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Diaphragm neurostimulation consists of placing electrodes directly on or in proximity to the phrenic nerve(s) to elicit diaphragmatic contractions. Since its initial description in the 18th century, indications have shifted from cardiopulmonary resuscitation to long-term ventilatory support. Recently, the technical development of devices for temporary diaphragm neurostimulation has opened up the possibility of a new era for the management of mechanically ventilated patients. Combining positive pressure ventilation with diaphragm neurostimulation offers a potentially promising new approach to the delivery of mechanical ventilation which may benefit multiple organ systems. Maintaining diaphragm contractions during ventilation may attenuate diaphragm atrophy and accelerate weaning from mechanical ventilation. Preventing atelectasis and preserving lung volume can reduce lung stress and strain and improve homogeneity of ventilation, potentially mitigating ventilator-induced lung injury. Furthermore, restoring the thoracoabdominal pressure gradient generated by diaphragm contractions may attenuate the drop in cardiac output induced by positive pressure ventilation. Experimental evidence suggests diaphragm neurostimulation may prevent neuroinflammation associated with mechanical ventilation. This review describes the historical development and evolving approaches to diaphragm neurostimulation during mechanical ventilation and surveys the potential mechanisms of benefit. The review proposes a research agenda and offers perspectives for the future of diaphragm neurostimulation assisted mechanical ventilation for critically ill patients. [ABSTRACT FROM AUTHOR]

Purpose: Whether undocumented migrants admitted to intensive care units (ICUs) have specific features is unknown. We aimed to determine the features and outcomes of undocumented migrants admitted to French ICUs. Methods: We retrospectively included all undocumented adult migrants admitted in 2011–2018 and compared them to the general ICU population. We also compared these two groups matched on age, sex, severity, comorbidities, reason for ICU admission and public/private hospital. Results: We identified 14,554 ICU stays, with an increase from 2 to 4‰ of all ICU admissions over time. Shock (16.7%), post-operative care (13.8%), and trauma (10.5%) were the main reasons for ICU admission. Compared to general ICU patients, migrants were younger and had greater disease severity. After adjustment on age and sex, the following were more common in migrants: shock (OR 1.2 [1.14–1.25]; P < 0.0001), infections (1.48 [1.38–1.54]; P < 0.001), acute respiratory failure (1.09 [1.03–1.15]; P = 0.006), acute kidney injury (1.12 [1.05–1.19]; P < 0.001), obstetric events (1.53 [1.66–1.81]; P < 0.0001), and neurological deficits (1.19 [1.12–1.27]; P < 0.0001). In the matched study, migrants more often required vasopressors, mechanical ventilation, and renal replacement therapy; had longer ICU stays (median 4 [2–8] vs. 4 [2–7] days; P < 0.0001) and hospital stays (10 [5–20] vs. 8 [4–15]; P < 0.0001) and had higher hospital costs (14.2 ± 23.6 vs. 13.4 ± 11.5 K€; P < 0.0001). Hospital mortality was similar (6.7% vs. 6.6%; P = 0.69). Conclusion: Admissions of undocumented migrants to French ICUs doubled from 2011 to 2018. The patients were younger and, although sicker, achieved similar outcomes to those in general ICU patients. [ABSTRACT FROM AUTHOR]

Background: Dexamethasone decreases mortality in patients with severe coronavirus disease 2019 (COVID-19) and has become the standard of care during the second wave of pandemic. Dexamethasone is an immunosuppressive treatment potentially increasing the risk of secondary hospital acquired infections in critically ill patients. We conducted an observational retrospective study in three French intensive care units (ICUs) comparing the first and second waves of pandemic to investigate the role of dexamethasone in the occurrence of ventilator-associated pneumonia (VAP) and blood stream infections (BSI). Patients admitted from March to November 2020 with a documented COVID-19 and requiring mechanical ventilation (MV) for ≥ 48 h were included. The main study outcomes were the incidence of VAP and BSI according to the use of dexamethasone. Secondary outcomes were the ventilator-free days (VFD) at day-28 and day-60, ICU and hospital length of stay and mortality. Results: Among the 151 patients included, 84 received dexamethasone, all but one during the second wave. VAP occurred in 63% of patients treated with dexamethasone (DEXA+) and 57% in those not receiving dexamethasone (DEXA−) (p = 0.43). The cumulative incidence of VAP, considering death, duration of MV and late immunosuppression as competing factors was not different between groups (p = 0.59). A multivariate analysis did not identify dexamethasone as an independent risk factor for VAP occurrence. The occurrence of BSI was not different between groups (29 vs. 30%; p = 0.86). DEXA+ patients had more VFD at day-28 (9 (0–21) vs. 0 (0–11) days; p = 0.009) and a reduced ICU length of stay (20 (11–44) vs. 32 (17–46) days; p = 0.01). Mortality did not differ between groups. Conclusions: In this cohort of COVID-19 patients requiring invasive MV, dexamethasone was not associated with an increased incidence of VAP or BSI. Dexamethasone might not explain the high rates of VAP and BSI observed in critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation. Methods: This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37). Results: The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0–51] and 0 [0–43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P =.845). Creatinine levels and blood cells counts did not differ significantly between the two groups. Conclusions: In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome. [ABSTRACT FROM AUTHOR]

Neuromuscular blocking agents (NMBAs) inhibit patient-initiated active breath and the risk of high tidal volumes and consequent high transpulmonary pressure swings, and minimize patient/ ventilator asynchrony in acute respiratory distress syndrome (ARDS). Minimization of volutrauma and ventilator-induced lung injury (VILI) results in a lower incidence of barotrauma, improved oxygenation and a decrease in circulating proinflammatory markers. Recent randomized clinical trials did not reveal harmful muscular effects during a short course of NMBAs. The use of NMBAs should be considered during the early phase of severe ARDS for patients to facilitate lung protective ventilation or prone positioning only after optimising mechanical ventilation and sedation. The use of NMBAs should be integrated in a global strategy including the reduction of tidal volume, the rational use of PEEP, prone positioning and the use of a ventilatory mode allowing spontaneous ventilation as soon as possible. Partial neuromuscular blockade should be evaluated in future trials. [ABSTRACT FROM AUTHOR]

Ventilator-associated pneumonia (VAP) is one of the most frequent ICU-acquired infections. Reported incidences vary widely from 5 to 40% depending on the setting and diagnostic criteria. VAP is associated with prolonged duration of mechanical ventilation and ICU stay. The estimated attributable mortality of VAP is around 10%, with higher mortality rates in surgical ICU patients and in patients with mid-range severity scores at admission. Microbiological confirmation of infection is strongly encouraged. Which sampling method to use is still a matter of controversy. Emerging microbiological tools will likely modify our routine approach to diagnosing and treating VAP in the next future. Prevention of VAP is based on minimizing the exposure to mechanical ventilation and encouraging early liberation. Bundles that combine multiple prevention strategies may improve outcomes, but large randomized trials are needed to confirm this. Treatment should be limited to 7 days in the vast majority of the cases. Patients should be reassessed daily to confirm ongoing suspicion of disease, antibiotics should be narrowed as soon as antibiotic susceptibility results are available, and clinicians should consider stopping antibiotics if cultures are negative. [ABSTRACT FROM AUTHOR]

Background Randomized clinical trials (RCTs) in hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP, respectively) are important for the evaluation of new antimicrobials. However, the heterogeneity in endpoints used in RCTs evaluating treatment of HABP/VABP may puzzle clinicians. The aim of this work was to reach a consensus on clinical endpoints to consider in future clinical trials evaluating antimicrobial treatment efficacy for HABP/VABP. Methods Twenty-six international experts from intensive care, infectious diseases, and the pharmaceutical industry were polled using the Delphi method. Results The panel recommended a hierarchical composite endpoint including, by priority order, (1) survival at day 28, (2) mechanical ventilation–free days through day 28, and (3) clinical cure between study days 7 and 10 for VABP; and (1) survival (day 28) and (2) clinical cure (days 7–10) for HABP. Clinical cure was defined as the combination of resolution of signs and symptoms present at enrollment and improvement or lack of progression of radiological signs. More than 70% of the experts agreed to assess survival and mechanical ventilation–free days though day 28, and clinical cure between day 7 and day 10 after treatment initiation. Finally, the hierarchical order of endpoint components was reached after 3 Delphi rounds (72% agreement). Conclusions We provide a multinational expert consensus on separate hierarchical composite endpoints for VABP and HABP, and on a definition of clinical cure that could be considered for use in future HABP/VABP clinical trials. [ABSTRACT FROM AUTHOR]

Background: Patients starting noninvasive ventilation (NIV) to treat acute respiratory failure are often unable to eat and therefore remain in the fasting state or receive nutritional support. Maintaining a good nutritional status has been reported to improve patient outcomes. In the present study, our primary objective was to describe the nutritional management of patients starting first-line NIV, and our secondary objectives were to assess potential associations between nutritional management and outcomes.Methods: Observational retrospective cohort study of a prospective database fed by 20 French intensive care units. Adult medical patients receiving NIV for more than 2 consecutive days were included and divided into four groups on the basis of nutritional support received during the first 2 days of NIV: no nutrition, enteral nutrition, parenteral nutrition only, and oral nutrition only.Results: Of the 16,594 patients admitted during the study period, 1075 met the inclusion criteria; of these, 622 (57.9%) received no nutrition, 28 (2.6%) received enteral nutrition, 74 (6.9%) received parenteral nutrition only, and 351 (32.7%) received oral nutrition only. After adjustment for confounders, enteral nutrition (vs. no nutrition) was associated with higher 28-day mortality (adjusted HR, 2.3; 95% CI, 1.2-4.4) and invasive mechanical ventilation needs (adjusted HR, 2.1; 95% CI, 1.1-4.2), as well as with fewer ventilator-free days by day 28 (adjusted relative risk, 0.7; 95% CI, 0.5-0.9).Conclusions: Nearly three-fifths of patients receiving NIV fasted for the first 2 days. Lack of feeding or underfeeding was not associated with mortality. The optimal route of nutrition for these patients needs to be investigated. [ABSTRACT FROM AUTHOR]

Background: Nosocomial infections occurring during extracorporeal membrane oxygenation (ECMO) support have already been reported, but few studied infections directly related to ECMO devices. This study aims to evaluate the rate of both colonisations and infections related to ECMO devices at the time of ECMO removal. Results: We included all consecutive adult patients treated with venovenous ECMO (VV-ECMO) for at least 48 h during a 34-month study. At the time of ECMO removal, blood cultures, swab cultures on insertion cannula site and intravascular cannula extremity cultures were systematically performed. Each ECMO device was classified according to the infectious status into three groups: (1) uninfected/uncolonised ECMO device, (2) ECMO device colonisation and (3) ECMO device infection. Ninety-nine patients underwent 103 VV-ECMO, representing 1472 ECMO days. The ECMO device infection rate was 9.7% (10 events), including 7 ECMO device-related bloodstream infections (6.8%). The ECMO device colonisation rate was 32% (33 events). No difference was observed between the three groups, regarding days of mechanical ventilation, ICU length of stay, ICU mortality and in-hospital mortality. We observed a longer ECMO duration in the ECMO device colonisation group as compared to the uninfected/uncolonised ECMO device group [12 (9-20 days) vs. 5 days (5-16 days), respectively, p < 0.05]. Conclusions: At the time of ECMO removal, systematic blood culture and intravascular extremity cannula culture may help to diagnose ECMO device-related infection. We reported a quite low infection rate related to ECMO device. Further studies are needed to evaluate the benefits of systematic strategies of cannula culture at the time of ECMO removal. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to concisely describe the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to extracorporeal membrane oxygenation (ECMO).Methods: Narrative review based on a systematic analysis of the medical literature, national and international guidelines, and expert opinion.Results: The use of venovenous ECMO (VV-ECMO) is increasing in the most severe forms of acute lung injury. In patients with cardiogenic shock, short-term veno-arterial ECMO (VA-ECMO) provides both pulmonary and circulatory support. Technological improvements and recently published studies suggest that ECMO is able to improve patients' outcomes. There are, however, many uncertainties regarding the real benefits of this technique both in hemodynamic and respiratory failure, the territorial organization to deliver ECMO, the indications and the use of concomitant treatments.Conclusions: Although there have been considerable advances regarding the use of ECMO in critically ill patients, the risk/benefit ratio remains underinvestigated. ECMO indications, organization of ECMO delivery, and use of adjuvant therapeutics need also to be explored. Ongoing and future studies may be able to resolve these issues. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is a dreaded complication of varicella-zoster virus (VZV) infection in adults; however, the data are limited. Our objective was to investigate the clinical features, management, and outcomes of critically ill patients with VZV-related community-acquired pneumonia (VZV-CAP).Methods: This was an observational study of patients with VZV-CAP admitted to 29 intensive care units (ICUs) from January 1996 to January 2015.Results: One hundred and two patients with VZV-CAP were included. Patients were young (age 39 years (interquartile range 32-51)) and 53 (52%) were immunocompromised. Time since respiratory symptom onset was 2 (1-3) days. There was a seasonal distribution of the disease, with more cases during spring and winter time. All but four patients presented with typical skin rash on ICU admission. Half the patients received mechanical ventilation within 1 (1-2) day following ICU admission (the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) = 150 (80-284), 80% with acute respiratory distress syndrome (ARDS)). Sequential Organ Failure Assessment (SOFA) score on day 1 (odds ratio (OR) 1.90 (1.33-2.70); p < 0.001), oxygen flow at ICU admission (OR 1.25 (1.08-1.45); p = 0.004), and early bacterial co-infection (OR 14.94 (2.00-111.8); p = 0.009) were independently associated with the need for mechanical ventilation. Duration of mechanical ventilation was 14 (7-21) days. ICU and hospital mortality rates were 17% and 24%, respectively. All patients were treated with aciclovir and 10 received adjunctive therapy with steroids. Compared to 60 matched steroid-free controls, patients treated with steroids had a longer mechanical ventilation duration, ICU length of stay, and a similar hospital mortality, but experienced more ICU-acquired infections.Conclusions: Severe VZV-CAP is responsible for an acute pulmonary involvement associated with a significant morbidity and mortality. Steroid therapy did not influence mortality, but increased the risk of superinfection. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether neuromuscular blocking agents (NMBA) exert beneficial effects in acute respiratory distress syndrome (ARDS) by reason of their action on respiratory mechanics, particularly transpulmonary pressures (P L).Methods: A prospective randomised controlled study in patients with moderate to severe ARDS within 48 h of the onset of ARDS. All patients were monitored by means of an oesophageal catheter and followed up for 48 h. Moderate ARDS patients were randomised into two groups according to whether they were given a 48-h continuous infusion of cisatracurium besylate or not (control group). Severe ARDS patients did not undergo randomisation and all received cisatracurium besylate per protocol. The changes during the 48-h study period in oxygenation and in respiratory mechanics, including inspiratory and expiratory P L and driving pressure, were assessed and compared. Delta P L (∆P L) was defined as inspiratory P L minus expiratory P L.Results: Thirty patients were included, 24 with moderate ARDS and 6 with severe ARDS. NMBA infusion was associated with an improvement in oxygenation in both moderate and severe ARDS, accompanied by a decrease in both plateau pressure and total positive end-expiratory pressure. The mean inspiratory and expiratory P L were higher in the moderate ARDS group receiving NMBA than in the control group. In contrast, there was no change in either driving pressure or ∆P L related to NMBA administration.Conclusions: NMBA could exert beneficial effects in patients with moderate ARDS, at least in part, by limiting expiratory efforts. [ABSTRACT FROM AUTHOR]

Purpose: Prone position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO2/FiO2 ratio <150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS.Methods: We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed.Results: Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO2 change was found according to oxygenation response or lung morphology.Conclusions: In ARDS patients with a PaO2/FiO2 ratio ≤150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP. [ABSTRACT FROM AUTHOR]

Despite expensive life-sustaining interventions delivered in the ICU, mortality and morbidity in patients with acute respiratory failure (ARF) remain unacceptably high. Extracorporeal membrane oxygenation (ECMO) has emerged as a promising intervention that may provide more efficacious supportive care to these patients. Improvements in technology have made ECMO safer and easier to use, allowing for the potential of more widespread application in patients with ARF. A greater appreciation of the complications associated with the placement of an artificial airway and mechanical ventilation has led clinicians and researchers to seek viable alternatives to providing supportive care in these patients. Thus, this review will summarize the current knowledge regarding the use of venovenous (VV)-ECMO for ARF and describe some of the recent controversies in the field, such as mechanical ventilation, anticoagulation and transfusion therapy, and ethical concerns in patients supported with VV-ECMO. [ABSTRACT FROM AUTHOR]

An editorial is presented which discusses a study by M. Cressoni and others on lung opening pressures and atelectrauma in acute respiratory distress syndrome (ARDS) patients. Topics include use of mechanical ventilation in ARDS patients to provide lung protection and set tidal volume; amount of lung that needs be recruited between 30 and 45 centimeter of water inspiration pressures in mild, moderate and severe ARDS; and change in homogeneity in distribution of lung aeration loss/tissue gain.

The article discusses various studies which appeared in "Intensive Care Medicine" journal in 2013. Information is presented on the study in Malaysia which assessed whether early sedation depth was independently associated with delayed extubation and increased mortality. An overview of a review article about efficient weaning and automatic ventilation modes for failing patients.

Introduction: It has been suggested that delayed intensive care unit (ICU) transfer is associated with increased mortality for patients with community-acquired pneumonia (CAP). However, ICU admission policies and patient epidemiology vary widely across the world depending on local hospital practices and organizational constraints. We hypothesized that the time from the onset of CAP symptoms to invasive mechanical ventilation could be a relevant prognostic factor. Methods: One hundred patients with a CAP and necessitating invasive mechanical ventilation were included. Prospectively collected data were retrospectively analysed. Two study groups were identified based on the time of the initiation of invasive mechanical ventilation (rapid respiratory failure requiring mechanical ventilation within 72 h of the onset of CAP and progressive respiratory failure requiring invasive mechanical ventilation 4 or more days after the onset of CAP). Results: Excepting more COPD patients in the rapid respiratory failure group and more patients with diabetes in the progressive respiratory failure group, these patients had similar characteristics. The overall in-hospital mortality rate was 28% in the rapid respiratory failure group and 51% in the progressive respiratory failure group (P = 0.03). The ICU and the day 30 mortality rates were higher in the progressive respiratory failure group (47% vs. 23%, P = 0.02; and 37.7% vs. 21.3%, P = 0.03; respectively). After adjusting for the propensity score and other potential confounding factors, progressive respiratory failure remained associated with hospital mortality only after 12 days of invasive mechanical ventilation. Conclusions: This study suggested that the duration or delay in the time to intubation from the onset of CAP symptoms was associated with the outcomes in those patients who ultimately required invasive mechanical ventilation. [ABSTRACT FROM AUTHOR]

Over the last two decades, the increasing use of noninvasive ventilation (NIV) has diminished the need for endotracheal ventilation, thus decreasing the rate of ventilation-induced complications. Thus, NIV has decreased both intubation rates and mortality rates in specific subsets of patients with acute respiratory failure (e.g., patients with hypercapnia, cardiogenic pulmonary edema, immune deficiencies, or post-transplantation acute respiratory failure). NIV is also increasingly used as a palliative strategy when endotracheal ventilation is deemed inappropriate. In this context, palliative NIV can either be administered to offer a chance for survival, or to alleviate the symptoms of respiratory distress in dying patients. The literature provides information from 10 studies published between 1992 and 2006, in which 458 patients received palliative NIV. The technique was feasible, usually well tolerated, and half of the patients survived. The objectives of this review article are to define palliative NIV, to delineate the place for palliative NIV among overall indications of NIV, and to define the contribution of NIV to the palliative strategies available for patients with acute respiratory failure. Potential benefits and harm from NIV in patients who are not eligible for endotracheal ventilation are discussed. The appropriateness of palliative NIV should be reported in a study that relies on both quantitative criteria (rate of palliative NIV use and mortality) and qualitative criteria (patient comfort, end-of-life process, family burden, and health-care provider satisfaction). [ABSTRACT FROM AUTHOR]

Purpose: To compare characteristics, clinical evolution and outcome in adult patients with influenza A (H1N1) acute respiratory distress syndrome (ARDS) treated with or without extracorporeal membrane oxygenation (ECMO). Methods: A prospective observational study of patients treated in Marseille South Hospital from October 2009 to January 2010 for confirmed influenza A (H1N1)-related ARDS. Clinical features, pulmonary dysfunction and mortality were compared between patients treated with and without ECMO. Results: Of 18 patients admitted, 6 were treated with veno-venous and 3 with veno-arterial ECMO after median (interquartile, IQR) duration of mechanical ventilation of 10 (6-96) h. Six ECMO were initiated in a referral hospital by a mobile team, a median (IQR) of 3 (2-4) h after phone contact. Before ECMO, patients had severe respiratory failure with median (IQR) PaO to FiO ratio of 52 (50-60) mmHg and PaCO of 85 (69-91) mmHg. Patients treated with or without ECMO had the same hospital mortality rate (56%, 5/9). Duration of ECMO therapy was 9 (4-14) days in survivors and 5 (2-25) days in non-survivors. Early improvement of PaO to FiO ratio was greater in ECMO survivors than non-survivors after ECMO initiation [295 (151-439) versus 131 (106-144) mmHg, p < 0.05]. Haemorrhagic complications occurred in four patients under ECMO, but none required surgical treatment. Conclusions: ECMO may be an effective salvage treatment for patients with influenza A (H1N1)-related ARDS presenting rapid refractory respiratory failure, particularly when provided by a mobile team allowing early cannulation prior to transfer to a reference centre. [ABSTRACT FROM AUTHOR]

The article explores whether the intensity of lung injury and inflammation that develops following aspiration during mechanical ventilation differed depending on the inflammatory activity of intensive care unit patients' gastric fluid. Results reveal that gastric juice from critically ill patients is proinflammatory and stimulates human pulmonary cells in vitro. A human gastric juice with high inflammatory activity is more toxic to the lung than one with low inflammatory activity.

Study objectives: To test whether routine quantitative cultures of endotracheal aspirates obtained before the onset of ventilator-associated pneumonia (VAP) could help to predict the causative microorganisms and to select early appropriate antimicrobial therapy before obtaining BAL culture results. Design: Prospective observational study. Setting: French medical ICU. Patients: A total of 299 patients received mechanical ventilation for at least 48 h. Interventions: Endotracheal aspiration (EA) was performed twice weekly in all mechanically ventilated patients. A diagnosis of VAP was made by BAL culture. Only the EA performed just before the suspicion of VAP (EA-pre) were evaluated. This strategy (ie, the EA-pre-based strategy) was compared with an antibiotic therapy that would have been prescribed if the recommendations of both the American Thoracic Society (ATS) and Trouillet et al (Am J Respir Crit Care Med 1998; 157:531–539) had been applied. Measurements and results: VAP was diagnosed (by BAL culture) in 41 of the 75 patients in whom BAL was performed. Among the 41 BAL specimens that were positive for VAP, EA-pre had identified the same microorganisms (with the same antibiotic resistance patterns) in 34 cases (83%). In one case, EA-pre was not available at the time BAL was performed (a case of early-onset VAP), but the empiric antibiotic therapy was adequate. While EA-pre did not give the same results as the BAL culture, the antibiotic therapy based on the results of the EA-pre was adequate in four other cases. Finally, antibiotic therapy was delayed in only two cases. Antibiotic treatment was therefore adequate in 38 of the 40 assessable cases (95%). If the Trouillet-based strategy had been used, the antibiotic treatment would have been adequate in 34 of the 41 cases (83%; p = 0.15 [vs EA-pre strategy]). Based on the ATS classification, the antibiotic treatment would have been adequately prescribed in only 28 of the 41 cases (68%; p = 0.005 [vs EA-pre strategy]). Conclusions: Routine EA performed twice a week makes it possible to prescribe adequate antibiotic therapy (while waiting for BAL culture results) in 95% of the patients in whom a VAP is ultimately diagnosed by BAL culture. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether helium-oxygen mixture reduces inspiratory work of breathing (WOB) in sedated, paralyzed, and mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).Design and Setting: Open, prospective, randomized, crossover study in the medical intensive care unit in a university hospital.Patients and Participants: 23 patients admitted for acute exacerbation of COPD and mechanically ventilated.Measurements: Total WOB (WOBt), elastic WOB (WOBel), resistive WOB (WOBres), and WOB due to PEEPi (WOBPeepi) were measured. Static intrinsic positive end expiratory pressure (PEEPi), static compliance (Crs), inspiratory resistance (Rins), inspiratory (tinsp) and expiratory time constant (texp) were also measured. These variables were compared between air-oxygen and helium-oxygen mixtures.Results: WOBt significantly decreased with helium-oxygen (2.34+/-1.04 to 1.85+/-1.01 J/l, p<0.001). This reduction was significant for WOBel (1.02+/-0.61 J/l to 0.87+/-0.47, p<0.01), WOBPeepi (0.77+/-0.38 J/l to 0.54+/-0.38, p<0.001), and WOBres (0.55+/-0.19 J/l to 0.44+/-0.24, p<0.05). PEEPi, Rins, tinsp and texp significantly decreased. Crs was unchanged.Conclusions: Helium-oxygen mixture decreases WOB in mechanically ventilated COPD patients. Helium-oxygen mixture could be useful to reduce the burden of ventilation. [ABSTRACT FROM AUTHOR]

Background: Driving pressure (ΔPrs) across the respiratory system is suggested as the strongest predictor of hospital mortality in patients with acute respiratory distress syndrome (ARDS). We wonder whether this result is related to the range of tidal volume (VT). Therefore, we investigated ΔPrs in two trials in which strict lung-protective mechanical ventilation was applied in ARDS. Our working hypothesis was that ΔPrs is a risk factor for mortality just like compliance (Crs) or plateau pressure (Pplat,rs) of the respiratory system.Methods: We performed secondary analysis of data from 787 ARDS patients enrolled in two independent randomized controlled trials evaluating distinct adjunctive techniques while they were ventilated as in the low VT arm of the ARDSnet trial. For this study, we used VT, positive end-expiratory pressure (PEEP), Pplat,rs, Crs, ΔPrs, and respiratory rate recorded 24 hours after randomization, and compared them between survivors and nonsurvivors at day 90. Patients were followed for 90 days after inclusion. Cox proportional hazard modeling was used for mortality at day 90. If colinearity between ΔPrs, Crs, and Pplat,rs was verified, specific Cox models were used for each of them.Results: Both trials enrolled 805 patients of whom 787 had day-1 data available, and 533 of these survived. In the univariate analysis, ΔPrs averaged 13.7 ± 3.7 and 12.8 ± 3.7 cmH2O (P = 0.002) in nonsurvivors and survivors, respectively. Colinearity between ΔPrs, Crs and Pplat,rs, which was expected as these variables are mathematically coupled, was statistically significant. Hazard ratios from the Cox models for day-90 mortality were 1.05 (1.02-1.08) (P = 0.005), 1.05 (1.01-1.08) (P = 0.008) and 0.985 (0.972-0.985) (P = 0.029) for ΔPrs, Pplat,rs and Crs, respectively. PEEP and VT were not associated with death in any model.Conclusions: When ventilating patients with low VT, ΔPrs is a risk factor for death in ARDS patients, as is Pplat,rs or Crs. As our data originated from trials from which most ARDS patients were excluded due to strict inclusion and exclusion criteria, these findings must be validated in independent observational studies in patients ventilated with a lung protective strategy.Trial Registration: Clinicaltrials.gov NCT00299650 . Registered 6 March 2006 for the Acurasys trial. Clinicaltrials.gov NCT00527813 . Registered 10 September 2007 for the Proseva trial. [ABSTRACT FROM AUTHOR]

Objective: Acute respiratory distress syndrome trials powered for mortality require significant resources, limiting the number of evaluable therapies. Validation of intermediate endpoints would enhance the feasibility of testing novel acute respiratory distress syndrome therapies in pilot studies and potentially reduce the frequency of failed large clinical trials. We sought to determine whether a change in the oxygenation index over the first 7 days of acute respiratory distress syndrome could discriminate between therapies likely or unlikely to show benefit in larger clinical trials. Design: A derivation cohort from three acute respiratory distress syndrome studies was used to estimate the 7-day change in oxygenation index. Receiver operating characteristic curves were used to calculate optimal thresholds and predictability of the change in oxygenation index for 28-day mortality and ventilator-free days. The thresholds were then validated in two cohorts. Then, for each individual acute respiratory distress syndrome study, the threshold 7-day oxygenation index change was tested as an outcome measure and compared with mortality and ventilator-free days as reported in the original study. Setting: Medical ICUs. Patients: Acute respiratory distress syndrome patients. Interventions: Various. Measurements and Main Results: Change in oxygenation index, 28-day mortality, and ventilator-free days. In the derivation cohort, the mean 7-day oxygenation index improved by 4.2 (± 11.7) in 28-day survivors compared with an increase of 2.4 (± 11.6) in 28-day nonsurvivors (p < 0.001). The mean 7-day oxygenation index decreased by 5.9 (± 8.4) in patients with more than 14 ventilator-free days, compared with a decrease of 1.9 (± 12.4) among those with less than 14 ventilator-free days (p = 0.001). The optimal 7-day oxygenation index threshold for predicting mortality was an increase of 1.71 and for predicting less than 14 ventilator-free days, a decrease of 2.34. When used as a surrogate endpoint, the optimal 7-day oxygenation index change closely approximated mortality and ventilator-free day outcomes in three Acute Respiratory Distress Syndrome Network studies used for the derivation cohort and a distinct study used for validation. The change in oxygenation index was a poor predictor of individual patient outcome. Conclusions: Failure to meet a threshold improvement in the oxygenation index over the first 7 days of therapy can be used to identify therapies unlikely to succeed in subsequent trials powered for mortality and ventilator-free days. By reducing trial time and costs, use of the 7-day oxygenation index change as an intermediate endpoint could increase the number of clinical trials of promising therapies for acute respiratory distress syndrome and reduce the number of large-scale trials of therapies unlikely to be of benefit. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the agreement between thermodilution and partial rebreathing and for the measurement of cardiac output and pulmonary capillary blood flow patients with acute respiratory distress syndrome. The study examines 20 consecutive patients who receive lung protective ventilation, and seven pairs of pulmonary capillary blood flows and cardiac output have been recorded to determine the accuracy of the methods used. It discusses the recorded bias, limit of agreement and percentage error for the measurement of cardiac output and capillary blood flow. It suggests that the accuracy of partial rebreathing is not a sufficient replacement for thermodilution for the pulmonary capillary blood flow and cardiac output measurement.

The article presents a study which assess the incidence, risk factors and outcome of active cytomegalovirus (CMV) infection to nonimmunosuppressed patients in intensive care unit (ICU). Result shows that patients with active CMV infection had longer mechanical ventilation and longer stay in ICU are at risk to develop bacterial nosocomial infections. Risk factors include enteral feeding and costicosteriod use prior to ICU admission were associated with the occurrence of active CMV infection.

The article examines the effect of high FI02 levels on the course of Pa02/FI02 ratio (P/F) in lung protective mechanically ventilated patients with acute respiratory distress syndrome. According to the authors, P/F variation was responsible for two thirds of patients changing from the acute respiratory distress syndrome to the acute lung injury stage of the American-European Consensus Conference definition.