The research focused on 102 infants with congenital pulmonary airway malformation, or CPAM, a developmental lung abnormality characterized by adenomatous overgrowth of the terminal bronchioles. CPAM accounts for roughly 40 percent of pediatric thoracoscopic lobectomies, making these infants a well-defined and clinically important population. All of the children, aged between birth and twelve months, underwent elective thoracoscopic lung resection between January 2022 and February 2025. After excluding nine patients for reasons including incomplete data, abandonment of one-lung ventilation, conversion to open surgery, or postoperative intensive care transfer, the researchers analyzed 93 infants divided into two groups based on the ventilator strategy actually delivered during surgery.

The dividing line between the groups was positive end-expiratory pressure, or PEEP, the pressure maintained in the airways at the end of each breath to keep the tiny air sacs of the lungs from collapsing. One group received a conventional fixed PEEP of 5 centimeters of water throughout one-lung ventilation, a standard choice in anesthetic practice meant to maintain basic alveolar recruitment. The other group received individualized PEEP titration guided by dynamic lung compliance, a physiological parameter that reflects the elasticity of lung tissue and the resistance of the airways. Compliance-guided titration works on a straightforward principle: the anesthesiologist increases PEEP step by step and measures how easily the lungs inflate at each level, then selects the lowest pressure at which compliance reaches its maximum, indicating optimal alveolar recruitment without overdistension.

The titration protocol was meticulous. After lung recruitment maneuvers, infants in the protocol-guided group started at zero PEEP, and the pressure was increased by 1 centimeter of water every ten respiratory cycles up to a maximum of 10 centimeters of water. At each step, dynamic compliance was calculated as the delivered tidal volume divided by the difference between peak airway pressure and PEEP. The pressure level yielding the highest compliance was then maintained for the remainder of one-lung ventilation. In practice, this individualized approach settled on a mean PEEP of about 7.1 centimeters of water, notably higher than the fixed 5 centimeters of water used in the conventional group. Ventilation itself followed a volume-controlled protocol with an inspired oxygen concentration of 0.5, a fresh gas flow of 2 liters per minute, and tidal volumes of 6 milliliters per kilogram during single-lung phases, with a bronchial blocker positioned under bronchoscopic guidance to isolate the operative lung.

The intraoperative results revealed a clear physiological advantage for the compliance-guided strategy. Using repeated-measures analysis of variance with group-by-time interaction as the principal inferential test, the researchers found significant differences in dynamic compliance, the ratio of arterial oxygen partial pressure to inspired oxygen fraction, and the alveolar-arterial oxygen gradient, a sensitive marker of gas exchange efficiency. At the measurement points thirty and sixty minutes after PEEP was established, compliance-guided infants showed substantially higher lung compliance, better oxygenation ratios, and smaller oxygen gradients than those on fixed PEEP. Notably, these benefits persisted even fifteen minutes after both lungs were returned to shared ventilation, suggesting that the individualized pressure settings had left the lungs in a better functional state. Crucially, heart rate, mean arterial pressure, and plateau pressure showed no significant between-group differences, indicating that the improved gas exchange came without hemodynamic cost.

The study’s primary outcome, however, lay beyond the operating room. The researchers turned to the Nursing Activities Score, or NAS, a validated instrument originally proposed by Miranda and colleagues in 2003 and tested across 99 intensive care units in 15 countries. The scale comprises 23 items that together estimate the percentage of a nurse’s time devoted to direct patient care over a 24-hour period, with a total score of 100 percent representing the work of one full-time nurse. Prior multicenter work has shown that NAS can account for 75 to 90 percent of the actual workload of intensive care nurses. In this study, attending PACU nurses prospectively recorded NAS for every infant throughout the recovery stay, with all 23 items applicable and no missing data.

The findings were striking. In the unadjusted analysis, infants managed with compliance-guided PEEP had a mean NAS of 24.10 points compared with 27.99 points in the conventional group, a difference of 3.89 points. After statistical adjustment for age, sex, body mass index, American Society of Anesthesiologists physical status, lesion laterality, and duration of one-lung ventilation, the adjusted mean difference remained significant at 3.75 points, with a 95 percent confidence interval spanning from 6.44 down to 1.07 points and a p-value of 0.007. The overall regression model was statistically significant, and no problematic collinearity was detected among the covariates. Although the minimal clinically important difference for NAS in a pediatric recovery unit has not been formally established, the authors interpret this difference as suggesting a genuinely lower observed nursing workload, encompassing reduced demands for monitoring, repositioning, medication administration, fluid management, and emergency resuscitation.

Supporting secondary outcomes reinforced the picture. Infants in the compliance-guided group were extubated roughly 3.3 minutes sooner on average and spent about 5.3 fewer minutes in the PACU, both differences statistically significant. Most notably, the composite rate of recorded adverse events, defined a priori as any occurrence of laryngospasm, coughing, hypoxemia, nausea and vomiting, or bradycardia, was 6.5 percent in the compliance-guided group versus 23.4 percent in the conventional group, an odds ratio of 0.23 with a Fisher’s exact p-value of 0.040. Hypoxemia, defined as oxygen saturation below 90 percent, was recorded in one infant in the guided group compared with six in the conventional group, though this individual comparison did not reach statistical significance given the small numbers. Measures of emergence delirium using the Paediatric Anaesthesia Emergence Delirium scale and pain using the FLACC scale showed no significant differences, nor did the need for propofol or pentazocine rescue medication. Postoperative hospital stay trended about 1.1 days shorter in the guided group but did not reach significance.

Exploratory subgroup analyses across age, lesion location, and duration of one-lung ventilation found no statistically significant heterogeneity in the association, with all interaction p-values exceeding 0.05, hinting that the benefit may be broadly consistent across these patient characteristics. The authors are careful, however, to frame their conclusions within the study’s limitations. The retrospective, single-center design and modest sample size mean residual and unmeasured confounding cannot be excluded. Post-exposure exclusions may have introduced selection bias, and a formal sensitivity analysis was not feasible because so few events occurred. The NAS instrument itself was developed for intensive care settings, and its validity in the infant recovery room remains uncertain, while total scores may also be influenced by the length of the PACU stay itself. Sparse adverse events and subgroup comparisons were underpowered, and the confidence interval around the adjusted NAS difference was relatively wide.

Even with those caveats, the study offers a compelling glimpse of how a physiological measurement made at the bedside of an anesthetized infant can echo through the entire perioperative journey. By tailoring PEEP to each child’s own lung mechanics rather than applying a one-size-fits-all pressure, anesthesiologists may achieve more homogeneous alveolar recruitment, less ventilation-perfusion mismatch, and a reduced risk of ventilator-induced lung injury, and the downstream effects appear to include smoother recoveries, fewer complications, and lighter nursing burdens in the critical first hour after surgery. The authors describe their findings as hypothesis-generating and call for confirmation in prospective studies, but the message for perioperative teams is clear: the ventilator settings chosen in the operating room may be among the most powerful determinants of what unfolds in the recovery unit, and individualizing them could transform care for the smallest surgical patients.

Subject of Research: Compliance-guided positive end-expiratory pressure during one-lung ventilation in infants and its association with post-anaesthesia care unit nursing workload and recovery outcomes

Article Title: Association Between Cdyn‐Guided PEEP and Nursing Activities During PACU Recovery in Infants Undergoing One‐Lung Ventilation: A Retrospective Observational Cohort Study

Article References: Hao, M., Zhang, B., Han, Y., Zhao, C., Dong, Z., & Song, B. (2026). Association Between Cdyn‐Guided PEEP and Nursing Activities During PACU Recovery in Infants Undergoing One‐Lung Ventilation: A Retrospective Observational Cohort Study. Nursing Open, 13(10), Article e70935. https://doi.org/10.1002/nop2.70935

Image Credits: AI Generated

DOI: 10.1002/nop2.70935

Keywords: one-lung ventilation, PEEP titration, dynamic lung compliance, infants, thoracoscopic surgery, PACU, Nursing Activities Score, lung-protective ventilation, congenital pulmonary airway malformation, pediatric anesthesia, oxygenation, adverse events

The new report, published in BMC Pediatrics, describes a retrospective single-center case series of seven children with pediatric acute respiratory distress syndrome, or PARDS, who also had acute kidney injury. In each case, the clinicians integrated extracorporeal carbon dioxide removal, known as ECCO₂R, into a CRRT circuit that had already been indicated for kidney support. Rather than adding a second large-bore extracorporeal circuit dedicated solely to lung support, the team adapted the existing blood purification circuit so that it could also strip carbon dioxide from the bloodstream. The study was retrospectively registered in the German Clinical Trials Register as DRKS00038799.

The physiological logic behind the technique is straightforward but demanding in practice. ECCO₂R works by passing blood through a gas exchanger, essentially an artificial membrane lung, where a controlled flow of oxygen sweeps carbon dioxide across the membrane and out of the blood. The removed CO₂ is then vented away, and the blood returns to the patient with a lower carbon dioxide tension. Because carbon dioxide diffuses through membranes far more readily than oxygen does, meaningful CO₂ clearance can be achieved at blood flows far lower than those required for full extracorporeal membrane oxygenation, or ECMO. In adults, this has made ECCO₂R attractive as a way to permit ultra-lung-protective ventilation, in which tidal volumes and airway pressures are driven down to minimize ventilator-induced lung injury while the artificial circuit takes over the burden of CO₂ elimination.

In children, however, the technique has remained largely unexplored territory. Pediatric patients have smaller blood volumes, lower cardiac outputs, and narrower vascular access, all of which complicate the extracorporeal circuits designed primarily for adults. The Freiburg team’s insight was that children who need both lung support and kidney support could, in principle, have both delivered through a single circuit. CRRT machines already circulate blood continuously through an extracorporeal loop; adding a gas exchanger in that loop converts the circuit into a dual-purpose organ support system without the need for additional large-bore cannulation.

To assess how this played out in practice, the researchers analyzed the first treatment episode for each of seven patients treated between November 2023 and November 2025, restricting the principal analysis to one episode per patient to avoid the statistical problems that arise when repeated observations from the same child are treated as independent. The children had a median age of 12 years, with an interquartile range of 6 to 14 years. ECCO₂R was delivered at a median blood flow of 270 milliliters per minute, with an interquartile range of 100 to 300 milliliters per minute. That flow corresponds to roughly 9 percent of the estimated cardiac output, with an interquartile range of 6 to 20 percent, a strikingly modest fraction compared with the much higher flows typical of ECMO.

The physiological results, analyzed with Friedman tests for longitudinal change, showed statistically significant improvements across all predefined principal outcomes. Median arterial carbon dioxide tension, or PaCO₂, fell by 10 millimeters of mercury within the first 24 hours, with an interquartile range of −27 to −3 millimeters of mercury. Peak inspiratory pressure dropped by a median of 11 millibars, driving pressure by 9 millibars, and tidal volume by 1.6 milliliters per kilogram of body weight. Each of these shifts points in the direction that lung-protective ventilation strategies aim for: less pressure, less stretch, less stress on injured lung tissue, achieved while carbon dioxide was being cleared extracorporeally rather than by aggressive ventilator settings.

On the safety front, the picture was cautiously reassuring but not unblemished. The investigators found no predefined major bleeding events, no clinically apparent hemolysis, no thromboembolic complications, and no device-related infections attributable to the integrated ECCO₂R-CRRT approach. The main complication observed was circuit clotting requiring circuit exchange, which occurred in two of the seven patients. Four of the seven children were successfully weaned from ECCO₂R during their treatment course. For a first-in-children application of an adapted circuit, these figures suggest that the approach can be delivered without an outsized burden of extracorporeal complications, though the small sample size and retrospective design make it impossible to draw firm conclusions about true event rates.

The authors are careful to frame their findings as hypothesis-generating rather than as evidence of treatment efficacy or device safety. This is a retrospective, uncontrolled, single-center case series with seven patients in the principal analysis, and the observed improvements in PaCO₂ and ventilatory pressures are temporally associated with ECCO₂R initiation rather than causally attributable to it. Children with PARDS and AKI are a heterogeneous group, and natural disease evolution, changes in sedation, adjustments in ventilator strategy, and concurrent therapies could all contribute to the measured changes. Still, the consistency of the physiological signal across multiple outcomes, and the fact that it emerged in a real-world pediatric intensive care setting rather than a highly controlled research protocol, gives the findings practical weight.

The study also highlights the interdisciplinary machinery required to make such an approach work. The authors specifically acknowledge the dialysis nursing team, the Division of Pediatric Nephrology, and the nursing staff of the Pediatric Intensive Care Unit at the Medical Center – University of Freiburg, noting that their expertise and dedication were essential to successful implementation. They also thank the family of the first child treated with integrated ECCO₂R-CRRT at the institution for supporting publication of the experience. The research received no dedicated financial support, with open access funding organized through Projekt DEAL, and the authors declare no competing interests.

Looking ahead, the Freiburg team argues that prospective multicenter studies are needed to define patient selection criteria, anticoagulation strategies, weaning protocols, and the broader role of integrated ECCO₂R-CRRT within pediatric extracorporeal respiratory support. If those questions can be answered, the approach could offer a pragmatic middle ground for carefully selected children who need both kidney and lung support, avoiding the cannulation burden and complexity of full ECMO while still relieving the ventilator of some of its most dangerous demands. For now, the message is one of cautious optimism: a technique borrowed from adult critical care, adapted to the constraints of pediatric physiology and existing dialysis infrastructure, appears technically feasible and physiologically promising in a small, carefully selected cohort.

Subject of Research: Extracorporeal carbon dioxide removal integrated into continuous renal replacement therapy for pediatric acute respiratory distress syndrome

Article Title: Extracorporeal carbon dioxide removal integrated into continuous renal replacement therapy in pediatric patients with ARDS: a retrospective single-center case series

Article References: Kuntz, M., Matheisl, D., Schüle, I., Klotz, D., Fuchs, H., & Schneider, H. (2026). Extracorporeal carbon dioxide removal integrated into continuous renal replacement therapy in pediatric patients with ARDS: a retrospective single-center case series. BMC Pediatrics, 26(1), Article 860. https://doi.org/10.1186/s12887-026-07656-y

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07656-y

Keywords: ECCO2R, continuous renal replacement therapy, pediatric ARDS, acute kidney injury, lung-protective ventilation, pediatric critical care, extracorporeal membrane oxygenation, carbon dioxide removal, case series, pediatric intensive care, ventilator pressures, BMC Pediatrics

ARDS arises from a heterogeneous set of inciting injuries—pneumonia, sepsis, aspiration, trauma—and produces its hallmark consequences of profound hypoxemia and diffuse lung damage through multiple, overlapping biological pathways. The alveolar-capillary barrier breaks down, protein-rich fluid floods the airspaces, and inflammation cascades across the lung parenchyma. Despite a new global definition of the syndrome published in 2024 and decades of research into targeted therapies, from corticosteroids to statins to interleukin-6 inhibitors, no pharmacological treatment has definitively reversed the underlying injury. What has saved lives is meticulous supportive care: lung-protective mechanical ventilation with low tidal volumes, appropriate positive end-expiratory pressure, attention to driving pressure and mechanical power, and, in selected patients, prone positioning and neuromuscular blockade. Sedation sits at the heart of that supportive framework, because mechanically ventilated patients with ARDS typically require deep sedation to tolerate the ventilator and to avoid self-inflicted lung injury from vigorous, asynchronous breathing efforts.

It is precisely here that volatile anesthetics promised something special. According to the review, these agents were proposed to achieve two aims simultaneously: they could provide effective, titratable sedation while also protecting against inflammatory lung injury. Preclinical work has been remarkably rich. Experimental studies have shown that volatile agents modulate immune cell function, dampen the release of inflammatory mediators, preserve the integrity of epithelial tight junctions that hold the alveolar barrier together, and promote alveolar epithelial wound healing. More recent laboratory work suggests prolonged antibacterial, anti-inflammatory, and surfactant-promoting effects, and in vitro studies have explored how sevoflurane, propofol, and opioids differentially shape the endothelial proinflammatory response. In surgical populations, meta-analyses have examined whether volatile anesthesia reduces postoperative pulmonary complications compared with total intravenous anesthesia, with results that kept the lung-protective hypothesis alive.

The respiratory effects of volatile agents added a second layer of appeal. Unlike most intravenous sedatives, sevoflurane and isoflurane are bronchodilators, which has made them a rescue therapy for life-threatening status asthmaticus when conventional treatment fails. Even more intriguingly, animal studies suggest that volatile anesthetics interact with central respiratory chemoreceptor neurons in ways that help maintain breathing drive during anesthesia—activating leak sodium conductances in retrotrapezoid nucleus neurons and modulating background potassium currents. For ARDS patients, preserving respiratory drive matters enormously. Deep intravenous sedation with propofol or midazolam suppresses spontaneous breathing, which can be protective in the earliest phase of lung injury but becomes a liability later, contributing to diaphragm atrophy and prolonged ventilation. The concept of lung-protective and diaphragm-protective sedation—precision sedation that balances patient effort against ventilator-induced injury—has become a major research frontier, and volatile agents were seen as natural candidates for it.

Early clinical data seemed to vindicate the enthusiasm. A randomized controlled pilot study published in 2017 by Jabaudon and colleagues found that sevoflurane sedation in ARDS patients reduced inflammatory mediators and improved oxygenation. Observational and feasibility studies explored whether volatile sedation could allow spontaneous breathing even during prone positioning or continuous lateral rotational therapy—situations where conventional sedation typically demands paralysis or deep unconsciousness. A large phase III non-inferiority trial in Germany and Slovenia compared inhaled isoflurane, delivered via an anesthetic conserving device, with propofol in invasively ventilated ICU patients and found the inhaled approach a viable alternative. Substudies examined the physiology in detail, including whether the devices used to deliver volatile agents add dead space that increases mechanical power, with recent work suggesting that low dead space reflectors do not increase mechanical power compared with standard heat and moisture exchangers.

Then came the trial that changed the conversation. The SESAR randomized clinical trial, published in JAMA in 2025 by Jabaudon and colleagues, enrolled patients with moderate-to-severe ARDS and compared inhaled sevoflurane sedation with standard intravenous propofol. The results ran counter to expectations: sevoflurane sedation reduced ventilator-free days at day 28 and increased mortality compared with propofol. For a field that had spent years building the mechanistic case for inhaled lung protection, the finding was a genuine shock. The review’s authors treat the result with appropriate seriousness, and it anchors their central recommendation: pending further high-quality data suggesting benefit, routine clinical use of volatile ICU sedation in ARDS is currently not recommended outside of clinical trials.

Why might a therapy with such compelling biology fail in the clinic? The review points to several open questions that future research must resolve. Dose is one: the concentrations of sevoflurane used for prolonged ICU sedation may differ meaningfully from the exposures that showed benefit in experimental models, and the therapeutic window between anti-inflammatory protection and harm remains poorly mapped. Agent selection is another—sevoflurane and isoflurane have distinct pharmacological profiles, and results with one cannot simply be extrapolated to the other. Duration of sedation is a third variable; the timing and length of volatile exposure could determine whether the drug protects or injures the healing lung. Perhaps most tantalizing is the question of heterogeneity of treatment effect across ARDS sub-phenotypes. ARDS is not one disease but a syndrome with inflammatory and non-inflammatory biological clusters, and a therapy that dampens inflammation might help hyperinflammatory patients while harming others. Precision-medicine approaches that stratify patients by sub-phenotype could yet rescue the volatile hypothesis.

The trial landscape remains active, even if no ongoing or recently completed studies are being conducted solely in ARDS patients. The SAVE-ICU trial is enrolling patients with COVID-19 and non-COVID-19 acute hypoxemic respiratory failure. The French INASED trial is testing inhaled sedation more broadly in the ICU. The INSPiRE-ICU1 and INSPiRE-ICU2 trials, sponsored by Sedana Medical and led from North American centers, are comparing inhaled sedation with propofol in respiratory failure. A 2025 meta-analysis of randomized trials of volatile sedation in mechanically ventilated critically ill adults, along with a 2026 systematic review focused specifically on inhaled versus intravenous sedation in ARDS, will help synthesize the accumulating evidence. Beyond efficacy, practical considerations loom: delivery devices add circuit complexity, environmental concerns about anesthetic gas emissions are mounting, and drug shortages have at times made inhaled sedation an unexpectedly useful fallback.

The story of volatile anesthetics in ARDS is, in the end, a story about how modern critical care science works. Mechanistic plausibility, preclinical elegance, and promising pilot data are necessary but not sufficient; only large, well-designed randomized trials can establish whether a therapy helps or harms. The SESAR trial delivered an unwelcome answer for sevoflurane in moderate-to-severe ARDS, and the review’s authors have responded not by abandoning the idea but by sharpening the questions—dose, agent, duration, and patient sub-phenotype—that will determine whether inhaled sedation earns a place in the ARDS armamentarium. For now, patients with ARDS should receive sedation according to established guidelines, and volatile agents should remain within the boundaries of clinical trials. The lungs of the sickest patients depend on that discipline, and the next generation of trials will tell us whether the operating room’s most trusted anesthetics can ever make the same claim in the intensive care unit.

Subject of Research: Volatile anesthetic sedation as a potential lung-protective therapy in acute respiratory distress syndrome

Article Title: Volatile anesthetic sedation in acute respiratory distress syndrome

Article References: O’Gara, B., Boncyk, C., Müller Wirtz, L. M., Molano Franco, D., Kotani, Y., Landoni, G., Jerath, A., L’Her, E., Bellgardt, M., Becher, T., Beck-Schimmer, B., Beitler, J. R., Constantin, J. M., Hughes, C. G., Meiser, A., & Jabaudon, M. (2026). Volatile anesthetic sedation in acute respiratory distress syndrome. Intensive Care Medicine. https://doi.org/10.1007/s00134-026-08613-0

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08613-0

Keywords: acute respiratory distress syndrome, volatile anesthetics, sevoflurane, isoflurane, ICU sedation, mechanical ventilation, lung injury, inflammation, SESAR trial, propofol, lung-protective ventilation, critical care

The review’s central reframing is subtle but consequential. Historically, adjuvant therapies were held back as rescue strategies, deployed only when refractory hypoxemia left clinicians with no other options. Current guidelines, by contrast, recommend applying them earlier in the disease course, reflecting the importance of minimizing stress and strain on the injured lung and potentially modulating the immune dysregulation that drives the syndrome. The authors organize commonly used adjuvants not by fashion or habit, but by the relative certainty of their utility and the frequency of their use—a taxonomy that reveals an uncomfortable truth: how often a therapy is used does not always match how well the evidence supports it.

At the top of the evidence hierarchy sits prone positioning, one of the most effective non-pharmacologic strategies for reducing mortality in moderate-to-severe ARDS. Its benefits extend well beyond improved oxygenation. Turning a patient face-down redistributes transpulmonary pressures more homogeneously across the lung, reduces overdistension of dorsal regions, recruits collapsed dependent lung tissue, and mitigates ventilator-induced lung injury. The PROSEVA trial demonstrated a substantial mortality reduction when prone positioning was applied early and for prolonged sessions in severe ARDS, and subsequent meta-analyses confirmed the benefit was greatest when it was combined with low-tidal-volume ventilation and sustained for more than sixteen hours per session. Despite this strong evidence and guideline endorsement, real-world adoption remains inconsistent, hampered by logistical demands and variability in clinician familiarity—a gap the authors describe as both common and serious.

Continuous neuromuscular blockade occupies a more contested middle ground. The physiological rationale is compelling: paralytic agents halt patient–ventilator dyssynchrony, eliminate excessively forceful spontaneous breathing efforts that can themselves injure the lung, control transpulmonary pressures, and reduce oxygen consumption. The ACURASYS trial showed improved survival and less barotrauma with a 48-hour course of early neuromuscular blockade in patients with moderate-to-severe but persistent ARDS. But the later ROSE trial, which applied the drugs slightly earlier in the disease course, found no mortality benefit. The discrepancy may reflect evolving practice—ROSE was conducted amid lighter sedation and higher PEEP, which may have blunted the incremental value of paralysis—or the fact that ACURASYS enrolled patients slightly later, enriching the study population for persistent, harder-to-treat disease. Current guidance favors short-course, targeted use, balanced against the risks of diaphragmatic inactivity and ICU-acquired weakness.

Conservative fluid management tells a different kind of story: modest evidence, near-universal adoption. Pulmonary edema worsens hypoxemia, decreases lung compliance, and amplifies ventilator-induced injury, so draining excess fluid with diuretics—or occasionally renal replacement therapy—directly supports the goals of lung-protective ventilation. The FACTT trial found that a conservative fluid strategy improved oxygenation, shortened the duration of mechanical ventilation, and reduced ICU length of stay, though it produced no mortality benefit. Even without a survival signal, the approach has become standard supportive care, fitting neatly into a broader philosophy of de-resuscitation: meticulous fluid stewardship for critically ill patients who have already received aggressive resuscitation, regardless of whether they carry an ARDS diagnosis.

Corticosteroids, meanwhile, have ridden decades of enthusiasm and disappointment. By attenuating the inflammatory cascade underlying ARDS, steroids promise reduced alveolar inflammation and less fibroproliferation. Recent trials and meta-analyses suggest early corticosteroids may shorten mechanical ventilation and ICU stays, particularly when initiated early in moderate-to-severe disease, and the COVID-19 pandemic cemented dexamethasone as standard care for severe hypoxemic viral pneumonia. Yet uncertainty persists over optimal dosing, duration, and applicability across etiologies. In late-phase ARDS, the evidence is mixed at best: an early trial of prolonged methylprednisolone in unresolving disease was followed by a larger study that failed to replicate a mortality benefit and raised a late mortality signal when treatment began more than fourteen days after ARDS onset. The authors conclude that steroids are best considered a phenotype-dependent therapy rather than a universally effective one, with trial heterogeneity likely reflecting biological differences among patients rather than absent efficacy.

Then there are the therapies that persist despite thin evidence. Inhaled pulmonary vasodilators—nitric oxide and epoprostenol—offer an elegant physiological fix for severe hypoxemia, selectively directing blood flow toward better-ventilated alveoli and reducing pulmonary vascular resistance. Studies consistently show transient oxygenation improvements, but none has demonstrated a mortality benefit, and harms such as renal dysfunction are documented. Guidelines do not recommend routine use. Nevertheless, inhaled vasodilators remain widely employed as short-term bridges to prone positioning, transfer, or escalation to extracorporeal support, and they may ease right ventricular afterload in acute cor pulmonale, though that indication has never been tested in randomized trials. Their persistence, the authors note, embodies the recurring tension between immediate physiological rescue and outcome-based evidence.

The deeper message of the review is that the right question is no longer whether an adjuvant works, but which therapy should be applied, in which patient, at what stage of disease, and to achieve which physiological objective. Timing matters as much as selection: prone positioning early and for long sessions in severe disease, neuromuscular blockade selectively when dyssynchrony and injurious breathing efforts dominate, fluids tightened once resuscitation is complete, steroids matched to inflammatory phenotype and etiology. The authors propose a framework mapping each adjuvant onto the evolving phases of ARDS, treating the syndrome as a moving target rather than a static diagnosis. Static classification at the bedside, they suggest, may ultimately matter less than dynamic reassessment throughout the illness.

Looking forward, the future of adjuvant therapy may be defined less by discovering new drugs than by deploying existing ones better. Advances in phenotyping—biological, physiological, and imaging-based—could identify which patients benefit from which interventions. The hyperinflammatory and hypoinflammatory subphenotypes described by Calfee and colleagues have already shown differential responses to several therapies, suggesting treatment effect varies with host biology rather than the syndrome label alone. Physiological phenotyping—respiratory mechanics, recruitability, respiratory drive, right ventricular function—may sharpen selection further. Equally important, the authors argue, is a willingness to de-adopt therapies lacking a strong evidence base. Adjuvants, they conclude, should not be regarded as rescue therapies of last resort but as targeted tools applied thoughtfully within a broader lung-protective strategy. The goal is deceptively simple to state and hard to achieve: the right adjuvant, for the right patient, at the right time.

Subject of Research: Adjuvant therapies for acute respiratory distress syndrome across the course of the disease

Article Title: Beyond the ventilator: deploying adjuvant therapies across the course of ARDS

Article References: Munshi, L., Rubenfeld, G., & Wunsch, H. (2026). Beyond the ventilator: deploying adjuvant therapies across the course of ARDS. Intensive Care Medicine, 52(9), 2026-2030. https://doi.org/10.1007/s00134-026-08594-0

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08594-0

Keywords: ARDS, mechanical ventilation, prone positioning, neuromuscular blockade, corticosteroids, conservative fluid management, inhaled pulmonary vasodilators, lung-protective ventilation, phenotyping, critical care, ventilator-induced lung injury, intensive care medicine