Sepsis Resuscitation Research Articles

Equipoise in Appropriate Initial Volume Resuscitation for Patients in Septic Shock With Heart Failure: Results of a Multicenter Clinician Survey.

International clinical practice guidelines call for initial volume resuscitation of at least 30 mL/kg body weight for patients with sepsis-induced hypotension or shock. Although not considered in the guidelines, preexisting cardiac dysfunction may be an important factor clinicians weigh in deciding the quantity of volume resuscitation for patients with septic shock. We conducted a multicenter survey of clinicians who routinely treat patients with sepsis to evaluate their beliefs, behaviors, knowledge, and perceived structural barriers regarding initial volume resuscitation for patients with sepsis and concomitant heart failure with reduced ejection fraction (HFrEF) <40%. Initial volume resuscitation preferences were captured as ordinal values, and additional testing for volume resuscitation preferences was performed using McNemar and Wilcoxon signed rank tests as indicated. Univariable logistic regression models were used to identify significant predictors of ≥30 mL/kg fluid administration. A total of 317 clinicians at 9 US hospitals completed the survey (response rate 47.3%). Most respondents were specialists in either internal medicine or emergency medicine. Substantial heterogeneity was found regarding sepsis resuscitation preferences for patients with concomitant HFrEF. The belief that patients with septic shock and HFrEF should be exempt from current sepsis bundle initiatives was shared by 39.4% of respondents. A minimum fluid challenge of ∼30 mL/kg or more was deemed appropriate in septic shock by only 56.4% of respondents for patients with concomitant HFrEF, compared to 89.1% of respondents for patients without HFrEF (P < .01). Emergency medicine physicians were most likely to feel that <30 mL/kg was most appropriate in patients with septic shock and HFrEF. Clinical equipoise exists regarding initial volume resuscitation for patients with sepsis-induced hypotension or shock and concomitant HFrEF. Future studies and clinical practice guidelines should explicitly address resuscitation in this subpopulation.

Assessment of body water distribution in patients with sepsis during fluid resuscitation using multi-frequency direct segmental bioelectrical impedance analysis

Although initial fluid resuscitation in sepsis is critical for the treatment of tissue hypoperfusion, little evidence supports the distribution of infused fluid in patients with sepsis. This study was designed to assess the body water distribution in patients with sepsis using bioelectrical impedance analysis and correlate the trend in body water distribution during fluid treatment with the prognosis of patients with sepsis. A prospective study in a single emergency department was performed, and adult patients suspected of having sepsis were enrolled. Multi-frequency direct segmental bioelectrical impedance analysis (InBody S10, InBody) measuring total body water (TBW), intracellular water (ICW), and extracellular water (ECW) was applied to patients with sepsis at three periods: before, immediately after, and 1 hour after the fluid treatment. Survival data at 28 days after the fluid treatment were obtained. Forty-two patients were enrolled in this study. Overall, the ratios of TBW, ICW, and ECW to body weight increased throughout the fluid treatment except the ratio of ICW to body weight at 1 hour in non-survivors. While the ratio of ECW to TBW (ECW/TBW) and the ratio of ICW to TBW (ICW/TBW) in survivors remained stable over the period, the trend of ECW/TBW increased with corresponding decline of ICW/TBW in non-survivors (p=0.0085 and p=0.0034 between times and groups, respectively) such that ECW/TBW and ICW/TBW were significantly different at 1 hour after the fluid loading period (p=0.0120 and p=0.0085, respectively). This contrast pattern was equivalent with the trend of ECW/TBW in trunk but not that of the other extremities. During fluid resuscitation, the trend in ECW/TBW significantly increased with corresponding decrease of ICW/TBW in non-survivors compared with that in survivors, which suggests fluid resuscitation results intracellular dehydration and extracellular edema in non-survivors of patients with sepsis.

Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation

BackgroundIntravenous fluids, an essential component of sepsis resuscitation, may paradoxically worsen outcomes by exacerbating endothelial injury. Preclinical models suggest that fluid resuscitation degrades the endothelial glycocalyx, a heparan sulfate-enriched structure necessary for vascular homeostasis. We hypothesized that endothelial glycocalyx degradation is associated with the volume of intravenous fluids administered during early sepsis resuscitation.MethodsWe used mass spectrometry to measure plasma heparan sulfate (a highly sensitive and specific index of systemic endothelial glycocalyx degradation) after 6 h of intravenous fluids in 56 septic shock patients, at presentation and after 24 h of intravenous fluids in 100 sepsis patients, and in two groups of non-infected patients. We compared plasma heparan sulfate concentrations between sepsis and non-sepsis patients, as well as between sepsis survivors and sepsis non-survivors. We used multivariable linear regression to model the association between volume of intravenous fluids and changes in plasma heparan sulfate.ResultsConsistent with previous studies, median plasma heparan sulfate was elevated in septic shock patients (118 [IQR, 113–341] ng/ml 6 h after presentation) compared to non-infected controls (61 [45–79] ng/ml), as well as in a second cohort of sepsis patients (283 [155–584] ng/ml) at emergency department presentation) compared to controls (177 [144–262] ng/ml). In the larger sepsis cohort, heparan sulfate predicted in-hospital mortality. In both cohorts, multivariable linear regression adjusting for age and severity of illness demonstrated a significant association between volume of intravenous fluids administered during resuscitation and plasma heparan sulfate. In the second cohort, independent of disease severity and age, each 1 l of intravenous fluids administered was associated with a 200 ng/ml increase in circulating heparan sulfate (p = 0.006) at 24 h after enrollment.ConclusionsGlycocalyx degradation occurs in sepsis and septic shock and is associated with in-hospital mortality. The volume of intravenous fluids administered during sepsis resuscitation is independently associated with the degree of glycocalyx degradation. These findings suggest a potential mechanism by which intravenous fluid resuscitation strategies may induce iatrogenic endothelial injury.

COMBINATION OF CENTRAL VENO-ARTERIAL CARBON DIOXIDE GAP WITH ARTERIO-VENOUS OXYGEN CONTENT DIFFERENCE DURING RESUSCITATION AS A PREDICTOR OF MULTI-ORGAN DYSFUNCTION IN SEPTIC PATIENTS

Background: Venous-to-arterial carbon dioxide difference (PvaCO2) the Pcv-aCO2/arterial-to-venous oxygen content difference (Ca-cvO2) ratio may reflect the adequacy of blood flow during shock states. We sought to test whether the development of Pv-aCO2 PcvaCO2/ arterial-to-venous oxygen content difference ratio during the very early phases of resuscitation is related to multi-organ dysfunction and outcomes in a population of septic patients resuscitated targeting the usual oxygen-derived and hemodynamic parameters. Aim of the Work: To evaluate the changes in central venous-toarterial carbon dioxide difference (Pcv-aCO2 gap) and in PcvaCO2/ arterial-to-venous oxygen content difference (Ca-cvO2) ratio [Pcv-aCO2/Ca-cvO2 ratio] during the early resuscitation in sepsis and septic shock as a predictor for development of multi-organ dysfunction and mortality. Patients and Methods: This prospective observational study wasperformed in a 24-bed mixed ICU in a university-affiliated hospital. We examined all septic patients with a new episode admitted to the emergency room or proceeding from clinical wards during a 24-month period. After approval by Ethical Medical Committee and obtaining informed consent, simultaneous blood samples were collected from the central venous line and the arterial catheter for obtaining venous and arterial gases respectively at T0, and 6 hours (T6), 12 hours (T12) and 24 hours (T24) later. Patients were classified twice; the first one into groups (A and B) according to PcvO2 gap and the second one into groups (C and D) according to Pcv-aCO2/Ca-cvO2 ratio. Group (A) Decreasing PcvaCO2 (high at T0, declining at T6), Group (B) Persistently high PcvaCO2 (high at T0 and T6), Group (C) Decreasing Pcv-aCO2/Ca-cvO2ratio (high at T0, declining at T6), Group (D) Persistently high PcvaCO2/ Ca-cvO2 ratio (high at T0 and T6).Results: During the 24-month period, 58 septic patients older than 18 years with a new episode were screened. Patients with advanced cirrhosis (n = 4), patients with severe chronic obstructive pulmonary disease (n = 8) and pregnant women (n = 4) were not included for analysis; additionally, two patients refused the procedure. The final sample was therefore 40 patients. Our recent study found that patients with persistently high Pcv-aCO2 gradient at T6 [8.64 ± 1.66] developed more organ dysfunction and have had a higher mortality rate (61.1%). This study showed that the persistently elevated Pcv-aCO2/Pa-vO2 ratio at time 6 was associated with a mortality rate of 73.7% of the patients. While decreasing of PcvaCO2/ Pa-vO2 ratio within the first 6 hours of resuscitation was associated with a survival rate of 90.5%. Conclusion: Data support the hypothesis that persistence of high PCO2 Gap and high Pcv-aCO2/ Pa-vO2 ratio during the early resuscitation of patients in sepsis is associated with significant higher multi-organ dysfunction and poor outcomes in critically-ill patients.

SAT-306 Clinical Profile and outcome of Children who received Renal Replacement Therapy for Acute Kidney Injury in Tikur Anbessa Specialized Hospital; an ISN/ SRC trio experience.

Acute kidney injury (AKI) requiring Renal Replacement Therapy (RRT) is associated with high mortality. The study assessed the impact of the introduction of RRT on outcomes of patients with AKI in Pediatric Nephrology unit in Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia. We provide acute Peritoneal Dialysis and acute intermittent Heamodialysis with support from the ISN SRC trio program for few selected cases due to lack of resources. A single center retrospective study that evaluated the clinical profile and survival outcomes of patients with AKI requiring Intermittent Hemodialysis and Acute Peritoneal Dialysis (IHD/ APD) at a tertiary hospital in Addis Ababa, Ethiopia. Data was collected on patients who received RRT for AKI from July 2016 to October 2018. Patient demographics, commodities, clinical presentation, laboratory tests, and mortality were reviewed and analyzed. There were 35 children in this cohort; median age was 9 years (IQR 4 months – 15 years). Females comprised 54.3% of the cohort. Infectious diseases including Acute Gastroenteritis, Pneumonia, and severe Sepsis 7 (20%) and Acute Glomerulonephritis (AGN) 18 (54.28%) were the most frequent commodities. Oligo-anuria with pulmonary edema (91.4%) was the top indication for RRT. Overall mortality was 37.14%. Underlying severe sepsis and pulmonary edema in AGN patients were the most common causes of death. Twenty one (60%) of children had partial renal recovery on discharge. One child went home against medical advice. Eleven children received acute IHD in the adult Unit. Of the children who received APD, there was a 37.5% complication. Two children had catheter obstruction, 5 leaks from the insertion site and 2 children had peritonitis. We used a rigid catheters inserted at bedside with improvised fluids according to the ISPD guidelines using Ringer Lactate and Dextrose solutions. The availability of acute RRT in Pediatric Nephrology unit in TASH has resulted in improved patient survival. Early detection of AKI and prompt protocol based management are essential in reducing the morbidity and mortality related to AKI. We recommend vigorous resuscitation and management of sepsis to save lives. The ISN SRC program helped our unit in providing physicians' training and equipment to deliver a standardized health care service to children with AKI in our institution.

Mortality impact of empirical antimicrobial therapy inESBL- and AmpC-producing Enterobacteriaceae bacteremia in an Australian tertiary hospital.

Treatment of ESBL- and AmpC-producing Enterobacteriaceae bacteremia is often complicated by lack of appropriate antibiotics. We aimed to determine the predictors of mortality and impact of empirical antibiotics. A retrospective observational study was performed on consecutive adult cases of ESBL and AmpC bacteremia at the Alfred Hospital from 2014 through April 2018. Among 110 patients with ESBL (88.2%) and AmpC (14.5%) bacteremia episodes, 96.4% had comorbidities such as hematological malignancy (30%). Approximately 45% were on immunosuppressive drugs, while 69% had recent antibiotic exposure. Over 84% of bacteremias were hospital acquired or healthcare associated. Urinary tract was the main source of infection (40%) with E. coli being the commonest organism (66.4%). The isolates were least resistant to gentamicin (21.8%), which was often appropriately used in empirical therapy. About 34% of patients presented with severe sepsis or shock. The 30-day mortality rate was 20% with no correlation with inappropriate empirical antibiotics (52%). There was no significant mortality difference between carbapenem use in empirical and definitive therapy. Respiratory source [OR 11.77, 95% CI 1.30-106.85; p=0.03], severe sepsis or shock [OR 5.17, 95% CI 1.37-19.55; p=0.02] and inappropriate definitive therapy [OR 27.93, 95%CI 3.69-211.35; p=0.001] were independent predictors for mortality. The choice and appropriateness of empirical therapy were not associated with mortality in ESBL and AmpC bacteremia. Prudent use of carbapenem is reasonable with gentamicin as alternative. Emphasis should be on prompt resuscitation in severe sepsis and early detection of ESBL and AmpC to facilitate appropriate switch to definitive therapy.

Rules of anti-infection therapy for sepsis and septic shock.

Objective:Sepsis is a deadly infection that causes injury to tissues and organs. Infection and anti-infective treatment are the eternal themes of sepsis. The successful control of infection is a key factor of resuscitation for sepsis and septic shock. This review examines evidence for the treatment of sepsis. This evidence is combined with clinical experiments to reveal the rules and a standard flowchart of anti-infection therapy for sepsis.Data Sources:We retrieved information from the PubMed database up to October 2018 using various search terms and their combinations, including sepsis, septic shock, infection, antibiotics, and anti-infection.Study Selection:We included data from peer-reviewed journals printed in English on the relationships between infections and antibiotics.Results:By combining the literature review and clinical experience, we propose a 6Rs rule for sepsis and septic shock management: right patients, right time, right target, right antibiotics, right dose, and right source control. This rule encompasses rational decisions regarding the timing of treatment, the identification of the correct pathogen, the selection of appropriate antibiotics, the formulation of a scientifically based antibiotic dosage regimen, and the adequate control of infectious foci.Conclusions:This review highlights how to recognize and treat sepsis and septic shock and provides rules and a standard flowchart for anti-infection therapy for sepsis and septic shock for use in the clinical setting.

The value of volume substitution in patients with septic and haemorrhagic shock with respect to the microcirculation.

After decades of ordinary scientific interest, fluid resuscitation of patients with septic and haemorrhagic shock took centre stage in intensive care research at the turn of the millennium. By that time, resuscitation fluids were the mainstay of haemodynamic stabilisation, avoidance of vasopressors and treatment of hypovolaemia in patients in shock, but were accompanied by adverse events such as excessive tissue oedema. With the spread of early goal-directed therapy research intensified and it was realised that type, volume and timing of resuscitation fluids might affect the course and outcome of critically ill patients. At the same time, the importance of microvascular blood flow as target of resuscitation was accepted. Today, once-forbidden albumin is the recommended colloid in severe sepsis and septic shock, and the European Medical Agency is considering the removal of starch solutions from the European market because of an increased incidence of acute kidney injury and mortality. This is unprecedented, especially because the administration of low-molecular-weight starches seems to have advantages in indications other than sepsis, and because practices in fluid resuscitation have changed fundamentally since the negative starch studies. Crystalloids are still the mainstay of hypovolaemia treatment in critically ill patients, but awareness is increasing that electrolyte composition, strong ion gap, tonicity and the bicarbonate-substituting anion may have an effect on adverse effects and outcome. In haemorrhagic shock, the utilisation of crystalloids and colloids is retreating, and plasma and erythrocyte concentrates are gaining more importance in the resuscitation of the patient with acute bleeding. However, there are still influential voices warning against the liberal usage of plasma concentrates and erythrocytes in trauma and haemorrhagic shock. This review describes the evidence relating to fluid resuscitation in sepsis, septic shock and massive haemorrhage. Beside the scientific evidence based on clinical trials, possible effects on the microcirculation and, therefore, organ function will be illustrated and areas of future research highlighted. The critical appraisal of the existing evidence should enable the reader to choose the optimal volume substitution for an individual patient.

Conservative Fluid Management After Sepsis Resuscitation: A Pilot Randomized Trial.

The feasibility and clinical outcomes of conservative fluid management after sepsis resuscitation remain unknown. To evaluate the effect of a conservative fluid management protocol on fluid balance and intensive care unit (ICU)-free days among patients with sepsis. In a single-center phase II/III randomized trial, we enrolled adults with suspected infection, ≥2 systemic inflammatory response syndrome criteria, and either shock (mean arterial pressure <60 mm Hg or vasopressors) or respiratory insufficiency (mechanical ventilation or oxygen saturation <97% and fraction of inspired oxygen ≥0.3). Patients were randomized 1:1 to usual care or a conservative fluid management protocol. The protocol restricted intravenous fluid administration during shock to treatment of oliguria or increasing vasopressor requirement. In the absence of shock, loop diuretic infusion targeted equal fluid input and output each study day. The primary outcomes were mean daily fluid balance (phase II) and ICU-free days (phase III). At the completion of phase II (n = 30), the difference in mean daily fluid balance between groups (-398 mL) was less than the prespecified threshold (-500 mL) and the trial was stopped. Patients in the conservative fluid management (n = 15) and usual care (n = 15) groups experienced similar cumulative fluid input (8450 mL vs 7049 mL; P = .90) of which only 14% was intravenous crystalloid or colloid. Loop diuretic infusion occurred more frequently in the conservative fluid management group (40% vs 0%; P = .02), and cumulative fluid output was 10 645 mL in the conservative fluid management group compared to 6286 mL in the usual care group (P = .39). Hemodynamic, respiratory, and renal function did not differ between the groups. In this phase II trial, a conservative fluid management protocol did not decrease mean daily fluid balance by more than 500 mL among patients with sepsis. Clinicaltrials.gov; NCT02159079.

Recognition of acute organ failure and associated fluid and oxygen resuscitation by emergency medical services of emergency department patients with a suspected infection

IntroductionRecognition of acute organ failure is essential for recognition and resuscitation of sepsis by emergency medical services (EMS). We assessed how many EMS patients with suspected infection had clinical signs of acute organ failure (i.e. hypotension), received fluids and oxygen, and how many EMS patients without clinical signs of organ failure appeared to have organ failure in the emergency department (ED). MethodsWe interrogated an existing database in which consecutive ED patients hospitalized with suspected infection were prospectively collected. Outcomes were 1) number of patients without clinical signs of organ failure in the ambulance who developed clinical signs of organ failure or appeared to have biochemical signs of organ failure (i.e. hyperlactatemia) in the ED, and 2) number of patients who received fluids and oxygen in the ambulance. ResultsOf the 788 analyzed EMS patients, 529 (67.1%) had clinical signs of organ failure, of whom only 161 (30.4%) received fluids and 372 (70.3%) received oxygen. Clinical signs of organ failure were absent in 259 (32.9%) EMS patients, of which 165 patients (63.7%) developed organ failure in the ED. ConclusionsIn patients with suspected infection, acute organ failure is poorly recognized and treated by EMS, partly because of delayed development of organ failure.

Using peripheral perfusion index and venous-to-arterial CO(2) difference/arterial-central venous O(2) difference ratio to assess lactate clearance in septic patients after resuscitation

Objective: The relationship of venous-to-arterial CO(2) difference(Pv-aCO(2))/arterial-central venous O(2) difference (Ca-vO(2)) ratio, peripheral perfusion index(PI) and lactate clearance(LC) were investigated during resuscitation in septic patients. And, the meaning of the combination PI and Pv-aCO(2)/Ca-vO(2) ratio to interpret incoherence of lactate clear was explored. Methods: The patients with sepsis were prospectively observed, who admitted to critically care medicine department of Peking Union Medical College Hospital. The hemodynamic parameters, simultaneous arterial and central venous blood gas analysis and PI were obtained at the enrollment (T0) and 8 hours (T8) during resuscitation. The lactate clearance was defined as 8h-LC≥10% and non-lactate clearance was defined as 8h-LC ≤ 10%. Additionally, the patients were divided as three sub-groups according to the PI value at T8: the normalized PI group with PI≥1.4,the mild impaired PI with 1.4<PI<0.6 and severe impaired PI with PI≤0.6. Results: A total of 84 patients were enrolled in this study. There was no significant difference in Pv-aCO(2)/Ca-vO(2) ratio in the three groups. However, the PI≤0.6 group had a significantly higher Pv-aCO(2) than other groups. Moreover, the patients with non-lactate clearance (13/32) had a higher Pv-aCO(2)/Ca-vO(2) ratio than the patients with lactate clearance in PI≥1.4 group (1.9±0.7 vs. 1.3±1.0, P=0.01). Multivariate analysis showed both Pv-aCO(2)/Ca-vO(2) ratio [Exp(B) 2.235, 95% CI 1.232-4.055, P=0.008] and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) [Exp (B) 1.087, 95%CI 1.022-1.156, P=0.008] were independent risk factor of non-lactate clearance. 8h-PI was significantly negative correlated with the 8 h Pv-aCO(2) gap (r=-0.311, P=0.004), but not significantly with Pv-aCO(2)/Ca-vO(2) ratio (r=-0.094, P=0.385). Conclusions: Both high Pv-aCO(2)/Ca-vO(2) ratio and low PI were related to non-lactate clearance after resuscitation in sepsis. Combined PI and Pv-aCO(2)/Ca-vO(2) ratio could interpret incoherence of latacte clearance after resuscitation.

Emergency department charges may be associated with mortality in patients with severe sepsis and septic shock: a cohort study

BackgroundSepsis severity of illness is challenging to measure using claims, which makes sepsis difficult to study using administrative data. We hypothesized that emergency department (ED) charges may be associated with hospital mortality, and could be a surrogate marker of severity of illness for research purposes. The objective of this study was to measure concordance between ED charges and mortality in admitted patients with severe sepsis or septic shock.MethodsCohort study of all adult patients presenting to a 60,000-visit Midwestern academic ED with severe sepsis or septic shock (by ICD-9 codes) between July 1, 2008 and June 30, 2010. Data on demographics, admission APACHE-II score, and disposition was extracted from the medical record, and comorbidities were identified from diagnosis codes using the Elixhauser methodology. Summary statistics were reported and bivariate concordance was tested using Pearson correlation. Logistic regression models for 28-day mortality were developed to measure the independent association with mortality.ResultsWe included a total of 294 patients in the analysis. We found that ED charges were inversely related to mortality (adjusted OR 0.829 per $1000 increase in total ED charges, 95%CI 0.702–0.980). ED charges were also independently associated with 28-day hospital-free and ICU-free days (0.74 days increase per $1000 additional ED charges, 95%CI 0.06–1.41 and 0.81 days increase per $1000 additional ED charges, 95%CI 0.05–1.56, respectively). ED charges were also associated with APACHE-II score ($34 total ED charges per point increase in APACHE-II score, 95%CI $6–62).ConclusionsED charges in administrative data sets are associated with in-hospital mortality and health care utilization, likely related to both illness severity and intensity of early sepsis resuscitation. ED charges may have a role in risk adjustment models using administrative data for acute care research.

Indications for fluid resuscitation in patients with septic shock: Post-hoc analyses of the CLASSIC trial.

Fluid resuscitation is recommended in septic shock, but the specific indications for fluids have not been established. Our aim was to investigate the indications currently used for fluid resuscitation and the effect of fluid on these indications in patients with septic shock admitted to the intensive care unit (ICU). This was a post-hoc analysis of the CLASSIC trial, where patients with septic shock were randomized to fluid restriction or standard care. We recorded indications for and effect of each fluid bolus during the first 24hours. In total, 256 fluid boluses were administered on 515 indications to the 76 patients in the standard care group. The most frequent indications were low blood pressure/increase in noradrenalin dose (199 boluses, 78%), high lactate (94, 37%), and low urinary output (68, 27%). While the analyses of all 418 fluid boluses given in all 151 patients failed to show any effect of fluid on these variables, the data did suggest that time from randomization altered the effect; fluid may have increased urinary output when given early and increased noradrenalin dose when given later. For 56% of the fluid boluses given on the most frequent indications, a second fluid bolus was given on the same indication. In ICU patients with septic shock, low blood pressure, high lactate, and low urinary output were the most frequent indications for fluid. The effects of fluids when given on these indications were less clear, but may dependent on the time course of sepsis resuscitation.

Effect of fluid bolus triggers and their combination on fluid responsiveness in optimization phase of severe sepsis and septic shock resuscitation

to evaluate the fluid responsiveness according to fluid bolus triggers and their combination in severe sepsis and septic shock. observational study. patients with severe sepsis and septic shock who already received fluid after rescue phase of resuscitation. Fluid bolus (FB) was prescribed upon perceived hypovolemic manifestations: low central venous pressure (CVP), low blood pressure, tachycardia, low urine output (UOP), hyperlactatemia. FB was performed by Ringer lactate 500 ml/30 min and responsiveness was defined by increasing in stroke volume (SV) ≥15%. 84 patients were enrolled, among them 30 responded to FB (35.7%). Demographic and hemodynamic profi before fluid bolus were similar between responders and non-responders, except CVP was lower in responders (7.3 ± 3.4 mmHg vs 9.2 ± 3.6 mmHg) (p 0.018). Fluid response in low CVP, low blood pressure, tachycardia, low UOP, hyperlactatemia were 48.6%, 47.4%, 38.5%, 37.0%, 36.8% making the odd ratio (OR) of these triggers were 2.81 (1.09-7.27), 1.60 (0.54-4.78), 1.89 (0.58-6.18), 1.15 (0.41-3.27) and 1.27 (0.46-3.53) respectively. Although CVP &lt; 8 mmHg had a higher response rate, the association was not consistent at lower cut-offs. The combination of these triggers appeared to raise fluid response but did not reach statistical signifi 26.7% (1 trigger), 31.0% (2 triggers), 35.7% (3 triggers), 55.6% (4 triggers), 100% (5 triggers). fluid responsiveness was low in optimization phase of resuscitation. No fluid bolus trigger was superior to the others in term of providing a higher responsiveness, their combination did not improve fluid responsiveness as well.

Echocardiogram-guided resuscitation versus early goal-directed therapy in the treatment of septic shock: a randomized, controlled, feasibility trial

ObjectiveEchocardiography is often used to guide septic shock resuscitation, but without evidence for efficacy. We conducted an intensive care unit (ICU)-based randomized controlled feasibility trial comparing echocardiography-guided septic shock resuscitation (ECHO) with early goal-directed therapy (EGDT).MethodsWe conducted a single center, randomized controlled feasibility trial at a 468-bed academic tertiary care center in Utah, USA. Adult patients with early septic shock were assessed and treated at defined intervals over 6 h using an echocardiogram-guided resuscitation protocol or a slightly modified EGDT protocol. Feasibility outcomes were fluid balance, dobutamine administration, and time to lactate clearance. The primary clinical outcome was changed in sequential organ failure assessment score at 48 h (delta SOFA). Secondary outcomes included inpatient mortality, ICU-free days, and ventilator-free days at 28 days.ResultsThirty participants, 15 per group, were randomized and completed the study. Baseline characteristics were similar between groups. Patients were randomized within a median of 3.5 h of meeting inclusion criteria but had received a median of 3 L crystalloid by then. Fluid administration during the study protocol was similar in both groups (median ECHO 0 vs EGDT 1 L, p = 0.61). Eleven (73%) subjects in each arm received ≤ 1 L fluid. Dobutamine administration was also similar (20% vs 13%, p > 0.99). Twenty-one patients (70%) had lactate clearance prior to the first study assessment. No difference was observed in delta SOFA (median − 4 for ECHO vs − 6 for EGDT, p = 0.10) nor mortality (33% ECHO vs 20% EGDT, p = 0.68).ConclusionsNo experimental separation was observed in this randomized, controlled feasibility trial. Early lactate clearance, coupled with substantial fluid administration before randomization, suggests that patients were already resuscitated before arrival in the ICU. Future trials of echocardiogram-guided sepsis resuscitation will likely need to enroll in the emergency department.Trial registrationThis study was retrospectively registered at clinicaltrials.gov (identifier NCT02354742, title Echo vs EGDT in severe sepsis and septic shock) on February 3, 2015. Registration was completed before review or analysis of any data.

Mitochondrial dysfunction and resuscitation in sepsis

Considering that the pathological changes are inconsistent with severe organ dysfunction of sepsis.It is urgent to explore the other pathogenetic mechanisms besides inflammation and immunity.A extraordinary explanation for multiple organ dysfunction is associated with mitochondrial dysfunction during sepsis.Although the exact relationship between them is not proved, and therapeutic strategy is suggested to promote the organs function by improving mitochondrial metabolism for sepsis.This article focused on mitochondrial biology, mitochondrial dysfunction, metabolic disorder and mitochondrial resuscitation in sepsis. Key words: Sepsis; Mitochondrial dysfunction; Mitochondria resuscitation

Fluid Management in Sepsis.

Among critically ill adults, sepsis remains both common and lethal. In addition to antibiotics and source control, fluid resuscitation is a fundamental sepsis therapy. The physiology of fluid resuscitation for sepsis, however, is complex. A landmark trial found early goal-directed sepsis resuscitation reduced mortality, but 3 recent multicenter trials did not confirm this benefit. Multiple trials in resource-limited settings have found increased mortality with early fluid bolus administration in sepsis, and the optimal approach to early sepsis resuscitation across settings remains unknown. After initial resuscitation, excessive fluid administration may contribute to edema and organ dysfunction. Using dynamic variables such as passive leg raise testing can predict a patient's hemodynamic response to fluid administration better than static variables such as central venous pressure. Whether using measures of "fluid responsiveness" to guide fluid administration improves patient outcomes, however, remains unknown. New evidence suggests improved patient outcomes with the use of balanced crystalloids compared to saline in sepsis. Albumin may be beneficial in septic shock, but other colloids such as starches, dextrans, and gelatins appear to increase the risk of death and acute kidney injury. For the clinician caring for patients with sepsis today, the initial administration of 20 mL/kg of intravenous balanced crystalloid, followed by consideration of the risks and benefits of subsequent fluid administration represents a reasonable approach. Additional research is urgently needed to define the optimal dose, rate, and composition of intravenous fluid during the management of patients with sepsis and septic shock.

Comparison of machine learning method and logistic regression model in prediction of acute kidney injury in severely burned patients

Objective: To build risk prediction models for acute kidney injury (AKI) in severely burned patients, and to compare the prediction performance of machine learning method and logistic regression model. Methods: The clinical data of 157 severely burned patients in August 2nd Kunshan factory aluminum dust explosion accident conforming to the inclusion criteria were collected. Patients suffering AKI within 90 days after admission were enrolled in group AKI, while the others were enrolled in non-AKI group. Single factor analysis was used to choose independent factors associated with AKI, including sex, age, admission time, features of basic injuries, initial score on admission, treatment condition, and mortality on post injury days 30, 60, and 90. Data were processed with Mann-Whitney U test, chi-square test, and Fisher's exact test. Variables with P<0.1 in single factor analysis and those with possible clinical significance were brought into the establishment of prediction model. Logistic regression and XGBoost machine learning algorithm were used to build the prediction model of AKI. The area under receiver operating characteristic curve (AUC) was calculated, and the sensitivity and specificity for optimal threshold value were also calculated for each model. Nonparametric resampling test was used to compare the significance of difference of AUC of the two models. Results: (1) Eighty-nine (56.7%) patients developed AKI within 90 days from admission. Compared with 68 patients in non-AKI group, 89 patients in group AKI were older (Z=-2.203, P<0.05), with larger total burn area and full-thickness burn area (Z=-5.200, -6.297, P<0.01), worse acute physical and chronic health evaluation (APACHE) Ⅱ score, abbreviated burn severity index score, and sequential organ failure assessment (SOFA) score on admission (Z=-7.485, -4.739, -4.590, P<0.01), higher occurrence rate of sepsis (χ(2)=33.087, P<0.01), higher rates of accepting tracheotomy, mechanical ventilation, and continuous renal replacement therapy (χ(2)=12.373, 17.201, 43.763, P<0.01), larger first excision area (Z=-2.191, P<0.05), and higher mortality on post injury days 30, 60, and 90 (χ(2)=7.483, 37.259, 45.533, P<0.01). There were no statistically significant differences in sex, open decompression, admission time, 24-hour fluid volume after admission, 48-hour fluid volume after admission, the first 24-hour urine volume, the second 24 hour urine volume, the first excision time, and inhalation injury (χ(2)=0.529, 3.318, Z=-1.746, -0.016, -1.199, -1.824, -0.625, -1.747, P>0.05). The rates of deep vein catheterization of patients in the two groups were both 100%. (2) There were twenty possible prediction variables for preliminary establishment of model according to the difference results of single factor analysis and clinical significance of variables. (3) The logistic regression prediction model had three variables: APACHE Ⅱ score [odds ratio (OR)=1.36, 95% confidence interval (CI)=1.20-1.53, P<0.001], sepsis (OR=2.63, 95% CI=0.90-7.66, P>0.05), and the first 24-hour urine volume (OR=0.71, 95% CI=0.50-1.01, P>0.05). The AUC of the logistic regression prediction model was 0.875 (95% CI=0.821-0.930), with the specificity and sensitivity of optimal threshold value 84.4% and 77.7%, respectively. (4) XGBoost machine learning model had seven main predictive variables: APACHE Ⅱ score, full-thickness burn area, 24-hour fluid volume after admission, sepsis, the first 24-hour urine volume, SOFA score, and 48-hour fluid volume after admission. The AUC of machine learning model was 0.920 (95% CI=0.879-0.962), higher than that of logistic regression model (P<0.001), with the specificity and sensitivity of optimal threshold value 89.7% and 82.0%, respectively. Conclusions: Sepsis and fluid resuscitation are two important predictive variables that can be intervened for AKI in severely burned patients. Machine learning method has a better performance and can provide more accurate prediction for individuals than logistic regression prediction model, and therefore has good clinical application prospect.

Abstract PD-015: BALANCED SALT SOLUTION VERSUS NORMAL SALINE IN RESUSCITATION OF PEDIATRIC SEPSIS: A RANDOMIZED CONTROL TRIAL

Aims & Objectives: Rationale Pediatric sepsis is the leading cause of PICU admissions and mortality. Current evidences in resuscitation of adult sepsis pointed to the importance of types of crystalloid and fluid-related complication on resuscitation outcomes, but evidences are lacking in pediatric populations. Objectives To compare the outcomes of pediatric sepsis resuscitation with different types of crystalloid fluid. Methods We randomly assigned the participants into 3 groups to received NSS, RLS or Sterofundin as bolus fluid therapy. Other standard of cares were continued with primary care physicians’ judgment. Data were analysed using SPSS version 22. Results 31 patients were included into the study. Median age 33 mo. (IQR 21 – 60), PELODS-II score at 5 pts. (IQR 1 – 7), PRISM-III score at 5 pts. (IQR 2 – 9 pts.). Median dose of resuscitation fluid was 30 mL/kg (IQR 20 – 40). Baseline demographic data were not significantly different between 3 groups. After resuscitation, acid-base status parameters and fluid-related complications were not significantly different among groups. Subgroup analysis of patients received bolus fluid ≥ 30 mL/kg showed significant better lactate clearance after 24 hrs. in RLS group (p-value 0.046). Mortality, ventilator days, PICU & hospital LOS were not different between groups. Conclusions Resuscitation of pediatric sepsis with RLS when dosing ≥ 30 mL/kg, comparing with NSS, resulted in significant better lactate clearance at 24 hrs. after resuscitation. Balanced salt solution were not associated with significantly different rate of fluid-related complications.

Pyruvate-enriched resuscitation for shock.

This commentary addresses the recent retraction of an article which reported favorable outcomes in septic patients treated with intravenous pyruvate. The retracted report was cited in the authors' recent minireview on the cellular mechanisms and clinical application of pyruvate to improve cardiac performance. Because the retracted article reports pyruvate-enhanced resuscitation of critically ill patients, the authors wish to inform the readership, especially critical care providers, that this particular clinical application of pyruvate is not now supported by robust evidence. After discussing the retraction's implications for the clinical application of pyruvate-enriched resuscitation for sepsis, this commentary summarizes the extensive preclinical evidence of the efficacy and mechanisms of pyruvate resuscitation in animal models of hemorrhagic and septic shock, which argues for renewed clinical investigation of pyruvate-enriched resuscitation. Impact statement This commentary addresses the recent retraction of a clinical report of significant benefits of intravenous pyruvate resuscitation in septic patients, including sharply lowered mortality and decreased circulating pro-inflammatory cytokines, which was cited in the authors' minireview in Experimental Biology and Medicine. The potential implications of the retraction, and the extensive preclinical evidence supporting the use of pyruvate-enriched resuscitation for shock states, are summarized and discussed.