Domenico Luca Grieco

Sepsis and septic shock remain leading causes of disability, mortality and healthcare utilization worldwide. Increasing evidence has established sepsis as a time-dependent emergency in which delays in diagnosis and treatment are associated with worsening organ dysfunction and increased mortality. To standardize early management, the Surviving Sepsis Campaign (SSC) developed evidence-based care bundles, culminating in the current Hour-1 Bundle, which emphasizes rapid implementation of key diagnostic and therapeutic interventions. This narrative review critically examines the scientific rationale, clinical evidence, implementation challenges, and future perspectives surrounding the SSC Hour-1 Bundle. Lactate remains a valuable marker of illness severity and treatment response, although its interpretation requires consideration of multiple non-hypoperfusion-related mechanisms. Blood cultures represent the microbiological gold standard, while emerging rapid diagnostic technologies are transforming pathogen identification and antimicrobial stewardship. Early effective antimicrobial therapy remains strongly associated with improved outcomes, although balancing prompt treatment with antimicrobial stewardship remains challenging. Fluid resuscitation strategies have evolved from fixed-volume approaches toward individualized assessment of fluid responsiveness and tolerance, whereas early vasopressor initiation is increasingly recognized as complementary to fluid administration. Although observational studies frequently associate bundle adherence with improved outcomes, real-world compliance remains variable and evidence supporting strict one-hour completion targets remains heterogeneous. Future developments are expected to move beyond standardized protocols toward personalized sepsis management integrating rapid diagnostics, immune phenotyping, advanced haemodynamic monitoring, and artificial intelligence-driven clinical decision support. These innovations may enable more precise therapeutic strategies while preserving the fundamental principles of sepsis management, that remain the cornerstone of contemporary sepsis care.

Lung-protective ventilation is the current standard for mechanical ventilation of patients with acute respiratory distress syndrome (ARDS). Traditionally, this approach has focused on the controlled phase of mechanical ventilation, but emerging data suggest that how patients are managed during assisted ventilation may also impact clinical outcomes. Experimental and observational clinical data indicate that excessive respiratory effort may further damage already injured lungs and may also lead to diaphragm myotrauma. Conversely, insufficient effort and prolonged passive ventilation are associated with diaphragm atrophy and dysfunction. Recent non-invasive techniques to monitor respiratory drive and effort at the bedside have facilitated the development of a new strategy to protect both the lungs and the diaphragm. The lung- and diaphragm-protective (LDP) ventilation framework highlights the need to better integrate ventilation and sedation strategies to facilitate timely and safe spontaneous breathing. This new paradigm has driven the development of emerging supportive and therapeutic modalities, such as diaphragm neurostimulation and partial neuromuscular blockade. Clinical trials are needed to evaluate the impact of LDP strategies on patient-centered outcomes, using designs that account for the possibility of heterogeneity of treatment effect in the ARDS population. In this review, we summarize the physiological background for the LDP framework, as well as the current clinical evidence evaluating this strategy.

Rationale: In intubated patients, occlusion maneuvers allow noninvasive assessment of inspiratory effort, respiratory drive, and lung mechanics. Objectives: To assess the feasibility of occlusion maneuvers during noninvasive ventilation (NIV). Methods: In this multicenter study, 60 hypoxemic patients underwent 2 randomized 1-hour NIV sessions with oronasal and full-face masks after extubation. End-expiratory and end-inspiratory occlusions measured expiratory occlusion pressure (Pocc), 100-ms airway pressure drop (P0.1), and plateau pressure. Esophageal manometry, calibrated before extubation, provided reference values for inspiratory effort, assessed as esophageal pressure swing (ΔPes) and dynamic transpulmonary driving pressure (ΔPL,dyn = pressure support − ΔPes). Interface-specific conversion factors (K) translating Pocc into predicted ΔPes (K × Pocc) and predicted ΔPL,dyn (pressure support − predicted ΔPes) were derived through 100-interaction cross-validation (20-patient derivation set, 40-patient validation set). Measurements and Main Results: Pocc was measurable in all patients. Mean K was 0.71 with the oronasal mask and 0.80 with the full-face mask. Predicted ΔPes agreed with observed ΔPes (oronasal: bias −0.41 cm H2O, 95% limits of agreement −2.3 to 1.5; full-face: 0.09, −2.9 to 3.1), and predicted ΔPL,dyn agreed with observed ΔPL,dyn (oronasal bias: 0.03, −2.9 to 2.9; full-face: −0.04, −4.3 to 4.2). Predicted ΔPes identified observed ΔPes ≤ −10 cm H2O, with areas under the receiver operating characteristic curve of 0.98 (oronasal) and 0.97 (full-face). Ventilator-derived P0.1 did not precisely quantify respiratory drive, but values >2.7 cm H2O with the oronasal mask and >3 cm H2O with the full-face mask identified high drive with specificity >90%. Plateau pressure was unstable in 78% (oronasal) and 90% (full-face) of patients. More negative predicted ΔPes, higher predicted ΔPL,dyn, and lower predicted lung compliance (expiratory tidal volume/predicted ΔPL,dyn) were associated with subsequent reintubation. Conclusions: During NIV, Pocc-derived parameters provide noninvasive estimates of inspiratory effort, lung stress, and mechanics, whereas ventilator P0.1 and plateau pressure are less reliable.

Rationale: Tidal recruitment/derecruitment (R/D) is a well-known mechanism of lung injury in acute respiratory distress syndrome (ARDS) patients, but its bedside identification is challenging during assisted ventilation. Objectives: To investigate bedside determinants of tidal R/D assessed by electrical impedance tomography (EIT) in spontaneously breathing ARDS patients on pressure support ventilation (PSV). Methods: This is a secondary analysis of a previous study including lightly sedated ARDS patients ventilated on PSV at 2 positive end-expiratory pressure (PEEP) levels selected by EIT (PEEPEIT) and low PEEP/FiO2 table (PEEPTABLE). Detailed physiological assessment was performed, including respiratory mechanics, inspiratory drive and effort, regional mechanics, and tidal R/D measured by EIT. Measurements and Main Results: Of 30 original patients, 1 was excluded due to unstable end-expiratory lung impedance, leaving 29 patients for analysis. Median PEEP was 10.0 (IQR 8.0-12.0) cmH2O with PEEPEIT and 8.0 (IQR 5.0-10.0) cmH2O with PEEPTABLE. Overall, tidal R/D was 14.3% (IQR 9.0-33.0), but it was lower at PEEPEIT vs PEEPTABLE (11.3% [IQR 4.8-20.5] vs 21.9% [IQR 6.8-31.7]; P = .008). Recruitment/derecruitment reduction with PEEPEIT correlated with decreases in collapse (rho = 0.72; P < .001) and pendelluft (rho = 0.57; P = .002). Analyzing data from both randomized PEEPs together, mixed-effects models showed higher tidal R/D at lower PEEP (P < .001), more negative end-expiratory transpulmonary pressure (PLEnd-Exp) (P < .001), larger collapse (P < .001), and lower lung compliance (P = .002). Higher respiratory drive (P = .001), effort (P = .009), and dynamic driving transpulmonary pressure (P = .009) correlated with higher tidal R/D. Patients with nonfocal infiltrates presented higher tidal R/D (P = .005). At multivariable analysis, PLEnd-Exp, lung collapse, and nonfocal pattern were independently associated tidal R/D. Conclusion: In spontaneously breathing ARDS patients on PSV, the main determinants of tidal R/D are more negative PLEnd-Exp, higher lung collapse, and nonfocal infiltrates.

High-flow nasal cannula (HFNC) has become a cornerstone of contemporary respiratory support.(,) Initially introduced as an easy-to-use, simple, and comfortable alternative for respiratory support in hypoxemic respiratory failure in the intensive care unit, its indications have expanded rapidly across hospital settings, patient populations, and clinical contexts.(-) Randomized clinical trials have established HFNC as an effective […] High-flow nasal cannula (HFNC) has become a cornerstone of contemporary respiratory support.(,) Initially introduced as an easy-to-use, simple, and comfortable alternative for respiratory support in hypoxemic respiratory failure in the intensive care unit, its indications have expanded rapidly across hospital settings, patient populations, and clinical contexts.(-) Randomized clinical trials have established HFNC as an effective […]