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Biomedical subjects

S D Rubenstein

Publications and source records attributed to S D Rubenstein.

At least 19 recordsLinked to original sources
PubMed2001

Cardiac surgery in the low-birth weight neonate. New approaches.

The LBW infant with congenital heart defects is likely to be at a higher risk for postoperative death and complications than their normal-sized counterparts because of the effects of prematurity and other organ system dysfunction. Current experience, however, does not suggest that waiting to obtain an arbitrary weight before surgery significantly improves outcome. Survival for low-weight infants undergoing complex repairs, such as those for interruption of the aortic arch and HLHS, is decreased compared with larger babies having the same operation at the same institution; however, the absolute survival rates are still quite acceptable. Weight alone should not be considered a contraindication to surgery for complex CHD. A careful investigation for the cause of the LBW must be undertaken (e.g., prematurity, infection, multiple congenital anomalies, and genetic abnormalities) and appropriate therapies initiated. The medical and surgical teams should collaborate to determine the optimal timing and type of surgery, with body weight being only of minor importance.

Heart Defects, Congenital↗
PubMed1998

Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency.

To test the hypotheses that perfluorochemical (PFC) liquid rescue after natural surfactant (SF) treatment would improve pulmonary function and histology and that this profile would be influenced by PFC dose or ventilator strategy, anesthetized preterm lambs (n = 31) with respiratory distress were studied using nonpreoxygenated perflubron. All animals received SF at 1 h and were randomized at 2 h as follows and studied to 4 h postnatal age: 1) conventional mechanical gas ventilation (n = 8), 2) 30 ml/kg perflubron with gas ventilation [partial liquid ventilation (PLV)] at 60 breaths/min (n = 8), 3) 10 ml/kg perflubron with PLV at 60 breaths/min (n = 7), and 4) 10 ml/kg perflubron with PLV at 30 breaths/min (n = 8). All animals tolerated instillation without additional cardiopulmonary instability. All perflubron-rescued groups demonstrated sustained improvement in gas exchange, respiratory compliance, and reduction in pressure requirements relative to animals receiving SF alone. Improvement was directly related to perflubron dose and breathing frequency; peak inspiratory pressure required to achieve physiological gas exchange was lower in the higher-dose and -frequency groups, and mean airway pressure was lower in the lower-frequency group. Lung expansion was greater and evidence of barotrauma was less in the higher-dose and -frequency group; regional differences in expansion were not different as a function of dose but were greater in the lower-frequency group. Regional differences in lung perflubron content were reduced in the higher-dose and -frequency groups and greatest in the lower-dose and -frequency group. The results suggest that, whereas PLV of the SF-treated lung improves gas exchange and lung mechanics, the protective benefits of perflubron in the lung may depend on dose and ventilator strategy to optimize PFC distribution and minimize exposure of the alveolar-capillary membrane to a gas-liquid interface.

Animals↗
PubMed1997

A comparison of intratracheal and intravenous administration of gentamicin during liquid ventilation.

UNLABELLED: Pulmonary absorption of aminoglycosides is poor with intravenous administration, but may be enhanced by direct intratracheal administration of these drugs using perfluorochemical liquid ventilation (LV). To test this hypothesis, gentamicin sulfate was administered to two groups of newborn lambs during LV. Serum and lung tissue levels of gentamicin were compared after either pulmonary intratracheal (IT) or intravenous (IV) routes of administration. Serial serum levels of gentamicin were obtained every 15 min for the 1st h, every 30 min for the 2nd h, and then hourly until sacrifice (maximum 6 h). At sacrifice, representative samples of each lung lobe were homogenized and analyzed for tissue gentamicin content. At 1 h, serum gentamicin levels were similar in both groups: IT administration levels were 3.7 +/- 0.55 SE micrograms/ml and IV levels were 3.5 +/- 0.85 SE micrograms/ml. The peak serum gentamicin level of 4.8 +/- 0.8 SE micrograms/ml for the pulmonary administration group occurred 1.5 h after administration. Lung tissue levels of gentamicin for IT administration (4.04 +/- 0.62 SE micrograms/g) were significantly greater than for IV administration (1.75 +/- 0.33 SE micrograms/g; P < 0.05). There were no significant differences in interlobar gentamicin distribution for either mode of administration. CONCLUSION: Perfluorochemical can be used as a vehicle for intratracheal delivery of antimicrobials. This route provides equivalent serum levels at 1 h, higher lung tissue levels, and uniform interlobar distribution relative to intravenous administration of gentamicin. We speculate that pulmonary administered gentamicin during LV may provide an effective alternative treatment modality in the management of severe neonatal pneumonia.

Administration, Inhalation↗
PubMed1997

Partial liquid ventilation in critically ill infants receiving extracorporeal life support. Philadelphia Liquid Ventilation Consortium.

OBJECTIVES: To demonstrate that a period of partial liquid ventilation (PLV) with perflubron improves pulmonary function, without adverse events, in a select group of critically ill infants receiving extracorporeal life support (ECLS) with a high likelihood of mortality. METHODS: This was an open-label, noncontrolled, phase I and II trial of PLV in two infants with congenital diaphragmatic hernia and four infants with acute respiratory distress syndrome (ARDS) who were failing to improve while receiving ECLS. PLV was performed by instilling and maintaining a functional residual capacity of sterile perflubron for 4 to 96 hours. RESULTS: Four infants were successfully weaned off ECLS for at least 3 days, and two infants (both with ARDS) are long-term survivors after PLV. All infants demonstrated lung recruitment and improved lung compliance, and there were no adverse events related to PLV. CONCLUSIONS: The study suggests that perflubron PLV is safe, improves lung function, and recruits lung volume in critically ill infants receiving ECLS. PLV therapy for infants with ARDS seems to have a great deal of promise. Based on this and other phase I and II trials, studies of PLV on selected full-term infants before ECLS have been initiated.

Emulsions↗
PubMed1996

Partial liquid ventilation with perflubron in premature infants with severe respiratory distress syndrome. The LiquiVent Study Group.

BACKGROUND: The intratracheal administration of a perfluorocarbon liquid during continuous positive-pressure ventilation (partial liquid ventilation) improves lung function in animals with surfactant deficiency. Whether partial liquid ventilation is effective in the treatment of infants with severe respiratory distress syndrome is not known. METHODS: We studied the efficacy of partial liquid ventilation with perflubron in 13 premature infants with severe respiratory distress syndrome in whom conventional treatment, including surfactant therapy, had failed. Partial liquid ventilation was initiated by instilling perflubron during conventional mechanical ventilation to a volume approximating the functional residual capacity. Infants were considered to have completed the study if they received partial liquid ventilation for at least 24 hours. RESULTS: Ten infants received partial liquid ventilation for 24 to 76 hours. In the other three infants, partial liquid ventilation was discontinued within four hours in favor of high-frequency ventilation, which was not permitted by the protocol, and the data from these infants were excluded from the analysis. Within one hour after the instillation of perflubron, the arterial oxygen tension increased by 138 percent and the dynamic compliance increased by 61 percent; the mean (+/- SD) oxygenation index was reduced from 49 +/- 60 to 17 +/- 16. Chest radiographs showed symmetric filling, with patchy clearing during the return from partial liquid to gas ventilation. There were no adverse events clearly attributable to partial liquid ventilation. Infants were weaned from partial liquid to gas ventilation without complications. Eight infants survived to 36 weeks' corrected gestational age. CONCLUSIONS: Partial liquid ventilation leads to clinical improvement and survival in some infants with severe respiratory distress syndrome who are not predicted to survive.

Fluorocarbons↗
PubMed1995

Use of liquid ventilation with perflubron during extracorporeal membrane oxygenation: chest radiographic appearances.

PURPOSE: To assess the effectiveness of performing liquid ventilation with perflubron in neonates with severe respiratory failure or pulmonary hypertension who receive extracorporeal membrane oxygenation (ECMO) life support. MATERIALS AND METHODS: We studied an infant (aged 1 month) and a neonate with respiratory failure who underwent ECMO and liquid ventilation with perflubron, which was slowly instilled via an endotracheal tube (in the infant, 40 mL for more than 1 hour; in the neonate, 28 mL within 1 hour). RESULTS: The infant survived termination of ECMO support and has been breathing room air since 6 months of age. The neonate died soon after ECMO support was withdrawn. CONCLUSION: A minority of neonates or infants with severe respiratory failure or pulmonary hypertension do not respond adequately to treatment with ECMO and are almost certain to die with termination of ECMO support. Liquid ventilation with perflubron offers a potential salvage therapy in this patient population. In addition, perflubron is a good contrast agent to use in the evaluation of neonatal pulmonary abnormalities.

Extracorporeal Membrane Oxygenation↗
PubMed1994

Psychological aspects of parenting critically ill neonates.

This study was designed to objectively examine depression and distress levels in parents of ill versus parents of healthy neonates by utilizing two well-validated questionnaires, the Beck Depression Inventory (BDI) and Kellner Symptom Questionnaire (KSQ). In addition, morbidity of infants was assessed by the Minde-Whitelaw Neonatal Morbidity Scale, and parents completed a socioeconomic questionnaire. Analysis of mean BDI and KSQ scores revealed significant differences between parents of ill neonates and parents of healthy neonates in BDI, total KSQ scores, KSQ anxiety, and depression scale scores. Within these groups, respondents whose scores fell into moderate to severe ranges of distress on either questionnaire were referred for counseling. The BDI and KSQ can be tools for better understanding about distress levels in parents of ill and healthy neonates.

Adult↗
PubMed1994

Perfluorochemical liquid as a respiratory medium.

The use of perfluorochemical (PFC) liquids to facilitate or support respiration has been under study for several decades. The low surface tension and high respiratory gas solubility of liquid PFC enable adequate oxygenation and carbon dioxide removal at low insufflation pressures relative to gas ventilation in the immature or injured lung. Because liquid ventilation homogeneously inflates the lung and improves V/Q matching it has been studied as a vehicle for delivering biologically active agents to the lung tissues and systemic circulation. More recently, we have shown the utility of highly opaque PFC liquids as a high resolution computed tomographic (HRCT) bronchographic contrast agent either during LV or gas breathing after tracheal instillation of small quantities of PFC. As a result of extensive experimental work in premature animals as well as lung injury models, liquid PFC ventilation has been recently implemented as an investigational therapy for severe respiratory distress in human infants. This manuscript summarizes the physiological principles and applications of LV as well as the results of initial investigational clinical studies in human neonates with severe respiratory distress.

Clinical Trials as Topic↗
PubMed1993

Effect of exchange transfusion with a red blood cell substitute on neonatal hemodynamics and organ blood flows.

The present study was designed to evaluate the effect of a perfluorocarbon erythrocyte substitute on hemodynamics in the newborn lamb. Isovolumic double volume exchange transfusions were performed with perfluorocarbon emulsion (FC-43) on lambs who were ventilated to maintain normal acid base status. Hematocrit, fluorocrit, viscosity, arterial gas tensions, mean arterial pressure, and heart rate were determined before (control) and after (exchange) exchange transfusion. A radiolabeled microsphere technique was used and cardiac output, organ blood flow, organ vascular resistance, and oxygen delivery were calculated. As the hematocrit and viscosity decreased and the fluorocrit increased, there was a significant increase in PaO2 as well as a significant decrease in A-a gradient and oxygen content. There was no significant change in the acid-base status or the hemodynamic profile (heart rate, stroke volume, cardiac output, and mean arterial pressure). Blood flow to the heart and brain showed a significant increase, whereas flow to the cortex of the kidney showed a significant decrease. There was no significant change in flow to the gastrointestinal tract. Organ vascular resistance in the brain significantly decreased, increased in the kidney, and showed no significant change in the heart and gastrointestinal tract. Oxygen delivery significantly decreased in all organs except the heart. These data suggest that perfluorocarbon emulsions can acutely maintain hemodynamic stability in the newborn lamb and that the intrinsic properties of perfluorocarbons allow for the preservation of adequate oxygenation and acid-base status.

Animals↗
PubMed1993

Comparison of two preservation solutions for erythrocyte transfusions in newborn infants.

To determine whether one of the newer preservation solutions for packed red blood cells (PRBC) is safe and effective in the transfusion of the very low birth weight infant, we conducted a randomized trial comparing PRBC preserved with the anticoagulant solution mannitol-adenine-dextrose (AS-1) and PRBC preserved with citrate-phosphate-dextrose-adenine (CPDA-1). Sixteen infants (birth weight 863 +/- 218 gm) with a gestational age of 26 +/- 3 weeks received one to three small-volume replacement transfusions with PRBC, 17 ml/kg, preserved with either AS-1 or CPDA-1 in a double crossover design. Transfusion with AS-1-preserved PRBC resulted in an equivalent increase in hemoglobin concentration when adjustment was made for the difference in the hemoglobin concentration of the transfused PRBC. During the transfusion, the percentage decrease in serum glucose values was greater with the CPDA-1 preservative than with the AS-1 preservative (54% +/- 13% vs 42% +/- 11% at 1 hour; p < 0.001). No other significant difference in blood chemistry values was found. Urine output was unaffected by AS-1 in the posttransfusion period. We conclude that (1) small-volume PRBC transfusions with AS-1 can be used in the very low birth weight infant without apparent detriment, (2) AS-1-preserved cells are as effective as cells preserved with CPDA-1 for increasing hemoglobin concentration, and (3) the higher dextrose content of the AS-1-preserved blood allows for improved glucose homeostasis during transfusion.

Adenine↗
PubMed1993

Inadvertent administration of positive end-distending pressure during nasal cannula flow.

In the clinical setting, nasal cannulas are frequently used to deliver supplemental oxygen to neonates and are not believed to affect the general respiratory status. In contrast, it was hypothesized that clinical changes associated with nasal cannula gas flow may be related in part to the generation of positive end-distending pressure. To test this hypothesis, alterations in esophageal pressure were quantified as an indication of end-distending pressure and thoracoabdominal motion was quantified as an indication of breathing patterns in 13 preterm infants at gas flow levels of 0.5, 1, and 2 L/min delivered by nasal cannula with an outer diameter of either 0.2 or 0.3 cm. Changes in esophageal pressure were assessed by esophageal balloon manometry. Ventilatory patterns were assessed from thoracoabdominal motion by using respiratory inductive plethysmography. Thoracoabdominal motion was quantitated as a phase angle (theta); larger values represent greater asynchrony. The 0.2-cm nasal cannula did not deliver pressure or alter thoracoabdominal motion at any flow. In contrast, the 0.3-cm nasal cannula delivered positive end-distending pressure as a function of increasing levels of gas flow (r = .92) and reduced thoracoabdominal motion asynchrony. The mean pressure generated at 2 L/min was 9.8 cm H2O. These data demonstrate that nasal cannula gas flow can deliver positive end-distending pressure to infants and significantly alter their breathing strategy. This finding raises important concerns about the indiscriminate therapeutic use, size selection, and safety of nasal cannulas for the routine delivery of oxygen in preterm infants.

Equipment Design↗
PubMed1992

Comparison of gas and liquid ventilation: clinical, physiological, and histological correlates.

To differentiate the effects of gas and liquid ventilation on cardiopulmonary function during early development, we compared the clinical, physiological, and histological profiles of gas- and liquid-ventilated preterm lambs (n = 16; 108-116 days gestation). Immediately after cesarean section delivery, ventilation commenced using gas delivered by a volume ventilator (n = 9) or liquid perfluorochemical (n = 7) delivered by a mechanically assisted liquid ventilation system. Pulmonary gas exchange, acid-base status, vital signs, and respiratory compliance were assessed during the 3-h protocol; sections of the lungs were obtained for histological analyses when the animals were killed. Six of nine gas-ventilated lambs expired from respiratory failure before 3 h, with the remaining animals experiencing severe respiratory insufficiency, pneumothoraces, and cardiovascular deterioration. Six of seven liquid-ventilated lambs survived with good gas exchange and cardiovascular stability and without fluorothorax; one experienced ventricular fibrillation before 1 h and expired despite pulmonary stability. Respiratory compliance was significantly greater in the liquid- than in the gas-ventilated lambs. Histological analyses of gas-ventilated lungs demonstrated nonhomogeneous lung expansion, with thick-walled gas exchange spaces containing proteinaceous exudate, hemorrhage, and hyaline membranes. In contrast, liquid-ventilated lungs appeared clear, with thin-walled and uniformly expanded gas exchange spaces that were free of hyaline membranes and luminal debris. Morphometric analyses demonstrated that surface area and gas exchange index were greater in the liquid- than in the gas-ventilated lambs. These results indicate that elimination of surface active forces by liquid ventilation during early development provides more effective gas exchange with less barotrauma compared with gas ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of nasal CPAP on thoracoabdominal motion in neonates with respiratory insufficiency.

Thoracoabdominal motion (TAM) profiles were determined in ten infants requiring nasal continuous positive airway pressure (CPAP) and supplemental oxygen, in order to assess the influence of CPAP on chest wall function in infants with respiratory insufficiency. (TAM) was quantitated by respiratory inductive plethysmography, measuring relative motion of the rib cage and abdomen. Baseline pulmonary function (without CPAP support) was assessed from simultaneous measurements of transpulmonary pressure, air flow, and tidal volume. Measurements of (TAM) were acquired at baseline and at nasal CPAP levels of 0, 3, 5, and 8 cm H2O, in randomized order. Without CPAP, relative paradoxical motion occurred, i.e., the rib cage collapsed inward instead of expanding outward early in inspiration. With CPAP, TAM resembled the pattern in preterm infants, without lung disease. We found that nasal CPAP lowers the phase angle in infants with respiratory insufficiency (P less than 0.003), indicating improved synchrony of TAM. In addition, the improvement with nasal CPAP was related to the severity of pulmonary compromise at baseline. We speculate that changes in TAM associated with nasal CPAP arise from an interaction between pulmonary mechanics and an enhanced stability of the chest wall. In this context, the greater synchrony of TAM is suggestive of an improved breathing strategy. This may be a noninvasively obtainable marker of an effective nasal CPAP level in infants with altered pulmonary and chest wall mechanics.

Humans↗
PubMed1991

Immediate improvement in lung volume after exogenous surfactant: alveolar recruitment versus increased distention.

To determine whether changes in lung volume may be responsible for the clinical improvement in preterm infants given exogenous surfactant, we measured functional residual capacity (FRC), lung mechanics, and partial pressure of oxygen in seven ventilated neonates (birth weight 1080 +/- 361 gm (mean +/- SD); gestational age 28.3 +/- 2.6 weeks) less than 9 hours of age who had findings typical of hyaline membrane disease. All patients received 100 mg/kg calf lung surfactant extract. FRC was measured by a closed-circuit helium-dilution technique, and lung mechanics were determined by least mean squares analysis. FRC increased in all patients (range 56% to 330%; p less than 0.03). Dynamic lung compliance and total airway conductance did not change. Mean +/- SEM specific lung compliance (dynamic lung compliance/FRC) decreased 55.93% +/- 4.27% (p less than 0.02) and mean specific conductance (total airway conductance/FRC) decreased 45.91% +/- 9.74% (p less than 0.009). Mean alveolar/arterial partial pressure of oxygen ratio decreased 51.0% +/- 8.67% (p less than 0.01). These data indicate that the immediate improvement in oxygenation after surfactant administration is related to increased lung volumes. The decrease in specific lung compliance and specific airway conductance is suggestive of increased distention rather than recruitment of functional alveoli.

Functional Residual Capacity↗
PubMed1990

Liquid ventilation of human preterm neonates.

This report details the application of liquid perfluorochemical ventilation for investigational therapy in three human preterm neonates (gestational ages 28, 24, and 23 weeks) in whom conventional therapies for severe respiratory distress had failed. Liquid ventilation was performed without difficulty in each infant for two 3- to 5-minute cycles by means of gravity-assisted technique. Marked improvement in lung distensibility, without a change in cardiovascular status, occurred in all three infants after liquid ventilation; oxygenation improved in two. All infants died within 19 hours of liquid ventilation, and there was no evidence of retained perfluorochemical fluid in the lungs or pleural space. Death was probably related to the severity of lung disease before the initiation of liquid ventilation. This satisfactory initial outcome shows the feasibility and potential of this treatment of pulmonary dysfunction in the preterm neonate.

Airway Resistance↗
PubMed1990

Effect of exchange transfusion with a red blood cell substitute on the neonatal lung.

The present study was designed to evaluate the acute effects of a perfluorocarbon erythrocyte substitute on cardiopulmonary function in the newborn lamb. Isovolemic double volume exchange transfusions were performed with the perfluorocarbon emulsion (FC-43) during controlled ventilation and acid-base status. Cardiopulmonary function was determined pre (control) and post (exchange) exchange transfusion. As expected with perfluorocarbon transfusion, hematocrit decreased (from 31.3 +/- 1.35% to 6.7 +/- 0.8%, SEM, P less than 0.001) and fluorocrit increased (from 0 to 17.8 +/- 2%, P less than 0.001). These changes in blood composition were associated with a significant increase in arterial oxygen tension (from 317.0 +/- 22 mmHg to 419.0 +/- 22 mmHg, P less than 0.001) and decrease in arterial oxygen content (from 14.0 +/- 8 ml O2/dl blood + PFC to 5.4 +/- 0.3 ml O2/dl blood + PFC, P less than 0.001), A-a oxygen gradient (from 357.0 +/- 23 mmHg to 255.0 +/- 23 mmHg, P less than 0.001) and viscosity (from 3.4 +/- 0.1 cps to 2.1 +/- 0.1 cps, P less than 0.001). No significant change in lung mechanics or hemodynamics was observed. These preliminary data demonstrate cardiopulmonary and hemodynamic stability immediately following transfusion with perfluorocarbon emulsion and outline physiological responses associated with transfusion of perfluorocarbon emulsions, a potential adjunct to neonatal therapeutics.

Airway Resistance↗