Enteral nutrition management in critically ill adult patients and its relationship with intensive care unit-acquired muscle weakness: A national cohort study.

OBJECTIVE: To assess the incidence and determinants of ICU-acquired muscle weakness (ICUAW) in adult patients with enteral nutrition (EN) during the first 7 days in the ICU and mechanical ventilation for at least 48 hours. METHODS: A prospective, nationwide, multicentre cohort study in a national ICU network of 80 ICUs. ICU patients receiving invasive mechanical ventilation for at least 48 hours and EN the first 7 days of their ICU stay were included. The primary outcome was incidence of ICUAW. The secondary outcome was analysed, during days 3-7 of ICU stay, the relationship between demographic and clinical data to contribute to the onset of ICUAW, identify whether energy and protein intake can contribute independently to the onset of ICUAW and degree of compliance guidelines for EN. RESULTS: 319 patients were studied from 69 ICUs in our country. The incidence of ICUAW was 153/222 (68.9%; 95% CI [62.5%-74.7%]). Patients without ICUAW showed higher levels of active mobility (p = 0.018). The logistic regression analysis showed no effect on energy or protein intake on the onset of ICUAW. Overfeeding was observed on a significant proportion of patient-days, while more overfeeding (as per US guidelines) was found among patients with obesity than those without (42.9% vs 12.5%; p<0.001). Protein intake was deficient (as per US/European guidelines) during ICU days 3-7. CONCLUSIONS: The incidence of ICUAW was high in this patient cohort. Early mobility was associated with a lower incidence of ICUAW. Significant overfeeding and deficient protein intake were observed. However, energy and protein intake alone were insufficient to explain ICUAW onset. RELEVANCE TO CLINICAL PRACTICE: Low mobility, high incidence of ICUAW and low protein intake suggest the need to train, update and involve ICU professionals in nutritional care and the need for early mobilization of ICU patients.

Early mobilization in intensive care unit in Latin America: A survey based on clinical practice.

Background: The application of early mobilization (EM) in intensive care units (ICUs) has shown to improve the physical and ventilatory status of critically ill patients, even after ICU stay. This study aimed to describe the practices regarding EM in ICUs in Latin America. Methods: We conducted an observational, cross-sectional study of professionals from all countries in Latin America. Over 3 months, professionals working in ICU units in Latin America were invited to answer the survey, which was designed by an expert committee and incorporated preliminary questions based on studies about EM recommendations. Results: As many as 174 health professionals from 17 countries completed the survey. The interventions carried out within each ICU were active mobilization (90.5%), passive mobilization (85.0%), manual and instrumental techniques for drainage of mucus secretion (81.8%), and positioning techniques (81%). The professionals who most participated in the rehabilitation process in ICUs were physiotherapists (98.7%), intensive care physicians (61.6%), nurses (56.1%), and respiratory therapists (43.8%). In only 36.1% of the ICUs, protocols were established to determine when a patient should begin EM. In 38.1% of the cases, the onset of EM was established by individual evaluation, and in 25.0% of the cases, it was the medical indication to start rehabilitation and EM. Conclusion: This report shows us that EM of critically ill patients is an established practice in our ICUs like in other developed countries.

Effects of Mechanical Insufflation-Exsufflation With Different Pressure Settings on Respiratory Mucus Displacement During Invasive Ventilation.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) has been proposed as a potential strategy to generate high expiratory flows and simulate cough in the critically ill. However, efficacy and safety of MI-E during invasive mechanical ventilation are still to be fully elucidated. This study in intubated and mechanically ventilated pigs aimed to evaluate the effects of 8 combinations of insufflation-exsufflation pressures during MI-E on mucus displacement, respiratory flows, as well as respiratory mechanics and hemodynamics. METHODS: Six healthy Landrace-Large White female pigs were orotracheally intubated, anesthetized, and invasively ventilated for up to 72 h. Eight combinations of insufflation-exsufflation pressures (+40/-40, +40/-50, +40/-60, +40/-70, +50/-40, +50/-50, +50/-60, +50/-70 cm H2O) were applied in a randomized order. The MI-E device was set to automatic mode, medium inspiratory flow, and an inspiratory-expiratory time 3 and 2 s, respectively, with a 1-s pause between cycles. We performed 4 series of 5 insufflation-exsufflation cycles for each combination of pressures. Velocity and direction of movement of a mucus simulant containing radio-opaque markers were assessed through sequential lateral fluoroscopic images of the trachea. We also evaluated respiratory flows, respiratory mechanics, and hemodynamics before, during, and after each combination of pressures. RESULTS: In 3 of the animals, experiments were conducted twice; and for the remaining 3, they were conducted once. In comparison to baseline mucus movement (2.85 ± 2.06 mm/min), all insufflation-exsufflation pressure combinations significantly increased mucus velocity (P = .01). Particularly, +40/-70 cm H2O was the most effective combination, increasing mucus movement velocity by up to 4.8-fold (P < .001). Insufflation pressure of +50 cm H2O resulted in higher peak inspiratory flows (P = .004) and inspiratory transpulmonary pressure (P < .001) than +40 cm H2O. CONCLUSIONS: MI-E appeared to be an efficient strategy to improve mucus displacement during invasive ventilation, particularly when set at +40/-70 cm H2O. No safety concerns were identified although a transient significant increase of transpulmonary pressure was observed.

An Update on Cardiorespiratory Physiotherapy during Mechanical Ventilation.

Physiotherapists are integral members of the multidisciplinary team managing critically ill adult patients. However, the scope and role of physiotherapists vary widely internationally, with physiotherapists in some countries moving away from providing early and proactive respiratory care in the intensive care unit (ICU) and focusing more on early mobilization and rehabilitation. This article provides an update of cardiorespiratory physiotherapy for patients receiving mechanical ventilation in ICU. Common and some more novel assessment tools and treatment options are described, along with the mechanisms of action of the treatment options and the evidence and physiology underpinning them. The aim is not only to summarize the current state of cardiorespiratory physiotherapy but also to provide information that will also hopefully help support clinicians to deliver personalized and optimal patient care, based on the patient's unique needs and guided by accurate interpretation of assessment findings and the current evidence. Cardiorespiratory physiotherapy plays an essential role in optimizing secretion clearance, gas exchange, lung recruitment, and aiding with weaning from mechanical ventilation in ICU. The physiotherapists' skill set and scope is likely to be further optimized and utilized in the future as the evidence base continues to grow and they get more and more integrated into the ICU multidisciplinary team, leading to improved short- and long-term patient outcomes.

Rapid chest compression effects on intracranial pressure in patients with acute cerebral injury.

BACKGROUND: Patients with acute brain injury often require invasive mechanical ventilation, increasing the risk of developing complications such as respiratory secretions retention. Rapid chest compression is a manual chest physiotherapy technique that aims to improve clearance of secretions in these patients. However, the rapid chest compression technique has been suggested to be associated with increased intracranial pressure in patients with acute brain injury. The aim of this work is to elucidate the effects of the technique on intracranial pressure in mechanically ventilated patients with acute brain injury. Furthermore, the effects of the technique in different volumes and flows recorded by the ventilator and the relationship between the pressure applied in the intervention group and the different variables will also be studied. METHODS: Randomized clinical trial, double-blinded. Patients with acute brain injury on invasive mechanical ventilation > 48 h will be included and randomized in two groups. In the control group, a technique of passive hallux mobilization will be applied, and in the intervention group, it will be performed using the rapid chest compression technique. Intracranial pressure (main variable) will be collected with an intracranial pressure monitoring system placed at the lateral ventricles (Integra Camino). DISCUSSION: The safety of chest physiotherapy techniques in patients at risk of intracranial hyperpressure is still uncertain. The aim of this study is to identify if the rapid manual chest compression technique is safe in ventilated patients with acute brain injury. TRIAL REGISTRATION: NCT03609866 . Registered on 08/01/2018.

The impact of ABCDE bundle implementation on patient outcomes: A nationwide cohort study.

BACKGROUND: The ABCDE bundle is a set of evidence-based practices to systematically reduce the risks of sedation, delirium, and immobility in intensive care patients. Implementing the bundle improves clinical outcome. AIMS AND OBJECTIVES: To investigate the association between patient outcomes and compliance with bundle components ABC (analgosedation algorithms), D (delirium protocol), and E (early mobilization protocol). DESIGN: A Spanish multicentre cohort study of adult patients receiving invasive mechanical ventilation (IMV) for ≥48 h until extubation. METHODS: The primary outcome was pain level, cooperation to permit Medical Research Council Scale administration, patient days of delirium, and mobility. The secondary outcome was cumulative drug dosing by IMV days. Tertiary outcomes (ICU days, IMV days, bed rest days, ICU mortality, ICUAW) and independent variables (analgosedation, delirium, early mobilization protocols) were also studied. RESULTS: Data were collected from 605 patients in 80 ICUs and 5214 patient days with IMV. Two-thirds of the ICUs studied applied no protocols. Pain was not assessed on 83.6% of patient days. Patient cooperation made scale administration feasible on 20.7% of days. Delirium and immobility were found on 4.2% and 69.9% of days, respectively. Patients had shorter stays in ICUs with bundle protocols and fewer days of IMV in ICUs with delirium and mobilization bundle components (P = 0.006 and P = 0.03, respectively). Analgosedation protocols were associated with more opioid dosing (P = 0.02), and delirium and early mobilization protocols with more propofol (P = 0.001), dexmedetomidine (P = 0.001), and lower benzodiazepine dosing (P = 0.008). CONCLUSIONS: The implementation rate of ABCDE bundle components was very low in our Spanish setting, but when implemented, patients had a shorter ICU stay, more analgesia dosing, and lighter sedation. RELEVANCE TO CLINICAL PRACTICE: Applying some but not all the bundle components, there is increased analgesia and light sedation drug use, decreased benzodiazepines, and increased patient cooperation and mobility, resulting in a shorter ICU stay and fewer days of IMV.

Variables associated with mobility levels in critically ill patients: A cohort study.

BACKGROUND: Early mobilization in the intensive care unit (ICU) helps improve patients' functional status at discharge. However, many barriers hinder this practice. AIM AND OBJECTIVES: To identify mobility levels acquired by critically ill patients and their variables. DESIGN: A multi-centre cohort study was conducted in adult patients receiving invasive mechanical ventilation for at least 48 hours. METHODS: The primary outcome was level of mobility according to the ICU mobility scale. The secondary outcome was human resource availability and existence of ABCDEF bundle guidelines. A logistic regression was performed, based on days 3 to 5 of the ICU stay and significant association with active mobility. RESULTS: Six hundred and forty-two patients were included from 80 ICUs. Active moving in and out of bed was found on 9.9% of patient-days from day 8 of the ICU stay. Bed exercises, or passive transfers, and immobility were observed on 45.6% and 42.2% of patient-days, respectively. Patients achieving active mobility (189/642, 29.4%) were in ICUs with more physiotherapist hours. Active mobility was more likely with a 1:4 nurse-patient ratio (odds ratio [OR] 3.7 95% confidence interval [CI] [1.2-11.2]), high MRC sum-score (OR 1.05 95% CI [1.04-1.06]) and presence of delirium (OR 1.01 95% CI [1.00-1.02]). By contrast, active mobility was hindered by higher BMI (OR 0.92 95% CI [0.88-0.97]), a 1:3 nurse-patient ratio (OR 0.54 95% CI [0.32-0.93]), or a shift-dependent nurse-patient ratio (OR 0.27 95% CI [0.12-0.62]). CONCLUSIONS: Immobility and passive mobilization were prevalent. A high MRC sum-score and presence of delirium are protective factors of mobilization. A 1:4 nurse-patient ratio shows a stronger association with active mobility than a 1:3 ratio. RELEVANCE TO CLINICAL PRACTICE: Severity-criteria-based nurse-patient ratios hinder mobilization. Active mobilization may be enhanced by using nursing-intervention-based ratios, increasing physiotherapist hours, and achieving wider application of the ABCDEF bundle, resulting in more awake, cooperative patients.

Development and characterization of a new swine model of invasive pneumococcal pneumonia.

Streptococcus pneumoniae is the most common microbial cause of community-acquired pneumonia. Currently, there are no available models of severe pneumococcal pneumonia in mechanically ventilated animals to mimic clinical conditions of critically ill patients. We studied endogenous pulmonary flora in 4 healthy pigs and in an additional 10 pigs in which we intra-bronchially instilled S. pneumoniae serotype 19 A, characterized by its resistance to penicillin, macrolides and tetracyclines. The pigs underwent ventilation for 72 h. All pigs that were not challenged with S. pneumoniae completed the 72-h study, whereas 30% of infected pigs did not. At 24 h, we clinically confirmed pneumonia in the infected pigs; upon necropsy, we sampled lung tissue for microbiological/histological confirmation of pneumococcal pneumonia. In control pigs, Streptococcus suis and Staphylococcus aureus were the most commonly encountered pathogens, and their lung tissue mean ± s.e.m. concentration was 7.94 ± 20 c.f.u./g. In infected pigs, S. pneumoniae was found in the lungs of all pigs (mean ± s.e.m. pulmonary concentration of 1.26 × 105 ± 2 × 102 c.f.u./g). Bacteremia was found in 50% of infected pigs. Pneumococcal pneumonia was confirmed in all infected pigs at 24 h. Pneumonia was associated with thrombocytopenia, an increase in prothrombin time, cardiac output and vasopressor dependency index and a decrease in systemic vascular resistance. Upon necropsy, microbiological/histological pneumococcal pneumonia was confirmed in 8 of 10 pigs. We have therefore developed a novel model of penicillin- and macrolide-resistant pneumococcal pneumonia in mechanically ventilated pigs with bacteremia and severe hemodynamic compromise. The model could prove valuable for appraising the pathogenesis of pneumococcal pneumonia, the effects associated with macrolide resistance and the outcomes related to the use of new diagnostic strategies and antibiotic or complementary therapies.

Effects of Mechanical Insufflation-Exsufflation on Sputum Volume in Mechanically Ventilated Critically Ill Subjects.

BACKGROUND: Mechanical insufflation-exsufflation (MI-E) is a noninvasive technique performed to simulate cough and remove sputum from proximal airways. To date, the effects of MI-E on critically ill patients on invasive mechanical ventilation are not fully elucidated. In this randomized crossover trial, we evaluated the efficacy and safety of MI-E combined to expiratory rib cage compressions (ERCC). METHODS: Twenty-six consecutive subjects who were sedated, intubated, and on mechanical ventilation > 48 h were randomized to perform 2 sessions of ERCC with or without additional MI-E before tracheal suctioning in a 24-h period. The primary outcome was sputum volume following each procedure. Secondary end points included effects on respiratory mechanics, hemodynamics, and safety. RESULTS: In comparison to ERCC alone, median (interquartile range) sputum volume cleared was significantly higher during ERCC+MI-E (0.42 [0-1.39] mL vs 2.29 [1-4.67] mL, P < .001). The mean ± SD respiratory compliance improved in both groups immediately after the treatment, with the greater improvement in the ERCC+MI-E group (54.7 ± 24.1 mL/cm H2O vs 73.7 ± 35.8 mL/cm H2O, P < .001). Differences between the groups were not significant (P = .057). Heart rate increased significantly in both groups immediately after each intervention (P < .05). Additionally, a significant increase in oxygenation was observed from baseline to 1 h post-intervention in the ERCC+MI-E group (P < .05). Finally, several transitory hemodynamic variations occurred during both interventions, but these were nonsignificant and were considered clinically irrelevant. CONCLUSIONS: In mechanically ventilated subjects, MI-E combined with ERCC increased the sputum volume cleared without causing clinically important hemodynamic changes or adverse events. (ClinicalTrials.gov registration: NCT03316079.).

Physical Therapy and Rehabilitation in Chronic Obstructive Pulmonary Disease Patients Admitted to the Intensive Care Unit.

Chronic obstructive pulmonary disease (COPD) is a progressive lung condition that affects a person's ability to exercise and undertake normal physical function due to breathlessness, poor physical fitness, and muscle fatigue. Patients with COPD often experience exacerbations due to pulmonary infections, which result in worsening of their symptoms, more loss of function, and often require hospital treatment or in severe cases admission to intensive care units. Recovery from such exacerbations is often slow, and some patients never fully return to their previous level of activity. This can lead to permanent disability and premature death.Physical therapists play a key role in the respiratory management and rehabilitation of patients admitted to intensive care following acute exacerbation of COPD. This article discusses the key considerations for respiratory management of patients requiring invasive mechanical ventilation, providing an evidence-based summary of commonly used interventions. It will also explore the evidence to support the introduction of early and structured programs of rehabilitation to support recovery in both the short and the long term, as well as active mobilization, which includes strategies to minimize or prevent physical loss through early retraining of both peripheral and respiratory muscles.

Short-Term Appraisal of the Effects and Safety of Manual Versus Ventilator Hyperinflation in an Animal Model of Severe Pneumonia.

BACKGROUND: In patients on mechanical ventilation, lung hyperinflation is often performed to reverse atelectasis and clear retained mucus. We evaluated the effects of manual hyperinflation and ventilator hyperinflation on mucus clearance, gas exchange, pulmonary mechanics, and hemodynamics. METHODS: Six mechanically ventilated pigs with severe Pseudomonas aeruginosa pneumonia randomly received either 12 manual hyperinflation breaths over a period of 2 min (through a gradual manual compression of a resuscitation bag within 4 s to achieve 40 cm H2O of airway pressure), or 12 ventilator hyperinflation over 2 min to achieve the same ventilatory end points as in manual hyperinflation. Mucus clearance rate was measured through fluoroscopic tracking of tracheal markers. Prior to each maneuver and 15 min thereafter, we assessed arterial and mixed gas exchange, pulmonary mechanics, and hemodynamics. RESULTS: Both manual hyperinflation and ventilator hyperinflation significantly decreased inspiratory flow by approximately 16 L/min (P < .001) and increased peak expiratory flow by roughly 44 L/min (P < .001). The median (interquartile range) mucus clearance rate was 1.31 (0.84-2.30) prior to the interventions, and 0.70 (0.00-2.58) and 0.65 (0.45-1.47) during manual hyperinflation and ventilator hyperinflation, respectively (P = .09). Hyperinflations, whether delivered manually or through the ventilator, did not significantly modify pulmonary or hemodynamic parameters. CONCLUSIONS: In an animal model of severe P. aeruginosa pneumonia, neither manual hyperinflation nor ventilator hyperinflation improved mucus clearance. If confirmed in comprehensive clinical experimentations, these findings should promote reappraisal of indications for both manual hyperinflation and ventilator hyperinflation as a therapeutic technique for mucus clearance and atelectasis reversal.

Nebulized Amikacin and Fosfomycin for Severe Pseudomonas aeruginosa Pneumonia: An Experimental Study.

OBJECTIVES: Latest trials failed to confirm merits of nebulized amikacin for critically ill patients with nosocomial pneumonia. We studied various nebulized and IV antibiotic regimens in a porcine model of severe Pseudomonas aeruginosa pneumonia, resistant to amikacin, fosfomycin, and susceptible to meropenem. DESIGN: Prospective randomized animal study. SETTING: Animal Research, University of Barcelona, Spain. SUBJECTS: Thirty female pigs. INTERVENTIONS: The animals were randomized to receive nebulized saline solution (CONTROL); nebulized amikacin every 6 hours; nebulized fosfomycin every 6 hours; IV meropenem alone every 8 hours; nebulized amikacin and fosfomycin every 6 hours; amikacin and fosfomycin every 6 hours, with IV meropenem every 8 hours. Nebulization was performed through a vibrating mesh nebulizer. The primary outcome was lung tissue bacterial concentration. Secondary outcomes were tracheal secretions P. aeruginosa concentration, clinical variables, lung histology, and development of meropenem resistance. MEASUREMENTS AND MAIN RESULTS: We included five animals into each group. Lung P. aeruginosa burden varied among groups (p < 0.001). In particular, IV meropenem and amikacin and fosfomycin + IV meropenem groups presented lower P. aeruginosa concentrations versus amikacin and fosfomycin, amikacin, CONTROL, and fosfomycin groups (p < 0.05), without significant difference between these two groups undergoing IV meropenem treatment. The sole use of nebulized antibiotics resulted in dense P. aeruginosa accumulation at the edges of the interlobular septa. Amikacin, amikacin and fosfomycin, and amikacin and fosfomycin + IV meropenem effectively reduced P. aeruginosa in tracheal secretions (p < 0.001). Pathognomonic clinical variables of respiratory infection did not differ among groups. Resistance to meropenem increased in IV meropenem group versus amikacin and fosfomycin + meropenem (p = 0.004). CONCLUSIONS: Our findings corroborate that amikacin and fosfomycin alone efficiently reduced P. aeruginosa in tracheal secretions, with negligible effects in pulmonary tissue. Combination of amikacin and fosfomycin with IV meropenem does not increase antipseudomonal pulmonary tissue activity, but it does reduce development of meropenem-resistant P. aeruginosa, in comparison with the sole use of IV meropenem. Our findings imply potential merits for preemptive use of nebulized antibiotics in order to reduce resistance to IV meropenem.

Effects of a Combined Community Exercise Program in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial.

Physical activity is associated with a decreased prevalence of obstructive sleep apnea and improved sleep efficiency. Studies on the effects of a comprehensive exercise program in a community setting remain limited. Our objective was to investigate the effects of a combined physical and oropharyngeal exercise program on the apnea-hypopnea index in patients with moderate to severe obstructive sleep apnea. This was a randomized clinical trial where the intervention group followed an eight-week urban-walking program, oropharyngeal exercises, and diet and sleep recommendations. The control group followed diet and sleep recommendations. A total of 33 patients were enrolled and randomized and, finally, 27 patients were included in the study (IG, 14; CG, 13) Obstructive sleep apnea patients were analyzed with a median age of 67 (52⁻74) and median apnea-hypopnea index of 32 events/h (25⁻41). The apnea-hypopnea index did not differ between groups pre- and post-intervention. However, in intervention patients younger than 60 (n = 6) a reduction of the apnea-hypopnea index from 29.5 (21.8⁻48.3) to 15.5 (11⁻34) events/h (p = 0.028) was observed. While a comprehensive multimodal program does not modify the apnea-hypopnea index, it could reduce body weight and increase the walking distance of patients with moderate to severe obstructive sleep apnea. Patients younger than 60 may also present a decreased apnea-hypopnea index after intervention.

Hippocampal Damage During Mechanical Ventilation in Trendelenburg Position: A Secondary Analysis of an Experimental Study on the Prevention of Ventilator-Associated Pneumonia.

We previously corroborated benefits of the Trendelenburg position in the prevention of ventilator-associated pneumonia (VAP). We now investigate its potential effects on the brain versus the semirecumbent position. We studied 17 anesthetized pigs and randomized to be ventilated and positioned as follows: duty cycle (TI/TTOT) of 0.33, without positive end-expiratory pressure (PEEP), placed with the bed oriented 30° in anti-Trendelenburg (control group); positioned as in the control group, with TI/TTOT adjusted to achieve an expiratory flow bias, PEEP of 5 cm H2O (IRV-PEEP); positioned in 5° TP and ventilated as in the control group (TP). Animals were challenged into the oropharynx with Pseudomonas aeruginosa. We assessed hemodynamic parameters and systemic inflammation throughout the study. After 72 h, we evaluated incidence of microbiological/histological VAP and brain injury. Petechial hemorrhages score was greater in the TP group (P = 0.013). Analysis of the dentate gyrus showed higher cell apoptosis and deteriorating neurons in TP animals (P < 0.05 vs. the other groups). No differences in systemic inflammation were found among groups. Cerebral perfusion pressure was higher in TP animals (P < 0.001), mainly driven by higher mean arterial pressure. Microbiological/histological VAP developed in 0%, 67%, and 86% of the animals in the TP, control, and IRV-PEEP groups, respectively (P = 0.003). In conclusion, the TP prevents VAP; yet, we found deleterious neural effects in the dentate gyrus, likely associated with cerebrovascular modification in such position. Further laboratory and clinical studies are mandatory to appraise potential neurological risks associated with long-term TP.

Appraisal of systemic inflammation and diagnostic markers in a porcine model of VAP: secondary analysis from a study on novel preventive strategies.

BACKGROUND: We previously evaluated the efficacy of a ventilatory strategy to achieve expiratory flow bias and positive end-expiratory pressure (EFB + PEEP) or the Trendelenburg position (TP) for the prevention of ventilator-associated pneumonia (VAP). These preventive measures were aimed at improving mucus clearance and reducing pulmonary aspiration of bacteria-laden oropharyngeal secretions. This secondary analysis is aimed at evaluating the effects of aforementioned interventions on systemic inflammation and to substantiate the value of clinical parameters and cytokines in the diagnosis of VAP. METHODS: Twenty female pigs were randomized to be positioned in the semirecumbent/prone position, and ventilated with duty cycle 0.33 and without PEEP (control); positioned as in the control group, PEEP 5 cmH2O, and duty cycle to achieve expiratory flow bias (EFB+PEEP); ventilated as in the control group, but in the Trendelenburg position (Trendelenburg). Following randomization, P. aeruginosa was instilled into the oropharynx. Systemic cytokines and tracheal secretions P. aeruginosa concentration were quantified every 24h. Lung biopsies were collected for microbiological confirmation of VAP. RESULTS: In the control, EFB + PEEP, and Trendelenburg groups, lung tissue Pseudomonas aeruginosa concentration was 2.4 ± 1.5, 1.9 ± 2.1, and 0.3 ± 0.6 log cfu/mL, respectively (p = 0.020). Whereas, it was 2.4 ± 1.9 and 0.6 ± 0.9 log cfu/mL in animals with or without VAP (p < 0.001). Lower levels of interleukin (IL)-1ß (p = 0.021), IL-1RA (p < 0.001), IL-4 (p = 0.005), IL-8 (p = 0.008), and IL-18 (p = 0.050) were found in Trendelenburg animals. VAP increased IL-10 (p = 0.035), tumor necrosis factor-α (p = 0.041), and endotracheal aspirate (ETA) P. aeruginosa concentration (p = 0.024). A model comprising ETA bacterial burden, IL-10, and TNF-α yielded moderate discrimination for the diagnosis of VAP (area of the receiver operating curve 0.82, 95% CI 0.61-1.00). CONCLUSIONS: Our findings demonstrate anti-inflammatory effects associated with the Trendelenburg position. In this reliable model of VAP, ETA culture showed good diagnostic accuracy, whereas systemic IL-10 and TNF-α marginally improved accuracy. Further clinical studies will be necessary to confirm clinical value of the Trendelenburg position as a measure to hinder inflammation during mechanical ventilation and significance of systemic IL-10 and TNF-α in the diagnosis of VAP.

Randomized, multicenter trial of lateral Trendelenburg versus semirecumbent body position for the prevention of ventilator-associated pneumonia.

PURPOSE: The lateral Trendelenburg position (LTP) may hinder the primary pathophysiologic mechanism of ventilator-associated pneumonia (VAP). We investigated whether placing patients in the LTP would reduce the incidence of VAP in comparison with the semirecumbent position (SRP). METHODS: This was a randomized, multicenter, controlled study in invasively ventilated critically ill patients. Two preplanned interim analyses were performed. Patients were randomized to be placed in the LTP or the SRP. The primary outcome, assessed by intention-to-treat analysis, was incidence of microbiologically confirmed VAP. Major secondary outcomes included mortality, duration of mechanical ventilation, and intensive care unit length of stay. RESULTS: At the second interim analysis, the trial was stopped because of low incidence of VAP, lack of benefit in secondary outcomes, and occurrence of adverse events. A total of 194 patients in the LTP group and 201 in the SRP group were included in the final intention-to-treat analysis. The incidence of microbiologically confirmed VAP was 0.5% (1/194) and 4.0% (8/201) in LTP and SRP patients, respectively (relative risk 0.13, 95% CI 0.02-1.03, p = 0.04). The 28-day mortality was 30.9% (60/194) and 26.4% (53/201) in LTP and SRP patients, respectively (relative risk 1.17, 95% CI 0.86-1.60, p = 0.32). Likewise, no differences were found in other secondary outcomes. Six serious adverse events were described in LTP patients (p = 0.01 vs. SRP). CONCLUSIONS: The LTP slightly decreased the incidence of microbiologically confirmed VAP. Nevertheless, given the early termination of the trial, the low incidence of VAP, and the adverse events associated with the LTP, the study failed to prove any significant benefit. Further clinical investigation is strongly warranted; however, at this time, the LTP cannot be recommended as a VAP preventive measure. CLINICALTRIALS. GOV IDENTIFIER: NCT01138540.

The effects of direct hemoperfusion using a polymyxin B-immobilized column in a pig model of severe Pseudomonas aeruginosa pneumonia.

BACKGROUND: Hemoperfusion through a column containing polymyxin B-immobilized fiber (PMX-HP) is beneficial in abdominal sepsis. We assessed the effects of PMX-HP in a model of severe Pseudomonas aeruginosa pneumonia. METHODS: Eighteen pigs with severe P. aeruginosa pneumonia were mechanically ventilated for 76 h. Pigs were randomized to receive standard treatment with fluids and vasoactive drugs, or standard treatment with two 3-h PMX-HP sessions. Antibiotics against P. aeruginosa were never administered. We assessed endotoxemia through the endotoxin activity assay (EA). We measured the static lung elastance, ratio of arterial partial pressure per inspiratory fraction of oxygen (PaO2/FIO2), mean arterial pressure, cardiac output, systemic vascular resistance and inotropic score. Finally, every 24 h, we assessed complete blood count. RESULTS: In comparison with the control group, PMX-HP decreased percentage of circulating neutrophils from 47.4 ± 13.8 to 40.8 ± 11.5 % (p = 0.009). In a subgroup of animals with the worst hemodynamic impairment, EA in the control and PMX-HP groups was 0.50 ± 0.29 and 0.29 ± 0.14, respectively (p = 0.018). Additionally, in the control and PMX-HP groups, static lung elastance was 26.9 ± 8.7 and 25.3 ± 7.5 cm H2O/L (p = 0.558), PaO2/FIO2 was 347.3 ± 61.9 and 356.4 ± 84.0 mmHg (p = 0.118), mean arterial pressure was 81.2 ± 10.3 and 81.6 ± 13.1 mmHg (p = 0.960), cardiac output was 3.30 ± 1.11 and 3.28 ± 1.19 L/min (p = 0.535), systemic vascular resistance was 1982.6 ± 608.4 and 2011.8 ± 750.0 dyne/s/cm(-5) (p = 0.939), and inotropic score was 0.25 ± 0.10 and 0.26 ± 0.18 (p = 0.864). CONCLUSIONS: In mechanically ventilated pigs with severe P. aeruginosa pneumonia, PMX-HP does not have any valuable clinical benefit, and studies are warranted to fully evaluate a potential role of PMX-HP in septic shock associated with severe pulmonary infections.

Inter-Rater Agreement of Auscultation, Palpable Fremitus, and Ventilator Waveform Sawtooth Patterns Between Clinicians.

BACKGROUND: Clinicians often use numerous bedside assessments for secretion retention in participants who are receiving invasive mechanical ventilation. This study aimed to evaluate inter-rater agreement between clinicians when using standard clinical assessments of secretion retention and whether differences in clinician experience influenced inter-rater agreement. METHODS: Seventy-one mechanically ventilated participants were assessed by a research clinician and by one of 13 ICU clinicians. Each clinician conducted a standardized assessment of lung auscultation, palpation for chest-wall (rhonchal) fremitus, and ventilator inspiratory/expiratory flow-time waveforms for the sawtooth pattern. RESULTS: On the presence of breath sounds, agreement ranged from absolute to moderate in the upper zones and the lower zones, respectively. Kappa values for abnormal and adventitious lung sounds achieved moderate agreement in the upper zones, less than chance agreement to substantial agreement in the middle zones, and moderate agreement to almost perfect agreement in the lower zones. Moderate to almost perfect agreement was established for palpable fremitus in the upper zones, moderate to substantial agreement in the middle zones, and less than chance to moderate agreement in the lower zones. Inter-rater agreement on the presence of expiratory sawtooth pattern identification showed moderate agreement. The level of percentage agreement between the research and ICU clinicians for each respiratory assessment studied did not relate directly to level of clinical experience. CONCLUSIONS: Inter-rater agreement for all assessments showed variability between lung regions but maintained reasonable percentage agreement in mechanically ventilated participants. The level of percentage agreement achieved between clinicians did not directly relate to clinical experience for all respiratory assessments. Therefore, these respiratory assessments should not necessarily be viewed in isolation but interpreted within the context of a full clinical assessment.

Endotracheal tube biofilm translocation in the lateral Trendelenburg position.

INTRODUCTION: Laboratory studies demonstrated that the lateral Trendelenburg position (LTP) is superior to the semirecumbent position (SRP) in the prevention of ventilator-associated pulmonary infections. We assessed whether the LTP could also prevent pulmonary colonization and infections caused by an endotracheal tube (ETT) biofilm. METHODS: Eighteen pigs were intubated with ETTs colonized by Pseudomonas aeruginosa biofilm. Pigs were positioned in LTP and randomized to be on mechanical ventilatin (MV) up to 24 hour, 48 hour, 48 hour with acute lung injury (ALI) by oleic acid and 72 hour. Bacteriologic and microscopy studies confirmed presence of biofilm within the ETT. Upon autopsy, samples from the proximal and distal airways were excised for P.aeruginosa quantification. Ventilator-associated tracheobronchitis (VAT) was confirmed by bronchial tissue culture ≥3 log colony forming units per gram (cfu/g). In pulmonary lobes with gross findings of pneumonia, ventilator-associated pneumonia (VAP) was confirmed by lung tissue culture ≥3 log cfu/g. RESULTS: P.aeruginosa colonized the internal lumen of 16 out of 18 ETTs (88.89%), and a mature biofilm was consistently present. P.aeruginosa colonization did not differ among groups, and was found in 23.6% of samples from the proximal airways, and in 7.1% from the distal bronchi (P = 0.001). Animals of the 24 hour group never developed respiratory infections, whereas 20%, 60% and 25% of the animals in group 48 hour, 48 hour-ALI and 72 hour developed P.aeruginosa VAT, respectively (P = 0.327). Nevertheless, VAP never developed. CONCLUSIONS: Our findings imply that during the course of invasive MV up to 72 hour, an ETT P.aeruginosa biofilm hastily colonizes the respiratory tract. Yet, the LTP compartmentalizes colonization and infection within the proximal airways and VAP never develops.