Daily Ards Research Analysis

BACKGROUND: Mechanical power increases with positive end-expiratory pressure (PEEP). However, its injurious potential may depend on the available lung gas volume, which can be modified by alveolar recruitment. We investigated how PEEP-induced recruitment affects mechanical power. METHODS: We analyzed previously collected data on 20 patients with acute respiratory distress syndrome who underwent a decremental PEEP trial (15-5 cmH₂O). End-expiratory lung volume and respiratory mechanics were measured to quantify recruited volume, functional residual capacity (FRC), and the recruitment-to-inflation (R/I) ratio. Absolute power and power normalized to aerated lung volume (FRC + recruited volume) were calculated at each PEEP level. Patients were classified as having higher or lower recruitability according to the cohort median recruited volume accrued between PEEP 5 and 15 cmH₂O, expressed as a fraction of FRC (median 0.42). RESULTS: Absolute mechanical power increased linearly with rising PEEP (approximately + 1 J/min per cmH₂O), from 20 [16-23] J/min at 5 cmH₂O, to 31 [28-33] J/min at 15 cmH₂O, irrespective of recruitability (low recruitability: + 1.12 J/min per cmH₂O, p < 0.001; high recruitability: + 0.96 J/min per cmH₂O, p < 0.001, p for interaction = 0.12). Normalized power increased in patients with lower recruitability (+ 0.43 J/min/L per cmH CONCLUSIONS: Absolute mechanical power increases with higher PEEP, but power per aerated lung decreases when PEEP produces substantial recruitment. PEEP-induced increases in absolute power do not necessarily imply a higher mechanical load per alveolar unit. Recruited volume and compliance changes are the main physiological determinants of this effect. Among bedside tools, the R/I ratio best identifies whether and to what extent PEEP will reduce or increase mechanical power per alveolar unit.

Uterine contractions during labor reduce placental perfusion, which limits fetal oxygenation. Intrapartum fetal hypoxia and acidemia occur when there is insufficient reperfusion time between contractions or when placental dysfunction restricts oxygen transfer. The risks of hypoxic-ischemic injury during labor include intrapartum stillbirth, neonatal death, and neonatal encephalopathy. Emergency cesarean or instrumental deliveries are often required when fetal acidemia is suspected, though these interventions carry increased maternal and neonatal risk. Despite widespread use of electronic fetal heart rate monitoring to detect fetal compromise, rates of cerebral palsy, perinatal mortality, and other neonatal well-being measures have not improved. This highlights the need for more effective strategies to prevent adverse perinatal outcomes related to hypoxic injury. Phosphodiesterase type 5 inhibitors may be used to improve uteroplacental perfusion and enhance vasoconstriction in uterine and spinal arteries. Sildenafil citrate, a PDE5 inhibitor, has been used for indications related to placental dysfunction, to treat maternal hypertension, or both. A previous phase II randomized clinical trial (RCT) found that oral sildenafil reduced operative birth for fetal distress by 51% compared with placebo, but was underpowered to assess perinatal outcomes. The aim of this study was to assess whether oral sildenafil citrate during labor improves perinatal outcomes related to intrapartum hypoxia.The iSEARCH trial was a placebo-controlled, double-blind RCT conducted at 14 Australian hospitals from September 2021 to June 2024. Included were adult women with singleton or dichorionic twin pregnancies attempting vaginal birth at term, either by spontaneous labor or induction of labor. Excluded were those with monochorionic twins, triplets, higher-order multifetal gestation, or severe hepatic or kidney impairment. Also excluded were those taking nitrate-containing medications or other PDE inhibitors. Study participants were randomized 1:1 to receive 50 mg sildenafil citrate or a placebo every 8 hours for a maximum of 3 doses. The primary outcome was a composite of 10 intrapartum or neonatal events, including intrapartum stillbirth, 28-day neonatal death, Apgar score <4 at 5 minutes, acidosis at birth, hypoxic ischemic encephalopathy, neonatal seizure, neonatal respiratory support, admission to the neonatal unit, persistent pulmonary hypertension of the newborn, or meconium aspiration syndrome. Secondary outcomes included the 10 individual primary outcomes and emergency cesarean delivery or instrumental vaginal birth for fetal distress.A total of 3257 women were included in the analysis, with 1626 in the sildenafil citrate group and 1631 receiving placebos. The primary composite outcome occurred in 5.1% of women in the intervention group and 5.2% in the placebo group [relative risk (RR), 1.02; 95% CI, 0.75-1.37]. No cases of infant death occurred. The sildenafil group had no effect on the individual secondary outcomes. There was also no effect on emergency operative birth for fetal distress (RR, 1.12; 95% CI, 0.98-1.29). In conclusion, no differences were observed in the incidence of adverse perinatal outcomes or emergency operative birth between women who received sildenafil citrate or placebo during labor.

Up to 400 million individuals globally are estimated to experience persistent symptoms, including fatigue, muscle pain, and brain fog, following severe acute respiratory syndrome coronavirus type 2 infection. These persistent symptoms are referred to as Post-COVID-19 condition if they last for more than 12 weeks after infection and persist for at least 8 weeks and often causing significant distress and burden. The underlying pathological mechanisms have not yet been fully elucidated. Due to the heterogeneity of the disease a multifactorial origin is highly likely. Overall, evidence on optimal management is limited, and no medication has yet proven to be effective. Current symptom management and treatment guidelines suggest a biopsychosocial perspective and emphasize multidisciplinary approaches. Comprehensive interventions, adequate treatment access, and appropriate resources remain insufficiently available and implementing digital interventions might help mitigate these limitations. This protocol details a single-site feasibility and clinical evaluation study aiming to bridge this gap. By implementing an exploratory, open-label, digital interventional approach this study investigates the feasibility and efficacy of a 12-week program delivered by a cloud-based application. The program consists of 13 modules encompassing a wide range of topics (e.g., energy management, self-care, stress management) and includes informational (e.g., psychoeducational content) and interactive (e.g., exercises, self-reflection diaries) components. Customization options align the material with participant needs. A dedicated feedback section in each module captures feedback regarding usability and feasibility. Participants are monitored and checked for adherence throughout the study. The primary outcome is the post-intervention change in functional capacity measured by the World Health Organization Disability Assessment Schedule 2.0. All participants provide written informed consent. Key results from the study will be published in peer-reviewed journals.