The evaluation of a non-invasive respiratory monitor in ards patients in supine and prone position.

PURPOSE: The Prone positioning in addition to non invasive respiratory support is commonly used in patients with acute respiratory failure. The aim of this study was to assess the accuracy of an impedance-based non-invasive respiratory volume monitor (RVM) in supine and in prone position. METHODS: In sedated, paralyzed and mechanically ventilated patients in volume-controlled mode with acute respiratory distress syndrome scheduled for prone positioning it was measured and compared non-invasively tidal volume and respiratory rate provided by the RVM in supine and, subsequently, in prone position, by maintaining unchanged the ventilatory setting. RESULTS: Forty patients were enrolled. No significant difference was found between measurements in supine and in prone position either for tidal volume (p = 0.795; p = 0.302) nor for respiratory rate (p = 0.181; p = 0.604). Comparing supine vs. prone position, the bias and limits of agreements for respiratory rate were 0.12 bpm (-1.4 to 1.6) and 20 mL (-80 to 120) for tidal volume. CONCLUSIONS: The RVM is accurate in assessing tidal volume and respiratory rate in prone compared to supine position. Therefore, the RVM could be applied in non-intubated patients with acute respiratory failure receiving prone positioning to monitor respiratory function.

Mechanical power during robotic-assisted laparoscopic prostatectomy: an observational study.

BACKGROUND: Robotic-assisted laparoscopic radical prostatectomy (RALP) requires pneumoperitoneum and steep Trendelenburg position. Our aim was to investigate the influence of the combination of pneumoperitoneum and Trendelenburg position on mechanical power and its components during RALP. METHODS: Sixty-one prospectively enrolled patients scheduled for RALP were studied in supine position before surgery, during pneumoperitoneum and Trendelenburg position and in supine position after surgery at constant ventilatory setting. In a subgroup of 17 patients the response to increasing positive end-expiratory pressure (PEEP) from 5 to 10 cmH2O was studied. RESULTS: The application of pneumoperitoneum and Trendelenburg position increased the total mechanical power (13.8 [11.6 - 15.5] vs 9.2 [7.5 - 11.7] J/min, p < 0.001) and its elastic and resistive components compared to supine position before surgery. In supine position after surgery the total mechanical power and its elastic component decreased but remained higher compared to supine position before surgery. Increasing PEEP from 5 to 10 cmH2O within each timepoint significantly increased the total mechanical power (supine position before surgery: 9.8 [8.4 - 10.4] vs 12.1 [11.4 - 14.2] J/min, p < 0.001; pneumoperitoneum and Trendelenburg position: 13.8 [12.2 - 14.3] vs 15.5 [15.0 - 16.7] J/min, p < 0.001; supine position after surgery: 10.2 [9.4 - 10.7] vs 12.7 [12.0 - 13.6] J/min, p < 0.001), without affecting respiratory system elastance. CONCLUSION: Mechanical power in healthy patients undergoing RALP significantly increased both during the pneumoperitoneum and Trendelenburg position and in supine position after surgery. PEEP always increased mechanical power without ameliorating the respiratory system elastance.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

Mechanical Power Ratio and Respiratory Treatment Escalation in COVID-19 Pneumonia: A Secondary Analysis of a Prospectively Enrolled Cohort.

BACKGROUND: Under the hypothesis that mechanical power ratio could identify the spontaneously breathing patients with a higher risk of respiratory failure, this study assessed lung mechanics in nonintubated patients with COVID-19 pneumonia, aiming to (1) describe their characteristics; (2) compare lung mechanics between patients who received respiratory treatment escalation and those who did not; and (3) identify variables associated with the need for respiratory treatment escalation. METHODS: Secondary analysis of prospectively enrolled cohort involving 111 consecutive spontaneously breathing adults receiving continuous positive airway pressure, enrolled from September 2020 to December 2021. Lung mechanics and other previously reported predictive indices were calculated, as well as a novel variable: the mechanical power ratio (the ratio between the actual and the expected baseline mechanical power). Patients were grouped according to the outcome: (1) no-treatment escalation (patient supported in continuous positive airway pressure until improvement) and (2) treatment escalation (escalation of the respiratory support to noninvasive or invasive mechanical ventilation), and the association between lung mechanics/predictive scores and outcome was assessed. RESULTS: At day 1, patients undergoing treatment escalation had spontaneous tidal volume similar to those of patients who did not (7.1 ± 1.9 vs. 7.1 ± 1.4 ml/kgIBW; P = 0.990). In contrast, they showed higher respiratory rate (20 ± 5 vs. 18 ± 5 breaths/min; P = 0.028), minute ventilation (9.2 ± 3.0 vs. 7.9 ± 2.4 l/min; P = 0.011), tidal pleural pressure (8.1 ± 3.7 vs. 6.0 ± 3.1 cm H2O; P = 0.003), mechanical power ratio (2.4 ± 1.4 vs. 1.7 ± 1.5; P = 0.042), and lower partial pressure of alveolar oxygen/fractional inspired oxygen tension (174 ± 64 vs. 220 ± 95; P = 0.007). The mechanical power (area under the curve, 0.738; 95% CI, 0.636 to 0.839] P < 0.001), the mechanical power ratio (area under the curve, 0.734; 95% CI, 0.625 to 0.844; P < 0.001), and the pressure-rate index (area under the curve, 0.733; 95% CI, 0.631 to 0.835; P < 0.001) showed the highest areas under the curve. CONCLUSIONS: In this COVID-19 cohort, tidal volume was similar in patients undergoing treatment escalation and in patients who did not; mechanical power, its ratio, and pressure-rate index were the variables presenting the highest association with the clinical outcome.

Ventilation strategy during urological and gynaecological robotic-assisted surgery: a narrative review.

Robotic-assisted surgery has improved the precision and accuracy of surgical movements with subsequent improved outcomes. However, it requires steep Trendelenburg positioning combined with pneumoperitoneum that negatively affects respiratory mechanics and increases the risk of postoperative respiratory complications. This narrative review summarises the state of the art in ventilatory management of these patients in terms of levels of positive end-expiratory pressure (PEEP), tidal volume, recruitment manoeuvres, and ventilation modes during both urological and gynaecological robotic-assisted surgery. A review of the literature was conducted using PubMed/MEDLINE; after completing abstract and full-text review, 31 articles were included. Although different levels of PEEP were often evaluated within a protective ventilation strategy, including higher levels of PEEP, lower tidal volume, and recruitment manoeuvres vs a conventional ventilation strategy, we conclude that the best PEEP in terms of lung mechanics, gas exchange, and ventilation distribution has not been defined, but moderate PEEP levels (4-8 cm H2O) could be associated with better outcomes than lower or highest levels. Recruitment manoeuvres improved intraoperative arterial oxygenation, end-expiratory lung volume and the distribution of ventilation to dependent (dorsal) lung regions. Pressure-controlled compared with volume-controlled ventilation showed lower peak airway pressures with both higher compliance and higher carbon dioxide clearance. We propose directions to optimise ventilatory management during robotic surgery in light of the current evidence.

The intraoperative management of robotic-assisted laparoscopic prostatectomy.

PURPOSE OF REVIEW: Robotic-assisted laparoscopic radical prostatectomy has become the second most commonly performed robotic surgical procedure worldwide, therefore, anesthesiologists should be aware of the intraoperative pathophysiological consequences. The aim of this narrative review is to report the most recent updates regarding the intraoperative management of anesthesia, ventilation, hemodynamics and central nervous system, during robotic-assisted laparoscopic radical prostatectomy. RECENT FINDINGS: Surgical innovations and the advent of new technologies make it imperative to optimize the anesthesia management to provide the most holistic approach possible. In addition, an ageing population with an increasing burden of comorbidities requires multifocal attention to reduce the surgical stress. SUMMARY: Total intravenous anesthesia (TIVA) and balanced general anesthesia are similar in terms of postoperative complications and hospital stay. Reversal of rocuronium is associated with shorter hospital stay and postanesthesia recovery time. Adequate PEEP levels improve oxygenation and driving pressure, and the use of a single recruitment maneuver after the intubation reduces postoperative pulmonary complications. Restrictive intravenous fluid administration minimizes bladder-urethra anastomosis complications and facial edema. TIVA maintains a better autoregulation compared with balanced general anesthesia. Anesthesiologists should be able to optimize the intraoperative management to improve outcomes.

Positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome: the heterogeneous effects.

BACKGROUND: We hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5-15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients. METHODS: Sixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54-67] years, PaO2/FiO2 113 [79-158] mmHg and PEEP 10 [10-10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected. RESULTS: At 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial-venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP. CONCLUSIONS: In COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.

Latent class analysis to predict intensive care outcomes in Acute Respiratory Distress Syndrome: a proposal of two pulmonary phenotypes.

BACKGROUND: Acute respiratory distress syndrome remains a heterogeneous syndrome for clinicians and researchers difficulting successful tailoring of interventions and trials. To this moment, phenotyping of this syndrome has been approached by means of inflammatory laboratory panels. Nevertheless, the systemic and inflammatory expression of acute respiratory distress syndrome might not reflect its respiratory mechanics and gas exchange. METHODS: Retrospective analysis of a prospective cohort of two hundred thirty-eight patients consecutively admitted patients under mechanical ventilation presenting with acute respiratory distress syndrome. All patients received standardized monitoring of clinical variables, respiratory mechanics and computed tomography scans at predefined PEEP levels. Employing latent class analysis, an unsupervised structural equation modelling method, on respiratory mechanics, gas-exchange and computed tomography-derived gas- and tissue-volumes at a PEEP level of 5cmH2O, distinct pulmonary phenotypes of acute respiratory distress syndrome were identified. RESULTS: Latent class analysis was applied to 54 respiratory mechanics, gas-exchange and CT-derived gas- and tissue-volume variables, and a two-class model identified as best fitting. Phenotype 1 (non-recruitable) presented lower respiratory system elastance, alveolar dead space and amount of potentially recruitable lung volume than phenotype 2 (recruitable). Phenotype 2 (recruitable) responded with an increase in ventilated lung tissue, compliance and PaO2/FiO2 ratio (p < 0.001), in addition to a decrease in alveolar dead space (p < 0.001), to a standardized recruitment manoeuvre. Patients belonging to phenotype 2 (recruitable) presented a higher intensive care mortality (hazard ratio 2.9, 95% confidence interval 1.7-2.7, p = 0.001). CONCLUSIONS: The present study identifies two ARDS phenotypes based on respiratory mechanics, gas-exchange and computed tomography-derived gas- and tissue-volumes. These phenotypes are characterized by distinctly diverse responses to a standardized recruitment manoeuvre and by a diverging mortality. Given multicentre validation, the simple and rapid identification of these pulmonary phenotypes could facilitate enrichment of future prospective clinical trials addressing mechanical ventilation strategies in ARDS.

Critical illness neuropathy in severe COVID-19: a case series.

INTRODUCTION: Neurological complications of SARS-CoV-2 disease have received growing attention, but only few studies have described to date clinical and neurophysiological findings in COVID patients during their stay in intensive care units (ICUs). Here, we neurophysiologically assessed the presence of either critical illness neuropathy (CIP) or myopathy (CIM) in ICU patients. MATERIALS AND METHODS: Patients underwent a neurophysiological assessment, including bilateral examination of the median, ulnar, deep peroneal and tibial motor nerves and of the median, ulnar, radial and sural sensory nerves. Needle electromyography (EMG) was performed for both distal and proximal muscles of the lower and upper limbs. In order to differentiate CIP from CIM, Direct Muscle Stimulation (DMS) was applied either to the deltoid or tibialis anterior muscles. Peak to peak amplitudes and onset latencies of the responses evoked by DMS (DMSamp, DMSlat) or by motor nerve stimulation (MNSamp, MNSlat) were compared. The ratio MNSamp to DMSamp (NMR) and the MNSlat to DMSlat difference (NMD: MNSlat - DMSlat) were also evaluated. RESULTS: Nerve conduction studies showed a sensory-motor polyneuropathy with axonal neurogenic pattern, as confirmed by needle EMG. Both MNSamp and NMR were significantly reduced when compared to controls (p < 0.0001), whereas MNSlat and NMD were markedly increased (p = 0.0049). CONCLUSIONS: We have described COVID patients in the ICU with critical illness neuropathy (CIP). COVID-related CIP could have implications for the functional recovery and rehabilitation strategies.

Hysteresis and Lung Recruitment in Acute Respiratory Distress Syndrome Patients: A CT Scan Study.

OBJECTIVES: Hysteresis of the respiratory system pressure-volume curve is related to alveolar surface forces, lung stress relaxation, and tidal reexpansion/collapse. Hysteresis has been suggested as a means of assessing lung recruitment. The objective of this study was to determine the relationship between hysteresis, mechanical characteristics of the respiratory system, and lung recruitment assessed by a CT scan in mechanically ventilated acute respiratory distress syndrome patients. DESIGN: Prospective observational study. SETTING: General ICU of a university hospital. PATIENTS: Twenty-five consecutive sedated and paralyzed patients with acute respiratory distress syndrome (age 64 ± 15 yr, body mass index 26 ± 6 kg/m, PaO2/FIO2 147 ± 42, and positive end-expiratory pressure 9.3 ± 1.4 cm H2O) were enrolled. INTERVENTIONS: A low-flow inflation and deflation pressure-volume curve (5-45 cm H2O) and a sustained inflation recruitment maneuver (45 cm H2O for 30 s) were performed. A lung CT scan was performed during breath-holding pressure at 5 cm H2O and during the recruitment maneuver at 45 cm H2O. MEASUREMENTS AND MAIN RESULTS: Lung recruitment was computed as the difference in noninflated tissue and in gas volume measured at 5 and at 45 cm H2O. Hysteresis was calculated as the ratio of the area enclosed by the pressure-volume curve and expressed as the hysteresis ratio. Hysteresis was correlated with respiratory system compliance computed at 5 cm H2O and the lung gas volume entering the lung during inflation of the pressure-volume curve (R = 0.749, p < 0.001 and R = 0.851, p < 0.001). The hysteresis ratio was related to both lung tissue and gas recruitment (R = 0.266, p = 0.008, R = 0.357, p = 0.002, respectively). Receiver operating characteristic analysis showed that the optimal cutoff value to predict lung tissue recruitment for the hysteresis ratio was 28% (area under the receiver operating characteristic curve, 0.80; 95% CI, 0.62-0.98), with sensitivity and specificity of 0.75 and 0.77, respectively. CONCLUSIONS: Hysteresis of the respiratory system computed by low-flow pressure-volume curve is related to the anatomical lung characteristics and has an acceptable accuracy to predict lung recruitment.

Effect of mechanical power on intensive care mortality in ARDS patients.

BACKGROUND: In ARDS patients, mechanical ventilation should minimize ventilator-induced lung injury. The mechanical power which is the energy per unit time released to the respiratory system according to the applied tidal volume, PEEP, respiratory rate, and flow should reflect the ventilator-induced lung injury. However, similar levels of mechanical power applied in different lung sizes could be associated to different effects. The aim of this study was to assess the role both of the mechanical power and of the transpulmonary mechanical power, normalized to predicted body weight, respiratory system compliance, lung volume, and amount of aerated tissue on intensive care mortality. METHODS: Retrospective analysis of ARDS patients previously enrolled in seven published studies. All patients were sedated, paralyzed, and mechanically ventilated. After 20 min from a recruitment maneuver, partitioned respiratory mechanics measurements and blood gas analyses were performed with a PEEP of 5 cmH2O while the remaining setting was maintained unchanged from the baseline. A whole lung CT scan at 5 cmH2O of PEEP was performed to estimate the lung gas volume and the amount of well-inflated tissue. Univariate and multivariable Poisson regression models with robust standard error were used to calculate risk ratios and 95% confidence intervals of ICU mortality. RESULTS: Two hundred twenty-two ARDS patients were included; 88 (40%) died in ICU. Mechanical power was not different between survivors and non-survivors 14.97 [11.51-18.44] vs. 15.46 [12.33-21.45] J/min and did not affect intensive care mortality. The multivariable robust regression models showed that the mechanical power normalized to well-inflated tissue (RR 2.69 [95% CI 1.10-6.56], p = 0.029) and the mechanical power normalized to respiratory system compliance (RR 1.79 [95% CI 1.16-2.76], p = 0.008) were independently associated with intensive care mortality after adjusting for age, SAPS II, and ARDS severity. Also, transpulmonary mechanical power normalized to respiratory system compliance and to well-inflated tissue significantly increased intensive care mortality (RR 1.74 [1.11-2.70], p = 0.015; RR 3.01 [1.15-7.91], p = 0.025). CONCLUSIONS: In our ARDS population, there is not a causal relationship between the mechanical power itself and mortality, while mechanical power normalized to the compliance or to the amount of well-aerated tissue is independently associated to the intensive care mortality. Further studies are needed to confirm this data.

Oesophageal pressure and respiratory muscle ultrasonographic measurements indicate inspiratory effort during pressure support ventilation.

BACKGROUND: Bedside measures of patient effort are essential to properly titrate the level of pressure support ventilation. We investigated whether the tidal swing in oesophageal (ΔPes) and transdiaphragmatic pressure (ΔPdi), and ultrasonographic changes in diaphragm (TFdi) and parasternal intercostal (TFic) thickening are reliable estimates of respiratory effort. The effect of diaphragm dysfunction was also considered. METHODS: Twenty-one critically ill patients were enrolled: age 73 (14) yr, BMI 27 (7) kg m-2, and Pao2/Fio2 33.3 (9.2) kPa. A three-level pressure support trial was performed: baseline, 25% (PS-medium), and 50% reduction (PS-low). We recorded the oesophageal and transdiaphragmatic pressure-time products (PTPs), work of breathing (WOB), and diaphragm and intercostal ultrasonography. Diaphragm dysfunction was defined by the Gilbert index. RESULTS: Pressure support was 9.0 (1.6) cm H2O at baseline, 6.7 (1.3) (PS-medium), and 4.4 (1.0) (PS-low). ΔPes was significantly associated with the oesophageal PTP (R2=0.868; P<0.001) and the WOB (R2=0.683; P<0.001). ΔPdi was significantly associated with the transdiaphragmatic PTP (R2=0.820; P<0.001). TFdi was only weakly correlated with the oesophageal PTP (R2=0.326; P<0.001), and the correlation improved after excluding patients with diaphragm dysfunction (R2=0.887; P<0.001). TFdi was higher and TFic lower in patients without diaphragm dysfunction: 33.6 (18.2)% vs 13.2 (9.2)% and 2.1 (1.7)% vs 12.7 (9.1)%; P<0.0001. CONCLUSIONS: ΔPes and ΔPdi are adequate estimates of inspiratory effort. Diaphragm ultrasonography is a reliable indicator of inspiratory effort in the absence of diaphragm dysfunction. Additional measurement of parasternal intercostal thickening may discriminate a low inspiratory effort or a high effort in the presence of a dysfunctional diaphragm.

Internal clock and the surgical ICU patient.

PURPOSE OF REVIEW: The alteration of circadian rhythms in the postoperative period has been demonstrated to influence the outcomes. With this narrative review we would revise how anesthesia, surgery and intensive care can interfere with the circadian clock, how this could impact on the postsurgical period and how to limit the disruption of the internal clock. RECENT FINDINGS: Anesthesia affects the clock in relation to the day-time administration and the type of anesthetics, N-methyl-D-aspartate receptor antagonists or gamma-aminobutyric acid receptors agonists. Surgery causes stress and trauma with consequent alteration in the circadian release of cortisol, cytokines and melatonin. ICU represents a further challenge for the patient internal clock because of sedation, immobility, mechanical ventilation and alarms noise. SUMMARY: The synergic effect of anesthesia, surgery and postoperative intensive care on circadian rhythms require a careful approach to the patient considering a role for therapies and interventions aimed to re-establish the normal circadian rhythms. Over time, approach like the Awakening and Breathing Coordination, Delirium Monitoring and Management, Early Mobility and Family engagement and empowerment bundle can implement the clinical practice.

Respiratory Mechanics, Lung Recruitability, and Gas Exchange in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome.

OBJECTIVES: Acute respiratory distress syndrome is a clinical syndrome characterized by a refractory hypoxemia due to an inflammatory and high permeability pulmonary edema secondary to direct or indirect lung insult (pulmonary and extrapulmonary form). Aim of this study was to evaluate in a large database of acute respiratory distress syndrome patients, the pulmonary versus extrapulmonary form in terms of respiratory mechanics, lung recruitment, gas exchange, and positive end-expiratory pressure response. DESIGN: A secondary analysis of previously published data. PATIENTS: One-hundred eighty-one sedated and paralyzed acute respiratory distress syndrome patients (age 60 yr [46-72 yr], body mass index 25 kg/m [22-28 kg/m], and PaO2/FIO2 184 ± 66). INTERVENTIONS: Lung CT scan performed at 5 and 45 cm H2O. Two levels of positive end-expiratory pressure (5 and 15 cm H2O) were randomly applied. MEASUREMENTS AND MAIN RESULTS: Ninety-seven and 84 patients had a pulmonary and extrapulmonary acute respiratory distress syndrome. The median time from intensive care admission to the CT scan and respiratory mechanics analysis was 4 days (interquartile range, 2-6). At both positive end-expiratory pressure levels, pulmonary acute respiratory distress syndrome presented a significantly lower PaO2/FIO2 and higher physiologic dead space compared with extrapulmonary acute respiratory distress syndrome. The lung and chest wall elastance were similar between groups. The intra-abdominal pressure was significantly higher in extrapulmonary compared with pulmonary acute respiratory distress syndrome (10 mm Hg [7-12 mm Hg] vs 7 mm Hg [5-8 mm Hg]). The lung weight and lung recruitability were significantly higher in pulmonary acute respiratory distress syndrome (1,534 g [1,286-1,835 g] vs 1,342 g [1,090-1,507 g] and 16% [9-25%] vs 9% [5-14%]). CONCLUSIONS: In the early stage, pulmonary acute respiratory distress syndrome is characterized by a greater impairment of gas exchange and higher lung recruitability. The recognition of the origin of acute respiratory distress syndrome is important for a more customized ventilatory management.

Global and Regional Diagnostic Accuracy of Lung Ultrasound Compared to CT in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: Lung CT is the reference imaging technique for acute respiratory distress syndrome, but requires transportation outside the intensive care and x-ray exposure. Lung ultrasound is a promising, inexpensive, radiation-free, tool for bedside imaging. Aim of the present study was to compare the global and regional diagnostic accuracy of lung ultrasound and CT scan. DESIGN: A prospective, observational study. SETTING: Intensive care and radiology departments of a University hospital. PATIENTS: Thirty-two sedated, paralyzed acute respiratory distress syndrome patients (age 65 ± 14 yr, body mass index 25.9 ± 6.5 kg/m, and PaO2/FIO2 139 ± 47). INTERVENTIONS: Lung CT scan and lung ultrasound were performed at positive end-expiratory pressure 5 cm H2O. A standardized assessment of six regions per hemithorax was used; each region was classified for the presence of normal aeration, alveolar-interstitial syndrome, consolidation, and pleural effusion. Agreement between the two techniques was calculated, and diagnostic variables were assessed for lung ultrasound using lung CT as a reference. MEASUREMENTS AND MAIN RESULTS: Global agreement between lung ultrasound and CT ranged from 0.640 (0.391-0.889) to 0.934 (0.605-1.000) and was on average 0.775 (0.577-0.973). The overall sensitivity and specificity of lung ultrasound ranged from 82.7% to 92.3% and from 90.2% to 98.6%, respectively. Similar results were found with regional analysis. The diagnostic accuracy of lung ultrasound was significantly higher when those patterns not reaching the pleural surface were excluded (area under the receiver operating characteristic curve: alveolar-interstitial syndrome 0.854 [0.821-0.887] vs 0.903 [0.852-0.954]; p = 0.049 and consolidation 0.851 [0.818-0.884] vs 0.896 [0.862-0.929]; p = 0.044). CONCLUSIONS: Lung ultrasound is a reproducible, sensitive, and specific tool, which allows for bedside detections of the morphologic patterns in acute respiratory distress syndrome. The presence of deep lung alterations may impact the diagnostic performance of this technique.

Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study.

BACKGROUND AND OBJECTIVES: Critically ill patients present reduced endogenous melatonin blood levels, and they might benefit from its exogenous supplementation. The aim of this research was to evaluate the feasibility of different routes of administration and drug formulations of melatonin. The efficiency of absorption was assessed as well as the adequacy in achieving and maintaining the physiological nocturnal blood peak. METHODS: Twenty-one high-risk critically ill patients were randomly assigned to receive melatonin either: (a) per os, as a standard tablet (ST-OS), (b) per os, as a suspension in solid lipid nanoparticles (SLN-OS) or c) transdermal (TD), by applying a jellified melatonin microemulsion (µE) on the skin (µE-TD). SLN-OS and µE-TD were lipid-based colloidal systems. The endogenous melatonin blood values were observed for 24 hours; subsequently, melatonin 3 mg was administered and pharmacokinetics was studied for 24 hours further. RESULTS: In both groups that received ST-OS and SLN-OS, the median time-to-peak blood concentration was 0.5 hours; however, the area under the curve (AUC) after administration of SLN-OS was significantly higher than after ST-OS (157386 [65732-193653] vs 44441 [22319-90705] pg/mL*hours, P = 0.048). µE-TD presented a delayed time-to-peak blood concentration (4 hours), a lower bioavailability (AUC: 3142 [1344-14573] pg/mL*hours) and reached pharmacological peak concentration (388 [132-1583] pg/mL). CONCLUSIONS: SLN-melatonin enterally administered offers favourable pharmacokinetics in critically ill patients, with higher bioavailability with respect to the standard formulation; µE-TD provided effective pharmacological blood levels, with a time-concentration profile more similar to the physiological melatonin pattern.

Dynamic hyperinflation and intrinsic positive end-expiratory pressure in ARDS patients.

BACKGROUND: In ARDS patients, changes in respiratory mechanical properties and ventilatory settings can cause incomplete lung deflation at end-expiration. Both can promote dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEP). The aim of this study was to investigate, in a large population of ARDS patients, the presence of intrinsic PEEP, possible associated factors (patients' characteristics and ventilator settings), and the effects of two different external PEEP levels on the intrinsic PEEP. METHODS: We made a secondary analysis of published data. Patients were ventilated with a tidal volume of 6-8 mL/kg of predicted body weight, sedated, and paralyzed. After a recruitment maneuver, a PEEP trial was run at 5 and 15 cmH2O, and partitioned mechanics measurements were collected after 20 min of stabilization. Lung computed tomography scans were taken at 5 and 45 cmH2O. Patients were classified into two groups according to whether or not they had intrinsic PEEP at the end of an expiratory pause. RESULTS: We enrolled 217 sedated, paralyzed patients: 87 (40%) had intrinsic PEEP with a median of 1.1 [1.0-2.3] cmH2O at 5 cmH2O of PEEP. The intrinsic PEEP significantly decreased with higher PEEP (1.1 [1.0-2.3] vs 0.6 [0.0-1.0] cmH2O; p < 0.001). The applied tidal volume was significantly lower (480 [430-540] vs 520 [445-600] mL at 5 cmH2O of PEEP; 480 [430-540] vs 510 [430-590] mL at 15 cmH2O) in patients with intrinsic PEEP, while the respiratory rate was significantly higher (18 [15-20] vs 15 [13-19] bpm at 5 cmH2O of PEEP; 18 [15-20] vs 15 [13-19] bpm at 15 cmH2O). At both PEEP levels, the total airway resistance and compliance of the respiratory system were not different in patients with and without intrinsic PEEP. The total lung gas volume and lung recruitability were also not different between patients with and without intrinsic PEEP (respectively 961 [701-1535] vs 973 [659-1433] mL and 15 [0-32] % vs 22 [0-36] %). CONCLUSIONS: In sedated, paralyzed ARDS patients without a known obstructive disease, the amount of intrinsic PEEP during lung-protective ventilation is negligible and does not influence respiratory mechanical properties.

Oxidative Stress Markers to Investigate the Effects of Hyperoxia in Anesthesia.

Oxygen (O2) is commonly used in clinical practice to prevent or treat hypoxia, but if used in excess (hyperoxia), it may act as toxic. O2 toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that exceed the antioxidant defenses and generate oxidative stress. In this study, we aimed at assessing whether an elevated fraction of inspired oxygen (FiO2) during and after general anesthesia may contribute to the unbalancing of the pro-oxidant/antioxidant equilibrium. We measured five oxidative stress biomarkers in blood samples from patients undergoing elective abdominal surgery, randomly assigned to FiO2 = 0.40 vs. 0.80: hydroperoxides, antioxidants, nitrates and nitrites (NOx), malondialdehyde (MDA), and glutathionyl hemoglobin (HbSSG). The MDA concentration was significantly higher 24 h after surgery, and the body antioxidant defense lower, in the FiO2 = 0.80 group with respect to both the FiO2 = 0.40 group and the baseline values (p ≤ 0.05, Student's t-test). HbSSG in red blood cells was also higher in the FiO2 = 0.80 group at the end of the surgery. NOx was higher in the FiO2 = 0.80 group than the FiO2 = 0.40 group at t = 2 h after surgery. MDA, the main end product of the peroxidation of polyunsaturated fatty acids directly influenced by FiO2, may represent the best marker to assess the pro-oxidant/antioxidant equilibrium after surgery.