Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial.

IMPORTANCE: 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 MEASURES: The 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 RELEVANCE: In 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389555.

Initiation and Assessment of Timekeeping Roles During In-Hospital Cardiac Arrests to Track Rhythm Checks and Epinephrine Dosing.

OBJECTIVES: Compliance to advanced cardiac life support algorithm is low and associated with worse outcomes from in-hospital cardiac arrests. This study aims to improve algorithm compliance by delegation of two separate code team members for timing rhythm check and epinephrine administration in accordance to the advanced cardiac life support algorithm. DESIGN: Prospective intervention with historical controls. SETTING: Single academic medical center. PATIENTS: Patients who suffered in-hospital cardiac arrest during study period were considered for inclusion. Patients in which the advanced cardiac life support algorithm or new timekeeper roles were not used were excluded. INTERVENTIONS: Two existing code team members were delegated to time epinephrine and rhythm checks. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was deviations from the 2-minute rhythm check or 3- to 5-minute epinephrine administration. Each deviation outside allotted time intervals was counted as one deviation. However, instances in which multiple intervals passed were counted as multiple deviations. Algorithm adherence was analyzed before and after intervention. Secondary endpoints included return of spontaneous circulation rate, time until first dose of epinephrine, and anonymous survey data. Thirteen pre intervention in-hospital cardiac arrests were compared with 13 in-hospital cardiac arrests post. Prior to intervention, the median deviation per in-hospital cardiac arrest was 5 (interquartile range, 3-7) versus 1 post (interquartile range 0-1; p = 0.0003). The median time until first dose of epinephrine was administered pre intervention was 5 minutes (interquartile range, 0-4) versus post intervention median of 0 (interquartile range, 0-0; p = 0.02). Pre-intervention return of spontaneous circulation rate was 46.1% versus 69.2% post. Surveys demonstrated advanced cardiac life support providers felt time keeping roles made it easier to track epinephrine administration and rhythm checks and improved team communication. CONCLUSIONS: Two separate timekeeper roles during in-hospital cardiac arrests improved algorithm compliance, code team function, and was favored by code team members. Timekeeper roles may be associated with improved rates of return of spontaneous circulation and less time until the first dose of epinephrine was administered. This study is limited by small sample size and single-center design.

Physician Approaches to Conflict with Families Surrounding End-of-Life Decision-making in the Intensive Care Unit. A Qualitative Study.

RATIONALE: Families of critically ill patients are often asked to make difficult decisions to pursue, withhold, or withdraw aggressive care or resuscitative measures, exercising "substituted judgment" from the imagined standpoint of the patient. Conflict may arise between intensive care unit (ICU) physicians and family members regarding the optimal course of care. OBJECTIVES: To characterize how ICU physicians approach and manage conflict with surrogates regarding end-of-life decision-making. METHODS: Semistructured interviews were conducted with 18 critical care physicians from four academically affiliated hospitals. Interview transcripts were analyzed using methods of grounded theory. RESULTS: Physicians described strategies for engaging families to resolve conflict about end-of-life decision-making and tending to families' emotional health. Physicians commonly began by gauging family receptiveness to recommendations from the healthcare team. When faced with resistance to recommendations for less aggressive care, approaches ranged from deference to family wishes to various persuasive strategies designed to change families' minds, and some of those strategies may be counterproductive or harmful. The likelihood of deferring to family in the event of conflict was associated with the perceived sincerity of the family's "substituted judgment" and the ability to control patient pain and suffering. Physicians reported concern for the family's emotional needs and made efforts to alleviate the burden on families by assuming decision-making responsibility and expressing nonabandonment and commitment to the patient. Physicians were attentive to repairing damage to their relationship with the family in the aftermath of conflict. Finally, physicians described their own emotional responses to conflict, ranging from frustration and anxiety to satisfaction with successful resolution of conflict. CONCLUSIONS: Critical care physicians described a complex and multilayered approach to physician-family conflict. The reported strategies offer insight into pragmatic approaches to achieving resolution of conflict while attending to both family and physician emotional impact, and they also highlight some potentially unhelpful or harmful behaviors that should be avoided. Further research is needed to evaluate how these strategies are perceived by families and other ICU clinicians and how they affect patient, family, and clinician outcomes.

National down syndrome patient database: Insights from the development of a multi-center registry study.

The Down Syndrome Study Group (DSSG) was founded in 2012 as a voluntary, collaborative effort with the goal of supporting evidenced-based health care guidelines for individuals with Down syndrome (DS). Since then, 5 DS specialty clinics have collected prospective, longitudinal data on medical conditions that co-occur with DS. Data were entered by clinical staff or trained designees into the National Down Syndrome Patient Database, which we created using REDCap software. In our pilot year, we enrolled 663 participants across the U.S., ages 36 days to 70 years, from multiple racial and ethnic backgrounds. Here we report: (i) the demographic distribution of participants enrolled, (ii) a detailed account of our database infrastructure, and (iii) lessons learned during our pilot year to assist future researchers with similar goals for other patient populations.

Augmenting communication and decision making in the intensive care unit with a cardiopulmonary resuscitation video decision support tool: a temporal intervention study.

OBJECTIVE: Effective communication between intensive care unit (ICU) providers and families is crucial given the complexity of decisions made regarding goals of therapy. Using video images to supplement medical discussions is an innovative process to standardize and improve communication. In this six-month, quasi-experimental, pre-post intervention study we investigated the impact of a cardiopulmonary resuscitation (CPR) video decision support tool upon knowledge about CPR among surrogate decision makers for critically ill adults. METHODS: We interviewed surrogate decision makers for patients aged 50 and over, using a structured questionnaire that included a four-question CPR knowledge assessment similar to those used in previous studies. Surrogates in the post-intervention arm viewed a three-minute video decision support tool about CPR before completing the knowledge assessment and completed questions about perceived value of the video. RESULTS: We recruited 23 surrogates during the first three months (pre-intervention arm) and 27 surrogates during the latter three months of the study (post-intervention arm). Surrogates viewing the video had more knowledge about CPR (p=0.008); average scores were 2.0 (SD 1.1) and 2.9 (SD 1.2) (out of a total of 4) in pre-intervention and post-intervention arms. Surrogates who viewed the video were comfortable with its content (81% very) and 81% would recommend the video. CPR preferences for patients at the time of ICU discharge/death were distributed as follows: pre-intervention: full code 78%, DNR 22%; post-intervention: full code 59%, DNR 41% (p=0.23).

Exploring attitudes toward advance care directives in two diverse settings.

BACKGROUND: Advance care directives (ACD) are not used equally by different ethnic groups in the United States. Theories regarding this difference include lack of access to health care, mistrust of the health care system, absence of surrogate decision makers, and universal lack of knowledge on this topic. Few studies have investigated attitudes toward advance care planning for future end-of-life decision-making in the Latino and Cambodian communities. METHODS: Six focus groups were conducted, including a total of 20 Latino and 19 Cambodian patients of two community health centers. Focus groups were audiotaped, transcribed, and qualitatively analyzed to identify major themes regarding attitudes toward advance directives and engaging in discussion about advance care planning. RESULTS: Most patients did not have a health care proxy nor had discussed this topic with their doctor. Two broad themes were identified: integration of belief systems (including religion, suffering/destiny, and importance of quality of life) as well as process/preferences regarding decision-making (including family roles, provider roles, confusion/uncertainty regarding ACD, and openness to learning about ACD). CONCLUSIONS: In focus groups discussing end-of-life decision making among Latino and Cambodian patients, two main themes emerged: integration of belief systems and process/preferences regarding end-of-life care. In particular, efforts to improve completion of advance care directives in diverse populations should consider patients' emphasis on quality of life and destiny in end-of-life planning as well as the role of family consensus in decision-making.