The depth of neuromuscular blockade is not related to chest wall elastance and respiratory mechanics in moderate to severe acute respiratory distress syndrome patients. A prospective cohort study.

BACKGROUND: Data concerning the depth of neuromuscular blockade (NMB) required for effective relaxation of the respiratory muscles in ARDS are scarce. We hypothesised that complete versus partial NMB can modify respiratory mechanics. METHOD: Prospective study to compare the respiratory mechanics of ARDS patients according to the NMB depth. Each patient was analysed at two times: deep NMB (facial train of four count (TOFC) = 0) and intermediate NMB (TOFC >0). The primary endpoint was the comparison of chest wall elastance (ELCW) according to the NMB level. RESULTS: 33 ARDS patients were analysed. There was no statistical difference between the ELCW at TOFC = 0 compared to TOFC >0: 7 cmH2O/l [5.7-9.5] versus 7 cmH2O/l [5.3-10.8] (p = 0.36). The depth of NMB did not modify the expiratory nor inspiratory oesophageal pressure (Pesexp = 8 cmH2O [5-9.5] at TOFC = 0 versus 7 cmH2O [5-10] at TOFC >0; (p = 0.16) and Pesinsp = 10 cmH2O [8.2-13] at TOFC = 0 versus 10 cmH2O [8-13] at TOFC >0; (p = 0.12)). CONCLUSION: In ARDS, the relaxation of the respiratory muscles seems to be independent of the NMB level.

Prediction of pulmonary aspergillosis in patients with ventilator-associated pneumonia.

BACKGROUND: Predictors of ICU-acquired pulmonary aspergillosis (IPA) are not well-established in critically ill patients with ventilator-associated pneumonia (VAP), making IPA commonly misdiagnosed and anti-fungal therapy delayed. We aimed to develop a clinical score for prediction of IPA among patients with VAP. METHODS: Mechanically ventilated patients who developed VAP in 4 ICUs in Bretagne, Western France, were included. The score was constructed in a learning cohort, based on predictors of IPA in logistic regression model, and validated in a validation cohort. RESULTS: Among 1636 mechanically ventilated patients, 215 developed VAP but only 39 developed IPA (4 possible and 35 probable/putative) (18%). Most cases (31/39) were documented through a positive broncho-alveolar sample culture. Independent predictors of IPA were immunodepression (including onco-hematological disorder, immunomodulatory treatment, solid organ transplant, neutropenia < 0.5G/L and high-dose steroids ≥ 1 mg/kg/day of prednisolone equivalent) (p = 0.001; score = 1 point) and lymphocyte count at admission < 0.8 G/L (p = 0.019; score = 1 point). Operational values of the predictive score in the learning/validation cohort were 50%/52% sensitivity and 90%/87% specificity, respectively, for high PiPa score (score = 2) and 94%/91% sensitivity and 44%/46% specificity, respectively, for moderate PiPa score (score = 1). Finally, the AUC for the prediction of IPA was 0.783 in the learning cohort and 0.770 in the validation cohort. CONCLUSIONS: We evaluated a clinical score with good predictive value which may help to predict IPA in patient with VAP. External validation will be needed to confirm our preliminary findings.

Hydrocortisone in Severe Community-Acquired Pneumonia.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Multiple-site decontamination in mechanically ventilated ICU patients: A real-life study.

INTRODUCTION: Decontamination regimen decreases acquired infection (ICU-AI) incidence but has remained controversial, mostly because it contains a course of intravenous antibiotic. Multiple-site decontamination (MSD), which does not include systemic antibiotics, has been less widely studied but is associated with lower risks of ventilator-associated pneumonia (VAP), bloodstream infection (BSI) and multidrug resistant micro-organism (MDRO) acquisition. We aimed to confirm these favorable outcomes. METHODS: A prospective pre/post-observational study was conducted in 5 ICUs in western France. Among them, 4 implemented MSD, whereas the fifth applied standard care (SC) throughout the study period. Patients who required intubation were eligible for study and divided into two groups: the MSD group if they were admitted to an ICU that already implemented MSD, or the SC group. The primary objective was to measure ICU-AI incidence. RESULTS: Close to 1400 (1346) patients were available for analysis (334 in the MSD and 1012 patients in the SC group). In a multivariable Poisson regression model, MSD was independently associated with decreased incidence of ICU-AI (IRR = 0.33; 95 %CI [0.18-0.60] p < 0.001). Non-parsimonious propensity-score matching resulted in 334 patient-pairs with well-balanced baseline characteristics. There was a lower incidence of ICU-AI(6.3 % vs 20.7 % p < 0.001), VAP (3.6 % vs 16.2 % p < 0.001) and BSI (3.0 % vs 7.2 % p = 0.029) in the MSD group as compared with the SC group. Five (1.5 %) and 11 (3.3 %) patients respectively acquired MDRO (p = 0.206). CONCLUSION: MSD is associated with decreased risk of ICU-AI, VAP and BSI, with no increase in MDRO acquisition.

Prevention of acquired invasive fungal infection with decontamination regimen in mechanically ventilated ICU patients: a pre/post observational study.

BACKGROUND: Invasive fungal infections acquired in the intensive care unit (AFI) are life-threating complications of critical illness. However, there is no consensus on antifungal prophylaxis in this setting. Multiple site decontamination is a well-studied prophylaxis against bacterial and fungal infections. Data on the effect of decontamination regimens on AFI are lacking. We hypothesised that multiple site decontamination could decrease the rate of AFI in mechanically ventilated patients. METHODS: We conducted a pre/post observational study in 2 ICUs, on adult patients who required mechanical ventilation for >24 h. During the study period, multiple-site decontamination was added to standard of care. It consists of amphotericin B four times daily in the oropharynx and the gastric tube along with topical antibiotics, chlorhexidine body wash and nasal mupirocin. RESULTS: In 870 patients, there were 27 AFI in 26 patients. Aspergillosis accounted for 20/143 of ventilator-associated pneumonia and candidemia for 7/75 of ICU-acquired bloodstream infections. There were 3/308 (1%) patients with AFI in the decontamination group and 23/562 (4%) in the standard-care group (p = 0.011). In a propensity-score matched analysis, there were 3/308 (1%) and 16/308 (5%) AFI in the decontamination group and the standard-care group respectively (p = 0.004) (3/308 vs 11/308 ventilator-associated pulmonary aspergillosis, respectively [p = 0.055] and 0/308 vs 6/308 candidemia, respectively [p = 0.037]). CONCLUSION: Acquired fungal infection is a rare event, but accounts for a large proportion of ICU-acquired infections. Our study showed a preventive effect of decontamination against acquired fungal infection, especially candidemia.Take home messageAcquired fungal infection (AFI) incidence is close to 4% in mechanically ventilated patients without antifungal prophylaxis (3% for pulmonary aspergillosis and 1% for candidemia).Aspergillosis accounts for 14% of ventilator-associated pneumonia and candidemia for 9% of acquired bloodstream infections.Immunocompromised patients, those infected with SARS-COV 2 or influenza virus, males and patients admitted during the fall season are at higher risk of AFI.Mechanically ventilated patients receiving multiple site decontamination (MSD) have a lower risk of AFI.

Treating Acute Severe Eosinophilic Asthma with IL-5 Inhibitors in ICU.

Introduction: About 10% of the 300 million people worldwide who suffer from asthma have a severe disease that is uncontrolled despite treatment with inhaled corticosteroids and long-acting beta agonists. The eosinophilic inflammation pathway in the respiratory tract and blood is involved and interleukin-5 (IL-5) has recently been identified as a major promotor of this pathway. The anti-IL-5 antibodies reduce the incidence of exacerbation and allowed steroid sparing in severe asthma patients but only two case reports have been published on their use in critical care. Case Presentation. This report describes the extraordinary clinical improvement of a young patient with steroid-refractory eosinophilic acute severe asthma who required mechanical ventilation, VV-ECMO followed by treatment with mepolizumab. The salient point in this case is the use of an anti-IL-5 monoclonal antibody for a critically ill patient whose condition was deteriorating despite mechanical ventilation and VV-ECMO. The usual steroid treatment failed to control the increase in blood eosinophils or his bronchial inflammation and constriction. Conclusion: Anti-IL-5 antibodies are now a standard treatment for severe eosinophilic asthma that can also be useful in an emergency to treat steroid-refractory eosinophilic acute severe asthma.

Characteristics and prognosis of bloodstream infection in patients with COVID-19 admitted in the ICU: an ancillary study of the COVID-ICU study.

BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. PATIENTS AND METHODS: We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. RESULTS: Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05-1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. CONCLUSION: COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate.

Functional outcome of patients with prolonged hypoglycemic encephalopathy.

BACKGROUND: Little is known about the causes, clinical course and long-term outcome of comatose patients with prolonged hypoglycemic encephalopathy. METHODS: In a multicenter retrospective study conducted in patients hospitalized from July 1, 2004, to July 1, 2014, we investigated functional long-term prognosis and identified prognosis factors of patients admitted in an intensive care unit (ICU) with prolonged neurological manifestations related to hypoglycemia. Eligible patients were adults admitted to the ICU with a Glasgow Coma Score <8 due to hypoglycemia and persistent consciousness disorders after normalizing blood glucose levels. Patients with possible other causes of consciousness disorders, previous cognitive disorders, hypothermia <35 °C or circulatory arrest within 24 h after ICU admission, were excluded. Follow-up phone call was used to determine patients' functional outcome using modified Rankin Scale (mRS) at a minimum of 1-year follow-up with mRS 0-3 defining good and mRS 4-6 poor outcomes. RESULTS: Forty-nine patients were included. Causes of hypoglycemia were various, mainly including insulin or oral antidiabetic drugs abuse (65%) and neuroendocrine carcinoma (16%). Twenty (41%) patients died in the ICU, two (4%) patients further died and nine (18%) patients had a poor outcome at long-term follow-up. Five patients discharged from the ICU with mRS > 3 improved enough to be in the good outcome group 1 year later. Twenty-two (45%) patients underwent therapeutic limitation, mainly related to no expected hope for improvement. On multivariate analysis, only low mRS prior to ICU admission (OR 2.6; 95% CI 1.1-6.3; P = 0.03) and normal brain imaging (OR 7.1; 95% CI 1.1-44; P = 0.03) were significantly predictive of a good outcome. All patients (n = 15) who remained hypoglycemic >480 min had a poor outcome. CONCLUSION: Poor outcome was observed in about 60% of this population of hypoglycemic encephalopathy. However, some patients can recover satisfactorily over time.

Clinical assessment and train-of-four measurements in critically ill patients treated with recommended doses of cisatracurium or atracurium for neuromuscular blockade: a prospective descriptive study.

BACKGROUND: Despite few studies, a monitoring of a neuromuscular blockade with a train of four (TOF) is recommended in intensive care unit (ICU). Our objective was to compare the results of ulnar and facial TOF measurements with an overall clinical assessment for neuromuscular blockade in ICU patients treated with recommended doses of atracurium or cisatracurium, including patients with acute respiratory disease syndrome (ARDS). METHODS: We prospectively included in two ICUs 119 patients, 94 with ARDS, who required a neuromuscular blockade for more than 24 h. Three levels of neuromuscular blockade were defined: "over-paralyzed" (TOF = 0), "well-paralyzed" (TOF = 1-2), and "under-paralyzed" (TOF = 3-4). Physicians blinded for TOF counts were asked to classify patients clinically as "over-paralyzed," "well-paralyzed," or "under-paralyzed". Patients were assessed two times daily. RESULTS: For the whole population 996 ulnar and facial TOF measurements and clinical assessments were obtained (846 with cisatracurium and 150 with atracurium). Proportions of patients classified as over-paralyzed, well-paralyzed, and under-paralyzed based on TOF measurements and clinical assessments differed significantly (p < 0.0001). The number of observed agreements between clinical assessments and facial TOF measurements was of 19.08% (κ = 0.06) and of 17.37% with ulnar TOF measurements (κ = 0.04), while it was of 62.75% between ulnar and facial TOF measurements (κ = 0.45). Results were similar for cisatracurium and atracurium. Repeated facial TOF measurements performed on the first 4 days of mechanical ventilation in ARDS patients showed that the proportion of patients TOF = 1-2 was around 8% and did not vary significantly with time (p = 0.9), proportion of patients TOF = 3-4 increased from 24 to 40% (p = 0.01), proportion of patients TOF = 0 decreased from 71 to 53% (p = 0.005) while objectives for protective ventilation were achieved. Proportions of facial and ulnar TOF = 0 were significantly higher among patients with ICU-acquired weakness (ICU-AW) versus those who did not develop ICU-AW (51 vs. 40%, p = 0.03, and 76 vs. 62%, p = 0.006, respectively). CONCLUSIONS: The study provides data on clinical and TOF monitoring of neuromuscular blockade, which are widely divergent in ICU patients receiving recommended doses of benzylisoquinoliniums.

Functional outcome of prolonged refractory status epilepticus.

INTRODUCTION: To characterize etiology, clinical course and outcomes of patients in prolonged refractory status epilepticus (PRSE) and looking for prognostic factors. METHODS: Retrospective study conducted in patients hospitalized from January 1, 2001 to December 31, 2011 in 19 polyvalent intensive care units in French university and general hospitals. Patients were adults with a generalized convulsive refractory status epilepticus that lasted more than seven days, despite treatment including an anesthetic drug and mechanical ventilation. Patients with anoxic encephalopathy were excluded. Follow-up phone call was used to determine functional outcome using modified Rankin Scale (mRS) with mRS 0-3 defining good and mRS 4-6 poor outcome. RESULTS: 78 patients (35 female) were included. Median age was 57 years. Causes of status epilepticus were various, mainly including prior epilepsy (14.1%), CNS infection (12.8%), and stroke (12.8%). No etiology was found in 27 (34.6%) patients. PRSE was considered controlled in only 53 (67.9%) patients after a median duration of 17 (IQR 12-26) days. The median length of ICU stay was 28 (19-48) days. Forty-one (52.5%) patients died in the ICU, 26 from multiple organ failure, 8 from care withdrawal, 2 from sudden cardiac arrest, 1 from brain death and 4 from unknown causes. PRSE was previously resolved in 20 patients who died in the ICU. At one-year follow-up, there were 12 patients with good outcome and 58 with poor outcome and 8 lost of follow-up. On multivariate analysis, only vasopressor use was a predictor of poor outcome (OR 6.54; 95%CI 1.09-39.29; p = 0.04). CONCLUSION: Poor outcome was observed in about 80% of this population of PRSE. Most patients died from systemic complications linked to their ICU stay. Some patients can recover satisfactorily over time though we did not identify any robust factor of good outcome.

Takotsubo cardiomyopathy associated with Guillain-Barré syndrome: a differential diagnosis from dysautonomia not to be missed.

A 60-year-old woman presented with a 1-week progressive limb weakness and an areflexic tetraparesis. Both neurophysiological and cerebrospinal fluid examinations were consistent with diagnosis of Guillain-Barré syndrome (GBS) and a treatment by intravenous immunoglobulin over a 5-day period was started. At the end of the treatment, the patient suffered from an acute coronary syndrome (ACS) without stenosis at coronary arteriography. Left ventriculography showed segmental wall motion abnormalities with apical akinesis contrasting with hyperkinesis in basal segments, with a depressed left ventricular ejection fraction at 45%. Cardiac magnetic resonance imaging excluded the diagnosis of myocarditis. A diagnosis of "transient left ventricular apical ballooning syndrome" or "Takotsubo" syndrome was then made and a treatment by angiotensin-converting enzyme inhibitor and beta-blocker was introduced. Left ventricular dysfunction and electrocardiogram normalized within two weeks and the patient remained free from cardiovascular events at one year of follow-up. This cardiomyopathy is a recently known and now commonly diagnosed reversible systolic dysfunction mimicking ACS and is secondary to physical or emotional stress affecting mainly post-menopausal women. Electrocardiographic and echocardiographic abnormalities are often regressive in days or weeks, and rarely responsible for complications. This observation supports clinical evidence that electrocardiographic changes in GBS can be linked to Takotsubo syndrome, by means of the stressful trigger of GBS occurrence. This reversible cardiomyopathy needs adequate management and specific therapeutic strategies. Therefore, trans-thoracic echocardiography should be systematically performed when repolarisation abnormalities are present in this disease to rule out a Takotsubo syndrome, even in asymptomatic patients.

Late-onset ventilator-associated pneumonia in nontrauma intensive care unit patients.

BACKGROUND: Most studies designed to determine the factors associated with the acquisition of late-onset ventilator-associated pneumonia (VAP) were performed in critically ill trauma patients. The impact of enteral nutrition (EN) on the risk of acquiring VAP has been discussed. In this study, we assessed factors associated with late-onset VAP in nontrauma patients and determined whether nutrition provided early was associated with development of late-onset VAP in this population. METHODS: We performed a prospective observational cohort study in a 21-bed polyvalent intensive care unit in a university hospital. RESULTS: Three hundred sixty-one intubated adult patients with a duration of mechanical ventilation (MV) of 6 days or more were admitted over a 28-mo period. Late-onset VAP was confirmed in 76 patients (21%) by the presence of at least one microorganism at a concentration >or=10(4) colony-forming units/mL on the bronchoalveolar lavage. Gram-negative bacilli represented 75% and Staphylococcus aureus 21% of recovered organisms. Factors independently associated with late-onset VAP by multivariate analysis included a high simplified acute physiology score II score (odds ratio: 1.021; 95% confidence interval [CI]: 1.005-1.038; P = 0.01), development of acute respiratory distress syndrome during the first 5 days of MV (odds ratio: 1.98; 95% CI: 1.05-3.67; P = 0.04), and size of the endotracheal tube >or=7.5 (odds ratio: 2.06; 95% CI: 1.88-3.90; P = 0.03). EN started within 48 h of MV onset was not associated with a higher risk for late-onset VAP. CONCLUSION: In our nontrauma patient population, early EN was not associated with development of late-onset VAP. In this population, severity of the disease during the first 5 days of MV seemed to be associated with late-onset VAP. In addition, our results suggest that the risk of late-onset VAP is higher in patients with a tube size >or=7.5 than in patients with a tube size <7.5.

At-risk drinkers are at higher risk to acquire a bacterial infection during an intensive care unit stay than abstinent or moderate drinkers.

OBJECTIVES: To determine whether excessive alcohol consumption increases the risk for intensive care unit (ICU)-acquired bacterial infection, especially ventilator-associated pneumonia (VAP), in nontrauma patients. DESIGN: Prospective observational cohort study. SETTING: A 21-bed polyvalent ICU in a university hospital. PATIENTS: A total of 358 adult patients admitted over a 1-yr period who had an ICU stay > or = 3 days and in whom alcohol consumption could be assessed. INTERVENTIONS: None. MEASUREMENTS AND MEAN RESULTS: Thirty-one percent of the patients (111 of 358) were identified as at-risk drinkers according to the National Institute on Alcohol Abuse and Alcoholism criteria. Among these, 61 had a daily intake of five or more drinks per day and 73 had Simplified Michigan Alcohol Short Test scores > or = 3. ICU-acquired bacterial infections were diagnosed in 88 patients, and 69 patients had one or more VAPs. Forty (36%) at-risk drinkers acquired bacterial infections vs. 48 (19%) not-at-risk drinkers (p < .001). Among at-risk drinkers, the proportion of patients who developed bacterial infection was higher in at-risk drinkers consuming five or more drinks per day compared with at-risk drinkers consuming fewer than five drinks per day (p = .048). After adjustment for age, gender, Simplified Acute Physiology Score II, length of hospital stay before ICU admission, prior antibiotic administration within 24 hrs before ICU admission, type of admission, immunosuppression, duration of mechanical ventilation, and central venous and urinary catheter exposure, at-risk drinking remained significantly associated with the acquisition of bacterial infection at any site (hazard ratio 1.92; 95% confidence interval, 1.17-3.14; p = .009) and of VAP (hazard ratio 1.76; 95% confidence interval, 1.05-3.06; p = .04). CONCLUSIONS: At-risk drinking was a significant risk factor for acquisition of ICU-acquired bacterial infection.