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Background 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. Methods 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 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. Conclusions Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background The assessment of diaphragm function with diaphragm ultrasound seems to bring important clinical information to describe diaphragm work and weakness. When the diaphragm is weak, extradiaphragmatic muscles may play an important role, but whether ultrasound can also assess their activity and function is unknown. This study aimed to (1) evaluate the feasibility of measuring the thickening of the parasternal intercostal and investigate the responsiveness of this muscle to assisted ventilation; and (2) evaluate whether a combined evaluation of the parasternal and the diaphragm could predict failure of a spontaneous breathing trial. Methods First, an exploratory evaluation of the parasternal in 23 healthy subjects. Second, the responsiveness of parasternal to several pressure support levels were studied in 16 patients. Last, parasternal activity was compared in presence or absence of diaphragm dysfunction (assessed by magnetic stimulation of the phrenic nerves and ultrasound) and in case of success/failure of a spontaneous breathing trial in 54 patients. Results The parasternal was easily accessible in all patients. The interobserver reproducibility was good (intraclass correlation coefficient, 0.77 (95% CI, 0.53 to 0.89). There was a progressive decrease in parasternal muscle thickening fraction with increasing levels of pressure support (Spearman ρ = −0.61 [95% CI, −0.74 to −0.44]; P < 0.0001) and an inverse correlation between parasternal muscle thickening fraction and the pressure generating capacity of the diaphragm (Spearman ρ = −0.79 [95% CI, −0.87 to −0.66]; P < 0.0001). The parasternal muscle thickening fraction was higher in patients with diaphragm dysfunction: 17% (10 to 25) versus 5% (3 to 8), P < 0.0001. The pressure generating capacity of the diaphragm, the diaphragm thickening fraction and the parasternal thickening fraction similarly predicted failure or the spontaneous breathing trial. Conclusions Ultrasound assessment of the parasternal intercostal muscle is feasible in the intensive care unit and provides novel information regarding the respiratory capacity load balance. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background In supine patients with acute respiratory distress syndrome, the lung typically partitions into regions of dorsal atelectasis and ventral aeration (“baby lung”). Positive airway pressure is often used to recruit atelectasis, but often overinflates ventral (already aerated) regions. A novel approach to selective recruitment of dorsal atelectasis is by “continuous negative abdominal pressure.” Methods A randomized laboratory study was performed in anesthetized pigs. Lung injury was induced by surfactant lavage followed by 1 h of injurious mechanical ventilation. Randomization (five pigs in each group) was to positive end-expiratory pressure (PEEP) alone or PEEP with continuous negative abdominal pressure (−5 cm H2O via a plexiglass chamber enclosing hindlimbs, pelvis, and abdomen), followed by 4 h of injurious ventilation (high tidal volume, 20 ml/kg; low expiratory transpulmonary pressure, −3 cm H2O). The level of PEEP at the start was ≈7 (vs. ≈3) cm H2O in the PEEP (vs. PEEP plus continuous negative abdominal pressure) groups. Esophageal pressure, hemodynamics, and electrical impedance tomography were recorded, and injury determined by lung wet/dry weight ratio and interleukin-6 expression. Results All animals survived, but cardiac output was decreased in the PEEP group. Addition of continuous negative abdominal pressure to PEEP resulted in greater oxygenation (Pao2/fractional inspired oxygen 316 ± 134 vs. 80 ± 24 mmHg at 4 h, P = 0.005), compliance (14.2 ± 3.0 vs. 10.3 ± 2.2 ml/cm H2O, P = 0.049), and homogeneity of ventilation, with less pulmonary edema (≈10% less) and interleukin-6 expression (≈30% less). Conclusions Continuous negative abdominal pressure added to PEEP reduces ventilator-induced lung injury in a pig model compared with PEEP alone, despite targeting identical expiratory transpulmonary pressure.

Background Dual-control modes of ventilation adapt the pressure delivery to keep a volume target in response to changes in respiratory mechanics, but they may respond poorly to changes in ventilatory demand. Adaptive support ventilation (ASV), a complex minute volume-targeted pressure-regulated ventilation, was compared to adaptive pressure ventilation (APV), a dual-mode in which the pressure level is adjusted to deliver a preset tidal volume, and to pressure support ventilation (PSV) when facing an increase in ventilatory demand. Methods A total of 14 intensive care unit patients being weaned off mechanical ventilation were included in this randomized crossover study. The effect of adding a heat-and-moisture exchanger to augment circuit dead space was assessed with a same fixed level of ASV, PSV, and APV. Results Arterial blood gases, ventilator response, and patient respiratory effort parameters were evaluated at the end of the six periods. Adding dead space significantly increased minute ventilation and PaCO2 values with the three modes. Indexes of respiratory effort (pressure-time index of respiratory muscles and work of breathing) increased with all ventilatory modes after dead-space augmentation. This increase was significantly greater with APV than with PSV or ASV (P < 0.05). The assistance delivered during APV decreased significantly with dead-space from 12.7 +/- 2.6 to 6.7 +/- 1.4 cm H2O, whereas no change occurred with ASV and PSV. Conclusions ASV and PSV behaved differently but ended up with similar pressure level facing acute changes in ventilatory demand, by contrast to APV (a simple volume-guaranteed pressure-control mode), in which an increase in ventilatory demand results in a decrease in the pressure support provided by the ventilator.

Background Alveolar recruitment in response to positive end-expiratory pressure (PEEP) may differ between pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS), and alveolar recruitment values may differ when measured by pressure-volume curve compared with static compliance. Methods The authors compared PEEP-induced alveolar recruitment in 71 consecutive patients identified in a database. Patients were classified as having pulmonary, extrapulmonary, or mixed/uncertain ARDS. Pressure-volume curves with and without PEEP were available for all patients, and pressure-volume curves with two PEEP levels were available for 44 patients. Static compliance was calculated as tidal volume divided by pressure change for tidal volumes of 400 and 700 ml. Recruited volume was measured at an elastic pressure of 15 cm H2O. Results Volume recruited by PEEP (10 +/- 3 cm H2O) was 223 +/- 111 ml in the pulmonary ARDS group (29 patients), 206 +/- 164 ml in the extrapulmonary group (16 patients), and 242 +/- 176 ml in the mixed/uncertain group (26 patients) (P = 0.75). At high PEEP (14 +/- 2 cmH2O, 44 patients), recruited volumes were also similar (P = 0.60). With static compliance, recruitment was markedly underestimated and was dependent on tidal volume (226 +/- 148 ml using pressure-volume curve, 95 +/- 185 ml for a tidal volume of 400 ml, and 23 +/- 169 ml for 700 ml; P < 0.001). Conclusion In a large sample of patients, classification of ARDS was uncertain in more than one third of patients, and alveolar recruitment was similar in pulmonary and extrapulmonary ARDS. PEEP levels should not be determined based on cause of ARDS.

Background Accumulation of mucous secretions in an endotracheal tube (ETT) increases its resistance, and the amount of deposit may be affected by the quality of humidification and heating of the inspired gas. Methods The authors assessed the impact of two humidification systems, a heated humidifier (HH) and a hygroscopic-hydrophobic heat and moisture exchanger (HME), on the ETT patency in patients selected to require mechanical ventilation for more than 48 h. This comparison was performed over two consecutive periods and used the acoustic reflection method, which characterizes the amount and site of ETT obstruction and allows estimating ETT inner volume and resistance. Measurements were performed three times a week over the period of mechanical ventilation. Comparisons were performed at mid duration and at the end of the mechanical ventilation period. Results The HH was used in 34 patients, and the HME was used in 26 patients. The two groups had similar severity and duration of mechanical ventilation. At mid duration of mechanical ventilation (5.5 +/- 3.3 vs. 4.8 +/- 3.3 days; P = 0.4), no difference was observed in ETT volume and resistance between the two groups. At the end of the study period (10.5 +/- 5.8 vs. 9.6 +/- 6.3 days of mechanical ventilation; P = 0.4), ETT volume was reduced to a greater extent with HME than with HH (-3.3 +/- 2.9 vs. -5.1 +/- 2.5%; P = 0.008), and ETT resistance increased significantly more with the HME than with the HH (8.4 +/- 12.2 vs. 19.4 +/- 17.7%; P = 0.001). Conclusion Prolonged use of humidification systems results in progressive reduction of ETT patency, and to a greater extent with HMEs than with HHs.

Background Although the use of external positive end-expiratory pressure (PEEP) is recommended for patients with intrinsic PEEP, no simple method exists for bedside titration. We hypothesized that the occlusion pressure, measured from airway pressure during the phase of ventilator triggering (P0.1t), could help to indicate the effects of PEEP on the work of breathing (WOB). Methods Twenty patients under assisted ventilation with chronic obstructive pulmonary disease were studied with 0, 5, and 10 cm H2O of PEEP while ventilated with a fixed level of pressure support. Results PEEP 5 significantly reduced intrinsic PEEP (mean +/- SD, 5.2 +/- 2.4 cm H2O at PEEP 0 to 3.6 +/- 1.9 at PEEP 5; P < 0.001), WOB per min (12. 6 +/- 6.7 J/min to 9.1 +/- 5.9 J/min; P = 0.003), WOB per liter (1.2 +/- 0.4 J/l to 0.8 +/- 0.4 J/l; P < 0.001), pressure time product of the diaphragm (216 +/- 86 cm H2O. s-1. min-1 to 155 +/- 179 cm H2O. s-1. min-1; P = 0.001) and P0.1t (3.3 +/- 1.5 cm H2O to 2.3 +/- 1.4 cm H2O; P = 0.002). At PEEP 10, no further significant reduction in muscle effort nor in P0.1t (2.5 +/- 2.1 cm H2O) occurred, and transpulmonary pressure indicated an increase in end-expiratory lung volume. Significant correlations were found between WOB per min and P0.1t at the three levels of PEEP (P < 0.001), and between the changes in P0.1t versus the changes in WOB per min (P < 0.005), indicating that P0.1t and WOB changed in the same direction. A decrease in P0.1 with PEEP indicated a decrease in intrinsic PEEP with a specificity of 71% and a sensitivity of 88% and a decrease in WOB with a specificity of 86% and a sensitivity of 91%. Conclusion These results show that P0.1t may help to assess the effects of PEEP in patients with intrinsic PEEP.

Background During experimental cardiac arrest, continuous insufflation of air or oxygen (CIO) through microcannulas inserted into the inner wall of a modified intubation tube and generating a permanent positive intrathoracic pressure, combined with external cardiac massage, has previously been shown to be as effective as intermittent positive pressure ventilation (IPPV). Methods After basic cardiorespiratory resuscitation, the adult patients who experienced nontraumatic, out-of-hospital cardiac arrest with asystole, were randomized to two groups: an IPPV group tracheally intubated with a standard tube and ventilated with standard IPPV and a CIO group for whom a modified tube was inserted, and in which CIO at a flow rate of 15 l/min replaced IPPV (the tube was left open to atmosphere). Both groups underwent active cardiac compression-decompression with a device. Resuscitation was continued for a maximum of 30 min. Blood gas analysis was performed as soon as stable spontaneous cardiac activity was restored, and a second blood gas analysis was performed at admission to the hospital. Results The two groups of patients (47 in the IPPV and 48 in the CIO group) were comparable. The percentages of patients who underwent successful resuscitation (stable cardiac activity; 21.3 in the IPPV group and 27.1% in the CIO group) and the time necessary for successful resuscitation (11.8 +/- 1.8 and 12.8 +/- 1.9 min) were also comparable. The blood gas analysis performed after resuscitation (8 patients in the IPPV and 10 in the CIO group) did not show significant differences. The arterial blood gases performed after admission to the hospital and ventilation using a transport ventilator (seven patients in the IPPV group and six in the CIO group) showed that the partial pressure of arterial carbon dioxide (PaCO2) was significantly lower in the CIO group (35.7 +/- 2.1 compared with 72.7 +/- 7.4 mmHg), whereas the pH and the partial pressure of arterial oxygen (PaO2) were significantly higher (all P < 0.05). Conclusions Continuous insufflation of air or oxygen alone through a multichannel open tube was as effective as IPPV during out-of-hospital cardiac arrest. A significantly greater elimination of carbon dioxide and a better level of oxygenation in the group previously treated with CIO probably reflected better lung mechanics.

Background Pressure-controlled (PCV) and pressure-controlled inverse ratio ventilation (PCIRV) have been proposed instead of volume-controlled conventional ratio ventilation (VC) with positive end-expiratory pressure (PEEP) for patients with adult respiratory distress syndrome (ARDS). The advantages advocated with the use of PCIRV are to decrease airway pressures and to improve gas exchange. However, most studies did not compare PCIRV and VC while keeping both the level of ventilation and end-expiratory alveolar pressure (total-PEEP) constant. Methods Nine patients with moderate to severe ARDS (lung injury score 2.83 +/- 0.18) had their lungs ventilated with VC, PCV with a conventional ratio (I:E 1:2; PC 1/2), and PCIRV (I:E 2:1 and 3:1; PC 2/1 and PC 3/1, respectively). Ventilator settings were adjusted to keep tidal volume, respiratory rate, FIo2, and total-PEEP constant in every mode. With each mode, a complete set of ventilatory, hemodynamic, and gas exchange parameters was obtained after 30 min. Results In PC 3/1, the data obtained could not be strictly compared to the other modes because total-PEEP was higher despite external-PEEP being set at zero. For the other modes (VC, PC 1/2, and PC 2/1), despite differences in peak airway pressures, no difference was noted for end-inspiratory and end-expiratory static airway pressures (which better reflect alveolar pressures) nor for lung and respiratory system compliance. Arterial oxygenation deteriorated slightly with PC 2/1 despite a higher mean airway pressure, whereas alveolar ventilation tended to be slightly, but not significantly, improved (lower PaCo2). A decrease in systolic and mean arterial pressure also was observed with PC 2/1 without other significant hemodynamic change. Conclusions In this prospective controlled study, no short-term beneficial effect of PCV or PCIRV could be demonstrated over conventional VC with PEEP in patients with ARDS.

Breathing through an endotracheal tube and a demand valve may increase the work performed by the respiratory muscles. Inspiratory pressure support (PS) is known to reduce this work and might therefore compensate for this increased requirement. To test this hypothesis, we measured the work of breathing (WOB) in 11 patients whose tracheas were intubated. Five had no intrinsic lung disease, but six had chronic obstructive lung disease. We compared WOB measurements taken under several sets of conditions: during assisted breathing at four levels of PS, during unassisted breathing and connection to a T-piece, and after extubation of the trachea. During unassisted breathing via the ventilator circuit (PS set at 0 cmH20), the WOB per minute was greater than that after extubation, with a mean increase (+/- standard deviation) of 68 +/- 38% (10.3 +/- 5.1 vs. 6.5 +/- 3.7 J.min-1, P less than 0.01). While breathing through the T-piece, the WOB was 27 +/- 18% greater than after tracheal extubation (8.2 +/- 5.1 vs. 6.5 +/- 3.7 J.min-1, P less than 0.05). The principal reason why inspiratory work decreased after extubation was that the ventilatory requirement decreased. For each patient, we determined retrospectively, after extubation, the level of PS that had reduced WOB to its postextubation value and obtained levels ranging from 3.4 to 14.4 cmH2O. The PS level at which additional WOB was compensated for, was greater in patients with chronic lung disease than in those free of lung disease (12.0 +/- 1.9 vs. 5.7 +/- 1.5 cm H2O, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Background The morphologic effect of positive end-expiratory pressure (PEEP) and of two tidal volumes were studied by computed tomography to determine whether setting the tidal volume (Vt) at the upper inflection point (UIP) of the pressure-volume (P-V) curve of the respiratory system or 10 ml/kg have different effects on hyperinflation and alveolar recruitment. Methods Alveolar recruitment and hyperinflation were quantified by computed tomography in nine patients with the acute respiratory distress syndrome (ARDS). First, end expiration was compared without PEEP and with PEEP set at the lower inflection point of the P-V curve; second, at end inspiration above PEEP, a reduced Vt set at the UIP (rVt) and a standard 10 ml/kg Vt (Vt) ending above the UIP were compared. Three lung zones were defined from computed tomographic densities: hyperdense, normal, and hyperinflated zones. Results Positive end-expiratory pressure induced a significant decrease in hyperdensities (from 46.8 +/- 18% to 38 +/- 15.1% of zero end-expiratory pressure (ZEEP) area; P < 0.02) with a concomitant increase in normal zones (from 47.3 +/- 20.9% to 56.5 +/- 13.2% of the ZEEP area; P < 0.05), and a significant increase in hyperinflation (from 8.1 +/- 5.9% to 17.8 +/- 12.7% of ZEEP area; P < 0.01). At end inspiration, a significant increase in hyperinflated areas was observed with Vt compared with rVt (33.4 +/- 17.8 vs. 26.8 +/- 17.3% of ZEEP area; P < 0.05), whereas no significant difference was observed for both normal and hyperdense zones. Conclusions Positive end-expiratory pressure promotes alveolar recruitment; increasing Vt above the UIP seems to predominantly increase hyperinflation.

Background Limited data suggest that increased resistance to flow within endotracheal tubes (ETT) may occur in patients whose lungs are mechanically ventilated for more than 48 h, especially when airway humidification is inadequate. This could lead to sudden ETT obstruction or induce excessive loading during spontaneous breathing. Methods Twenty-three such patients were randomly assigned to three types of airway humidifier based on three different working principles: a Fisher Paykell hot water system (n = 7), a Pall BB2215 heat and moisture exchanger (HME) hydrophobic filter (n = 8), and a Dar Hygrobac 35254111 HME hygroscopic filter (n = 8). The decrease in internal pressure along the ETT and the flow rate were measured in each patient every 2 days. An "effective inner diameter" was derived from these measurements and allowed the inner ETT configuration to be monitored. Results On the first day of intubation, the mean diameter was similar in the three groups, and was slightly smaller than the in vitro diameter (mean +/- SD: 7.6 +/- 0.6 mm for Fisher-Paykell, 7.7 +/- 0.4 for Pall, and 7.5 +/- 0.4 for Dar). The mean diameter tended to decrease from day to day. At the end of the study, the overall reduction in mean diameter was significantly greater with the hydrophobic HME (Pall) than with the two other systems (Pall: -6.5 +/- 4% vs. 2.5 +/- 2.5% for Dar and 1.5 +/- 3% for Fisher-Paykell; P < 0.01 with analysis of variance). The same was true of the mean reduction in effective inner ETT diameter expressed per day of ventilation (-1.6 +/- 1.5% per day for Pall vs. -0.5 +/- 0.4% for Dar and -0.2 +/- 0.4% for Fisher-Paykell; P < 0.01). In four patients, the ETT became obstructed and emergency repeated tracheal intubation was required. The Pall HME and the Fisher-Paykell system were being used in three and one patient, respectively. Before obstruction, the reduction in ETT diameter was significantly greater for these four patients than for the remaining 23 patients (7.8 +/- 1.4% vs. 3.1 +/- 4.1%; P < 0.01). Conclusions During prolonged mechanical ventilation, significant alterations in inner ETT configuration occur frequently and are influenced by the type of humidification device used. In vivo monitoring of ETT mechanical properties might be clinically useful.

Background Although evidence suggests that secretions lining the inner wall of the endotracheal tube (ETT) often reduce its cross-sectional area, no data are available on the work of breathing as affected by the ETT. A noninvasive method is proposed for estimating the additional work of breathing necessitated by the ETT in patients whose lungs are mechanically ventilated. This method (the acoustic-Blasius method) involves (1) determining the inner geometry of the ETT using the acoustic reflection method and (2) using these geometric data to solve the Blasius equation that characterizes the ETT pressure drop-flow relation. Methods To evaluate the acoustic-Blasius method in vivo, the authors computed the work of breathing due to the ETT in four healthy persons breathing through an ETT connected to a pressure-support device and in five tracheally intubated patients receiving mechanical assistance in the pressure-support mode. For the tracheally intubated patients, the reference value was the work calculated from the ETT pressure drop measured between the two ends of the ETT using a pressure catheter. Results In the healthy participants and the tracheally intubated patients, there was close agreement between inspiratory work per cycle values estimated by directly measuring the ETT pressure drop and calculated using the acoustic-Blasius method: The difference was consistently less than 0.08 joules (< 10% of the reference value). Conclusions The data show that the acoustic-Blasius method allows noninvasive quantification of the ETT-related work of breathing in situ.