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Objectives: We investigated the effects of two different types of manual rib cage compression on expiratory flow and mucus clearance during prolonged mechanical ventilation in pigs., Design: Prospective randomized animal study., Setting: Animal research facility, University of Barcelona, Spain., Subjects: Nine healthy pigs., Measurement and Main Results: Pigs were tracheally intubated, sedated, paralyzed, and mechanically ventilated. The animals were prone on a surgical bed in the anti-Trendelenburg position. The experiments were carried out at approximately 60 and 80 hrs from the beginning of mechanical ventilation. Two types of manual rib cage compressions were tested: Hard and brief rib cage compressions synchronized with early expiratory phase (hard manual rib cage compression) and soft and gradual rib cage compressions applied during the late expiratory phase (soft manual rib cage compression). The interventions were randomly applied for 15min with a 15-min interval between treatments. Respiratory flow and mucus movement were assessed during the interventions. Respiratory mechanics and hemodynamics were assessed prior to and after the interventions. Peak expiratory flow increased to 60.1±7.1L/min in comparison to 51.2±4.6L/min without treatment (p < 0.0015) and 48.7±4.3L/min with soft manual rib cage compression (p = 0.0002). Similarly, mean expiratory flow increased to 28.4±5.2L/min during hard manual rib cage compression vs. 15.9±2.2 and 16.6±2.8L/min without treatment and soft manual rib cage compression, respectively (p = 0.0006). During hard manual rib cage compression, mucus moved toward the glottis (1.01 ± 2.37mm/min); conversely, mucus moved toward the lungs during no treatment and soft manual rib cage compression, -0.28 ± 0.61 and -0.15±0.95mm/min, respectively (p = 0.0283). Soft manual rib cage compression slightly worsened static lung elastance and cardiac output (p = 0.0391)., Conclusions: Hard manual rib cage compression improved mucus clearance in animals positioned in the anti-Trendelenburg position. The technique appeared to be safe. Conversely, soft manual rib cage compression was not effective and potentially unsafe. These findings corroborate the predominant role of peak expiratory flow on mucus clearance.

Objective: : We evaluated a new device designed to clean the endotracheal tube in mechanically ventilated patients, the Mucus Shaver., Design: : Prospective, randomized trial., Setting: : University hospital intensive care unit., Patients: : We enrolled 24 patients expected to remain ventilated for >72 hrs., Interventions: : The Mucus Shaver is a concentric inflatable catheter for the removal of mucus and secretions from the interior surface of the endotracheal tube. The Mucus Shaver is advanced to the distal endotracheal tube tip, inflated, and subsequently withdrawn over a period of 3-5 secs. Patients were prospectively randomized within 2 hrs of intubation to receive standard endotracheal tube suctioning treatment or standard suctioning plus Mucus Shaver use until extubation., Measurements and Main Results: : During the study period, demographic data, recent medical history, adverse events, and staff evaluation of the Mucus Shaver were recorded. At extubation, each endotracheal tube was removed, cultured, and analyzed by scanning electron microscopy. Twelve patients were assigned to the study group and 12 were assigned to the control group. No adverse events related to the use of the Mucus Shaver were observed. At extubation, only one endotracheal tube from the Mucus Shaver group was colonized, whereas in the control group ten endotracheal tubes were colonized (8% vs. 83%; p < .001). Scanning electron microscopy showed little secretions on the endotracheal tubes from the study group, whereas thick bacterial deposits were present on all the endotracheal tubes from the control group (p < .001 by Fisher exact test, using a maximum biofilm thickness of 30 μm as cut-off). The nursing staff was satisfied by the overall safety, feasibility, and efficacy of the Mucus Shaver., Conclusions: : The Mucus Shaver is a safe, feasible, and efficient device for endotracheal tube cleaning in the clinical setting. The Mucus Shaver is helpful in preventing endotracheal tube colonization by potentially harmful microorganisms.

Objective: : To demonstrate the technical feasibility of CO2 removal with a commercial hemofilter and a replacement solution containing sodium hydroxide to replace bicarbonate., Design: : Prospective animal experiment in sheep., Subjects: : Seven mixed-breed female sheep., Interventions: : Blood ultrafiltrate containing half of the metabolic production of CO2 was removed with a commercial hemofilter and a replacement solution containing sodium hydroxide was given as replacement. Minute ventilation was lowered to less than half of its baseline value. Ultrafiltration was stopped at 18 hrs, and Paco2 was allowed to increase for about 1 hr; at this time, the sheep were electively killed., Measurements and Main Results: : Every 6 hrs, blood was sampled from the carotid artery, the pulmonary artery, and from the extracorporeal perfusion circuit (before the hemofilter, immediately after the hemofilter, and after mixing with the replacement solution). To maintain normocapnia, minute ventilation was reduced from 3.8 +/- 0.1 L/min to 1.9 +/- 0.7 L/min; Paco2 remained near constant during the study. The average blood pH, after mixing with the replacement solution, was 7.64 +/- 0.12. One hour after the ultrafiltration had stopped, Paco2 had increased from 36.7 +/- 4.2 torr (4.9 +/- 0.6 kPa) to 59.6 +/- 9 torr (7.9 +/- 1.2 kPa) (p < .01) and blood pH had decreased from 7.317 +/- 0.041 to 7.151 +/- 0.051 (p < .01)., Conclusion: : CO2 removal with bicarbonate ultrafiltration may be an effective treatment for patients with respiratory failure.

Objectives: Critically ill intubated patients are positioned in the semirecumbent position to prevent pneumonia. In tracheally intubated sheep, we investigated the effects of gravitational force on tracheal mucus transport and on bacterial colonization of the respiratory system., Design: Prospective randomized animal study., Setting: Animal research facility at the National Institutes of Health., Subjects: Sixteen healthy sheep., Interventions: Spontaneously breathing or mechanically ventilated sheep were randomized to be positioned with the orientation of the trachea above (40 degrees, trachea-up) or below (5 degrees, trachea-down) horizontal., Measurements and Main Results: Tracheal mucus velocity was measured through radiographic tracking of radiopaque tantalum disks, insufflated into the trachea. After 24 hrs, sheep were euthanized, and samples from the airways and lungs were taken for microbiological analysis. The proximal trachea was colonized in all sheep. In trachea-down sheep, all mucus moved toward the glottis at a mean velocity of 2.1 +/- 1.1 mm/min. When mucus reached the endotracheal tube, it either entered the endotracheal tube or was lodged at the inflated endotracheal tube cuff. In all trachea-up sheep, abnormal tracheal mucus clearance was found. Mucus, mostly on the nondependent part of the trachea, moved toward the glottis at an average velocity of 2.2 +/- 2.0 mm/min and constantly accumulated at the inflated endotracheal tube cuff. From the proximal trachea, mucus eventually moved toward the lungs on the dependent part of the trachea, leading to an "intratracheal route" of colonization of the lungs. Pneumonia was found in 6/8 of trachea-up sheep and the same microorganisms were isolated from the lungs and the proximal trachea. No pneumonia was found in trachea-down sheep (p = .007)., Conclusions: The study indicates that following tracheal intubation gravitational force influences tracheal mucus clearance. When the trachea is oriented above horizontal, a flow of mucus from the proximal trachea toward the lungs is highly associated with bacterial colonization of the airways and pneumonia.

Objective: Continuous aspiration of subglottic secretions (CASS) is believed to lower the incidence of ventilator-associated pneumonia. Animal studies to establish safety and efficacy of CASS have not been conducted., Design: Prospective randomized animal study., Setting: Animal-research facility at the U.S. National Institutes of Health., Subjects: Twenty-two sheep., Interventions: Sheep were randomized into three groups. In group C (control), eight sheep were kept prone, intubated with a standard endotracheal tube (ETT), and mechanically ventilated for 72 hrs with head and ETT elevated at an angle of 30 degrees. In group CASS-HU (CASS, head up), seven sheep were managed as group C and intubated with a Hi-Lo Evac, Mallinckrodt ETT (CASS suction kept at < or =20 mm Hg). In group CASS-HD (CASS, head down), seven sheep were kept prone with CASS, and the ETT and trachea were horizontal to promote spontaneous drainage of mucus from the ETT., Measurements and Results: The lower respiratory tract in the CASS-HU group was heavily colonized in all seven sheep (median 4.6 x 10(9), range, 1.5 x 10(8) to 7.9 x 10(9) colony-forming units/g), with a reduction of lung bacterial colonization compared with the C group (p = .05). In group CASS-HD, the lower respiratory tract was not colonized in six of seven sheep. One sheep showed low levels of bacterial growth (median, 0; range, 0-2.2 x 10(5)). At autopsy, in all 14 sheep with CASS, we found tracheal mucosal injury of different degrees of severity at the level of the suction port of the ETT., Conclusions: In group CASS-HU, regardless of finding a marginal decrease of the bacterial colonization of the lower airways, there was pervasive trachea-bronchial-lung bacterial colonization. Second, there was minimal, or absent, bacterial colonization when the orientation of the CASS ETT was at, or just below, horizontal. Third, there was widespread injury to tracheal mucosa/submucosa from the use of CASS. Note that results of studies conducted in an animal model are always difficult to extrapolate to the clinical practice due to anatomical and functional differences.

We investigated a new method of pulmonary ventilation that included a minitracheostomy, a reverse thrust catheter to deliver continuous flow of gas to the carina, and a threshold valve to avoid lung overinflation. In six lightly sedated healthy sheep, at a continuous flow of 5, 10, or 15 L/min and a threshold valve of 5, 10, 15, or 20 cm H(2)O, we observed a novel respiratory pattern that was characterized either by active lung inflation followed by passive and prolonged inspiratory hold (mixed pattern) or by an absence of all active inspiratory effort and only passive inflation of the lungs (passive pattern). We correlated airway pressure changes with direct visualization of the glottic opening through a fiberoptic bronchoscope. We measured airway pressures at the level of the carina, the subglottic level, and in the pleural space, and respiratory events were monitored through inductive plethysmography. An increase in continuous flow, threshold valve, or both resulted in 1) an increase in glottic breathing; 2) a decrease in respiratory rate, with a decrease in inspiratory pleural pressure excursion; or 3) an increased inspiratory/expiratory ratio and mean airway pressure. During transtracheal gas insufflation, as in this study, a novel respiratory pattern evolved that was modulated by the glottis, accompanied by a decreased effort of breathing; coughing and swallowing remained, and vocalization remained unimpaired.

Objective: We report the evolution of severe ventilator-induced lung injury associated with lethal systemic capillary leak syndrome, when sheep were ventilated at a peak inspiratory pressure of 50 cm H2O, at a respiratory rate of 8 breaths.min, with an inspiratory time of 2.5 secs., Design: A prospective laboratory animal study., Setting: Experimental animal research laboratory., Subjects: Mixed breed sheep., Interventions: Sheep were anesthetized, paralyzed, and mechanically ventilated., Measurements and Main Results: This sheep model was characterized by a rapidly evolving massive anasarca, hemoconcentration, cardiac dysfunction, multiple system organ failure, and severe ventilator-induced lung injury. Cardiovascular changes and profound hemoconcentration developed within 6 hrs from the start of mechanical ventilation, along with a major decline in pulmonary compliance and deterioration in arterial blood gases. When total static lung compliance decreased to 0.15 mL (cm H2O)(-1) x kg(-1) (7-30 hrs), the sheep were randomized to two groups. Group I received high (recruitive) positive end-expiratory pressure (9-20 cm H2O), adjusted as needed; group II received low (supportive) positive end-expiratory pressure (2-6 cm H2O). Sheep in both groups progressively deteriorated and died with cardiocirculatory failure and multiple system organ failure within 12-24 hrs from start of treatment., Conclusions: This model of lethal systemic capillary leak syndrome with multiple system organ failure differs greatly from our previous sheep model of acute ventilator-induced lung injury in which sheep were ventilated with a peak inspiratory pressure of 50 cm H2O, a respiratory rate of 4 breaths x min(-1), and an inspiratory time of 1.35 secs, without inducing capillary leak syndrome. The mere change of respiratory rate from 4 to 8 breaths x min(-1), with a near doubling of the inspiratory time to 2.5 secs, although maintaining eucapnia, resulted in lethal systemic capillary leak syndrome and multiple system organ failure with both gross and microscopic pathology of lungs greatly different from our previous model of mechanical ventilation-induced acute respiratory distress syndrome.

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