Intratracheal Catheter Research Articles

Comparing the Effects of Two Surfactant Administration Methods: Minimally Invasive Surfactant Therapy (MIST) with Intubation (INSURE) in Infants with Respiratory Distress Syndrome.

The aim of this study is to investigate and compare the effects of administering a surfactant through a fine intra-tracheal catheter during spontaneous breathing with the usual INSURE method in premature infants. In this clinical trial, premature babies with respiratory distress syndrome who required surfactant administration were randomly assigned to two groups: an intervention group (MIST) and a control group (INSURE). The treatment results were compared in terms of complications related to treatment (desaturation, apnea, bradycardia, and surfactant reflux), respiratory complications (requirement for mechanical ventilation, duration of nCPAP, duration of oxygen requirement, frequency of pneumothorax, and pulmonary hemorrhage), complications related to prematurity (incidence of IVH, NEC, BPD, and PDA), the need for a second dose of surfactant, and the duration of hospitalization. a total of 160 premature babies with a gestational age of 26-34 weeks were randomly divided into two groups. The results showed that the need for mechanical ventilation, the duration of CPAP needed, and the duration of oxygen therapy were significantly lower in the MIST group than in the INSURE group. Additionally, the incidence of BPD was less common in the MIST group compared to the INSURE group. However, surfactant reflux was more common in the MIST group than in the INSURE group. There were no significant differences between the two groups in other outcomes, including the length of hospital stay and complications such as IVH, PDA, NEC, pneumothorax, and pulmonary hemorrhage. The results of this research demonstrate that the less invasive method of surfactant therapy (MIST) is a feasible, effective, and low-risk alternative to the INSURE method.

Intratracheal oxygen administration increases FIO2 and PaO2 compared with intranasal administration in healthy, standing horses.

To evaluate the efficacy of 2 different oxygen delivery strategies-intranasal and tracheal insufflation-on the inspired fraction of oxygen (FIO2) in standing horses and to determine the time needed for arterial oxygen partial pressure (PaO2) equilibration. 6 healthy adult horses. In this blinded, randomized crossover design study, horses were randomly assigned to receive oxygen via nasal cannula (group N) or transcutaneous tracheal catheter (group T). After placement of venous and arterial catheters, FIO2 was measured through a catheter placed into the distal portion of the trachea. After baseline measurements were obtained, horses received oxygen at up to 25 mL/kg/min for 1 hour via either intranasal or intratracheal catheter. The FIO2 and PaO2 were recorded at 5, 10, 15, 20, 25, 30, 45, and 60 minutes during and 5, 10, 15, 20, and 30 minutes after oxygen insufflation. Data were analyzed by use of a 2-way repeated measures ANOVA with Tukey-Kramer post hoc testing for pairwise comparisons (P < 0.05). During oxygen administration, FIO2 and PaO2 increased significantly when compared with baseline, resulting in significantly higher values for group T (37.7 ± 2.4%; 214.6 ± 18 mm Hg) than for group N (34.3 ± 3.9%; 184.1 ± 11 mm Hg). The equilibration time was less than 10 minutes. Intratracheal oxygen administration resulted in better oxygenation than nasal insufflation and should therefore be considered in standing horses that are experiencing severe respiratory compromise. The equilibration between FIO2 and PaO2 is rapid in adult horses.

Simplifying Transcutaneous Intratracheal Drug Delivery in the Newborn Preterm Rabbit.

Intratracheal (IT) drug delivery allows the direct delivery of pharmaceutical substances to the lung, maximizing potential pulmonary benefit and minimizing systemic drug exposure. The transcutaneous technique is simple and allows for the IT delivery of substances to the lung of prematurely born rabbits shortly after birth. Newborn pups are anesthetized with inhaled Isoflurane before being placed in a supine position with the neck extended. The larynx is identified and stabilized before transcutaneous placement of a 26-gauge (G) catheter into the trachea. Following catheterization of the trachea, a 30 G blunt needle attached to a Hamilton syringe is introduced into the IT catheter and is used for delivering a precise volume into the trachea during spontaneous respiration. After the IT injection is completed, the needle and catheter are withdrawn, and the pup is allowed to recover from anesthesia. Transcutaneous IT injection delivers a large proportion of the injected substance to the lung, with the majority remaining in the lung 3 hours after the intervention. The injections are well tolerated from the day of birth and can be repeated for multiple consecutive days without influencing survival. This technique can be used to investigate the effect of pharmaceutical agents on lung development and in the prevention of neonatal lung injury in preterm rabbits.

Study of Tidal Volume and Positive End-Expiratory Pressure on Alveolar Recruitment Using Spiro Dynamics in Mechanically Ventilated Patients.

Background and Aims:Ventilator setting in the intensive care unit patients is a topic of debate and setting of tidal volume (TV) should be patient-specific based on lung mechanics. In this study, we have evaluated to develop optimal ventilator strategies through continuous and thorough monitoring of respiratory mechanics during ongoing ventilator support to prevent alveolar collapse and alveolar injury in mechanically ventilated patients.Methods:In our monocentric, randomized, observational study, we had recruited 60 patients and divided them into two groups of 30 each. In Group 1 patients, TV and positive end-expiratory pressure (PEEP) were set according to pressure–volume (P/V) curve obtained by the mechanical ventilator in a conventional manner (control group), and in Group 2, TV and PEEP were set according to P/V curve obtained by the mechanical ventilator using intratracheal catheter. PEEP and TV were set accordingly. TV, PEEP, and PaO2/FiO2 (P/F) ratio at days 1, 3, and 7, mortality within 7 days and mortality within 28 days were measured in each group and compared.Results:We found a significant difference between PEEP and P/F ratio in both groups while intragroup comparison at days 1, 3, and 7. After the intergroup comparison of Group 1 and 2, we observed a significant difference of PEEP and P/F ratio between the groups at day 7 and not on day 1 or 3.Conclusion:This study concludes that optimal PEEP is more accurate using an intratracheal catheter than the conventional method of deciding ventilator setting. Hence, it is recommended to use intratracheal catheter to obtain more accurate ventilator settings.

A Comparative Study of the Efficacy of Surfactant Administration through a Thin Intratracheal Catheter and its Administration via an Endotracheal Tube in Neonatal Respiratory Distress Syndrome

Background: The cornerstone of the treatment of respiratory distress syndrome (RDS) is respiratory support and surfactant replacement therapy. The administration of surfactant through a thin intratracheal catheter is one of the methods used to reduce one of the standard technique complications of a surfactant injection (Intubation-Surfactant-Extubation method [INSURE]). The aim of this study was to compare the effectiveness of this method on the treatment of RDS in neonates with one of the INSURE technique. Methods: In this double blind clinical trial, 104 neonates with RDS were randomly allocated to two groups, one group received surfactant via an endotracheal tube (INSURE) and the other received surfactant without intubation (SWI) via a thin intratracheal catheter. Subsequently the outcomes of the two groups were compared. Results: The incidence of hypoxemia during surfactant administration was significantly lower in the SWI group (11.5%) than in the INSURE group (28.8% , P< 0.05). no significant difference was observed in the need for intubation and mechanical ventilation during the first 72 hours of life, the duration of mechanical ventilation, the need for nasal continuous positive airway pressure (NCPAP), the need for oxygen, the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, pulmonary hemorrhage ,and death in the two groups. Conclusion: Administration of surfactant through a thin intratracheal catheter is a safe and easy technique. This method is as effective as the INSURE method in improving the outcomes of RDS treatment.

Early administration of surfactant via a thin intratracheal catheter in preterm infants with respiratory distress syndrome: Feasibility and outcome.

Objective:Currently, the method of early nasal continuous positive airway pressure (nCPAP) and selective administration of surfactant via an endotracheal tube is widely used in the treatment of respiratory distress syndrome (RDS) in premature infants. To prevent complications related to endotracheal intubation and even a brief period of mechanical ventilation, in this study, we compared the effectiveness of surfactant administration via a thin intratracheal catheter versus the current method using an endotracheal tube.Methods:Thirty eight preterm infants ≤34 weeks' gestation with birth weight of 1000–1800 g who were putted on nCPAP for RDS within the first hour of life, were randomly assigned to receive surfactant either via endotracheal tube (ET group) or via thin intratracheal catheter (CATH group). The primary outcomes were the need for mechanical ventilation and duration of oxygen therapy. Data were analyzed by independent t-test, Mann-Whitney U-test, and Chi-square test, using SPSS v. 21.Findings:There was no significant difference between groups regarding to need for mechanical ventilation during the first 72 h of birth (3 [15.8%] in ET group vs. 2 [10.5%] in CATH group; P = 0.99). Duration of oxygen therapy in CATH group was significantly lower than ET group (243.7 ± 74.3 h vs. 476.8 ± 106.8 h, respectively; P = 0.018). The incidence of adverse events during all times of surfactant administration was not statistically significant between groups (P = 0.14), but the number of infants who experienced adverse events during surfactant administration was significantly lower in CATH group than ET group (6 [31.6%] vs. 12 [63.2%], respectively; P = 0.049). All other outcomes, including duration of treatment with CPAP and mechanical ventilation, times of surfactant administration and the need for more than one dose of the drug, the rate of intraventricular hemorrhage, mortality and combined outcome of chronic lung disease or mortality were statistically similar between the groupsConclusion:Surfactant administration via thin intratracheal catheter in preterm infants receiving nCPAP for treatment of RDS has similar efficacy, feasibility and safety to its administration via endotracheal tube.

Neonatal Lung Disease and Respiratory Failure

Neonatal Lung Disease and Respiratory Failure

Aerosolized perfluorocarbon improves gas exchange and pulmonary mechanics in preterm lambs with severe respiratory distress syndrome

Aerosolized perfluorocarbon (PFC) has been proposed as an alternative method of PFC administration; however, the efficacy of aerosolized PFC in a preterm animal model has not yet been demonstrated. Twelve preterm lambs were randomized to two groups: a perfluorodecalin (PFD) aerosol group (n = 6) receiving 10 ml/kg/h of PFD delivered by an intratracheal inhalation catheter followed by 4 h of mechanical ventilation (MV) or the control group, in which animals (n = 6) were managed for 6 h with MV. Gas exchange, pulmonary mechanics, cardiovascular parameters, and cerebral blood flow (CBF) were measured. Both groups developed hypoxia, hypercarbia, and acidosis at baseline. Aerosolized PFD improved oxygenation (P < 0.0001) and pulmonary mechanics (P < 0.0001) and changed carbon dioxide values to normal physiological levels, unlike the treatment given to the controls (P < 0.0003). The time course of mean arterial blood pressure and CBF were significantly affected by PFD aerosolization, especially during the first hour of life. CBF gradually decreased during the first hour in the PFD aerosol group and remained stable until the end of the follow-up, whereas CBF remained higher in the control group (P < 0.0028). Aerosolized PFD improves pulmonary function in preterm lambs and should be further investigated as an alternative mode of PFC administration.

Surfactant and Perfluorocarbon Aerosolization During Different Mechanical Ventilation Strategies by Means of Inhalation Catheters: An In Vitro Study

Aerosol delivery of surfactant and perfluorocarbon (PFC) is a desirable therapeutic approach for the treatment of various lung diseases in patients undergoing mechanical ventilation. However, the behavior of these substances during aerosolization differs significantly from that of aqueous solutions. In particular, the high vapor pressure of many PFCs tends to result in greater evaporation during mechanical ventilation. Three PFCs and surfactant were aerosolized during mechanical ventilation by means of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, and IC-1.4), with their aerosol generating tip placed at the distal end of the endotracheal tube (i.d. 4 mm). The influence of four different ventilation strategies on aerosol production rate and PFC and surfactant recovery was studied. The changes in intrapulmonary pressure produced by the air jets of each IC were measured. With IC-1.23 and IC-1.1, the highest rates of aerosol production were achieved using FC75 (2.27±0.18 and 0.76±0.01, respectively) followed by PFOB (1.74±0.06 and 0.56±0.04), PFD (0.82±0.01 and 0.21±0.01), and surfactant (0.42±0.05 and 0.092±0.01). With IC-1.4 modest aerosol production was obtained irrespective of the aerosolized compound. Mechanical ventilation influenced aerosol recovery, with the trend being toward recovering higher percentages of the compounds with lower peak inspiratory pressure (PIP) and lower respiratory rate (RR) settings. The highest percentages of the initial volume were recovered with IC-1.23 (between 65.43%±4.2 FC75 and 90.21%±4.71 surfactant) followed by IC-1.1 (between 46.48%±4.46 FC75 and 73.19%±2.82 PFOB) and IC-1.4 (between 4.65%±4.36 FC75 and 63.24%±9.71 surfactant). Each of three of the ICs were found to increase the intrapulmonary pressure by about 2-3 cmH₂O during mechanical ventilation. Despite of mechanical ventilation, IC-1.23 and IC-1.1 were able to deliver significant amounts of surfactant and perfluorocarbon to the lung model. Changes in PIP and RR directly influence the percentage of surfactant and perfluorocarbon recovered.

Surfactant and Perfluorocarbon Aerosolization by Means of Inhalation Catheters for the Treatment of Respiratory Distress Syndrome: An In Vitro Study

The aerosolization of perfluorocarbons or surfactant has emerged as a feasible alternative to instillation, for the treatment of experimental respiratory distress syndrome. However, the biophysical properties that make these compounds useful in such therapies, significantly affect the performance of nebulizers. Therefore, in vitro studies are required to assess the suitability of new aerosolization technologies for use with these compounds. The aim of the present in vitro study was to investigate the influence of the biophysical properties of perfluorocarbons (PFD, FC75, and PFOB) and a natural porcine surfactant, Curosurf®; on aerosolization and to assess the suitability of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, IC-1.4) coupled to a jet nebulizer, for aerosol delivery of these compounds. With IC-1.23 significantly higher aerosol production rates were achieved (p < 0.0001), ranging between 6.05 ± 0.17 mL/min (FC75) and 1.94 ± 0.09 mL/min (Curosurf®), and lower percentage losses of the compound (5-21%), compared to IC-1.1 and IC-1.4 catheters. The lowest aerosolization rates were produced with IC-1.4 ranging from 0.58 ± 0.02 mL/min (FC75) to 0.14 ± 0.01 mL/min (Curosurf®), and this catheter also resulted in the highest percentage losses (25-60%). The mass median aerodynamic diameter (MMAD) ranged between 0.77 μm (PFD) and 8.29 μm (Curosurf®) with IC-1.1, whereas higher MMAD values, of between 4.84 μm (FC75) and 13.42 μm (PFOB), were observed with IC-1.23. Regardless of the catheter used during aerosolization, the perfluorocarbon with the highest kinematic viscosity showed the lowest aerosolization and emission rates and vice versa, which reveals the substantial contribution of this parameter that should accordingly be considered in the design of perfluorocarbon aerosol drug delivery systems. Jet aerosolization of perfluorocarbons or surfactant with the intratracheal inhalation catheters seems to be a suitable method for treating experimental respiratory distress syndrome, because it delivers relatively high doses of perfluorocarbons and surfactant to the lungs in a respirable size droplets.

Frank J. Murphy, M.D., C.M., 1900–1972

Frank J. Murphy, M.D., C.M., 1900–1972

Pulmonary Gene Silencing in Transgenic EGFP Mice Using Aerosolised Chitosan/siRNA Nanoparticles

This work describes the production and application of an aerosolised formulation of chitosan nanoparticles for improved pulmonary siRNA delivery and gene silencing in mice. Aerosolised chitosan/siRNA nanoparticles were pneumatically formed using a nebulising catheter and sized by laser diffraction. In vitro silencing of aerosolised and non-aerosolised formulations was evaluated in an EGFP endogenous-expressing H1299 cell line by flow cytometry. Non-invasive intratracheal insertion of the catheter was used to study nanoparticle deposition by histological detection of Cy3-labeled siRNA and gene silencing in transgenic EGFP mouse lungs using a flow cytometric method. Flow cytometric analysis demonstrated minimal alteration in gene silencing efficiency before (68%) and after (62%) aerosolisation in EGFP-expressing H1299 cells. Intratracheal catheter administration in mice resulted in nanoparticle deposition throughout the entire lung in both alveoli and bronchiolar regions using low amounts of siRNA. Transgenic EGFP mice dosed with the aerosolised nanoparticle formulation showed significant EGFP gene silencing (68% reduction compared to mismatch group). This work provides a technology platform for effective pulmonary delivery and gene silencing of RNAi therapeutics with potential use in preclinical studies of respiratory disease treatment.

Intratracheal catheter suction removes the same volume of meconium with less impact on desaturation compared with meconium aspirator in meconium aspiration syndrome

Objective To evaluate the impact of suction technique on the rate of meconium removal, oxygenation, and hemodynamics in an animal experimental model of meconium aspiration syndrome (MAS). Methods MAS was induced in ventilated rabbits using 3.5 ml/kg of 20% human meconium. Tracheal suction with either catheter suction (CS) or meconium aspirator (MA) was performed after meconium instillation. Percentage of meconium collection rate, PaO 2 trends for 2 h after tracheal suction, and acute-phase SpO 2 trends were compared between CS and the other three groups, the tube was withdrawn while meconium was aspirated with an MA, then the trachea was reintubated 5, 10 or 15 s after suctioning of meconium. Results Percentage of meconium collection rate and PaO 2 showed no significant differences between groups. The MA group taking 15 s for reintubation after meconium suctioning, showed a significantly lower acute-phase SpO 2 than the CS group ( P < 0.05). The time for SpO 2 to return to ≥ 90% was also longer in the MA group taking 15 s for reintubation than in the CS group ( P < 0.05). Conclusion Intratracheal CS removed the same volume of meconium with less impact on desaturation compared with meconium aspiration in an animal model of MAS. Intratracheal CS may be benefit to remove meconium in non-vigorous infants with meconium-stained amniotic fluid at birth.

Early administration of surfactant in spontaneous breathing with nCPAP: feasibility and outcome in extremely premature infants (postmenstrual age ≤27 weeks)

Spontaneous breathing supported by nasal continuous positive airway pressure (nCPAP) is thought to have some advantages compared with mechanical ventilation in extremely premature infants. In addition, early or prophylactic surfactant administration has been shown to be superior to delayed use. A strategy to combine these two principles was tested in our neonatal intensive care unit (NICU). The aim of this feasibility study was to describe the procedure and compare short-term results with a historical control. The study took place in a level III NICU. In the observational period all extremely premature infants with clinical signs of moderate to severe respiratory distress syndrome despite nCPAP received 100 mg.kg(-1) of a natural surfactant preparation via an intratracheal catheter during spontaneous breathing. In the historical control period those infants were intubated and ventilated to receive surfactant. Twenty-nine of 42 infants fulfilled the criteria and were treated with the new approach. In five cases ventilation with manual bag was necessary after administration of surfactant but all infants could be retransferred to nCPAP within a few minutes. Ten infants were intubated later during the first 3 days. Mortality was 7% in the group of infants treated in this way and 12% in all infants treated during the observational period. Mortality was 35% in the historical control period. Morbidity was within ranges reported by other authors. Surfactant administration during nCPAP is feasible. First results indicate that early complications are rare. This warrants a prospective randomized trial.

Aerosol delivery of an enhanced helper-dependent adenovirus formulation to rabbit lung using an intratracheal catheter

Poor transduction of the ciliated airway epithelium and inefficient airway delivery of viral vectors are common difficulties encountered in lung gene therapy trials with large animals and humans. We delivered a helper-dependent adenovirus vector, incorporating a human epithelial cell-specific expression cassette, to rabbit lung. An intratracheal device was used to aerosolize a moderate dose of virus (5 x 10(11) particles), mixed with the enhancing agent LPC (L-alpha-lysophosphatidylcholine), directly into the airways. Lung mechanics, body weight and temperature, transgene expression and histopathology were studied at day 5. Transgene expression was seen in the epithelium of large and small airways, from trachea to terminal bronchioles, with a strong tendency toward the right lung. All cell types of the surface epithelium were transduced. Extensive transduction of the epithelium (66% of cells in trachea) was obtained using virus formulated in isotonic 0.1% LPC, while virus formulated in 0.01% LPC transduced fewer cells (24% in trachea). A transient decrease in dynamic lung compliance was observed immediately following aerosol delivery. Fever and mild-to-moderate patchy pneumonia without edema were also observed. These data demonstrate a strategy for efficient and effective transduction of airway epithelium in a large animal.

Capnographic documentation of nasoesophageal and nasogastric feeding tube placement in dogs

AbstractObjective: To evaluate the ability of capnography to document proper placement of nasoesophageal (NE) and nasogastric (NG) feeding tubes. This study was conducted in 3 phases. Phase I of this study was designed in order to test the efficacy of capnography to distinguish placement of a feeding tube in the alimentary tract versus the respiratory tract. Phase II was designed in order to document that carbon dioxide (CO2) could be measured through a polyvinyl chloride (PVC) feeding tube. Phase III was performed in order to evaluate the technique of continuous monitoring during insertion of the feeding tube into the esophagus and stomach as would be performed during a clinical‐tube placement.Design: Prospective study.Setting: Research laboratory.Animals: 24 adult dogs.Interventions: In Phase I, sedated dogs were instrumented with an intratracheal catheter and an 8 French feeding tube placed nasally into the distal esophagus and later advanced into the stomach. In Phase II, dogs were anesthetized and an 8 French feeding tube was placed down the endotracheal tube, then into the esophagus and later advanced into the stomach. In Phase III, sedated dogs were instrumented with an 8 French feeding tube inserted intranasally and then advanced to the level of the nasopharynx, distal esophagus and, lastly, the stomach. Fluoroscopy was used in order to determine location of the feeding tube.Measurements and main results: Phase I measurements included respiratory rate and CO2 from the trachea, esophagus, and stomach and pH of gastric fluid sample. Phase II measurements included respiratory rate and CO2 from the endotracheal tube, feeding tube in the endotracheal tube, feeding tube in the distal esophagus, and feeding tube in the stomach. Phase III data collection included respiratory rate and CO2 as the tube was passed through the nasal cavity, nasopharynx, esophagus and stomach. Phase I fluid samples were collected from 5 of the 9 dogs and had pH values from 1.68 to 4.20. In both phases, values for the respiratory rate and CO2 from the esophagus and stomach were 0 ± 0, significantly lower (P &lt; 0.001) than the values from the trachea. In Phase II, there was no significant difference between the respiratory rates (P = 0.886) and CO2 (P = 0.705) readings obtained from the endotracheal tube compared to readings from the feeding tube in the endotracheal tube. In Phase III, there was a significant difference (P &lt; 0.001) between the respiratory rates and CO2 readings obtained from the nasal cavity and the nasopharynx when compared to those readings obtained from the esophagus and stomach. Measurement of CO2 and respiratory rate resulted in a reading of 0 every time the feeding tube was in the esophagus or stomach.Conclusions: Capnography may be used in order to detect airway placement of NE and NG tubes.

Fetal lung growth after short-term tracheal occlusion is linearly related to intratracheal pressure.

Prenatal tracheal occlusion (TO) has been shown to accelerate fetal lung growth, yet the mechanism is poorly understood. The goal of this study was to determine the relationship between fetal intratracheal pressure (Pitr) and fetal lung growth after TO. Fetal lambs underwent placement of an intratracheal catheter and a reference catheter at 115--120 days gestation (term, 145 days). Fetal Pitr was continuously controlled at three levels (high, 8 mmHg; moderate, 4 mmHg; low, 1 mmHg) by a servo-regulated pump. The animals were killed after 4 days, and the parameters of lung growth were compared. Lung volume (136.0 +/- 16.7, 94.9 +/- 9.7, 55.5 +/- 12.4 ml/kg), lung-to-body weight ratio (6.31 +/- 0.70, 4.89 +/- 0.38, 3.39 +/- 0.22%), whole right lung dry weight (3.01 +/- 0.29, 2.53 +/- 0.15, 2.07 +/- 0.24 g/kg), right lung DNA (130.0 +/- 11.3, 116.7 +/- 8.6, 97.5 +/- 10.9 mg/kg), and protein contents (1,865.5 +/- 92.5, 1,657.6 +/- 106.8, 1,312.0 +/- 142.5 mg/kg) in high, moderate, and low groups, respectively, all increased in the moderate compared with the low group and increased further in the high compared with the moderate group. Morphometry confirmed a stepwise increase in the volume of respiratory region and alveolar surface area. We conclude that lung growth in the first 4 days after TO is closely correlated with fetal Pitr, offering additional evidence that an increase in lung expansion is one of the major factors responsible for TO-induced lung growth.

Lung growth induced by tracheal occlusion in the sheep is augmented by airway pressurization

Background/Purpose: Prenatal tracheal occlusion (TO) has been shown to accelerate lung growth, yet the mechanism for this effect is poorly understood. Increased intratracheal pressure (ITP) with accumulation of lung fluid and secondary airway distension (stretch) may provide a mechanical stimulus for growth. In this study, ITP after TO is measured continuously, and the effect of altering ITP on lung growth is examined.Methods: Fetal lambs of 115 to 120 days of gestation (term, 145 days) underwent placement of an intratracheal catheter and an amniotic fluid reference catheter. First, ITP was monitored continuously in normal controls (n = 4) and in fetuses undergoing TO (n = 6). In a subsequent study, 2 groups of fetuses were compared. In the TO group (n = 5) ITP was monitored after TO. In the pressurized group (n = 5) ITP was maintained at 7 to 8 mm Hg by a continuous servo regulated pump that maintains a preset pressure by lactated Ringers infusion. The animals were killed after 4 days, and lung growth was compared.Results: In the control animals, ITP remained constant at 0.4 to 1.5 mm Hg. In the TO animals, ITP increased gradually during the initial 24 hours and plateaued at 4 to 5 mm Hg. In the second set of animals, ITP in the pressurized group was maintained at approximately 8 mm Hg using the infusion system. Lung volume (135.7 ± 17.4 v 95.2 ± 14.8 mL/kg P < .01), lung weight to body weight (6.70 ± 0.73 v 5.33 ± 0.77%; P < .05), whole right lung dry weight (3.10 ± 0.22 v 2.63 ± 0.20 mg/kg; P < .05), and right lung DNA and protein contents (87.3 ± 6.0 v 74.6 ± 8.1 mg/kg, 2,310 ± 248 v 1,860 ± 196 mg/kg, respectively; P < .05) were increased significantly in the pressurized group compared with the TO group. Morphometry confirmed greater volume of respiratory region and increased alveolar surface area in the pressurized lung.Conclusions: TO results in a gradual increase in ITP over 15 to 24 hours, which plateaus at 4 to 5 mm Hg. Further increasing ITP by infusion of crystalloid significantly augments lung growth beyond that observed with TO alone. These data support the hypothesis that airway pressure and secondary mechanical stretch are the primary stimuli of TO induced lung growth.

Time-course changes of eosinophil counts in premature infants: no effects of medical manipulation, except erythropoietin treatment, on eosinophilia.

In order to determine the factors responsible for eosinophilia during the neonatal period, we counted the eosinophils of premature infants every week and compared the medical profiles of infants with eosinophil counts above the 95th percentile and those below that percentile during the course of study. Medical treatments such as mechanical ventilation, antibiotics administration and intravenous catheterization had no significant effects on the increase of eosinophils. Furthermore, the incidence of eosinophil counts above the 95th percentile was not different between breast-fed and formula-fed infants. The infants treated with erythropoietin had greater eosinophil counts than those with no treatment. It is probable that medical manipulation using foreign bodies such as intratracheal tube, intravenous catheter, antibiotics and artificial formula had no significant effects on the increase of eosinophil counts, except for exogenous erythropoietin.

Prolonged partial liquid ventilation in spontaneously breathing awake animals.

To date, studies of partial liquid ventilation (PLV) have examined its effects acutely in anesthetized and mechanically ventilated subjects. We set out to develop a model of prolonged PLV in awake, spontaneously breathing animals. Animal case series Cardiopulmonary physiology laboratory. Fifteen New Zealand white rabbits (3.2+/-0.39 kg). Animals were anesthetized and instrumented with a novel technique allowing percutaneously assisted placement of an intratracheal catheter with a subcutaneously tunneled externalized free end. After anesthetic recovery, PLV was performed in spontaneously breathing unsedated animals. Evaporative losses were determined using a single 10 mL/kg perflubron dose (n = 5); hourly radiographs were obtained until residual perflubron was minimal. For prolonged PLV (n = 10), a 10-mL/kg initial perflubron dose was followed every 4 hrs with 5-mL/kg supplements. Radiographs were obtained immediately before and after perflubron administration and were scored (0-5) by a radiologist blinded to dosing regimen and time interval. Data were analyzed with ANOVA and Student's t-test with correction for multiple comparisons. Initial filling was nearly complete (score = 4.8+/-0.42); lungs were maintained approximately half-filled through 4 hrs (score = 2.53+/-0.71). By 6 hrs, the majority of perflubron had evaporated (score = 1.75+/-0.53). Over 24 hrs, radiographs documented continuous perflubron exposure (postffill = 4.53+/-0.64, prefill = 3.40+/-0.71, average = 3.97+/-0.43); scores were comparatively higher after filling (after = 4.53+/-0.64, before = 3.4+/-0.71, p< .001). Left and right lung volumes were equivalent (left = 4.06+/-0.47, right = 3.89+/-0.39, p = .027). All animals survived the 24 hrs of PLV. Percutaneously assisted intratracheal cannulation with catheter exteriorization permits prolonged PLV in spontaneously breathing, unsedated animals. Continuous perfluorocarbon exposure with this method is reproducible, consistent, and well tolerated for 24 hrs in uninjured animals.