The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock.OBJECTIVE To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019.INTERVENTIONS Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). MAIN OUTCOMES AND MEASURESThe primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. RESULTS Among 205 randomized patients (mean age, 68 [SD,15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [−4.7] points with intervention vs 9.2 to 5.1 [−4.1] points with placebo; adjusted mean difference, −0.8; 95% CI, −1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, −0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). CONCLUSIONS AND RELEVANCEIn patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock.

The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.

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Objective We sought to investigate if the chloride content of fluids used in resuscitation was associated with short and long-term outcomes. Design We identified patients who received large volume fluid resuscitation (LVR), defined as greater than 60ml/kg over a 24 hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during LVR multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis (HCA), AKI and survival among those with higher and lower chloride loads. Setting University Medical Center Patients Patients admitted to intensive care units (ICUs) from 2000–2008 Interventions None Main Results Among 4,710 patients receiving LVR HCA was documented in 523 (11%). Crude rates of HCA, AKI and hospital mortality all increased significantly as chloride load increased (p<0.001). However, chloride load was no longer associated with HCA or AKI after controlling for total fluids, age, and baseline severity. Conversely, each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death even after controlling for total fluid volume, age and severity (p=0.0015) over one year. Conclusions Chloride load is associated with significant adverse effects on survival out to one year even after controlling for total fluid load, age and baseline severity of illness. However the relationship between chloride load and development of HCA or AKI is less clear and further research is needed to elucidate the mechanisms underlying the adverse effects of chloride load on survival.

Mechanical circulatory assist devices are now commonly used in the treatment of severe heart failure as bridges to cardiac transplant, as destination therapy for patients who are not transplant candidates, and as bridges to recovery and "decision-making". These devices, which can be used to support the left or right ventricles or both, restore circulation to the tissues, thereby improving organ function. Left ventricular assist devices (LVADs) are the most common support devices. To care for patients with these devices, health care providers in emergency departments (EDs) and intensive care units (ICUs) need to understand the physiology of the devices, the vocabulary of mechanical support, the types of complications patients may have, diagnostic techniques, and decision-making regarding treatment. Patients with LVADs who come to the ED or are admitted to the ICU usually have nonspecific clinical symptoms, most commonly shortness of breath, hypotension, anemia, chest pain, syncope, hemoptysis, gastrointestinal bleeding, jaundice, fever, oliguria and hematuria, altered mental status, headache, seizure, and back pain. Other patients are seen for cardiac arrest, psychiatric issues, sequelae of noncardiac surgery, and trauma. Although most patients have LVADs, some may have biventricular support devices or total artificial hearts. Involving a team of cardiac surgeons, perfusion experts, and heart-failure physicians, as well as ED and ICU physicians and nurses, is critical for managing treatment for these patients and for successful outcomes. This review is designed for critical care providers who may be the first to see these patients in the ED or ICU.

Introduction:The potential for disasters exists in all communities. To mitigate the potential catastrophes that confront humanity in the new millennium, an evidence-based approach to disaster management is required urgently. This study moves toward such an evidence-based approach by identifying peer-reviewed publications following a range of disasters and events over the past three decades.Methods:Peer-reviewed, event-specific literature was identified using a comprehensive search of the electronically indexed database, MEDLINE (1956–January 2009). An extended comprehensive search was conducted for one event to compare the event-specific literature indexed in MEDLINE to other electronic databases (EMBASE, CINAHL, AMED, CENTRAL, Psych Info, Maternity and Infant Care, EBM Reviews).Results:Following 25 individual disasters or overwhelming crises, a total of 2,098 peer-reviewed, event-specific publications were published in 789 journals (652 publications following disasters/events caused by natural hazards, 966 following human-made/technological disasters/events, and 480 following conflict/complex humanitarian events).The event with the greatest number of peer-reviewed, event-specific publications was the 11 September 2001 terrorist attacks (686 publications). Prehospital and Disaster Medicine published the greatest number of peer-reviewed, event-specific publications (54), followed by Journal of Traumatic Stress (42), Military Medicine (40), and Psychiatric Services (40). The primary topics of event-specific publications were mental health, medical health, and response. When an extended, comprehensive search was conducted for one event, 75% of all peer-reviewed, event-specific publications were indexed in MEDLINE.Conclusions:A broad range of multi-disciplinary journals publish peer-reviewed, event-specific publications. While the majority of peer-reviewed, event-specific literature is indexed in MEDLINE, comprehensive search strategies should include EMBASE to increase yield.

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