopathologic scoring system was used to grade tissue changes in the trachea, carina, and both mainstem bronchi. Compared with the nonventilated control animals, injury was produced with both forms of mechanical ventilation (P less than 0.01 for both instruments); however, the degree of damage was mild, with no significant difference in the extent of injury between the two treatment groups. High-frequency oscillatory ventilation appears to result in no greater degree of airway damage than conventional positive pressure ventilation.

Animals↗

Patent ductus arteriosus during high-frequency ventilation for hyaline membrane disease.

The cardiovascular effects of a patent ductus arteriosus (PDA) in a premature baboon model of hyaline membrane disease treated with conventional positive-pressure ventilation (CPPV) or high-frequency ventilation (HFV) were studied. Twenty-seven (84%) of 32 infant baboons delivered at 75% gestation had positive retrograde aortograms at one hour of life. Eleven (34%) of these infant baboons had persisting evidence for retrograde flow over the first 24 h by Doppler examination. Significantly higher fluid requirements and bicarbonate requirements were present in the animals with a persisting PDA. Mean aortic BP values were significantly lower in these same animals. No significant differences were found between groups when mean airway pressure, heart rate, urine output, or form of ventilation were compared. The only significant differences found between the conventional and high-frequency ventilated animals with PDA were higher peak airway pressures and lower PEEP levels in the conventionally ventilated infants. The premature baboons can be a useful primate model to study the PDA. There appears to be no significant difference regarding the clinical effects of HFV and CPPV on PDA.

Acidosis↗

Extracorporeal membrane oxygenation and high-frequency oscillatory ventilation: potential therapeutic relationships.

Eighteen neonates 33 to 42 wk gestational age with severe respiratory failure were referred for extracorporeal membrane oxygenation (ECMO). Sixteen ultimately met the ECMO criteria, of whom 15 were first offered high-frequency oscillatory ventilation (HFOV). Seven responded to HFOV alone and did not require ECMO treatment. Eight of the nine remaining patients were placed on ECMO support with HOFV. Infants who responded to HFOV alone tended to have pneumonia more than meconium aspiration, to be smaller and more immature, to have higher Apgar scores, and to have suffered severe hypoxia (alveolar-arterial oxygen pressure difference over 600 torr) for less time than the ECMO group. Although patient numbers are small, a trend is noted which favors HFOV treatment alone in terms of the duration of HFOV, the total duration of assisted ventilation, the rapidity with which extubation was accomplished, and the length of hospital stay.

Birth Weight↗

Normal standards for kidney length in premature infants: determination with US. Work in progress.

In 52 healthy premature infants, 104 kidneys were sonographically examined and kidney length was measured. Kidney length was compared with four parameters: body weight, body length, body surface area, and gestational age. Scatter plots of these data demonstrated that kidney length versus body weight conformed well to a linear distribution with a high correlation coefficient. A nomogram for kidney length versus body weight in premature infants is also presented.

Body Height↗

Oxygen toxicity in the premature baboon with hyaline membrane disease.

Immaturity, pulmonary barotrauma, and oxygen toxicity have been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). Although the physiologic and biochemical consequences of oxygen toxicity have been described in newborn and adult animals, there have been no controlled observations in prematures. We compared the physiologic and morphologic effects of prolonged hyperoxia with those of clinically appropriate oxygen in premature baboons with hyaline membrane disease (HMD) supported with conventional positive pressure ventilation and continuous distending airway pressure (PPV/PEEP). Twenty-one premature baboons were delivered at 140 days gestation, intubated and resuscitated, and supported with PPV/PEEP and standard NICU techniques for 11 days. The FIO2, PaO2, PaCO2, pHa, ventilator and airway pressures, and blood pressure were intermittently measured and recorded. The physiologic observations could be divided into 3 distinct phases. During Phase 1 (0 to 42 h) there were no significant intergroup differences, and (a/A)PO2 and IO2 (oxygenation index; (a/A)PO2/Paw) remained stable. In Phase 2 (43 to 96 h) there was a rapid improvement in (a/A)PO2 and IO2 in both groups, but the response in the hyperoxic animals was significantly dampened. During Phase 3 (97 to 264 h) there was continued improvement in the "prn" animals, which contrasted with progressive deterioration in those exposed to FIO2 1.0. Five of 11 "prn" and 3 of 10 FIO2 1.0 baboons developed air leaks during Phase 1 or early Phase 2. Four of 10 of the hyperoxic animals died after the late onset of air leak. Pathologic changes of BPD were found in all FIO2 1.0 animals surviving more than 6 days but in none of the "prn" long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ventilatory management of infant baboons with hyaline membrane disease: the use of high frequency ventilation.

We tested the hypothesis that high frequency oscillatory ventilation (HFOV) would result in decreased pulmonary barotrauma in infants with hyaline membrane disease by comparing HFOV at 10 Hz to conventional positive pressure ventilation with continual distending airway pressure (PPV/PEEP) in premature baboons with hyaline membrane disease. Nineteen baboon fetuses were randomized to one of two treatment groups, delivered at 140 +/- 2 days, and, after stabilization and instrumentation of PPV/PEEP, placed in their respective ventilator group. Animals on conventional ventilation were managed by adjustment of tidal volume and frequency (to 1 Hz) to keep PaCO2 below 55 and by adjustment of the mean airway pressure. One of the "HFOV" group died of cardiovascular complications before going on HFOV and was eliminated from data analysis. The remaining HFOV baboons survived the 11-day experimental period without evidence of airleak. Six of the 11 prematures treated with PPV/PEEP developed pulmonary interstitial emphysema and/or pneumothorax and five of the animals died within 48 h. The intergroup differences in airleak were significant (p less than 0.05). Mean airway pressure (measured at the proximal airway) was higher initially with HFOV but then was lowered more rapidly than in the PPV/PEEP animals. The arterial to alveolar oxygen ratio rose and the FIO2 could be lowered more rapidly with HFOV than with conventional ventilation. These differences reached significance by 20 h. After 60 h there were no significant differences between HFOV and the PPV/PEEP survivors. HFOV resulted in more uniform saccular expansion, higher arterial to alveolar oxygen ratio, less oxygen exposure, and decreased acute barotrauma when compared to PPV/PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Dense pulmonary opacification in neonates treated with extracorporeal membrane oxygenation.

Chest radiographic findings in three neonates with respiratory failure secondary to meconium aspiration treated with extracorporeal membrane oxygenation (ECMO) are described. The degree of pulmonary opacification on the chest radiographs failed to correlate with the patients' clinical status as measured by the arterial oxygen levels but correlated well with the peak airway pressure (PAP) and continuous positive airway pressure (CPAP) settings on the mechanical ventilator. Because a variable portion of the arterial blood oxygenation is performed by the extracorporeal membrane oxygenator and unusually large fluctuations in airway pressure settings can occur in these patients while on ECMO, it is important to realize that the chest radiograph may not be an accurate predictor of the patients' clinical status.

Extracorporeal Circulation↗

A nonpulmonary complication of high-frequency oscillation.

High-frequency ventilation (HFV) has been suggested as an alternative to standard positive-pressure ventilation with positive end-expiratory pressure (PPV/PEEP) in the treatment of infants with hyaline membrane disease. To assess the relative safety and efficacy of HFV, we compared standard PPV to HFV delivered by oscillation (HFO) and HFV delivered by a flow interrupter (HFFI) in a previously validated preterm baboon model of hyaline membrane disease. At necropsy, the livers of several animals were unexpectedly found to have severe fatty change and/or cytoplasmic vacuolization and edema. There was a strong correlation between use of HFO and the development of liver lesions. The hepatic lesion may reflect decreased cardiac output with a concomitant fall in splenic perfusion and/or alterations in normal intrathoracic pressure that increase resistance in the hepatic vasculature. Although the etiology cannot be determined precisely, these data suggest the potential for nonpulmonary complications of HFV in the immature newborn and mandate further investigation before its widespread clinical application.

Animals↗

Pulmonary interstitial emphysema treated by high-frequency oscillatory ventilation.

Twenty-seven low birth weight infants who developed pulmonary interstitial emphysema (PIE) and respiratory failure while on conventional ventilation were treated with high-frequency oscillatory ventilation (HFOV). The mean birth weight was 1.2 kg (range 0.55 to 2) with gestational age of 28 wk (range 25 to 34). Ten patients died, six of whom had documented sepsis with shock and were therefore excluded from analysis. All patients showed initial improvement on HFOV. Surviving patients showed continued improvement in oxygenation and ventilation at increasingly lower fraction of inspired oxygen and proximal airway pressure with resolution of PIE, while nonsurvivors progressively developed chronic respiratory insufficiency with continued PIE from which recovery was not possible. Overall survival in nonseptic patients was 80% (16 of 20). We found HFOV to be effective in the treatment of PIE and hypothesize that interstitial airleak is decreased during HFOV because adequate ventilation is provided at lower peak distal airway pressures.

Critical Care↗

Progressive chest radiographic changes in wet lung disease.

Delayed clearance of fetal lung fluid, or wet lung disease (WLD), is a common, well described clinico-radiographic diagnosis. Unusual chest roentgenographic findings in six infants with WLD are reported. All infants had either delayed development of pleural fluid collections or transient apparent worsening of pulmonary parenchymal infiltrates simulating infection. Five of the six patients were treated with antibiotics. The patients were clinically well, radiographically normal, and culture negative by 72 hours. Our findings suggest that worsening of pulmonary parenchymal opacities and the appearance of pleural effusions can be part of the WLD spectrum. An initial radiographic impression of neonatal pneumonia can be changed to WLD and antibiotics stopped after 72 hours if subsequent radiographs show clearing, cultures are negative, and clinical findings resolve as they did in our patients.

Diagnosis, Differential↗

Pulmonary interstitial emphysema in the premature baboon with hyaline membrane disease.

During experiments designed to develop an appropriate ventilatory strategy for high-frequency ventilation (HFV) in the premature baboon with hyaline membrane disease (HMD), we observed the development of pulmonary interstitial emphysema (PIE). Four study groups of 5 animals each received positive-pressure ventilation and positive end-expiratory pressure (PPV/PEEP) or HFV and 1 of 3 sighing techniques. Pathologically, all animals ventilated with PPV/PEEP or HFV with a carefully controlled intermittent sigh developed dilatation of the distal conducting airway and alveolar duct, with poorly expanded pulmonary saccules. The imposition of a sigh with inappropriate timing or excessive volume ruptured the dilated airway walls and caused interstitial air to accumulate. This was evident from the location of striking dilation of the distal airways and pseudocysts in areas of atelectasis. Thus, early in the course of HMD when saccular aeration is minimal, the pathogenesis of PIE is related to airway rather than alveolar rupture.

Animals↗

High-frequency ventilation compared to conventional positive-pressure ventilation in the treatment of hyaline membrane disease in primates.

High-frequency ventilation (HFV) has been suggested as an alternative to conventional positive-pressure ventilation (PPV) in the treatment of infants with hyaline membrane disease (HMD). Using a previously validated primate model of HMD, 15 baboon fetuses were delivered at 75% of gestation and randomly assigned to 1 of 3 ventilator treatment groups: PPV, HFV delivered by an oscillator (HFO), or HFV delivered by a flow interrupter (HFFI). All animals had clinical and radiographic evidence of HMD. At 96 h of life, all animals were sacrificed and clinical and pathologic findings were analyzed. During the first 10 h of the experiment, the HFO animals required higher mean proximal airway pressures than either the HFFI or PPV groups. However, both the HFFI and HFO animals had higher PaO2/PAO2 ratios than the PPV controls, suggesting earlier saccular recruitment. Thus, HFV is as effective as PPV in the treatment of HMD in baboons. Whether it will decrease the risk of bronchopulmonary dysplasia is not known.

Animals↗