Clinical validation of a capnodynamic method for measuring end-expiratory lung volume in critically ill patients.

RATIONALE: End-expiratory lung volume (EELV) is reduced in mechanically ventilated patients, especially in pathologic conditions. The resulting heterogeneous distribution of ventilation increases the risk for ventilation induced lung injury. Clinical measurement of EELV however, remains difficult. OBJECTIVE: Validation of a novel continuous capnodynamic method based on expired carbon dioxide (CO2) kinetics for measuring EELV in mechanically ventilated critically-ill patients. METHODS: Prospective study of mechanically ventilated patients scheduled for a diagnostic computed tomography exploration. Comparisons were made between absolute and corrected EELVCO2 values, the latter accounting for the amount of CO2 dissolved in lung tissue, with the reference EELV measured by computed tomography (EELVCT). Uncorrected and corrected EELVCO2 was compared with total CT volume (density compartments between - 1000 and 0 Hounsfield units (HU) and functional CT volume, including density compartments of - 1000 to - 200HU eliminating regions of increased shunt. We used comparative statistics including correlations and measurement of accuracy and precision by the Bland Altman method. MEASUREMENTS AND MAIN RESULTS: Of the 46 patients included in the final analysis, 25 had a diagnosis of ARDS (24 of which COVID-19). Both EELVCT and EELVCO2 were significantly reduced (39 and 40% respectively) when compared with theoretical values of functional residual capacity (p < 0.0001). Uncorrected EELVCO2 tended to overestimate EELVCT with a correlation r2 0.58; Bias - 285 and limits of agreement (LoA) (+ 513 to - 1083; 95% CI) ml. Agreement improved for the corrected EELVCO2 to a Bias of - 23 and LoA of (+ 763 to - 716; 95% CI) ml. The best agreement of the method was obtained by comparison of corrected EELVCO2 with functional EELVCT with a r2 of 0.59; Bias - 2.75 (+ 755 to - 761; 95% CI) ml. We did not observe major differences in the performance of the method between ARDS (most of them COVID related) and non-ARDS patients. CONCLUSION: In this first validation in critically ill patients, the capnodynamic method provided good estimates of both total and functional EELV. Bias improved after correcting EELVCO2 for extra-alveolar CO2 content when compared with CT estimated volume. If confirmed in further validations EELVCO2 may become an attractive monitoring option for continuously monitor EELV in critically ill mechanically ventilated patients. TRIAL REGISTRATION: clinicaltrials.gov (NCT04045262).

Intraoperative open lung condition and postoperative pulmonary complications. A secondary analysis of iPROVE and iPROVE-O2 trials.

BACKGROUND: The preventive role of an intraoperative recruitment maneuver plus open lung approach (RM + OLA) ventilation on postoperative pulmonary complications (PPC) remains unclear. We aimed at investigating whether an intraoperative open lung condition reduces the risk of developing a composite of PPCs. METHODS: Post hoc analysis of two randomized controlled trials including patients undergoing abdominal surgery. Patients were classified according to the intraoperative lung condition as "open" (OL) or "non-open" (NOL) if PaO2 /FIO2 ratio was ≥ or <400 mmHg, respectively. We used a multivariable logistic regression model that included potential confounders selected with directed acyclic graphs (DAG) using Dagitty software built with variables that were considered clinically relevant based on biological mechanism or evidence from previously published data. PPCs included severe acute respiratory failure, acute respiratory distress syndrome, and pneumonia. RESULTS: A total of 1480 patients were included in the final analysis, with 718 (49%) classified as OL. The rate of severe PPCs during the first seven postoperative days was 6.0% (7.9% in the NOL and 4.4% in the OL group, p = .007). OL was independently associated with a lower risk for severe PPCs during the first 7 and 30 postoperative days [odds ratio of 0.58 (95% CI 0.34-0.99, p = .04) and 0.56 (95% CI 0.34-0.94, p = .03), respectively]. CONCLUSIONS: An intraoperative open lung condition was associated with a reduced risk of developing severe PPCs in intermediate-to-high risk patients undergoing abdominal surgery. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT02158923 (iPROVE), NCT02776046 (iPROVE-O2).

Perioperative Continuous Noninvasive Cardiac Output Monitoring in Cardiac Surgery Patients by a Novel Capnodynamic Method.

OBJECTIVES: To test the clinical performance of a novel continuous noninvasive cardiac output (CO) monitoring based on expired carbon dioxide kinetics in cardiac surgery patients. DESIGN: A prospective feasibility pragmatic clinical study. SETTING: A single-center, large community hospital. PARTICIPANTS: Thirty-two patients undergoing cardiac surgery were studied during the intraoperative (before cardiopulmonary bypass) and postoperative (in the intensive care unit before extubation) periods. INTERVENTIONS: CO was measured simultaneously by the continuous capnodynamic method and by transpulmonary thermodilution during changes in the patient's hemodynamic and/or respiratory conditions. MEASUREMENTS AND MAIN RESULTS: The current recommended comparative statistics for CO measurement methods were analyzed, including bias, precision, and percentage error obtained from Bland-Altman analysis, and concordance between methods obtained from the four-quadrant plot analysis to evaluate the trending ability. Bias ± limits of agreement and percentage error were -0.6 (-1.9 to +0.8; 95% CI of 3.73-5.25) L/min and 31% (n = 147 measurements) for the intraoperative period, -0.8 (-2.4 to +0.9; 95% CI of 3.03-5.21) L/min and 41% (n = 66) for the postoperative period, and -0.6 (-2.1 to +0.8; 95% CI of 3.74-5.00) L/min and 34% (n = 213) for the pooled data. The trending analysis obtained a concordance of 82% (n = 65) for the intraoperative and 71% (n = 24) for the early postoperative periods. Aggregation of both data sets gave a concordance of 79% (n = 89). CONCLUSIONS: The continuous capnodynamic method was reliable and in good agreement with the reference method, and had an accuracy and trending ability good enough to make it a possible future alternative for hemodynamic monitoring in the studied population of elective adult cardiac surgery patients.

Positive end-expiratory pressure individualization guided by continuous end-expiratory lung volume monitoring during laparoscopic surgery.

To determine whether end-expiratory lung volume measured with volumetric capnography (EELVCO2) can individualize positive end-expiratory pressure (PEEP) setting during laparoscopic surgery. We studied patients undergoing laparoscopic surgery subjected to Fowler (F-group; n = 20) or Trendelenburg (T-group; n = 20) positions. EELVCO2 was measured at 0° supine (baseline), during capnoperitoneum (CP) at 0° supine, during CP with Fowler (head up + 20°) or Trendelenburg (head down - 30°) positions and after CP back to 0° supine. PEEP was adjusted to preserve baseline EELVCO2 during and after CP. Baseline EELVCO2 was statistically similar to predicted FRC in both groups. At supine and CP, EELVCO2 decreased from baseline values in F-group [median and IQR 2079 (768) to 1545 (725) mL; p = 0.0001] and in T-group [2164 (789) to 1870 (940) mL; p = 0.0001]. Change in body position maintained EELVCO2 unchanged in both groups. PEEP adjustments from 5.6 (1.1) to 10.0 (2.5) cmH2O in the F-group (p = 0.0001) and from 5.6 (0.9) to 10.0 (2.6) cmH2O in T-group (p = 0.0001) were necessary to reach baseline EELVCO2 values. EELVCO2 increased close to baseline with PEEP in the F-group [1984 (600) mL; p = 0.073] and in the T-group [2175 (703) mL; p = 0.167]. After capnoperitoneum and back to 0° supine, PEEP needed to maintain EELVCO2 was similar to baseline PEEP in F-group [5.9 (1.8) cmH2O; p = 0.179] but slightly higher in the T-group [6.5 (2.2) cmH2O; p = 0.006]. Those new PEEP values gave EELVCO2 similar to baseline in the F-group [2039 (980) mL; p = 0.370] and in the T-group [2150 (715) mL; p = 0.881]. Breath-by-breath noninvasive EELVCO2 detected changes in lung volume induced by capnoperitoneum and body position and was useful to individualize the level of PEEP during laparoscopy.Trial registry: Clinicaltrials.gov NCT03693352. Protocol started 1st October 2018.

Comparison between capnodynamic and thermodilution method for cardiac output monitoring during major abdominal surgery: An observational study.

BACKGROUND: Cardiac output (CO) monitoring is the basis of goal-directed treatment for major abdominal surgery. A capnodynamic method estimating cardiac output (COEPBF) by continuously calculating nonshunted pulmonary blood flow has previously shown good agreement and trending ability when evaluated in mechanically ventilated pigs. OBJECTIVES: To compare the performance of the capnodynamic method of CO monitoring with transpulmonary thermodilution (COTPTD) in patients undergoing major abdominal surgery. DESIGN: Prospective, observational, method comparison study. Simultaneous measurements of COEPBF and COTPTD were performed before incision at baseline and before and after increased (+10 cmH2O) positive end-expiratory pressure (PEEP), activation of epidural anaesthesia and intra-operative events of hypovolemia and low CO. The first 25 patients were ventilated with PEEP 5 cmH2O (PEEP5), while in the last 10 patients, lung recruitment followed by individual PEEP adjustment (PEEPadj) was performed before protocol start. SETTING: Karolinska University Hospital, Stockholm, Sweden. PATIENTS: In total, 35 patients (>18 years) scheduled for major abdominal surgery with advanced hemodynamic monitoring were included in the study. MAIN OUTCOME MEASURES AND ANALYSIS: Agreement and trending ability between COEPBF and COTPTD at different clinical moments were analysed with Bland--Altman and four quadrant plots. RESULTS: In total, 322 paired values, 227 in PEEP5 and 95 in PEEPadj were analysed. Respectively, the mean COEPBF and COTPTD were 4.5 ±â€Š1.0 and 4.8 ±â€Š1.1 in the PEEP5 group and 4.9 ±â€Š1.2 and 5.0 ±â€Š1.0 l min-1 in the PEEPadj group. Mean bias (levels of agreement) and percentage error (PE) were -0.2 (-2.2 to 1.7) l min-1 and 41% for the PEEP5 group and -0.1 (-1.7 to 1.5) l min-1 and 31% in the PEEPadj group. Concordance rates during changes in COEPBF and COTPTD were 92% in the PEEP5 group and 90% in the PEEPadj group. CONCLUSION: COEPBF provides continuous noninvasive CO estimation with acceptable performance, which improved after lung recruitment and PEEP adjustment, although not interchangeable with COTPTD. This method may become a tool for continuous intra-operative CO monitoring during general anaesthesia in the future. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03444545.

Prevention of atelectasis by continuous positive airway pressure in anaesthetised children: A randomised controlled study.

BACKGROUND: Continuous positive airway pressure (CPAP) prevents peri-operative atelectasis in adults, but its effect in children has not been quantified. OBJECTIVE: The aim of this study was to evaluate the role of CPAP in preventing postinduction and postoperative atelectasis in children under general anaesthesia. DESIGN: A randomised controlled study. SETTING: Single-institution study, community hospital, Mar del Plata. Argentina. PATIENTS: We studied 42 children, aged 6 months to 7 years, American Society of Anesthesiologists physical status class I, under standardised general anaesthesia. INTERVENTIONS: Patients were randomised into two groups: Control group (n = 21): induction and emergence of anaesthesia without CPAP; and CPAP group (n = 21): 5 cmH2O of CPAP during induction and emergence of anaesthesia. Lung ultrasound (LUS) imaging was performed before and 5 min after anaesthesia induction. Children without atelectasis were ventilated in the same manner as the Control group with standard ventilatory settings including 5 cmH2O of PEEP. Children with atelectasis received a recruitment manoeuvre followed by standard ventilation with 8 cmH2O of PEEP. Then, at the end of surgery, LUS images were repeated before tracheal extubation and 60 min after awakening. MAIN OUTCOME MEASURES: Lung aeration score and atelectasis assessed by LUS. RESULTS: Before anaesthesia, all children were free of atelectasis. After induction, 95% in the Control group developed atelectasis compared with 52% of patients in the CPAP group (P < 0.0001). LUS aeration scores were higher (impaired aeration) in the Control group than the CPAP group (8.8 ±â€Š3.8 vs. 3.5 ±â€Š3.3 points; P < 0.0001). At the end of surgery, before tracheal extubation, atelectasis was observed in 100% of children in the Control and 29% of the CPAP group (P < 0.0001) with a corresponding aeration score of 9.6 ±â€Š3.2 and 1.8 ±â€Š2.3, respectively (P < 0.0001). After surgery, 30% of children in the Control group and 10% in the CPAP group presented with residual atelectasis (P < 0.0001) also corresponding to a higher aeration score in the Control group (2.5 ±â€Š3.1) when compared with the CPAP group (0.5 ±â€Š1.5; P < 0.01). CONCLUSION: The use of 5 cmH2O of CPAP in healthy children of the studied age span during induction and emergence of anaesthesia effectively prevents atelectasis, with benefits maintained during the first postoperative hour. TRIAL REGISTRY: Clinicaltrials.gov NCT03461770.

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study.

BACKGROUND: Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone. METHODS: Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP. RESULTS: A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95% CI 0.53-1.43), p = 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0-2.5) vs 2 IQR 1.0-3.0] days (p = 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95% CI 0.40-2.72), p = 0.92]. CONCLUSION: In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.

Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy: a randomised controlled trial.

BACKGROUND: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. METHODS: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. RESULTS: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. CONCLUSIONS: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. CLINICAL TRIAL REGISTRATION: NCT02776046.

Clinical and experimental validation of a capnodynamic method for end-expiratory lung volume assessment.

INTRODUCTION: Lung protective ventilation can decrease post-operative pulmonary complications. The aim of this study was to evaluate a capnodynamic method estimating effective lung volume (ELV) as a proxy for end-expiratory lung volume in response to PEEP changes in patients, healthy subjects and a porcine model. METHODS: Agreement and trending ability for ELV in anaesthetized patients and agreement in awake subjects were evaluated using nitrogen multiple breath wash-out/in and plethysmography as a reference respectively. Agreement and trending ability were evaluated in pigs during PEEP elevations with inert gas wash-out as reference. RESULTS: In anaesthetized patients bias (95% limits of agreement [LoA]) and percentage error (PE) at PEEP 0 cm H2 O were 133 mL (-1049 to 1315) and 71%, at PEEP 5 cm H2 O 161 mL (-1291 to 1613 mL) and 66%. In healthy subjects: 21 mL (-755 to 796 mL) and 26%. In porcines, at PEEP 5-20 cm H2 O bias decreased from 223 mL to 136 mL LoA (34-412) to (-30 to 902) and PE 29%-49%. Trending abilities in anaesthetized patients and porcines were 100% concordant. CONCLUSION: The ELV-method showed low bias but high PE in anaesthetized patients. Agreement was good in awake subjects. In porcines, agreement was good at lower PEEP levels. Concordance related to PEEP changes reached 100% in all settings. This method may become a useful trending tool for monitoring lung function during mechanical ventilation, if findings are confirmed in other clinical contexts.

Multimodal non-invasive monitoring to apply an open lung approach strategy in morbidly obese patients during bariatric surgery.

To evaluate the use of non-invasive variables for monitoring an open-lung approach (OLA) strategy in bariatric surgery. Twelve morbidly obese patients undergoing bariatric surgery received a baseline protective ventilation with 8 cmH2O of positive-end expiratory pressure (PEEP). Then, the OLA strategy was applied consisting in lung recruitment followed by a decremental PEEP trial, from 20 to 8 cmH2O, in steps of 2 cmH2O to find the lung's closing pressure. Baseline ventilation was then resumed setting open lung PEEP (OL-PEEP) at 2 cmH2O above this pressure. The multimodal non-invasive variables used for monitoring OLA consisted in pulse oximetry (SpO2), respiratory compliance (Crs), end-expiratory lung volume measured by a capnodynamic method (EELVCO2), and esophageal manometry. OL-PEEP was detected at 15.9 ± 1.7 cmH2O corresponding to a positive end-expiratory transpulmonary pressure (PL,ee) of 0.9 ± 1.1 cmH2O. ROC analysis showed that SpO2 was more accurate (AUC 0.92, IC95% 0.87-0.97) than Crs (AUC 0.76, IC95% 0.87-0.97) and EELVCO2 (AUC 0.73, IC95% 0.64-0.82) to detect the lung's closing pressure according to the change of PL,ee from positive to negative values. Compared to baseline ventilation with 8 cmH2O of PEEP, OLA increased EELVCO2 (1309 ± 517 vs. 2177 ± 679 mL) and decreased driving pressure (18.3 ± 2.2 vs. 10.1 ± 1.7 cmH2O), estimated shunt (17.7 ± 3.4 vs. 4.2 ± 1.4%), lung strain (0.39 ± 0.07 vs. 0.22 ± 0.06) and lung elastance (28.4 ± 5.8 vs. 15.3 ± 4.3 cmH2O/L), respectively; all p < 0.0001. The OLA strategy can be monitored using noninvasive variables during bariatric surgery. This strategy decreased lung strain, elastance and driving pressure compared with standard protective ventilatory settings.Clinical trial number NTC03694665.

Continuous monitoring of intrinsic PEEP based on expired CO2 kinetics: an experimental validation study.

BACKGROUND: Quantification of intrinsic PEEP (PEEPi) has important implications for patients subjected to invasive mechanical ventilation. A new non-invasive breath-by-breath method (etCO2D) for determination of PEEPi is evaluated. METHODS: In 12 mechanically ventilated pigs, dynamic hyperinflation was induced by interposing a resistance in the endotracheal tube. Airway pressure, flow, and exhaled CO2 were measured at the airway opening. Combining different I:E ratios, respiratory rates, and tidal volumes, 52 different levels of PEEPi (range 1.8-11.7 cmH2O; mean 8.45 ± 0.32 cmH2O) were studied. The etCO2D is based on the detection of the end-tidal dilution of the capnogram. This is measured at the airway opening by means of a CO2 sensor in which a 2-mm leak is added to the sensing chamber. This allows to detect a capnogram dilution with fresh air when the pressure coming from the ventilator exceeds the PEEPi. This method was compared with the occlusion method. RESULTS: The etCO2D method detected PEEPi step changes of 0.2 cmH2O. Reference and etCO2D PEEPi presented a good correlation (R2 0.80, P < 0.0001) and good agreement, bias - 0.26, and limits of agreement ± 1.96 SD (2.23, - 2.74) (P < 0.0001). CONCLUSIONS: The etCO2D method is a promising accurate simple way of continuously measure and monitor PEEPi. Its clinical validity needs, however, to be confirmed in clinical studies and in conditions with heterogeneous lung diseases.

Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV).

OBJECTIVE: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. DESIGN: International, multicenter, prospective, randomized controlled clinical trial. SETTING: A network of university hospitals. PARTICIPANTS: The study comprises 1,380 patients scheduled for thoracic surgery. INTERVENTIONS: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. MEASUREMENTS AND MAIN RESULTS: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients.

Standardized Unloading of Respiratory Muscles during Neurally Adjusted Ventilatory Assist: A Randomized Crossover Pilot Study.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Currently, there is no standardized method to set the support level in neurally adjusted ventilatory assist (NAVA). The primary aim was to explore the feasibility of titrating NAVA to specific diaphragm unloading targets, based on the neuroventilatory efficiency (NVE) index. The secondary outcome was to investigate the effect of reduced diaphragm unloading on distribution of lung ventilation. METHODS: This is a randomized crossover study between pressure support and NAVA at different diaphragm unloading at a single neurointensive care unit. Ten adult patients who had started weaning from mechanical ventilation completed the study. Two unloading targets were used: 40 and 60%. The NVE index was used to guide the titration of the assist in NAVA. Electrical impedance tomography data, blood-gas samples, and ventilatory parameters were collected. RESULTS: The median unloading was 43% (interquartile range 32, 60) for 40% unloading target and 60% (interquartile range 47, 69) for 60% unloading target. NAVA with 40% unloading led to more dorsal ventilation (center of ventilation at 55% [51, 56]) compared with pressure support (52% [49, 56]; P = 0.019). No differences were found in oxygenation, CO2, and respiratory parameters. The electrical activity of the diaphragm was higher during NAVA with 40% unloading than in pressure support. CONCLUSIONS: In this pilot study, NAVA could be titrated to different diaphragm unloading levels based on the NVE index. Less unloading was associated with greater diaphragm activity and improved ventilation of the dependent lung regions.

Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

OBJECTIVES: To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. DESIGN: Experimental study. SETTING: University animal research laboratory. SUBJECTS: Twelve pigs (30.8 ± 2.5 kg). INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. MEASUREMENTS AND MAIN RESULTS: Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005). CONCLUSIONS: In this experimental model, Acute Respiratory Distress Syndrome Network and open lung approach affected pulmonary vascular mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome.

OBJECTIVE: To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome. DESIGN: Experimental study. SETTING: Animal research laboratory. SUBJECTS: Ten pigs, 35 ± 5.2 kg. INTERVENTIONS: Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation. The positive end-expiratory pressure level resulting in highest compliance during a decremental positive end-expiratory pressure trial after lung recruitment was determined. Thereafter, three positive end-expiratory pressure levels were applied in a random order: hyperinflation, 6 cm H2O above; open lung approach, 2 cm H2O above; and collapse, 6 cm H2O below the highest compliance level. High fidelity pressure and flow sensors were placed at the main pulmonary artery for measuring pulmonary artery resistance (Z0), effective arterial elastance, compliance, and reflected pressure waves. MEASUREMENTS AND MAIN RESULTS: After inducing acute respiratory distress syndrome, Z0 and effective arterial elastance increased (from 218 ± 94 to 444 ± 115 dyn.s.cm and from 0.27 ± 0.14 to 0.62 ± 0.22 mm Hg/mL, respectively; p < 0.001), vascular compliance decreased (from 2.76 ± 0.86 to 1.48 ± 0.32 mL/mm Hg; p = 0.003), and reflected waves arrived earlier (0.23 ± 0.07 vs 0.14 ± 0.05, arbitrary unit; p = 0.002) compared with baseline. Comparing the three positive end-expiratory pressure levels, open lung approach resulted in the lowest: 1) Z0 (297 ± 83 vs 378 ± 79 dyn.s.cm, p = 0.033, and vs 450 ± 119 dyn.s.cm, p = 0.002); 2) effective arterial elastance (0.37 ± 0.08 vs 0.50 ± 0.15 mm Hg/mL, p = 0.04, and vs 0.61 ± 0.12 mm Hg/mL, p < 0.001), and 3) reflection coefficient (0.35 ± 0.17 vs 0.48 ± 0.10, p = 0.024, and vs 0.53 ± 0.19, p = 0.005), comparisons with hyperinflation and collapse, respectively. CONCLUSIONS: In this experimental setting, positive end-expiratory pressure consistent with the open lung approach resulted in the best pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressure settings.

A Quantile Analysis of Plateau and Driving Pressures: Effects on Mortality in Patients With Acute Respiratory Distress Syndrome Receiving Lung-Protective Ventilation.

OBJECTIVES: The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome. DESIGN: A secondary analysis of existing data from previously reported observational studies. SETTING: A network of ICUs. PATIENTS: We studied 778 patients with moderate to severe acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome patients. Tidal volume and positive end-expiratory pressure had no impact on mortality. We identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death. We identified a driving pressure cut-off value of 19 cm H2O where an ordinal increment was accompanied by an increment of risk of death. When we cross tabulated patients with plateau pressure less than 30 and plateau pressure greater than or equal to 30 with those with driving pressure less than 19 and driving pressure greater than or equal to 19, plateau pressure provided a slightly better prediction of outcome than driving pressure in both the derivation and validation cohorts (p < 0.0000001). CONCLUSIONS: Plateau pressure was slightly better than driving pressure in predicting hospital death in patients managed with lung-protective ventilation evaluated on standardized ventilator settings 24 hours after acute respiratory distress syndrome onset.

Advanced Uses of Pulse Oximetry for Monitoring Mechanically Ventilated Patients.

Pulse oximetry is an undisputable standard of care in clinical monitoring. It combines a spectrometer to detect hypoxemia with a plethysmograph for the diagnosis, monitoring, and follow-up of cardiovascular diseases. These pulse oximetry capabilities are extremely useful for assessing the respiratory and circulatory status and for monitoring of mechanically ventilated patients. On the one hand, the key spectrography-derived function of pulse oximetry is to evaluate a patient's gas exchange that results from a particular ventilatory treatment by continuously and noninvasively measuring arterial hemoglobin saturation (SpO2). This information helps to maintain patients above the hypoxemic levels, leading to appropriate ventilator settings and inspired oxygen fractions. However, whenever higher than normal oxygen fractions are used, SpO2 can mask existing oxygenation defects in ventilated patients. This limitation, resulting from the S shape of the oxyhemoglobin saturation curve, can be overcome by reducing the oxygen fraction delivered to the patient in a controlled and stepwise manner. This results in a SpO2/FIO2 diagram, which allows a rough characterization of a patient's gas exchange, shunt, and the amount of lung area with a low ventilation/perfusion ratio without the need of blood sampling. On the other hand, the photoplethysmography-derived oximeter function has barely been exploited for the purpose of monitoring hemodynamics in mechanically ventilated patients. The analysis of the photoplethysmography contour provides useful real-time and noninvasive information about the interaction of heart and lungs during positive pressure ventilation. These hemodynamic monitoring capabilities are related to both the assessment of preload dependency-mainly by analyzing the breath-by-breath variation of the photoplethysmographic signals-and the analysis of arterial impedance, which examines the changes in the plethysmographic amplitude, contour, and derived indexes. In this article, we present and describe these extended monitoring capabilities and propose a more holistic monitoring concept that takes advantage of these advanced uses of pulse oximetry in the monitoring of ventilated patients. Today's monitors need to be improved if such novel functionalities were to be offered for clinical use. Future developments and clinical evaluations are needed to establish the true potential of these advanced monitoring uses of pulse oximetry.

Lung recruitment improves right ventricular performance after cardiopulmonary bypass: A randomised controlled trial.

BACKGROUND: Atelectasis after cardiopulmonary bypass (CPB) can affect right ventricular (RV) performance by increasing its outflow impedance. OBJECTIVE: The aim of this study was to determine whether a lung recruitment manoeuvre improves RV function by re-aerating the lung after CPB. DESIGN: Randomised controlled study. SETTING: Single-institution study, community hospital, Córdoba, Argentina. PATIENTS: Forty anaesthetised patients with New York Heart Association class I or II, preoperative left ventricular ejection fraction at least 50% and Euroscore 6 or less scheduled for cardiac surgery with CPB. INTERVENTIONS: Patients were assigned to receive either standard ventilation with 6 cmH2O of positive end-expiratory pressure (PEEP; group C, n = 20) or standard ventilation with a recruitment manoeuvre and 10 cmH2O of PEEP after surgery (group RM, n = 20). RV function, left ventricular cardiac index (CI) and lung aeration were assessed by transoesophageal echocardiography (TOE) before, at the end of surgery and 30 min after surgery. MAIN OUTCOME MEASURES: RV function parameters and atelectasis assessed by TOE. RESULTS: Haemodynamic data and atelectasis were similar between groups before surgery. At the end of surgery, CI had decreased from 2.9 ±â€Š1.1 to 2.6 ±â€Š0.9 l min m in group C (P = 0.24) and from 2.8 ±â€Š1.0 to 2.6 ±â€Š0.8 l min m in group RM (P = 0.32). TOE-derived RV function parameters confirmed a mild decrease in RV performance in 95% of patients, without significant differences between groups (multivariate Hotelling t-test P = 0.16). Atelectasis was present in 18 patients in group C and 19 patients in group RM (P = 0.88). After surgery, CI decreased further from 2.6 to 2.4 l min m in group C (P = 0.17) but increased from 2.6 to 3.7 l min m in group RM (P < 0.001). TOE-derived RV function parameters improved only in group RM (Hotelling t-test P < 0.001). Atelectasis was present in 100% of patients in group C but only in 10% of those in group RM (P < 0.001). CONCLUSION: Atelectasis after CPB impairs RV function but this can be resolved by lung recruitment using 10 cmH2O of PEEP. TRIAL REGISTRATION: Protocol started on October 2014.

Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial.

OBJECTIVE: The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial. We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach resulting in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome. DESIGN: A prospective, multicenter, pilot, randomized controlled trial. SETTING: A network of 20 multidisciplinary ICUs. PATIENTS: Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study. INTERVENTIONS: At 12-36 hours after acute respiratory distress syndrome onset, patients were assessed under standardized ventilator settings (FIO2≥0.5, positive end-expiratory pressure ≥10 cm H2O). If Pao2/FIO2 ratio remained less than or equal to 200 mm Hg, patients were randomized to open lung approach or Acute Respiratory Distress Syndrome network protocol. All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight. MEASUREMENTS AND MAIN RESULTS: From 1,874 screened patients with acute respiratory distress syndrome, 200 were randomized: 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol. Main outcome measures were 60-day and ICU mortalities, and ventilator-free days. Mortality at day-60 (29% open lung approach vs. 33% Acute Respiratory Distress Syndrome Network protocol, p = 0.18, log rank test), ICU mortality (25% open lung approach vs. 30% Acute Respiratory Distress Syndrome network protocol, p = 0.53 Fisher's exact test), and ventilator-free days (8 [0-20] open lung approach vs. 7 [0-20] d Acute Respiratory Distress Syndrome network protocol, p = 0.53 Wilcoxon rank test) were not significantly different. Airway driving pressure (plateau pressure - positive end-expiratory pressure) and PaO2/FIO2 improved significantly at 24, 48 and 72 hours in patients in open lung approach compared with patients in Acute Respiratory Distress Syndrome network protocol. Barotrauma rate was similar in both groups. CONCLUSIONS: In patients with established acute respiratory distress syndrome, open lung approach improved oxygenation and driving pressure, without detrimental effects on mortality, ventilator-free days, or barotrauma. This pilot study supports the need for a large, multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome.