Randomized controlled trials provide foundational evidence in clinical medicine. However, the quality of evidence generated by clinical trials depends on the quality of their design, conduct, and analysis. A comprehensive protocol is essential for conducting a rigorous, high-quality trial, and publication of the protocol is an important step in transparent trial reporting. Protocol papers summarize key elements of the protocol for a clinical audience. Such papers afford trialists with an opportunity to explain study design choices and provide details about protocol execution that aid in trial interpretation but do not necessarily fit within the main trial manuscript. Consumers of protocol papers should understand the standards for adequate reporting and use a systematic approach to evaluate the planned trial and identify potential threats to its quality. As pragmatic trials have become increasingly common in critical care, their protocols merit special consideration due to unique trial design features that impact trial interpretation, such as embedding trial operations in clinical practice and using electronic health record data. In this perspective, we review components of protocol papers, discuss current reporting guidelines, and highlight key considerations for writing and reading critical care protocol papers, with a specific focus on pragmatic trials.
Insufficient inspiratory gas humidification in intubated patients is associated with several complications, including life-threatening endotracheal tube occlusion (ETO). Passive humidifiers, or heat-and-moisture exchangers (HMEs), are widely used in clinical practice, and their performance is commonly assessed using the ISO 9360 standard, implemented more than 30 years ago. Recent evidence suggests that this standard is insufficient to detect poorly performing HMEs. During the COVID-19 pandemic, unexpectedly high rates of ETO were reported in patients ventilated with HMEs that complied with ISO requirements, prompting renewed interest in reassessing humidification performance evaluation.We conducted a narrative and critical review of current methods used to evaluate HME and propose changes to improve device assessment. The ISO method relies on gravimetric measurements, a technique with several limitations, and assumes an expiratory absolute humidity (AH) of 44 mg H2O/L, which is substantially higher than the AH actually entering the HMEs. As a result, bench performance overestimates the humidity delivered. In addition, the ISO standard uses derived metrics rather than directly reporting absolute humidity, the parameter most closely associated with clinical outcomes.This review highlights the limitations of the current ISO approach and proposes several key revisions: adoption of validated hygrometric measurements; use of physiologic expiratory humidity (∼35 mg H2O/L); and definition of humidity thresholds adapted to clinical settings (≥28 mg H2O/L for prolonged ventilation, 20–25 mg H2O/L for the operating room, and intermediate values for short-term ventilation). Revising the ISO standard appears warranted to further improve purchasing decisions for the safe use of HMEs.
Background Positive end-expiratory pressure (PEEP) titration targeting end-expiratory transpulmonary pressure close to zero was associated with favorable clinical outcomes in a secondary analysis of the EPVent-2 trial in adults with acute respiratory distress syndrome (ARDS). However, its relevance in children remains unknown. Research Question Is end-expiratory transpulmonary pressure close to zero associated with 28-day ventilator-free days in pediatric ARDS? Study Design and Methods We conducted a post hoc secondary analysis of a randomized controlled trial enrolling children with pediatric ARDS at a single center. End-expiratory transpulmonary pressure close to zero was defined as –2 to +2 cmH2O. The primary outcome was 28-day ventilator-free days, with ICU mortality and length of mechanical ventilation in survivors evaluated as its components. Secondary outcomes were respiratory system compliance and PaO2/FIO2 ratio. Results There were 198 patients included. Median end-expiratory transpulmonary pressure was -0.1 (IQR -2.5, 1.9) cmH2O, PEEP was 10.3 (8.3, 12.3) cmH2O, and end-expiratory esophageal pressure was 10.9 (8.6, 13.3) cmH2O. In primary analyses, end-expiratory transpulmonary pressure close to zero was not associated with more 28-day ventilator-free days, lower ICU mortality, or shorter length of mechanical ventilation in survivors. In secondary analyses, it was not associated with respiratory system compliance or PaO2/FIO2 ratio. Interpretation In this cohort, end-expiratory transpulmonary pressure close to zero was not associated with favorable clinical outcomes in pediatric ARDS, nor with respiratory mechanics or oxygenation. Prospective titration studies are needed to clarify the physiological relevance of end-expiratory transpulmonary pressure in pediatric ARDS.
Background Pulse oximeter performance may vary by skin pigmentation, but most data are retrospective with key limitations. Research Question Does pulse oximeter bias in critically-ill adults differ by skin pigmentation? Study Design and Methods In this prospective single-center study of 631 ICU patients (2022–2024) we directly observed simultaneous pulse oximeter oxygen saturation (SpO2) and arterial blood functional oxygen saturation (SaO2). Skin pigment was assessed using the subjective Monk Skin Tone Scale and objective spectrophotometry measurement (Individual Typology Angle [ITA]). We quantified pulse oximeter bias [mean difference between SpO2 and SaO2, and average root mean square error (ARMS) and estimated adjusted effects of skin pigment on bias or ARMS with targeted maximum likelihood estimation. Results Among 1,760 paired measurements, median SaO2 was 98% (IQR 96%, 99%) with 40 episodes of stable hypoxemia (SpO2<90%). SpO2 systematically underestimated SaO2 [median bias= -1.70 IQR (-2.84, -0.50)]. Bias was less in patients with darker skin (ITA <-30°) [-1.05 (-2.44, -0.10)] vs lighter skin (ITA >30°) [-2.01 (-3.34, -1.00)] and remained significantly different in adjusted analyses. ARMS was 3.87 (95% CI 3.25, 4.53) overall and 4.49 (95% CI 2.63, 7.07) in patients with darker skin. Interpretation In this large ICU cohort, hypoxemia was rare, FDA-cleared pulse oximeter SpO2 systematically underestimated SaO2, and performance varied by skin pigment. Bias was less in patients with darker skin. Pulse oximeter inaccuracies in ICU patients may be more substantial than clinicians recognize. Additional real-world studies with multiple oximeter brands and more stable hypoxemia are needed to further understand bias variation with skin pigment.
BACKGROUND Low socioeconomic position (SEP) generally is associated with poor health, but whether & is associated with mortality in critically ill patients is unclear. RESEARCH QUESTION: Is low SEP associated with mortality among Danish adults receiving invasive mechanical ventilation (IMV)? STUDY DESIGN AND METHODS: This population-based cohort study included nonsurgical patients 25 years of age receiving incident IMV from January 2005 through December 2022 using data from national registries. We evaluated indicators of SEP by age: household income (25-04 years) or liquid assets (>= 65 years); education; and employment (25-64 years). The rhain outcome was 1-year mortality. We performed descriptive analyses and computed hazard ratios (HRs) via Cox proportional hazards regression with age- and sex-adjustment and with propensity score weighting. RESULTS: Among those 25 to 64 years of age (n = 23, 451) crude 1-year mortality for low-income, medlum-income, and high-income groups was 39.5%, 40.7%, and 36.2%, respec-tively. Patients with low vs high income and with low vs high education showed elevated weighted HR: 1.50 (95% CI, 1.24-1.82) and 1.24 (95% CI, 1.14-1.36), respectively. Unem-ployed male patients showed higher mortality than employed male patients (HR, 1.28; 951.111.48); results were null for female patients. Among patients >= 65 years of age (n = 31, 636) <^> I crude 1-year mortality for low-income, medium-income, and high-income groups 65.0%, 63.6%, and 59.9%, respectively. A slightly increased hazard of mortal-ity was seen for older patients with low vs high income (HR, 1.15; 95% CI, 1.08-1.22). INTERPRETATION: Our results show that although Danish residents have access to tax-funded health care, we observed evidence of increased mortality hazard among patients receiving IMV with lower SEP, particularly in younger adults. CHEST Critical Care 2026; 4(3):100275
Severe acidemia (pH < 7.20) involving metabolic acidosis affects 2% to 10% of patients in the ICU and is associated with high mortality rates. This condition can arise from various clinical contexts and often accompanies organ dysfunction, particularly cardiovascular impairment. Although addressing the underlying cause is crucial, the role of adjunctive interventions like buffer therapy or renal replacement therapy (RRT) remains debated. This article presents a clinical case to illustrate the diagnostic workup and provides an evidence-based update on current management strategies. It discusses phenotyping metabolic acidosis, consequences of severe metabolic acidemia, and available therapeutic strategies in the ICU. Buffers to mitigate acidemia in certain patients and the pros and cons of sodium bicarbonate (HCO3-) infusion vs RRT are considered. A tailored approach, considering sodium HCO3- use to raise and maintain blood pH to > 7.20 in some patients, potentially delaying or avoiding RRT, may be useful. However, the optimal dose and duration of sodium HCO3- infusion remain unestablished, and further research is needed to refine decision-making processes in managing severe metabolic acidosis.
