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Introduction Sepsis is a global health priority with nearly 50 million cases annually. Cardiovascular dysfunction is common, frequently manifesting as hypotension that persists despite fluid resuscitation. Most affected patients require the use of intravenous (IV) vasoactive agents, typically necessitating intensive care unit (ICU)-level monitoring, invasive interventions and contributing substantially to healthcare costs. Midodrine, an oral alpha-1 agonist approved for orthostatic hypotension, has increasingly been used off-label as a vasopressor-sparing (reducing IV vasopressor use) strategy in sepsis, despite limited and inconsistent evidence. This pragmatic, randomised, open-label trial evaluates the efficacy and safety of midodrine in patients with sepsis-associated hypotension. We hypothesise that, compared with standard care, midodrine administration will reduce the duration of IV vasopressor use. Methods and analysis A total of 308 adult patients with sepsis-associated hypotension will be enrolled (154 per arm). The intervention group will, in addition to standard of care, receive enteral midodrine 10 mg three times daily. Outcomes will be ascertained pragmatically via electronic health record-based data retrieval and adjudicated by research coordinators blinded to treatment assignment. The primary outcome is time alive and off IV vasopressors in the first 28 days (in hours) after randomisation. Secondary outcomes include cumulative vasopressor exposure; use and duration of central venous access; cumulative fluid balance over the first 48 hours and up to 7 days of ICU stay; ICU and hospital length of stay; and ICU-, hospital-, and organ support-free days through day 28. Safety outcomes include adverse events potentially attributable to midodrine during hospitalisation including acute kidney injury. Primary analyses will follow an intention-to-treat framework, including all randomised participants according to their assigned treatment groups. Primary and secondary outcomes will be compared using a van Elteren test stratified by randomisation factors. A predefined secondary Bayesian analysis of the primary outcome will provide complementary estimates of treatment effect. Safety outcomes will be summarised descriptively without formal between-arm hypothesis testing. Ethics and dissemination The Mayo Clinic Institutional Review Board approved this protocol and required written informed consent from all participants (IRB# 24–0 00 121). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT06319248 .

Introduction: Life-support limits (i.e., code status), the first step in the continuum of palliation and end-of-life (EoL) care, stem from decisions made by patients and their providers to align care near the EoL with patients’ wishes. The pandemic created health care strain that may have influenced life-support limitation practices among patients with serious COVID-19. In this study, we examine variations in life-support limitations (do-not-resuscitate, DNR; do-not-intubate, DNI) depending on the hospital and period of hospitalization. Methods: We included all adults admitted to a hospital in the United States with COVID-19 from January 2020 to December 2021 using the VIRUS registry. Our outcome was any life-support limitation on admission (DNR, DNI, or both) using regression modeling. Main exposures were hospital and period of hospitalization (early vs. late pandemic). Covariates included age, sex, race/ethnicity, comorbidities, and hospitalization diagnoses. Results: There were 42,383 patients from 75 hospitals in the US. The median age was 63 (interquartile range: 50–75), 46.5% were female, and 37.5% were non-Hispanic White. The life-support limitation rate was 7.9%, and the palliative care consultation rate was 2.3%. The odds of life-support limitation were 1.86 (95% CI: 1.6–2.1) depending on the hospital, but the period of hospitalization was not associated with odds of life-support limitation. Older age was associated with the greatest increased odds (4.1 per standard deviation ∼ 17.9 years, 95% CI: 3.9–4.4), followed by comorbidities including paralysis (2.4, 95% CI: 1.8–3.0) and dementia (2.3, 95% CI: 2.0–2.6). Conclusions: After adjusting for patient-level factors, we report significant inter-hospital but no temporal variation in life-support limitation upon admission with COVID-19. Future studies should investigate specific practices that led to health care resilience to temporal practice variations in life-support limitation during the pandemic.

Introduction: Heparin-induced thrombocytopenia (HIT) is an autoimmune life-threatening prothrombotic syndrome associated with low platelet count after heparin exposure. Spontaneous heparin-induced thrombocytopenia (S-HIT) is an even less frequent variant of HIT, with only a handful of reports available in the literature, where unexplained thrombocytopenia and/or thrombosis without recent heparin exposure occurs in the setting of positive anti-PF4 antibodies. Case Presentation: We report a case of S-HIT associated with pulmonary artery embolism, left internal jugular vein, and cerebral vein sinus thrombosis complicated with ipsilateral acute intracerebral hemorrhage. Discussion: It is important to highlight that in patients with otherwise unexplained thrombocytopenia and prior exposure to an inflammatory process, S-HIT should be on the differential. Conclusions: Recognition and avoidance of heparin exposure is the most important aspect of S-HIT, as the management is otherwise similar to HIT.

OBJECTIVES: Conduct a systematic review and meta-analysis to assess prevalence and timing of acute kidney injury (AKI) development after acute respiratory distress syndrome (ARDS) and its association with mortality. DATA SOURCES: Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO database, Scopus, and Web of Science thought April 2023. STUDY SELECTION: Titles and abstracts were screened independently and in duplicate to identify eligible studies. Randomized controlled trials and prospective or retrospective cohort studies reporting the development of AKI following ARDS were included. DATA EXTRACTION: Two reviewers independently extracted data using a pre piloted abstraction form. We used Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) and Open Meta software (Brown University, Providence, RI) for statistical analyses. DATA SYNTHESIS: Among the 3646 studies identified and screened, 17 studies comprising 9359 ARDS patients met the eligibility criteria and were included in the meta-analysis. AKI developed in 3287 patients (40%) after the diagnosis of ARDS. The incidence of AKI at least 48 hours after ARDS diagnosis was 20% (95% CI, 0.18–0.21%). The pooled risk ratio (RR) for the hospital (or 30-d) mortality among ARDS patients who developed AKI was 1.93 (95% CI, 1.71–2.18). AKI development after ARDS was identified as an independent risk factor for mortality in ARDS patients, with a pooled odds ratio from multivariable analysis of 3.69 (95% CI, 2.24–6.09). Furthermore, two studies comparing mortality between patients with late vs. early AKI initiation after ARDS revealed higher mortality in late AKI patients with RR of 1.46 (95% CI, 1.19–1.8). However, the certainty of evidence for most outcomes was low to very low. CONCLUSIONS: While our findings highlight a significant association between ARDS and subsequent development of AKI, the low to very low certainty of evidence underscores the need for cautious interpretation. This systematic review identified a significant knowledge gap, necessitating further research to establish a more definitive understanding of this relationship and its clinical implications.

Background Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. Methods This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. Results Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. Conclusion Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

Objectives To describe incidence and risk factors of loss of previous independent living through nonhome discharge or discharge home with health assistance in survivors of intensive care unit (ICU) admission for coronavirus disease 2019 (COVID-19). Design Multicenter observational study including patients admitted to the ICU from January 2020 till June 30, 2021. Hypothesis We hypothesized that there is a high risk of nonhome discharge in patients surviving ICU admission due to COVID-19. Setting Data were included from 306 hospitals in 28 countries participating in the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 registry. Patients Previously independently living adult ICU survivors of COVID-19. Interventions None. Measurements and Main Results The primary outcome was nonhome discharge. Secondary outcome was the requirement of health assistance among patients who were discharged home. Out of 10 820 patients, 7101 (66%) were discharged alive; 3791 (53%) of these survivors lost their previous independent living status, out of those 2071 (29%) through nonhome discharge, and 1720 (24%) through discharge home requiring health assistance. In adjusted analyses, loss of independence on discharge among survivors was predicted by patient age ≥ 65 years (adjusted odds ratio [aOR] 2.78, 95% confidence interval [CI] 2.47-3.14, P < .0001), former and current smoking status (aOR 1.25, 95% CI 1.08-1.46, P = .003 and 1.60 (95% CI 1.18-2.16), P = .003, respectively), substance use disorder (aOR 1.52, 95% CI 1.12-2.06, P = .007), requirement for mechanical ventilation (aOR 4.17, 95% CI 3.69-4.71, P < .0001), prone positioning (aOR 1.19, 95% CI 1.03-1.38, P = .02), and requirement for extracorporeal membrane oxygenation (aOR 2.28, 95% CI 1.55-3.34, P < .0001). Conclusions More than half of ICU survivors hospitalized for COVID-19 are unable to return to independent living status, thereby imposing a significant secondary strain on health care systems worldwide.