Characteristics and Outcomes of Patients Requiring Repeat Intensive Care Unit Consults.

Objective: To better understand the mortality and notable characteristics of patients initially denied intensive care unit (ICU) admission that are later admitted on reconsultation. Patients and Methods: We collected data regarding all adult inpatients (n=3725) who received one or more ICU consults at an academic tertiary care hospital medical center between January 1, 2018 and October 1, 2021. We compared patients who were initially denied ICU admission and later admitted on reconsultation (C2A1, n=144) with those who were admitted after the first consultation (C1A1, n=2286) and those denied at first consult and never later admitted (C1A0, n=1295). Results: Ten percent of patients initially rejected by the ICU were later admitted on reconsultation. There was no significant difference in the adjusted hospital death odds ratios between C1A1 and C2A1 (0.67; 95% CI 0.43-1.01; P=.11). Assessing subgroups of the C2A1 population, we found that 8.2% (n=100) of full code patients were later admitted to the ICU on reconsultation vs 23.2% (n=40) of do not attempt resuscitation patients (P<.001); 7.6% (n=77) of patients initially consulted from the emergency department were later admitted to the ICU on reconsultation vs 15.1% (n=52) of patients initially consulted from an inpatient setting (P<.001). Conclusion: In this cohort, we demonstrated that patients admitted on repeat ICU consultation have no significant difference in mortality compared with equivalent patients admitted after the first consultation. Understanding and further exploring the consequences of these ICU reconsultations is vital to developing optimal critical care triaging practices.

Patients Who Decompensate and Trigger Rapid Response Immediately Upon Hospital Admission Have Higher Mortality Than Equivalent Patients Without Rapid Responses.

BACKGROUND: Rapid response teams (RRTs) have impacted the management of decompensating patients, potentially improving mortality. Few studies address the significance of RRT timing relative to hospital admission. We aimed to identify outcomes of adult patients who trigger immediate RRT activation, defined as within 4 hours of admission and compare with RRT later in admission or do not require RRT activation, and identify risk factors that predispose toward immediate RRT activation. METHODS: A retrospective case-control study was performed using an RRT activation database, comprising 201,783 adult inpatients at an urban, academic, tertiary care hospital. This group was subdivided by timing of RRT activation regarding admission: within the first 4 hours (immediate RRT), between 4 and 24 hours (early RRT), and after 24 hours (late RRT). The primary outcome was 28-day all-cause mortality. Individuals triggering an immediate RRT were compared with demographically matched controls. Mortality was adjusted for age, Quick Systemic Organ Failure Assessment score, intensive care unit admission, and Elixhauser Comorbidity Index. RESULTS: Patients with immediate RRT had adjusted 28-day all-cause mortality of 7.1% (95% confidence interval [CI], 5.6%-8.5%) and death odds ratio of 3.27 (95% CI, 2.5-4.3) compared with those who did not (mortality, 2.9%; 95%CI, 2.8%-2.9%; P < 0.0001). Patients triggering an immediate RRT were more likely to be Black, be older, and have higher Quick Systemic Organ Failure Assessment scores than those who did not trigger RRT activation. CONCLUSIONS: In this cohort, patients who require immediate RRT experienced higher 28-day all-cause mortality, potentially because of evolving or unrecognized critical illness. Further exploring this phenomenon may create opportunities for improved patient safety.

Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS.

(1) Background: The disease-modifying mechanisms of high-dose intravenous vitamin C (HDIVC) in sepsis induced acute respiratory distress syndrome (ARDS) is unclear. (2) Methods: We performed a post hoc study of plasma biomarkers from subjects enrolled in the randomized placebo-controlled trial CITRIS-ALI. We explored the effects of HDIVC on cell-free DNA (cfDNA) and syndecan-1, surrogates for neutrophil extracellular trap (NET) formation and degradation of the endothelial glycocalyx, respectively. (3) Results: In 167 study subjects, baseline cfDNA levels in HDIVC (84 subjects) and placebo (83 subjects) were 2.18 ng/µL (SD 4.20 ng/µL) and 2.65 ng/µL (SD 3.87 ng/µL), respectively, p = 0.45. At 48-h, the cfDNA reduction was 1.02 ng/µL greater in HDIVC than placebo, p = 0.05. Mean baseline syndecan-1 levels in HDIVC and placebo were 9.49 ng/mL (SD 5.57 ng/mL) and 10.83 ng/mL (SD 5.95 ng/mL), respectively, p = 0.14. At 48 h, placebo subjects exhibited a 1.53 ng/mL (95% CI, 0.96 to 2.11) increase in syndecan-1 vs. 0.75 ng/mL (95% CI, 0.21 to 1.29, p = 0.05), in HDIVC subjects. (4) Conclusions: HDIVC infusion attenuated cell-free DNA and syndecan-1, biomarkers associated with sepsis-induced ARDS. Improvement of these biomarkers suggests amelioration of NETosis and shedding of the vascular endothelial glycocalyx, respectively.

Vasopressin versus norepinephrine as the first-line vasopressor in septic shock: A systematic review and meta-analysis.

Background and Aim: Norepinephrine is currently the first-line vasopressor for septic shock. We conducted this meta-analysis to examine the outcomes of adult patients with septic shock who received vasopressin instead of norepinephrine. Methods: We selected studies in adults with septic shock that compared the outcomes of patients treated with vasopressin versus norepinephrine. Cochrane ROB 2.0 and the Joanna Briggs Institute quality assessment tools were used to assess the risk of bias in RCTs and observational studies. Meta-analysis was conducted using RevMan 5.4. Results: Eight studies were included in this meta-analysis. There were no significant differences in 28-day mortality rates (OR, 1.07; CI, 0.80-1.44) and intensive care unit (ICU) mortality (OR, 0.74; CI, 0.21-2.67) between the two groups. Similarly, length of ICU stay, length of hospital stay, mean arterial pressure at 24 h, urine output at 24 h, and serious adverse events also did not differ significantly. However, the odds of renal replacement therapy (RRT) requirement in the vasopressin group were substantially lower than in the norepinephrine group (OR, 0.68; CI, 0.47-0.98). Conclusion: There were no differences in mortality, duration of hospitalization, and adverse effects in adults with septic shock across the two groups. However, the patients treated with vasopressin had lower chances of requiring RRT. Relevance for Patients: Vasopressin use as the first-line vasopressor in septic shock showed a significant reduction in RRT, though there were no significant differences in terms of mortality and other adverse events. Therefore, vasopressin can be considered as a first-line vasopressor in septic shock patients with other risk factors which may contribute to renal failure requiring RRT.

Hypothermia versus normothermia after out-of-hospital cardiac arrest: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The current guidelines recommend targeted temperature management (TTM) as part of the post-resuscitation care for comatose patients following out-of-hospital cardiac arrest. These recommendations are based on the weak evidence of benefit seen in the early clinical trials. Recent large multicentered trials have failed to show a meaningful clinical benefit of hypothermia, unlike the earlier studies. Thus, to fully appraise the available data, we sought to perform this systematic review and meta-analysis of randomized controlled trials. METHODS: We searched four databases for randomized controlled trials comparing therapeutic hypothermia (32-34 °C) with normothermia (≥36 °C with control of fever) in adult patients resuscitated after out-of-hospital cardiac arrest. Independent reviewers did the title and abstract screening, full-text screening, and extraction. The primary outcome was mortality six months after cardiac arrest, and secondary outcomes were neurological outcomes and adverse effects. RELEVANCE FOR PATIENTS: Six randomized controlled trials were included in this review. There was no significant difference between the hypothermia and normothermia groups in mortality till 6 months follow up after out-of-hospital cardiac arrest (OR 0.88, 95% CI 0.67-1.16; n = 3243; I2 = 51%), or favorable neurological outcome (OR 1.31, 95% CI 0.93-1.84; n = 3091; I2 = 68%). Rates of arrhythmias were notably higher in the hypothermia group than the normothermia group (OR 1.43, 95% CI 1.20-1.71; n = 3029; I2 = 4%). However, odds for development of pneumonia showed no significant differences across two groups (OR 1.13, 95% CI 0.98-1.31; n = 3056; I2 = 22%). Therefore, targeted hypothermia with a target temperature of 32-34 °C does not provide mortality benefit or better neurological outcome in patients resuscitated after the out-of-hospital cardiac arrest when compared with normothermia.

Endotracheal Tube Size Is Associated With Mortality in Patients With Status Asthmaticus.

BACKGROUND: There is limited evidence on the clinical importance of the endotracheal tube (ETT) size selection in patients with status asthmaticus who require invasive mechanical ventilation. We set out to explore the clinical outcomes of different ETT internal diameter sizes in subjects mechanically ventilated with status asthmaticus. METHODS: This was a retrospective study of intubated and non-intubated adults admitted for status asthmaticus between 2014-2021. We examined in-hospital mortality across subgroups with different ETT sizes, as well as non-intubated subjects, using logistic and generalized linear mixed-effects models. We adjusted for demographics, Charlson comorbidities, the first Sequential Organ Failure Assessment score, intubating personnel and setting, COVID-19, and the first PaCO2 . Finally, we calculated the post-estimation predictions of mortality. RESULTS: We enrolled subjects from 964 status asthmaticus admissions. The average age was 46.9 (SD 14.5) y; 63.5% of the encounters were women and 80.6% were Black. Approximately 72% of subjects (690) were not intubated. Twenty-eight percent (275) required endotracheal intubation, of which 3.3% (32) had a 7.0 mm or smaller ETT (ETT ≤ 7 group), 16.5% (159) a 7.5 mm ETT (ETT ≤ 7.5 group), and 8.6% (83) an 8.0 mm or larger ETT (ETT ≥ 8 group). The adjusted mortality was 26.7% (95% CI 13.2-40.2) for the ETT ≤ 7 group versus 14.3% ([(95% CI 6.9-21.7%], P = .04) for ETT ≤ 7.5 group and 11.0% ([95% CI 4.4-17.5], P = .02) for ETT ≥ 8 group, respectively. CONCLUSIONS: Intubated subjects with status asthmaticus had higher mortality than non-intubated subjects. Intubated subjects had incrementally higher observed mortality with smaller ETT sizes. Physiologic mechanisms can support this dose-response relationship.

Pulmonary barotrauma in COVID-19: A systematic review and meta-analysis.

BACKGROUND: An ever-increasing number of studies have reported an increased incidence of spontaneous pulmonary barotrauma such as pneumothorax, pneumomediastinum, and subcutaneous emphysema in patients with COVID-19. We conducted this systematic review and meta-analysis to assess the value and significance of the available data. METHODS: A thorough systematic search was conducted to identify studies of barotrauma in hospitalized patients with COVID-19. Data analysis of case reports was done using a statistical package for the social sciences (SPSS) version 22, and meta-analysis was performed using CMA-3. RESULTS: We identified a total of 4488 studies after thorough database searching.118 case reports and series, and 15 observational studies were included in the qualitative analysis. Fifteen studies were included in the quantitative analysis. The observational studies reported barotrauma in 4.2% (2.4-7.3%) among hospitalized patients; 15.6% (11-21.8%) among critically ill patients; and 18.4% (13-25.3%) in patients receiving invasive mechanical ventilation, showing a linear relationship of barotrauma with the severity of the disease. In addition, barotrauma was associated with a longer length of hospital stay, more extended ICU stay, and higher in-hospital mortality. Also, a slightly higher odds of barotrauma was seen in COVID-19 ARDS compared with non-COVID-19 ARDS. CONCLUSION: COVID-19 pneumonia is associated with a higher incidence of barotrauma. It presents unique challenges for invasive and non-invasive ventilation management. Further studies are required to unravel the underlying pathophysiology and develop safer management strategies.

Vitamin C in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin C is a water-soluble antioxidant vitamin. Oxidative stress and its markers, along with inflammatory markers, are high during critical illness. Due to conflicting results of the published literature regarding the efficacy of vitamin C in critically ill patients, and especially the concerns for nephrotoxicity raised by some case reports, this meta-analysis was carried out to appraise the evidence and affirmation regarding the role of vitamin C in critically ill patients. METHODS: We searched the database thoroughly to collect relevant studies that assessed intravenous vitamin C use in critically ill patients published until 25 February 2021. We included randomized controlled trials and observational studies with 20 or more critically ill patients who have received intravenous ascorbic acid (vitamin C). After screening 18,312 studies from different databases, 53 were included in our narrative synthesis, and 48 were included in the meta-analysis. We used the Covidence software for screening of the retrieved literature. Review Manager (RevMan) 5.4 was used for the pooling of data and Odds Ratios (OR) and Mean difference (MD) as measures of effects with a 95% confidence interval to assess for explanatory variables. RESULTS: Pooling data from 33 studies for overall hospital mortality outcomes using a random-effect model showed a 19% reduction in odds of mortality among the vitamin C group (OR, 0.81; 95% CI, 0.66-0.98). Length of hospital stay (LOS), mortality at 28/30 days, ICU mortality, new-onset AKI and Renal Replacement Therapy (RRT) for AKI did not differ significantly across the two groups. Analysis of data from 30 studies reporting ICU stay disclosed 0.76 fewer ICU days in the vitamin C group than the placebo/standard of care (SOC) group (95% CI, -1.34 to -0.19). This significance for shortening ICU stay persisted even when considering RCTs only in the analysis (MD, -0.70; 95% CI, -1.39 to -0.02). CONCLUSION: Treatment of critically ill patients with intravenous vitamin C was relatively safe with no significant difference in adverse renal events and decreased in-hospital mortality. The use of vitamin C showed a significant reduction in the length of ICU stays in critically ill patients.

Safety and efficacy of human serum albumin treatment in patients with cirrhotic ascites undergoing paracentesis: A systematic review and meta-analysis.

Ascites is the most common presentation of decompensated liver cirrhosis. It is treated with therapeutic paracentesis which is associated with several complications. The role of human albumin in patients with cirrhotic ascites remains elusive and has been extensively studied with conflicting results. Thus, in order to fully appraise the available data we sought to perform this systematic review and meta-analysis. Herein we included studies comparing the efficacy and safety of human albumin comparing with other volume expanders and vasoactive agents in patients undergoing paracentesis in cirrhotic ascites. Odds ratio (OR) and mean difference (MD) were used to estimate the outcome with a 95% confidence interval (CI). Albumin use reduced the odds of paracentesis induced circulatory dysfunction (PICD) by 60% (OR 0.40, 95% CI 0.27-0.58). While performing subgroup analysis, albumin use lowered the odds of PICD significantly (OR 0.34, 95% CI 0.22-0.52) in comparison to other colloid volume expanders, but did not lower the odds of PICD in comparison to vasoconstrictor therapy (OR 0.93, 95% CI 0.35-2.45). Albumin was associated with a statistically significant lower incidence of hyponatremia (OR 0.59, 95% CI 0.39-0.88). Albumin did not reduce the overall mortality, readmission rate, recurrence of ascites, mean arterial pressure, incidence of renal impairment, hepatic encephalopathy, and gastrointestinal (GI) bleeding. Thus, treatment with albumin in cirrhotic ascites reduced PICD and hyponatremia although there was no benefit in terms of mortality, readmission rate, recurrence of ascites, hepatic encephalopathy, and GI bleeding.

Patiromer and Sodium Zirconium Cyclosilicate in Treatment of Hyperkalemia: A Systematic Review and Meta-Analysis.

BACKGROUND: Patiromer and sodium zirconium cyclosilicate (SZC) are newer options for hyperkalemia treatment. This systematic review and meta-analysis were conducted to assess the safety and side effect profile of patiromer and SZC compared with placebo or other standards of care in the management of hyperkalemia. METHODS: We searched electronic databases for relevant articles. The screening was performed independently and data were extracted among the selected studies. We performed a statistical analysis on Revman 5.4 software. The odds ratio (OR) was used for outcome estimation with a 95% CI. RESULTS: Patiromer had lower rates of hyperkalemia (OR = 0.44; 95% CI, 0.22-0.89) compared with standard of care. The analysis showed no significant differences between the 2 groups in terms of overall adverse effects, any serious/specific adverse effects, or treatment discontinuation as a result of adverse effects. Comparing the SZC-10 group with standard of care showed no significant differences in the occurrence of hyperkalemia during treatment, overall adverse effects, any serious/specific adverse effects, or treatment discontinuation as a result of adverse effects but showed a higher rate of edema in the treatment group (OR = 6.77; 95% CI, 1.03-44.25). Similarly, no significant differences were seen between the 2 SZC doses for the occurrence of any adverse effects, hyperkalemia, constipation, diarrhea, or urinary tract infection, whereas edema was higher among patients receiving SZC-10 (OR = 3.13; 95% CI, 1.19-8.27). CONCLUSIONS: In patients with acute hyperkalemia, SZC is the drug of choice due to its more rapid reduction of serum potassium level, whereas in patients with chronic hyperkalemia, patiromer appears to be the drug of choice because SZC is associated with an increase in edema, likely due to an increase in sodium absorption, which could have important adverse consequences in patients with chronic kidney disease and or heart failure. Thus, both drugs were found to be safe while treating hyperkalemia. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

Effect of thiamine supplementation in critically ill patients: A systematic review and meta-analysis.

INTRODUCTION: Several studies have previously shown the benefit of thiamine supplementation in critically ill patients. In order to fully appraise the available data, we performed a meta-analysis of 18 published studies. METHODS: A thorough systematic search was conducted. The studies enrolling critically ill patients receiving thiamine supplementation was compared with the standard of care (SOC) group. Data was analyzed using RevMan 5.4. Clinical outcomes were pooled using Odds Ratio (OR) and mean differences. RESULT: Eighteen studies (8 RCTs and 10 cohort studies) met the criteria for quantitative synthesis. In the analysis of RCTs, thiamine supplementation showed 42% lower odds of developing ICU delirium (OR 0.58, 95% CI, 0.34-0.98). A reduction in mortaliy was observed on performing fixed effect model analysis however, a level of statistical significance could not be reached on performing random effect model analysis (OR, 0.78; 95% CI, 0.59 to 1.04). Further sub-group analysis of 13 studies in patients with sepsis, there was no difference in mortality between the two groups (OR, 0.83; 95% CI, 0.63 to 1.09). CONCLUSION: Thiamine supplementation in critically ill patients showed a reduction in the incidence of ICU delirium among RCTs. However, there was no significant benefit in terms of overall mortality, and mortality in patients with sepsis. Further, large scale randomized prospective studies are warranted to investigate the role of thiamine supplementation in critically ill patients.

Identifying High-Risk Subphenotypes and Associated Harms From Delayed Antibiotic Orders and Delivery.

OBJECTIVES: Early antibiotic administration is a central component of sepsis guidelines, and delays may increase mortality. However, prior studies have examined the delay to first antibiotic administration as a single time period even though it contains two distinct processes: antibiotic ordering and antibiotic delivery, which can each be targeted for improvement through different interventions. The objective of this study was to characterize and compare patients who experienced order or delivery delays, investigate the association of each delay type with mortality, and identify novel patient subphenotypes with elevated risk of harm from delays. DESIGN: Retrospective analysis of multicenter inpatient data. SETTING: Two tertiary care medical centers (2008-2018, 2006-2017) and four community-based hospitals (2008-2017). PATIENTS: All patients admitted through the emergency department who met clinical criteria for infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, vitals, laboratory values, medication order and administration times, and in-hospital survival data were obtained from the electronic health record. Order and delivery delays were calculated for each admission. Adjusted logistic regression models were used to examine the relationship between each delay and in-hospital mortality. Causal forests, a machine learning method, was used to identify a high-risk subgroup. A total of 60,817 admissions were included, and delays occurred in 58% of patients. Each additional hour of order delay (odds ratio, 1.04; 95% CI, 1.03-1.05) and delivery delay (odds ratio, 1.05; 95% CI, 1.02-1.08) was associated with increased mortality. A patient subgroup identified by causal forests with higher comorbidity burden, greater organ dysfunction, and abnormal initial lactate measurements had a higher risk of death associated with delays (odds ratio, 1.07; 95% CI, 1.06-1.09 vs odds ratio, 1.02; 95% CI, 1.01-1.03). CONCLUSIONS: Delays in antibiotic ordering and drug delivery are both associated with a similar increase in mortality. A distinct subgroup of high-risk patients exist who could be targeted for more timely therapy.

Sepsis-Induced Cardiomyopathy: a Comprehensive Review.

PURPOSE OF REVIEW: To briefly review epidemiology and pathophysiology of SICM and provide a more extensive review of the data on diagnostic and management strategies. RECENT FINDINGS: SICM is likely underdiagnosed and that has mortality implications. Current evidence supports speckle tracking echocardiography to identify decreased contractility irrespective of left ventricular ejection fraction for the diagnosis of SICM. There continues to be a dearth of large clinical trials evaluating the treatment of SICM and current consensus focuses on supportive measures such as vasopressors and inotropes. Sepsis is a significant cause of mortality, and sepsis-induced cardiomyopathy has both prognostic and management implications for these patients. Individualized work-up and management of these patients is crucial to improving outcomes.

The Emerging Role of Vitamin C as a Treatment for Sepsis.

Sepsis, a life-threatening organ dysfunction due to a dysregulated host response to infection, is a leading cause of morbidity and mortality worldwide. Decades of research have failed to identify any specific therapeutic targets outside of antibiotics, infectious source elimination, and supportive care. More recently, vitamin C has emerged as a potential therapeutic agent to treat sepsis. Vitamin C has been shown to be deficient in septic patients and the administration of high dose intravenous as opposed to oral vitamin C leads to markedly improved and elevated serum levels. Its physiologic role in sepsis includes attenuating oxidative stress and inflammation, improving vasopressor synthesis, enhancing immune cell function, improving endovascular function, and epigenetic immunologic modifications. Multiple clinical trials have demonstrated the safety of vitamin C and two recent studies have shown promising data on mortality improvement. Currently, larger randomized controlled studies are underway to validate these findings. With further study, vitamin C may become standard of care for the treatment of sepsis, but given its safety profile, current treatment can be justified with compassionate use.

A Handoffs Software Led to Fewer Errors of Omission and Better Provider Satisfaction: A Randomized Control Trial.

BACKGROUND: Computer-assisted communication is shown to prevent critical omissions ("errors") in the handoff process. OBJECTIVE: The aim of the study was to study this effect and related provider satisfaction, using a standardized software. METHODS: Fourteen internal medicine house officers staffed 6 days and 1 cross-covering teams were randomized to either the intervention group or control, employing usual handoff, so that handoff information was exchanged only between same-group subjects (daily, for 28 days). RESULTS: In the intervention group, fewer omissions (among those studied) occurred intravenous access (17 versus 422, P < 0.001), code status (1 versus 158, P < 0.001), diet/nothing per mouth (28 versus 477, P < 0.001), and deep venous thrombosis prophylaxis (17 versus 284, P < 0.001); duration to compose handoff was similar; and physicians perceived less workload adjusted for patient census and provider characteristics (P = 0.004) as well as better handoff quality (P < 0.001) and clarity (P < 0.001). CONCLUSIONS: The intervention was associated with fewer errors and superior provider satisfaction.

Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial.

Importance: Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). Objective: To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. Design, Setting, and Participants: The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Interventions: Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. Main Outcomes and Measures: The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Results: Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 µg/mL; difference, 7.94 µg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. Conclusions and Relevance: In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT02106975.

Near-simultaneous intensive care unit (ICU) admissions and all-cause mortality: a cohort study.

PURPOSE: Prior studies have reported the adverse effects of strain on patient outcomes. There is a paucity of literature about a type of strain that may be caused by near-simultaneous intensive care unit (ICU) admissions. We hypothesized that when multiple admissions arrive nearly at the same time, the ICU teams are excessively strained, and this leads to unfavorable patient outcomes. METHODS: This is a retrospective cohort study of consecutive adult patients admitted to an academic medical ICU of a tertiary referral center over five consecutive years. Primary outcomes were the all-cause hospital and ICU mortality. RESULTS: We enrolled 13,234 consecutive ICU admissions during the study period. One-fourth of the admissions had an elapsed time since the last admission (ETLA) of < 55 min. Near-simultaneous admissions (NSA) had on average, a higher unadjusted odds ratio (OR) of ICU death of 1.16 (95% CI 1-1.35, P = 0.05), adjusted 1.23 (95% CI 1.04-1.44, P = 0.01), unadjusted hospital death of 1.11 (95% CI 0.99-1.24, P = 0.06), adjusted 1.20 (95% 1.05-1.35, P = 0.004), and a lower adjusted OR of home discharge of 0.91 (95% CI 0.84-0.99, P = 0.04). NSA was associated with 0.16 (95% CI 0.04-0.29, P = 0.01) added days in the ICU. For each incremental unit increase of the logarithmic transformation of ETLA [log (ETLA in minutes)], the average adjusted hospital mortality OR incrementally decreased by an added average OR of 0.93 (95% CI 0.89‒0.97, P = 0.001). CONCLUSION: Our results suggest that near-simultaneous ICU admissions (NSA) are frequent and are associated with a dose-dependent effect on mortality, length of stay, and odds of home versus nursing facility discharge.

Supply Chain Delays in Antimicrobial Administration After the Initial Clinician Order and Mortality in Patients With Sepsis.

OBJECTIVES: There is mounting evidence that delays in appropriate antimicrobial administration are responsible for preventable deaths in patients with sepsis. Herein, we examine the association between potentially modifiable antimicrobial administration delays, measured by the time from the first order to the first administration (antimicrobial lead time), and death among people who present with new onset of sepsis. DESIGN: Observational cohort and case-control study. SETTING: The emergency department of an academic, tertiary referral center during a 3.5-year period. PATIENTS: Adult patients with new onset of sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled 4,429 consecutive patients who presented to the emergency department with a new diagnosis of sepsis. We defined 0-1 hour as the gold standard antimicrobial lead time for comparison. Fifty percent of patients had an antimicrobial lead time of more than 1.3 hours. For an antimicrobial lead time of 1-2 hours, the adjusted odds ratio of death at 28 days was 1.28 (95% CI, 1.07-1.54; p = 0.007); for an antimicrobial lead time of 2-3 hours was 1.07 (95% CI, 0.85-1.36; p = 0.6); for an antimicrobial lead time of 3-6 hours was 1.57 (95% CI, 1.26-1.95; p < 0.001); for an antimicrobial lead time of 6-12 hours was 1.36 (95% CI, 0.99-1.86; p = 0.06); and for an antimicrobial lead time of more than 12 hours was 1.85 (95% CI, 1.29-2.65; p = 0.001). CONCLUSIONS: Delays in the first antimicrobial execution, after the initial clinician assessment and first antimicrobial order, are frequent and detrimental. Biases inherent to the retrospective nature of the study apply. Known biologic mechanisms support these findings, which also demonstrate a dose-response effect. In contrast to the elusive nature of sepsis onset and sepsis onset recognition, antimicrobial lead time is an objective, measurable, and modifiable process.

Early goal-directed resuscitation of patients with septic shock: current evidence and future directions.

Severe sepsis and septic shock are among the leading causes of mortality in the intensive care unit. Over a decade ago, early goal-directed therapy (EGDT) emerged as a novel approach for reducing sepsis mortality and was incorporated into guidelines published by the international Surviving Sepsis Campaign. In addition to requiring early detection of sepsis and prompt initiation of antibiotics, the EGDT protocol requires invasive patient monitoring to guide resuscitation with intravenous fluids, vasopressors, red cell transfusions, and inotropes. The effect of these measures on patient outcomes, however, remains controversial. Recently, three large randomized trials were undertaken to re-examine the effect of EGDT on morbidity and mortality: the ProCESS trial in the United States, the ARISE trial in Australia and New Zealand, and the ProMISe trial in England. These trials showed that EGDT did not significantly decrease mortality in patients with septic shock compared with usual care. In particular, whereas early administration of antibiotics appeared to increase survival, tailoring resuscitation to static measurements of central venous pressure and central venous oxygen saturation did not confer survival benefit to most patients. In the following review, we examine these findings as well as other evidence from recent randomized trials of goal-directed resuscitation. We also discuss future areas of research and emerging paradigms in sepsis trials.