The respiratory quotient (RQ) reflects metabolic substrate utilization and is traditionally measured using indirect calorimetry techniques, e.g. Douglas bag, which are technically demanding and not always feasible in clinical practice. The alveolar gas equation (AGE) provides a theoretical relationship between oxygen tension, carbon dioxide tension and RQ and may be rearranged to estimate RQ using standard respiratory measurements. This study aimed to validate a novel method for estimating RQ by reversing the alveolar gas equation. In this prospective experimental study, twelve anesthetized, mechanically ventilated pigs were studied under steady-state conditions. RQ was determined using two methods: (1) reference measurement via Douglas bag collection using Haldane transformation (RQref), and (2) calculation from the rearranged alveolar gas equation using inspired and expired gas measurements (RQcalc). Agreement between methods was assessed using paired t-tests, Bland-Altman analysis with bootstrap confidence intervals, and linear regression. Mean RQref was 0.877 (95
Andes virus causes hantavirus cardiopulmonary syndrome (HCPS), a severe disease found in central and southern parts of Chile and Argentina. Recently a case-outbreak of HCPS was reported on a cruise ship, therefore contemporary data on organ support and outcomes is required. The objective of this study was to assess organ support use and patient outcomes in patients admitted with HCPS. We used the Diagnosis-Related Groups (DGR) database to analyse patients admitted in 31 Chilean hospitals between January 1, 2019, and December 31, 2024. They were stratified by the maximal respiratory support received: no respiratory support, non-invasive ventilation (NIV), invasive mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO). Hospital length of stay (LOS) and in-hospital mortality were the main outcomes assessed. In-hospital mortality was further analysed by pre-COVID-19 pandemic, pandemic, and post-pandemic periods. A total of 215 patients with HCPS were identified, of whom 69.3
Abstract Background Septic shock induces skeletal muscle wasting and neuromuscular dysfunction, contributing to ICU-acquired weakness (ICUAW) and poor recovery after critical illness. Conventional ultrasound primarily captures structural changes but provides limited insight into early muscle mechanical alterations or their relationships with clinical factors. Shear-wave elastography (SWE) enables non-invasive assessment of muscle stiffness, but its performance in critically ill patients remains poorly understood. Methods In this prospective study, adults with septic shock requiring invasive ventilation underwent daily muscle ultrasound during the first five ICU days. Rectus femoris muscle cross-sectional area, echogenicity and SWE-derived shear modulus (SM RF ) were assessed bilaterally using conventional ultrasound and shear-wave elastography in both longitudinal and transverse orientations at two anatomical sites within the rectus femoris . An exploratory anisotropy estimate was derived from the transverse-to-longitudinal stiffness ratio. ICUAW was evaluated at the time of extubation. Associations between ultrasound markers and clinical variables were explored using correlation and regression analyses. Results Twenty-seven patients (66.7% male, mean age 61 ± 12 years) were analysed (125 sessions, 4,971 images). Rectus femoris cross-sectional area declined from 3.90 cm² on Day 1 to 2.97 cm² by Day 5 (− 21%, p < 0.01), while echogenicity remained stable. Shear modulus (SM RF ) demonstrated region- and orientation-dependent behaviour. At the lower-third region, longitudinal SM RF remained relatively stable (7.08 to 7.72 kPa), whereas transverse SM RF declined significantly (15.20 to 12.30 kPa, p = 0.009), resulting in dynamic changes in the transverse-to-longitudinal stiffness ratio. Muscle atrophy trajectories were similar in patients with and without ICUAW, and no significant between-group differences in SM RF measures were identified. Higher illness severity (SOFA score, β = 18.18, p = 0.003) and cumulative fluid balance (β = 3.32, p = 0.002) were associated with increases in longitudinal SM RF . Greater early caloric intake (β = 0.076, p = 0.006) and increases in echogenicity (β = −0.91, p = 0.027) were associated with changes in transverse SM RF . Conclusions Rapid muscle loss during early septic shock was accompanied by distinct, site- and direction-specific stiffness changes. Dual-plane SWE identified early mechanical changes, although these measures did not discriminate ICUAW status in this cohort. Associations with clinical variables suggest that SWE may help capture early physiological muscle changes in critical illness.
Differential hypoxemia, or Harlequin syndrome, is a critical concern during veno-arterial extracorporeal membrane oxygenation (VA-ECMO), especially when femoral artery cannulation delivers retrograde flow. This phenomenon may impair cerebral oxygenation and promote brain injury. We investigated whether the arterial cannulation site and ventilation strategy influence acute cerebral injury in a rat cardiopulmonary bypass (CPB) model. Forty male Wistar rats were randomized into four groups (n = 10 each) according to the arterial cannulation site (carotid [anterograde, A-CPB] or femoral [retrograde, R-CPB]) and ventilation strategy (normal [NV, 100
Intensive Care Unit–acquired weakness (ICUAW) is a frequent complication that significantly impairs functional recovery in critically ill patients. Fluid overload during critical illness has been associated with adverse outcomes, but its relationship with peripheral muscle quality and strength remains uncertain. This study aimed to evaluate the association between cumulative fluid balance, ultrasound-assessed muscle quality, and muscle strength in critically ill patients. We conducted a retrospective analysis of routinely collected data between May and October 2024 in adult ICU patients who were deeply sedated, mechanically ventilated, and had an ICU length of stay ≥24 hours. Muscle and subcutaneous tissue measurements were obtained using ultrasound of the vastus intermedius and rectus femoris within the first 24 hours of ICU admission (day 1) and at clinical awakening. Muscle quality was assessed at both time points using the Heckmatt scale. Global muscle strength was assessed only at clinical awakening using the Medical Research Council Sum Score (MRC-SS), once patients were able to follow commands. Patients without complete ultrasound measurements at both time points were excluded from the final analysis. Eighty patients were included (mean age 51 ± 14 years; APACHE II score 18 ± 5). The main admission diagnoses were predominantly respiratory and septic conditions. Mean cumulative fluid balance at awakening was 2400 ± 800 mL. From ICU admission to awakening, quadriceps thickness decreased, whereas subcutaneous tissue thickness increased and muscle quality deteriorated, as reflected by higher Heckmatt scores. At awakening, cumulative fluid balance showed a strong inverse correlation with global muscle strength (rho = −0.70, p < 0.001) and a moderate positive correlation with subcutaneous tissue thickness. Muscle quality assessed by the Heckmatt scale was moderately inversely correlated with MRC-SS (rho = −0.43, p< 0.001). In multivariable analysis adjusted for age, disease severity, and duration of mechanical ventilation, cumulative fluid balance remained independently associated with lower muscle strength at awakening. Qualitative muscle ultrasound assessment using the Heckmatt scale provides complementary information to muscle thickness measurements. The observed association between cumulative fluid balance and poorer muscle quality suggests that fluid status should be considered when interpreting qualitative muscle ultrasound findings in critically ill patients.
Ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia requiring mechanical ventilation (vHAP) are frequent in intensive care units and require prompt diagnosis. The FilmArray Pneumonia Panel (FAPP) enables fast pathogen identification, but its clinical impact remains uncertain. To assess whether adding FAPP to conventional microbiology increases the rate of targeted antimicrobial therapy (AMT) in patients with suspected VAP or vHAP. Open-label, multicenter randomized-controlled trial in immunocompetent adults with suspected VAP or vHAP. Patients were randomized to management with FAPP plus conventional microbiology or conventional microbiology alone. The primary outcome was the proportion of patients receiving targeted AMT 24 h after inclusion. From June 2020 to September 2023, 156 patients were randomized; 146 were analyzed (74 intervention, 72 control), as 10 did not provide consent for continued participation. Median age was 58 years (interquartile range, 43–70), 67.8
To investigate whether respiratory system elastance (ERS) modifies the associations of tidal volume (VT) and respiratory rate with clinical outcomes in mechanically ventilated patients with acute brain injury. In this post hoc analysis of the VENTIBRAIN study, ERS was computed as the ratio of driving pressure (ΔP) to VT/PBW. Effect modification by ERS on outcome associations was assessed. In 1158 patients, VT was similar across ERS tertiles (median 7.9, 7.6 and 7.1 mL/kg), resulting in a marked ΔP gradient across tertiles (median 5, 9, and 12 cmH2O). Higher VT was associated with lower ICU mortality in patients with low ERS (OR 0.52, 95
Septic shock in cancer patients remains associated with a grim prognosis. With regard to the high prevalence of anemia, the optimal hemoglobin target to restore tissue oxygenation remains uncertain. This was a multicenter superiority randomized controlled trial carried out in 18 centers in France. Adult patients with hematological or solid malignancies presenting with septic shock with lactate level > 2.0 mmol/L and hemoglobin level < 9.0 g/dL were randomly assigned to liberal or restrictive red blood cell (RBC) transfusion directed by hemoglobin thresholds of 9.0 g/dL or 7.0 g/dL during the first 48 h of resuscitation. The primary endpoint was 12-h lactate reduction, defined as normalization ≤ 2.0 mmol/L or relative decrease by 30
Corticosteroids modulate key inflammatory and fibroproliferative pathways involved in ARDS through genomic and non-genomic glucocorticoid receptor signaling. Advances in ARDS pathophysiology have highlighted the importance of timing, inflammatory burden, and host response in determining treatment efficacy. Clinical evidence supports corticosteroid use in moderate-to-severe ARDS, particularly in COVID-19 ARDS and severe community-acquired pneumonia, with reductions in mortality and duration of mechanical ventilation. However, treatment effects remain heterogeneous across etiologies and biological subphenotypes. Recent identification of hyperinflammatory and hypoinflammatory ARDS phenotypes suggests that corticosteroid responsiveness is not uniform. Hyperinflammatory phenotypes and septic ARDS appear more likely to benefit, whereas evidence remains limited or conflicting in influenza-associated and non-septic ARDS. Long-term effects and adverse outcomes, including metabolic complications and ICU-acquired weakness, remain insufficiently characterized. Future research is increasingly focused on precision medicine approaches integrating biomarkers, adaptive platform trials, and phenotype-guided strategies. Emerging developments include lung-targeted corticosteroid delivery systems and selective glucocorticoid receptor modulators designed to improve efficacy while reducing systemic toxicity. Corticosteroids should therefore be considered a context-dependent therapy whose benefit is influenced by etiology, disease stage, inflammatory phenotype, and timing of administration.
Randomised controlled trials (RCTs) have reshaped intensive care medicine (ICM), a discipline defined by acute, interacting organ failures, time-sensitive decisions, biological uncertainty, and heterogeneous recovery trajectories. Many interventions supported by strong physiological rationale failed to improve patient-centred outcomes, whereas durable advances often emerged from optimisation of supportive care, avoidance of iatrogenic harm, and reassessment of established practices. We conducted an interpretive historical review of landmark multicentre RCTs in adult ICM from the early 1990s onwards. PubMed searches, reference lists from major trials and reviews, and international guidelines were used to identify trials with conceptual influence on practice, guidelines, physiological reasoning, therapeutic strategy, research priorities, de-implementation, or outcome framing. Evidence was organised into overlapping paradigms rather than rigid chronological periods. Across haemodynamic support, mechanical ventilation, renal replacement therapy, antimicrobial treatment, nutrition, glucose control, transfusion, and sedation, landmark RCTs describe more than therapeutic expansion. Early biological and haemodynamic trials exposed the limits of reductionist strategies in syndromic critical illness. Protocol-driven approaches improved timeliness and consistency, but later pragmatic trials showed that rigid targets and invasive algorithms often added little once high-quality usual care was established. More recent trials challenge the assumption that greater intervention intensity improves outcomes, emphasising timing, disease phase, baseline risk, heterogeneity, patient selection, and treatment-related harm. Modern ICM RCTs have clarified not only what works, but what can be reduced, delayed, avoided, or applied selectively. Future progress requires biologically informed, context-sensitive trials focussed on meaningful survival, recovery, and long-term function.
