Thiamine as a metabolic resuscitator after out-of-hospital cardiac arrest.

INTRODUCTION: Thiamine is a key cofactor for aerobic metabolism, previously shown to improve mortality and neurological outcomes in a mouse model of cardiac arrest. We hypothesized that thiamine would decrease lactate and improve outcomes in post-arrest patients. METHODS: Single center, randomized, blinded, placebo-controlled, Phase II trial of thiamine in adults within 4.5 hours of return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA), with coma and lactate ≥ 3 mmol/L. Participants received 500 mg IV thiamine or placebo twice daily for 2 days. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. The primary outcome of lactate was checked at baseline, 6, 12, and 24 hours, and compared using a linear mixed model to account for repeated measures. Secondary outcomes included SOFA score, pyruvate dehydrogenase, renal injury, neurological outcome, and mortality. RESULTS: Of 93 randomized patients, 76 were enrolled and included in the analysis. There was no difference in lactate over 24 hours (mean difference 0.34 mmol/L (95% CI: -1.82, 2.50), p = 0.43). There was a significant interaction between randomization lactate subgroup and the effect of the intervention on mortality (p = 0.01) such that mortality was higher with thiamine in the lactate > 5 mmol/L group and lower with thiamine in the < 5 mmol/L group. This subgroup difference prompted the Data and Safety Monitoring Board to recommend the study be terminated early. PDH activity increased over 72 hours in the thiamine group. There were no differences in other secondary outcomes. CONCLUSION: In this single-center randomized trial, thiamine did not affect lactate over 24 hours after OHCA.

Thiamine for Renal Protection in Septic Shock (TRPSS): A Randomized, Placebo-controlled, Clinical Trial.

Rationale: Kidney injury is common and associated with worse outcomes in patients with septic shock. Mitochondrial resuscitation with thiamine (vitamin B1) may attenuate septic kidney injury. Objectives: To assess whether thiamine supplementation attenuates kidney injury in septic shock. Methods: The TRPSS (Thiamine for Renal Protection in Septic Shock) trial was a multicenter, randomized, placebo-controlled trial of thiamine versus placebo in septic shock. The primary outcome was change in serum creatinine between enrollment and 72 hours after enrollment. Measurements and Main Results: Eighty-eight patients were enrolled (42 patients received the intervention, and 46 received placebo). There was no significant between-groups difference in creatinine at 72 hours (mean difference, -0.57 mg/dl; 95% confidence interval, -1.18, 0.04; P = 0.07). There was no difference in receipt of kidney replacement therapy (14.3% vs. 21.7%, P = 0.34), acute kidney injury (as defined by stage 3 of the Kidney Disease: Improving Global Outcomes acute kidney injury scale; 54.7% vs. 73.9%, P = 0.07), or mortality (35.7% vs. 54.3%, P = 0.14) between the thiamine and placebo groups. Patients who received thiamine had more ICU-free days (median [interquartile range]: 22.5 [0.0-25.0] vs. 0.0 [0.0-23.0], P < 0.01). In the thiamine-deficient cohort (27.4% of patients), there was no difference in rates of kidney failure (57.1% thiamine vs. 81.5% placebo) or in-hospital mortality (28.6% vs. 68.8%) between groups. Conclusions: In the TRPSS trial, there was no statistically significant difference in the primary outcome of change in creatinine over time. Patients who received thiamine had more ICU-free days, but there was no difference in other secondary outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT03550794).

Esmolol to Treat the Hemodynamic Effects of Septic Shock: A Randomized Controlled Trial.

INTRODUCTION: Septic shock is often characterized by tachycardia and a hyperdynamic hemodynamic profile. Use of the beta antagonist esmolol has been proposed as a therapy to lower heart rate, thereby improving diastolic filling time and improving cardiac output, resulting in a reduction in vasopressor support. METHODS: We conducted a two-center, open-label, randomized, Phase II trial comparing esmolol to placebo in septic shock patients with tachycardia. The primary endpoint was improvement in hemodynamics as measured by the difference in norepinephrine equivalent dose (NED) between groups at 6 hours after initiation of study drug. Secondary outcomes included assessing differences in inflammatory biomarkers and oxygen consumption (VO2). RESULTS: A total of 1,122 patients were assessed for eligibility and met inclusion criteria; 42 underwent randomization, and 40 received study interventions (18 in the esmolol arm and 22 in the usual care arm). The mean NED at 6 h was 0.30 ±â€Š0.17 mcg/kg/min in the esmolol arm compared to 0.21 ±â€Š0.19 in the standard care arm (P = 0.15). There was no difference in number of shock free days between the esmolol (2, IQR 0, 5) and control groups (2.5, IQR 0, 6) (P = 0.32). There were lower levels of C-reactive protein at 12 and 24 h in the esmolol arm, as well as a statistically significant difference in trend over time between groups. There were no differences in terms of IL-4, IL-6, IL-10, and TNFα. Among a subset who underwent VO2 monitoring, there was decreased oxygen consumption in the esmolol patients; the mean difference between groups at 24 h was -2.07 mL/kg/min (95% CI -3.82, -0.31) (P = 0.02), with a significant difference for the trend over time (P < 0.01). CONCLUSION: Among patients with septic shock, infusion of esmolol did not improve vasopressor requirements or time to shock reversal. Esmolol was associated with decreased levels of C-reactive protein over 24 h. TRIAL REGISTRATION: www.clinicaltrials.gov. Registered February 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02369900.

A Trigger and Response System for Preventing Cardiac Arrest in the ICU.

Although patients in the ICU are closely monitored, some ICU cardiac arrest events may be preventable. In this study, we sought to reduce the rate of cardiac arrests occurring in the ICU through a quality improvement initiative. DESIGN: Prospective, observational study. SETTING: ICUs of a single tertiary care center. PATIENTS: Patients hospitalized in the ICUs between August 2017 and November 2019. INTERVENTIONS: A comprehensive trigger and response tool. MEASUREMENT AND MAIN RESULTS: Forty-three patients experienced an ICU cardiac arrest in the preintervention epoch (6.79 arrests per 1,000 discharges), and 59 patients experienced an ICU cardiac arrest in the intervention epoch (7.91 arrests per 1,000 discharges). In the intervention epoch, the clinical trigger and response tool was activated 106 times over a 1-year period, most commonly due to unexpected new/worsening hypotension. There was no step change in arrest rate (2.24 arrests/1,000 patients; 95% CI, -1.82 to 6.28; p = 0.28) or slope change (-0.02 slope of arrest rate; 95% CI, -0.14 to 0.11; p = 0.79) comparing the preintervention and intervention time epochs. Cardiac arrests in the preintervention epoch were more likely to be "potentially preventable" than that in the intervention epoch (25.6% vs 12.3%, respectively; odds ratio, 0.58; 95% CI, 0.20-0.88; p < 0.01). CONCLUSIONS: A novel trigger-and-response tool did not reduce the frequency of ICU cardiac arrest. Additional investigation is needed into the optimal approach for ICU cardiac arrest prevention.

Ubiquinol (reduced coenzyme Q10) as a metabolic resuscitator in post-cardiac arrest: A randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Ubiquinol (reduced coenzyme Q10) is essential for adequate aerobic metabolism. The objective of this trial was to determine whether ubiquinol administration in patients resuscitated from cardiac arrest could increase physiological coenzyme Q10 levels, improve oxygen consumption, and reduce neurological biomarkers of injury. MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled trial in patients successfully resuscitated from cardiac arrest. Patients were randomized to receive enteral ubiquinol (300 mg) or placebo every 12 h for up to 7 days. The primary endpoint was total coenzyme Q10 plasma levels at 24 h after enrollment. Secondary endpoints included neuron specific enolase, S100B, lactate, cellular and global oxygen consumption, neurological status, and in-hospital mortality. RESULTS: Forty-three patients were included in the modified intention-to-treat analysis. Median coenzyme Q10 levels were significantly higher in the ubiquinol group as compared to the placebo group at 24 h (441 [IQR, 215-510] ηg/mL vs. 113 [IQR, 94-208] ηg/mL, P < 0.001). Similar results were observed at 48 and 72 h. There were no differences between the two groups in any of the secondary endpoints. Median neuron specific enolase levels were not different between the two groups at 24 h (16.8 [IQR, 9.5-19.8] ηg/mL vs. 8.2 [IQR, 4.3-19.1] ηg/mL, P = 0.61). CONCLUSIONS: Administration of enteral ubiquinol increased plasma coenzyme Q10 levels in post-cardiac arrest patients as compared to placebo. There were no differences in neurological biomarkers and oxygen consumption between the two groups.

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Health-Related Quality of Life in Sepsis.

Patients who experience sepsis often have long-term effects that may impact health-related quality of life. This study aimed to investigate whether the combination of ascorbic acid, corticosteroids, and thiamine compared with placebo improves health-related quality of life in patients with septic shock. DESIGN: Secondary analysis of the Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis randomized controlled trial (NCT03389555). SETTING: Thirteen tertiary-care hospitals in the United States. PATIENTS: Patients who were enrolled in Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis, survived to 90 days post enrollment and were able to be contacted by telephone. INTERVENTIONS: Patients were randomly assigned to parenteral ascorbic acid (1,500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days or placebo. MEASUREMENTS AND MAIN RESULTS: One hundred seventeen patients (59%) survived to 90 days and were administered the Short Form 36 questionnaire; of these, 72 (62%) completed the Short Form 36 (38 [53%] in the intervention group, 34 [47%] in placebo). Sixty-six (92%) completed all survey questions (36 [95%] in the intervention group, 30 [88%] in placebo). There was no significant difference in overall Short Form 36 score between intervention and placebo group (median score: 39.4 [interquartile range, 31.2-45.4] vs 43.2 [37.0-46.7], respectively, p = 0.18). We found no statistically significant difference between the two groups in any of the other health-related quality of life domains used. CONCLUSIONS: We found no difference in the health-related quality of life in patients with septic shock treated with a combination of ascorbic acid, corticosteroids, and thiamine compared to placebo.

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.

Continuous Neuromuscular Blockade Following Successful Resuscitation From Cardiac Arrest: A Randomized Trial.

Background Neuromuscular blockade (NMB) agents are often administered to control shivering during targeted temperature management following cardiac arrest. In this study, we hypothesized that early, continuous NMB would result in a greater reduction in serum lactate levels among comatose patients after cardiac arrest. Methods and Results Randomized trial of continuous NMB for 24 hours versus usual care following cardiac arrest conducted at 5 urban centers in the United States. Adult patients who achieved return of spontaneous circulation, remained unresponsive, and underwent targeted temperature management after cardiac arrest were included. The primary outcome was change in lactate over 24 hours. A total of 83 patients were randomized, and 80 were analyzed (37 and 43 in the NMB and usual care arms, respectively). There was no significant interaction between time and treatment group with respect to change in lactate over 24 hours (median lactate change from 4.2 to 2.0 mmol/L [-2.2 mmol/L] in the NMB arm versus 4.0 to 1.7 mmol/L [-2.3 mmol/L] in the usual care arm; geometric mean difference, 1.3 [95% CI, 1.0-1.8]; P=0.07 for the interaction term). There was no difference in hospital survival (38% [NMB] versus 33% [usual care]; P=0.63) or survival with good functional outcome (30% [NMB] versus 21% [usual care]; P=0.35). There were no adverse events in either arm attributed to study interventions. Conclusions Continuous NMB compared with usual care did not reduce lactate over the first 24 hours after enrollment compared with usual care. There was no difference in overall hospital survival, hospital survival with good neurologic outcome, or adverse events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02260258.

Infections in out-of-hospital and in-hospital post-cardiac arrest patients.

This study aims to describe infectious complications in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) patients with sustained return of spontaneous circulation (ROSC) and to compare differences in antimicrobial treatment and outcomes between the two groups. This was a retrospective, single-center, observational study. Adult patients (≥ 18 years) with OHCA or IHCA who had sustained ROSC between December 2007 to March 2015 were included. Blood, urine, sputum, and other fluid cultures, as well as radiologic imaging, were obtained at the discretion of the treating clinical teams. 275 IHCA and 318 OHCA patients were included in the analysis. We found evidence of infection in 181 IHCA and 168 OHCA patients. Significant differences were found between the IHCA and OHCA group in terms of initial rhythm, duration of arrest (10 min vs. 20, p = < 0.001), targeted temperature management (30% vs. 73%, p = < 0.001), and post-arrest infection rates (66% vs 53%, p = 0.001). 95% of IHCA and 82% of OHCA patients received antimicrobial treatment in the post-cardiac arrest period. The source of infection in both groups was largely respiratory, followed by urinary. Gram-positive cocci and gram-negative rods were the most common organisms identified among subjects with culture-proven bacteremia. Infections in the post-arrest period were common in both OHCA and IHCA. We found significantly more infections in IHCA compared to OHCA patients. The most common infection category was respiratory and the most common organism isolated from sputum cultures was Staphylococcus aureus coagulase-positive. The incidence of culture-positive bacteremia was similar in both OHCA and IHCA cohorts but overall lower than previously reported.

Predicting Outcome After Out-of-Hospital Cardiac Arrest: Lactate, Need for Vasopressors, and Cytochrome c.

BACKGROUND: Outcome prediction after out-of-hospital cardiac arrest (OHCA) is difficult. We hypothesized that lactate and need for vasopressors would predict outcome, and that addition of a mitochondrial biomarker would enhance performance of the tool. METHODS: Prospective observational study of OHCA patients presenting to an academic medical center September 2008 to April 2016. We conducted univariate and multivariate logistic regressions. RESULTS: Patients were divided based on 2 variables: vasopressor status and initial lactate (<5 mmol/L, 5-10, ≥10). Three hundred fifty-two patients were evaluated; 249 had a lactate within 3 hours and were included. Patients on vasopressors had higher mortality (74% vs 40%; P < .001). A stepwise increase in mortality is associated with increasing lactate (45% lactate <5, 66% 5-10, and 83% ≥10; P < 001). Multivariable models with lactate group and vasopressors as predictors demonstrated excellent discrimination (area under the receiver operating curve [AUC]: 0.73 [95% confidence interval, CI: 0.66-0.79]; adjusted for additional covariates: AUC: 0.81 [95% CI: 0.75-0.86]). Thirty-six patients had cytochrome c levels available; among these 36, when comparing models with and without cytochrome c, there was no difference (AUC: 0.88 [95% CI: 0.76-1.00] vs AUC: 0.85 [95% CI: 0.73-0.98], respectively; P = .30). CONCLUSION: In this prospective validation, the combination of lactate and vasopressors in the immediate postarrest period is predictive of mortality. Cytochrome c offered minimal additional predictive power.

Cardiac arrest in the intensive care unit: An assessment of preventability.

AIM: Cardiac arrest in the intensive care unit (ICU-CA) is a common and highly morbid event. We investigated the preventability of ICU-CAs and identified targets for future intervention. METHODS: This was a prospective, observational study of ICU-CAs at a tertiary care center in the United States. For each arrest, the clinical team was surveyed regarding arrest preventability. An expert, multi-disciplinary team of physicians and nurses also reviewed each arrest. Arrests were scored 0 (not at all preventable) to 5 (completely preventable). Arrests were considered 'unlikely but potentially preventable' or 'potentially preventable' if at least 50% of reviewers assigned a score of ≥1 or ≥3 respectively. Themes of preventability were assessed for each arrest. RESULTS: 43 patients experienced an ICU-CA and were included. A total of 14 (32.6%) and 13 (30.2%) arrests were identified as unlikely but potentially preventable by the expert panel and survey respondents respectively, and an additional 11 (25.6%) and 10 (23.3%) arrests were identified as potentially preventable. Timing of response to clinical deterioration, missed/incorrect diagnosis, timing of acidemia correction, timing of escalation to a more senior clinician, and timing of intubation were the most commonly cited contributors to potential preventability. Additional themes identified included the administration of anxiolytics/narcotics for agitation later identified to be due to clinical deterioration and misalignment between team and patient/family perceptions of prognosis and goals-of-care. CONCLUSIONS: ICU-CAs may have preventable elements. Themes of preventability were identified and addressing these themes through data-driven quality improvement initiatives could potentially reduce CA incidence in critically-ill patients.

Coenzyme Q10 in acute influenza.

OBJECTIVES: The goal of this investigation was to determine if acute influenza infection is associated with depletion of CoQ10 compared to healthy controls and to determine any associations between CoQ10 levels and illness severity and inflammatory biomarkers. PATIENTS AND METHODS: We analyzed serum CoQ10 concentrations of patients with acute influenza enrolled in a randomized clinical trial prior to study drug administration. Patients were enrolled at a single urban tertiary care center over 3 influenza seasons (December 27, 2013 to March 31, 2016). Wilcoxon rank sum test was used to compare CoQ10 levels between influenza patients and healthy controls. Correlations with inflammatory biomarkers and severity of illness were assessed using Spearman correlation coefficient. RESULTS: We analyzed CoQ10 levels from 50 patients with influenza and 29 controls. Overall, patients with acute influenza had lower levels of CoQ10 (.53 µg/mL, IQR .37-.75 vs .72, IQR .58-.90, P = .004). Significantly more patients in the influenza group had low CoQ10 levels (<.5 µg/mL) compared to controls (48% vs 7%, P < .001). Among influenza patients, there were significant but weak correlations between CoQ10 levels and IL-2 (r = -.30, P = .04), TNF-alpha (r = -.35, P = .01) and VEGF (r = .38, P = .007), but no correlation with IL-6, IL-10, VCAM or influenza severity of illness score (all P > .05). CONCLUSIONS: We found that CoQ10 levels were significantly lower in patients with acute influenza infection and that these levels had significant although weak correlations with several inflammatory biomarkers.

Performance of the CURB-65 Score in Predicting Critical Care Interventions in Patients Admitted With Community-Acquired Pneumonia.

STUDY OBJECTIVE: Confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older (CURB-65) is a clinical prediction rule intended to stratify patients with pneumonia by expected mortality. We assess the predictive performance of CURB-65 for the proximal endpoint of receipt of critical care intervention in emergency department (ED) patients admitted with community-acquired pneumonia. METHODS: We performed a retrospective analysis of electronic health records from a single tertiary center for ED patients admitted as inpatients with a primary diagnosis of pneumonia from 2010 to 2014. Patients with a history of malignancy, tuberculosis, bronchiectasis, HIV, or readmission within 14 days were excluded. We assessed the predictive accuracy of CURB-65 for receipt of critical care interventions (ie, vasopressors, large-volume intravenous fluids, invasive catheters, assisted ventilation, insulin infusions, or renal replacement therapy) and inhospital mortality. Logistic regression was performed to assess the increase in odds of critical care intervention or inhospital mortality by increasing CURB-65 score. RESULTS: There were 2,322 patients admitted with community-acquired pneumonia in the study cohort; 630 (27.1%) were admitted to the ICU within 48 hours of ED triage and 343 (14.8%) received a critical care intervention. Of patients with a CURB-65 score of 0 to 1, 181 (15.6%) were admitted to the ICU, 74 (6.4%) received a critical care intervention, and 7 (0.6%) died. Of patients with a CURB-65 score of 2, 223 (27.0%) were admitted to the ICU, 127 (15.4%) received a critical care intervention, and 47 (5.7%) died. Among patients with CURB-65 score greater than or equal to 3, 226 (67.0%) were admitted to the ICU, 142 (42.1%) received a critical care intervention, and 43 (12.8%) died. The areas under the receiver operating characteristic for CURB-65 as a predictor of critical care intervention and mortality were 0.73 and 0.77, whereas sensitivity of CURB-65 score greater than or equal to 2 in predicting critical care intervention was 78.4%; for mortality, 92.8%. CONCLUSION: Patients with CURB-65 score less than or equal to 2 were often admitted to the ICU and received critical care interventions. Given this finding and the relatively low sensitivity of CURB-65 for critical care intervention, clinicians should exercise caution when using CURB-65 to guide disposition. Future ED-based clinical prediction rules may benefit from calibration to proximal endpoints.

Quick Sequential Organ Failure Assessment and Systemic Inflammatory Response Syndrome Criteria as Predictors of Critical Care Intervention Among Patients With Suspected Infection.

OBJECTIVES: The Sepsis III clinical criteria for the diagnosis of sepsis rely on scores derived to predict inhospital mortality. In this study, we introduce the novel outcome of "received critical care intervention" and investigate the related predictive performance of both the quick Sequential Organ Failure Assessment and the Systemic Inflammatory Response Syndrome criteria. DESIGN: This was a single-center, retrospective analysis of electronic health records. SETTING: Tertiary care hospital in the United States. PATIENTS: Patients with suspected infection who presented to the emergency department and were admitted to the hospital between January 2010 and December 2014. INTERVENTIONS: Systemic Inflammatory Response Syndrome and quick Sequential Organ Failure Assessment scores were calculated, and their relationships to the receipt of critical care intervention and inhospital mortality were determined. MEASUREMENT AND MAIN RESULTS: A total of 24,164 patients were included of whom 6,693 (27.7%) were admitted to an ICU within 48 hours; 4,453 (66.5%) patients admitted to the ICU received a critical care intervention. Among those with quick Sequential Organ Failure Assessment less than 2, 13.4% received a critical care intervention and 3.5% died compared with 48.2% and 13.4%, respectively, for quick Sequential Organ Failure Assessment greater than or equal to 2. The area under the receiver operating characteristic was similar whether quick Sequential Organ Failure Assessment was used to predict receipt of critical care intervention or inhospital mortality (0.74 [95% CI, 0.73-0.74] vs 0.71 [0.69-0.72]). The area under the receiver operating characteristic of Systemic Inflammatory Response Syndrome for critical care intervention (0.69) and mortality (0.66) was lower than that for quick Sequential Organ Failure Assessment (p < 0.001 for both outcomes). The sensitivity of quick Sequential Organ Failure Assessment for predicting critical care intervention was 38%. CONCLUSIONS: Emergency department patients with suspected infection and low quick Sequential Organ Failure Assessment scores frequently receive critical care interventions. The misclassification of these patients as "low risk," in combination with the low sensitivity of quick Sequential Organ Failure Assessment greater than or equal to 2, may diminish the clinical utility of the quick Sequential Organ Failure Assessment score for patients with suspected infection in the emergency department.

Outcomes in variceal hemorrhage following the use of a balloon tamponade device.

BACKGROUND: Variceal hemorrhage is associated with high morbidity and mortality. A balloon tamponade device (BTD), such as the Sengstaken-Blakemore or Minnesota tube, may be used in cases of variceal hemorrhage. While these devices may be effective at controlling acute bleeding, the effect on patient outcomes remains less clear. We sought to describe the number of patients with variceal hemorrhage and a BTD who survive to discharge, survive to one-year, and develop complications related to a BTD. METHODS: In this retrospective study, we identified patients at a single, tertiary care center who underwent placement of a BTD for upper gastrointestinal hemorrhage between 2003 and 2014. Patient characteristics and outcomes were summarized using descriptive statistics. RESULTS: 34 patients with a BTD were identified. Median age was 57.5 (IQR 47-63) and 76% (26/34) were male. Approximately 59% (20/34) of patients survived to discharge, and 41% (13/32) were alive after one year. Two patients were lost to follow-up. Of those surviving to discharge, 95% (19/20) had undergone transjugular intrahepatic portosystemic shunt (TIPS), while 36% (5/14) of patients who did not survive to discharge had TIPS (p<0.01). One complication, an esophageal perforation, was identified and managed conservatively. CONCLUSION: In this cohort of patients undergoing BTD placement for variceal hemorrhage, approximately 59% of patients were alive at discharge and 41% were alive after one year. Placement of a BTD as a temporizing measure in the management of acute variceal hemorrhage may be helpful, particularly when utilized as a bridge to more definitive therapy.

Predicting in-hospital mortality for initial survivors of acute respiratory compromise (ARC) events: Development and validation of the ARC Score.

AIM: Acute respiratory compromise (ARC) is a common and highly morbid event in hospitalized patients. To date, however, few investigators have explored predictors of outcome in initial survivors of ARC events. In the present study, we leveraged the American Heart Association's Get With The Guidelines®-Resuscitation (GWTG-R) ARC data registry to develop a prognostic score for initial survivors of ARC events. METHODS: Using GWTG-R ARC data, we identified 13,193 index ARC events. These events were divided into a derivation cohort (9807 patients) and a validation cohort (3386 patients). A score for predicting in-hospital mortality was developed using multivariable modeling with generalized estimating equations. RESULTS: The two cohorts were well balanced in terms of baseline demographics, illness-types, pre-event conditions, event characteristics, and overall mortality. After model optimization, nine variables associated with the outcome of interest were included. Age, hypotension preceding the event, and intubation during the event were the greatest predictors of in-hospital mortality. The final score demonstrated good discrimination in both the derivation and validation cohorts. The score was also very well calibrated in both cohorts. Observed average mortality was <10% in the lowest score category of both cohorts and >70% in the highest category, illustrating a wide range of mortality separated effectively by the scoring system. CONCLUSIONS: In the present study, we developed and internally validated a prognostic score for initial survivors of in-hospital ARC events. This tool will be useful for clinical prognostication, selecting cohorts for interventional studies, and for quality improvement initiatives seeking to risk-adjust for hospital-to-hospital comparisons.

Acute Respiratory Compromise in the Emergency Department: A Description and Analysis of 3571 Events from the Get With the Guidelines-Resuscitation® Registry.

BACKGROUND: Respiratory events requiring the use of assisted ventilation are relatively common in the emergency department (ED), and can be associated with substantial morbidity and mortality. OBJECTIVE: The aim of this study was to describe and elucidate patient and event characteristics associated with mortality and progression to cardiac arrest in ED patients with acute respiratory compromise. METHODS: Data were obtained from the multicenter Get With the Guidelines-Resuscitation® registry. We included patients with acute respiratory compromise defined as absent, agonal, or inadequate respiration that required emergency assisted ventilation. All adult patients between January 2005 and December 2014 with an index event in the ED were included. We used multivariable logistic regression models to assess the association between patient and event characteristics and in-hospital mortality, with cardiac arrest during the event as a secondary outcome. RESULTS: A total of 3571 events were included. The in-hospital mortality was 34%. Twelve percent of events progressed to cardiac arrest, with a subsequent 82% in-hospital mortality. When adjusting for patient and event characteristics, we found no temporal changes in in-hospital mortality from 2005 to 2014. Several characteristics were associated with increased mortality, such as pre-event hypotension, septicemia, and acute stroke. Similarly, multiple characteristics, including pre-event hypotension, were associated with progression to cardiac arrest. CONCLUSIONS: Patient with acute respiratory compromise in the ED had an in-hospital mortality of 34% in the current study. These patients also have a high risk of progressing to cardiac arrest, with a subsequent increase in in-hospital mortality to 82%. Potentially reversible characteristics, such as hypotension before the event, showed a strong association to in-hospital mortality, along with multiple other patient and event characteristics.

Reasons for death in patients with sepsis and septic shock.

PURPOSE: Understanding the underlying cause of mortality in sepsis has broad implications for both clinical care and interventional trial design. However, reasons for death in sepsis remain poorly understood. We sought to characterize reasons for in-hospital mortality in a population of patients with sepsis or septic shock. MATERIALS AND METHODS: We performed a retrospective review of patients admitted to the intensive care unit with sepsis or septic shock who died during their index admission. Reasons for death were classified into 6 categories determined a priori by group consensus. Interrater reliability was calculated and Fleiss κ reported. The associations between selected patient characteristics (eg, serum lactate) and reason for death were also assessed. RESULTS: One hundred fifteen patients were included. Refractory shock (40%) and comorbid withdrawal of care (44%) were the most common reasons for death. Overall interrater agreement was substantial (κ = 0.61, P<.01). Lactate was higher in patients who died because of refractory shock as compared with those who died for other reasons (4.7 vs 2.8 mmol/L, P<.01). CONCLUSION: In this retrospective cohort, refractory shock and comorbid withdrawal of care were the most common reasons for death. Following prospective validation, the classification methodology presented here may be useful in the design/interpretation of trials in sepsis.

Acute respiratory compromise on inpatient wards in the United States: Incidence, outcomes, and factors associated with in-hospital mortality.

AIM: To estimate the United States' incidence and in-hospital mortality of acute respiratory events on inpatient wards and to identify factors associated with mortality. METHODS: This is an analysis of prospectively collected data from the Get With the Guidelines(®) - Resuscitation registry. We included adult patients with index acute respiratory events on inpatient wards from January 2005 to December 2013. A negative binomial regression model was used to estimate the 2012 United States incidence and a multivariable logistic regression model was used to examine time trends and characteristics associated with in-hospital mortality. RESULTS: There were 13,086 index events from 320 hospitals included in the analysis. Using 2012 data, the estimated number of events in the United States was 44,551 (95%CI: 25,170-95,371). The in-hospital mortality for the entire cohort was 39.4% (95%CI: 38.5, 40.2) and rose to 82.6% (95%CI: 79.9, 85.2) for events leading to cardiac arrest. There was a decrease in in-hospital mortality over time (48.3% in 2005 to 34.5% in 2013, p<0.001). Characteristics associated with mortality included agonal breathing, hypotension and septicemia. CONCLUSIONS: Acute respiratory events on inpatient wards in the US is common with an associated in-hospital mortality of approximately 40% that has been decreasing over the past decade. Multiple factors were associated with in-hospital mortality.

Thiamine as an adjunctive therapy in cardiac surgery: a randomized, double-blind, placebo-controlled, phase II trial.

BACKGROUND: Thiamine is a vitamin that is essential for adequate aerobic metabolism. The objective of this study was to determine if thiamine administration prior to coronary artery bypass grafting would decrease post-operative lactate levels as a measure of increased aerobic metabolism. METHODS: We performed a randomized, double-blind, placebo-controlled trial of patients undergoing coronary artery bypass grafting. Patients were randomized to receive either intravenous thiamine (200 mg) or placebo both immediately before and again after the surgery. Our primary endpoint was post-operative lactate levels. Additional endpoints included pyruvate dehydrogenase activity, global and cellular oxygen consumption, post-operative complications, and hospital and intensive care unit length of stay. RESULTS: Sixty-four patients were included. Thiamine levels were significantly higher in the thiamine group as compared to the placebo group immediately after surgery (1200 [683, 1200] nmol/L vs. 9 [8, 13] nmol/L, p < 0.001). There was no difference between the groups in the primary endpoint of lactate levels immediately after the surgery (2.0 [1.5, 2.6] mmol/L vs. 2.0 [1.7, 2.4], p = 0.75). Relative pyruvate dehydrogenase activity was lower immediately after the surgery in the thiamine group as compared to the placebo group (15% [11, 37] vs. 28% [15, 84], p = 0.02). Patients receiving thiamine had higher post-operative global oxygen consumption 1 hour after the surgery (difference: 0.37 mL/min/kg [95% CI: 0.03, 0.71], p = 0.03) as well as cellular oxygen consumption. We found no differences in clinical outcomes. CONCLUSIONS: There were no differences in post-operative lactate levels or clinical outcomes between patients receiving thiamine or placebo. Post-operative oxygen consumption was significantly increased among patients receiving thiamine. TRIAL REGISTRATION: clinicaltrials.gov NCT02322892, December 14, 2014.