Venoarterial extracorporeal membrane oxygenation as mechanical circulatory support in adult septic shock: a systematic review and meta-analysis with individual participant data meta-regression analysis.

BACKGROUND: While recommended by international societal guidelines in the paediatric population, the use of venoarterial extracorporeal membrane oxygenation (VA ECMO) as mechanical circulatory support for refractory septic shock in adults is controversial. We aimed to characterise the outcomes of adults with septic shock requiring VA ECMO, and identify factors associated with survival. METHODS: We searched Pubmed, Embase, Scopus and Cochrane databases from inception until 1st June 2021, and included all relevant publications reporting on > 5 adult patients requiring VA ECMO for septic shock. Study quality and certainty in evidence were assessed using the appropriate Joanna Briggs Institute checklist, and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, respectively. The primary outcome was survival to hospital discharge, and secondary outcomes included intensive care unit length of stay, duration of ECMO support, complications while on ECMO, and sources of sepsis. Random-effects meta-analysis (DerSimonian and Laird) were conducted. DATA SYNTHESIS: We included 14 observational studies with 468 patients in the meta-analysis. Pooled survival was 36.4% (95% confidence interval [CI]: 23.6%-50.1%). Survival among patients with left ventricular ejection fraction (LVEF) < 20% (62.0%, 95%-CI: 51.6%-72.0%) was significantly higher than those with LVEF > 35% (32.1%, 95%-CI: 8.69%-60.7%, p = 0.05). Survival reported in studies from Asia (19.5%, 95%-CI: 13.0%-26.8%) was notably lower than those from Europe (61.0%, 95%-CI: 48.4%-73.0%) and North America (45.5%, 95%-CI: 16.7%-75.8%). GRADE assessment indicated high certainty of evidence for pooled survival. CONCLUSIONS: When treated with VA ECMO, the majority of patients with septic shock and severe sepsis-induced myocardial depression survive. However, VA ECMO has poor outcomes in adults with septic shock without severe left ventricular depression. VA ECMO may be a viable treatment option in carefully selected adult patients with refractory septic shock.

Management of sepsis and septic shock in the emergency department.

Early management of sepsis and septic shock is crucial for patients' prognosis. As the Emergency Department (ED) is the place where the first medical contact for septic patients is likely to occur, emergency physicians play an essential role in the early phases of patient management, which consists of accurate initial diagnosis, resuscitation, and early antibiotic treatment. Since the issuing of the Surviving Sepsis Campaign guidelines in 2016, several studies have been published on different aspects of sepsis management, adding a substantial amount of new information on the pathophysiology and treatment of sepsis and septic shock. In light of this emerging evidence, the present narrative review provides a comprehensive account of the recent advances in septic patient management in the ED.

Pediatric Acute Pancreatitis: Changes in Management and Disease Outcomes Over 16 Years.

OBJECTIVE: To examine the changes over time of pediatric acute pancreatitis (AP) severity, management, and disease outcomes at our academic tertiary center. METHODS: We reviewed 223 pediatric AP admissions (2002-2018) and used a time-to-event regression model to study changes over time. Disease outcomes were analyzed using a subgroup of 89 patients in whom only the AP event determined length of hospital stay and duration of opioid use. RESULTS: There was an increase in mild, but not severe, AP episodes over the examined period. June 2014 was identified as a single cutoff point for change in AP management and disease outcomes independent of each other and of disease severity. Timing of initiating enteral nutrition decreased from 5 to 1.6 days (P < 0.0001) in the entire cohort and from 4.1 to 1.8 days in the subgroup (P = 0.0001) after June 2014. Length of hospitalization decreased from 6 to 3.3 days (P = 0.0008) and days of opioid use from 4.1 to 1.3 (P = 0.002) after June 2014. CONCLUSIONS: Timing of initiating enteral nutrition has significantly reduced at our center after June 2014. In parallel, we observed a significant improvement in disease outcomes.

Variation in acute fluid resuscitation among pediatric burn centers.

BACKGROUND: Accurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates. METHODS: Five pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received. RESULTS: Differences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers' resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35ml/kg/% TBSA, p<0.001), (4.90 versus 6.35ml/kg/TBSA, p=0.002) and (3.38 versus 6.35ml/kg/TBSA, p<0.0001). CONCLUSIONS: This variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.

Effect of fluid strategy on stroke volume, cardiac output, and fluid responsiveness in adult patients undergoing major abdominal surgery: a sub-study of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial.

BACKGROUND: We designed a prospective sub-study of the larger Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial to measure differences in stroke volume and other haemodynamic parameters at the end of the intraoperative fluid protocols. The haemodynamic effects of the two fluid regimens may increase our understanding of the observed perioperative outcomes. METHODS: Stroke volume and cardiac output were measured with both an oesophageal Doppler ultrasound monitor and arterial pressure waveform analysis. Stroke volume variation, pulse pressure variation, and plethysmographic variability index were also obtained. A passive leg raise manoeuvre was performed to identify fluid responsiveness. RESULTS: Analysis of 105 patients showed that the primary outcome, Doppler monitor-derived stroke volume index, was higher in the liberal group: restrictive 38.5 (28.6-48.8) vs liberal 44.0 (34.9-61.9) ml m-2; P=0.043. Similarly, there was a higher cardiac index in the liberal group: 2.96 (2.32-4.05) vs 2.42 (1.94-3.26) L min-1 m-2; P=0.015. Arterial-pressure-based stroke volume and cardiac index did not differ, nor was there a significant difference in stroke volume variation, pulse pressure variation, or plethysmographic variability index. The passive leg raise manoeuvre showed fluid responsiveness in 40% of restrictive and 30% of liberal protocol patients (not significant). CONCLUSIONS: The liberal fluid group from the RELIEF trial had significantly higher Doppler ultrasound monitor-derived stroke volume and cardiac output compared with the restrictive fluid group at the end of the intraoperative period. Measures of fluid responsiveness did not differ significantly between groups. CLINICAL TRIAL REGISTRATION: ACTRN12615000125527.

Oral rehydration therapies in Senegal, Mali, and Sierra Leone: a spatial analysis of changes over time and implications for policy.

BACKGROUND: Oral rehydration solution (ORS) is a simple intervention that can prevent childhood deaths from severe diarrhea and dehydration. In a previous study, we mapped the use of ORS treatment subnationally and found that ORS coverage increased over time, while the use of home-made alternatives or recommended home fluids (RHF) decreased, in many countries. These patterns were particularly striking within Senegal, Mali, and Sierra Leone. It was unclear, however, whether ORS replaced RHF in these locations or if children were left untreated, and if these patterns were associated with health policy changes. METHODS: We used a Bayesian geostatistical model and data from household surveys to map the percentage of children with diarrhea that received (1) any ORS, (2) only RHF, or (3) no oral rehydration treatment between 2000 and 2018. This approach allowed examination of whether RHF was replaced with ORS before and after interventions, policies, and external events that may have impacted healthcare access. RESULTS: We found that RHF was replaced with ORS in most Sierra Leone districts, except those most impacted by the Ebola outbreak. In addition, RHF was replaced in northern but not in southern Mali, and RHF was not replaced anywhere in Senegal. In Senegal, there was no statistical evidence that a national policy promoting ORS use was associated with increases in coverage. In Sierra Leone, ORS coverage increased following a national policy change that abolished health costs for children. CONCLUSIONS: Children in parts of Mali and Senegal have been left behind during ORS scale-up. Improved messaging on effective diarrhea treatment and/or increased ORS access such as through reducing treatment costs may be needed to prevent child deaths in these areas.

Current and evolving standards of care for patients with ARDS.

Care for patients with acute respiratory distress syndrome (ARDS) has changed considerably over the 50 years since its original description. Indeed, standards of care continue to evolve as does how this clinical entity is defined and how patients are grouped and treated in clinical practice. In this narrative review we discuss current standards - treatments that have a solid evidence base and are well established as targets for usual care - and also evolving standards - treatments that have promise and may become widely adopted in the future. We focus on three broad domains of ventilatory management, ventilation adjuncts, and pharmacotherapy. Current standards for ventilatory management include limitation of tidal volume and airway pressure and standard approaches to setting PEEP, while evolving standards might focus on limitation of driving pressure or mechanical power, individual titration of PEEP, and monitoring efforts during spontaneous breathing. Current standards in ventilation adjuncts include prone positioning in moderate-severe ARDS and veno-venous extracorporeal life support after prone positioning in patients with severe hypoxemia or who are difficult to ventilate. Pharmacotherapy current standards include corticosteroids for patients with ARDS due to COVID-19 and employing a conservative fluid strategy for patients not in shock; evolving standards may include steroids for ARDS not related to COVID-19, or specific biological agents being tested in appropriate sub-phenotypes of ARDS. While much progress has been made, certainly significant work remains to be done and we look forward to these future developments.

Hydroxyethyl starch for perioperative goal-directed fluid therapy in 2020: a narrative review.

BACKGROUND: Perioperative fluid management - including the type, dose, and timing of administration -directly affects patient outcome after major surgery. The objective of fluid administration is to optimize intravascular fluid status to maintain adequate tissue perfusion. There is continuing controversy around the perioperative use of crystalloid versus colloid fluids. Unfortunately, the importance of fluid volume, which significantly influences the benefit-to-risk ratio of each chosen solution, has often been overlooked in this debate. MAIN TEXT: The volume of fluid administered during the perioperative period can influence the incidence and severity of postoperative complications. Regrettably, there is still huge variability in fluid administration practices, both intra-and inter-individual, among clinicians. Goal-directed fluid therapy (GDFT), aimed at optimizing flow-related variables, has been demonstrated to have some clinical benefit and has been recommended by multiple professional societies. However, this approach has failed to achieve widespread adoption. A closed-loop fluid administration system designed to assist anesthesia providers in consistently applying GDFT strategies has recently been developed and tested. Such an approach may change the crystalloid versus colloid debate. Because colloid solutions have a more profound effect on intravascular volume and longer plasma persistence, their use in this more "controlled" context could be associated with a lower fluid balance, and potentially improved patient outcome. Additionally, most studies that have assessed the impact of a GDFT strategy on the outcome of high-risk surgical patients have used hydroxyethyl starch (HES) solutions in their protocols. Some of these studies have demonstrated beneficial effects, while none of them has reported severe complications. CONCLUSIONS: The type and volume of fluid used for perioperative management need to be individualized according to the patient's hemodynamic status and clinical condition. The amount of fluid given should be guided by well-defined physiologic targets. Compliance with a predefined hemodynamic protocol may be optimized by using a computerized system. The type of fluid should also be individualized, as should any drug therapy, with careful consideration of timing and dose. It is our perspective that HES solutions remain a valid option for fluid therapy in the perioperative context because of their effects on blood volume and their reasonable benefit/risk profile.

Goal-directed versus Standard Fluid Therapy to Decrease Ileus after Open Radical Cystectomy: A Prospective Randomized Controlled Trial.

BACKGROUND: Postoperative ileus is a common complication of intraabdominal surgeries, including radical cystectomy with reported rates as high as 32%. Perioperative fluid administration has been associated with improvement in postoperative ileus rates, but it is difficult to generalize because earlier studies lacked standardized definitions of postoperative ileus and other relevant outcomes. The hypothesis was that targeted individualized perioperative fluid management would improve postoperative ileus in patients receiving radical cystectomy. METHODS: This is a parallel-arm, double-blinded, single-center randomized trial of goal-directed fluid therapy versus standard fluid therapy for patients undergoing open radical cystectomy. The primary outcome was postoperative ileus, and the secondary outcome was complications within 30 days post-surgery. Participants were at least 21 yr old, had a maximum body mass index of 45 kg/m and no active atrial fibrillation. The intervention in the goal-directed therapy arm combined preoperative and postoperative stroke volume optimization and intraoperative stroke volume variation minimization to guide fluid administration, using advanced hemodynamic monitoring. RESULTS: Between August 2014 and April 2018, 283 radical cystectomy patients (142 goal-directed fluid therapy and 141 standard fluid therapy) were included in the analysis. Postoperative ileus occurred in 25% (36 of 142) of patients in the goal-directed fluid therapy arm and 21% (30 of 141) of patients in the standard arm (difference in proportions, 4.1%; 95% CI, -5.8 to 13.9; P = 0.418). There was no difference in incidence of high-grade complications between the two arms (20 of 142 [14%] vs. 23 of 141 [16%]; difference in proportions, -2.2%; 95% CI, -10.6 to 6.1; P = 0.602), with the exception of acute kidney injury, which was more frequent in the goal-directed fluid therapy arm (56% [80 of 142] vs. 40% [56 of 141] in the standard arm; difference in proportions, 16.6%; 95% CI, 5.1 to 28.1; P = 0.005; P = 0.170 after adjustment for multiple testing). CONCLUSIONS: Goal-directed fluid therapy may not be an effective strategy for lowering the risk of postoperative ileus in patients undergoing open radical cystectomy.

Contemporary resuscitation of hemorrhagic shock: What will the future hold?

Resuscitation of the critically ill patient with fluid and blood products is one of the most widespread interventions in medicine. This is especially relevant for trauma patients, as hemorrhagic shock remains the most common cause of preventable death after injury. Consequently, the study of the ideal resuscitative product for patients in shock has become an area of great scientific interest and investigation. Recently, the pendulum has swung towards increased utilization of blood products for resuscitation. However, pathogens, immune reactions and the limited availability of this resource remain a challenge for clinicians. Technologic advances in pathogen reduction and innovations in blood product processing will allow us to increase the safety profile and efficacy of blood products, ultimately to the benefit of patients. The purpose of this article is to review the current state of blood product based resuscitative strategies as well as technologic advancements that may lead to safer resuscitation.

Outcomes related to intravenous fluid administration in sickle cell patients during vaso-occlusive crisis.

While fluid replacement therapy is a primary treatment modality used in vaso-occlusive crises for sickle cell disease, data is limited on its safety, efficacy, and variability. We performed a retrospective analysis on 157 unique patient encounters from 49 sickle cell patients hospitalized with a vaso-occlusive episode at our institution from 2013 to 2017. The median length of hospital stay was 4 days (IQR 2-7). The mean total amount of intravenous fluid administered during the hospitalization was 7.4 L (Std 9.6). The mean total amount of fluid intake including intravenous fluids, blood transfusions, and oral fluids was 14.2 L (Std 18.2). Multivariate analyses revealed significant associations between the development of any adverse event (including a new oxygen requirement, acute chest syndrome, aspiration event, other hospital-acquired infection, acute kidney injury, and intensive care unit transfer) and the following variables: intravenous fluid administered in the first 24 h (p = 0.001, OR 1.899, 95% CI 1.319-2.733), total amount of intravenous fluid administered (p = 0.005, OR 1.081, 95% CI 1.023-1.141), and total amount of fluid intake including oral fluids, blood transfusions, and intravenous fluids (p = 0.009, OR 1.046, 95% CI 1.011-1.081). Other factors found to be significantly associated with any adverse event were dialysis dependence prior to admission (p < 0.001, OR 12.984, 95% CI 3.660-46.056) and admission to an inpatient service versus an emergency room or observation unit (p = 0.008, OR 3.201, 95% CI 1.346-7.612). While fluid administration may theoretically slow the sickling process, this data suggests that fluid administration during a vaso-occlusive episode, and especially total volume given in the first 24 h, may also lead to adverse events.

Variation in contrast-associated acute kidney injury prophylaxis for percutaneous coronary intervention: insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) program.

BACKGROUND: Contrast-Associated Acute Kidney Injury (CA-AKI) is a serious complication associated with percutaneous coronary intervention (PCI). Patients with chronic kidney disease (CKD) have an elevated risk for developing this complication. Although CA-AKI prophylactic measures are available, the supporting literature is variable and inconsistent for periprocedural hydration and N-acetylcysteine (NAC), but is stronger for contrast minimization. METHODS: We assessed the prevalence and variability of CA-AKI prophylaxis among CKD patients undergoing PCI between October 2007 and September 2015 in any cardiac catheterization laboratory in the VA Healthcare System. Prophylaxis included periprocedural hydration with normal saline or sodium bicarbonate, NAC, and contrast minimization (contrast volume to glomerular filtration rate ratio ≤ 3). Multivariable hierarchical logistic regression models quantified site-specific prophylaxis variability. As secondary analyses, we also assessed CA-AKI prophylaxis measures in all PCI patients regardless of kidney function, periprocedural hydration in patients with comorbid CHF, and temporal trends in CA-AKI prophylaxis. RESULTS: From 2007 to 2015, 15,729 patients with CKD underwent PCI. 6928 (44.0%) received periprocedural hydration (practice-level median rate 45.3%, interquartile range (IQR) 35.5-56.7), 5107 (32.5%) received NAC (practice-level median rate 28.3%, IQR 22.8-36.9), and 4656 (36.0%) received contrast minimization (practice-level median rate 34.5, IQR 22.6-53.9). After adjustment for patient characteristics, there was significant site variability with a median odds ratio (MOR) of 1.80 (CI 1.56-2.08) for periprocedural hydration, 1.95 (CI 1.66-2.29) for periprocedural hydration or NAC, and 2.68 (CI 2.23-3.15) for contrast minimization. These trends were similar among all patients (with and without CKD) undergoing PCI. Among patients with comorbid CHF (n = 5893), 2629 (44.6%) received periprocedural hydration, and overall had less variability in hydration (MOR of 1.56 (CI 1.38-1.76)) compared to patients without comorbid CHF (1.89 (CI 1.65-2.18)). Temporal trend analysis showed a significant and clinically relevant decrease in NAC use (64.1% of cases in 2008 (N = 1059), 6.2% of cases in 2015 (N = 128, p = < 0.0001)) and no significant change in contrast-minimization (p = 0.3907). CONCLUSIONS: Among patients with CKD undergoing PCI, there was low utilization and significant site-level variability for periprocedural hydration and NAC independent of patient-specific risk. This low utilization and high variability, however, was also present for contrast minimization, a well-established measure. These findings suggest that a standardized approach to CA-AKI prophylaxis, along with continued development of the evidence base, is needed.

Fluid intake-related association between urine output and mortality in acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS), a complex response to various insults, has a high mortality rate. As pulmonary edema resulting from increased vascular permeability is a hallmark of ARDS, management of the fluid status, including the urine output (UO) and fluid intake (FI), is essential. However, the relationships between UO, FI, and mortality in ARDS remain unclear. This retrospective study aimed to investigate the interactive associations among UO, FI, and mortality in ARDS. METHODS: This was a secondary analysis of a prospective randomized controlled trial performed at 10 centers within the ARDS Network of the National Heart, Lung, and Blood Institute research network. The total UO and FI volumes within the 24-h period preceding the trial, the UO to FI ratio (UO/FI), demographic data, biochemical measurements, and other variables from 835 patients with ARDS, 539 survivors, and 296 non-survivors, were analyzed. The associations among UO, FI, the UO/FI, and mortality were assessed using a multivariable logistic regression. RESULTS: In all 835 patients, an increased UO was significantly associated with decreased mortality when used as a continuous variable (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.98-0.99, P = 0.002) and as a quartile variable (OR of Q2 to Q4: 0.69-0.46, with Q1 as reference). To explore the interaction between UO and FI, the UO/FI was calculated, and a cut-off value of 0.5 was detected for the association with mortality. For patients with a UO/FI ≤0.5, an increased UO/FI was significantly associated with decreased mortality (OR: 0.09, 95% CI: 0.03-0.253, P <  0.001); this association was not significant for patients with UO/FI ratios > 0.5 (OR: 1.04, 95% CI: 0.96-1.14, P = 0.281). A significant interaction was observed between UO and the UO/FI. The association between UO and mortality was significant in the subgroup with a UO/FI ≤0.5 (OR: 0.97, 95% CI: 0.96-0.99, P = 0.006), but not in the subgroup with a UO/FI > 0.5. CONCLUSIONS: The association between UO and mortality was mediated by the UO/FI status, as only patients with low UO/FI ratios benefitted from a higher UO.

Fluid volumes infused during burn resuscitation 1980-2015: A quantitative review.

INTRODUCTION: 'Fluid creep' or excessive fluid delivered to burn patients during early resuscitation has been suggested by several studies from individual burn centers. METHODS: We performed a Medline search from 1980 to 2015 in order to identify studies of burn patients predominantly resuscitated with lactated Ringers with infusion adjusted per urinary output. Data was abstracted for 48 publications (3196 patients) that met entry criteria. RESULTS: Higher resuscitation volumes compared to Parkland estimates were reported, but the trend of increasing resuscitation volumes over the last 30 years is not supported by regression of total fluid infused versus year of study. Mean 24h fluid infused for all studies was 5.2±1.1mL/kg per %TBSA. The mean 24h urinary output reported in 30 studies was 1.2±0.5mL/kg per hr. Burns with inhalation injuries (5 studies) received significantly more fluid than non-inhalation injured burn patients (5.0±1.3 versus 3.9±0.9mL/kg per %TBSA). Fluid infused and urinary outputs were similar for adults and pediatric patients. The most striking finding of our analyses was the great ranges of the means and high standard deviations of volumes infused compared to the original Baxter publication that introduced the Parkland formula CONCLUSIONS: These analyses suggest that burn units currently administer volumes larger than Parkland formula with great patient variability. Individual patient hourly data is needed to better understand the record of burn resuscitation and Fluid Creep.

Profound Intraoperative Hypotension Associated With Transfusion via the Belmont Fluid Management System.

This retrospective observational case series conducted at 2 large academic centers over a 4-year period consists of 15 cases of profound hypotension in surgical patients immediately after initiation of the Belmont Fluid Management System for rapid transfusion of blood products. Halting the infusion and administering vasoactive agents led to resolution of hypotension. Repeat transfusion with the Belmont system resulted in repeat hypotension unless counteracted with vasopressors. No etiology was elucidated. This represents the largest documented association of acute hypotensive transfusion reaction with any rapid infusion system in surgical patients.

NIVAS 2019: facing the future in vascular access and infusion therapy.

The 7th National Infusion and Vascular Access Society (NIVAS) conference was held in Manchester, 12-13 June 2019.

Alterations of the iNKT cell compartment in brain-injured patients.

BACKGROUND: Brain injury (BI) induces a state of immunodepression leading to pneumonia. We investigated the invariant natural killer T (iNKT) cell compartment. METHODS: This is an observational study in two surgical intensive care units (ICUs) of a single institution and a research laboratory. Clinical data and samples from a prospective cohort were extracted. Severe brain-injured patients (n = 33) and sex- and age-matched healthy donors (n = 40) were studied. RESULTS: We observed the presence of IL-10 in serum, a loss of IFN-γ and IL-13 production by peripheral blood mononuclear cells (PBMCs) following IL-2 stimulation, and downregulation of HLA-DR expression on both monocytes and B cells early after BI. Inversely, CD1d, the HLA class I-like molecule involved in antigen presentation to iNKT cells, was over-expressed on patients' monocytes and B cells. The antigen-presenting activity to iNKT cells of PBMCs was increased in the patients who developed pneumonia, but not in those who remained free of infection. Frequencies of iNKT cells among PBMCs were dramatically decreased in patients regardless of their infection status. Following amplification, an increased frequency of CD4+ iNKT cells producing IL-4 was noticed in the group of patients free of infection compared with those who became infected and with healthy donors. Finally, serum from BI patients inhibited the iNKT cells' specific response as well as the non-specific IL-2 stimulation of PBMCs, and the expression of the beta-2 adrenergic receptor was elevated at the surface of patients T lymphocytes. CONCLUSIONS: We observed severe alterations of the iNKT cell compartment, including the presence of inhibitory serum factors. We demonstrate for the first time that the decreased capacity to present antigens is not a generalized phenomenon because whereas the expression of HLA-DR molecules is decreased, the capacity for presenting glycolipids through CD1d expression is higher in patients.

Sepsis - What's new in 2019?

PURPOSE OF REVIEW: Sepsis-3 guidelines have implications in a deeper understanding of the biopathology of the disease. Further, the review focuses on timely topics and new literature on fluid resuscitation, the value of steroids in sepsis, and new therapeutic options such as angiotensin II, vitamin C, and thiamine as well as the emerging role of procalcitonin (PCT) in managing antibiotics. RECENT FINDINGS: Traditional therapies such as type of crystalloid fluid administration and steroid therapy for sepsis are currently under re-evaluation. Angiotensin II is investigated for reversing vasodilatory shock. The role of capillary endothelium leak and cellular metabolism can be affected by vitamin C and thiamine levels. Biomarker level trends, specifically PCT, can aid clinical suspicion of infection. SUMMARY: Sepsis-3 shifts the focus from a noninfectious inflammatory process and an emphasis on a dysregulated host response to infection. Hyperchloremic crystalloid resuscitation is associated with poor clinical outcomes. Steroid administration can reverse shock physiology; however, mortality benefits remain uncertain. Angiotensin II, vitamin C, and thiamine are novel treatment options that need further validation. PCT assays can help discern between infectious and noninfectious inflammation.