Physiological effects and safety of bed verticalization in patients with acute respiratory distress syndrome.

BACKGROUND: Trunk inclination in patients with Acute Respiratory Distress Syndrome (ARDS) in the supine position has gained scientific interest due to its effects on respiratory physiology, including mechanics, oxygenation, ventilation distribution, and efficiency. Changing from flat supine to semi-recumbent increases driving pressure due to decreased respiratory system compliance. Positional adjustments also deteriorate ventilatory efficiency for CO2 removal, particularly in COVID-19-associated ARDS (C-ARDS), indicating likely lung parenchyma overdistension. Tilting the trunk reduces chest wall compliance and, to a lesser extent, lung compliance and transpulmonary driving pressure, with significant hemodynamic and gas exchange implications. METHODS: A prospective, pilot physiological study was conducted on early ARDS patients in two ICUs at CHU Clermont-Ferrand, France. The protocol involved 30-min step gradual verticalization from a 30° semi-seated position (baseline) to different levels of inclination (0°, 30°, 60°, and 90°), before returning to the baseline position. Measurements included tidal volume, positive end-expiratory pressure (PEEP), esophageal pressures, and pulmonary artery catheter data. The primary endpoint was the variation in transpulmonary driving pressure through the verticalization procedure. RESULTS: From May 2020 through January 2021, 30 patients were included. Transpulmonary driving pressure increased slightly from baseline (median and interquartile range [IQR], 9 [5-11] cmH2O) to the 90° position (10 [7-14] cmH2O; P < 10-2 for the overall effect of position in mixed model). End-expiratory lung volume increased with verticalization, in parallel to decreases in alveolar strain and increased arterial oxygenation. Verticalization was associated with decreased cardiac output and stroke volume, and increased norepinephrine doses and serum lactate levels, prompting interruption of the procedure in two patients. There were no other adverse events such as falls or equipment accidental removals. CONCLUSIONS: Verticalization to 90° is feasible in ARDS patients, improving EELV and oxygenation up to 30°, likely due to alveolar recruitment and blood flow redistribution. However, there is a risk of overdistension and hemodynamic instability beyond 30°, necessitating individualized bed angles based on clinical situations. Trial registration ClinicalTrials.gov registration number NCT04371016 , April 24, 2020.

Impact of advance directives on the variability between intensivists in the decisions to forgo life-sustaining treatment.

BACKGROUND: There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists. METHODS: We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients' characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD). RESULTS: A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p < 0.001). High inter-intensivist variability did not change with ADs (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain. CONCLUSIONS: ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist's decision took priority. Further research is needed to improve the matching of the physicians' decision with the patient's wishes. Trial registration ClinicalTrials.gov Identifier: NCT03013530. Registered 6 January 2017; https://clinicaltrials.gov/ct2/show/NCT03013530 .

Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study.

RATIONALE: Sevoflurane improves gas exchange, and reduces alveolar edema and inflammation in preclinical studies of lung injury, but its therapeutic effects have never been investigated in acute respiratory distress syndrome (ARDS). OBJECTIVES: To assess whether sevoflurane would improve gas exchange and inflammation in ARDS. METHODS: We did a parallel, open-label single-center randomized controlled trial at three intensive care units from a French university hospital between April 2014 and February 2016. Adult patients were randomized within 24 hours of moderate-to-severe ARDS onset to receive either intravenous midazolam or inhaled sevoflurane for 48 hours. The primary outcome was the PaO2/FiO2 ratio on Day 2. Secondary endpoints included alveolar and plasma levels of cytokines and soluble form of the receptor for advanced glycation end-products, and safety. Investigators who did the analyses were masked to group allocation. Analysis was by intention to treat. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were assigned to the sevoflurane group and 25 to the midazolam group. On Day 2, PaO2/FiO2 ratio was higher in the sevoflurane group than in the midazolam group (mean ± SD, 205 ± 56 vs. 166 ± 59, respectively; P = 0.04). There was a significant reduction over time in cytokines and soluble form of the receptor for advanced glycation end-products levels in the sevoflurane group, compared with the midazolam group, and no serious adverse event was observed with sevoflurane. CONCLUSIONS: In patients with ARDS, use of inhaled sevoflurane improved oxygenation and decreased levels of a marker of epithelial injury and of some inflammatory markers, compared with midazolam. Clinical trial registered with www.clinicaltrials.gov (NCT 02166853).

Cost assessment of a new oral care program in the intensive care unit to prevent ventilator-associated pneumonia.

OBJECTIVES: Ventilator-associated pneumonia (VAP) is the most frequent hospital-acquired infections in intensive care units (ICU). In the bundle of care to prevent the VAP, the oral care is very important strategies, to decrease the oropharyngeal bacterial colonization and presence of causative bacteria of VAP. In view of the paucity of medical economics studies, our objective was to determine the cost of implementing this oral care program for preventing VAP. MATERIALS AND METHODS: In five ICUs, during period 1, caregivers used a foam stick for oral care and, during period 2, a stick and tooth brushing with aspiration. Budgetary effect of the new program from the hospital's point of view was analyzed for both periods. The costs avoided were calculated from the incidence density of VAP (cases per 1000 days of intubation). The cost study included device cost, benefit lost, and ICU cost (medication, employer and employee contributions, blood sample analysis…). RESULTS: A total of 2030 intubated patients admitted to the ICUs benefited from oral care. The cost of implementing the study protocol was estimated to be €11,500 per year. VAP rates decreased significantly between the two periods (p1 = 12.8% and p2 = 8.5%, p = 0.002). The VAP revenue was ranged from €28,000 to €45,000 and the average cost from €39,906 to €42,332. The total cost assessment calculated was thus around €1.9 million in favor of the new oral care program. CONCLUSION AND CLINICAL RELEVANCE: Our study showed that the implementation of a simple strategy improved the quality of patient care is economically viable. TRIAL REGISTRATION: NCT02400294.

A cardiac arrest: when recommended mild therapeutic hypothermia reveals the mechanism*.

AIM: Describe the interaction between the use of mild induced hypothermia and acute diffuse coronary spasm. METHODS: We report the case of a 52-yr-old Caucasian woman resuscitated after initial cardiac arrest, with normal postresuscitation electrocardiogram, sufficient hemodynamic conditions, and decreased level of consciousness, who received mild induced hypothermia to reduce brain damage as suggested by cardiopulmonary resuscitation guidelines. RESULTS: After the beginning of mild therapeutic hypothermia, the patient experienced malignant diffuse coronary artery spasm, so-called Prinzmetal's angina, leading to myocardial ischemia and ventricular tachycardia, which was only resolved by intracoronary vasodilator injection. CONCLUSION: Mild induced hypothermia was apparently the trigger of a severe and diffuse coronary artery spasm.

Impact of Macintosh blade size on endotracheal intubation success in intensive care units: a retrospective multicenter observational MacSize-ICU study.

PURPOSE: To investigate the impact of Macintosh blade size used during direct laryngoscopy (DL) on first-attempt intubation success of orotracheal intubation in French intensive care units (ICUs). We hypothesized that success rate would be higher with Macintosh blade size No3 than with No4. METHODS: Multicenter retrospective observational study based on data from prospective trials conducted in 48 French ICUs of university, and general and private hospitals. After each intubation using Macintosh DL, patients' and operators' characteristics, Macintosh blade size, results of first DL and alternative techniques used, as well as the need of a second operator were collected. Complications rates associated with intubation were investigated. Primary outcome was success rate of first DL using Macintosh blade. RESULTS: A total of 2139 intubations were collected, 629 with a Macintosh blade No3 and 1510 with a No4. Incidence of first-pass intubation after first DL was significantly higher with Macintosh blade No3 (79.5 vs 73.3%, p = 0.0025), despite equivalent Cormack-Lehane scores (p = 0.48). Complications rates were equivalent between groups. Multivariate analysis concluded to a significant impact of Macintosh blade size on first DL success in favor of blade No3 (OR 1.44 [95% CI 1.14-1.84]; p = 0.0025) without any significant center effect on the primary outcome (p = 0.18). Propensity scores and adjustment analyses concluded to equivalent results. CONCLUSION: In the present study, Macintosh blade No3 was associated with improved first-passed DL in French ICUs. However, study design requires the conduct of a nationwide prospective multicenter randomized trial in different settings to confirm these results.

Soluble form of the receptor for advanced glycation end products is a marker of acute lung injury but not of severe sepsis in critically ill patients.

OBJECTIVES: Levels of the soluble form of the receptor for advanced glycation end products (sRAGE) are elevated during acute lung injury. However, it is not known whether this increase is linked to its involvement in alveolar epithelium injury or in systemic inflammation. Whether sRAGE is a marker of acute lung injury and acute respiratory distress syndrome, regardless of associated severe sepsis or septic shock, remains unknown in the intensive care unit setting. DESIGN: Prospective, observational, clinical study. SETTING: Intensive care unit of an academic medical center. PATIENTS: A total of 64 consecutive subjects, divided into four groups: acute lung injury/acute respiratory distress syndrome (n=15); acute lung injury/acute respiratory distress syndrome plus severe sepsis/septic shock (n=18); severe sepsis/septic shock (n=16); and mechanically ventilated controls (n=15). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma sRAGE levels were measured at baseline and on days 3, 6, and 28 (or at intensive care unit discharge, whichever occurred first). Baseline plasma levels of sRAGE were significantly higher in patients with acute lung injury/acute respiratory distress syndrome, with (median, 2951 pg/mL) or without (median, 3761 pg/mL) severe sepsis, than in patients with severe sepsis (median, 488 pg/mL) only and in mechanically ventilated controls (median, 525 pg/mL). Levels of sRAGE were correlated with acute lung injury/acute respiratory distress syndrome severity and decreased over time but were not associated with outcome. Lower baseline plasma sRAGE was associated with focal loss of aeration based on computed tomography lung morphology. CONCLUSIONS: sRAGE levels were elevated during acute lung injury/acute respiratory distress syndrome, regardless of the presence or absence of severe sepsis. The plasma level of sRAGE was correlated with clinical and radiographic severity in acute respiratory distress syndrome patients and decreased over time, suggesting resolution of the injury to the alveolar epithelium. Further study is warranted to test the clinical utility of this biomarker in managing such patients and to better understand its relationship with lung morphology during acute lung injury/acute respiratory distress syndrome.

Central venous O2 saturation and venous-to-arterial CO2 difference as complementary tools for goal-directed therapy during high-risk surgery.

INTRODUCTION: Central venous oxygen saturation (ScvO2) is a useful therapeutic target in septic shock and high-risk surgery. We tested the hypothesis that central venous-to-arterial carbon dioxide difference (P(cv-a)CO2), a global index of tissue perfusion, could be used as a complementary tool to ScvO2 for goal-directed fluid therapy (GDT) to identify persistent low flow after optimization of preload has been achieved by fluid loading during high-risk surgery. METHODS: This is a secondary analysis of results obtained in a study involving 70 adult patients (ASA I to III), undergoing major abdominal surgery, and treated with an individualized goal-directed fluid replacement therapy. All patients were managed to maintain a respiratory variation in peak aortic flow velocity below 13%. Cardiac index (CI), oxygen delivery index (DO2i), ScvO2, P(cv-a)CO2 and postoperative complications were recorded blindly for all patients. RESULTS: A total of 34% of patients developed postoperative complications. At baseline, there was no difference in demographic or haemodynamic variables between patients who developed complications and those who did not. In patients with complications, during surgery, both mean ScvO2 (78 ± 4 versus 81 ± 4%, P = 0.017) and minimal ScvO2 (minScvO2) (67 ± 6 versus 72 ± 6%, P = 0.0017) were lower than in patients without complications, despite perfusion of similar volumes of fluids and comparable CI and DO2i values. The optimal ScvO2 cut-off value was 70.6% and minScvO2 < 70% was independently associated with the development of postoperative complications (OR = 4.2 (95% CI: 1.1 to 14.4), P = 0.025). P(cv-a)CO2 was larger in patients with complications (7.8 ± 2 versus 5.6 ± 2 mmHg, P < 10-6). In patients with complications and ScvO2 ≥ 71%, P(cv-a)CO2 was also significantly larger (7.7 ± 2 versus 5.5 ± 2 mmHg, P < 10-6) than in patients without complications. The area under the receiver operating characteristic (ROC) curve was 0.785 (95% CI: 0.74 to 0.83) for discrimination of patients with ScvO2 ≥ 71% who did and did not develop complications, with 5 mmHg as the most predictive threshold value. CONCLUSIONS: ScvO2 reflects important changes in O2 delivery in relation to O2 needs during the perioperative period. A P(cv-a)CO2 < 5 mmHg might serve as a complementary target to ScvO2 during GDT to identify persistent inadequacy of the circulatory response in face of metabolic requirements when an ScvO2 ≥ 71% is achieved. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00852449.

A recruitment maneuver increases oxygenation after intubation of hypoxemic intensive care unit patients: a randomized controlled study.

INTRODUCTION: Tracheal intubation and anaesthesia promotes lung collapse and hypoxemia. In acute lung injury patients, recruitment maneuvers (RMs) increase lung volume and oxygenation, and decrease atelectasis. The aim of this study was to evaluate the efficacy and safety of RMs performed immediately after intubation. METHODS: This randomized controlled study was conducted in two 16-bed medical-surgical intensive care units within the same university hospital. Consecutive patients requiring intubation for acute hypoxemic respiratory failure were included. Patients were randomized to undergo a RM immediately (within 2 minutes) after intubation, consisting of a continuous positive airway pressure (CPAP) of 40 cmH2O over 30 seconds (RM group), or not (control group). Blood gases were sampled and blood samples taken for culture before, within 2 minutes, 5 minutes, and 30 minutes after intubation. Haemodynamic and respiratory parameters were continuously recorded throughout the study. Positive end expiratory pressure (PEEP) was set at 5 cmH2O throughout. RESULTS: The control (n = 20) and RM (n = 20) groups were similar in terms of age, disease severity, diagnosis at time of admission, and PaO2 obtained under 10-15 L/min oxygen flow immediately before (81 +/- 15 vs 83 +/- 35 mmHg, P = 0.9), and within 2 minutes after, intubation under 100% FiO2 (81 +/- 15 vs 83 +/- 35 mmHg, P = 0.9). Five minutes after intubation, PaO2 obtained under 100% FiO2 was significantly higher in the RM group compared with the control group (93 +/- 36 vs 236 +/- 117 mmHg, P = 0.008). The difference remained significant at 30 minutes with 110 +/- 39 and 180 +/- 79 mmHg, respectively, for the control and RM groups. No significant difference in haemodynamic conditions was observed between groups at any time. Following tracheal intubation, 15 patients had positive blood cultures, showing microorganisms shared with tracheal aspirates, with no significant difference in the incidence of culture positivity between groups. CONCLUSIONS: Recruitment maneuver following intubation in hypoxemic patients improved short-term oxygenation, and was not associated with increased adverse effects. TRIAL REGISTRATION: NCT01014299.

Respiratory effects of different recruitment maneuvers in acute respiratory distress syndrome.

INTRODUCTION: Alveolar derecruitment may occur during low tidal volume ventilation and may be prevented by recruitment maneuvers (RMs). The aim of this study was to compare two RMs in acute respiratory distress syndrome (ARDS) patients. METHODS: Nineteen patients with ARDS and protective ventilation were included in a randomized crossover study. Both RMs were applied in each patient, beginning with either continuous positive airway pressure (CPAP) with 40 cm H2O for 40 seconds or extended sigh (eSigh) consisting of a positive end-expiratory pressure maintained at 10 cm H2O above the lower inflection point of the pressure-volume curve for 15 minutes. Recruited volume, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2), and hemodynamic parameters were recorded before (baseline) and 5 and 60 minutes after RM. All patients had a lung computed tomography (CT) scan before study inclusion. RESULTS: Before RM, PaO2/FiO2 was 151 +/- 61 mm Hg. Both RMs increased oxygenation, but the increase in PaO2/FiO2 was significantly higher with eSigh than CPAP at 5 minutes (73% +/- 25% versus 44% +/- 28%; P < 0.001) and 60 minutes (68% +/- 23% versus 35% +/- 22%; P < 0.001). Only eSigh significantly increased recruited volume at 5 and 60 minutes (21% +/- 22% and 21% +/- 25%; P = 0.0003 and P = 0.001, respectively). The only difference between responders and non-responders was CT lung morphology. Eleven patients were considered as recruiters with eSigh (10 with diffuse loss of aeration) and 6 with CPAP (5 with diffuse loss of aeration). During CPAP, 2 patients needed interruption of RM due to a drop in systolic arterial pressure. CONCLUSION: Both RMs effectively increase oxygenation, but CPAP failed to increase recruited volume. When the lung is recruited with an eSigh adapted for each patient, alveolar recruitment and oxygenation are superior to those observed with CPAP.

Low doses of ketamine reduce delirium but not opiate consumption in mechanically ventilated and sedated ICU patients: A randomised double-blind control trial.

CONTEXT: Low doses of ketamine are commonly used to decrease opiates tolerance, hyperalgesia and delirium in perioperative theatre but these properties have never been studied in intensive care unit (ICU) patients. PURPOSE: To determine the impact of ketamine infusion on opiates consumption when added to standard care in ICU patients requiring sedation for mechanical ventilation. METHODS: Patients admitted in a general ICU of a university hospital and undergoing mechanical ventilation (n = 162) with nurse-driven sedation protocol were randomly assigned into ketamine (2 mg/kg/h) or placebo in a double-blinded control trial. Patients were assessed for sedation and analgesia levels, opiates consumption and delirium (using the Confusion Assessment Method for ICU). RESULTS: Daily consumption of remifentanil (7.9 ± 1.0 vs. 9.3 ± 1.0 µg/kg/h, P = 0.548) and increase in remifentanil doses required for equianalgesia (0.107 ± 0.17 and 0.11 ± 0.18 µg/kg/min, P = 0.78) were not different between ketamine and control groups. The incidence was higher in the placebo group 30/82 (37%) than in the ketamine group 17/80 (21%) (P = 0.03). The duration of delirium was lower in ketamine group (5.3 ± 4.7 vs. 2.8 ± 3 days, P = 0.005). Mortality rates, ventilator-free days and ICU length of stay (LOS) were non-statistically different in both groups. CONCLUSIONS: When the best practices of sedation (nurse-driven sedation, a consistent light-to-moderate sedation level, and delirium monitoring) are used for all patients, the addition of low doses of ketamine does not decrease opiate consumption but reduces delirium incidence and its duration in medico-surgical ICU patients with no effect on mortality rate and ICU LOS.

Remifentanil-based sedation to treat noninvasive ventilation failure: a preliminary study.

OBJECTIVE: To assess the feasibility and safety of remifentanil-based sedation during noninvasive ventilation (NIV) in patients with NIV failure. DESIGN AND SETTING: Prospective clinical investigation in a 16-bed intensive care unit of a university hospital in France. PATIENTS: Thirteen patients in NIV failure due to discomfort and/or refusal to continue this ventilatory support: 10 with acute respiratory failure and 3 with acute hypercapnic respiratory failure. INTERVENTION: Patients were administered methylene blue and were sedated (Ramsay scale 2-3) by a continuous perfusion of remifentanil during NIV. Cardiorespiratory and ventilatory parameters, blood gas analysis, and adverse events were prospectively recorded. MEASUREMENTS AND RESULTS: The 13 patients received a total of 125 NIV sessions, totaling 1200 h, of NIV under remifentanil-based sedation (mean remifentanil dose 0.1+/-0.03 microg/kg per minute). Three patients also required propofol. PaO2/FIO2 ratio increased from 134+/-69 to 187+/-43 mmHg after 1 h. In patients with acute respiratory failure respiratory rate decreased from 34+/-12 per minute before remifentanil to 25+/-4 per minute after 1h. In the three patients with acute hypercapnic respiratory failure PaCO2 decreased from 69+/-7 to 42+/-5 mmHg. Four patients required endotracheal intubation without aspiration pneumonia. Twelve of the 13 patients left the ICU. CONCLUSION: This pilot study shows that remifentanil-based sedation is safe and effective in the treatment of NIV failure due to low tolerance.

Comparative study of 2 oral care protocols in intensive care units.

BACKGROUND: The quality of oral care is important in limiting the emergence of ventilator-associated pneumonia (VAP) in intubated patients. Our main objective was to measure the quality improvement in oral care following the implementation of a new oral care protocol. We also monitored VAP rates. MATERIAL/METHODS: This was a cohort study of patients in 5 adult ICUs covering different specialties. During period 1, caregivers used a foam stick for oral care and during period 2 a stick and tooth brushing with aspiration. Oral chlorhexidine was used during both periods. The caregivers rated improvement in oral health on the basis of 4 criteria (tongue, mucous membranes, gingivae, and teeth). Caregiver satisfaction was also assessed. The incidence of VAP was monitored. RESULTS: A total of 2,030 intubated patients admitted to intensive care units benefited from oral care. The patient populations during the 2 periods were similar with regard to demographic data and VAP potential risk factors. Oral health was significantly better from the third day of oral care in period 2 onward (period 1, 6.4 ± 2.1; period 2, 5.6 ± 1.8; P = .043). Caregivers found the period 2 protocol easier to implement and more effective. VAP rates decreased significantly between the 2 periods (period 1, 12.8%; period 2, 8.5%; P = .002). CONCLUSIONS: Our study showed that the implementation of a simple strategy improved the quality of oral care of patients in intensive care units, and decreased VAP rates.

Lemierre's syndrome and genetic polymorphisms: a case report.

BACKGROUND: Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. CASE PRESENTATION: A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. CONCLUSION: The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology.

Net alveolar fluid clearance is associated with lung morphology phenotypes in acute respiratory distress syndrome.

BACKGROUND: The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that encompasses multiple phenotypes, e.g. with regards to lung morphology as assessed by computed tomography (CT). Focal or non-focal lung morphology may influence the response to positive end-expiratory pressure (PEEP), recruitment manoeuvres and prone position. Lung morphology has been hypothesized to be associated with alveolar fluid clearance (AFC), thus explaining various responses to such therapeutic interventions; however, this hypothesis has not been specifically studied in humans. METHODS: We measured net AFC rates in 30 patients with ARDS as a secondary data analysis of a prospective single-centre study. Net AFC rates were compared between patients with focal ARDS and those with non-focal ARDS, as assessed by lung CT-scans. RESULTS: Net AFC rates were significantly lower in patients with non-focal ARDS (n=23; median [interquartile range], 1.5 [0-5.5] %/h) as compared to those with focal ARDS (n=7; 10.3 [4.5-15] %/h) (P=0.01). The area under the receiver-operating characteristic curve when net AFC rates were used to differentiate the presence from absence of non-focal ARDS was 0.93 (95% confidence interval, 0.81-1). Tidal volumes and PEEP levels differed between focal and non-focal ARDS patients, but there was no difference in arterial oxygenation or in alveolar-capillary permeability. CONCLUSIONS: Non-focal lung morphology may be characterized by a functional endotype consistent with marked AFC impairment. Despite study limitations and the need for validating studies in larger cohorts, such novel findings may reinforce our understanding of the association between ARDS phenotypes and therapeutic responses.

Soluble Forms and Ligands of the Receptor for Advanced Glycation End-Products in Patients with Acute Respiratory Distress Syndrome: An Observational Prospective Study.

BACKGROUND: The main soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated during acute respiratory distress syndrome (ARDS). However other RAGE isoforms and multiple ligands have been poorly reported in the clinical setting, and their respective contribution to RAGE activation during ARDS remains unclear. Our goal was therefore to describe main RAGE isoforms and ligands levels during ARDS. METHODS: 30 ARDS patients and 30 mechanically ventilated controls were prospectively included in this monocenter observational study. Arterial, superior vena cava and alveolar fluid levels of sRAGE, endogenous-secretory RAGE (esRAGE), high mobility group box-1 protein (HMGB1), S100A12 and advanced glycation end-products (AGEs) were measured in duplicate ELISA on day 0, day 3 and day 6. In patients with ARDS, baseline lung morphology was assessed with computed tomography. RESULTS: ARDS patients had higher arterial, central venous and alveolar levels of sRAGE, HMGB1 and S100A12, but lower levels of esRAGE and AGEs, than controls. Baseline arterial sRAGE, HMGB1 and S100A12 were correlated with nonfocal ARDS (AUC 0.79, 0.65 and 0.63, respectively). Baseline arterial sRAGE, esRAGE, S100A12 and AGEs were associated with severity as assessed by PaO2/FiO2. CONCLUSIONS: This is the first kinetics study of levels of RAGE main isoforms and ligands during ARDS. Elevated sRAGE, HMGB1 and S100A12, with decreased esRAGE and AGEs, were found to distinguish patients with ARDS from those without. Our findings should prompt future studies aimed at elucidating RAGE/HMGB1/S100A12 axis involvement in ARDS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01270295.

Effects of a recruitment maneuver on plasma levels of soluble RAGE in patients with diffuse acute respiratory distress syndrome: a prospective randomized crossover study.

PURPOSE: The soluble form of the receptor for advanced glycation end-products (sRAGE) is a promising marker for epithelial dysfunction, but it has not been fully characterized as a biomarker of acute respiratory distress syndrome (ARDS). Whether sRAGE could inform on the response to ventilator settings has been poorly investigated, and whether a recruitment maneuver (RM) may influence plasma sRAGE remains unknown. METHODS: Twenty-four patients with moderate/severe, nonfocal ARDS were enrolled in this prospective monocentric crossover study and randomized into a "RM-SHAM" group when a 6-h-long RM sequence preceded a 6-h-long sham evaluation period, or a "SHAM-RM" group (inverted sequences). Protective ventilation was applied, and RM consisted of the application of 40 cmH2O airway pressure for 40 s. Arterial blood was sampled for gas analyses and sRAGE measurements, 5 min pre-RM (or 40-s-long sham period), 5, 30 min, 1, 4, and 6 h after the RM (or 40-s-long sham period). RESULTS: Mean PaO2/FiO2, tidal volume, PEEP, and plateau pressure were 125 mmHg, 6.8 ml/kg (ideal body weight), and 13 and 26 cmH2O, respectively. Median baseline plasma sRAGE levels were 3,232 pg/ml. RM induced a significant decrease in sRAGE (-1,598 ± 859 pg/ml) in 1 h (p = 0.043). At 4 and 6 h post-RM, sRAGE levels increased back toward baseline values. Pre-RM sRAGE was associated with RM-induced oxygenation improvement (AUC 0.84). CONCLUSIONS: We report the first kinetics study of plasma sRAGE after RM in ARDS. Our findings reinforce the value of plasma sRAGE as a biomarker of ARDS.

Epidural analgesia in the intensive care unit: An observational series of 121 patients.

BACKGROUND: Epidural analgesia (EA) has been more investigated during the perioperative period than in the intensive care unit (ICU) setting. Recent studies support beneficial effects for EA beyond analgesia itself. However, data on feasibility and safety are still lacking in the ICU. Our goal was to assess the feasibility and practice of EA in ICU patients. METHODS: Multicentre observational study in 3 ICUs over a 10-month period. Goals were to report the incidence of EA-related complications and EA duration. All ICU patients receiving EA were included, whether EA was initiated in the ICU or elsewhere, e.g. in the operating room. Demographics, clinical and biological data were prospectively recorded. Epidural catheter tips were sent to the microbiology laboratory for culture. RESULTS: One hundred and twenty-one patients were included (mean age 60 years), with mean SOFA and median SAPS II scores of 3.2 and 32, respectively. Reasons for EA initiation included trauma (14%), postoperative pain management after major surgery (42%), and pancreatitis (31%). No EA-related neurologic complication was recorded, and one case of epidural abscess is discussed. No other EA-related infectious complications were observed. Median duration of EA was 11 days. Reasons for EA discontinuation included efficient analgesia without EA (60%) and accidental catheter removal (17%). 22% of epidural catheter cultures were positive for skin flora bacteria. CONCLUSION: EA seems feasible in the ICU. Its apparent safety should be further validated in larger cohorts, but these preliminary results may stimulate more interest in the assessment of potential benefits associated with EA in the ICU setting.