Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

BACKGROUND: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets. METHODS: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed. FINDINGS: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032). INTERPRETATION: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications. FUNDING: French Ministry of Health.

Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

INTRODUCTION: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. METHODS AND ANALYSIS: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. ETHICS AND DISSEMINATION: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03573739.

Antiplatelet Drugs and Risk of Bleeding After Bedside Pleural Procedures: A National Multicenter Cohort Study.

BACKGROUND: The decision-making on antiplatelet drug withdrawal or continuation before performing a pleural procedure is based on the balance between the risk of bleeding associated with the antiplatelet therapy and the risk of arterial thrombosis due to its interruption. Knowledge on antiplatelet therapy-associated risk of bleeding after pleural procedures is lacking. RESEARCH QUESTION: Is the risk of bleeding associated with antiplatelet drugs increased in patients undergoing pleural procedures? STUDY DESIGN AND METHODS: We conducted a French multicenter cohort study in 19 centers. The main outcome was the occurrence of bleeding, defined as hematoma, hemoptysis, or hemothorax, during the 24 h following a pleural procedure. Serious bleeding events were defined as bleeding requiring blood transfusion, respiratory support, endotracheal intubation, embolization, or surgery, or as death. RESULTS: A total of 1,124 patients was included (men, 66%; median age, 62.6 ± 27.7 years), of whom 182 were receiving antiplatelet therapy and 942 were not. Fifteen patients experienced a bleeding event, including eight serious bleeding events. The 24-h incidence of bleeding was 3.23% (95% CI, 1.08%-5.91%) in the antiplatelet group and 0.96% (95% CI, 0.43%-1.60%) in the control group. The occurrence of bleeding events was significantly associated with antiplatelet therapy in univariate analysis (OR, 3.44; 95% CI, 1.14-9.66; P = .021) and multivariate analysis (OR, 4.13; 95% CI, 1.01-17.03; P = .044) after adjusting for demographic data and the main risk factors for bleeding. Likewise, antiplatelet therapy was significantly associated with serious bleeding in univariate analysis (OR, 8.61; 95% CI, 2.09-42.3; P = .003) and multivariate analysis (OR, 7.27; 95% CI, 1.18-56.1; P = .032) after adjusting for the number of risk factors for bleeding. INTERPRETATION: Antiplatelet therapy was associated with an increased risk of post-pleural procedure bleeding and serious bleeding. Future guidelines should take into account these results for patient safety.

Assessing physicians' and nurses' experience of dying and death in the ICU: development of the CAESAR-P and the CAESAR-N instruments.

BACKGROUND: As an increasing number of deaths occur in the intensive care unit (ICU), studies have sought to describe, understand, and improve end-of-life care in this setting. Most of these studies are centered on the patient's and/or the relatives' experience. Our study aimed to develop an instrument designed to assess the experience of physicians and nurses of patients who died in the ICU, using a mixed methodology and validated in a prospective multicenter study. METHODS: Physicians and nurses of patients who died in 41 ICUs completed the job strain and the CAESAR questionnaire within 24 h after the death. The psychometric validation was conducted using two datasets: a learning and a reliability cohort. RESULTS: Among the 475 patients included in the main cohort, 398 nurse and 417 physician scores were analyzed. The global score was high for both nurses [62/75 (59; 66)] and physicians [64/75 (61; 68)]. Factors associated with higher CAESAR-Nurse scores were absence of conflict with physicians, pain control handled with physicians, death disclosed to the family at the bedside, and invasive care not performed. As assessed by the job strain instrument, low decision control was associated with lower CAESAR score (61 (58; 65) versus 63 (60; 67), p = 0.002). Factors associated with higher CAESAR-Physician scores were room dedicated to family information, information delivered together by nurse and physician, families systematically informed of the EOL decision, involvement of the nurse during implementation of the EOL decision, and open visitation. They were also higher when a decision to withdraw or withhold treatment was made, no cardiopulmonary resuscitation was performed, and the death was disclosed to the family at the bedside. CONCLUSION: We described and validated a new instrument for assessing the experience of physicians and nurses involved in EOL in the ICU. This study shows important areas for improving practices.

Benefit-to-risk balance of bronchoalveolar lavage in the critically ill. A prospective, multicenter cohort study.

PURPOSE: To assess the benefit-to-risk balance of bronchoalveolar lavage (BAL) in intensive care unit (ICU) patients. METHODS: In 16 ICUs, we prospectively collected adverse events during or within 24 h after BAL and assessed the BAL input for decision making in consecutive adult patients. The occurrence of a clinical adverse event at least of grade 3, i.e., sufficiently severe to need therapeutic action(s), including modification(s) in respiratory support, defined poor BAL tolerance. The BAL input for decision making was declared satisfactory if it allowed to interrupt or initiate one or several treatments. RESULTS: We included 483 BAL in 483 patients [age 63 years (interquartile range (IQR) 53-72); female gender: 162 (33.5%); simplified acute physiology score II: 48 (IQR 37-61); immunosuppression 244 (50.5%)]. BAL was begun in non-intubated patients in 105 (21.7%) cases. Sixty-seven (13.9%) patients reached the grade 3 of adverse event or higher. Logistic regression showed that a BAL performed by a non-experienced physician (non-pulmonologist, or intensivist with less than 10 years in the specialty or less than 50 BAL performed) was the main predictor of poor BAL tolerance in non-intubated patients [OR: 3.57 (95% confidence interval 1.04-12.35); P = 0.04]. A satisfactory BAL input for decision making was observed in 227 (47.0%) cases and was not predictable using logistic regression. CONCLUSIONS: Adverse events related to BAL in ICU patients are not infrequent nor necessarily benign. Our findings call for an extreme caution, when envisaging a BAL in ICU patients and for a mandatory accompaniment of the less experienced physicians.

Severe leptospirosis in non-tropical areas: a nationwide, multicentre, retrospective study in French ICUs.

PURPOSE: To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone. METHODS: LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes. RESULTS: The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations. CONCLUSIONS: Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

Differential Perceptions of Noninvasive Ventilation in Intensive Care among Medical Caregivers, Patients, and Their Relatives: A Multicenter Prospective Study-The PARVENIR Study.

BACKGROUND: Noninvasive ventilation (NIV) requires a close "partnership" between a conscious patient and the patient's caregivers. Specific perceptions of NIV stakeholders and their impact have been poorly described to date. The objectives of this study were to compare the perceptions of NIV by intensive care unit (ICU) physicians, nurses, patients, and their relatives and to explore factors associated with caregivers' willingness to administer NIV and patients' and relatives' anxiety in relation to NIV. METHODS: This is a prospective, multicenter questionnaire-based study. RESULTS: Three hundred and eleven ICU physicians, 752 nurses, 396 patients, and 145 relatives from 32 ICUs answered the questionnaire. Nurses generally reported more negative feelings and more frequent regrets about providing NIV (median score, 3; interquartile range, [1 to 5] vs. 1 [1 to 5]; P < 0.0001) compared to ICU physicians. Sixty-four percent of ICU physicians and only 32% of nurses reported a high level of willingness to administer NIV, which was independently associated with NIV case-volume and workload. A high NIV session-related level of anxiety was observed in 37% of patients and 45% of relatives. "Dyspnea during NIV," "long NIV session," and "the need to have someone at the bedside" were identified as independent risk factors of high anxiety in patients. CONCLUSIONS: Lack of willingness of caregivers to administer NIV and a high level of anxiety of patients and relatives in relation to NIV are frequent in the ICU. Most factors associated with low willingness to administer NIV by nurses or anxiety in patients and relatives may be amenable to change. Interventional studies are now warranted to evaluate how to reduce these risk factors and therefore contribute to better management of a potentially traumatic experience. (Anesthesiology 2016; 124:1347-59).

CAESAR: a new tool to assess relatives' experience of dying and death in the ICU.

PURPOSE: To develop an instrument designed specifically to assess the experience of relatives of patients who die in the intensive care unit (ICU). METHODS: The instrument was developed using a mixed methodology and validated in a prospective multicentre study. Relatives of patients who died in 41 ICUs completed the questionnaire by telephone 21 days after the death, then completed the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised and Inventory of Complicated Grief after 3, 6, and 12 months. RESULTS: A total of 600 relatives were included, 475 in the main cohort and 125 in the reliability cohort. The 15-item questionnaire, named CAESAR, covered the patient's preferences and values, interactions with/around the patient and family satisfaction. We defined three groups based on CAESAR score tertiles: lowest (≤59, n = 107, 25.9 %), middle (n = 185, 44.8 %) and highest (≥69, n = 121, 29.3 %). Factorial analysis showed a single dimension. Cronbach's alpha in the main and reliability cohorts was 0.88 (0.85-0.90) and 0.85 (0.79-0.89), respectively. Compared to a high CAESAR score, a low CAESAR score was associated with greater risks of anxiety and depression at 3 months [1.29 (1.13-1.46), p = 0.001], post-traumatic stress-related symptoms at 3 [1.34 (1.17-1.53), p < 0.001], 6 [OR = 1.24 (1.06-1.44), p = 0.008] and 12 [OR = 1.26 (1.06-1.50), p = 0.01] months and complicated grief at 6 [OR = 1.40 (1.20-1.63), p < 0.001] and 12 months [OR = 1.27 (1.06-1.52), p = 0.01]. CONCLUSIONS: The CAESAR score 21 days after death in the ICU is strongly associated with post-ICU burden in the bereaved relatives. The CAESAR score should prove a useful primary endpoint in trials of interventions to improve relatives' well-being.

Complicated grief after death of a relative in the intensive care unit.

An increased proportion of deaths occur in the intensive care unit (ICU). We performed this prospective study in 41 ICUs to determine the prevalence and determinants of complicated grief after death of a loved one in the ICU. Relatives of 475 adult patients were followed up. Complicated grief was assessed at 6 and 12 months using the Inventory of Complicated Grief (cut-off score >25). Relatives also completed the Hospital Anxiety and Depression Scale at 3 months, and the Revised Impact of Event Scale for post-traumatic stress disorder symptoms at 3, 6 and 12 months. We used a mixed multivariate logistic regression model to identify determinants of complicated grief after 6 months. Among the 475 patients, 282 (59.4%) had a relative evaluated at 6 months. Complicated grief symptoms were identified in 147 (52%) relatives. Independent determinants of complicated grief symptoms were either not amenable to changes (relative of female sex, relative living alone and intensivist board certification before 2009) or potential targets for improvements (refusal of treatment by the patient, patient died while intubated, relatives present at the time of death, relatives did not say goodbye to the patient, and poor communication between physicians and relatives). End-of-life practices, communication and loneliness in bereaved relatives may be amenable to improvements.

Safety of performing fiberoptic bronchoscopy in critically ill hypoxemic patients with acute respiratory failure.

BACKGROUND: The safety of fiberoptic bronchoscopy (FOB) in nonintubated critically ill patients with acute respiratory failure has not been extensively evaluated. We aimed to measure the incidence of intubation and the need to increase ventilatory support following FOB and to identify predictive factors for this event. METHODS: A prospective multicenter observational study was carried out in eight French adult intensive care units. The study included 169 FOB performed in patients with a PaO(2)/FiO(2) ratio ≤ 300. The main end-point was intubation rate. The secondary end-point was rate of increased ventilatory support defined as an increase in oxygen requirement >50 %, the need to start noninvasive positive pressure ventilation (NI-PPV) or increase NI-PPV support. RESULTS: Within 24 h, an increase in ventilatory support was required following 59 bronchoscopies (35 %), of which 25 (15 %) led to endotracheal intubation. The existence of chronic obstructive pulmonary disease (COPD; OR 5.2, 95 % CI 1.6-17.8; p = 0.007) or immunosuppression (OR 5.4, 95 % CI 1.7-17.2; p = 0.004] were significantly associated with the need for intubation in the multivariable analysis. None of the baseline physiological parameters including the PaO(2)/FiO(2) ratio was associated with intubation. CONCLUSIONS: Bronchoscopy is often followed by an increase in ventilatory support in hypoxemic critically ill patients, but less frequently by the need for intubation. COPD and immunosuppression are associated with the need for invasive ventilation in the 24 h following bronchoscopy.

Identification of prolonged phrenic nerve conduction time in the ICU: magnetic versus electrical stimulation.

PURPOSE: Retrospective study of prospectively collected data to assess the reliability of cervical magnetic stimulation (CMS) to detect prolonged phrenic nerve (PN) conduction time at the bedside. Because PN injuries may cause diaphragm dysfunction, their diagnosis is relevant in intensive care units (ICU). This is achieved by studying latency and amplitude of diaphragm response to PN stimulation. Electrical stimulation (ES) is the gold standard, but it is difficult to perform in the ICU. CMS is an easy noninvasive tool to assess PN integrity, but co-activates muscles that could contaminate surface chest electromyographic recordings. METHODS: In a first set of 56 ICU patients with suspected PN injury, presence and latency of compound motor action potentials elicited by CMS and ES were compared. With ES as the reference method, CMS was evaluated as a test designed to indicate presence or absence of PN injury. In eight additional patients, intramuscular diaphragm recordings were compared with surface diaphragm recordings and with the electromyograms of possible contamination sources. RESULTS: The sensitivity of CMS to diagnose abnormal PN conduction was 0.91, and specificity was 0.84, whereas positive and negative predictive values were 0.81 and 0.92, respectively. Passing-Bablok regression analysis suggested no differences between the two measures. The correlation between PN latency in response to CMS and ES was significant. The "diaphragm surface" and "needle" latencies were close, and were significantly different from those of possibly contaminating muscles. One hemidiaphragm showed likely signal contamination. CONCLUSION: CMS provides an easy reliable tool to detect prolonged PN conduction time in the ICU.

Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized controlled trial.

RATIONALE: Respiratory events are common in hematology and oncology patients and manifest as hypoxemic acute respiratory failure (ARF) in up to half the cases. Identifying the cause of ARF is crucial. Fiberoptic bronchoscopy with bronchoalveolar lavage (FO-BAL) is an invasive test that may cause respiratory deterioration. Recent noninvasive diagnostic tests may have modified the risk/benefit ratio of FO-BAL. OBJECTIVES: To determine whether FO-BAL in cancer patients with ARF increased the need for intubation and whether noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL. METHODS: We performed a multicenter randomized controlled trial with sample size calculations for both end points. Patients with cancer and ARF of unknown cause who were not receiving ventilatory support at intensive care unit admission were randomized to early FO-BAL plus noninvasive tests (n = 113) or noninvasive tests only (n = 106). The primary end point was the number of patients needing intubation and mechanical ventilation. The major secondary end point was the number of patients with no identified cause of ARF. MEASUREMENTS AND MAIN RESULTS: The need for mechanical ventilation was not significantly greater in the FO-BAL group than in the noninvasive group (35.4 vs. 38.7%; P = 0.62). The proportion of patients with no diagnosis was not smaller in the noninvasive group (21.7 vs. 20.4%; difference, -1.3% [-10.4 to 7.7]). CONCLUSIONS: FO-BAL performed in the intensive care unit did not significantly increase intubation requirements in critically ill cancer patients with ARF. Noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL for identifying the cause of ARF. Clinical trial registered with www.clinicaltrials.gov (NCT00248443).

Neurally adjusted ventilatory assist increases respiratory variability and complexity in acute respiratory failure.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a partial ventilatory support mode where positive pressure is provided in relation to diaphragmatic electrical activity (EAdi). Central inspiratory activity is normally not monotonous, but it demonstrates short-term variability and complexity. The authors reasoned that NAVA should produce a more "natural" or variable breathing pattern than other modes. This study compared respiratory variability and complexity during pressure support ventilation (PSV) and NAVA. METHODS: Flow and EAdi were recorded during routine PSV (tidal volume approximately 6-8 ml/kg) and four NAVA levels (1-4 cm H2O/microVEAdi) in 12 intubated patients. Breath-by-breath variability of flow and EAdi-related variables was quantified by the coefficient of variation (CV) and autocorrelation analysis. Complexity of flow and EAdi was described using noise titration, largest Lyapunov exponent, Kolmogorov-Sinai entropy, and three-dimensional phase portraits. RESULTS: Switching from PSV to NAVA increased the CV and decreased the autocorrelation for most flow-related variables in a dose-dependent manner (P < 0.05, partial eta for the CV of mean inspiratory flow 0.642). The changes were less marked for EAdi. A positive noise limit was consistently found for flow and EAdi. Largest Lyapunov exponent and Kolmogorov-Sinai entropy for flow were greater during NAVA than PSV and increased with NAVA level (P < 0.05, partial eta 0.334 and 0.312, respectively). Largest Lyapunov exponent and Kolmogorov-Sinai entropy for EAdi were not influenced by ventilator mode. CONCLUSIONS: Compared with PSV, NAVA increases the breathing pattern variability and complexity of flow, whereas the complexity of EAdi is unchanged. Whether this improves clinical outcomes remains to be determined.

Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.

BACKGROUND: Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting. METHODS: In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667. FINDINGS: Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001). INTERPRETATION: A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes. FUNDING: Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.

Invasive pulmonary aspergillosis in patients with decompensated cirrhosis: case series.

BACKGROUND: Opportunistic invasive fungal infections are increasingly frequent in intensive care patients. Their clinical spectrum goes beyond the patients with malignancies, and for example invasive pulmonary aspergillosis has recently been described in critically ill patients without such condition. Liver failure has been suspected to be a risk factor for aspergillosis. CASE PRESENTATION: We describe three cases of adult respiratory distress syndrome with sepsis, shock and multiple organ failure in patients with severe liver failure among whom two had positive Aspergillus antigenemia and one had a positive Aspergillus serology. In all cases bronchoalveolar lavage fluid was positive for Aspergillus fumigatus. Outcome was fatal in all cases despite treatment with voriconazole and aggressive symptomatic treatment. CONCLUSION: Invasive aspergillosis should be among rapidly raised hypothesis in cirrhotic patients developing acute respiratory symptoms and alveolar opacities.

Reduced breathing variability as a predictor of unsuccessful patient separation from mechanical ventilation.

OBJECTIVES: To compare descriptors of the breath-to-breath respiratory variability during a 60-min spontaneous breathing trial in patients successfully and unsuccessfully separated from the ventilator and the endotracheal tube and to assess the usefulness of these predictors in discriminating these two categories of patients. DESIGN: Prospective observational study. SETTING: Four general intensive care units in university hospitals. PATIENTS: A total of 51 consecutive patients mechanically ventilated for >24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tidal volume, respiratory period, inspiratory time, expiratory time, mean inspiratory flow (tidal volume/inspiratory time), and duty cycle (inspiratory time/respiratory period) were obtained from the flow signal. Breath-by-breath variability was expressed in terms of their coefficients of variation (CV), the number of breaths among which a significant correlation was found (lag), and the autocorrelation coefficient between one breath and the following one. Five patients were excluded because of nonstationarity of the data, leaving 46 cases for analysis. Between-group comparison was conducted with the Mann-Whitney test, and a nonparametric classification and regression tree was used to identify variables discriminating "success" (n = 32) and "failure" patients (n = 14). All coefficients of variation were significantly higher in success patients, who also exhibited significantly less respiratory autocorrelation (shorter "short memory"). The classification and regression tree analysis allocated all success patients to a group defined by a coefficient of variation of tidal volume/inspiratory time of > or =19% and a coefficient of variation of inspiratory time/respiratory period of > or =10% that did not contain any failure patient. All failure patients belonged to a group with coefficient of variation of tidal volume/inspiratory time of <19%, a lag tidal volume of > or =11, and that contained no success patient. CONCLUSIONS: In intensive care unit patients undergoing a spontaneous breathing trial, breathing variability is greater in patients successfully separated from the ventilator and the endotracheal tube. Variability indices are sufficient to separate success from failure cases.

Patients aged 90 years or older in the intensive care unit.

BACKGROUND: Age is an important prognostic factor in patients admitted to intensive care units (ICUs), but it is not as important as illness severity. However, age seems to remain an important independent triage criterion for ICU admission, and 90 years of age seems to represent a psychological barrier for many ICU physicians. The aim of this preliminary study is to compare the management and outcome of patients aged 90 years or older admitted to a respiratory ICU with those of patients aged 70 years or younger. METHODS: In our matched case-control study over a 6-year period, 36 patients aged 90 years or older (case patients) were selected and matched according to sex with 72 controls chosen in the 20- to 69-year age range. The Simplified Acute Physiology Score (SAPS) II was then computed without using age as a variable. RESULTS: Pre-existing comorbidities were significantly less frequent in cases than in controls (5.1% vs 30.5%, p <.01). Compared to controls, cases were more frequently admitted for cardiac failure (22% vs 7%, p <.05) and less frequently for neurological diseases (0% vs 11%, p <.05). The use of advanced life-support measures in the ICU such as mechanical ventilation, central venous or arterial catheterization, and vasoactive and/or inotropic drugs was not significantly different between case patients and controls. This was also the case for ICU mortality and for the mean duration of ICU and hospital stay. Although there was a trend toward a higher hospital mortality among case patients than among controls, it did not reach statistical significance (47% vs 27%, p =.07). CONCLUSION: Our results reinforce the idea that age alone is not a relevant criterion for ICU admission.

[Diagnosis and management of exacerbations and acute respiratory failure in patients with chronic obstructive pulmonary disease]. / Exacerbations et décompensations de la bronchopneumopathie chronique obstructive.

Acute episode of chronic obstructive pulmonary disease occurs in almost all patients, during which cough, expectoration and dyspnea increase. When the underlying disease is not severe and the acute episode not life-threatening, the term "exacerbation" is appropriate, and the patients can be managed at home. When the underlying disease is advanced and the acute episode possibly life-threatening, the terms of "acute respiratory failure" or "decompensation" can be used. These patients are most often admitted to the hospital, and at times to the intensive care unit. Bronchodilators and respiratory physiotherapy form the basis of the management of acute episodes of COPD. In severe cases, oxygen must be administered, and the decision of an hospitalisation considered. Antibiotics and corticosteroids shoud not be prescribed in a systematic manner. In the most severe cases, non-invasive ventilation must be accessible. The prevention of acute episodes of COPD is best achieved through tobacco cessation and influenza vaccine. Finally, an acute episode may be an opportunity to make a diagnosis of COPD if this has not been done before.

Cardiac troponin I in patients with severe exacerbation of chronic obstructive pulmonary disease.

OBJECTIVES: Co-morbid conditions including risk factors for cardiovascular diseases and left ventricular dysfunction are common in patients with chronic obstructive pulmonary disease (COPD). This study assessed the incidence of cardiac troponin I (cTnI) elevation, a specific marker for cardiac injury, and its prognostic significance during severe exacerbation of COPD. DESIGN: Prospective cohort study. SETTING: Two intensive care units. PARTICIPANTS: Seventy-one consecutive patients admitted for severe exacerbation of COPD. INTERVENTION: None. MEASUREMENTS AND RESULTS: Cardiac troponin I was assayed in blood samples obtained on admission and 24 h later (Stratus II immunoassay analyser, Dade International). Levels above 0.5 ng/ml were considered positive. The following data were recorded prospectively: clinical symptoms, co-morbidities, cause of the exacerbation, diagnostic procedures and treatment, general severity score (SAPS II) and in-hospital outcome. CTnI was positive in 18% of patients (95% confidence interval (CI(95)), 11-29%), with a median value at 1.00 ng/ml; CI(95 )(0.60-1.70). Eighteen patients died in the hospital (25%; CI(95), 17-37%). Only cTnI (adjusted odds ratio (ORa), 6.52; CI(95),1.23-34.47) and SAPS II 24 h after admission (ORa, 1.07; CI(95), 1.01-1.13) were independent predictors of in-hospital mortality. CONCLUSION: Elevated cTnI is a strong and independent predictor of in-hospital death in patients admitted for acutely exacerbated COPD.