High vs Low PEEP in Patients With ARDS Exhibiting Intense Inspiratory Effort During Assisted Ventilation: A Randomized Crossover Trial.

BACKGROUND: Positive end-expiratory pressure (PEEP) can potentially modulate inspiratory effort (ΔPes), which is the major determinant of self-inflicted lung injury. RESEARCH QUESTION: Does high PEEP reduce ΔPes in patients with moderate-to-severe ARDS on assisted ventilation? STUDY DESIGN AND METHODS: Sixteen patients with Pao2/Fio2 ≤ 200 mm Hg and ΔPes ≥ 10 cm H2O underwent a randomized sequence of four ventilator settings: PEEP = 5 cm H2O or PEEP = 15 cm H2O + synchronous (pressure support ventilation [PSV]) or asynchronous (pressure-controlled intermittent mandatory ventilation [PC-IMV]) inspiratory assistance. ΔPes and respiratory system, lung, and chest wall mechanics were assessed with esophageal manometry and occlusions. PEEP-induced alveolar recruitment and overinflation, lung dynamic strain, and tidal volume distribution were assessed with electrical impedance tomography. RESULTS: ΔPes was not systematically different at high vs low PEEP (pressure support ventilation: median, 20 cm H2O; interquartile range (IQR), 15-24 cm H2O vs median, 15 cm H2O; IQR, 13-23 cm H2O; P = .24; pressure-controlled intermittent mandatory ventilation: median, 20; IQR, 18-23 vs median, 19; IQR, 17-25; P = .67, respectively). Similarly, respiratory system and transpulmonary driving pressures, tidal volume, lung/chest wall mechanics, and pendelluft extent were not different between study phases. High PEEP resulted in lower or higher ΔPes, respiratory system driving pressure, and transpulmonary driving pressure according to whether this increased or decreased respiratory system compliance (r = -0.85, P < .001; r = -0.75, P < .001; r = -0.80, P < .001, respectively). PEEP-induced changes in respiratory system compliance were driven by its lung component and were dependent on the extent of PEEP-induced alveolar overinflation (r = -0.66, P = .006). High PEEP caused variable recruitment and systematic redistribution of tidal volume toward dorsal lung regions, thereby reducing dynamic strain in ventral areas (pressure support ventilation: median, 0.49; IQR, 0.37-0.83 vs median, 0.96; IQR, 0.62-1.56; P = .003; pressure-controlled intermittent mandatory ventilation: median, 0.65; IQR, 0.42-1.31 vs median, 1.14; IQR, 0.79-1.52; P = .002). All results were consistent during synchronous and asynchronous inspiratory assistance. INTERPRETATION: The impact of high PEEP on ΔPes and lung stress is interindividually variable according to different effects on the respiratory system and lung compliance resulting from alveolar overinflation. High PEEP may help mitigate the risk of self-inflicted lung injury solely if it increases lung/respiratory system compliance. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04241874; URL: www. CLINICALTRIALS: gov.

Thirty-Day Complications, Unplanned Hospital Encounters, and Mortality after Endosonography and/or Guided Bronchoscopy: A Prospective Study.

BACKGROUND AND OBJECTIVE: Limited data exist regarding the adverse events of advanced diagnostic bronchoscopy, with most of the available information derived from retrospective datasets that primarily focus on early complications. METHODS: We conducted a 15-month prospective cohort study among consecutive patients undergoing endosonography and/or guided bronchoscopy under general anesthesia. We evaluated the 30-day incidence of severe complications, any complication, unplanned hospital encounters, and deaths. Additionally, we analyzed the time of onset (immediate, within 1 h of the procedure; early, 1 h-24 h; late, 24 h-30 days) and identified risk factors associated with these events. RESULTS: Thirty-day data were available for 697 out of 701 (99.4%) enrolled patients, with 85.6% having suspected malignancy and multiple comorbidities (median Charlson Comorbidity Index (IQR): 4 (2-5)). Severe complications occurred in only 17 (2.4%) patients, but among them, 10 (58.8%) had unplanned hospital encounters and 2 (11.7%) died within 30 days. A significant proportion of procedure-related severe complications (8/17, 47.1%); unplanned hospital encounters (8/11, 72.7%); and the two deaths occurred days or weeks after the procedure. Low-dose attenuation in the biopsy site on computed tomography was independently associated with any complication (OR: 1.87; 95% CI 1.13-3.09); unplanned hospital encounters (OR: 2.17; 95% CI 1.10-4.30); and mortality (OR: 4.19; 95% CI 1.74-10.11). CONCLUSIONS: Severe complications arising from endosonography and guided bronchoscopy, although uncommon, have significant clinical consequences. A substantial proportion of adverse events occur days after the procedure, potentially going unnoticed and exerting a negative clinical impact if a proactive surveillance program is not implemented.

Bloodstream infections in COVID-19 patients undergoing extracorporeal membrane oxygenation in ICU: An observational cohort study.

BACKGROUND: COVID-19 patients undergoing ECMO are at highly increased risk of nosocomial infections. OBJECTIVES: To study incidence, clinical outcomes and microbiological features of bloodstream infections (BSI) occurring during ECMO in COVID-19 patients. METHODS: Observational prospective cohort study enrolling consecutive COVID-19 patients undergoing veno-venous-ECMO in an Italian ICU from March 2020 to March 2022. RESULTS: In the study population of 68 patients (age 53 [49-60] years, 82% males), 30 (44%) developed bloodstream infections (BSI group) while 38 did not (N-BSI group) with an incidence of 32 events/1000 days of ECMO. In BSI group pre-ECMO respiratory support was shorter (6 [4-9] vs 9 [5-12] days, p = 0.02) and ECMO treatment was longer (18 [10-29] vs 11 [7-18] days, p = 0.03) than in N-BSI group. The overall ECMO and ICU mortality were 50% and 59%, respectively, without any inter-group difference (p = 1.00). A longer ECMO treatment was independently correlated with higher rate of BSI (p = 0.04, OR [95% CI] 1.06 [1.02-1.11]). Sixteen primary and 14 secondary infectious events were documented. Gram-positive pathogens were more common in primary than secondary BSI (88% vs 43%, p = 0.02) and Enterococcus faecalis (56%) was the most frequent one. Conversely, Gram-negative microorganisms were more often isolated in secondary rather than primary BSI (57% vs 13%, p = 0.02), with Acinetobacter baumannii (21%) and Pseudomonas aeruginosa (21%) as most represented species. The administration of Sars-CoV-2 antiviral drug showed independent correlation with a reduced rate of ICU mortality (p = 0.01, OR [95% CI] 0.22 [0.07-0.73]). CONCLUSIONS: Bloodstream infections represented a frequent complication without worsening clinical outcomes in our COVID-19 patients undergoing ECMO. Primary and secondary BSI events showed peculiar microbiological profiles.

An Observational Study to Develop a Predictive Model for Bacterial Pneumonia Diagnosis in Severe COVID-19 Patients-C19-PNEUMOSCORE.

In COVID-19 patients, antibiotics overuse is still an issue. A predictive scoring model for the diagnosis of bacterial pneumonia at intensive care unit (ICU) admission would be a useful stewardship tool. We performed a multicenter observational study including 331 COVID-19 patients requiring invasive mechanical ventilation at ICU admission; 179 patients with bacterial pneumonia; and 152 displaying negative lower-respiratory samplings. A multivariable logistic regression model was built to identify predictors of pulmonary co-infections, and a composite risk score was developed using ß-coefficients. We identified seven variables as predictors of bacterial pneumonia: vaccination status (OR 7.01; 95% CI, 1.73-28.39); chronic kidney disease (OR 3.16; 95% CI, 1.15-8.71); pre-ICU hospital length of stay ≥ 5 days (OR 1.94; 95% CI, 1.11-3.4); neutrophils ≥ 9.41 × 109/L (OR 1.96; 95% CI, 1.16-3.30); procalcitonin ≥ 0.2 ng/mL (OR 5.09; 95% CI, 2.93-8.84); C-reactive protein ≥ 107.6 mg/L (OR 1.99; 95% CI, 1.15-3.46); and Brixia chest X-ray score ≥ 9 (OR 2.03; 95% CI, 1.19-3.45). A predictive score (C19-PNEUMOSCORE), ranging from 0 to 9, was obtained by assigning one point to each variable, except from procalcitonin and vaccine status, which gained two points each. At a cut-off of ≥3, the model exhibited a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 84.9%, 55.9%, 69.4%, 75.9%, and 71.6%, respectively. C19-PNEUMOSCORE may be an easy-to-use bedside composite tool for the early identification of severe COVID-19 patients with pulmonary bacterial co-infection at ICU admission. Its implementation may help clinicians to optimize antibiotics administration in this setting.

Usefulness of differential time to positivity between catheter and peripheral blood cultures for diagnosing catheter-related bloodstream infection: Data analysis from routine clinical practice in the intensive care unit.

PURPOSE: To assess the accuracy of differential time to positivity (DTP) method for the diagnosis of catheter-related bloodstream infections (CRBSI) in the routine practice of our intensive care unit (ICU). MATERIALS AND METHODS: Over a five-year study period, ICU patients with a central venous catheter in place for ≥48 h and undergoing DTP test with catheter tip culture were analyzed. We investigated: the accuracy of DTP test with the usual threshold of 120 min in confirming the clinical suspicion of CRBSI; the most accurate threshold value of DTP to detect CRBSI; the diagnostic accuracy of the ratio (rather than the difference) between times to positivity. RESULTS: Among 278 episodes of paired blood cultures, 13% were CRBSIs. DTP value ≥120 min used for the diagnosis of CRBSI yielded 41% sensitivity and 74% specificity. Performance of DTP values in predicting CRBSI was low (AUC = 0.60 [95%CI: 0.48-0.72]). Cutoff value of the ratio between times to positivity was 0.80, with 46% sensitivity and 79% specificity. CONCLUSIONS: The routine use of the DTP method at any cutoff point has inadequate accuracy in detecting CRBSI in the real every day clinical practice. Not even the ratio between times to positivity seems to be clinically useful.

Ceftolozane and tazobactam for the treatment of hospital acquired pneumonia.

INTRODUCTION: Patients admitted to hospitals are at risk of developing nosocomial infections. These types of infections typically occur in immune-compromised patients. Furthermore, nosocomial infections are frequently caused by resistant organisms, including nonfermenting gram-negative bacilli such as Pseudomonas aeruginosa. AREAS COVERED: P. aeruginosa is a hazardous pathogen. It can resist numerous antibiotics, due to several resistance mechanisms. It is associated with serious illnesses, particularly hospital-acquired infections including ventilator-associated pneumonia. In the past, only a limited number of anti-pseudomonal drugs were available. However, several therapeutic advancements have been made, in recent years, to target P. aeruginosa, including the development of the new cephalosporin: ceftolozane-tazobactam. EXPERT OPINION: Ceftolozane-tazobactam is a combination of a novel semi-synthetic fifth-generation cephalosporin with a well-established beta-lactamase inhibitor. From a structural perspective, ceftolozane-tazobactam has attested increased stability to AmpC ß-lactamases. Additionally, ceftolozane-tazobactam is less affected by changes in efflux pumps and porin permeability due to an enhanced affinity to certain penicillin-binding proteins (PBPs). This enables the molecule to overcome the most common anti-drug resistant mechanisms of bacteria. According to previous clinical trials conducted, ceftolozane-tazobactam must be considered when treating patients with confirmed or suspected P. aeruginosa respiratory tract infections, either nosocomial pneumonia or ventilator-associated pneumonia.

Microbiologic surveillance through subglottic secretion cultures during invasive mechanical ventilation: a prospective observational study.

PURPOSE: Whether subglottic secretions (SS) culture during invasive mechanical ventilation may aid microbiological surveillance is unknown. We conducted a prospective study to assess SS cultures predictivity of endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) isolates. MATERIALS AND METHODS: 109 patients receiving mechanical ventilation for ≥48 hours underwent SS and ETA surveillance cultures twice weekly; blind BAL was performed in case of clinically suspected pneumonia. RESULTS: SS and ETA cultures were fully concordant in 170 (81%-overall accuracy) of 211 sample pairs. As compared to ETA, SS culture global sensitivity and specificity were 84% [95%CI: 77 to 91] and 74% [95%CI: 66 to 82]; negative and positive predictive values were 82% and 77%. Forty-four episodes of clinically suspected pneumonia were observed. Compared to BAL, SS culture global sensitivity and specificity were 68% [95%CI: 45 to 81] and 63% [95%CI: 44 to 82]; negative and positive predictive values were both 65%. SS sensitivity, specificity, positive and negative predictive values in anticipating BAL isolates were comparable to ETA (all p > 0.20). CONCLUSIONS: SS cultures show worthy accuracy in identifying ETA isolates, with excellent sensitivity and good negative predictivity. SS cultures may be not inferior to ETA in predicting BAL results in case of ventilator-associated pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03153241. Registered on 15 May 2017, https://clinicaltrials.gov/ct2/show/NCT03153241.

Effects of Thyroid Hormone Treatment on Diaphragmatic Efficiency in Mechanically Ventilated Subjects With Nonthyroidal Illness Syndrome.

BACKGROUND: Several respiratory abnormalities can be present in primary hypothyroidism and can be reversed with adequate hormone treatment. However, the role of thyroid hormone replacement therapy on the respiratory system in patients with nonthyroidal illness syndrome is still unclear. This physiologic study evaluated the effect of thyroid hormone treatment on respiratory muscle function in subjects with nonthyroidal illness syndrome and while on mechanical ventilation. The primary end point was neuromechanical efficiency, which provides an estimate of the efficiency of diaphragmatic contraction. Secondary end points were the transdiaphragmatic pressure-time product and the swing of the electrical activity of the diaphragm, which reflect the work of breathing and inspiratory effort, respectively. METHODS: Fifteen subjects on mechanical ventilation for ≥48 h and with a diagnosis of nonthyroidal illness syndrome who had a failed spontaneous breathing trial, received intravenous triiodothyronine. The hormone was administered as an intravenous bolus of 0.4 µg/kg triiodothyronine, followed by continuous perfusion at 0.6 µg/kg for 24 h. Neuromechanical efficiency was calculated as the ratio between the drop in airway pressure during an expiratory occlusion and the corresponding electrical activity of the diaphragm peak. Recordings were taken at baseline and after 3, 6, and 24 h. RESULTS: After study completion, free triiodothyronine serum concentrations increased in all the subjects (mean ± SD increase, 0.84 ± 0.34 pg/mL). Neuromechanical efficiency showed no significant changes throughout the study (mean ± SD baseline, 1.40 ± 0.87 cm H2O/µV; 3 h, 1.28 ± 0.64 cm H2O/µV; 6 h, 1.33 ± 0.87 cm H2O/µV; 24 h, 1.41 ± 0.96 cm H2O/µV). Similarly, no variations in transdiaphragmatic pressure-time product per min (mean ± SD baseline, 238.1 ± 124 cm H2O × s/min; 3 h, 242.5 ± 140.3 cm H2O × s /min; 6 h, 247.5 ± 161.7 cm H2O × s/min; 24 h, 281.2 ± 201.2 cm H2O × s/min) or swing of electrical activity of the diaphragm (mean ± baseline, 20.9 ± 13.1 µV; 3 h, 17.2 ± 8.3 µV; 6 h, 17.4 ± 11.3 µV; 24 h, 20.3 ± 13.7 µV) were observed during hormone administration. CONCLUSIONS: In the subjects on mechanical ventilation who were admitted to the ICU with nonthyroidal illness syndrome, thyroid hormone replacement treatment did not yield any benefit on respiratory muscle function when assessed by neuromechanical efficiency, which indicated that, in these subjects restoring normal levels of serum thyroid hormones is debatable. (ClinicalTrials.gov registration NCT03157466.).

Regional distribution of ventilation in patients with obstructive sleep apnea: the role of thoracic electrical impedance tomography (EIT) monitoring.

PURPOSE: The aim of our study was to apply the electrical impedance tomography (EIT) technique to the study of ventilation during wake and NREM and REM sleep in patients with obstructive sleep apneas (OSA). METHODS: This is a prospective, observational, monocentric, pilot study in a neurology department with a sleep disorder center. Inclusion criteria were age ≥18 years, both gender, and diagnosis of OSA. Exclusion criteria were the contraindications to the thoracic EIT. All patients underwent laboratory-based polysomnography (PSG) alongside thoracic EIT. Primary endpoint was to compare the global impedance (GI) among the conditions: "Wake" vs "Sleep," "NREM" vs "REM," and "OSA" vs "Non-OSA." Secondary endpoint was to measure the regional distribution of impedance in the four regions of interest (ROIs), in each condition. RESULTS: Of the 17 consecutive patients enrolled, two were excluded because of poor-quality EIT tracings. Fifteen were analyzed, 10 men and 5 women, mean age 51.6 ± 14.4 years. GI was higher in Wake vs Sleep (Wake 13.24 ± 11.23; Sleep 12.56 ± 13.36; p < 0.01), in NREM vs REM (NREM 13.48 ± 13.43; REM 0.59 ± 0.01; p < 0.01), and in Non-OSA vs OSA (Non-OSA 10.50 ± 12.99; OSA 18.98 ± 10.06; p < 0.01). No significant differences were observed in the regional distribution of impedance between Wake and Sleep (χ 2 = 3.66; p = 0.299) and between Non-OSA and OSA (χ 2 = 1.00; p = 0.799); conversely, a significant difference was observed between NREM and REM sleep (χ 2 = 62.94; p < 0.001). CONCLUSIONS: To our knowledge, this is the first study that addresses the issue of regional ventilation in OSA patients during sleep. Thoracic electrical impedance changes through the sleep-wake cycle and during obstructive events. The application of thoracic EIT can prove a valuable additional strategy for the evaluation of OSA patients.