IMPORTANCE: Patients with in-hospital cardiac arrest have poor outcomes. Sodium bicarbonate is commonly administered during cardiac arrest, but the effects on clinical outcomes are unknown. OBJECTIVE: To determine whethe...IMPORTANCE: Patients with in-hospital cardiac arrest have poor outcomes. Sodium bicarbonate is commonly administered during cardiac arrest, but the effects on clinical outcomes are unknown. OBJECTIVE: To determine whether administration of sodium bicarbonate during in-hospital cardiac arrest increases the proportion of patients with return of spontaneous circulation. DESIGN, SETTING, AND PARTICIPANTS: Randomized, parallel-group, double-blind, placebo-controlled clinical trial conducted at 21 hospitals in Denmark. Participants were adults with in-hospital cardiac arrest, who received at least 1 dose of epinephrine. Patients were enrolled from February 6, 2023, to February 11, 2026, with the last 90-day follow-up conducted on May 4, 2026. Final statistical analysis was conducted on May 5, 2026. INTERVENTION: Sodium bicarbonate (up to 100 mmol) or placebo intravenously. MAIN OUTCOMES AND MEASURES: The primary outcome was sustained return of spontaneous circulation. Key secondary outcomes were survival at 30 days and survival at 30 days with a favorable neurologic outcome, defined by a score of 0 to 3 on the modified Rankin Scale (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS: A total of 2913 patients with in-hospital cardiac arrest were screened; 913 patients were randomized, of which 779 were eligible for the primary analyses, with 372 randomized to receive sodium bicarbonate and 407 randomized to receive placebo. The median (IQR) age of patients was 73 (64-79) years and 502 were male (64%). Sustained return of spontaneous circulation occurred in 146 patients (39%) in the sodium bicarbonate group and 150 (37%) in the placebo group (risk ratio, 1.05 [95% CI, 0.88-1.24]; P = .62). At 30 days, 45 patients (12%) in the sodium bicarbonate group and 37 (9.1%) in the placebo group were alive (risk ratio, 1.25 [95% CI, 0.84-1.88]); a favorable neurologic outcome at 30 days occurred in 30 patients (8.1%) and 22 patients (5.4%), respectively (risk ratio, 1.39 [95% CI, 0.82-2.34]). Alkalosis and hypernatremia after cardiac arrest were more common in the sodium bicarbonate group. CONCLUSIONS AND RELEVANCE: There was no significant difference in sustained return of spontaneous circulation between sodium bicarbonate and placebo in adults with in-hospital cardiac arrest. These findings do not support routine administration of sodium bicarbonate for patients with in-hospital cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05564130; ClinicalTrialsRegister.eu Identifier: 2022-501304-10-00.
IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate...IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. INTERVENTIONS: A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. MAIN OUTCOMES AND MEASURES: Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). RESULTS: Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P = .04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P = .34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P = .03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P < .001). CONCLUSIONS AND RELEVANCE: In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06343545.
IMPORTANCE: Severe burn injury triggers systemic inflammation that can lead to multiple organ dysfunctions and death. High-dose intravenous vitamin C has been proposed to mitigate these effects, but strong evidence in pa...IMPORTANCE: Severe burn injury triggers systemic inflammation that can lead to multiple organ dysfunctions and death. High-dose intravenous vitamin C has been proposed to mitigate these effects, but strong evidence in patients with burn injury is lacking. OBJECTIVE: To evaluate the efficacy of high-dose intravenous vitamin C in patients with severe burn injury. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled phase 3 trial conducted across 24 burn centers in North, Central, and South America; Europe; and Asia. Adults (≥18 years) with deep second- and/or third-degree burns covering 20% or more of total body surface area and requiring skin grafting were enrolled between August 18, 2020, and September 12, 2025. Final follow-up was completed in March 2026. The trial was stopped early after the first prespecified interim analysis for futility/harm. INTERVENTIONS: Patients were randomly assigned (1:1) to receive intravenous vitamin C (50 mg/kg every 6 hours for 96 hours) or matched placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of 28-day mortality and persistent organ dysfunction (defined as dependence on mechanical ventilation, kidney replacement therapy, or vasopressor/inotrope support at day 28). The main secondary outcome was time to discharge alive from hospital within 90 days. RESULTS: Among 238 patients enrolled (mean age, 48.9 [SD, 19.1] years; 79% male; mean total body surface area, 37.0% [SD, 14.6%]), 120 were assigned to vitamin C and 118 to placebo. The primary composite outcome occurred in 49 patients (40.8%) in the vitamin C group and 35 patients (29.7%) in the placebo group (adjusted risk ratio [RR], 1.28 [95% CI, 0.99-1.65]; P = .06), crossing the prespecified futility/harm threshold and prompting early trial termination. Time to discharge alive from hospital within 90 days was not improved (adjusted subdistribution hazard ratio, 0.85 [95% CI, 0.62-1.16]; P = .31). Twenty-eight-day mortality was higher in the vitamin C group (15.0% vs 7.6%; adjusted RR, 1.96 [95% CI, 1.32-2.90]; P = .001), as was hospital mortality (23.3% vs 16.1%; adjusted RR, 1.44 [95% CI, 1.03-2.00]; P = .03). CONCLUSIONS AND RELEVANCE: Among patients with severe burn injury, high-dose intravenous vitamin C did not reduce 28-day mortality and persistent organ dysfunction and is possibly harmful. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04138394.
Writing Committee for the PEARL Investigators, Yang X, He X
… +63 more, Xu Y, Pan D, Li K, Chen Y, Zhu Y, Pan Y, Yi T, Zhang M, Peng H, Huang W, Li D, Feng J, Chen J, Lu W, Liao B, Xie Y, Liao B, Yang L, Tang L, Han B, Liu Y, Lin P, Chen J, Liang Y, Li D, Weng G, Huang H, Li H, Li C, Peng Z, Li H, He B, Xue R, Bao M, Sun H, Hou H, Zhou H, Xiao Y, Li J, Zhang W, Chen X, Yan W, Pi Y, Deng Z, Wang J, Xie D, Liu M, Li H, Peng Q, Fang W, Lin X, Chen Z, Li H, Lin Y, Lin Q, Xiao S, Miao Z, Wang D, Nguyen TN, Nogueira RG, Liu Y, Tang Y, PEARL investigators
IMPORTANCE: Functional outcomes in patients with acute ischemic stroke due to large-vessel occlusion who undergo thrombectomy remain suboptimal, and the benefits of intra-arterial alteplase after thrombectomy remain unce...IMPORTANCE: Functional outcomes in patients with acute ischemic stroke due to large-vessel occlusion who undergo thrombectomy remain suboptimal, and the benefits of intra-arterial alteplase after thrombectomy remain uncertain. OBJECTIVE: To investigate whether treatment with intra-arterial alteplase after successful endovascular reperfusion improves functional outcomes among patients with acute, anterior-circulation, large-vessel occlusion stroke. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized clinical trial recruited patients with anterior-circulation, large-vessel occlusion stroke within 24 hours of symptom onset who achieved successful reperfusion (expanded Thrombolysis in Cerebral Infarction scale score of ≥2b50) after thrombectomy. Guideline-based intravenous thrombolysis was allowed. Patients were randomized between August 1, 2023, and October 16, 2024, and the trial was conducted at 28 hospitals in China. Final follow-up occurred on January 7, 2025. INTERVENTIONS: Intra-arterial alteplase treatment (n = 164) with 0.225 mg/kg (maximum dose of 20 mg) vs standard treatment (n = 160). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days (score range, 0 [no symptoms] to 6 [death]; a score of 0 or 1 indicates an excellent outcome). The safety outcomes included symptomatic intracranial hemorrhage within 36 hours of randomization, all-cause mortality within 90 days, and any intracranial hemorrhage within 36 hours. RESULTS: Of the 324 patients randomized (median age, 68 years [IQR, 58-75 years]; 99 were female [30.6%]), 1 patient in each group was lost to follow-up. The proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days was 44.8% (73/163) in the intra-arterial alteplase group vs 30.2% (48/159) in the standard treatment group (adjusted risk ratio [RR], 1.45 [95% CI, 1.08-1.96]; P = .01). The proportion of patients with symptomatic intracranial hemorrhage within 36 hours was 4.3% (7/164) in the intra-arterial alteplase group vs 5.0% (8/160) in the standard treatment group (adjusted RR, 0.85 [95% CI, 0.43-1.69]; P = .67). The proportion of patients with all-cause mortality within 90 days was 17.1% (28/164) in the intra-arterial alteplase group vs 11.3% (18/160) in the standard treatment group (adjusted hazard ratio, 1.60 [95% CI, 0.88-2.89]; P = .12). The proportion of patients with any intracranial hemorrhage within 36 hours was 32.9% (54/164) in the intra-arterial alteplase group vs 26.9% (43/160) in the standard treatment group (adjusted RR, 1.22 [95% CI, 0.92-1.63]; P = .17). CONCLUSIONS AND RELEVANCE: Among patients with acute, anterior-circulation, large-vessel occlusion stroke who achieved successful endovascular reperfusion by mechanical thrombectomy, intra-arterial alteplase resulted in a higher likelihood of excellent outcomes at 90 days. The incidence of all-cause mortality and any intracranial hemorrhage was higher in patients who received intra-arterial alteplase, although these differences were not statistically significant. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05856851.
IMPORTANCE: Cyanotic congenital heart diseases, which occur in approximately 0.2% of live births in the United States, have high mortality rates if untreated, but survival to adulthood is common with current surgical int...IMPORTANCE: Cyanotic congenital heart diseases, which occur in approximately 0.2% of live births in the United States, have high mortality rates if untreated, but survival to adulthood is common with current surgical interventions. OBSERVATIONS: Approximately 80% of all cyanotic congenital heart diseases are caused by tetralogy of Fallot (TOF), D-loop transposition of the great arteries (TGA), and congenital heart disease with single-ventricle circulation. Survivors of cyanotic congenital heart diseases benefit from multidisciplinary care including pediatric and adult cardiologists, congenital cardiac surgeons, and electrophysiologists. Ninety percent of patients with TOF survive more than 30 years after surgery to close the ventricular septal defect and repair the right ventricular outflow tract. Nearly all adults with repaired TOF develop right ventricular volume overload due to pulmonary regurgitation, and atrial tachycardias and atrial fibrillation occur in approximately 20% to 45% of patients by age 45 years. For D-loop TGA, which involves the aorta arising from the right ventricle and the pulmonary artery arising from the left ventricle, arterial switch procedures result in survival rates of 93% to 97% to age 30 years. After atrial switch operation, 30% to 50% of patients develop moderate or severe right ventricle dysfunction by age 25 years; atrial tachycardia occurs in 48% to 63% of patients at 32 to 40 years postsurgery, and sinus node dysfunction is common. Sudden cardiac death occurs at a mean age of 30 to 35 years (SD, 6.4 years) in up to 15% of adults who have undergone an atrial switch operation. Infants born with a single ventricle that supplies both systemic and pulmonary circulation are most often treated with staged open-heart surgical interventions, typically performed during a period from neonatal age to 6 years of age, culminating in the Fontan procedure, which connects the inferior and superior vena cava to the pulmonary arteries, allowing deoxygenated blood to flow to the lungs without a pumping ventricle. Survival rates for children who undergo the Fontan procedure are 50% to 80% at age 40 to 50 years, although these patients may develop New York Heart Association functional class III or IV (0.35% per person-year) and have increased risk of early death or heart transplant requirement (0.36% per person-year). CONCLUSIONS AND RELEVANCE: With surgical intervention, survival to adulthood is common among patients with TOF, D-loop TGA, and single ventricle. However, these survivors of cyanotic congenital heart diseases are at risk of valve dysfunction, arrhythmias, heart failure, and premature death. Optimal care involves multidisciplinary management including pediatric and adult cardiologists, congenital cardiac surgeons, and electrophysiologists.