Recruitment-to-inflation Ratio Assessed through Sequential End-expiratory Lung Volume Measurement in Acute Respiratory Distress Syndrome.

BACKGROUND: Positive end-expiratory pressure (PEEP) benefits in acute respiratory distress syndrome are driven by lung dynamic strain reduction. This depends on the variable extent of alveolar recruitment. The recruitment-to-inflation ratio estimates recruitability across a 10-cm H2O PEEP range through a simplified maneuver. Whether recruitability is uniform or not across this range is unknown. The hypotheses of this study are that the recruitment-to-inflation ratio represents an accurate estimate of PEEP-induced changes in dynamic strain, but may show nonuniform behavior across the conventionally tested PEEP range (15 to 5 cm H2O). METHODS: Twenty patients with moderate-to-severe COVID-19 acute respiratory distress syndrome underwent a decremental PEEP trial (PEEP 15 to 13 to 10 to 8 to 5 cm H2O). Respiratory mechanics and end-expiratory lung volume by nitrogen dilution were measured the end of each step. Gas exchange, recruited volume, recruitment-to-inflation ratio, and changes in dynamic, static, and total strain were computed between 15 and 5 cm H2O (global recruitment-to-inflation ratio) and within narrower PEEP ranges (granular recruitment-to-inflation ratio). RESULTS: Between 15 and 5 cm H2O, median [interquartile range] global recruitment-to-inflation ratio was 1.27 [0.40 to 1.69] and displayed a linear correlation with PEEP-induced dynamic strain reduction (r = -0.94; P < 0.001). Intraindividual recruitment-to-inflation ratio variability within the narrower ranges was high (85% [70 to 109]). The relationship between granular recruitment-to-inflation ratio and PEEP was mathematically described by a nonlinear, quadratic equation (R2 = 0.96). Granular recruitment-to-inflation ratio across the narrower PEEP ranges itself had a linear correlation with PEEP-induced reduction in dynamic strain (r = -0.89; P < 0.001). CONCLUSIONS: Both global and granular recruitment-to-inflation ratio accurately estimate PEEP-induced changes in lung dynamic strain. However, the effect of 10 cm H2O of PEEP on lung strain may be nonuniform. Granular recruitment-to-inflation ratio assessment within narrower PEEP ranges guided by end-expiratory lung volume measurement may aid more precise PEEP selection, especially when the recruitment-to-inflation ratio obtained with the simplified maneuver between PEEP 15 and 5 cm H2O yields intermediate values that are difficult to interpret for a proper choice between a high and low PEEP strategy.

Lung-protective ventilation during Trendelenburg pneumoperitoneum surgery: A randomized clinical trial.

Study objective To assess the effects of a protective ventilation strategy during Trendelenburg pneumoperitoneum surgery on postoperative oxygenation. DESIGNS: Parallel-group, randomized trial. SETTING: Operating room of a university hospital, Italy. PATIENTS: Morbidly obese patients undergoing Trendelenburg pneumoperitoneum gynaecological surgery. INTERVENTIONS: Participants were randomized to standard (SV: tidal volume = 10 ml/kg of predicted body weight, PEEP = 5 cmH2O) or protective (PV: tidal volume = 6 ml/kg of predicted body weight, PEEP = 10 cmH2O, recruitment maneuvers) ventilation during anesthesia. MEASUREMENTS: Primary outcome was PaO2/FiO2 one hour after extubation. Secondary outcomes included day-1 PaO2/FiO2, day-2 respiratory function and intraoperative respiratory/lung mechanics, assessed through esophageal manometry, end-expiratory lung volume (EELV) measurement and pressure-volume curves. MAIN RESULTS: Sixty patients were analyzed (31 in SV group, 29 in PV group). Median [IqR] tidal volume was 350 ml [300-360] in PV group and 525 [500-575] in SV group. Median PaO2/FiO2 one hour after extubation was 280 mmHg [246-364] in PV group vs. 298 [250-343] in SV group (p = 0.64). Day-1 PaO2/FiO2, day-2 forced vital capacity, FEV-1 and Tiffenau Index were not different between groups (all p > 0.10). Intraoperatively, 59% of patients showed complete airway closure during pneumoperitoneum, without difference between groups: median airway opening pressure was 17 cmH2O. In PV group, airway and transpulmonary driving pressure were lower (12 ± 5 cmH2O vs. 17 ± 7, p < 0.001; 9 ± 4 vs. 13 ± 7, p < 0.001), PaCO2 and respiratory rate were higher (48 ± 8 mmHg vs. 42 ± 12, p < 0.001; 23 ± 5 breaths/min vs. 16 ± 4, p < 0.001). Intraoperative EELV was similar between PV and SV group (1193 ± 258 ml vs. 1207 ± 368, p = 0.80); ratio of tidal volume to EELV was lower in PV group (0.45 ± 0.12 vs. 0.32 ± 0.09, p < 0.001). CONCLUSIONS: In obese patients undergoing Trendelenburg pneumoperitoneum surgery, PV did not improve postoperative oxygenation nor day-2 respiratory function. PV was associated with intraoperative respiratory mechanics indicating less injurious ventilation. The high prevalence of complete airway closure may have affected study results. TRIAL REGISTRATION: Prospectively registered on http://clinicaltrials.govNCT03157479 on May 17th, 2017.

Severe Recurrent COVID-Associated Pulmonary Aspergillosis: A Challenging Case.

We report a rare case of severe COVID-19-associated pulmonary aspergillosis presenting as invasive pulmonary aspergillosis and subsequently invasive tracheobronchial aspergillosis during hospitalization in a critically ill patient who developed a further Aspergillus infection after home discharge. He needed readmission to the ICU and mechanical ventilation. We therefore strongly encourage a high degree of attention to fungal complications, even after viral recovery and ICU discharge.

Gas conditioning during helmet noninvasive ventilation: effect on comfort, gas exchange, inspiratory effort, transpulmonary pressure and patient-ventilator interaction.

BACKGROUND: There is growing interest towards the use of helmet noninvasive ventilation (NIV) for the management of acute hypoxemic respiratory failure. Gas conditioning through heat and moisture exchangers (HME) or heated humidifiers (HHs) is needed during facemask NIV to provide a minimum level of humidity in the inspired gas (15 mg H2O/L). The optimal gas conditioning strategy during helmet NIV remains to be established. METHODS: Twenty patients with acute hypoxemic respiratory failure (PaO2/FiO2 < 300 mmHg) underwent consecutive 1-h periods of helmet NIV (PEEP 12 cmH2O, pressure support 12 cmH2O) with four humidification settings, applied in a random order: double-tube circuit with HHs and temperature set at 34 °C (HH34) and 37 °C (HH37); Y-piece circuit with HME; double-tube circuit with no humidification (NoH). Temperature and humidity of inhaled gas were measured through a capacitive hygrometer. Arterial blood gases, discomfort and dyspnea through visual analog scales (VAS), esophageal pressure swings (ΔPES) and simplified pressure-time product (PTPES), dynamic transpulmonary driving pressure (ΔPL) and asynchrony index were measured in each step. RESULTS: Median [IqR] absolute humidity, temperature and VAS discomfort were significantly lower during NoH vs. HME, HH34 and HH37: absolute humidity (mgH2O/L) 16 [12-19] vs. 28 [23-31] vs. 28 [24-31] vs. 33 [29-38], p < 0.001; temperature (°C) 29 [28-30] vs. 30 [29-31] vs. 31 [29-32] vs 32. [31-33], p < 0.001; VAS discomfort 4 [2-6] vs. 6 [2-7] vs. 7 [4-8] vs. 8 [4-10], p = 0.03. VAS discomfort increased with higher absolute humidity (p < 0.01) and temperature (p = 0.007). Higher VAS discomfort was associated with increased VAS dyspnea (p = 0.001). Arterial blood gases, respiratory rate, ΔPES, PTPES and ΔPL were similar in all conditions. Overall asynchrony index was similar in all steps, but autotriggering rate was lower during NoH and HME (p = 0.03). CONCLUSIONS: During 1-h sessions of helmet NIV in patients with hypoxemic respiratory failure, a double-tube circuit with no humidification allowed adequate conditioning of inspired gas, optimized comfort and improved patient-ventilator interaction. Use of HHs or HME in this setting resulted in increased discomfort due to excessive heat and humidity in the interface, which was associated with more intense dyspnea. Trail Registration Registered on clinicaltrials.gov (NCT02875379) on August 23rd, 2016.

High Failure Rate of Noninvasive Oxygenation Strategies in Critically Ill Subjects With Acute Hypoxemic Respiratory Failure Due to COVID-19.

BACKGROUND: The efficacy of noninvasive oxygenation strategies (NIOS) in treating COVID-19 disease is unknown. We conducted a prospective observational study to assess the rate of NIOS failure in subjects treated in the ICU for hypoxemic respiratory failure due to COVID-19. METHODS: Patients receiving first-line treatment NIOS for hypoxemic respiratory failure due to COVID-19 in the ICU of a university hospital were included in this study; laboratory data were collected upon arrival, and 28-d outcome was recorded. After propensity score matching based on Simplified Acute Physiology (SAPS) II score, age, [Formula: see text] and [Formula: see text] at arrival, the NIOS failure rate in subjects with COVID-19 was compared to a previously published cohort who received NIOS during hypoxemic respiratory failure due to other causes. RESULTS: A total of 85 subjects received first-line treatment with NIOS. The most frequently used methods were helmet noninvasive ventilation and high-flow nasal cannula; of these, 52 subjects (61%) required endotracheal intubation. Independent factors associated with NIOS failure were SAPS II score (P = .009) and serum lactate dehydrogenase at enrollment (P = .02); the combination of SAPS II score ≥ 33 with serum lactate dehydrogenase ≥ 405 units/L at ICU admission had 91% specificity in predicting the need for endotracheal intubation. In the propensity-matched cohorts (54 pairs), subjects with COVID-19 showed higher risk of NIOS failure than those with other causes of hypoxemic respiratory failure (59% vs 35%, P = .02), with an adjusted hazard ratio of 2 (95% CI 1.1-3.6, P = .01). CONCLUSIONS: As compared to hypoxemic respiratory failure due to other etiologies, subjects with COVID-19 who were treated with NIOS in the ICU were burdened by a 2-fold higher risk of failure. Subjects with a SAPS II score ≥ 33 and serum lactate dehydrogenase ≥ 405 units/L represent the population with the greatest risk.

Respiratory physiology of COVID-19-induced respiratory failure compared to ARDS of other etiologies.

BACKGROUND: Whether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes. METHODS: Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmH2O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO2/FiO2, FiO2, PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study. RESULTS: Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th-75th percentiles] PaO2/FiO2 in the two groups was 119 mmHg [101-142] and 116 mmHg [87-154]. Average compliance (41 ml/cmH2O [32-52] vs. 36 ml/cmH2O [27-42], p = 0.045) and ventilatory ratio (2.1 [1.7-2.3] vs. 1.6 [1.4-2.1], p = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO2/FiO2 was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO2/FiO2 in both cohorts, but more remarkably in COVID-19 patients (p = 0.005). Recruitability was not different between cohorts (p = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP. CONCLUSIONS: Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small.

Physiological Comparison of High-Flow Nasal Cannula and Helmet Noninvasive Ventilation in Acute Hypoxemic Respiratory Failure.

Rationale: High-flow nasal cannula (HFNC) and helmet noninvasive ventilation (NIV) are used for the management of acute hypoxemic respiratory failure.Objectives: Physiological comparison of HFNC and helmet NIV in patients with hypoxemia.Methods: Fifteen patients with hypoxemia with PaO2/FiO2 < 200 mm Hg received helmet NIV (positive end-expiratory pressure ≥ 10 cm H2O, pressure support = 10-15 cm H2O) and HFNC (50 L/min) in randomized crossover order. Arterial blood gases, dyspnea, and comfort were recorded. Inspiratory effort was estimated by esophageal pressure (Pes) swings. Pes-simplified pressure-time product and transpulmonary pressure swings were measured.Measurements and Main Results: As compared with HFNC, helmet NIV increased PaO2/FiO2 (median [interquartile range]: 255 mm Hg [140-299] vs. 138 [101-172]; P = 0.001) and lowered inspiratory effort (7 cm H2O [4-11] vs. 15 [8-19]; P = 0.001) in all patients. Inspiratory effort reduction by NIV was linearly related to inspiratory effort during HFNC (r = 0.84; P < 0.001). Helmet NIV reduced respiratory rate (24 breaths/min [23-31] vs. 29 [26-32]; P = 0.027), Pes-simplified pressure-time product (93 cm H2O ⋅ s ⋅ min-1 [43-138] vs. 200 [168-335]; P = 0.001), and dyspnea (visual analog scale 3 [2-5] vs. 8 [6-9]; P = 0.002), without affecting PaCO2 (P = 0.80) and comfort (P = 0.50). In the overall cohort, transpulmonary pressure swings were not different between treatments (NIV = 18 cm H2O [14-21] vs. HFNC = 15 [8-19]; P = 0.11), but patients exhibiting lower inspiratory effort on HFNC experienced increases in transpulmonary pressure swings with helmet NIV. Higher transpulmonary pressure swings during NIV were associated with subsequent need for intubation.Conclusions: As compared with HFNC in hypoxemic respiratory failure, helmet NIV improves oxygenation, reduces dyspnea, inspiratory effort, and simplified pressure-time product, with similar transpulmonary pressure swings, PaCO2, and comfort.

Physiological effects of high-flow oxygen in tracheostomized patients.

BACKGROUND: High-flow oxygen therapy via nasal cannula (HFOTNASAL) increases airway pressure, ameliorates oxygenation and reduces work of breathing. High-flow oxygen can be delivered through tracheostomy (HFOTTRACHEAL), but its physiological effects have not been systematically described. We conducted a cross-over study to elucidate the effects of increasing flow rates of HFOTTRACHEAL on gas exchange, respiratory rate and endotracheal pressure and to compare lower airway pressure produced by HFOTNASAL and HFOTTRACHEAL. METHODS: Twenty-six tracheostomized patients underwent standard oxygen therapy through a conventional heat and moisture exchanger, and then HFOTTRACHEAL through a heated humidifier, with gas flow set at 10, 30 and 50 L/min. Each step lasted 30 min; gas flow sequence during HFOTTRACHEAL was randomized. In five patients, measurements were repeated during HFOTTRACHEAL before tracheostomy decannulation and immediately after during HFOTNASAL. In each step, arterial blood gases, respiratory rate, and tracheal pressure were measured. RESULTS: During HFOTTRACHEAL, PaO2/FiO2 ratio and tracheal expiratory pressure slightly increased proportionally to gas flow. The mean [95% confidence interval] expiratory pressure raise induced by 10-L/min increase in flow was 0.2 [0.1-0.2] cmH2O (ρ = 0.77, p < 0.001). Compared to standard oxygen, HFOTTRACHEAL limited the negative inspiratory swing in tracheal pressure; at 50 L/min, but not with other settings, HFOTTRACHEAL increased mean tracheal expiratory pressure by (mean difference [95% CI]) 0.4 [0.3-0.6] cmH2O, peak tracheal expiratory pressure by 0.4 [0.2-0.6] cmH2O, improved PaO2/FiO2 ratio by 40 [8-71] mmHg, and reduced respiratory rate by 1.9 [0.3-3.6] breaths/min without PaCO2 changes. As compared to HFOTTRACHEAL, HFOTNASAL produced higher tracheal mean and peak expiratory pressure (at 50 L/min, mean difference [95% CI]: 3 [1-5] cmH2O and 4 [1-7] cmH2O, respectively). CONCLUSIONS: As compared to standard oxygen, 50 L/min of HFOTTRACHEAL are needed to improve oxygenation, reduce respiratory rate and provide small degree of positive airway expiratory pressure, which, however, is significantly lower than the one produced by HFOTNASAL.

Airway Closure during Surgical Pneumoperitoneum in Obese Patients.

BACKGROUND: Airway closure causes lack of communication between proximal airways and alveoli, making tidal inflation start only after a critical airway opening pressure is overcome. The authors conducted a matched cohort study to report the existence of this phenomenon among obese patients undergoing general anesthesia. METHODS: Within the procedures of a clinical trial during gynecological surgery, obese patients underwent respiratory/lung mechanics and lung volume assessment both before and after pneumoperitoneum, in the supine and Trendelenburg positions, respectively. Among patients included in this study, those exhibiting airway closure were compared to a control group of subjects enrolled in the same trial and matched in 1:1 ratio according to body mass index. RESULTS: Eleven of 50 patients (22%) showed airway closure after intubation, with a median (interquartile range) airway opening pressure of 9 cm H2O (6 to 12). With pneumoperitoneum, airway opening pressure increased up to 21 cm H2O (19 to 28) and end-expiratory lung volume remained unchanged (1,294 ml [1,154 to 1,363] vs. 1,160 ml [1,118 to 1,256], P = 0.155), because end-expiratory alveolar pressure increased consistently with airway opening pressure and counterbalanced pneumoperitoneum-induced increases in end-expiratory esophageal pressure (16 cm H2O [15 to 19] vs. 27 cm H2O [23 to 30], P = 0.005). Conversely, matched control subjects experienced a statistically significant greater reduction in end-expiratory lung volume due to pneumoperitoneum (1,113 ml [1,040 to 1,577] vs. 1,000 ml [821 to 1,061], P = 0.006). With airway closure, static/dynamic mechanics failed to measure actual lung/respiratory mechanics. When patients with airway closure underwent pressure-controlled ventilation, no tidal volume was inflated until inspiratory pressure overcame airway opening pressure. CONCLUSIONS: In obese patients, complete airway closure is frequent during anesthesia and is worsened by Trendelenburg pneumoperitoneum, which increases airway opening pressure and alveolar pressure: besides preventing alveolar derecruitment, this yields misinterpretation of respiratory mechanics and generates a pressure threshold to inflate the lung that can reach high values, spreading concerns on the safety of pressure-controlled modes in this setting.

Goal-directed hemodynamic management in patients undergoing primary debulking gynaecological surgery: A matched-controlled precision medicine study.

BACKGROUND: Usefulness of intraoperative goal-directed hemodynamic management (GDHM) for patients without comorbidities is debated. After clinical implementation of a pulse contour analysis-guided GDHM protocol, which foresees early vasopressor use for recruiting unstressed volume, we conducted a matched-controlled analysis to explore its impact on the amount of fluids intraoperatively administered to patients without comorbidities who underwent extended abdominal surgery for ovarian cancer. METHODS: After 1:1 matching accounting for body mass index, oncologic disease severity and intraoperative blood losses, 22 patients treated according to this GDHM protocol were compared to a control group of 22 patients who had been managed according to the clinical decision of attending physicians, taken without advanced monitoring. Results are displayed as median[interquartile range]. RESULTS: All analyzed patients underwent radical hysterectomy, bilateral adnexectomy, bowel resection, peritonectomy and extended pelvic/periaortic lymphadenectomy; median length of surgery was 517[480-605] min in patients receiving GDHM and 507[480-600] min in control group. Intraoperatively, patients undergoing GDHM received less fluids (crystalloids 2950[2700-3300] vs. 5150[4700-6000] mL, p < 0.001; colloids 100[50-200] vs. 750[500-1000] mL, p < 0.001) and showed a trend to more frequent vasopressor administration (32 vs 9%, p = 0.13). Greater intraoperative diuresis (540[480-620] mL vs. 450[400-500] mL, p = 0.007), lower blood lactates at surgery end (1.5[1.1-2] vs. 4.1[3.3-5] mmol/L, p < 0.001), shorter time to bowel function recovery (1 [1, 2] vs. 4 [3-5] days, p < 0.001) and hospital discharge (7 [6-8] vs 12 [9-16] days, p < 0.0001) were detected in patients receiving GDHM. CONCLUSIONS: In high-tumor load gynaecological patients without comorbidities who receive radical and prolonged surgery, intraoperative use of this novel GDHM protocol helped limit fluids administration with safety.

Continuous intravenous analgesia with fentanyl or morphine after gynecological surgery: a cohort study.

PURPOSE: This retrospective study aims to compare postoperative pain relief offered by continuous intravenous infusion of either fentanyl or morphine. METHODS: Sixty American Society of Anesthesiologists Physical Status I and II women who had undergone open gynecological surgery were enrolled. All patients received total intravenous postoperative analgesia for 24 h with continuous infusion of either fentanyl or morphine at comparable doses (38 patients received 0.3 µg/kg/h fentanyl and 22 received 0.02 mg/kg/h morphine). The primary endpoint was the need for analgesic rescue therapy during the postoperative period as assessed by an experienced nurse blinded to the design of the study, while the time to gastrointestinal bowel recovery was the main safety outcome measure. Visual analog scale was used to evaluate postoperative pain. Ramsay sedation score, multiparametric monitoring, bowel function and adverse effects were also recorded at 1, 6, 12, 18 and 24 h after the end of surgery. RESULTS: Data analysis showed that four patients (10 %) in the fentanyl group versus eight patients (36 %) in the morphine group needed to be treated with analgesic rescue drugs [unadjusted OR for fentanyl 0.2 (0.05-0.80); p = 0.02]. Patients treated with fentanyl showed a faster gastrointestinal recovery [1 (1-2) vs 3 (2.7-4) days; p < 0.001] and a shorter hospital length of stay [4 (3-5) vs 5.5 (5-7.2) days; p < 0.001]. CONCLUSION: In low-risk patients undergoing open gynecological surgery, continuous intravenous infusion of both fentanyl and morphine for postoperative pain relief is effective. In our cohort of patients, continuous intravenous infusion of fentanyl was associated with lower need for analgesic rescue drug, faster bowel recovery and shorter hospital length of stay.

Socioeconomic disparities in the uptake of breast and cervical cancer screening in Italy: a cross sectional study.

BACKGROUND: Breast and cervical cancer screening are widely recognized as effective preventive procedures in reducing cancer mortality. The aim of this study was to evaluate the impact of socioeconomic disparities in the uptake of female screening in Italy, with a specific focus on different types of screening programs. METHODS: A cross-sectional study was conducted using data from the 2004-2005 national health interview survey. A sample of 15, 486 women aged 50-69 years for mammography and one of 35, 349 women aged 25-64 years for Pap smear were analysed. Logistic regression models were used to estimate the association between socioeconomic factors and female screening utilization. RESULTS: Education and occupation were positively associated with attendance to both screening. Women with higher levels of education were more likely to have a mammogram than those with a lower level (OR = 1.28; 95% CI = 1.10-1.49). Women of intermediate and high occupational classes were more likely to use breast cancer screening (OR = 1.77; 95% CI = 1.55-2.03, OR = 1.63; 95% CI = 1.40-1.91) compared to unemployed women. Women in the highest occupational class had a higher likelihood of cervical cancer screening compared to those in the lowest class (OR = 1.81; 95% CI = 1.63-2.01). Among women who attended screening, those with lower levels of education and lower occupational classes were more likely than more advantaged women to attend organized screening programs rather than being screened on the basis of their own initiative. CONCLUSIONS: Inequalities in the uptake of female screening widely exist in Italy. Organized screening programs may have an important role in increasing screening attendance and tackling inequalities.