Analysis of Mortality in Patients Treated With Phenylephrine in Septic Shock.

BACKGROUND: Phenylephrine is a selective α1-receptor agonist used to manage shock. Current guidelines for septic shock recommend limited utilization of phenylephrine due to the lack of evidence available. This deviates from previous guidelines, which had recommendations of when utilization may be appropriate. OBJECTIVE: The primary objective of this study was to evaluate mortality in patients receiving phenylephrine for the management of septic shock. METHODS: This was a retrospective chart review from September 2015 to September 2017 evaluating all adult patients admitted to an intensive care unit (ICU) on vasopressors for management of septic shock. Patients were divided into 2 groups, those treated with phenylephrine and those treated without phenylephrine. The primary outcome was mortality. Secondary objectives included days on vasopressors and ICU length of stay. Two subgroup analyses were performed: 1 for phenylephrine as first-line therapy and 1 for patients with tachycardia at initiation of vasopressors. Patients started on phenylephrine for salvage therapy were excluded from this study. RESULTS: 499 patients enrolled in the study. 148 (32%) were enrolled in the phenylephrine group. Phenylephrine was associated with an increase in mortality (56% vs 41%; p = 0.003). There was no difference in the days on vasopressors or ICU length of stay. Patients who had ongoing tachycardia were associated with increased mortality with phenylephrine (54% vs 36%, p = 0.02). There was no difference in mortality when phenylephrine was started as the initial vasopressor. CONCLUSION: Utilization of phenylephrine in septic shock patients, especially those with ongoing tachycardia, was associated with an increased rate of mortality.

The DOOR to Antibiotic Stewardship: Refining Assessments of Interventions With Desirability of Outcome Ranking.

BACKGROUND: Limited sample size and disparate outcome measures can hinder the ability of antimicrobial stewardship programs to assess the utility of their quality improvement interventions. Desirability of outcome ranking (DOOR) is a novel methodology that incorporates multiple outcomes into a single value to more comprehensively compare therapeutic strategies. The objective of this study was to apply DOOR to a single center antibiotic stewardship intervention. METHODS: A pre- and post-interventional study was conducted evaluating the impact of prospective pharmacist review of rapid molecular diagnostic testing (RDT) of blood cultures on antibiotic optimization. Outcomes included the percentage of patients who were switched to appropriate therapy, the time to appropriate therapy, and the percentage of patients who had missed de-escalation opportunities. RESULTS: A total of 19 and 29 patients were included in the final analysis. The percentage of patients reaching appropriate therapy was 84% (16/19) and 97% ([28/29], p = 0.16) in the pre-intervention and post-intervention groups respectively. Median time to appropriate therapy was 26 hours and 36 minutes (IQR 13:05-50:45) and 22:40 (IQR 3:42-48:23, p = 0.32), respectively. One missed de-escalation opportunity was identified in the post-intervention group (0% vs 3%, p = 1.00). DOOR analysis indicated that the probability of a better outcome for the post-intervention group than the pre-intervention group was 58% (95% CI 54-62). CONCLUSION: In this analysis, DOOR revealed a benefit that would not have been apparent with traditional outcomes assessments. Antimicrobial stewardship programs conducting quality improvement studies should consider incorporating DOOR into their methodology.

Evaluating the Addition of a Clinical Pharmacist Service to a Midlevel Provider-Driven Culture Follow-up Program in a Community Emergency Department.

Background: The impact that an antimicrobial stewardship program can have on an inpatient setting has been well documented, but there are limited data on the use of an antimicrobial stewardship program in the emergency department (ED). Objective: The objective of this study was to assess the impact of adding a pharmacist service to a midlevel provider-driven culture follow-up program in the ED on achieving optimal therapy. Methods: This was a quasi-experimental study with designations of pre- and post-interventions conducted at a large community hospital with the pre-intervention phase occurring from June 1, 2019, to August 31, 2019, and the post-intervention phase occurring from January 1, 2020, to March 31, 2020. The primary outcome was optimal antimicrobial therapy: a composite of optimal antibiotic, dose, and duration, prescribed after the culture resulted. Secondary outcomes included optimal antibiotic, dose, duration, and return to the ED within 30 days due to infection. Results: Optimal antimicrobial therapy received after the culture resulted occurred in 59 patients (26.81%) in the pre-implementation phase and 40 patients (43.96%) in the implementation phase (P = .003). For the secondary outcomes, optimal antibiotic choice occurred in 115 patients (52.27%) in the pre-implementation phase and 66 patients (72.53%) in the implementation phase (P = .001). Optimal antibiotic dose occurred in 113 patients (51.36%) in the pre-implementation phase and 65 patients (71.43%) in the implementation phase (P = .001). Optimal antibiotic duration occurred in 65 patients (29.55%) in the pre-implementation phase and 40 patients (43.96%) in the implementation phase (P = .014). Conclusions: The addition of a clinical pharmacist service in a midlevel provider-driven ED culture callback program resulted in an increased rate of achieving optimal antimicrobial therapy.

Retrospective analysis of anti-inflammatory therapies during the first wave of COVID-19 at a community hospital.

BACKGROUND: Our understanding of the severe acute respiratory syndrome coronavirus 2 has evolved since the first reported cases in December 2019, and a greater emphasis has been placed on the hyper-inflammatory response in severely ill patients. The purpose of this study was to determine risk factors for mortality and the impact of anti-inflammatory therapies on survival. AIM: To determine the impact of various therapies on outcomes in severe coronavirus disease 2019 patients with a focus on anti-inflammatory and immune-modulating agents. METHODS: A retrospective analysis was conducted on 261 patients admitted or transferred to the intensive care unit in two community hospitals between March 12, 2020 and June 17, 2020. Totally 167 patients received glucocorticoid (GC) therapy. Seventy-three patients received GC alone, 94 received GC and tocilizumab, 28 received tocilizumab monotherapy, and 66 received no anti-inflammatory therapy. RESULTS: Patient survival was associated with GC use, either alone or with tocilizumab, and decreased vasopressor requirements. Delayed administration of GC was found to decrease the survival benefit of GC therapy. No difference in survival was found with varying anticoagulant doses, convalescent plasma, tocilizumab monotherapy; prone ventilation, hydroxychloroquine, azithromycin, or intravenous ascorbic acid use. CONCLUSION: This analysis demonstrated the survival benefit associated with anti-inflammatory therapy of GC, with or without tocilizumab, with the combination providing the most benefit. More studies are needed to assess the optimal timing of anti-inflammatory therapy initiation.

A 33-mRNA Classifier Is Able to Produce Inflammopathic, Adaptive, and Coagulopathic Endotypes with Prognostic Significance: The Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis (ORANGES) Trial.

BACKGROUND: Retrospective analysis of the transcriptomic host response in sepsis has demonstrated that sepsis can be separated into three endotypes-inflammatory (IE), adaptive (AE), and coagulopathic (CE), which have demonstrated prognostic significance. We undertook a prospective transcriptomic host response analysis in a subgroup of patients enrolled in the Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis (ORANGES) trial. METHODS: Blood was obtained from 51 patients and profiled using a pre-established 33-mRNA classifier to determine sepsis endotypes. Endotypes were compared to therapy subgroups and clinical outcomes. RESULTS: We redemonstrated a statistically significant difference in mortality between IE, AE, and CE patients, with CE patients demonstrating the highest mortality (40%), and AE patients the lowest mortality (5%, p = 0.032). A higher CE score was a predictor of mortality; coronary artery disease (CAD) and elevated CE scores were associated with an increase in mortality (CAD: HR = 12.3, 95% CI 1.5-101; CE score: HR = 15.5 95% CI 1.15-211). Kaplan-Meier (KM) analysis of the entire cohort (n = 51) demonstrated a decrease survival in the CE group, p = 0.026. KM survival analysis of hydrocortisone, ascorbic acid, and thiamine (HAT) therapy and control patients not receiving steroids (n = 45) showed CE and IE was associated with a decrease in survival (p = 0.003); of interest, there was no difference in survival in CE patients after stratifying by HAT therapy (p = 0.18). These findings suggest a possible treatment effect of corticosteroids, HAT therapy, endotype, and outcome. CONCLUSION: This subset of patients from the ORANGES trial confirmed previous retrospective findings that a 33-mRNA classifier can group patients into IE, AE, and CE endotypes having prognostic significance. A novel finding of this study identifying an association between endotype and corticosteroid therapy warrants further study in support of future diagnostic use of the endotyping classifier.

A Case of Splenic Injury After Shockwave Lithotripsy Presenting as Septic Shock.

BACKGROUND: Shockwave lithotripsy (SWL) is a common procedure, which can result in rare, life-threatening complications, such as splenic rupture, perinephric hematoma, sepsis, and ureteral colic from retained stone. Being able to identify these complications can result in successful diagnosis and expedited management. CASE REPORT: We describe the case of an 82-year-old female presenting to the emergency department (ED) for hypotension and vomiting. The patient had undergone SWL for a kidney stone earlier in the day. On initial evaluation, the patient was hypotensive and reported mild abdominal pain. Although initially evaluated and treated for presumed sepsis, thorough testing was able to diagnose splenic rupture and hemoperitoneum. Splenic rupture is a rare complication of SWL and the patient's initial symptoms of hypotension and fever, with a potential source of infection, suggested a common presentation of sepsis and made this case a unique diagnostic challenge. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diagnosis is always a challenge in the ED, due to the variability of patients that can be seen. Often times, a patient's medical and surgical history will provide guidance. For this reason, it is important to know what complications exist with outpatient procedures, how they may present, and what patient risk factors may lead to an increased incidence.

Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis: The ORANGES Trial.

BACKGROUND: Sepsis is a major public health burden resulting in 25% to 30% in-hospital mortality and accounting for over 20 billion dollars of US hospital costs. RESEARCH QUESTION: Does hydrocortisone, ascorbic acid, thiamine (HAT) therapy improve clinical outcomes in sepsis and septic shock? STUDY DESIGN AND METHODS: This was a randomized, double-blinded, placebo-controlled trial conducted from February 2018 to June 2019, assessing an HAT treatment bundle for the management of septic and septic shock patients admitted to an ICU. The primary outcomes were resolution of shock and change in Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes included 28-day mortality, ICU mortality, hospital mortality, procalcitonin clearance (PCT-c), hospital length of stay (LOS), ICU LOS, and ventilator-free days. RESULTS: One hundred thirty-seven patients were randomized to the treatment group (n = 68) and comparator group (n = 69), respectively, with no significant differences in baseline characteristics. A statistically significant difference was found in the time patients required vasopressors, indicating quicker reversal of shock in the HAT group compared with the comparator group (27 ± 22 vs 53 ± 38 hours, P < .001). No statistically significant change in SOFA score was found between groups 3 (1 - 6) vs 2 (0 - 4), P = .17. No significant differences were found between study arms in ICU and hospital mortality, ICU and hospital LOS, ventilator free days, and PCT-c. INTERPRETATION: Our results suggest that the combination of IV ascorbic acid, thiamine, and hydrocortisone significantly reduced the time to resolution of shock. Additional studies are needed to confirm these findings and assess any potential mortality benefit from this treatment. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03422159; URL: www.clinicaltrials.gov.