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RATIONALE: The stressful work environment of ICUs can lead to burnout. Burnout can impact on the welfare and performance of caregivers, and may lead them to resign their job. The shortage of ICU caregivers is becoming a real threat for health care leaders. OBJECTIVES: To investigate the factors associated with burnout on a national level in order to determine potential important factors. METHODS: Prospective, multicenter, observational survey of all caregivers from 74 of the 92 Swiss ICUs, measuring the prevalence of burnout among the caregivers and the pre-specified center-, patient- and caregiver-related factors influencing its prevalence. MEASUREMENTS AND MAIN RESULTS: Out of the 4322 questionnaires distributed from March 2006 to April 2007, 3052 (71%) were returned, with a response rate of 72% by center, 69% from nurse-assistants, 73% from nurses and 69% from physicians. A high proportion of female nurses among the team was associated with a decreased individual risk of high burnout (OR 0.98, 95% CI:0.97-0.99 for every %). The caregiver-related factors associated with a high risk of burnout were being a nurse-assistant, being a male, having no children and being under 40 years old. CONCLUSIONS: The findings of this study seem to open a new frontier concerning burnout in ICUs, highlighting the importance of team composition. Our results should be confirmed in a prospective multicenter, multinational study. Whether our results can be exported to other medical settings where team-working is pivotal remains to be investigated. [ABSTRACT FROM AUTHOR]

RATIONALE: Many sources of conflict exist in intensive care units (ICUs). Few studies recorded the prevalence, characteristics, and risk factors for conflicts in ICUs. OBJECTIVES: To record the prevalence, characteristics, and risk factors for conflicts in ICUs. METHODS: One-day cross-sectional survey of ICU clinicians. Data on perceived conflicts in the week before the survey day were obtained from 7,498 ICU staff members (323 ICUs in 24 countries). MEASUREMENTS AND MAIN RESULTS: Conflicts were perceived by 5,268 (71.6%) respondents. Nurse-physician conflicts were the most common (32.6%), followed by conflicts among nurses (27.3%) and staff-relative conflicts (26.6%). The most common conflict-causing behaviors were personal animosity, mistrust, and communication gaps. During end-of-life care, the main sources of perceived conflict were lack of psychological support, absence of staff meetings, and problems with the decision-making process. Conflicts perceived as severe were reported by 3,974 (53%) respondents. Job strain was significantly associated with perceiving conflicts and with greater severity of perceived conflicts. Multivariate analysis identified 15 factors associated with perceived conflicts, of which 6 were potential targets for future intervention: staff working more than 40 h/wk, more than 15 ICU beds, caring for dying patients or providing pre- and postmortem care within the last week, symptom control not ensured jointly by physicians and nurses, and no routine unit-level meetings. CONCLUSIONS: Over 70% of ICU workers reported perceived conflicts, which were often considered severe and were significantly associated with job strain. Workload, inadequate communication, and end-of-life care emerged as important potential targets for improvement. [ABSTRACT FROM AUTHOR]

Purpose: The use of coercion, in a clinical context as imposing a measure against a patient's opposition or declared will, can occur in various forms in intensive care units (ICU). One prime example of a formal coercive measure in the ICU is the use of restraints, which are applied for patients' own safety. Through a database search, we sought to evaluate patient experiences related to coercive measures., Results: For this scoping review, clinical databases were searched for qualitative studies. A total of nine were identified that fulfilled the inclusion and the CASP criteria. Common themes emerging from the studies on patient experiences included communication issues, delirium, and emotional reactions. Statements from patients revealed feelings of compromised autonomy and dignity that came with a loss of control. Physical restraints were only one concrete manifestation of formal coercion as perceived by patients in the ICU setting., Conclusion: There are few qualitative studies focusing on patient experiences of formal coercive measures in the ICU. In addition to the experience of restricted physical movement, the perception of loss of control, loss of dignity, and loss of autonomy suggests that restraining measures are just one element in a setting that may be perceived as informal coercion., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2022.)

Objective: To investigate staff attitudes toward assisted suicide in the hospital setting in Switzerland., Design: Cross-sectional study., Setting: Two University Hospitals in French speaking regions of Switzerland., Participants: 13'834 health care professionals, including all personnel caring for patients, were invited to participate., Main Outcome Measures and Other Variables: Attitudes towards the participation of hospital health care professionals in assisted suicide were investigated with an online questionnaire., Results: Among all invited professionals, 5'127 responded by filling in the survey at least partially (response rate 37.0%), and 3'683 completed the entire survey (26.6%). 73.0% of participants approved that this practice should be authorized in their hospital and saw more positive than negative effects. 57.6% would consider assisted suicide for themselves. Non-medical professionals were 1.28 to 5.25 times more likely to approve assisted suicide than physicians (p<0.001). 70.7% of respondents indicated that each professional should have the choice of whether to assist in suicide., Conclusions: This multiprofessional survey sheds light on hospital staff perceptions of assisted suicide happening within hospital walls, which may inform the development of rules considering their wishes but also their reluctances. Further research using a mixed-methods approach could help reach an in-depth understanding of staff's attitudes and considerations towards assisted suicide practices., Competing Interests: The authors have declared that no competing interests exist.

Background: The need for an ethical debate about the use of coercion in intensive care units (ICU) may not be as obvious as in other areas of medicine, such as psychiatry. Coercive measures are often necessary to treat critically ill patients in the ICU. It is nevertheless important to keep these measures to a minimum in order to respect the dignity of patients and the cohesion of the clinical team. A deeper understanding of what patients and their relatives perceive during their ICU stay will shed different light on intensive care management. Patients' experiences of loss of control, dependency and abandonment may lead to a new approach towards a broader approach to the concept of coercion in intensive care. The aim of our research is to explore the experiences of patients and relatives in the ICU and to determine when it might be possible to reduce feelings and memories of coercion., Methods: We conducted and analysed 29 semi-structured interviews with patients and relatives who had been in the ICU a few months previously. Following a coding and categorisation process in MAXQDA™, a rigorous qualitative methodology was used to identify themes relevant to our research., Results: Five main themes emerged: memory issues; interviewees' experiences of restricting measures and coercive treatment; patients' negative perception of situational and relational dependency with the risk of informal coercion; patients' perceptions of good care in a context of perceived dependency; progression from perception of coercion and dependency to respect for the person. All patients were grateful to have survived. However, coercion in the form of restraint, restriction of movement, and coercive treatment in the ICU was also acknowledged by patients and relatives. These included elements of informal coercion beyond restraints, such as a perceived negative sense of dependence, surrender, and asymmetrical interaction between the patient and health providers., Conclusions: To capture the full range of patients' experiences of coercion, it is necessary to expand the concept of coercion to include less obvious forms of informal coercion that may occur in dependency situations. This will help identify solutions to avoid or reduce negative recollections that may persist long after discharge and negatively affect the patients' quality of life., (© 2022. The Author(s).)

Objectives: The aim of this study was to determine the prevalence and forms of gender discrimination and sexual harassment experienced by medical students and physicians in French-speaking part of Switzerland., Design and Setting: We conducted an online survey using a questionnaire of 9 multiple-choice and 2 open questions between 24 January 2019 and 24 February 2019. Our target population was medical students and physicians working at hospitals and general practitioners from the French-speaking part of Switzerland. The online survey was sent via social media platforms and direct emails. We compared answers between male-determined and female-determined respondents using either χ 2 or Fisher's exact tests., Results: Among 1071 responders, a total of 893 were included (625 females, 264 males, 4 non-binary and 1 non-binary and male). 178 were excluded because they did not mention their working place or were working only outside Switzerland. Because of the small number of non-binary participants, they were not contemplated in further statistical analysis. Of 889 participants left, 199 (31.8%) women and 18 (6.8%) men reported having personally experienced gender discrimination, in terms of sexism, difficulties in career development and psychological pressure. Among women, senior attendings were the most affected (55.2%), followed by residents (44.1%) and junior attendings (41.1%). Sexual harassment was equally observed among women (19.0%) and men (16.7%). Compared with men (47.0%), women (61.4%) expressed the need to promote equality and inclusivity in medicine more frequently (p<0.001), as well as the need for support in their professional development (38.7% women and 23.9% men; p<0.001)., Conclusions: Gender discrimination in medicine in French-speaking Switzerland affects one-third of women, in particular, those working in hospital settings and senior positions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine physicians' decision making and its determinants about admission to intensive care., Data Sources/study Setting: ICU physicians (n = 12) and internists (n = 12) working in a Swiss tertiary care hospital., Study Design: We conducted in-depth interviews., Data Collection/extraction Methods: Interviews were analyzed using an inductive thematic approach., Principal Findings: Admission decisions regarding seriously ill or elderly patients with comorbidities are complex. Nonmedical factors such as ICU beds availability, health care resources on the ward, information about patient preferences, and family behavior determine the decision. Code status and the quality of interaction between physicians are key determinants. The absence of code status or poor documentation of code status discussions makes decisions more difficult and laden emotionally, as physicians feel they are making a life-death decision. Mutual respect and collaborative decision making facilitate the decision. Tensions arise due to ICU physicians' postponing the decision because of lack of beds, ICU physicians' dismissive attitudes, perceived shortcomings in the other physician's completion of expected tasks, and preconceptions about the other physician., Conclusions: Systematic documentation of code status, and fostering collaboration between ICU physicians and internists would facilitate ICU admission decisions in complex clinical situations., (© Health Research and Educational Trust.)

Background: A higher chance of survival is a key justification for admission to the intensive care unit (ICU). This implies that physicians should be able to accurately estimate a patient's prognosis, whether cared for on the ward or in the ICU. We aimed to determine whether physicians' survival predictions correlate with the admission decisions and with patients' observed survival. Consecutive ICU consultations for internal medicine patients were included. The ICU physician and the internist were asked to predict patient survival with intensive care and with care on the ward using 5 categories of probabilities (< 10%, 10-40%, 41-60%, 61-90%, > 90%). Patient mortality at 28 days was recorded., Results: Thirty ICU physicians and 97 internists assessed 201 patients for intensive care. Among the patients, 140 (69.7%) were admitted to the ICU. Fifty-eight (28.9%) died within 28 days. Admission to intensive care was associated with predicted survival gain in the ICU, particularly for survival estimates made by ICU physicians. Observed survival was associated with predicted survival, for both groups of physicians. The discrimination of the predictions for survival with intensive care, measured by the area under the ROC curve, was 0.63 for ICU physicians and 0.76 for internists; for survival on the ward the areas under the ROC curves were 0.69 and 0.74, respectively., Conclusions: Physicians are able to predict survival probabilities when they assess patients for intensive care, albeit imperfectly. Internists are more accurate than ICU physicians. However, ICU physicians' estimates more strongly influence the admission decision. Closer collaboration between ICU physicians and internists is needed.

Background: Intensive care Unit (ICU) admission decisions involve collaboration between internists and intensivists. Clear perception of each other's roles is a prerequisite for good collaboration. The objective was to explore how internists and intensivists perceive their roles during admission decisions., Methods: Individual in-depth interviews with 12 intensivists and 12 internists working at a Swiss teaching hospital. Interviews were analyzed using a thematic approach., Results: Roles could be divided into practical roles and identity roles. Internist and intensivists had the same perception of each other's practical roles. Internists' practical roles were: recognizing signs of severity when the patient becomes acutely ill, calling the intensivist at the right moment, having the relevant information about the patient and having determined the goals of care. Intensivists' practical roles were: assessing the patient on the ward, giving expert advice, making quick decisions, managing access to the ICU, having the final decision power and, sometimes, deciding whether or not to limit treatment. In complex situations, perceived flaws in performing practical roles could create tensions between the doctors. Intensivists' identity roles included those of leader, gatekeeper, life-death decision maker, and supporting colleague doctors (consultant, senior and helper). These roles could be perceived as emotionally burdensome. Internists' identity roles were those of leader and partner., Conclusions: Despite a common perception of each other's practical roles, tensions can arise between internists and intensivists in complex situations of ICU admission decisions. Training in communication skills and interprofessional education interventions aimed at a better understanding of each other roles would improve collaboration.

Advances in intensive care medicine have created a new disease called the chronic critical illness. While a significant proportion of severely ill patients who twenty years ago would have died survive the acute phase, they remain heavily dependent on intensive care for a prolonged period of time. These patients, who can be called "Patient Long Séjour" in French (PLS) or Prolonged Length of Stay patients in English, develop specific health issues that are still poorly recognised. They require special care, which differs from treatments that are given during the acute phase of their illness. A multidisciplinary team dedicated to ensuring their management and follow-up acquired a wide range of knowledge and expertise about these PLSs. Many new monitoring tools and diverse human approaches were implemented to ensure that care was targeted to these patients' needs. This multimodal care management aims to optimise the patients' and their families' quality of life during and following intensive care, whilst maintaining the motivation of the healthcare team of the unit. The purpose of this article is to present new management techniques to hospital and ambulatory caregivers, physicians and nurses, who may be taking care of such patients.

Advance directives (AD) were developed to respect patient autonomy. However, very few patients have AD, even in cases when major cardiovascular surgery is to follow. To understand the reasons behind the low prevalence of AD and to help decision making when patients are incompetent, it is necessary to focus on the impact of prehospital practitioners, who may contribute to an increase in AD by discussing them with patients. The purpose of this study was to investigate self-rated communication skills and the attitudes of physicians potentially involved in the care of cardiovascular patients toward AD.Self-administered questionnaires were sent to general practitioners, cardiologists, internists, and intensivists, including the Quality of Communication Score, divided into a General Communication score (QOCgen 6 items) and an End-of-life Communication score (QOCeol 7 items), as well as questions regarding opinions and practices in terms of AD.One hundred sixty-four responses were received. QOCgen (mean (±SD)): 9.0/10 (1.0); QOCeol: 7.2/10 (1.7). General practitioners most frequently start discussions about AD (74/149 [47%]) and are more prone to designate their own specialty (30/49 [61%], P < 0.0001). Overall, only 57/159 (36%) physicians designated their own specialty; 130/158 (82%) physicians ask potential cardiovascular patients if they have AD and 61/118 (52%) physicians who care for cardiovascular patients talk about AD with some of them.The characteristics of physicians who do not talk about AD with patients were those who did not personally have AD and those who work in private practices.One hundred thirty-three (83%) physicians rated the systematic mention of patients' AD in the correspondence between physicians as good, while 114 (71%) at the patients' first registration in the private practice.Prehospital physicians rated their communication skills as good, whereas end-of-life communication was rated much lower. Only half of those surveyed speak about AD with cardiovascular patients. The majority would prefer that physicians of another specialty, most frequently general practitioners, initiate conversation about AD. In order to increase prehospital AD incidence, efforts must be centered on improving practitioners' communication skills regarding death, by providing trainings to allow physicians to feel more at ease when speaking about end-of-life issues., Competing Interests: The authors have no conflicts of interest to disclose.

Question Under Study: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis. Survival and quality of life of ALS patients have improved through the implementation of multidisciplinary approaches, the use of percutaneous gastrostomy and of noninvasive (NIV) or invasive ventilation. The question of whether or not to propose invasive ventilation (by tracheostomy: TPPV) to ALS patients remains a matter of debate., Methods: The study reviews the medical literature, the practice in three Swiss and two large French ALS expert centres and reports the results of a workgroup on invasive ventilation in ALS., Results: Improved management of secretions and use of different interfaces allows NIV to be used 24-hours-a-day for prolonged periods, thus avoiding TPPV in many cases. TPPV is frequently initiated in emergency situations with lack of prior informed consent. TPPV appears associated with a lesser quality of life and a higher risk of institutionalisation than NIV. The high burden placed on caregivers who manage ALS patients is a major problem with a clear impact on their quality of life., Conclusions: Current practice in Switzerland and France tends to discourage the use of TPPV in ALS. Fear of a "locked-in syndrome", the high burden placed on caregivers, and unmasking cognitive disorders occurring in the evolution of ALS are some of the caveats when considering TPPV. Most decisions about TPPV are taken in emergency situations in the absence of advance directives. One exception is that of young motivated patients with predominantly bulbar disease who "fail" NIV.

Ageing of the world's population raises important questions about the utilisation of the health care system. It is not clear how much should be invested in the last years of life whereas the costs are known to increase in parallel. Since intensive care units (ICU) are costly with highly specialised personnel, it seems of paramount importance that they would be used efficiently. Indeed, in the present context of predicted shortage of physicians in Switzerland, society and politics will need evidence that the care provided by ICUs is appropriate. There is no explicit limitation of care in any country according to age and nonagerians are admitted nowadays into ICUs with critical illness. This review article will address the question of elderly patients in ICU and their outcome. Outcome does not imply surviving ICU but only later during the hospital stay and after discharge. Furthermore, we emphasise the need of examining not solely the hospital survival but the quality of life of the patients when they return to their real life. The fundamental questions are actually "Do they go back to life?" "What is life for elderly people?" These questions lead to more basic questions such as "Are they able to go back home or are they institutionalised? How is their quality of life and functional status after ICU?". We tried to address these questions through the existing literature and our experience while caring for these particular patients. Some clues on the prognostic factors related to their outcome are reported.

Intubated patients frequently become colonized by Pseudomonas aeruginosa, which is subsequently responsible for ventilator-associated pneumonia. This pathogen readily acquires resistance against available antimicrobials. Depending on the resistance mechanism selected for, resistance might either be lost or persist after removal of the selective pressure. We investigated the rapidity of selection, as well as the persistence, of antimicrobial resistance and determined the underlying mechanisms. We selected 109 prospectively collected P. aeruginosa tracheal isolates from two patients based on their prolonged intubation and colonization periods, during which they had received carbapenem, fluoroquinolone (FQ), or combined beta-lactam-aminoglycoside therapies. We determined antimicrobial resistance phenotypes by susceptibility testing and used quantitative real-time PCR to measure the expression of resistance determinants. Within 10 days after the initiation of therapy, all treatment regimens selected resistant isolates. Resistance to beta-lactam and FQ was correlated with ampC and mexC gene expression levels, respectively, whereas imipenem resistance was attributable to decreased oprD expression. Combined beta-lactam-aminoglycoside resistance was associated with the appearance of small-colony variants. Imipenem and FQ resistance persisted for prolonged times once the selecting antimicrobial treatment had been discontinued. In contrast, resistance to beta-lactams disappeared rapidly after removal of the selective pressure, to reappear promptly upon renewed exposure. Our results suggest that resistant P. aeruginosa is selected in less than 10 days independently of the antimicrobial class. Different resistance mechanisms lead to the loss or persistence of resistance after the removal of the selecting agent. Even if resistant isolates are not evident upon culture, they may persist in the lung and can be rapidly reselected.

Patients in critical care lose their capability to make a judgement, and constitute a 'vulnerable population' needing special and reinforced protection. Even if the standard of informed consent is an essential way of demonstrating respect for the patient's autonomy, the usual informed-consent procedure is not as applicable as required or sufficient to warrant this ethical principle in critical care.

Introduction: Rapid diagnostic tests may allow early identification of previously unknown methicillin-resistant Staphylococcus aureus (MRSA) carriers at intensive care unit (ICU) admission. The aim of this study was twofold: first, to assess whether a new molecular MRSA screening test can substantially decrease the time between ICU admission and identification of MRSA carriers; and, second, to examine the combined effect of rapid testing and pre-emptive contact isolation on MRSA infections., Method: Since November 2003, patients admitted for longer than 24 hours to two adult ICUs were screened systematically on admission using quick, multiplex immunocapture-coupled PCR (qMRSA). Median time intervals from admission to notification of test results were calculated for a five-month intervention phase (November 2003-March 2004) and compared with a historical control period (April 2003-October 2003) by nonparametric tests. ICU-acquired MRSA infection rates were determined for an extended surveillance period (January 2003 through August 2005) and analyzed by Poisson regression methods., Results: During the intervention phase, 97% (450/462) of patients admitted to the surgical ICU and 80% (470/591) of patients admitted to the medical ICU were screened. On-admission screening identified the prevalence of MRSA to be 6.7% (71/1053). Without admission screening, 55 previously unknown MRSA carriers would have been missed in both ICUs. Median time from ICU admission to notification of test results decreased from 87 to 21 hours in the surgical ICU (P < 0.001) and from 106 to 23 hours in the medical ICU (P < 0.001). In the surgical ICU, 1,227 pre-emptive isolation days for 245 MRSA-negative patients were saved by using the qMRSA test. After adjusting for colonization pressure, the systematic on-admission screening and pre-emptive isolation policy was associated with a reduction in medical ICU acquired MRSA infections (relative risk 0.3, 95% confidence interval 0.1-0.7) but had no effect in the surgical ICU (relative risk 1.0, 95% confidence interval 0.6-1.7)., Conclusion: The qMRSA test decreased median time to notification from four days to one day and helped to identify previously unknown MRSA carriers rapidly. A strategy linking the rapid screening test to pre-emptive isolation and cohorting of MRSA patients substantially reduced MRSA cross-infections in the medical but not in the surgical ICU.

Introduction: Patients in the intensive care unit (ICU) may be in an inadequate condition to give their informed consent for research. The aim of this study was to analyse the ability to recall participation in a clinical trial for which ICU patients had given their consent., Methods: The data presented are a two-step observational study: first, a protocolled informed consent procedure was conducted then the informed consent was given by the patient, and second, a patient interview was held 10 +/- 2 days later by the same investigator. The primary endpoints were the ability to recall their participation in the clinical trial, as well as its purpose and related risks. As secondary endpoints, we investigated whether asking questions about the clinical trial or reading the informative leaflet was related to the recall. To be included in the study, the patient had to have a Glasgow Coma Scale score of 15, be fully oriented and free of mechanical ventilation, and be judged competent by both the investigator and the attending physician. Patients admitted to the ICU after major surgery or trauma were eligible. However, patients who refused to participate, or those whose next-of-kin gave consent, were excluded., Results: Of the 44 patients, 35 (80%) recognized, 10 to 12 days after informed consent had been obtained, that they had participated in the clinical trial, but only 14 out of 44 (32%) could recall the clinical trial purpose and its related risks. More patients with complete recall had read the informative leaflet or asked at least one question before signing the informed consent. Asking at least one question was associated with complete recall., Conclusion: Our results confirm that obtaining informed consent for research during an ICU stay is associated with poor patient recall of participation in a clinical trial and its components (purpose and risk). Whether encouraging reading the informative leaflet and asking questions about the clinical trial improves the informed consent procedure remains to be fully investigated.

Atelectasis is common after cardiac surgery and may result in impaired gas exchange. Continuous positive airway pressure (CPAP) is often used to prevent or treat postoperative atelectasis. We hypothesized that noninvasive pressure support ventilation (NIPSV) by increasing tidal volume could improve the evolution of atelectasis more than CPAP. One-hundred-fifty patients admitted to our surgical intensive care unit (SICU) with a Radiological Atelectasis Score >or=2 after cardiac surgery were randomly assigned to receive either CPAP or NIPSV four times a day for 30 min. Positive end-expiratory pressure was set at 5 cm H(2)O in both groups. In the NIPSV group, pressure support was set to provide a tidal volume of 8-10 mL/kg. At SICU discharge, we observed an improvement of the Radiological Atelectasis Score in 60% of the patients with NIPSV versus 40% of those receiving CPAP (P = 0.02). There was no difference in oxygenation (Pao(2)/fraction of inspired oxygen at SICU discharge: 280 +/- 38 in the CPAP group versus 301 +/- 40 in the NIPSV group), pulmonary function tests, or length of stay. Minor complications, such as gastric distensions, were similar in the two groups. NIPSV was superior to CPAP regarding the improvement of atelectasis based on radiological score but did not confer any additional clinical benefit, raising the question of its usefulness for altering outcome.

To determine whether acute respiratory distress syndrome (ARDS) complicating bacteremic sepsis independently affects mortality in critically ill patients, we conducted a 3-year retrospective cohort study in a surgical intensive care unit. We included all consecutive patients with blood culture-positive sepsis and measured organ dysfunctions and mortality. Among 4,530 admissions, 196 cases of bacteremic sepsis were recorded. ARDS occurred in 31 (16%) of these patients. The case fatality rate was 58% in patients with ARDS compared with 31% in patients without ARDS. Using Cox proportional hazards regression with time-dependent variables, the unadjusted hazard ratio for death was 1.8 (95% confidence interval [CI], 1.0-3.2). After adjusting for comorbid factors that were present before the onset of sepsis, the hazard ratio was 2.2 (95% CI, 1.2-3.9). After further adjustment was made for nonpulmonary organ dysfunctions and microbiologic factors that were independently associated with mortality, the adjusted hazard ratio for ARDS was 0.6 (95% CI, 0.3-1.2). Among critically ill surgical patients, ARDS complicating bacteremic sepsis remains common, but it is not independently associated with short-term mortality, after adjusting for severity of illness and nonpulmonary organ dysfunctions evolving after the onset of sepsis.

Acute respiratory distress syndrome (ARDS) is characterized by an extensive alveolar capillary leak, permitting contact between intra-alveolar factors and the endothelium. To investigate whether factors contained in the alveolar milieu induce cell death in human lung microvascular endothelial cells, we exposed these cells in vitro to bronchoalveolar lavage fluid (BALF) supernatants from control patients, patients at risk of developing ARDS, and patients with early- and late-phase ARDS. In contrast to BALF from control patients, a significant cytotoxicity was found in BALF from patients at risk of developing ARDS, with late-phase ARDS, and especially from patients with early-phase ARDS. Subsequently, we determined the levels of factors known to exert cytotoxicity in endothelial cells, i.e., tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and angiostatin. BALF from patients at risk of developing ARDS, with early-phase ARDS, and with late-phase ARDS, contained increased levels of TNF-alpha and angiostatin, but not of TGF-beta1, as compared with BALF from control patients. Whereas inhibition of TGF-beta1 had no effect in this setting, neutralization of TNF-alpha or angiostatin inhibited the cytotoxic activity on endothelial cells of part of the early-phase ARDS BALF. These results indicate that TNF-alpha and angiostatin may contribute to ARDS-related endothelial injury.

To assess the diagnostic value of procalcitonin (PCT), interleukin (IL)-6, IL-8, and standard measurements in identifying critically ill patients with sepsis, we performed prospective measurements in 78 consecutive patients admitted with acute systemic inflammatory response syndrome (SIRS) and suspected infection. We estimated the relevance of the different parameters by using multivariable regression modeling, likelihood-ratio tests, and area under the receiver operating characteristic curves (AUC). The final diagnosis was SIRS in 18 patients, sepsis in 14, severe sepsis in 21, and septic shock in 25. PCT yielded the highest discriminative value, with an AUC of 0.92 (CI, 0.85 to 1.0), followed by IL-6 (0.75; CI, 0.63 to 0.87), and IL-8 (0.71; CI, 0.59 to 0.83; p < 0.001). At a cutoff of 1.1 ng/ml, PCT yielded a sensitivity of 97% and a specificity of 78% to differentiate patients with SIRS from those with sepsis-related conditions. Median PCT concentrations on admission (ng/ ml, range) were 0.6 (0 to 5.3) for SIRS; 3.5 (0.4 to 6.7) for sepsis; 6.2 (2.2 to 85) for severe sepsis; and 21.3 (1.2 to 654) for septic shock (p < 0.001). The addition of PCT to a model based solely on standard indicators improved the predictive power of detecting sepsis (likelihood ratio test; p = 0.001) and increased the AUC value for the routine value-based model from 0.77 (CI, 0.64 to 0.89) to 0.94 (CI, 0.89 to 0.99; p = 0.002). In contrast, no additive effect was seen for IL-6 (p = 0.56) or IL-8 (p = 0.14). Elevated PCT concentrations appear to be a promising indicator of sepsis in newly admitted, critically ill patients capable of complementing clinical signs and routine laboratory parameters suggestive of severe infection.

Microvascular endothelial cells (MVEC), which differ from large vessel endothelial cells, have been isolated successfully from lungs of various species, including man. However, contamination by nonendothelial cells remains a major problem in spite of several technical improvements. In view of the organ specificity of MVEC, endothelial cells should be derived from the tissue involved in the diseases one wishes to study. Therefore, to investigate some of the immunopathological mechanisms leading to acute respiratory distress syndrome (ARDS), we have attempted to isolate lung MVEC from patients undergoing thoracic surgery for lung carcinoma and patients dying of ARDS. The method described here includes four main steps: (1) full digestion of pulmonary tissue with trypsin and collagenase, (2) aggregation of MVEC induced by human plasma, (3) Percoll density centrifugation, and (4) selection and transfer of MVEC after local digestion with trypsin/EDTA under light microscopy. Normal and ARDS-derived lung MVEC purified by this technique presented contact inhibition (i.e., grew in monolayer), and expressed classical endothelial markers, including von Willebrand factor (vWF), platelet endothelial cell adhesion molecule 1(PECAM-1, CD31), and transcripts for the angiotensin converting enzyme (ACE). The cells also formed capillarylike structures, took up high levels of acetylated low-density lipoprotein (Ac-LDL), and exhibited ELAM-1 inducibility in response to TNF. Contaminant cells, such as fibroblasts, smooth muscle cells, or pericytes, were easily recognized on the basis of morphology and were eliminated by selection of plasma-aggregated cells under light microscopy. The technique presented here allows one to study the specific involvement and contribution of pulmonary endothelium in various lung diseases.

Background: Nitric oxide (NO) is administered frequently in patients with acute respiratory distress syndrome (ARDS) and pulmonary hypertension. The efficacy of this therapy over several days is not well known. The authors first determined the consistency of the response to repeated administration of NO and then the baseline variables that were associated with improvement in patients with severe ARDS., Methods: In a prospective trial, 32 mechanically ventilated patients with severe ARDS received 10 parts per million NO by inhalation. In 22 of these patients, its effect was tested repeatedly (up to four times) in several days. Improvement was defined as an increase >10% in the ratio of pressure of oxygen in arterial blood (P(aO2)) to the inspiratory pressure of oxygen (FIO2) from baseline. Patients showing such an improvement were maintained on NO inhalation., Results: Twelve of the 22 patients (54%) showed a clinically significant and reproducible increase in the P(aO2)/FIO2 ratio with NO, from 74 +/- 30 mmHg (mean +/- SD) to 95 +/- 41 mmHg (P < 0.001). In three patients (14%), P(aO2) did not improve, even with multiple exposures. In seven patients (32%), an inconsistent response was seen on different days. Mean pulmonary artery pressure decreased for the entire group from 34 +/- 10 mmHg to 29 +/- 9 mmHg (P < 0.01), but this decrease did not correlate with the increase in P(aO2) in individual patients. The baseline P(aO2)/FIO2 ratio and mixed venous oxygenation (P(vO2)) were significantly lower, and the venous admixture was greater in patients showing beneficial effects of NO inhalation on P(aO2)., Conclusions: Repeated NO inhalation caused a consistent improvement in P(aO2) in about one half of these patients with severe ARDS; no significant benefit or inconsistent effects on pulmonary gas exchange were noted in the others. These findings could be related to the complexity of the mechanisms regulating the vasomotor changes in this syndrome. Severe baseline hypoxemia may be associated with a more favorable effect of NO on P(aO2).

The microvascular endothelial cell (MVEC) is a major target of inflammatory cytokines overproduced in conditions such as sepsis and infectious diseases. We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM). To identify functional and phenotypical changes occurring in MVEC during sepsis, we isolated these cells from the lungs of patients who died of ARDS. The constitutive expression of ICAM-1 and, to a lesser extent, VCAM-1, CD14, and TNFR2 were significantly increased on MVEC isolated from ARDS patients compared with control MVEC, whereas ELAM-1 and TNFR1 were not increased. We found that lung MVEC from ARDS patients present a procoagulant profile and a higher production capacity of interleukin-6 (IL-6) and IL-8 when compared with those from controls. As in pulmonary MVEC derived from ARDS patients, the only TNFR type found up-regulated in brain microvessels during CM was TNFR2. This increase in TNFR2 expression only occurred in CM-susceptible mice at the onset of the neurological syndrome. We therefore investigated the role of TNFR2 in the development of this brain pathology by comparing the incidence of CM in wild-type and TNF receptor knock-out mice. Unexpectedly, the genetic deficiency in TNFR2, but not in TNFR1, conferred protection against CM and its associated mortality. No ICAM-1 up-regulation was detected in the brain of Tnfr2 knockout mice, indicating a close correlation between protection against CM-associated brain damage, absence of TNFR2, and absence of ICAM-1 up-regulation in the brain. Our results in ARDS and CM indicate a specific up-regulation of TNFR2, but not of TNFR1, on lung and brain MVEC, respectively. This increased expression leads to a reduced sensitivity toward TNFR1-mediated phenomena, such as the sensitized TNF cytolytic activity on lung MVEC. In contrast, the sensitivity toward TNFR2-mediated effects, such as ICAM-1 induction by membrane-bound TNF, is increased on brain and lung MVEC expressing increased levels of TNFR2. Therefore, the ICAM-1-inducing effect, rather than the direct cytotoxicity of inflammatory cytokines, such as TNF, appears to be crucial in ARDS and CM-induced endothelial damage, and TNFR2 seems to play an important role in this activity in vivo.