Peak Transpulmonary Pressure Research Articles

Effect and mechanical mechanism of spontaneous breathing on oxygenation and lung injury in mild or moderate animal ARDS

ObjectiveThe present study aimed to determine the effect and mechanical mechanism of spontaneous breathing during mechanical ventilation on oxygenation and lung injury using Beagles dogs mild or moderate acute respiratory distress syndrome (ARDS) model.MethodsAfter inducing mild or moderate ARDS by infusion of oleic acid, Eighteen Beagles dogs were randomly split into Spontaneous breathing group (BIPAPSB, n = 6), and Complete muscle paralysis group (BIPAPPC, n = 6),Six Beagles without ventilator support comprised the control group. Both groups were ventilated for 8 h under BIPAP mode. High-pressure was titrated TV to 6 ml/kg. A multi-pair esophageal balloon electrode catheter was used to measure respiratory mechanics and electromyogram. End-expiratory lung volume (EELV), gas exchange and respiratory variables were recorded in the process of mechanical ventilation. The contents of Interleukin (IL)-6 and IL-8 in lung tissue were measure using qRT-PCR. Besides, lung injury score was calculated in the end of mechanical ventilation.ResultsBased on the comparable setting of ventilator, BIPAPSB group exhibited higher safety peak transpulmonary pressure, abdominal pressure, EELV and P/F(PaO2/FiO2) than BIPAPPC group, whereas mean transpulmonary pressure, the mRNA levels of the IL-6 and IL-8 in the lung tissues and lung injury score in BIPAPSB group were lower than those in BIPAPPC group.ConclusionIn mild to moderate ARDS animal models, during mechanical ventilation, SB may improve respiratory function and reduce ventilator-induced lung injury. The mechanism may be that spontaneous inspiration up-regulates peak transpulmonary pressure and EELV; Spontaneous expiration decreases mean transpulmonary pressure by up-regulating intra-abdominal pressure, thereby reducing stress and strain.

Preliminary experience of transcatheter pulmonary valve replacement using domestic balloon-expandable valve

Objectives: To evaluate the feasibility and preliminary clinical results of transcatheter pulmonary valve replacement (TPVR) with the domestically-produced balloon-expandable Prizvalve system. Methods: This is a prospective single-center observational study. Patients with postoperative right ventricular outflow tract (RVOT) dysfunction, who were admitted to West China Hospital of Sichuan University from September 2021 to March 2023 and deemed anatomically suitable for TPVR with balloon-expandable valve, were included. Clinical, imaging, procedural and follow-up data were analyzed. The immediate procedural results were evaluated by clinical implant success rate, which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation<moderate and peak trans-pulmonary pressure gradient<40 mmHg (1 mmHg=0.133 kPa). Results: A total of 5 patients were included, with 4 males, aged 14 to 37 years. The initial diagnosis included Tetralogy of Fallot (2 cases), truncus arteriosus (1 case), pulmonary atresia (1 case) and subaortic stenosis (1 case, prior Ross procedure). Four patients underwent RVOT reconstruction with homograft or artificial conduit, and one patient was treated with trans-annular patch technique. The indications of TPVR included RVOT obstruction and regurgitation (3 cases), isolated obstruction (1 case), and isolated regurgitation (1 case). Of the 4 patients with varying severity of ROVT obstruction, the average preprocedural peak jet velocity of RVOT was 3.5 m/s, and the average peak pressure gradient was 50.0 mmHg. Except for one patient, who had previously been implanted with a covered Cheatham-Platinum (CP) stent due to severe stenosis of the main pulmonary artery, other patients underwent pre-stenting with a covered CP stent before TPVR. Clinical implant success was achieved in all of the 5 patients, and there was no serious periprocedural complications. The average trans-pulmonary peak jet velocity and peak pressure gradient derived from postprocedural echocardiography was 2.3 m/s and 21.2 mmHg, respectively. All patients experienced significant symptom relief after the procedure. All patients completed 3-month follow-up, and 4 completed 6-month follow-up. There was no case of infectious endocarditis during follow-up. All patients were graded as NYHA functional class one at the latest follow-up. Conclusions: TPVR using the domestically-produced balloon-expandable Prizvalve system is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable landing-zone anatomy. The safety, effectiveness, and long-term valve durability of the Prizvalve system deserve further research.

Phrenic Nerve Block and Respiratory Effort in Pigs and Critically Ill Patients with Acute Lung Injury.

Strong spontaneous inspiratory efforts can be difficult to control and prohibit protective mechanical ventilation. Instead of using deep sedation and neuromuscular blockade, the authors hypothesized that perineural administration of lidocaine around the phrenic nerve would reduce tidal volume (VT) and peak transpulmonary pressure in spontaneously breathing patients with acute respiratory distress syndrome. An established animal model of acute respiratory distress syndrome with six female pigs was used in a proof-of-concept study. The authors then evaluated this technique in nine mechanically ventilated patients under pressure support exhibiting driving pressure greater than 15 cm H2O or VT greater than 10 ml/kg of predicted body weight. Esophageal and transpulmonary pressures, electrical activity of the diaphragm, and electrical impedance tomography were measured in pigs and patients. Ultrasound imaging and a nerve stimulator were used to identify the phrenic nerve, and perineural lidocaine was administered sequentially around the left and right phrenic nerves. Results are presented as median [interquartile range, 25th to 75th percentiles]. In pigs, VT decreased from 7.4 ml/kg [7.2 to 8.4] to 5.9 ml/kg [5.5 to 6.6] (P < 0.001), as did peak transpulmonary pressure (25.8 cm H2O [20.2 to 27.2] to 17.7 cm H2O [13.8 to 18.8]; P < 0.001) and driving pressure (28.7 cm H2O [20.4 to 30.8] to 19.4 cm H2O [15.2 to 22.9]; P < 0.001). Ventilation in the most dependent part decreased from 29.3% [26.4 to 29.5] to 20.1% [15.3 to 20.8] (P < 0.001). In patients, VT decreased (8.2 ml/ kg [7.9 to 11.1] to 6.0 ml/ kg [5.7 to 6.7]; P < 0.001), as did driving pressure (24.7 cm H2O [20.4 to 34.5] to 18.4 cm H2O [16.8 to 20.7]; P < 0.001). Esophageal pressure, peak transpulmonary pressure, and electrical activity of the diaphragm also decreased. Dependent ventilation only slightly decreased from 11.5% [8.5 to 12.6] to 7.9% [5.3 to 8.6] (P = 0.005). Respiratory rate did not vary. Variables recovered 1 to 12.7 h [6.7 to 13.7] after phrenic nerve block. Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation.

Effects of pressure support ventilation on ventilator-induced lung injury in mild acute respiratory distress syndrome depend on level of positive end-expiratory pressure: A randomised animal study.

Harmful effects of spontaneous breathing have been shown in experimental severe acute respiratory distress syndrome (ARDS). However, in the clinical setting, spontaneous respiration has been indicated only in mild ARDS. To date, no study has compared the effects of spontaneous assisted breathing with those of fully controlled mechanical ventilation at different levels of positive end-expiratory pressure (PEEP) on lung injury in ARDS. To compare the effects of assisted pressure support ventilation (PSV) with pressure-controlled ventilation (PCV) on lung function, histology and biological markers at two different PEEP levels in mild ARDS in rats. Randomised controlled experimental study. Basic science laboratory. Thirty-five Wistar rats (weight ± SD, 310 ± 19) g received Escherichia coli lipopolysaccharide (LPS) intratracheally. After 24 h, the animals were anaesthetised and randomly allocated to either PCV (n=14) or PSV (n=14) groups. Each group was further assigned to PEEP = 2 cmH2O or PEEP = 5 cmH2O. Tidal volume was kept constant (≈6 ml kg). Additional nonventilated animals (n=7) were used as a control for postmortem analysis. Ventilatory and mechanical parameters, arterial blood gases, diffuse alveolar damage score, epithelial integrity measured by E-cadherin tissue expression, and biological markers associated with inflammation (IL-6 and cytokine-induced neutrophil chemoattractant, CINC-1) and type II epithelial cell damage (surfactant protein-B) were evaluated. In both PCV and PSV, peak transpulmonary pressure was lower, whereas E-cadherin tissue expression, which is related to epithelial integrity, was higher at PEEP = 5 cmH2O than at PEEP = 2 cmH2O. In PSV, PEEP = 5 cmH2O compared with PEEP = 2 cmH2O was associated with significantly reduced diffuse alveolar damage score [median (interquartile range), 11 (8.5 to 13.5) vs. 23 (19 to 26), P = 0.005] and expressions of IL-6 and CINC-1 (P = 0.02 for both), whereas surfactant protein-B mRNA expression increased (P = 0.03). These changes suggested less type II epithelial cell damage at a PEEP of 5 cmH2O. Peak transpulmonary pressure correlated positively with IL-6 [Spearman's rho (ρ) = 0.62, P = 0.0007] and CINC-1 expressions (ρ = 0.50, P = 0.01) and negatively with E-cadherin expression (ρ = -0.67, P = 0.0002). During PSV, PEEP of 5 cmH2O, but not a PEEP of 2 cmH2O, reduced lung damage and inflammatory markers while maintaining epithelial cell integrity.

Quantification of myocardial stiffness using magnetic resonance elastography in right ventricular hypertrophy: initial feasibility in dogs

IntroductionMyocardial stiffness is an important determinant of cardiac function and is currently invasively and indirectly assessed by catheter angiography. This study aims to demonstrate the feasibility of quantifying right ventricular (RV) stiffness noninvasively using cardiac magnetic resonance elastography (CMRE) in dogs with severe congenital pulmonary valve stenosis (PVS) causing RV hypertrophy, and compare it to remote myocardium in the left ventricle (LV). Additionally, correlations between stiffness and selected pathophysiologic indicators from transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging were explored. MethodsIn-vivo CMRE was performed on nine dogs presenting severe congenital PVS using a 1.5T MRI scanner. T1-MOLLI, T2-prepared-bSSFP, gated-cine GRE-MRE and LGE (PSIR) sequences were used to acquire a basal short-axis slice. RV and LV-free-wall (FW) stiffness measurements were compared against each other and also correlated to ventricular mass, RV and LV FW thickness, T1 and T2 relaxation times, and extracellular volume fraction (ECV). Peak transpulmonary pressure gradient and myocardial strain were also acquired on eight dogs by TTE and correlated to RV-FW systolic stiffness. Potential correlations were evaluated by Spearman's rho (rs). ResultsRV-FW stiffness was found to be significantly higher than the LV-FW stiffness both during end-systole (ES) (p=0.002) and end-diastole (ED) (p=0.029). Significant correlations were observed between RV-FW ES and LV-FW ED stiffness versus ECV (rs=0.75; p-value=0.05). Non-significant moderate correlations were found between LV-FW ES (rs=0.54) and RV-FW ED (rs=0.61) stiffness versus ECV. Furthermore, non-significant correlations were found between RV or LV-FW stiffness and the remaining variables (rs<0.54; p-value>0.05). ConclusionThis study demonstrates the feasibility of determining RV stiffness. The positive correlations between stiffness and ECV might indicate some interdependence between stiffness and myocardial extracellular matrix alterations. However, further studies are warranted to validate our initial observations.

Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs

We previously demonstrated a markedly dependent distribution of ventilator-induced lung injury in oleic acid-injured supine animals ventilated with large tidal volumes and positive end-expiratory pressure > or =10 cm H2O. Because pleural pressure distributes more uniformly in the prone position, we hypothesized that the extent of injury induced by purely mechanical forces applied to the lungs of normal animals might improve and that the distribution of injury might be altered with prone positioning. To compare the extent and distribution of histologic changes and edema resulting from identical patterns of high end-inspiratory/low end-expiratory airway pressures in both supine and prone normal dogs. We ventilated 10 normal dogs (5 prone, 5 supine) for 6 hrs with identical ventilatory patterns (a tidal volume that generated a peak transpulmonary pressure of 35 cm H2O when implemented in the supine position before randomization, positive end-expiratory pressure = 3 cm H2O). Ventilator-induced lung injury was assessed by gravimetric analysis and histologic grading. Wet weight/dry weight ratios (WW/DW) and histologic scores were greater in the supine than the prone group (8.8+/-2.8 vs. 6.1+/-0.7; p = .01 and 1.4+/-0.3 vs. 1+/-0.3; p = .037, respectively). In the supine group, WW/DW and histologic scores were significantly greater in dependent than nondependent regions (9.4+/-1.9 vs. 6.7+/-0.9; p = .01 and 2.0+/-0.4 vs. 0.9+/-0.4; p = .043, respectively). In the prone group, WW/DW also was greater in dependent regions (6.7+/-1.1 vs. 5.8+/-0.5; p = .054), but no significant differences were found in histologic scores between dependent and nondependent regions (p = .42). In this model of lung injury induced solely by mechanical forces, the prone position resulted in a less severe and more homogeneous distribution of ventilator-induced lung injury. These results parallel those previously obtained in oleic acid-preinjured animals ventilated with higher positive end-expiratory pressure.

MECHANICAL VENTILATION OF PATIENTS WITH ACUTE LUNG INJURY

Ventilatory management of patients with acute lung injury (ALI), particularly its most severe subset, acute respiratory distress syndrome (ARDS), is complex. Newer lung protective strategies emphasize measures to enhance alveolar recruitment and avoid alveolar overdistention, thus minimizing the risk of ventilator-induced lung injury (VILI). Key components of such strategies include the use of smaller-than-conventional tidal volumes which maintain peak transpulmonary pressure below the pressure associated with overdistention, and titration of positive end-expiratory pressure to promote maximal alveolar recruitment. Novel techniques, including prone positioning, inverse ratio ventilation, tracheal gas insufflation, and high frequency ventilation, are considerations in severe ARDS. No single approach is best for all patients; adjustment of ventilatory parameters to individual characteristics, such as lung mechanics and gas exchange, is required.

Mechanisms of cigarette smoke-induced stimulation of rapidly adapting receptors in canine lungs

The stimulation of rapidly adapting receptors (RARs) in the lungs evoked by cigarette smoke consists of an initial and either a type I or a type II delayed response (Kou and Lee, J. Appl. Physiol. 68: 1203, 1990). In the type I response, receptor activity increased during expirations and exhibited a prominent cardiac modulation, whereas in the type II response, receptor discharge reached its peak during inspiration at peak transpulmonary pressure. To investigate the mechanisms of this stimulation, we recorded the vagal afferent activity arising from 39 RARs and delivered a single breath (120 ml) of cigarette smoke in 15 anesthetized, open-chest and artificially ventilated dogs. Studies were repeated after a pretreatment with aerosolized hexamethonium (3–8 breaths, 10%), aerosolized isoproterenol (12–15 breaths, 2%), or after the cardiac impact on the lung had been minimized by elevating the apex of the heart. The initial response of RARs was totally abolished by hexamethonium but was not affected by isoproterenol. The increase of total lung resistance induced by cigarette smoke and the concomitant type II delayed response of RARs were both abolished by isoproterenol. The type I delayed response of RARs was eliminated or largely attenuated after the apex of the heart had been elevated. Based upon these results, we conclude that a direct effect of nicotine on these receptors may be responsible for the immediate stimulation while the systemic effects of absorbed nicotine may play a part in evoking the delayed stimulation.

Neonatal gastric intubation: Differential respiratory effects between nasogastric and orogastric tubes

The acute effects of nasogastric (NG) and orogastric (OG) tube placement on pulmonary function of neonates was assessed as a function of infant weight. Lung function was obtained on 14 healthy infants weighing less than 2 kg and 10 infants heavier than 2 kg with an NG and an OG tube in place. Additionally, 15 infants were studied for a third time without gastric intubation. Lung function was determined with an esophageal balloon and by pneumotachography (PeDS) via the least mean square analysis technique. Neither the below-2 kg infants nor the above-2 kg infants had apparent clinical compromise with NG and OG tube placement. Infants weighing less than 2 kg, however, demonstrated diminished minute ventilation and respiratory rate and had increased pulmonary resistance, resistive work of breathing, and peak transpulmonary pressure change with NG tube, as compared to OG tube, placement. The above-2 kg infants demonstrated no change in pulmonary function with NG vs. OG tube placement. These data indicate that small neonates demonstrate significant pulmonary compromise with NG placement that may not be clinically apparent.

Assessment of Spontaneous Ventilation in Anesthetized Children with Use of a Pediatric Circle or a Jackson-Rees System

To compare respiratory workloads, inspiratory efforts were evaluated in 11 children anesthetized with halothane while breathing through a pediatric circle or a Jackson-Rees system. All underwent urogenital surgery and received caudal analgesia after tracheal intubation. Anesthesia was maintained with O2/air at an end-tidal halothane concentration of 0.8%. A pediatric circle system at a fresh gas flow (FGF) of 0.5 and 1.5 x min ventilation (VE) (C0.5 and C1.5, respectively) and a Jackson-Rees system at FGF of 1.5 and 3.0 x VE (JR1.5 and JR3.0, respectively) were used in each patient in a random order. Tidal volume (VT), mean inspiratory flow (VT divided by the duration of inspiration TI, VT/TI), and the initial fast slopes of the airway occlusion pressure phase (delta P degrees/delta t FAST) were significantly lower (P less than 0.05) with the Jackson-Rees than with the circle system, indicating greater impedence to spontaneous breathing with the Jackson-Rees system. The Jackson-Rees system also required a greater peak transpulmonary pressure (PtpMAXe) than did the circle system to achieve the same peak expiratory flows (VMAXe, P less than 0.05), again suggesting an increased resistance with the Jackson-Rees system. These results are most likely explained by the difference in elastic loads (two to three times more with the Jackson-Rees systems) between the two systems. The pediatric circle system appears to be a reliable alternative to the Jackson-Rees system.

Effect of nicotine aerosol on slowly adapting receptors in the airways of the dog.

The response of slowly adapting airway stretch receptors to nicotine aerosol was studied in the paralyzed, artificially ventilated, anesthetized dog. Single-unit stretch receptor recordings were made from individual vagus nerve filaments placed on a pair of platinum hook electrodes. Administration of 2% nicotine aerosol for five consecutive breaths caused an increase in both the peak transpulmonary pressure (Ptp) and in the activity of the slowly adapting stretch receptors (SARs). The results suggest that tracheal SARs were more affected than those receptors located distal to the carina. Administration of nicotine aerosols following pretreatment with isoproterenol, a bronchodilator, failed to significantly increase Ptp and, concomitantly, the activity of SARs. Therefore, the stimulatory effect of nicotine on SARs appeared to involve primarily an indirect activation of SARs via nicotine-induced bronchoconstriction. It is suggested that the activation of SARs may be involved in the reported nicotine-dependent cigarette smoke-induced apnea.

PRETERM BABOONS WITH HYALINE MEMBRANE DISEASE (HMD) DEMONSTRATE SIGNIFICANT IMPROVEMENT IN OPENING AND PEAK PRESSURES BY THE THIRD DAY

Ventilated preterm baboons (140±2da) with HMD show a significant reduction in opening and peak pressures on pressure volume curves on the third day (74±2 hr) compared to initial studies (3±1hr). Thirteen preterm baboons (140±2da) were delivered by Cesarean section, resuscitated, and ventilated with a conventional neonatal ventilator (Bear Cub) or one of 2 high-frequency ventilators. After ketamine and succinylcholine intravenously the intubated animals were tested in a constant volume plethysmograph with an esophageal balloon in place. The inspiratory limb of the pressure volume curves at 0.5 Hz were analyzed for the opening pressure, defined as the pressure at the point of departure from an isovolumetric transpulmonary pressure change. The peak transpulmonary pressure was defined as the highest pressure required to ventilate the animal. Opening and peak pressures were significantly improved by the third day. Differences due to ventilator type were not apparent. Changes in opening and peak pressures may be a sensitive measure of improvement in HMD in preterm baboons.

Comparison of a Pressure and a Volume Cycled Respirator in Chronic Obstructive Lung Disease

A volume cycled (Engstrom) and a pressure cycled respirator (Bird Mark VII) were compared in 20 patients in chronic respiratory failure with a carbon dioxide tension (Pco₂) of over 50 mm Hg. The volume cycled respirator produced twice as great a reduction in Pco₂ (-7.5 mm Hg vs −3.5 mm Hg) and increase in oxygen tension (Pco₂ +8.3 mm Hg vs +3.6 mm Hg) as the pressure cycled respirator. With the volume cycled respirator the transpulmonary pressure and inspiratory flow changed rapidly, the peak inspiratory transpulmonary pressure occurring immediately after peak flow was reached. With the pressure cycled respirator transpulmonary pressure changed more slowly, peak inspiratory flow was less and peak transpulmonary pressure occurred at the end of inspiration. Peak mouth pressure was similar with both respirators (15 cm H₂O). The volume cycled respirator produced a significant increase in peak inspiratory flow and transpulmonary pressure and a decrease in pulmonary resistance while the only significant change with the pressure cycled respirator was an increase in peak expiratory flow.

THE EFFECTS OF INTERMITTENT POSITIVE PRESSURE VENTILATION ON LUNG FUNCTION IN HYALINE MEMBRANE DISEASE

SUMMARY Fifty-eight infants with hyaline membrane disease were admitted to an intensive care unit. Twenty of these developed respiratory failure despite bicarbonate and oxygen therapy. They were then treated by intermittent positive pressure ventilation and 13 of the 20 survived. The mechanism of IPPV was determined in 12 of these by the measurement of lung function and blood-gas tensions. Results indicated that a normal alveolar ventilation could be produced in these infants by a 50 per cent increase in their original minute volume. An adequate tidal volume (20 ml) could only be obtained by a high peak transpulmonary pressure (35 cm H 2 O) and this volume had to be delivered at a mean rate of 56 cycles per minute. A reduction in either transpulmonary pressure or the rate of cycling resulted in an inadequate alveolar ventilation and a precipitious fall in Pa o2 . Assisted breathing appeared to be more effective than passive ventilation over a short period of time. Measurements were made within 4 minutes of paralyzing the respiratory muscles, and must therefore be accepted with reserve.