Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study.

BACKGROUND: Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged. METHODS: Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death. RESULTS: From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21-42), 40% (95% CI 26-55) and 21% (95% CI 15-28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92-61.91)]. CONCLUSION: Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.

Nutritional status, swallowing disorders, and respiratory prognosis in adult Duchenne muscular dystrophy patients.

Malnutrition and swallowing disorders are common in Duchenne muscular dystrophy (DMD) patients. We assessed, in adult DMD with home mechanical ventilation (HMV) and cough assist device, its prevalence and the relationships with respiratory muscle strength and long-term respiratory prognosis. We reviewed the patients (n = 117, age 18-39 years [median 24]), followed in a reference center, from 2006 to 2015, to obtain clinical baseline, nutritional status, vital capacity (VC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). The median body mass index (BMI) was low (15.6 kg/m²). Included patients had severe restrictive respiratory function with a median VC of 10.5% [7-17] of the predicted value. All patients were on HMV. Prevalence of malnutrition, swallowing disorders, and gastrostomy were respectively 62%, 34%, and 11%. BMI and serum albumin level were significantly associated with MIP, MEP, and VC. The 1-year/5-years cumulative incidences of respiratory events (pulmonary sepsis and acute respiratory distress) were, respectively, 20.7%/44.5%. Using univariate analysis, predictive factors for respiratory events were swallowing disorders (p = .001), transthyretinemia (p = .034), MIP (p = .039), and MEP (p = .03) but not BMI or albuminemia. Using multivariate analysis, only swallowing disorders remained significantly associated with respiratory events (OR = 4.2, IC 95% 1.31-12.2, p = .01). In conclusion, this study highlights the interrelationships between nutritional intake, swallowing function, airway clearance, and respiratory function in adult DMD. A multidisciplinary approach focusing on these previous factors is essential to optimize DMD patient health.

M Mode Ultrasound and Tissue Doppler Imaging to Assess Diaphragm Feature in Late Onset Pompe Disease.

Late-onset Pompe disease (LOPD) is an autosomal recessive lysosomal storage disease. Clinical features include skeletal muscle deficiency and diaphragm weakness. Clinical management relies on supportive treatment and mechanical ventilation in patients with chronic respiratory failure. M mode ultrasound and sniff tissue Doppler imaging can be used to assess and follow diaphragm function.

Early mechanical ventilation in patients with Guillain-Barré syndrome at high risk of respiratory failure: a randomized trial.

INTRODUCTION: About 30% of patients with Guillain-Barré syndrome become ventilator dependent, of whom roughly 75% develop pneumonia. This trial aimed at assessing the impact of early mechanical ventilation (EMV) on pneumonia occurrence in GBS patients. We hypothesize that EMV will reduce the incidence of pneumonia. METHODS: This was a single centre, open-label, randomized controlled trial performed on two parallel groups. 50 intensive care unit adults admitted for Guillain-Barré syndrome and at risk for acute respiratory failure. Patients were randomized to early mechanical ventilation via face-mask or endotracheal intubation owing to the presence or absence of impaired swallowing (experimental arm), or to conventional care (control arm). The primary outcome was the incidence of pneumonia up to intensive care unit discharge (or 90 days, pending of which occurred first). FINDINGS: Twenty-five patients were randomized in each group. There was no significant difference between groups for the incidence of pneumonia (10/25 (40%) vs 9/25 (36%), P = 1). There was no significant difference between groups for the time to onset of pneumonia (P = 0.50, Gray test). During follow-up, there were 16/25 (64%) mechanically ventilated patients in the control group, and 25/25 (100%) in the experimental arm (P < 000·1). The time on ventilator was non-significantly shorter in the experimental arm (14 [7; 29] versus 21.5 [17.3; 35.5], P = 0.10). There were no significant differences between groups for length of hospital stay, neurological scores, the proportion of patients who needed tracheostomy, in-hospital death, or any serious adverse events. CONCLUSIONS: In the present study including adults with Guillain-Barré syndrome at high risk of respiratory failure, we did not observe a prevention of pneumonia with early mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov under the number NCT00167622. Registered 9 September 2005, https://clinicaltrials.gov/ct2/show/NCT00167622?cond=Guillain-Barre+Syndrome&cntry=FR&draw=2&rank=1.

Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study.

BACKGROUND: Patients with COVID-19 who develop severe acute respiratory distress syndrome (ARDS) can have symptoms that rapidly evolve to profound hypoxaemia and death. The efficacy of extracorporeal membrane oxygenation (ECMO) for patients with severe ARDS in the context of COVID-19 is unclear. We aimed to establish the clinical characteristics and outcomes of patients with respiratory failure and COVID-19 treated with ECMO. METHODS: This retrospective cohort study was done in the Paris-Sorbonne University Hospital Network, comprising five intensive care units (ICUs) and included patients who received ECMO for COVID-19 associated ARDS. Patient demographics and daily pre-ECMO and on-ECMO data and outcomes were collected. Possible outcomes over time were categorised into four different states (states 1-4): on ECMO, in the ICU and weaned off ECMO, alive and out of ICU, or death. Daily probabilities of occupation in each state and of transitions between these states until day 90 post-ECMO onset were estimated with use of a multi-state Cox model stratified for each possible transition. Follow-up was right-censored on July 10, 2020. FINDINGS: From March 8 to May 2, 2020, 492 patients with COVID-19 were treated in our ICUs. Complete day-60 follow-up was available for 83 patients (median age 49 [IQR 41-56] years and 61 [73%] men) who received ECMO. Pre-ECMO, 78 (94%) patients had been prone-positioned; their median driving pressure was 18 (IQR 16-21) cm H2O and PaO2/FiO2 was 60 (54-68) mm Hg. At 60 days post-ECMO initiation, the estimated probabilities of occupation in each state were 6% (95% CI 3-14) for state 1, 18% (11-28) for state 2, 45% (35-56) for state 3, and 31% (22-42) for state 4. 35 (42%) patients had major bleeding and four (5%) had a haemorrhagic stroke. 30 patients died. INTERPRETATION: The estimated 60-day survival of ECMO-rescued patients with COVID-19 was similar to that of studies published in the past 2 years on ECMO for severe ARDS. If another COVID-19 outbreak occurs, ECMO should be considered for patients developing refractory respiratory failure despite optimised care. FUNDING: None.

Thiamine status and lactate concentration in sepsis: A prospective observational study.

Thiamine is an essential co-factor for aerobic metabolism. Both thiamine deficiency and sepsis may be associated with hyperlactatemia and hypotension. We assessed the relationship between thiamine compounds, lactate concentrations and clinical outcomes in septic patients.We undertook a prospective observational single-center study. Erythrocyte levels of total thiamine, free thiamine, thiamine mono, di and triphosphate (TMP, TDP, and TTP respectively), the erythrocyte transketolase activity (ETKA) and the effect of thiamine diphosphate on ETKA were measured in septic patients by high performance liquid chromatography and correlated with arterial lactate. Vital status at the end of intensive care unit stay was recorded.Overall, 28 patients suffering from sepsis were included. Median (interquartile range [IQR]) age was 60 [44-77.3] years, 15 (53.6%) patients were male, median [IQR] simplified acute physiology score II was 40 [27-50]. There was no correlation between total thiamine and lactate levels (P = .33). There was no correlation between free thiamine (P = .81), TMP (P = .71), TDP (P = .31), TTP (P = .86), and lactate levels in our population. There was no correlation between ETKA (P = .58) or the effect of TDP on ETKA (P = .40) and lactate concentration. Total thiamine and TDP concentration were significantly higher in intensive care unit (ICU) survivors than in nonsurvivors (P = .03 and P = .03). The effect of TDP on ETKA was significantly higher in nonsurvivors compared to survivors (P = .04).We found no correlation between thiamine compounds and lactate concentration in sepsis. Thiamine deficiency in sepsis may be associated with ICU-mortality.

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.

Diaphragm sniff ultrasound: Normal values, relationship with sniff nasal pressure and accuracy for predicting respiratory involvement in patients with neuromuscular disorders.

BACKGROUND: In patients with neuromuscular disorders, assessment of respiratory function relies on forced vital capacity (FVC) measurements. Providing complementary respiratory outcomes may be useful for clinical trials. Diaphragm sniff ultrasound (US) is a noninvasive technique that can assess diaphragm function that may be affected in patients with neuromuscular disorders. PURPOSE: We aimed to provide normal values of sniff diaphragm ultrasound, to assess the relationship between sniff diaphragm US, vital capacity (VC) and sniff nasal pressure. Additionally, we aimed to evaluate the diagnostic accuracy of sniff diaphragm US for predicting restrictive pulmonary insufficiency. MATERIALS AND METHODS: We included patients with neuromuscular disorders that had been tested with a sniff diaphragm US and functional respiratory tests. Healthy subjects were also included to obtain normal diaphragm sniff ultrasound. We performed diaphragm tissue Doppler imaging (TDI) and time movement (TM) diaphragm echography combined with sniff maneuver. RESULTS: A total of 89 patients with neuromuscular diseases and 27 healthy subjects were included in our study. In patients, the median age was 32 years [25; 50] and the median FVC was 34% of predicted [18; 55]. Sniff diaphragm motion using TM ultrasound was significantly associated with sniff nasal pressure, both for the right hemidiaphragm (r = 0.6 p <0.0001) and the left hemidiaphragm (r = 0.63 p = 0.0008). Right sniff peak TDI velocity was also significantly associated with FVC (r = 0.72, p<0.0001) and with sniff nasal pressure (r = 0.66 p<0.0001). Sniff diaphragm ultrasound using either TM mode or TDI displayed significant accuracy for predicting FVC<60% with an area under curve (AUC) reaching 0.93 (p<0.0001) for the right sniff diaphragm ultrasound in TM mode and 0.86 (p<0.001) for right peak diaphragm TDI velocity. CONCLUSION: Sniff diaphragm TM and TDI measures were significantly associated with sniff nasal pressure. Sniff diaphragm TM and TDI had a high level of accuracy to reveal respiratory involvement in patients with neuromuscular disorders. This technique is useful to assess and follow up diaphragm function in patients with neuromuscular disorders. It may be used as a respiratory outcome for clinical trials.

Echographic Assessment of Diaphragmatic Function in Duchenne Muscular Dystrophy from Childhood to Adulthood.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic muscle disorder. Respiratory muscle function is classically affected in this disease. Ultrasound recently emerged as a non-invasive tool to assess diaphragm function. However, there are only a few studies using diaphragm ultrasound (US) in DMD. PURPOSE: We aimed to assess diaphragm ultrasound patterns in DMD, their relationship with age and their association with home mechanical ventilation (HMV). METHODS: We included DMD patients followed at Raymond Poincaré Hospital who benefited from diaphragm ultrasound and pulmonary function tests. RESULTS: There were 110 DMD patients and 17 male sex-matched healthy subjects included. In all, 94% of patients were permanent wheelchair users. Median body mass index (BMI) was 18 kg/m2. DMD patients disclosed a reduced forced vital capacity (VC) (12% of predicted value), and 78% of patients were on HMV. In patients, right and left diaphragmatic motions on deep inspiration were reduced and end expiratory diaphragm thickness was borderline normal. In patients, right and left diaphragmatic thickening fractions (TF) were reduced 12.7% and 15.5%, respectively. Age and end expiratory thickness were significantly inversely associated (p = 0.005 for the right diaphragm, p = 0.018 for the left diaphragm). Diaphragm TF was significantly inversely associated with age (p = 0.001 for the right side, p < 0.0001 for the left side). Right and left inspiratory diaphragm motions were significantly inversely associated with age (p < 0.0001). CONCLUSION: This study describes the severity of diaphragm dysfunction in patients with DMD. Diaphragm US may be a non-invasive outcome measure for DMD.

Immune Effects of Corticosteroids in Sepsis.

Sepsis, a life-threatening organ dysfunction, results from a dysregulated host response to invading pathogens that may be characterized by overwhelming systemic inflammation or some sort of immune paralysis. Sepsis remains a major cause of morbidity and mortality. Treatment is nonspecific and relies on source control and organ support. Septic shock, the most severe form of sepsis is associated with the highest rate of mortality. Two large multicentre trials, undertaken 15 years apart, found that the combination of hydrocortisone and fludrocortisone significantly reduces mortality in septic shock. The corticosteroids family is composed of several molecules that are usually characterized according to their glucocorticoid and mineralocorticoid power, relative to hydrocortisone. While the immune effects of glucocorticoids whether mediated or not by the intracellular glucocorticoid receptor have been investigated for several decades, it is only very recently that potential immune effects of mineralocorticoids via non-renal mineralocorticoid receptors have gained popularity. We reviewed the respective role of glucocorticoids and mineralocorticoids in counteracting sepsis-associated dysregulated immune systems.

Effects of Home Mechanical Ventilation on Left Ventricular Function in Sarcoglycanopathies (Limb Girdle Muscular Dystrophies).

Cardiac and respiratory function may be impaired in sarcoglycanopathies, a subgroup of muscular dystrophies due to sarcoglycan proteins (α, ß, γ, and δ) genes mutations. Management of patients with restrictive respiratory failure mainly relies on home mechanical ventilation (HMV). Little is known about the cardiac effects of prolonged mechanical ventilation in patients with muscular dystrophy and restrictive respiratory insufficiency. We aimed to assess the effects of HMV on cardiac function in sarcoglycanopathies. We retrospectively included 10 genetically proven patients with sarcoglycanopathy followed at the HMV unit of the Raymond Poincare University Hospital (4 patients with α-sarcoglycanopathy and 6 patients with γ-sarcoglycanopathy). We collected cardiorespiratory clinical baseline data and left ventricular ejection fraction (LVEF) at baseline before initiation of HMV and at the end of follow-up. At baseline, median age was 30.5 years (27 to 39) and median pulmonary vital capacity was 27% of the predicted value (21 to 36). Forty percent of the patients had documented sleep apnea. Cardiomyopathy, defined as LVEF <50%, was found in 3 patients with γ-sarcoglycanopathy. After a median follow-up of 3 years (1.0 to 4.5), there was a significant increase in LVEF after initiation of HMV, that is, 62% (48 to 65) versus 53% (45.5 to 56.5) (p = 0.0039). In conclusion, HMV in sarcoglycanopathies is not harmful and may protect left ventricular function by its thoracic physiological effects.

Accuracy of B-natriuretic peptide for the diagnosis of decompensated heart failure in muscular dystrophies patients with chronic respiratory failure.

Heart failure and restrictive respiratory insufficiency are complications in muscular dystrophies. We aimed to assess the accuracy of the B-natriuretic peptide (BNP) for the diagnosis of decompensated heart failure in muscular dystrophy. We included patients with muscular dystrophy and chronic respiratory insufficiency admitted in the Intensive Care Unit of the Raymond Poincare hospital (Garches, France) for suspected decompensated heart failure. Thirtyseven patients were included, among them, 23 Duchenne muscular dystrophy (DMD) (62%), 10 myotonic dystrophy type 1(DM1) (27%). Median age was 35 years [27.5; 48.5]. 86.5% of patients were on home mechanical ventilation (HMV). Median left ventricular ejection fraction (LVEF) was 47% [35.0; 59.5]. Median BNP blood level was 104 pg/mL [50; 399]. The BNP level was significantly inversely associated with LVEF (r= -0.37, p 0.03) and positively associated with the LVEDD (left ventricular end diastolic diameter) (r=0.59, P<0.001). The discriminative value of the BNP level for the diagnosis of decompensated heart failure was high with an AUROC=0.94 (P<0.001). The best discriminating BNP threshold was 307 pg/mL (Youden index 0.85). The BNP level measurement may add a supplemental key for the final diagnosis of decompensated heart failure.