Agreement between the thromboelastography reaction time parameter using fresh and citrated whole blood during extracorporeal membrane oxygenation with Teg®5000 and Teg®6s.

PURPOSE: We aimed at assessing the correlation between TEG reaction time (TEG-R) in citrated and fresh blood samples with TEG5000 and TEG 6S during heparin administration in patients with and without ECMO support. MATERIALS AND METHODS: Paired TEG5000 (fresh and citrated whole blood, kaolin and kaolin-heparinase) and TEG6S (citrated whole blood) samples were obtained, together with standard coagulation laboratory tests. Bland-Altman analysis and Lin's concordance correlation coefficient were used to assess agreement. RESULTS: Thirteen consecutive ECMO patients and eight consecutive non-ECMO patients were enrolled and TEG was performed for a total of 84 paired samples. ECMO patients received 19.2 (12.6-25.8) U/kg/h of heparin. Five of the non-ECMO patients did not receive heparin, two of them received a very low prophylactic dose (1.6 and 2.9 IU/kg/h, respectively), and one of them 13.1 U/kg/h of heparin. Using TEG®5000, TEG-R was 21.0 (-23.4; 65.5) min longer on fresh compared to citrated blood in patients receiving heparin while only 1.58 (-5.5; 8.7) min longer in patients not-receiving heparin. These differences were reverted by heparinase. CONCLUSIONS: Using citrated-recalcified blood to perform TEG might lead to underestimation of the effect of heparin.

The role of inflammation and antithrombin supplementation on thromboelastographic parameters during veno-venous ECMO for respiratory failure.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) may act as a driver or propagator of systemic inflammation. In turn, cytokine release can modify thromboelastographic (TEG) tests which are commonly used for anticoagulation monitoring. In this context, antithrombin (AT) supplementation might further modify TEG. METHODS: This is a pre-specified sub-study of the "Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation" study (investigator-initiated, randomized, single-blind, two-arm trial) conducted in two Italian ECMO referral ICUs. Adult patients requiring vv-ECMO for respiratory failure and undergoing unfractioned heparin (UFH) administration were enrolled and randomized whether to receive AT supplementation. Plasma samples for cytokine assay (IL-8, IL-10, IL-6, IL-1ß, TNF-α and Pro-ADM) and heparinase TEG were collected from every patient before ECMO start, 24 h and 72 h after ECMO start, before ECMO removal, and 7 days after ECMO removal or upon ICU discharge whichever happened first. AT concentration, coagulation and clinical data were collected before ECMO start and at pre-fixed time points. RESULTS: Thirty-nine patients were enrolled (21 treatments, 18 controls). TEG-R had a weak-to-moderate positive correlation with IL-8, IL-6, IL-10 and TNF-α and a moderate positive correlation with Pro-ADM. TEG-ANG showed a weak negative correlation with IL-8, IL-6 and TNF-α, while TEG-MA negatively correlated with IL-8, TNF-α and Pro-ADM. AT supplementation seemed to modify the association between TEG-MA and IL-8, IL-10 and Pro-ADM; conversely, AT did not affect the relationship among TEG-R or TEG-ANG and the studied cytokines. CONCLUSIONS: High concentrations of systemic cytokines correlated with longer reaction times and decreased angle and amplitude at TEG, suggesting that an increase in inflammation is related with hypocoagulability as revealed by thromboelastography.

Incidence, microbiological and immunological characteristics of ventilator-associated pneumonia assessed by bronchoalveolar lavage and endotracheal aspirate in a prospective cohort of COVID-19 patients: CoV-AP study.

BACKGROUND: No univocal recommendation exists for microbiological diagnosis of ventilator-associated pneumonia (VAP). Sampling of either proximal or distal respiratory tract likely impacts on the broad range of VAP incidence between cohorts. Immune biomarkers to rule-in/rule-out VAP diagnosis, although promising, have not yet been validated. COVID-19-induced ARDS made VAP recognition even more challenging, often leading to overdiagnosis and overtreatment. We evaluated the impact of different respiratory samples and laboratory techniques on VAP incidence and microbiological findings in COVID-19 patients. METHODS: Prospective single-centre cohort study conducted among COVID-19 mechanically ventilated patients in Policlinico Hospital (Milan, Italy) from January 2021 to May 2022. Microbiological confirmation of suspected VAP (sVAP) was based on concomitant endotracheal aspirates (ETA) and bronchoalveolar lavage (BAL). Conventional and fast microbiology (FILMARRAY® Pneumonia Panel plus, BALFAPPP) as well as immunological markers (immune cells and inflammatory cytokines) was analysed. RESULTS: Seventy-nine patients were included. Exposure to antibiotics and steroid therapy before ICU admission occurred in 51/79 (64.6%) and 60/79 (65.9%) patients, respectively. Median duration of MV at VAP suspicion was 6 (5-9) days. Incidence rate of microbiologically confirmed VAP was 33.1 (95% CI 22.1-44.0) and 20.1 (95% CI 12.5-27.7) according to ETA and BAL, respectively. Concordance between ETA and BAL was observed in 35/49 (71.4%) cases, concordance between BALFAPPP and BAL in 39/49 (79.6%) cases. With BAL as reference standard, ETA showed 88.9% (95% CI 70.8-97.7) sensitivity and 50.0% (95% CI 28.2-71.8) specificity (Cohen's Kappa 0.40, 95% CI 0.16-0.65). BALFAPPP showed 95.0% (95% CI 75.1-99.9) sensitivity and 69% (95% CI 49.2-84.7) specificity (Cohen's Kappa 0.60, 95% CI 0.39-0.81). BAL IL-1ß differed significantly between VAP (135 (IQR 11-450) pg/ml) and no-VAP (10 (IQR 2.9-105) pg/ml) patients (P = 0.03). CONCLUSIONS: In COVID-19 ICU patients, differences in microbial sampling at VAP suspicion could lead to high variability in VAP incidence and microbiological findings. Concordance between ETA and BAL was mainly limited by over 20% of ETA positive and BAL negative samples, while BALFAPPP showed high sensitivity but limited specificity when evaluating in-panel targets only. These factors should be considered when comparing results of cohorts with different sampling. BAL IL-1ß showed potential in discriminating microbiologically confirmed VAP. CLINICAL TRIAL REGISTRATION: NCT04766983, registered on February 23, 2021.

Inhaled amikacin for pneumonia treatment and dissemination prevention: an experimental model of severe monolateral Pseudomonas aeruginosa pneumonia.

BACKGROUND: Pseudomonas aeruginosa pneumonia is commonly treated with systemic antibiotics to ensure adequate treatment of multidrug resistant (MDR) bacteria. However, intravenous (IV) antibiotics often achieve suboptimal pulmonary concentrations. We therefore aimed to evaluate the effect of inhaled amikacin (AMK) plus IV meropenem (MEM) on bactericidal efficacy in a swine model of monolateral MDR P. aeruginosa pneumonia. METHODS: We ventilated 18 pigs with monolateral MDR P. aeruginosa pneumonia for up to 102 h. At 24 h after the bacterial challenge, the animals were randomized to receive 72 h of treatment with either inhaled saline (control), IV MEM only, or IV-MEM plus inhaled AMK (MEM + AMK). We dosed IV MEM at 25 mg/kg every 8 h and inhaled AMK at 400 mg every 12 h. The primary outcomes were the P. aeruginosa burden and histopathological injury in lung tissue. Secondary outcomes included the P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage fluid, the development of antibiotic resistance, the antibiotic distribution, and the levels of inflammatory markers. RESULTS: The median (25-75th percentile) P. aeruginosa lung burden for animals in the control, MEM only, and MEM + AMK groups was 2.91 (1.75-5.69), 0.72 (0.12-3.35), and 0.90 (0-4.55) log10 CFU/g (p = 0.009). Inhaled therapy had no effect on preventing dissemination compared to systemic monotherapy, but it did have significantly higher bactericidal efficacy in tracheal secretions only. Remarkably, the minimum inhibitory concentration of MEM increased to > 32 mg/L after 72-h exposure to monotherapy in 83% of animals, while the addition of AMK prevented this increase (p = 0.037). Adjunctive therapy also slightly affected interleukin-1ß downregulation. Despite finding high AMK concentrations in pulmonary samples, we found no paired differences in the epithelial lining fluid concentration between infected and non-infected lungs. Finally, a non-significant trend was observed for higher amikacin penetration in low-affected lung areas. CONCLUSIONS: In a swine model of monolateral MDR P. aeruginosa pneumonia, resistant to the inhaled AMK and susceptible to the IV antibiotic, the use of AMK as an adjuvant treatment offered no benefits for either the colonization of pulmonary tissue or the prevention of pathogen dissemination. However, inhaled AMK improved bacterial eradication in the proximal airways and hindered antibiotic resistance.

A long-lasting porcine model of ARDS caused by pneumonia and ventilator-induced lung injury.

BACKGROUND: Animal models of acute respiratory distress syndrome (ARDS) do not completely resemble human ARDS, struggling translational research. We aimed to characterize a porcine model of ARDS induced by pneumonia-the most common risk factor in humans-and analyze the additional effect of ventilator-induced lung injury (VILI). METHODS: Bronchoscopy-guided instillation of a multidrug-resistant Pseudomonas aeruginosa strain was performed in ten healthy pigs. In six animals (pneumonia-with-VILI group), pulmonary damage was further increased by VILI applied 3 h before instillation and until ARDS was diagnosed by PaO2/FiO2 < 150 mmHg. Four animals (pneumonia-without-VILI group) were protectively ventilated 3 h before inoculum and thereafter. Gas exchange, respiratory mechanics, hemodynamics, microbiological studies and inflammatory markers were analyzed during the 96-h experiment. During necropsy, lobar samples were also analyzed. RESULTS: All animals from pneumonia-with-VILI group reached Berlin criteria for ARDS diagnosis until the end of experiment. The mean duration under ARDS diagnosis was 46.8 ± 7.7 h; the lowest PaO2/FiO2 was 83 ± 5.45 mmHg. The group of pigs that were not subjected to VILI did not meet ARDS criteria, even when presenting with bilateral pneumonia. Animals developing ARDS presented hemodynamic instability as well as severe hypercapnia despite high-minute ventilation. Unlike the pneumonia-without-VILI group, the ARDS animals presented lower static compliance (p = 0.011) and increased pulmonary permeability (p = 0.013). The highest burden of P. aeruginosa was found at pneumonia diagnosis in all animals, as well as a high inflammatory response shown by a release of interleukin (IL)-6 and IL-8. At histological examination, only animals comprising the pneumonia-with-VILI group presented signs consistent with diffuse alveolar damage. CONCLUSIONS: In conclusion, we established an accurate pulmonary sepsis-induced ARDS model.

Mechanical Ventilation for COVID-19 Patients.

Non-invasive ventilation (NIV) or invasive mechanical ventilation (MV) is frequently needed in patients with acute hypoxemic respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While NIV can be delivered in hospital wards and nonintensive care environments, intubated patients require intensive care unit (ICU) admission and support. Thus, the lack of ICU beds generated by the pandemic has often forced the use of NIV in severely hypoxemic patients treated outside the ICU. In this context, awake prone positioning has been widely adopted to ameliorate oxygenation during noninvasive respiratory support. Still, the incidence of NIV failure and the role of patient self-induced lung injury on hospital outcomes of COVID-19 subjects need to be elucidated. On the other hand, endotracheal intubation is indicated when gas exchange deterioration, muscular exhaustion, and/or neurological impairment ensue. Yet, the best timing for intubation in COVID-19 is still widely debated, as it is the safest use of neuromuscular blocking agents. Not differently from other types of acute respiratory distress syndrome, the aim of MV during COVID-19 is to provide adequate gas exchange while avoiding ventilator-induced lung injury. At the same time, the use of rescue therapies is advocated when standard care is unable to guarantee sufficient organ support. Nevertheless, the general shortage of health care resources experienced during SARS-CoV-2 pandemic might affect the utilization of high-cost, highly specialized, and long-term supports. In this article, we describe the state-of-the-art of NIV and MV setting and their usage for acute hypoxemic respiratory failure of COVID-19 patients.

CPAP Effects on Oxygen Delivery in One-Lung Ventilation During Minimally Invasive Surgical Ablation for Atrial Fibrillation in The Supine Position.

OBJECTIVE: In minimally invasive surgical ablation for atrial fibrillation during video-assisted thoracoscopy surgery, one-lung ventilation (OLV) with a double- lumen tube is commonly employed. In contrast with the majority of thoracic procedures, the patient lies supine; thus, the protective effect of gravity is lost and intrapulmonary shunt remains high. To decrease intrapulmonary shunt and to increase oxygenation, many strategies are utilized: high inspiratory fraction of oxygen (FIO2), positive end-expiratory pressure on the ventilated lung, and continuous positive airway pressure (CPAP) on the deflated lung. DESIGN: The authors performed a prospective, single- center, randomized study to evaluate the effect of additional CPAP in the nonventilated lung on oxygen delivery during surgical ablation for atrial fibrillation via video-assisted thoracoscopy in the supine position. SETTING: University hospital Centro Cardiologico Monzino IRCCS, Milano, Italy. PARTICIPANTS: Twenty-two patients scheduled for minimally invasive surgical ablation for atrial fibrillation. INTERVENTIONS: The patients underwent pressure-controlled ventilation, adjusting inspiratory pressure to obtain a tidal volume of 7 mL/kg while keeping FIO2 constantly 1.0, a respiratory rate to maintain arterial partial pressure of carbon dioxide (PaCO2) between 35 and 40 mmHg, and positive end-expiratory pressure of 5 cmH2O. During OLV, inspiratory pressure was reduced to obtain a tidal volume of 5 mL/kg, maintaining FIO2 of 1.0, a respiratory rate to maintain PaCO2 between 35 and 40 mmHg with capnothorax of 10 cmH2O. The patients were then randomized into the CPAP group (CPAP 10 cmH20 on deflated lung) and NO CPAP group. Inotropic agents (dopamine or dobutamine) were used if cardiac index fell below 1.5 L/min/m2. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients were enrolled, randomized, and completed the study. Median age was 62 years. The difference in arterial partial pressure of oxygen between the 2 groups was shy of significance, p = 0.16. Cardiac index progressively increased during OLV until the end of the procedure in both groups (p < 0.01) and was maintained above 1.5 mL/min/m2 during the whole study time. Arterial oxygen content remained stable during the entire procedure in both groups (p = 0.27). Oxygen delivery index (DO2I) increased significantly during the procedure (p < 0.01); nevertheless, the difference in DO2I between the CPAP and NO CPAP group was nonsignificant (p = 0.61). Intrapulmonary shunt (Qs/Qt) increased during OLV (p < 0.01 for the time effect) and remained high until total lung ventilation was reintroduced. No difference in Qs/Qt was observed between the CPAP and NO CPAP groups (p = 0.98). Similarly, mean pulmonary artery pressure increased significantly during OLV and remained high at the end of the procedure in both groups (time effect p < 0.01). CONCLUSIONS: During OLV for atrial fibrillation surgical ablation in the supine position, CPAP on the deflated lung seemed to be ineffective to reduce Qs/Qt or to increase arterial partial pressure of oxygen and DO2I, provided cardiac output was maintained above 1.5 L/min/m2.

Agreement Between Viscoelastic Coagulation Monitor (VCM), TEG 5000, and Coagulation Tests in Critically Ill Patients: A Multicenter Study.

The performance of viscoelastic coagulation monitor (VCM) compared with TEG 5000 (TEG) is unknown. In this multicenter study, the authors evaluated the agreement among VCM/TEG parameters and their relationship with standard coagulation tests in critically ill patients. Viscoelastic coagulation monitor, TEG, and laboratory samples were analyzed simultaneously. Viscoelastic coagulation monitor/TEG agreement was computed by Bland and Altman's plots, association with laboratory parameters was studied with Spearman's correlation coefficient and random-intercept linear models. One-hundred and twenty-seven patients enrolled, 320 paired observations: 210 (65.6%) under unfractioned heparin (UFH), 94 (29.4%) under low molecular weight heparin (LMWH), 16 (5.0%) no heparin. Under UFH prolonged clot formation times and reduced the amplitude of viscoelastic tracings on both devices, especially on TEG. The type of heparin affected the agreement between VCM/TEG homolog parameters. Reaction time (TEG-R) resulted 23.1 min longer than the homolog clotting time (VCM-CT) under UFH; maximum amplitude (TEG-MA) resulted 29.5 mm higher than maximum clot firmness (VCM-MCF) under LMWH. Weak correlation was observed between VCM-CT/TEG-R and activated partial thromboplastin time (aPTT)/anti-Xa; no correlation was found between VCM-alpha/TEG-angle and fibrinogen concentration. Viscoelastic coagulation monitor-MCF showed strong (LWMH) to moderate (UFH) correlation with platelet count, while TEG-MA only showed lower correlation. Viscoelastic coagulation monitor and TEG are differently affected by heparin. The platelet count is well represented by VCM-MCF even during UFH administration.

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.

Different Inspiratory Flow Waveform during Volume-Controlled Ventilation in ARDS Patients.

The most used types of mechanical ventilation are volume- and pressure-controlled ventilation, respectively characterized by a square and a decelerating flow waveform. Nowadays, the clinical utility of different inspiratory flow waveforms remains unclear. The aim of this study was to assess the effects of four different inspiratory flow waveforms in ARDS patients. Twenty-eight ARDS patients (PaO2/FiO2 182 ± 40 and PEEP 11.3 ± 2.5 cmH2O) were ventilated in volume-controlled ventilation with four inspiratory flow waveforms: square (SQ), decelerating (DE), sinusoidal (SIN), and trunk descending (TDE). After 30 min in each condition, partitioned respiratory mechanics and gas exchange were collected. The inspiratory peak flow was higher in the DE waveform compared to the other three waveforms, and in SIN compared to the SQ and TDE waveforms, respectively. The mean inspiratory flow was higher in the DE and SIN waveforms compared with TDE and SQ. The inspiratory peak pressure was higher in the SIN and SQ compared to the TDE waveform. Partitioned elastance was similar in the four groups; mechanical power was lower in the TDE waveform, while PaCO2 in DE. No major effect on oxygenation was found. The explored flow waveforms did not provide relevant changes in oxygenation and respiratory mechanics.

Viscoelastic Coagulation Monitor as a Novel Device to Assess Coagulation at the Bedside. A Single-Center Experience During the COVID-19 Pandemic.

Viscoelastic coagulation monitor (VCM) is a portable device developed to evaluate the viscoelastic properties of whole blood activated by contact with glass. In this study, VCM was employed to analyze the viscoelastic profiles of 36 COVID-19 intensive care patients. Full anticoagulant dose heparin (unfractionated [UFH]; low molecular weight [LMWH]) was administrated to all patients. The association between VCM and laboratory parameters was retrospectively analyzed. The administration of UFH-influenced VCM parameters prolonging clotting time (CT) and clot formation time (CFT) and reducing angle (alpha) and amplitudes of the VCM tracings (A10, A20, and maximum clot firmness [MCF]) compared with LMWH therapy. A tendency toward hypercoagulation was observed by short CT and CFT in patients receiving LMWH. Clotting time was correlated with UFH dose (Spearman's rho = 0.48, p ≤ 0.001), and no correlation was found between CT and LMWH. All VCM tracings failed to show lysis at 30 and 45 minutes, indicating the absence of fibrinolysis. A10, A20, and MCF exhibited very-good to good diagnostic accuracy for detecting platelet count and fibrinogen above the upper reference limit of the laboratory. In conclusion, VCM provided reliable results in COVID-19 patients and was easy to perform with minimal training at the bedside.

Lateral position during severe mono-lateral pneumonia: an experimental study.

Patients with mono-lateral pneumonia and severe respiratory failure can be positioned in lateral decubitus, with the healthy lung dependent, to improve ventilation-perfusion coupling. Oxygenation response to this manoeuvre is heterogeneous and derecruitment of dependent lung has not been elucidated. Nine pigs (32.2 ± 1.2 kg) were sedated and mechanically ventilated. Mono-lateral right-sided pneumonia was induced with intrabronchial challenge of Pseudomonas aeruginosa. After 24 h, lungs were recruited and the animals were randomly positioned on right or left side. After 3 h of lateral positioning, the animals were placed supine; another recruitment manoeuvre was performed, and the effects of contralateral decubitus were assessed. Primary outcome was lung ultrasound score (LUS) of the dependent lung after 3-h lateral positioning. LUS of the left non-infected lung worsened while positioned in left-lateral position (from 1.33 ± 1.73 at baseline to 6.78 ± 4.49; p = 0.005). LUS of the right-infected lung improved when placed upward (9.22 ± 2.73 to 6.67 ± 3.24; p = 0.09), but worsened in right-lateral position (7.78 ± 2.86 to 13.33 ± 3.08; p < 0.001). PaO2/FiO2 improved in the left-lateral position (p = 0.005). In an animal model of right-lung pneumonia, left-lateral decubitus improved oxygenation, but collapsed the healthy lung. Right-lateral orientation further collapsed the diseased lung. Our data raise potential clinical concerns for the use of lateral position in mono-lateral pneumonia.

Optimal approaches to preventing severe community-acquired pneumonia.

Introduction: Community-acquired pneumonia (CAP) has the highest rate of mortality of all infectious diseases, especially among the elderly. Severe CAP (sCAP) is defined as a CAP in which intensive care management is required and is associated with an unfavorable clinical course. Areas covered: This review aims to identify prevention strategies for reducing the incidence of CAP and optimized management of sCAP. We highlight the main prevention approaches for CAP, focusing on the latest vaccination plans and on the influence of health-risk behaviors. Lastly, we report the latest recommendations about the optimal approach for sCAP when CAP has already been diagnosed, including prompt admission to ICU, early empirical antibiotic therapy, and optimization of antibiotic use. Expert opinion: Despite improvements in the diagnosis and treatment of sCAP, more efforts are needed to combat preventable causes, including the implementation and improvement of vaccine coverage, anti-tobacco campaigns and correct oral hygiene. Moreover, future research should aim to assess the benefits of early antimicrobial therapy in primary care. Pharmacokinetic studies in the target population may help clinicians to adjust dosage regimens in critically ill patients with CAP and thus reduce rates of treatment failure.

Risk and Prognostic Factors in Very Old Patients with Sepsis Secondary to Community-Acquired Pneumonia.

BACKGROUND: Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). Methods: We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. Consecutive patients hospitalized with CAP were included if they were very old (≥80 years) and divided into those with and without sepsis for comparison. Sepsis was diagnosed based on the Sepsis-3 criteria. The main clinical outcome was 30-day mortality. Results: Among the 4219 patients hospitalized with CAP during the study period, 1238 (29%) were very old. The prevalence of sepsis in this age group was 71%. Male sex, chronic renal disease, and diabetes mellitus were independent risk factors for sepsis, while antibiotic therapy before admission was independently associated with a lower risk of sepsis. Thirty-day and intensive care unit (ICU) mortality did not differ between patients with and without sepsis. In CAP-sepsis group, chronic renal disease and neurological disease were independent risk factors for 30-day mortality. Conclusion: In very old patients hospitalized with CAP, in-hospital and 1-year mortality rates were increased if they developed sepsis. Antibiotic therapy before hospital admission was associated with a lower risk of sepsis.

An in-vitro study to evaluate high-volume low-pressure endotracheal tube cuff deflation dynamics.

BACKGROUND: High-volume low-pressure (HVLP) endotracheal tube (ETT) cuffs for critically ill patients often deflate during the course of mechanical ventilation. We performed an in-vitro study to comprehensively assess HVLP cuff deflation dynamics and potential preventive measures. METHODS: We evaluated 24-hour deflation of seven HVLP cuffs of cylindrical or tapered shape, and made of polyvinylchloride or polyurethane. Experiments were performed within a thermostated chamber set at 37 °C. In the first stage of experiments, the cuff pilot balloon valve was not manipulated. The cuff internal pressure was assessed hourly for 24 hours, via a linear position sensor which monitored cuff deflation displacements. Then, we re-evaluated cuff deflation of the worst-performing ETT cuffs with the cuff pilot balloon valve sealed. Finally, we inflated ETT cuffs within an artificial trachea to evaluate deflation dynamics during mechanical ventilation. RESULTS: Initial tests showed an exponential decrease in cuff internal pressure in five out of seven cuffs. Cuffs of cylindrical shape and made of polyurethane demonstrated the fastest deflation rates (P<0.050 vs. cuffs of conical shape and made of polyvinylchloride). When the cuff pilot balloon valve was not sealed, the internal cuff pressure deflation rate differed significantly among ETTs (P=0.005). Yet, upon sealing the cuff pilot balloon valve and during mechanical ventilation, cuff deflation rates decreased (P<0.050). CONCLUSIONS: In controlled in-vitro settings, ETT cuffs consistently deflate over time, and the cuff pilot balloon valve plays a central role in this occurrence. Deflation rate decreases when cuffs are inflated within a plastic artificial tracheal model and mechanical ventilation is activated.

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.

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.