BACKGROUND: The optimal crystalloid for sepsis resuscitation and whether choice should differ under restrictive vs liberal strategy remains uncertain. RESEARCH QUESTION: Do outcomes differ by fluid type within liberal vs restrictive resuscitation strategies? STUDY DESIGN AND METHODS: We performed a secondary analysis of the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis study. Patients were categorized by the predominant crystalloid in the first 24 hours (> 80%; balanced crystalloids [BCs], normal saline [NS], or mixed) and were stratified by randomized resuscitation strategy (liberal vs restrictive). The primary outcome was death before discharge by day 90. Secondary outcomes included new renal replacement therapy (RRT), organ support-free days, and adverse events. Analysis used inverse probability weighting with covariate balancing and tested a fluid-type by strategy interaction. RESULTS: Among 1,563 patients, 423 patients (27%) received BCs, 226 patients (15%) received NS, and 914 patients (58%) receiving mixed fluids. The association of fluid type with mortality varied by strategy (chi(2) = 118.5 with 9 degrees of freedom; P < .001). For new RRT, the strategy by fluid interaction was significant (F-4,F-1,F-518 = 2.5; P = .041); for RRT-free days, it was not (F-4,F-1,F-437 = 0.369; P = .831). In the liberal arm, adjusted mortality was lower with BCs than NS or mixed fluids (BCs, 12.6% [95% CI, 10.4-15.1]; NS, 16.8% [95% CI, 14.3-19.7]; mixed fluids, 16.1% [95% CI, 13.6-18.9]). In the restrictive arm, adjusted mortality was higher with BCs than NS (BCs, 16.3% [95% CI, 13.9-19.1]; NS, 13.2% [95% CI, 10.9-15.9]; mixed fluids, 14.1% [95% CI, 11.8-16.8]). For new RRT, NS vs BCs was lower in the liberal arm (1.6% vs 2.9%; adjusted OR, 0.43; 95% CI, 0.20-0.90; P = .02) with no difference in the restrictive arm (5.1% vs 3.7%; OR, 1.42; 95% CI, 0.85-2.37; P = .18). RRT-free days were similar across arms. INTERPRETATION: Outcomes differed by fluid type and resuscitation strategy. In the liberal arm, BCs were associated with lower mortality than NS or mixed fluids; this was not seen with a restrictive strategy. Early sepsis resuscitation should consider both fluid composition and strategy.

Importance:Prolonged exposure to broad-spectrum antibiotics (BSA) may be associated with patient harm. Objective:To assess outcomes of BSA de-escalation compared with continuation on encounter day 4 in patients hospitalized for community-onset sepsis. Design, Setting, and Participants:This target trial emulation study was conducted at 67 hospitals participating in the Michigan Hospital Medicine Safety Consortium. Patients 18 years and older hospitalized for community-onset sepsis from June 2020 through September 2024 who initiated empiric BSA therapy without evidence of multidrug-resistant organism infection were included. Data were analyzed from September 2024 to November 2025. Exposure:Inverse probability of treatment-weighted cohort exposed to de-escalation of BSA vs continuation at day 4. Main Outcomes and Measures:The primary outcome was 90-day all-cause mortality. Secondary outcomes included in-hospital mortality, 30-day mortality, length of hospitalization, and days of antibiotic therapy. Results:Among 36 924 patients with community-onset sepsis, 18 559 (50.3%) were female, 18 365 (49.7%) were male, and the median (IQR) age was 71 (61-80) years. A total of 6926 (18.8%) and 11 149 (30.2%) were eligible for target trial emulations evaluating de-escalation of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-Pseudomonas aeruginosa (PSA; or other resistant gram-negative bacteria) antibiotics, respectively. Of these, 2993 (43.2%) and 2493 (22.4%) were de-escalated from anti-MRSA and anti-PSA coverage. After weighting, patients who were de-escalated vs continued on BSA were well balanced on baseline characteristics. In weighted analyses, anti-MRSA and anti-PSA de-escalation were associated with similar 90-day mortality as continued BSA therapy (anti-MRSA: odds ratio, 1.00; 95% CI, 0.88-1.14; anti-PSA: odds ratio, 0.98; 95% CI, 0.86-1.13). Additionally, anti-MRSA and anti-PSA de-escalation were associated with fewer days of antibiotics to day 14 (anti-MRSA de-escalation: risk ratio [RR], 0.91; 95% CI, 0.89-0.93; anti-PSA de-escalation: RR, 0.91; 95% CI, 0.88-0.93) and shorter length of hospitalization (anti-MRSA de-escalation: RR, 0.88; 95% CI, 0.85-0.92; anti-PSA de-escalation: RR, 0.91; 0.88-0.93). All other secondary outcomes were similar. Across 67 hospitals, the proportion of eligible patients de-escalated from BSA varied more than 2-fold (anti-MRSA de-escalation, 27.3% to 61.7%; anti-PSA de-escalation, 6.9% to 37.7%). Conclusions and Relevance:In this study, de-escalation of empiric BSA therapy at day 4 was associated with similar safety outcomes, fewer antibiotic days, and shorter length of hospitalization among patients with community-onset sepsis compared with those who continued BSA therapy but varied widely in practice.

Background The optimal crystalloid for sepsis resuscitation and whether choice should differ under restrictive vs liberal strategy remains uncertain. Research Question Do outcomes differ by fluid type within liberal vs restrictive resuscitation strategies? Study Design and Methods We performed a secondary analysis of CLOVERS. Patients were categorized by the predominant crystalloid in the first 24-hours (>80%; balanced crystalloids [BC], normal saline [NS], or mixed) and stratified by randomized resuscitation strategy (liberal vs. restrictive). Primary outcome was death before discharge by day 90. Secondary outcomes included new renal replacement therapy (RRT), organ support-free days, and adverse events. Analysis used inverse probability weighting with covariate balancing and tested a fluid-type × strategy interaction. Results Among 1,563 patients, 423 (27%) received BC, 226 (15%) NS, and 914 (58%) mixed fluids. The association of fluid type with mortality varied by strategy (χ2[9] = 118.5, p < 0.001). For new RRT, the strategy×fluid interaction was significant (F(4,1518)=2.5, p=0.041); for RRT-free days, it was not (F(4,1437)=0.369, p=0.831). In the liberal arm, adjusted mortality was lower with BC than NS or mixed (BC 12.6% [95% CI 10.4–15.1], NS 16.8% [14.3–19.7], mixed 16.1% [13.6–18.9]). In the restrictive arm, adjusted mortality was higher with BC than NS (BC 16.3% [13.9–19.1], NS 13.2% [10.9–15.9], mixed 14.1% [11.8–16.8]). For new RRT, NS vs. BC was lower in the liberal arm (1.6% vs 2.9%; adjusted OR 0.43, 95% CI 0.20–0.90; p=0.02) with no difference in the restrictive arm (5.1% vs 3.7%; OR 1.42, 95% CI 0.85–2.37; p=0.18). RRT-free days were similar across arms. Interpretation Outcomes differed by fluid type and resuscitation strategy. In the liberal arm, BC was associated with lower mortality than NS or mixed; this was not seen with a restrictive strategy. Early sepsis resuscitation should consider both fluid composition and strategy.

Introduction: Despite the importance of early antibiotics in sepsis, antibiotic administration is often delayed. We sought to understand factors associated with timely antibiotic administration in patients with sepsis-induced hypotension. Methods: This is a retrospective cohort study of adult patients hospitalized with community-acquired sepsis from 11/2020 to 5/2024 at 67 hospitals participating in the Michigan Hospital Medicine Safety Consortium Sepsis Initiative (HMS-Sepsis). HMS-Sepsis registry data are professionally abstracted, including patients’ presenting symptoms as documented in provider notes. We included patients with sepsis (infection and acute organ dysfunction) and hypotension within 2 hours of presentation to ED. We excluded patients with positive COVID-19 or influenza testing. Antibiotics were considered timely if administered within 3 hours of presentation—a relaxed cut-off compared to Surviving Sepsis recommendations (antibiotics ≤1 hour of sepsis onset) to account for sepsis recognition time. We compared symptoms of patients receiving timely vs delayed antibiotics using Chi-squared tests. We used logistic regression to measure the association between patient factors and timely antibiotics with hospital as a random effect. Results: Of 6,759 HMS-Sepsis patients with sepsis-induced hypotension, 4,427 (65.5%) received timely antibiotics while 2,332 (34.5%) received delayed antibiotics. Median time from ED presentation to antibiotic delivery was 1.6 hours (IQR 1.1-2.2) vs 4.5 hours (IQR 3.6-6.7) in the timely vs delayed groups, respectively. Patients receiving timely antibiotics had different presenting symptoms: more frequent subjective fever (48.6% vs 36.9%, p<0.01), altered mental status (63.2% vs 55.2%, p<0.01), respiratory symptoms (71.9% vs 67.1%, p<0.01), and less frequent GI symptoms (40.8% vs 46.8%, p<0.01). Urinary symptoms were similar (23.9% vs 24.4%, p=0.62). In adjusted models, odds of timely antibiotics increased with male sex [aOR 1.13 (95% CI: 1.02, 1.27)], admission from a facility [aOR 1.32 (1.13, 1.55)], higher predicted mortality [aOR 1.72 (1.22, 2.42)], and subjective fever [aOR 1.40 (1.23, 1.58)]. Vital sign derangements on presentation (hypo/hyperthermia, tachycardia, tachypnea, hypoxia) were each associated with increased odds of timely antibiotics. Odds of timely antibiotics decreased with heart failure history [aOR 0.82 (0.72, 0.94)] and GI symptoms [aOR 0.85 (0.75, 0.96)]. While hospital-level variation was low (adjusted median OR: 1.02), at 5/67 (7.5%) hospitals <50% of patients received timely antibiotics (Figure 1). Conclusion: This study provides insight into factors associated with antibiotic delays, highlighting the importance of subjective symptoms, which are often not captured in electronic databases, and possible gender and hospital disparities. Understanding risk factors for antibiotic delays is important for developing interventions to improve sepsis recognition.

Introduction: While fluids are a key component of sepsis management, administering too little or too much fluid can cause harm. Guiding fluids based on stroke volume (SV) responsiveness represents a promising approach to personalizing fluids. SV can be measured by bedside tools like non-invasive cardiac output monitors (NICOM), which use bioreactance technology. The recent FRESH trial found that for ICU patients with sepsis, a SV-guided fluid protocol improved outcomes compared to usual care. We sought to evaluate the implementation of a SV-guided protocol at our institution. Methods: In March 2024, our medical and surgical ICUs introduced a SV-guided fluid protocol based on the FRESH trial. Before this, non-invasive cardiac monitors were not used in these ICUs. The new protocol targets patients with sepsis-induced hypotension and recommends guiding fluids based on dynamic assessments of fluid-responsiveness. These dynamic assessments include pairing a fluid challenge—small fluid bolus or passive leg raise (PLR) — with assessment of SV change, which is measured using a non-invasive cardiac output monitor. If SV increases ≥10%, fluids are recommended; if SV increases <10%, vasopressors are recommended. Reassessment is advised every 30 minutes for patients who remain hypotensive. Education was provided to ICU clinicians (nurses, advanced practice providers, residents, fellows, attendings) from January-March 2024. We evaluated uptake of the SV-guided fluid protocol from April-July 2024. During this period, we also sought feedback from teams through interviews and focus groups. Results: From April to July 2024, the SV-guided fluid protocol was used for 78 patients. Use doubled each month (Figure 1). About half of patients (40/78, 51.3%) were fluid-responsive (SV change ≥10%). Of patients who were fluid-responsive, 22/40 (55.0%) had only one assessment, representing a potential missed opportunity to repeat evaluation and provide additional fluid. Of the 23 patients who received multiple assessments, 14 (60.9%) had varying fluid-responsiveness on repeat assessments. Teams identified several major challenges, including additional workload burden for nursing, frequent protocol non-adherence (i.e., physicians choosing not giving fluid to fluid-responsive patients), and lack of mechanisms for monitoring use in real-time. Conclusions: Implementing a SV-guided fluid protocol using non-invasive cardiac output monitoring was feasible in the medical and surgical ICU, with use incrementally increasing after introduction. Consistent with prior studies, about half of patients were fluid-responsive. We are partnering with teams to address challenges by providing additional education, fostering nursing-physician collaboration, and developing real-time tracking tools. Future work will examine the impact of protocol implementation on sepsis fluid practices.

Rationale Guidelines for the management of sepsis and septic shock do not differentiate between bacterial and viral sepsis. However, little is known regarding how sepsis treatment practices differ for patients with viral vs bacterial sepsis nor how frequently treatment for viral sepsis adheres to general sepsis treatment recommendations. Methods We performed a retrospective cohort study of adult (≥18 years) patients from the Michigan Hospital Medicine Safety Consortium Sepsis registry discharged between January 2022 and July 2024. The registry consists of a random sample of patients hospitalized with community-onset sepsis at 67 participating hospitals. We identified cases of presumed viral vs bacterial sepsis using ICD-10 discharge diagnosis codes and microbiology results within 2 days of admission; patients who met criteria for both viral and bacterial sepsis were categorized as bacterial (Figure). Differences in patient characteristics were assessed using the Wilcoxon rank sum test for continuous variables and chi-squared statistic for categorical variables. Using logistic regression, we assessed odds of receiving recommended sepsis care practices for presumed viral vs bacterial sepsis, adjusting for patient-level characteristics and hospital as a random effect. Results Of 31,253 sepsis hospitalizations, 3,463 (11.1%) met criteria for presumed viral sepsis and 27,790 (88.9%) for presumed bacterial sepsis (Figure). Groups were demographically similar except viral sepsis patients were less likely admitted from a facility (11.0% vs 14.6%) or hospitalized in prior 90 days (26.0% vs 33.6%), and had lower median Charlson comorbidity indices (2 vs 3), p<0.01 for all. Patients with presumed viral sepsis were less likely than bacterial to receive the following recommended sepsis care: initial lactate within 3 hours of arrival (63.1 vs 75.0%, aOR 0.58, 95%CI 0.54-0.63), repeat lactate within 4 hours of first if elevated (62.2 vs 65.2%, aOR 0.86, 95%CI 0.75-0.97), receipt of ≥30 ml/kg actual body weight IV fluid within 6 hours if indicated (46.5 vs 59.4%, aOR 0.58, 95%CI 0.5-0.68), or use of balanced solutions over normal saline among those receiving ≥ 1L fluid (14.0 vs 15.8%, aOR 0.82, 95%CI 0.71-0.95). There were no differences in receipt of vasopressors within 6 hours of persistent hypotension, use of norepinephrine as first-line vasopressor, or use of adjunctive steroids in refractory septic shock. Conclusions Compared to patients presenting with community-onset presumed bacterial sepsis, patients with viral sepsis were less likely to receive many recommended sepsis care practices. Further study is needed to assess the impact of recommendation-compliant care on patient outcomes in viral sepsis.

RATIONALE: Sepsis is a leading cause of mortality in the U.S., and intravenous fluid (IVF) resuscitation remains a cornerstone of sepsis care. The optimal choice of fluids for resuscitation remains uncertain, with some suggesting balanced crystalloid (BC) solutions may reduce mortality compared to normal saline (NS). This study evaluates the impact of fluid type on mortality and renal replacement therapy (RRT) in septic patients using data from the CLOVERS trial. METHODS: This secondary analysis compared septic patients predominantly receiving NS (>80% of IVF) with those receiving BC solutions (>80% of IVF). Of those included, 410 received BC and 227 received NS. The liberal fluid group comprised 56.7% BC and 56.2% NS patients, while the restrictive group had 43.3% and 43.8%, respectively. Median IVF volumes over 6 hours were 2,000 mL (IQR 1,017-2,500) for BC and 1,850 mL (IQR 800-2,500) for NS (difference: 127 mL, 95% CI: -11, 312). Over 24 hours, BC patients received 2,693 mL (IQR 1,847-3,935) vs. 2,450 mL (IQR 1,233-3,670) for NS (difference: 391 mL, 95% CI: 143, 638). Vasopressor use within 24 hours was reported in 44% of BC and 40% of NS patients (difference: 4.0%, 95% CI: -4.3%, 12%). We used inverse probability weighting (IPTW) with Bayesian additive regression trees (BART) to control for confounders and estimate the average treatment effect (ATE) of BC vs. NS on mortality and RRT rates. RESULTS: In the IPTW-weighted cohort, the mean difference in mortality risk between NS and BC groups was 0.016 (95% CI: [-0.073, 0.105]) in the liberal fluid group and 0.096 (95% CI: [-0.017, 0.209]) in the restrictive group. The pooled mean difference (liberal – restrictive) in mortality was -0.08 (95% CI: [-0.223, 0.064]). For RRT, the mean risk difference between NS and BC was -0.013 (95% CI: [-293.087, 293.062]) in the liberal group and -0.003 (95% CI: [-0.342, 0.336]) in the restrictive group, with an overall mean difference of -0.01 (95% CI: [-293.085, 293.065]). Kaplan-Meier plots of survival and RRT-free probability showed overlapping trends across liberal and restrictive volume strategies. CONCLUSIONS: Our findings indicate no significant differences in mortality or RRT requirements between septic patients resuscitated with NS vs. BC solutions, regardless of volume strategy (liberal vs. restrictive). These results suggest flexibility in fluid choice, allowing clinicians to tailor resuscitation based on patient needs rather than fluid type. Further research is warranted to confirm these observations across varied clinical settings.

Critical care uses syndromic definitions to describe patient groups for clinical practice and research. There is growing recognition that a "precision medicine" approach is required and that integrated biologic and physiologic data identify reproducible subpopulations that may respond differently to treatment. This article reviews the current state of the field and considers how to successfully transition to a precision medicine approach. To impact clinical care, identification of subpopulations must do more than differentiate prognosis. It must differentiate response to treatment, ideally by defining subgroups with distinct functional or pathobiological mechanisms (endotypes). There are now multiple examples of reproducible subpopulations of sepsis, acute respiratory distress syndrome, and acute kidney or brain injury described using clinical, physiological, and/or biological data. Many of these subpopulations have demonstrated the potential to define differential treatment response, largely in retrospective studies, and that the same treatment-responsive subpopulations may cross multiple clinical syndromes (treatable traits). To bring about a change in clinical practice, a precision medicine approach must be evaluated in prospective clinical studies requiring novel adaptive trial designs. Several such studies are underway, but there are multiple challenges to be tackled. Such subpopulations must be readily identifiable and be applicable to all critically ill populations around the world. Subdividing clinical syndromes into subpopulations will require large patient numbers. Global collaboration of investigators, clinicians, industry, and patients over many years will therefore be required to transition to a precision medicine approach and ultimately realize treatment advances seen in other medical fields.

Vasopressors are potent vasoconstricting medications commonly used to treat shock. Until recently, guidelines recommended that vasopressors be administered only via central venous catheters (CVCs).1 This practice was based on early case reports of catastrophic tissue injury caused by vasopressor extravasation from peripheral IVs (PIVs).2 However, there is growing interest in peripheral vasopressor administration, to expedite vasopressor initiation and potentially avoid CVC placement and its complications.

Background Vasopressors traditionally are administered via central access, but newer data suggest that peripheral administration may be safe and may avoid delays and complications associated with central line placement. Research Question How commonly are vasopressors initiated through peripheral IV lines in routine practice? Is vasopressor initiation route associated with in-hospital mortality? Study Design and Methods This retrospective cohort study included adults hospitalized with sepsis (November 2020-September 2022) at 29 hospitals in the Michigan Hospital Medicine Safety Consortium, a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan. We assessed route of early vasopressor initiation, factors and outcomes associated with peripheral initiation, and timing of central line placement. Results Five hundred ninety-four patients received vasopressors within 6 h of hospital arrival and were included in this study. Peripheral vasopressor initiation was common (400/594 [67.3%]). Patients with peripheral vs central initiation were similar; BMI was the only patient factor associated independently with initiation route (adjusted OR [aOR] of peripheral initiation [per 1-kg/m2 increase], 0.98; 95% CI, 0.97-1.00; P = .015). The specific hospital showed a large impact on initiation route (median OR, 2.19; 95% CI, 1.31-3.07). Compared with central initiation, peripheral initiation was faster (median, 2.5 h vs 2.7 h from hospital arrival; P = .002), but was associated with less initial norepinephrine use (84.3% vs 96.8%; P = .001). We found no independent association between initiation route and in-hospital mortality (32.3% vs 42.2%; aOR, 0.66; 95% CI, 0.39-1.12). No tissue injury from peripheral vasopressors was documented. Of patients with peripheral initiation, 135 of 400 patients (33.8%) never received a central line. Interpretation Peripheral vasopressor initiation was common across Michigan hospitals and had practical benefits, including expedited vasopressor administration and avoidance of central line placement in one-third of patients. However, the findings of wide practice variation that was not explained by patient case mix and lower use of first-line norepinephrine with peripheral administration suggest that additional standardization may be needed.

BACKGROUND:When comparing outcomes after sepsis, it is essential to account for patient case mix to make fair comparisons. We developed a model to assess risk-adjusted 30-day mortality in the Michigan Hospital Medicine Safety sepsis initiative (HMS-Sepsis). RESEARCH QUESTION:Can HMS-Sepsis registry data adequately predict risk of 30-day mortality? Do performance assessments using adjusted vs unadjusted data differ? STUDY DESIGN AND METHODS:Retrospective cohort of community-onset sepsis hospitalizations in the HMS-Sepsis registry (April 2022-September 2023), with split derivation (70%) and validation (30%) cohorts. We fit a risk-adjustment model (HMS-Sepsis mortality model) incorporating acute physiologic, demographic, and baseline health data and assessed model performance using concordance (C) statistics, Brier scores, and comparisons of predicted vs observed mortality by deciles of risk. We compared hospital performance (first quintile, middle quintiles, fifth quintile) using observed vs adjusted mortality to understand the extent to which risk adjustment impacted hospital performance assessment. RESULTS:Among 17,514 hospitalizations from 66 hospitals during the study period, 12,260 hospitalizations (70%) were used for model derivation and 5,254 hospitalizations (30%) were used for model validation. Thirty-day mortality for the total cohort was 19.4%. The final model included 13 physiologic variables, two physiologic interactions, and 16 demographic and chronic health variables. The most significant variables were age, metastatic solid tumor, temperature, altered mental status, and platelet count. The model C statistic was 0.82 for the derivation cohort, 0.81 for the validation cohort, and ≥ 0.78 for all subgroups assessed. Overall calibration error was 0.0%, and mean calibration error across deciles of risk was 1.5%. Standardized mortality ratios yielded different assessments than observed mortality for 33.9% of hospitals. INTERPRETATION:The HMS-Sepsis mortality model showed strong discrimination and adequate calibration and reclassified one-third of hospitals to a different performance category from unadjusted mortality. Based on its strong performance, the HMS-Sepsis mortality model may aid in fair hospital benchmarking, assessment of temporal changes, and observational causal inference analysis.

Munroe, Elizabeth1; Prevalska, Ina2; Meurer, William3; Mosier, Jarrod4; Tidswell, Mark5; Prescott, Hallie1; Wang, Henry6; Fung, Christopher3 Author Information

IMPORTANCE:Patients presenting to the emergency department (ED) with hypoxemia often have mixed or uncertain causes of respiratory failure. The optimal treatment for such patients is unclear. Both high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are used. OBJECTIVES:We sought to compare the effectiveness of initial treatment with HFNC versus NIV for acute hypoxemic respiratory failure. DESIGN SETTING AND PARTICIPANTS:We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with HFNC or NIV within 24 hours of arrival to the University of Michigan adult ED from January 2018 to December 2022. We matched patients 1:1 using a propensity score for odds of receiving NIV. MAIN OUTCOMES AND MEASURES:The primary outcome was major adverse pulmonary events (28-d mortality, ventilator-free days, noninvasive respiratory support hours) calculated using a win ratio. RESULTS:A total of 1154 patients were included. Seven hundred twenty-six (62.9%) received HFNC and 428 (37.1%) received NIV. We propensity score matched 668 of 1154 (57.9%) patients. Patients on NIV versus HFNC had lower 28-day mortality (16.5% vs. 23.4%, p = 0.033) and required noninvasive treatment for fewer hours (median 7.5 vs. 13.5, p < 0.001), but had no difference in ventilator-free days (median [interquartile range]: 28 [26, 28] vs. 28 [10.5, 28], p = 0.199). Win ratio for composite major adverse pulmonary events favored NIV (1.38; 95% CI, 1.15-1.65; p < 0.001). CONCLUSIONS AND RELEVANCE:In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with NIV compared with HFNC was associated with lower mortality and fewer composite major pulmonary adverse events calculated using a win ratio. These findings underscore the need for randomized controlled trials to further understand the impact of noninvasive respiratory support strategies.