Management Of Septic Patients Research Articles

Epigenetic Mechanisms in Sepsis-Associated Acute Kidney Injury.

Sepsis, the dysregulated immune response of the host to infections, leads to numerous complications, including multiple organ dysfunction with sepsis-associated acute kidney injury (SA-AKI) being a frequent complication associated with increased risk of mortality and the progression toward chronic kidney disease (CKD). Several mechanisms have been widely investigated in understanding the complex pathophysiology of SA-AKI, including hemodynamic alterations, inflammation, oxidative stress, and direct cellular injury driven by pathogens or cell-derived products (pathogen-associated molecular patterns and damage-associated molecular patterns). Despite advancements in the management of septic patients, the prognosis of SA-AKI patients remains significantly poor and is associated with high in-hospital mortality and adverse long-term outcomes. Therefore, recent research has focused on the early identification of specific SA-AKI endotypes and subphenotypes through epigenetic analysis and the use of potential biomarkers, either alone or in combination with clinical data, to improve prognosis. Epigenetic regulation, such as DNA methylation, histone modifications, and noncoding RNA modulation, is crucial in modulating gene expression in response to stress and renal injury in SA-AKI. At the same time, these modifications are dynamic and reversible processes that can alter gene expression in several pathways implicated in the context of SA-AKI, including inflammation, immune response, and tolerance status. In addition, specific epigenetic modifications may exacerbate renal damage by causing persistent inflammation or cellular metabolic reprogramming, leading to progression toward CKD. This review aims to provide a comprehensive understanding of the epigenetic characteristics that define SA-AKI, also exploring targeted therapies that can improve patient outcomes and limit the chronic progression of this syndrome.

Oxidative Stress in Sepsis: A Focus on Cardiac Pathology.

This study aims to analyze post-mortem human cardiac specimens, to verify and evaluate the existence or extent of oxidative stress in subjects whose cause of death has been traced to sepsis, through immunohistological oxidative/nitrosative stress markers. Indeed, in the present study, i-NOS, NOX2, and nitrotyrosine markers were higher expressed in the septic death group when compared to the control group, associated with also a significant increase in 8-OHdG, highlighting the pivotal role of oxidative stress in septic etiopathogenesis. In particular, 70% of cardiomyocyte nuclei from septic death specimens showed positivity for 8-OHdG. Furthermore, intense and massive NOX2-positive myocyte immunoreaction was noticed in the septic group, as nitrotyrosine immunostaining intense reaction was found in the cardiac cells. These results demonstrated a correlation between oxidative and nitrosative stress imbalance and the pathophysiology of cardiac dysfunction documented in cases of sepsis. Therefore, subsequent studies will focus on the expression of oxidative stress markers in other organs and tissues, as well as on the involvement of the intracellular pattern of apoptosis, to better clarify the complex pathogenesis of multi-organ failure, leading to support the rationale for including therapies targeting redox abnormalities in the management of septic patients.

Microcirculation-guided resuscitation in sepsis: the next frontier?

Microcirculatory dysfunction plays a key role in the pathogenesis of tissue dysoxia and organ failure in sepsis. Sublingual videomicroscopy techniques enable the real-time non-invasive assessment of microvascular blood flow. Alterations in sublingual microvascular perfusion were detected during sepsis and are associated with poor outcome. More importantly, sublingual videomicroscopy allowed to explore the effects of commonly applied resuscitative treatments in septic shock, such as fluids, vasopressors and inotropes, and showed that the optimization of macro-hemodynamic parameters may not be accompanied by an improvement in microvascular perfusion. This loss of "hemodynamic coherence," i.e., the concordance between the response of the macrocirculation and the microcirculation, advocates for the integration of microvascular monitoring in the management of septic patients. Nonetheless, important barriers remain for a widespread use of sublingual videomicroscopy in the clinical practice. In this review, we discuss the actual limitations of this technique and future developments that may allow an easier and faster evaluation of the microcirculation at the bedside, and propose a role for sublingual microvascular monitoring in guiding and titrating resuscitative therapies in sepsis.

Fluids and Early Vasopressors in the Management of Septic Shock: Do We Have the Right Answers Yet?

Septic shock is a common condition associated with hypotension and organ dysfunction. It is associated with high mortality rates of up to 60% despite the best recommended resuscitation strategies in international guidelines. Patients with septic shock generally have a Mean Arterial Pressure below 65 mmHg and hypotension is the most important determinant of mortality among this group of patients. The extent and duration of hypotension are important. The two initial options that we have are 1) administration of intravenous (IV) fluids and 2) vasopressors, The current recommendation of the Surviving Sepsis Campaign guidelines to administer 30 ml/kg fluid cannot be applied to all patients. Complications of fluid over-resuscitation further delay organ recovery, prolong ICU and hospital length of stay, and increase mortality. The only reason for administering intravenous fluids in a patient with circulatory shock is to increase the mean systemic filling pressure in a patient who is volume-responsive, such that cardiac output also increases. The use of vasopressors seems to be a more appropriate strategy, the very early administration of vasopressors, preferably during the first hour after diagnosis of septic shock, may have a multimodal action and potential advantages, leading to lower morbidity and mortality in the management of septic patients. Vasopressor therapy should be initiated as soon as possible in patients with septic shock.

Genes regulating oxidative-inflammatory response in circulating monocytes and neutrophils in septic syndrome.

Despite significant progress in the past decades, sepsis still lacks a specific treatment. Under normal conditions, leucocytes play a critical role in controlling infection and it is suggested that their activity is impaired during sepsis which contribute to the dysregulation of immune reactions. Indeed, in response to infection, several intracellular pathways are affected mainly those regulating the oxidative- inflammatory axis. Herein, we focused on the contribution of NF-kB, iNOS, Nrf2, HO-1 and MPO genes in the pathophysiology of septic syndrome, by analyzing the differential expression of their transcripts in circulating monocytes and neutrophils, and monitoring the nitrosative/oxidative status in septic syndrome patients. Circulating neutrophils of septic patients displayed a significant overexpression of NF-kB compared to other groups. In monocytes, patients with septic shock expressed the highest levels of iNOS and NF-kB mRNA. However, genes involved in cytoprotective response had increased expression in patients with sepsis, in particular, the Nrf2 and its target gene HO-1. Moreover, patient monitoring indicates that the iNOS enzyme expression and NO plasma levels may play a role in assessing the severity of septic conditions. Overall, in either monocytes or neutrophils, we pointed out the major role of NF-κB and Nrf2 in the pathophysiological process. Therefore, therapies targeted to redox abnormalities may be useful for better management of septic patients.

Implementing Alfred60AST in a clinical lab: Clinical impact on the management of septic patients and financial analysis

Sepsis is an important cause of morbidity and mortality. An accelerated microbiology diagnosis is crucial in order to reduce the time to initiate targeted antibiotic therapy. The Alfred60AST system is able to provide phenotypic Antimicrobial Susceptibility Testing (AST) results within hours. This study has two objectives: assess the clinical impact of this technology and determine its cost-effectiveness. During a ten-week period, all new enterobacterial or enterococcal bloodstream infection was analyzed with the Alfred60AST system, in parallel with routine methods. Its impact on the clinician's therapeutic strategy was studied. In order to assess the financial and practical aspects of the method, an analysis of the extracosts and a survey of the technical staff were conducted. Fifty-three cases of bacteriemia were included. For the Enterobacteriaceae bacteriemias, a clinical impact was shown in 18.9% of the cases (e.g, treatment modification). The financial analysis highlighted an increase in costs (+38% for Enterobacteriaceae, +50% for Enterococci), compared to the theoretical costs reported by the firm, due to the workflow and the volumes of samples used. Finally, results of the technical staff survey were favorable in terms of ease of use of the system. In addition to its ease of use, the Alfred60AST system is able to provide an AST in a record time. This study shows a real interest of the technique in the therapeutic management of patients with enterobacterial sepsis. However, its routine implementation requires an increase of the analyzed volumes as well as a 24/7 organization of the laboratory in order to be profitable.

Trends in mortality in septic patients according to the different organ failure during 15 years

BackgroundThe incidence of sepsis can be estimated between 250 and 500 cases/100.000 people per year and is responsible for up to 6% of total hospital admissions. Identified as one of the most relevant global health problems, sepsis is the condition that generates the highest costs in the healthcare system. Important changes in the management of septic patients have been included in recent years; however, there is no information about how changes in the management of sepsis-associated organ failure have contributed to reduce mortality.MethodsA retrospective analysis was conducted from hospital discharge records from the Minimum Basic Data Set Acute-Care Hospitals (CMBD-HA in Catalan language) for the Catalan Health System (CatSalut). CMBD-HA is a mandatory population-based register of admissions to all public and private acute-care hospitals in Catalonia. Sepsis was defined by the presence of infection and at least one organ dysfunction. Patients hospitalized with sepsis were detected, according ICD-9-CM (since 2005 to 2017) and ICD-10-CM (2018 and 2019) codes used to identify acute organ dysfunction and infectious processes.ResultsOf 11.916.974 discharges from all acute-care hospitals during the study period (2005–2019), 296.554 had sepsis (2.49%). The mean annual sepsis incidence in the population was 264.1 per 100.000 inhabitants/year, and it increased every year, going from 144.5 in 2005 to 410.1 in 2019. Multiorgan failure was present in 21.9% and bacteremia in 26.3% of cases. Renal was the most frequent organ failure (56.8%), followed by cardiovascular (24.2%). Hospital mortality during the study period was 19.5%, but decreases continuously from 25.7% in 2005 to 17.9% in 2019 (p < 0.0001). The most important reduction in mortality was observed in cases with cardiovascular failure (from 47.3% in 2005 to 31.2% in 2019) (p < 0.0001). In the same way, mean mortality related to renal and respiratory failure in sepsis was decreased in last years (p < 0.0001).ConclusionsThe incidence of sepsis has been increasing in recent years in our country. However, hospital mortality has been significantly reduced. In septic patients, all organ failures except liver have shown a statistically significant reduction on associated mortality, with cardiovascular failure as the most relevant.

Role of Caveolin-1 in Sepsis – A Mini-Review

Sepsis is a generalized disease characterized by an extreme response to a severe infection. Moreover, challenges remain in the diagnosis, treatment and management of septic patients. In this mini-review we demonstrate developments on cellular pathogenesis and the role of Caveolin-1 (Cav-1) in sepsis. Studies have shown that Cav-1 has a significant role in sepsis through the regulation of membrane traffic and intracellular signaling pathways. In addition, activation of apoptosis/autophagy is considered relevant for the progression and development of sepsis. However, how Cav-1 is involved in sepsis remains unclear, and the precise mechanisms need to be further investigated. Finally, the role of Cav-1 in altering cell permeability during inflammation, in sepsis caused by microorganisms, apoptosis/autophagy activation and new therapies under study are discussed in this mini-review.

Beyond the bundle: Clinical controversies in the management of sepsis in emergency medicine patients.

Sepsis is a condition characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. The emergency department (ED) serves as a crucial entry point for patients presenting with sepsis. Given the heterogeneous presentation and high mortality rate associated with sepsis and septic shock, several clinical controversies have emerged in the management of sepsis. These include the use of novel therapeutic agents like angiotensin II, hydrocortisone, ascorbic acid, thiamine ("HAT") therapy, and levosimendan, Additionally, controversies with current treatments in vasopressor dosing, and the use of and balanced or unbalanced crystalloid are crucial to consider. The purpose of this review is to discuss clinical controversies in the management of septic patients, including the use of novel medications and dosing strategies, to assist providers in appropriately determining what treatment strategy is best suited for patients.

Prognostic scores and early management of septic patients in the emergency department of a secondary hospital: results of a retrospective study

BackgroundSequential Organ Failure Assessment (SOFA) and other illness prognostic scores predict adverse outcomes in critical patients. Their validation as a decision-making tool in the emergency department (ED) of secondary hospitals is not well established. The aim of this study was to compare SOFA, NEWS2, APACHE II, and SAPS II scores as predictors of adverse outcomes and decision-making tool in ED.MethodsData of 121 patients (age 73 ± 10 years, 58% males, Charlson Comorbidity Index 5.7 ± 2.1) with a confirmed sepsis were included in a retrospective study between January 2017 and February 2020. Scores were computed within the first 24 h after admission. Primary outcome was the occurrence of either in-hospital death or mechanical ventilation within 7 days. Secondary outcome was 30-day all-cause mortality.ResultsPatients older than 64 years (elderly) represent 82% of sample. Primary and secondary outcomes occurred in 40 and 44%, respectively. Median 30-day survival time of dead patients was 4 days (interquartile range 1–11). The best predictive score based on the area under the receiver operating curve (AUROC) was SAPS II (0.823, 95% confidence interval, CI, 0.744–0.902), followed by APACHE II (0.762, 95% CI 0.673–0.850), NEWS2 (0.708, 95% CI 0.616–0.800), and SOFA (0.650, 95% CI 0.548–0.751). SAPS II cut-off of 49 showed the lowest false-positive rate (12, 95% CI 5–20) and the highest positive predictive value (80, 95% CI 68–92), whereas NEWS2 cut-off of 7 showed the lowest false-negative rate (10, 95% CI 2–19) and the highest negative predictive value (86, 95% CI 74–97). By combining NEWS2 and SAPS II cut-offs, we accurately classified 64% of patients. In survival analysis, SAPS II cut-off showed the highest difference in 30-day mortality (Hazards Ratio, HR, 5.24, 95% CI 2.99–9.21, P < 0.001). Best independent negative predictors of 30-day mortality were body temperature, mean arterial pressure, arterial oxygen saturation, and hematocrit levels. Positive predictors were male sex, heart rate and serum sodium concentration.ConclusionsSAPS II is a good prognostic tool for discriminating high-risk patient suitable for sub-intensive/intensive care units, whereas NEWS2 for discriminating low-risk patients for low-intensive units. Our results should be limited to cohorts with a high prevalence of elderly or comorbidities.

Temporal Trends in the Microbiological Characteristics of Sepsis in the United States: A Population Based Study.

Epidemiologic studies are needed for monitoring population-level trends in sepsis. This study examines sepsis-causing microorganisms from 2006 to 2014 in the United States using data from the Nationwide Inpatient Sample database. 7 860 686 adults hospitalized with sepsis were identified using a validated ICD-9 coding approach. Associated microorganisms were identified by ICD-9 code and classified by major groups (Gram-positive, Gram-negative, fungi, anaerobes) and specific species for analysis of their incidence and mortality. The rate of sepsis incidence has increased for all four major categories of pathogens, while the mortality rate decreased. In 2014, Gram-negative pathogens had a higher incidence than Gram-positives. Anaerobes increased the fastest with an average annual increase of 20.17% (p < 0.001). Fungi had the highest mortality (19.28%) and the slowest annual decrease of mortality (-2.31%, p = 0.006) in 2013, while anaerobic sepsis had the highest hazard of mortality (adjusted HR 1.60, 95% CI 1.53-1.66). Gram-negative pathogens have replaced Gram-positives as the leading cause of sepsis in the United States in 2014 during the study period (2006-2014). The incidence of anaerobic sepsis has an annual increase of 20%, while the mortality of fungal sepsis has not decreased at the same rate as other microorganisms. These findings should inform the diagnosis and management of septic patients, as well as the implementation of public health programs.

A Practical Approach to Antibiotic Use in Critically Ill Obstetric Patients.

In recent years, several new antimicrobials have become available that are safer and more effective compared with older agents commonly used in obstetrics. Basic knowledge of these agents is of paramount importance to obstetricians and maternal fetal medicine specialists, as administration of early adequate broad-spectrum empiric antibiotic coverage plays a pivotal role in the management of septic patients. Of particular importance is the critically ill pregnant patient with life-threatening infectious processes in whom poor initial antibiotic selection may result in higher mortality and significant side effects from antibiotics themselves. In this article we aim to provide a guide for clinicians to select an adequate empirical antibiotic regimen for the most common severe infections that may affect pregnant individuals.

Dysregulated Immunity and Immunotherapy after Sepsis.

Implementation of protocolized surveillance, diagnosis, and management of septic patients, and of surgical sepsis patients in particular, is shown to result in significantly increased numbers of patients surviving their initial hospitalization. Currently, most surgical sepsis patients will rapidly recover from sepsis; however, many patients will not rapidly recover, but instead will go on to develop chronic critical illness (CCI) and experience dismal long-term outcomes. The elderly and comorbid patient is highly susceptible to death or CCI after sepsis. Here, we review aspects of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) endotype to explain the underlying pathobiology of a dysregulated immune system in sepsis survivors who develop CCI; then, we explore targets for immunomodulatory therapy.

Immunomodulatory effects of anaesthetic sevoflurane in septic mouse model.

Sepsis is one among the dangerous medical threat that is very much related to body’s immune system having no proper treatment for this condition. About19 million cases of sepsis have been recorded and out of which 5 million cases die every year. Sevoflurane other than controlling the depth of anaesthesia, it does have a vital role in immunomodulations. The study is focused on investigating the immunomodulatory effects of sevoflurane in the septic mouse model induced by CLP. Mortality rate, organ damage, inflammatory mediators, bacterial load, coagulopathy, hepto and renal functional changes, serum lactate, blood glucose, neutrophil sequestration and finally histopathological examination were investigated. The results were interesting that exposure to sevoflurane improves the polymicrobial abdominal sepsis outcome. Mice exposed to sevoflurane after CLP significantly improved outcomes of polymicrobial abdominal sepsis and reduced mortality by improving overall 7-day survival (83.3%) compared to mice without sevoflurane (no treatment group 16.6%) additionally decreasing the surrogate marker levels in the experimental sepsis animal model conducted. Our study suggests that the selection of certain anaesthetic drugs could be critical in the management of septic patients because their immunomodulatory effects could be large enough to affect sepsis pathophysiology.

A study on adherence to surviving sepsis campaign bundle at a tertiary care hospital in Sri Lanka

Background: The global incidence of sepsis is increasing and mortality remains high. The mortality is even higher in resource poor countries where facilities and equipment is limited. The Surviving Sepsis Campaign(SSC) recommends an updated Hour-1 Bundle based on the evidence from the International guidelines for management of sepsis and septic shock 2016. to reduce mortality from sepsis, compliance with the “bundle” is essential. Data from developing countries like Sri Lanka on the management of sepsis according to the SSCs guidelines are not available. Hence, this study looks at the patient characteristics and management of septic patients at a tertiary care hospital in Sri Lanka. Methods and materials: Patients admitted to the university medical unit of Colombo south teaching hospital from January to August 2019 fulfilling the inclusion criteria were included. The hour-1 sepsis bundle adherence, demographic data and management were recorded. Results: There were 387 patients: 163 males and 224 females. The age range was 15–95 with a mean age of 63. 83.7% were direct admissions while 16.3% were transfers from a peripheral hospital. Most common source of infection was urine 82(21.2%) followed by blood stream 105 (27.1%), and skin and soft tissue 114 (29.5%). One hour SSC bundle compliance: administration of intravenous fluids: 42 (10.9%), blood cultures before antibiotics: 225 (58.1%), first dose antibiotic: 15 (3.9%), Arterial blood gas: 60 (15.5%). Staffing capacity did not make a difference to adherence to the bundle. The study mortality rate was 37 (9.6%). Binary logistic regression indicates that Quick sequential organ failure assessment score (qSOFA) is a significant predictor of mortality, [ChiSquare = 35.08, df = 3 and p = 0.000 (<0.05)] with an odds ratio (OR) of 7.529 (95% CI 3.597-14.323). The other predictors’ age, sex, adherence to sepsis care bundle, co morbidities were not significant. Conclusion: In conclusion, mortality of sepsis is high and adherence to sepsis care bundle is poor in Sri Lanka even at a tertiary care hospital. Education and training of staff is needed to boost adherence. This will in turn improve quality of care and outcomes of septic patients in resource poor countries.

A Descriptive Study on Sepsis: Causes, Outcomes, and Adherence to Guidelines on Patients with Sepsis at a Tertiary Care Hospital in Sri Lanka.

The global incidence of sepsis is increasing, and mortality remains high. The mortality is even higher in resource-poor countries where facilities and equipment are limited. The Surviving Sepsis Campaign (SSC) recommends an updated hour-1 bundle based on the evidence from the International Guidelines for Management of Sepsis and Septic Shock 2018. To reduce mortality from sepsis, compliance with the “bundle” is essential. Data from developing countries like Sri Lanka on the management of sepsis according to the SSC guidelines are not available. Hence, this study looks at the patient characteristics and management of septic patients at a tertiary care hospital in Sri Lanka. Patients admitted to the University Medical Unit of Colombo South Teaching Hospital from January to August 2019 fulfilling the inclusion criteria were included. The hour-1 sepsis bundle adherence, demographic data, and management were recorded. There were 387 patients: 163 males and 224 females. The age range was 15-95 with a mean age of 63. 83.7% were direct admissions while 16.3% were transfers from a peripheral hospital. The most common source of infection was urine (82 (21.2%)) followed by blood stream (105 (27.1%)) and skin and soft tissue (114 (29.5%)). One-hour SSC bundle compliance is as follows: administration of intravenous fluids: 42 (10.9%), blood cultures before antibiotics: 225 (58.1%), first dose antibiotic: 15 (3.9%), and arterial blood gas: 60 (15.5%). Staffing capacity did not make a difference to adherence to the bundle. The study mortality rate was 37 (9.6%). Binary logistic regression indicates that quick sequential organ failure assessment (qSOFA) score is a significant predictor of mortality (chi‐square = 35.08, df = 3, and p = 0.001 (<0.05)) with an odds ratio (OR) of 7.529 (95% CI 3.597-14.323). The other predictors, age, sex, adherence to sepsis care bundle, and comorbidities, were not significant. In conclusion, mortality of sepsis is high and adherence to sepsis care bundle is poor in Sri Lanka even at a tertiary care hospital. Education and training of staff are needed to boost adherence. This will in turn improve quality of care and outcomes of septic patients in resource-poor countries.

Transthoracic echocardiographic versus cardiometry derived indices in management of septic patients

ABSTRACT Background: Sepsis and sepsis shock are leading causes of mortality around the world. Early identification, proper management and close monitoring are associated with improved patient outcomes. Echocardiography allows proper monitoring of fluid-guided therapy and early identification of patients requiring vasopressors and inotropic drugs, although it requires special training and has some limitations. This study aims to compare echocardiography (echo) derived indices to cardiometry-derived indices in management of septic patients. Methods: This prospective, randomized study was carried out on 90 patients with sepsis. The patients were divided into three groups: cardiometry group, which included those who underwent evaluation by the electrical cardiometry monitor; echo group, which included patients who underwent resting transthoracic echocardiography; and early goal-directed therapy (EGDT) group, which included those who received intravenous fluid. Thirty-day mortality was recorded, in addition to total infused fluid, total dose of vasopressor and inotrope, mechanical ventilation (MV) duration, and the intensive care unit (ICU) and hospital stay period. Results: Mortality in echo and cardiometry-guided therapy was significantly lower than in the EGDT group. There was significantly higher norepinephrine and dobutamine doses, prolonged time to weaning of vasopressors, MV, longer ICU and hospital stay duration in echo and cardiometry groups compared to the EGDT group. On the other hand, all measurements were comparable in echo and cardiometry groups. Conclusion: Evidence supports the usefulness of echocardiogram-guided treatment, similar to cardiometry hemodynamic management. However, cardiometry showed the advantage of being a simple and noninvasive technique that does not require a trained cardiologist. Trial registration: Pan African clinical trial registry on 08/05/2019 with unique identification number: PACTR201911842779294.

Beta-blockers' effect on Levels of Lactate in patients with suspected sepsis - The BeLLa study.

In the assessment and management of septic patients in the emergency department (ED), serum lactate is often measured to stratify severity to guide decision making. Increased adrenergic drive has been postulated as a contributory factor for hyperlactatemia in sepsis. We aim to prospectively evaluate the effect of chronic beta-blocker use on serum lactate levels in sepsis at initial presentation to the ED. We conducted a prospective observational study at the ED of a tertiary care academic medical center in Singapore. One hundred and ninety-five ED patients who fulfilled all of the following: (1) age 45years and above, (2) tympanic temperature≥37.8°C or clinically suspected to have an infection, and (3) quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score≥1 were included in the study. Serum venous lactate was sampled within two hours from presentation to the ED. The primary outcome measure was the difference in initial serum venous lactate concentration at presentation to the ED in patients on chronic beta-blockers versus patients without. Seventy patients (35.9%) were on long-term beta-blocker therapy. The primary outcome of mean initial serum venous lactate concentration was similar between patients prescribed chronic beta-blocker therapy and patients without (1.78mmol/L versus 1.70mmol/L, p=.540). Chronic beta-blocker therapy also did not significantly affect mean initial serum venous lactate concentration across all subgroups of sepsis risk stratification. Long-term beta-blocker therapy did not significantly affect initial serum venous lactate concentration in ED patients with suspected sepsis.

HYPERGLYCEMIA-ASSOCIATED LACTIC ACIDOSIS IN SEPSIS

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Lactate is a nonspecific lab test widely used as a marker for tissue hypoperfusion in management of sepsis. Elevated blood lactate has been shown to be associated with higher mortality in sepsis. Lactate is frequently trended to assess improvement of sepsis and need for further resuscitative fluids. This case highlights the elevation of lactic acid due to nonischemic mechanisms in a patient with sepsis, which can lead to unnecessary administration of IV fluids and lab testing. CASE PRESENTATION: A 75-year-old female with past medical history including CAD, HTN, HLD, poorly controlled DM2, GERD, and remote history of small bowel resection (secondary to fibroid tumor) presented to the ED with several days of progressively worsening fatigue, dyspnea, productive cough, and wheezing. Patient was recently discharged from the hospital three days prior after treatment of AKI and cystitis. On presentation patient met SIRS criteria with WBC 14.1 and pulse 97. Other vitals were within normal limits. Due to lactate of 4.7 with clinical evidence of pulmonary infection, she was treated for septic shock. In the ED she was treated with 30cc/kg IV fluids, ceftriaxone, azithromycin, and IV solumedrol. The morning after admission patient felt significantly improved. Her repeat lactic acid originally improved from 4.7 to 4.3 after completion of 30cc/kg fluids. Repeat lactate the following morning increased to 5.4, then 5.7. Glucose levels were also elevated concomitantly with the increasing lactic acid levels, likely secondary to IV solumedrol. There was no hypotension, elevated troponins, AKI, or other evidence of tissue hypoperfusion. Metformin and glipizide had been held prior to admission. Abdominal exam was benign. Her insulin regimen was adjusted and as blood glucose levels improved lactic acidosis improved as well. DISCUSSION: In the Cori cycle pyruvate combines with NADH using lactate dehydrogenase to produce lactate and NAD. Lactate is then used by the liver, kidneys, and heart for gluconeogenesis. Lactic acidosis is defined by lactate levels >4 mmol/L and is divided into types A, B, and D. Type A lactic acidosis is related to sepsis, shock, tissue hypoperfusion and ischemia. Type B lactic acidosis is associated with diabetes, malignancy, ethanol, certain drugs, and toxins. Type D lactic acidosis is associated with short bowel syndrome, DKA, and propylene glycol. In this patient elevated lactic acid was likely secondary to nonoxidative glycolysis from diabetes. The mechanism for lactic acidosis in diabetes is not fully understood, but may involve inhibition of pyruvate dehydrogenase or deficiencies in pathway for oxidative glycolysis. CONCLUSIONS: Lactate is a nonspecific marker used in management of septic patients. Due to the numerous processes that can cause elevated lactic acid, it should be used judiciously in septic patients to avoid unnecessary testing and administration of IV fluids. Reference #1: Causes of Lactic Acidosis . www.uptodate.com. https://www.uptodate.com/contents/causes-of-lactic-acidosis. Published September 19, 2017. Accessed March 15, 2019. Reference #2: Association of blood lactate with type 2 diabetes: the Atherosclerosis Risk in Communities Carotid MRI Study. Int J Epidemiol. December 2010. Reference #3: Association of blood lactate with type 2 diabetes: the Atherosclerosis Risk in Communities Carotid MRI Study. Int J Epidemiol. December 2010. DISCLOSURES: No relevant relationships by Niloufar Gharib, source=Web Response

Real World Patterns of Antimicrobial Use and Microbiology Investigations in Patients with Sepsis outside the Critical Care Unit: Secondary Analysis of Three Nation-Wide Point Prevalence Studies.

Recent description of the microbiology of sepsis on the wards or information on the real-life antibiotic choices used in sepsis is lacking. There is growing concern of the indiscriminate use of antibiotics and omission of microbiological investigations in the management of septic patients. We performed a secondary analysis of three annual 24-h point-prevalence studies on the general wards across all Welsh acute hospitals in years 2016–2018. Data were collected on patient demographics, as well as radiological, laboratory and microbiological data within 48-h of the study. We screened 19,453 patients over the three 24 h study periods and recruited 1252 patients who fulfilled the entry criteria. 775 (64.9%) patients were treated with intravenous antibiotics. Only in 33.65% (421/1252) of all recruited patients did healthcare providers obtain blood cultures; in 25.64% (321/1252) urine cultures; in 8.63% (108/1252) sputum cultures; in 6.79% (85/1252) wound cultures; in 15.25% (191/1252) other cultures. Out of the recruited patients, 59.1% (740/1252) fulfilled SEPSIS-3 criteria. Patients with SEPSIS-3 criteria were significantly more likely to receive antibiotics than the non-septic cohort (p < 0.0001). In a multivariable regression analysis increase in SOFA score, increased number of SIRS criteria and the use of the official sepsis screening tool were associated with antibiotic administration, however obtaining microbiology cultures was not. Our study shows that antibiotics prescription practice is not accompanied by microbiological investigations. A significant proportion of sepsis patients are still at risk of not receiving appropriate antibiotics treatment and microbiological investigations; this may be improved by a more thorough implementation of sepsis screening tools.