Maurizio Cereda

Effects of periodic lung recruitment maneuvers on gas exchange and respiratory mechanics in mechanically ventilated acute respiratory distress syndrome (ARDS) patients.

Objective: We wished to investigate whether volume recruitment maneuvers (VRMs) could improve alveolar recruitment and oxygenation in acute respiratory distress syndrome (ARDS) patients, ventilated at relatively low positive end-expiratory pressure (PEEP). Setting: General intensive care unit (ICU) located in a teaching hospital. Patients: 15 PEEP responder ARDS patients undergoing continuous positive pressure ventilation (CPPV) with sedation and muscle paralysis. Interventions: We identified a low (9.4 ± 3 cmH2O) and a high (16.0 ± 2 cmH2O) level of PEEP associated with target oxygenation values. Using a custom modified mechanical ventilator, we applied in random order three steps lasting 30 min: (1) CPPV at the low PEEP level (CPPVlo); (2) CPPV at the high PEEP level (CPPVhi); (3) CPPV at low PEEP with the superimposition of periodic VRMs (CPPVvrm). VRMs were performed twice a minute by increasing PEEP to the high level for two breaths. Each brace of two breaths was spaced 30 seconds from the preceding one. Measurements and results: We measured gas exchange, hemodynamics, respiratory mechanics, and the end expiratory lung volume (EELV). Compared to CPPVlo, CPPVvrm resulted in higher PaO2 (117.9 ± 40.6 vs 79.4 ± 13.6 mmHg, P < 0.01) and EELV (1.50 ± 0.62 vs 1.26 ± 0.50 l, P < 0.05), and in lower venous admixture (Qva/Qt) (0.42 ± 0.07 vs 0.48 ± 0.07, P < 0.01). During CPPVhi, we observed significantly higher PaO2 (139.3 ± 32.5 mmHg) and lower Qva/Qt (0.37 ± 0.08) compared to CPPVlo (P < 0.01) and to CPPVvrm (P < 0.05). Conclusions: VRMs can improve oxygenation and alveolar recruitment during CPPV at relatively low PEEP, but are relatively less effective than a continuous high PEEP level.

Sigh improves gas exchange and lung volume in patients with acute respiratory distress syndrome undergoing pressure support ventilation.

Background The aim of our study was to assess the effect of periodic hyperinflations (sighs) during pressure support ventilation (PSV) on lung volume, gas exchange, and respiratory pattern in patients with early acute respiratory distress syndrome (ARDS). Methods Thirteen patients undergoing PSV were enrolled. The study comprised 3 steps: baseline 1, sigh, and baseline 2, of 1 h each. During baseline 1 and baseline 2, patients underwent PSV. Sighs were administered once per minute by adding to baseline PSV a 3- to 5-s continuous positive airway pressure (CPAP) period, set at a level 20% higher than the peak airway pressure of the PSV breaths or at least 35 cm H2O. Mean airway pressure was kept constant by reducing the positive end-expiratory pressure (PEEP) during the sigh period as required. At the end of each study period, arterial blood gas tensions, air flow and pressures traces, end-expiratory lung volume (EELV), compliance of respiratory system (Crs), and ventilatory parameters were recorded. Results Pao2 improved (P < 0.001) from baseline 1 (91.4 ± 27.4 mmHg) to sigh (133 ± 42.5 mmHg), without changes of Paco2. EELV increased (P < 0.01) from baseline 1 (1,242 ± 507 ml) to sigh (1,377 ± 484 ml). Crs improved (P < 0.01) from baseline 1 (40.2 ± 12.5 ml/cm H2O) to sigh (45.1 ± 15.3 ml/cm H2O). Tidal volume of pressure-supported breaths and the airway occlusion pressure (P0.1) decreased (P < 0.01) during the sigh period. There were no significant differences between baselines 1 and 2 for all parameters. Conclusions The addition of 1 sigh per minute during PSV in patients with early ARDS improved gas exchange and lung volume and decreased the respiratory drive.

Continuous Positive Airway Pressure via the Boussignac System Immediately after Extubation Improves Lung Function in Morbidly Obese Patients with Obstructive Sleep Apnea Undergoing Laparoscopic Bariatric Surgery

Background:Morbidly obese patients are at elevated risk of perioperative pulmonary complications, including airway obstruction and atelectasis. Continuous positive airway pressure may improve postoperative lung mechanics and reduce postoperative complications in patients undergoing abdominal surgery. Methods:Forty morbidly obese patients with known obstructive sleep apnea undergoing laproscopic bariatric surgery with standardized anesthesia care were randomly assigned to receive continuous positive airway pressure via the Boussignac system immediately after extubation (Boussignac group) or supplemental oxygen (standard care group). All subjects had continuous positive airway pressure initiated 30 min after extubation in the postanesthesia care unit via identical noninvasive ventilators. The primary outcome was the relative reduction in forced vital capacity from baseline to 24 h after extubation. Results:Forty patients were enrolled into the study, 20 into each group. There were no significant differences in baseline characteristics between the groups. The intervention predicted less reduction in all measured lung functions: forced expiratory volume in 1 s (coefficient 0.37, SE 0.13, P = 0.003, CI 0.13–0.62), forced vital capacity (coefficient 0.39, SE 0.14, P = 0.006, CI 0.11–0.66), and peak expiratory flow rate (coefficient 0.82, SE 0.31, P = 0.008, CI 0.21–0.1.4). Conclusions:Administration of continuous positive airway pressure immediately after extubation maintains spirometric lung function at 24 h after laparoscopic bariatric surgery better than continuous positive airway pressure started in the postanesthesia care unit.

Pressure support ventilation in patients with acute lung injury.

Objectives: To assess the success rate of pressure support ventilation (PSV) in acute lung injury patients undergoing continuous positive pressure ventilation (CPPV), to study physiologic changes after the transition from CPPV to PSV, and to investigate differences between patients who succeed and patients who fail PSV according to predetermined criteria. Design: Observational study. Setting: General intensive care unit in a teaching hospital. Subjects: We studied 48 patients having acute lung injury, as defined by a PaO2/FIO2 <300 mm Hg and the presence of bilateral infiltrates on chest radiograph, and ventilated with CPPV. We included patients with PaO2 >80 mm Hg, at positive end‐expiratory pressure of <15 cm H2O and with FIO2 up to 1.0. Interventions: After enrollment, PSV was instituted and patients were strictly monitored during the following 48 hrs. Subjects who met any of the predefined PSV failure criteria during this period were returned to CPPV (Group F). PSV was continued in the remaining patients (Group S). Measurements and Main Results: Gas exchange, respiratory mechanics, and hemodynamics measurements were collected before switching from CPPV to PSV and were repeated at 24 hrs after beginning PSV, or immediately before return to CPPV in Group F patients. The physiologic deadspace volume to tidal volume ratio (VD/VT) was obtained by the Enghoffs equation from the measurement of the mixed expired CO2 fraction. PSV resulted in a significant PaCO2 decrease (49.2 ± 10.9 mm Hg to 44.4 ± 7.2 mm Hg) and significant increases in minute volume (&OV0312;E) (9.0 ± 2.3 L/min to 12.0 ± 4.0 L/min) and arterial blood pH (7.405 ± 0.054 to 7.435 ± 0.064), with stable oxygenation and hemodynamics. In patients who were hypercapnic (PaCO2 >50 mm Hg) during CPPV, the &OV0312;E increase was higher than in normocapnic patients. In the latter patients, PaCO2 and pH did not change significantly going from CPPV to PSV. A total of 38 patients (79%) were allocated to Group S and the remaining 10 patients were included in Group F. In Group S, positive endexpiratory pressure of 9.4 ± 2.9 cm H2O (range, 3‐14 cm H2O) and a PSV level of 14.9 ± 3.8 cm H2O (range, 9‐22 cm H2O) were applied. In Group F, positive end‐expiratory pressure of 8.9 ± 3.1 cm H2O (range, 5‐15 cm H2O) and a PSV level of 21.6 ± 4.6 cm H2O (range, 16‐31 cm H2O) were adopted. Compared with Group S, Group F had a longer duration of intubation (20.2 ± 19.2 days vs. 9.2 ± 13.5 days), a lower static compliance of the respiratory system (30.4 ± 16.5 mL/cm H2O vs. 41.7 ± 15.0 mL/cm H2O), and a higher VD/VT (0.70 ± 0.09 vs. 0.52 ± 0.10), but similar oxygenation and positive end‐expiratory pressure. &OV0312;E was higher in Group F during both CPPV and PSV. Conclusions: In a relatively high proportion of the investigated patients, PSV was successful. The institution of PSV led to no major changes in oxygenation or in hemodynamics. PSV was associated with increases in &OV0312;E and respiratory frequency. In patients who had been hypercapnic during CPPV, PaCO2 decreased despite a compensated pH. Compared with PSV success patients, patients who failed PSV appeared to be sicker, as shown by the higher duration of respiratory support, increased ventilatory needs, and decreased respiratory system compliance, despite similar arterial oxygenation and positive end‐expiratory pressure.

Effects of carbon dioxide insufflation for laparoscopic cholecystectomy on the respiratory system

The changes occurring in total respiratory system, lung and chest wall mechanics, lung volume and gas‐exchange during abdominal insufflation with carbon dioxide for laparoscopic cholecystectomy were studied. Using the technique of rapid airway occlusion during constant flow inflation together with an oesophageal balloon, we computed compliance and maximum resistance of the respiratory system, subsequently apportioning it into its lung and chest wall components. Maximum resistance of the respiratory system was further divided into airway resistance and the viscoelastic properties of the lung and the chest wall. In 10 patients (group 1), we measured respiratory system, lung and chest wall mechanics (compliance and resistance), functional residual capacity, end‐tidal carbon dioxide tension and oxygen saturation. In addition, arterial blood gas analysis and end‐tidal carbon dioxide tension were measured in a second group of 10 patients (group 2). Measurements, in both groups, were obtained in the reverse Trendelenburg position, at 15 min after the induction of anaesthesia, 5 min and 45 min after abdominal insufflation and at 15 min after abdominal deflation. Tidal volume, respiratory rate, inspiratory flow and the fraction of inspired oxygen were similar in both groups and maintained constant during the procedure. We found that abdominal carbon dioxide insufflation caused: a reduction in compliance of the respiratory system (both lung and chest wall components) and of functional residual capacity; a marked increase in the maximum resistance of the respiratory system (mainly due to increases in the viscoelastic properties of the lung and chest wall); no change in oxygenation, but an increase in the end‐tidal carbon dioxide tension (which was correlated closely with the arterial carbon dioxide tension). These changes were not affected by the duration of anaesthesia.

Sepsis-induced cholestasis, steatosis, hepatocellular injury, and impaired hepatocellular regeneration are enhanced in interleukin-6 -/- mice.

Objective:Hepatic dysfunction is an important but poorly understood component of sepsis. In severe sepsis, liver dysfunction is characterized by cholestasis, steatosis, hepatocellular injury, impaired regeneration, a decreased response to the cytokine interleukin-6, and high mortality. To determine whether loss of interleukin-6 activity caused hepatic dysfunction and mortality, we induced sepsis in wild-type (interleukin-6 +/+) and interleukin-6 knockout (interleukin-6 −/−) mice. We hypothesized that sepsis in interleukin-6 −/− mice would increase cholestasis, steatosis, hepatocellular injury, and mortality and impair hepatocyte regeneration. Design:Randomized prospective experimental study. Setting:University medical laboratory. Subjects:Male adolescent C57Bl6 interleukin-6 +/+ and interleukin-6 −/− mice. Interventions:Mild sepsis was induced using cecal ligation and single puncture (CLP). Severe, lethal sepsis was induced using cecal ligation and double puncture (2CLP). Some mice received recombinant human interleukin-6 at the time of CLP/2CLP. All animals were fluid resuscitated at the time of surgery and every 24 hrs thereafter. In survival cohorts, mortality at 16, 24, 48, and 72 hrs was recorded. In separate cohorts, surviving animals were killed at 24 and 48 hrs, and liver tissue was harvested. A separate cohort of mice received bromodeoxyuridine for detection of regeneration. Measurements and Main Results:2CLP was 100% fatal within the first 12 hrs in interleukin-6 −/− mice. Mortality from 2CLP in interleukin-6 +/+ mice before 24 hrs was nil but was 90% by 72 hrs. At 72 hrs, CLP was 40% fatal in interleukin-6 +/+ mice but 90% in interleukin-6 −/− mice. CLP induced cholestasis, steatosis, and hepatocellular injury in interleukin-6 −/−, but not interleukin-6 +/+, mice. Regeneration was absent following CLP in interleukin-6 −/− animals but occurred in interleukin-6 +/+ mice. Early administration of recombinant human interleukin-6 did not reverse abnormalities in interleukin-6 −/− mice. Conclusions:The absence of interleukin-6 is an important determinant of hepatic dysfunction and mortality in sepsis.

Noninvasive ventilation immediately after extubation improves lung function in morbidly obese patients with obstructive sleep apnea undergoing laparoscopic bariatric surgery.

BACKGROUND Noninvasive positive pressure ventilation (NIPPV) may improve postoperative lung function and reduce postoperative complications in patients undergoing abdominal surgery. The purpose of our study was to determine whether the timing of postoperative NIPPV affects lung function 1 day postoperatively. METHODS Forty morbidly obese patients with known obstructive sleep apnea undergoing laparoscopic bariatric surgery with standardized anesthesia care were randomly assigned to receive NIPPV immediately after tracheal extubation (immediate group) or supplemental oxygen (standard group). All patients had continuous positive airway pressure initiated 30 minutes after extubation in the postanesthesia care unit (PACU) via identical noninvasive ventilators. Spirometry was performed by a blinded observer in the perioperative holding area 1 hour after admission to the PACU and 1 day postoperatively. The primary outcome was the change in forced vital capacity (FVC) from baseline to 24 hours (FVC baseline-FVC 24 hours). RESULTS Forty patients, 20 in each group, were enrolled in the study. Forced expiratory volume in 1 second, FVC, and peak expiratory flow rate were significantly reduced in both groups from perioperative values throughout the study. At 24 hours, the intervention group had lost only 0.7 L FVC, versus 1.3 L for the intervention group (P = 0.0005). An analysis of covariance confirmed this and indicated that the immediate postoperative NIPPV better preserved spirometric function at 1 and 24 hours postoperatively. Specifically, the differences in the primary outcome were statistically significant. CONCLUSIONS NIPPV given immediately after extubation significantly improves spirometric lung function at 1 hour and 1 day postoperatively, compared with continuous positive airway pressure started in the PACU, in morbidly obese patients with obstructive sleep apnea undergoing laparoscopic bariatric surgery.

Imaging the interaction of atelectasis and overdistension in surfactant-depleted lungs.

Objective:Atelectasis and surfactant depletion may contribute to greater distension—and thereby injury—of aerated lung regions; recruitment of atelectatic lung may protect these regions by attenuating such overdistension. However, the effects of atelectasis (and recruitment) on aerated airspaces remain elusive. We tested the hypothesis that during mechanical ventilation, surfactant depletion increases the dimensions of aerated airspaces and that lung recruitment reverses these changes. Design:Prospective imaging study in an animal model. Setting:Research imaging facility. Subjects:Twenty-seven healthy Sprague Dawley rats. InterventionsSurfactant depletion was obtained by saline lavage in anesthetized, ventilated rats. Alveolar recruitment was accomplished using positive end-expiratory pressure and exogenous surfactant administration. Measurements and Main Results:Airspace dimensions were estimated by measuring the apparent diffusion coefficient of 3He, using diffusion-weighted hyperpolarized gas magnetic resonance imaging. Atelectasis was demonstrated using computerized tomography and by measuring oxygenation. Saline lavage increased atelectasis (increase in nonaerated tissue from 1.2% to 13.8% of imaged area, p < 0.001), and produced a concomitant increase in mean apparent diffusion coefficient (~33%, p < 0.001) vs. baseline; the heterogeneity of the computerized tomography signal and the variance of apparent diffusion coefficient were also increased. Application of positive end-expiratory pressure and surfactant reduced the mean apparent diffusion coefficient (~23%, p < 0.001), and its variance, in parallel to alveolar recruitment (i.e., less computerized tomography densities and heterogeneity, increased oxygenation). Conclusions:Overdistension of aerated lung occurs during atelectasis is detectable using clinically relevant magnetic resonance imaging technology, and could be a key factor in the generation of lung injury during mechanical ventilation. Lung recruitment by higher positive end-expiratory pressure and surfactant administration reduces airspace distension.

Quantitative imaging of alveolar recruitment with hyperpolarized gas MRI during mechanical ventilation

The aim of this study was to assess the utility of (3)He MRI to noninvasively probe the effects of positive end-expiratory pressure (PEEP) maneuvers on alveolar recruitment and atelectasis buildup in mechanically ventilated animals. Sprague-Dawley rats (n = 13) were anesthetized, intubated, and ventilated in the supine position ((4)He-to-O(2) ratio: 4:1; tidal volume: 10 ml/kg, 60 breaths/min, and inspiration-to-expiration ratio: 1:2). Recruitment maneuvers consisted of either a stepwise increase of PEEP to 9 cmH(2)O and back to zero end-expiratory pressure or alternating between these two PEEP levels. Diffusion MRI was performed to image (3)He apparent diffusion coefficient (ADC) maps in the middle coronal slices of lungs (n = 10). ADC was measured immediately before and after two recruitment maneuvers, which were separated from each other with a wait period (8-44 min). We detected a statistically significant decrease in mean ADC after each recruitment maneuver. The relative ADC change was -21.2 ± 4.1 % after the first maneuver and -9.7 ± 5.8 % after the second maneuver. A significant relative increase in mean ADC was observed over the wait period between the two recruitment maneuvers. The extent of this ADC buildup was time dependent, as it was significantly related to the duration of the wait period. The two postrecruitment ADC measurements were similar, suggesting that the lungs returned to the same state after the recruitment maneuvers were applied. No significant intrasubject differences in ADC were observed between the corresponding PEEP levels in two rats that underwent three repeat maneuvers. Airway pressure tracings were recorded in separate rats undergoing one PEEP maneuver (n = 3) and showed a significant relative difference in peak inspiratory pressure between pre- and poststates. These observations support the hypothesis of redistribution of alveolar gas due to recruitment of collapsed alveoli in presence of atelectasis, which was also supported by the decrease in peak inspiratory pressure after recruitment maneuvers.

Clearance of Mucus from Endotracheal Tubes during Intratracheal Pulmonary Ventilation

Background: Intratracheal pulmonary ventilation (ITPV) is a form of tracheal gas insufflation in which all gas emerges in a cephalad direction from the tip of a reverse‐thrust catheter positioned within an endotracheal tube. In vitro experiments have shown that this rapid gas flow, with 5 ml/h of normal saline added to the gas flow, continuously removes tracheal secretions from within the endotracheal tube. The authors evaluated its effectiveness to remove mucus in long‐term studies in sheep. Methods: Fourteen healthy sheep were tracheally intubated and ventilated for 3 days with ITPV or with volume‐controlled ventilation. Measurements were made of the total amount of secretions within the endotracheal tubes (weight gain), the protein content within the endotracheal tubes, and the increase in resistance to constant air flow. The structure of the airways was examined grossly and histologically. Three additional sheep were ventilated for 24 h with ITPV, and Evans Blue dye was added to the saline to assess the distribution of the infused saline. Results: There was significantly less mucus in endotracheal tubes of sheep ventilated with ITPV than with conventional ventilation, as shown by minimal weight gain (0.70 +/‐ 0.14 g vs. 2.44 +/‐ 0.81 g; P < 0.001), lower protein content (14.09 +/‐ 10.79 mg vs. 294.99 +/‐ 153.06 mg; P <0.001), and lower resistance to constant air flow (6.15 +/‐ 0.54 cm H2 O [center dot] l sup ‐1 [center dot] s sup ‐1 vs. 15.34 +/‐ 5.28 cm H2 O [center dot] l sup ‐1 [center dot] s sup ‐1; P < 0.001). Results of gross and histological examinations of the tracheas of animals in both groups were similar, and the tracheas were well preserved. More than 95% of the instilled saline was recovered during ITPV. Only traces of Evans Blue dye were found near the tip of the endotracheal tubes. Conclusion: Intratracheal pulmonary ventilation makes it possible to keep the endotracheal tubes of sheep ventilated for 3 days free of mucus without suctioning.