Purpose
To evaluate the effects of early combination therapy with intravenous vitamin C and thiamine on recovery from organ failure in patients with septic shock.
Methods
The ascorbic acid and ...thiamine effect in septic shock (ATESS) trial was a multi-centre, double-blind, randomized, controlled trial conducted in four academic emergency departments, enrolling adult patients with septic shock from December 2018 through January 2020. Patients were randomly assigned in a 1:1 ratio to either the treatment group intravenous vitamin C (50 mg/kg, maximum single dose 3 g) and thiamine (200 mg) administration every 12 h for a total of 48 h or the placebo group (identical volume of 0.9% saline with the same protocol). The primary outcome was Δ Sequential Organ Failure Assessment (SOFA) score (SOFA score at enrolment–SOFA score after 72 h). Eighteen secondary outcomes were predefined, including shock reversal and 28-day mortality.
Results
A total of 111 patients were enrolled, of which 53 were assigned to the treatment group and 58 were assigned to the placebo group. There was no significant difference in ΔSOFA scores between the treatment group and the placebo group 3, interquartile range (IQR) − 1 to 5 vs. 3, IQR 0–4, respectively,
p
= 0.96. Predefined secondary outcomes were also not significantly different between the groups.
Conclusion
In this study, vitamin C and thiamine administration in the early phase of septic shock did not improve organ function compared with placebo, despite improvements in vitamin C and thiamine levels.
Precise criteria for extracorporeal cardiopulmonary resuscitation (ECPR) are still lacking in patients with out-of-hospital cardiac arrest (OHCA). We aimed to investigate whether adopting our ...hypothesized criteria for ECPR to patients with refractory OHCA could benefit. This before-after study compared 4.5 years after implementation of ECPR for refractory OHCA patients who met our criteria (Jan, 2015 to May, 2019) and 4 years of undergoing conventional CPR (CCPR) prior to ECPR with patients who met the criteria (Jan, 2011 to Jan, 2014) in the emergency department. The primary and secondary outcomes were good neurologic outcome at 6-months and 1-month respectively, defined as 1 or 2 on the Cerebral Performance Category score. A total of 70 patients (40 with CCPR and 30 with ECPR) were included. For a good neurologic status at 6-months and 1-month, patients with ECPR (33.3%, 26.7%) were superior to those with CCPR (5.0%, 5.0%) (all Ps < 0.05). Among patients with ECPR, a group with a good neurologic status showed shorter low-flow time, longer extracorporeal membrane oxygenation duration and hospital stays, and lower epinephrine doses used (all Ps < 0.05). The application of the detailed indication before initiating ECPR appears to increase a good neurologic outcome rate.
Indications of extracorporeal cardiopulmonary resuscitation (ECPR) are still debatable, particularly in patients with cancer. Prediction of the prognosis of in-hospital cardiac arrest (IHCA) in ...patients with cancer receiving ECPR is important given the increasing prevalence and survival rate of cancer. We compared the neurologic outcomes and survival rates of IHCA patients with and without cancer receiving ECPR. Data from the extracorporeal membrane oxygenation registry between 2015 and 2019 were used in a retrospective manner. The primary outcome was 6-month good neurologic outcome, defined as a Cerebral performance category score of 1 or 2. The secondary outcomes were 1- and 3-month good neurologic outcome, and 6-month survival. Among 247 IHCA patients with ECPR, 43 had active cancer. The 6-month good neurologic outcome rate was 27.9% and 32.4% in patients with and without active cancer, respectively (P > 0.05). Good neurologic outcomes at 1-month (30.2% vs. 20.6%) and 3-month (30.2% vs. 28.4%), and the survival rate at 6-month (39.5% vs. 36.5%) were not significantly different (all P > 0.05) Active cancer was not associated with 6-month good neurologic outcome by logistic regression analyses. Therefore, patients with IHCA should not be excluded from ECPR solely for the presence of cancer itself.
Abstract
This study determined the occurrence of cognitive impairment and mood disorders in out-of-hospital cardiac arrest (OHCA) survivors with good neurologic outcomes. We performed a ...retrospective, cross-sectional, single-center study with a total of 97 patients. We evaluated cognitive dysfunction via the Montreal Cognitive Assessment and Alzheimer’s disease-8 mood disorders via the Patient Health Questionnaire-9 and the Hospital Anxiety and Depression Scale. We measured quality of life with the European Quality of Life 5-Dimension 5-Levels questionnaire. Cognitive impairment and mood disorders were common among patients with good neurologic recovery. There were 23 patients who experienced cognitive impairments (23.7%) and 28 who suffered from mood disorders (28.9%). Age (adjusted OR 1.07, 95% CI 1.02–1.12), mood disorders (adjusted OR 22.80, 95% CI 4.84–107.49) and hospital length of stay (adjusted OR 1.05, 95% CI 1.02–1.09) were independent risk factors for cognitive impairment. The occurrence of cognitive impairments (adjusted OR 9.94, 95% CI 2.83–35.97) and non-cardiac causes of cardiac arrest (adjusted OR 11.51, 95% CI 3.15–42.15) were risk factors for mood disorders. Quality of life was significantly lower in the OHCA survivors with each disorder than the healthy individuals. Routine screening and intervention are needed for OHCA survivors.
The objective of this study was to evaluate the prognostic value of C-reactive protein (CRP), procalcitonin (PCT), and their combination for mortality in patients with septic shock. This multicenter, ...prospective, observational study was conducted between November 2015 and December 2017. A total of 1,772 septic shock patients were included, and the overall 28-day mortality was 20.7%. Although both CRP and PCT were elevated in the non-survivor group, only CRP had statistical significance (11.9 mg/dL vs. 14.7 mg/dL, p = 0.003, 6.4 ng/mL vs. 8.2 ng/mL, p = 0.508). Multivariate analysis showed that CRP and PCT were not independent prognostic markers. In the subgroup analysis of the CRP and PCT combination matrix using their optimal cut-off values (CRP 14.0 mg/dL, PCT 17.0 ng/dL), both CRP and PCT elevated showed significantly higher mortality (Odds ratio 1.552 95% Confidence intervals 1.184-2.035) than both CRP and PCT not elevated (p = 0.001) and only PCT elevated (p = 0.007). However, both CRP and PCT elevated was also not an independent predictor in multivariate analysis. Initial levels of CRP and PCT alone and their combinations in septic shock patients had a limitation to predict 28-day mortality. Future research is needed to determine new biomarkers for early prognostication in patients with septic shock.
The predictive value of the respiratory rate‑oxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from ...patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits.
We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure.
Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively.
The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.
The modified accelerated diagnostic protocol (ADP) to assess patients with chest pain symptoms using troponin as the only biomarker (mADAPT), the History, ECG, Age, Risk factors, and Troponin (HEART) ...pathway, and the Emergency Department Assessment of Chest Pain Rule (EDACS)-ADP, are the three most well-known ADPs for patients with chest pain. These ADPs define major adverse cardiac event (MACE) as components of acute myocardial infarction, revascularization, and death; unstable angina is not included as an endpoint.
We performed a single-center prospective observational study comparing the performance of these 3 ADPs for patients with 30-day MACE with and without unstable angina. We hypothesized that these ADPs will have high sensitivities for MACE without unstable angina, a definition used for score derivation studies. However, when unstable angina is included in the MACE, their performances would be lower than the acceptable rate of >99% sensitivity.
A total of 1,214 patients were included in the analysis. When unstable angina was not included in the endpoint, sensitivities for MACE were 99.1% (95% confidence interval CI: 96.7–99.9%), 99.5% (95% CI: 97.4–100%), and 100% (95% CI: 98.3–100%) for mADAPT, EDACS-ADP, and HEART pathway, respectively. The HEART pathway had the highest proportion of patients classified as low risk (39.2%, 95% CI: 35.8–42.9%), followed by EDACS-ADP (31.3%, 95% CI: 28.2–34.6%) and mADAPT (29.3%, 95% CI: 26.4–32.5%). However, when unstable angina was included in the MACE, sensitivities were 96.6% (95% CI: 94.4–98.1%) for mADAPT, 97.3% (95% CI: 95.3–98.6%) for EDACS-ADP, and 97.3% (95% CI: 95.3–98.6%) for the HEART pathway, respectively. There were 15 false-negative cases with mADAPT, and 12 false-negative cases each for EDACS-ADP and HEART pathway.
All three ADPs—mADAPT, EDACS-ADP, and HEART pathway—were similarly accurate in their discriminatory performance for the risk stratification of ED patients presenting with possible ACS when unstable angina was not included in the endpoint. The HEART pathway showed the best combination of sensitivity and proportion of patients that can be classified as safe for early discharge. However, when unstable angina was added to the endpoint, all three ADPs did not show appropriate safety levels and their performances were lower than the acceptable risk of MACE.
A decrease in skeletal muscle mass has been shown to increase hospital mortality. Nevertheless, little is known about the association between progressive muscle loss over time and clinical outcomes. ...We aimed to evaluate whether progressive loss of muscle mass in septic shock patients was associated with mortality. We reviewed prospectively enrolled registry of septic shock which had 817 consecutive patients. Of these, 175 patients who had computed tomography (CT) at a time of admission as well as 3-6 months prior to admission were included. Between these two CTs, the change in total abdominal muscle area index (TAMAI) was evaluated for progressive muscle loss. The change in TAMAI was higher in the non-survivors (-7.6 cm
/m
, 19.0% decrease) than the survivors (-4.0 cm
/m
, 10.5% decrease) with statistical significance (p = 0.002). Multiple logistic regression showed that the patients who had more than a 6.4 cm
/m
(16.7%) reduction of TAMAI had a 4.42-fold higher risk for mortality at 28 days (OR, 4.42; 95% CI, 1.41-13.81, p = 0.011). Our study suggested that progressive loss of muscle mass might be a useful prognostic factor for septic shock patients. This implication will need to be further explored in future prospective studies.
Previously conducted physician-centered trials on the usefulness of vasopressin have yielded negative results; thus, patient-oriented trials have been warranted. We hypothesize that ...Augmented-Medication CardioPulmonary Resuscitation could be helpful for selected patients with out-of-hospital cardiac arrest (OHCA).
This is a double-blind, single-center, randomized, placebo-controlled trial conducted in the emergency department in a tertiary, university-affiliated hospital in Seoul, Korea. A total of 148 adults with non-traumatic OHCA who had initial diastolic blood pressure (DBP) < 20 mm Hg via invasive arterial monitoring during the early cardiac compression period were randomly assigned to two groups. Patients received a dose of 40 IU of vasopressin or placebo with initial epinephrine. The primary endpoint was a sustained return of spontaneous circulation. Secondary endpoints were survival discharge, and neurologic outcomes at discharge.
Of the 180 included patients, 32 were excluded, and 148 were enrolled in the trial. A sustained return of spontaneous circulation was achieved by 27 patients (36.5%) in the vasopressin group and 24 patients (32.4%) in the control group (risk difference, 4.1%; P = .60). Survival discharge and good neurologic outcomes did not differ between groups. The trial group had significantly higher median DBPs during resuscitation than the control group (16.0 vs. 14.5 mm Hg, P < 0.01). There was no difference in end-tidal carbon dioxide, acidosis, and lactate levels at baseline, 10 min, and end-time.
Among patients with refractory vasodilatory shock in OHCA, administration of vasopressin, compared with placebo, did not significantly increase the likelihood of return of spontaneous circulation.
The clinical characteristics and laboratory values of patients with septic shock who experience in-hospital cardiac arrest (IHCA) have not been well studied. This study aimed to evaluate the ...prevalence of IHCA after admission into the emergency department and to identify the factors that increase the risk of IHCA in septic shock patients. This observational cohort study used a prospective registry of septic shock patients and was conducted at the emergency department of a university-affiliated hospital. The data of 887 adult (age ≥ 18 years) septic shock (defined using the Sepsis-3 criteria) patients who were treated with a protocol-driven resuscitation bundle therapy and were admitted to the intensive care unit between January 2010 and September 2018 were analyzed. The primary endpoint was the occurrence of sepsis-associated cardiac arrest. The patient mean age was 65 years, and 61.8% were men. Sepsis-associated cardiac arrest occurred in 25.3% of patients (n = 224). The 28-day survival rate after cardiac arrest was 6.7%. Multivariate logistic regression identified chronic pulmonary disease (odds ratio (OR) 2.06), hypertension (OR 0.48), unknown infection source (OR 1.82), a hepatobiliary infection source (OR 0.25), C-reactive protein (OR 1.03), and serum lactate level 6 h from shock (OR 1.34). Considering the high mortality rate of sepsis-associated cardiac arrest after cardiopulmonary resuscitation, appropriate monitoring is required in septic shock patients with major risk factors for IHCA.
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