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Background: The optimal target for partial pressure of arterial carbon dioxide (PaCO₂) remains uncertain in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) following out-of-hospital cardiac arrest (OHCA).

Research question: Are PaCO₂ levels associated with functional outcomes in patients receiving VA-ECMO after OHCA?

Study design: and Methods: This multicenter, registry-based observational study, conducted from 2014 to 2020, included non-traumatic adult OHCA patients on VA-ECMO with PaCO₂ levels measured within six hours of initiation (initial PaCO₂ set) and at 18-30 hours post-initiation (24-hour PaCO₂ set). PaCO₂ levels were categorized into five groups: hypocapnia (<30 mmHg), low normocapnia (30-<40 mmHg), high normocapnia (40-<50 mmHg), mild hypercapnia (50-<60 mmHg), and moderate to severe hypercapnia (≥60 mmHg). The primary outcome was the favorable functional outcome at 30 days, analyzed using multivariable logistic regression. PaCO₂ trajectories from initial to 24-hour levels were also explored.

Results: A total of 1,454 and 572 patients were analyzed in the initial and 24-hour PaCO₂ sets, respectively. Compared to high normocapnia, low normocapnia was associated with worse functional outcomes in both initial and 24-hour PaCO₂ analyses, with adjusted odds ratios of 0.59 (95% CI, 0.38-0.89) for initial low normocapnia and 0.56 (95% CI, 0.33-0.95) for 24-hour low normocapnia. Other categories were similarly associated with worse functional outcomes in both PaCO₂ analyses. In exploratory analyses, trajectories ending in high normocapnia demonstrated higher proportions of the favorable functional outcome than those ending in low normocapnia, regardless of initial PaCO₂ levels.

Interpretation: In non-traumatic adult OHCA patients on VA-ECMO, high normocapnia was associated with better functional outcomes than low normocapnia in both initial and 24-hour PaCO₂ analyses. These findings suggest a hypothesis that maintaining high normocapnia levels, irrespective of initial PaCO₂, may improve functional outcomes for patients on VA-ECMO after OHCA.

Background: Ventilator-associated pneumonia (VAP) rates are higher in low- and middle-income countries (LMICs) than in high-income countries (HICs).

Research question: Could differences in ventilator bundle adherence, ventilation practices, and critical care staffing be driving variations in VAP risk between LMICs and HICs?

Study design and methods: This secondary analysis of the multicenter, international CERTAIN study included mechanically ventilated patients at risk for VAP from eleven LMICs and five HICs. We included oral care, head-of-bed elevation, spontaneous breathing assessments, and sedation breaks in the ventilator bundle. Staffing was assessed by the number of physicians and nurses per bed. Multivariable analyses were adjusted for severity, baseline characteristics, and checklist implementation. The primary outcome was VAP development.

Results: Among 2,253 patients, 1,755 were from LMICs and 498 from HICs. Compared to HICs, patients from LMICs were younger, had lower comorbidity burden, and were less severely ill. Lower country income level was independently associated with VAP development (aOR 2.11; 95% C.I., 1.37-3.24). Ventilator bundle adherence was not significantly associated with VAP. Increased total duration of ventilation was associated with an increased risk of VAP (aOR 1.04; 95% C.I., 1.03-1.05), while higher nursing (aOR 0.88; 95CI 0.79-0.98) and physician staffing ratios (aOR 0.69; 95% C.I., 0.50-0.87) were associated with lower VAP rates.

Interpretation: Patients in LMICs have a twofold higher risk of VAP, independent of bundle adherence. Prolonged mechanical ventilation was an independent predictor of VAP, while higher staffing ratios were associated with decreased risk for VAP development. Unmeasured factors like infrastructure and infection control practices may explain the higher VAP rates in LMICs.

Background: Pulmonary rehabilitation (PR) is a beneficial intervention for people with interstitial lung disease (ILD), however the effect of PR on survival is unclear. This study compared the survival outcomes in people with ILD who were allocated to PR versus those who were allocated to control in two published randomised controlled trials (RCTs).

Research question: Does participation in PR impact survival among people with ILD?

Study design and methods: The combined data from the two previous RCTs of PR in ILD were included. Time from start of PR until date of death, lung transplantation or censoring was calculated. Kaplan-Meir and Cox proportional hazard regression analysis were used to assess the impact of PR on survival. Baseline variables of age at time of PR, gender, FVC, 6-minute walk distance (6MWD), exertional nadir SpO₂ and diagnosis of idiopathic pulmonary fibrosis (IPF) were included as covariates.

Results: Of the 182 participants with ILD (87 IPF, 109 males, mean (SD) age 69(10), FVC%pred 76(19), TLCO%pred 48(16)), death occurred in 62%, 6% were transplanted, 20% were alive and 12% were lost to follow-up. Median survival for those who completed PR was 6.1 years (95% CI 4.4 to 7.9) compared to 4.7 years (95%CI 3.4 to 6.0) for those in the control group, however this was not significantly different (log rank p=0.7). After adjusting for baseline variables, at 5 years, completion of PR was associated a 44% lower risk of mortality (HR 0.56 (0.36-0.88), p=0.01). At 10 years, no difference in survival was observed between the PR and control group.

Interpretation: Participation in PR among people with ILD may impact survival at 5 years. Along with clinical improvements following PR, the potential for a survival benefit further strengthens the importance of PR in the standard care of people with ILD.

Background: Airway management is a critical component of the care of patients experiencing cardiac arrest, but data from randomized trials on the use of video vs direct laryngoscopy for intubation in the setting of cardiac arrest are limited. Current AHA guidelines recommend placement of an endotracheal tube either during CPR or shortly after return of spontaneous circulation but do not provide guidance around intubation methods, including the choice of laryngoscope.

Research question: Does use of video laryngoscopy improve the incidence of successful intubation on the first attempt, compared to use of direct laryngoscopy, among adults undergoing tracheal intubation after experiencing cardiac arrest?

Study design and methods: This secondary analysis of the Direct versus Video Laryngoscope (DEVICE) trial compared video laryngoscopy versus direct laryngoscopy in the subgroup of patients who were intubated following cardiac arrest. The primary outcome was the incidence of successful intubation on the first attempt. Additional outcomes included the duration of laryngoscopy.

Results: Among the 1,417 patients in the DEVICE trial, 113 (7.9%) had experienced cardiac arrest prior to intubation, of whom 48 were randomized to the video laryngoscopy group and 65 to the direct laryngoscopy group. Successful intubation on the first attempt occurred in 40 of 48 patients (83.3%) in the video laryngoscopy group and 42 of 65 patients (64.6%) in the direct laryngoscopy group (absolute risk difference, 18.7 percentage points; 95% confidence interval [CI], 1.2 to 36.2; P = 0.03). The mean duration of laryngoscopy was 48.0 seconds (standard deviation [SD], 37.3 seconds) in the video laryngoscope group and 98.0 seconds (SD, 122.4) in the direct laryngoscopy group (mean difference, -50.0; 95% CI, -86.8 to -13.3, P = 0.004).

Interpretation: Among adults undergoing tracheal intubation after experiencing cardiac arrest, use of video laryngoscopy was associated with increased incidence of successful intubation on the first attempt and shortened duration of laryngoscopy, compared to use of direct laryngoscopy.

Background: Delirium is a common and serious syndrome of acute brain dysfunction associated with negative outcomes. Melatonin may have a role in delirium prevention for critically ill adults based on data from non-critically ill patient populations. Our objective was to assess the feasibility of a multi-centre, randomized, placebo-controlled trial testing the hypothesis that low-dose melatonin prevents delirium in critically ill adults.

Methods: We conducted this three-arm feasibility trial in three tertiary academic ICUs. Included participants were ≥18 years old, confirmed free from delirium at enrollment, and anticipated >48 hours intensive care unit (ICU) stay. We randomized participants to nightly melatonin 0.5mg or 2mg or placebo. Feasibility outcomes were protocol adherence and recruitment rates. Our primary feasibility target was ≥85% (±5% margin of error) of drug doses administered as per protocol. Secondary objectives were to explore adverse drug effects, melatonin pharmacokinetics, and clinical outcomes.

Results: We screened 2259 patients, excluding 1863 (82.5%), resulting in 396 eligible patients, of whom 71 consented; recruitment rate 0.8 patients/month/site. Median (IQR) age was 60.5 (48,67) years; median admission SOFA score 7 (3,10). Percentage drug administration protocol adherence per patient was median 100% (IQR 92.3%, 100%) or mean 88.7% (SD 24.4). There were 25 protocol violations with no differences between groups. Fourteen (20%) patients developed delirium during the study period; 25 (36%) experienced sub-syndromal delirium; no differences between study groups. No serious adverse effects were detected.

Conclusion: Our trial protocol comparing two low doses of melatonin and placebo for delirium prevention in critically ill adults demonstrated feasibility for protocol adherence. However, trial eligibility rates were modest primarily due to delirium being present or the inability to screen. Consent rates were also low. This finding suggests that conducting delirium prevention trials that require delirium to be absent on enrolment is particularly challenging in the ICU.

Background: Changes in body composition, including loss of muscle mass and obesity, adversely affect lung function.

Research question: What is the relationship between lung function, visceral adiposity, and skeletal muscle mass, considering myosteatosis measured using CT scans in middle-aged Korean adults?

Study design and methods: We reviewed 15,827 participants (9,237 men and 6,590 women) with a mean (SD) age of 52.5 (8.3) years who underwent comprehensive health examinations, including abdominal CT imaging and spirometry. Selected CT scans were segmented automatically to quantify total abdominal muscle area (TAMA), visceral fat area (VFA), and subcutaneous fat area. Muscle quality was assessed by categorizing TAMA into 3 regions based on CT scan density: good-quality muscle (normal-attenuation muscle area [NAMA]), fatty muscle (low attenuation muscle area), and intermuscular and intramuscular fat areas. Low lung function was defined as FVC % predicted and FEV₁ < 80% predicted. Standardized residuals for CT scan-derived measurements, adjusted for age and BMI using linear regression, were calculated and stratified into quartiles for lung function comparison. Multivariate logistic regression was used to analyze associations between low lung function and variables.

Results: NAMA was correlated positively with FVC and FEV₁, whereas VFA was correlated negatively with both. In men, low FVC and FEV₁ were associated significantly with lower NAMA and higher VFA. Among women with obesity (BMI ≥ 25 kg/m²), low FVC and FEV₁ were associated significantly with higher VFA and lower NAMA (FVC only); among women without obesity, low FVC and FEV₁ were associated negatively with NAMA.

Interpretation: Lung function was associated significantly with visceral adiposity and skeletal muscle quality, which differed according to sex and BMI. Improving lung function may require tailored management, including reducing visceral fat, enhancing skeletal muscle quality based on CT scan-body composition analysis, or both.

Topic importance: Accurate assessment of a patient's volume status is crucial in many conditions, informing decisions on fluid prescribing, vasoactive agents, and decongestive therapies. Determining a patient's volume status is challenging, due to limitations in examination and investigations and the complexities of fluid homeostasis in disease states. Point-of-care ultrasound (POCUS) is useful in assessing hemodynamic parameters related to volume status, fluid responsiveness, and fluid tolerance. It requires understanding several physiologic concepts to accurately interpret and integrate POCUS findings into volume-related clinical decision-making.

Review findings: The following concepts serve as a scaffold for a comprehensive volume status assessment: central venous pressure, right heart function, left heart assessment, extravascular volume, and venous congestion. POCUS allows us access to these hemodynamic and structural data points as an extension and refinement of the physical exam. Often, multiple POCUS applications are employed, and findings must be integrated with the rest of the clinical evaluation. We illustrate this using three common scenarios: hypotension, hypoxia, and acute kidney injury. Clinicians must be aware of the strengths and weaknesses of findings in different physiologic states, and potential pitfalls of image acquisition and interpretation. Further studies are necessary to determine the benefits and clinical outcomes of a POCUS-directed volume status assessment.

Summary: Volume status assessment is ubiquitous, yet challenging to perform. This review summarizes foundational physiologic concepts relevant to volume status evaluation, and highlights how multiorgan POCUS informs on hemodynamic parameters that can be combined with the conventional clinical assessment to make fluid-related decisions.