Adult Septic Shock Research Articles

One--Year Progression and Risk Factors for the Development of Chronic Kidney Disease in Septic Shock Patients with Acute Kidney Injury: A Single-Centre Retrospective Cohort Study.

(1) Background: Sepsis-associated acute kidney injury (AKI) can lead to permanent kidney damage, although the long-term prognosis in patients with septic shock remains unclear. This study aimed to identify risk factors for the development of chronic kidney disease (CKD) in septic shock patients with AKI. (2) Methods: A single-site, retrospective cohort study was conducted using a registry of adult septic shock patients. Data from patients who had developed AKI between January 2011 and April 2017 were extracted, and 1-year follow-up data were analysed to identify patients who developed CKD. (3) Results: Among 2208 patients with septic shock, 839 (38%) had AKI on admission (stage 1: 163 (19%), stage 2: 339 (40%), stage 3: 337 (40%)). After one year, kidney function had recovered in 27% of patients, and 6% had progressed to CKD. In patients with stage 1 AKI, 10% developed CKD, and mortality was 13% at one year; in patients with stage 2 and 3 AKI, the CKD rate was 6%, and the mortality rate was 42% and 47%, respectively. Old age, female, diabetes, low haemoglobin levels and a high creatinine level at discharge were seen to be risk factors for the development of CKD. (4) Conclusions: AKI severity correlated with mortality, but it did not correlate with the development of CKD, and patients progressed to CKD, even when initial AKI stage was not severe. Physicians should focus on the recovery of renal function, and ensure the careful follow-up of patients with risk factors for the development of CKD.

Low Interleukin-7 Receptor Messenger RNA Expression Is Independently Associated With Day 28 Mortality in Septic Shock Patients.

Septic shock is the primary cause of death in ICUs. A better comprehension of its pathophysiology, in particular, the immune alteration mechanisms, opened new therapeutic perspectives such as the recombinant interleukin-7. The use of biomarkers could improve the identification of eligible patients for this therapy. The soluble form of the interleukin-7 appears as a promising candidate in this regard since an association between its high plasmatic level and mortality in critically ill patients has been demonstrated. Because there are no data available on the transcriptional regulation of the interleukin-7 receptor in such patients, this study aimed to explore the expression level of different interleukin-7 receptor transcripts after septic shock and evaluate their association with mortality. Retrospective discovery cohort (30 patients) and validation cohort (177 patients). Two French ICUs (discovery study) and six French ICUs (validation study). Adult septic shock patients. None. The quantification of several interleukin-7 receptor transcripts using specific reverse transcription quantitative polymerase chain reaction designs allowed for global evaluation of interleukin-7 receptor gene expression in whole blood. In the discovery cohort, all interleukin-7 receptor transcripts studied were expressed at lower levels in septic shock patients than in healthy volunteers. Interleukin-7 receptor gene expression at day 3 after septic shock diagnosis was associated with day 28 mortality. Patients at a lower risk of death showed higher expression levels. These results were confirmed in the independent validation cohort. Interestingly, using a threshold obtained on the discovery cohort, we observed in the validation cohort a high negative predictive value for day 28 mortality for the transcript encoding the membrane form of interleukin-7 receptor (0.86; 95% CI, 0.79-0.93). Interleukin-7 receptor transcripts appear as biomarkers of impaired adaptive immune response in septic shock patients and as a promising tool for patient stratification in clinical trials evaluating immunoadjuvant therapies.

Potential mortality and cost reduction in adult severe sepsis and septic shock through the use of an innovative fluid delivery device.

BackgroundWhile early fluid resuscitation has been shown to significantly improve health and economic metrics in septic shock, providers are often unable to achieve fluid delivery guidelines using current techniques.PurposeTo examine expected clinical and economic consequences of more consistent achievement of fluid resuscitation guidelines through use of a novel fluid delivery technology.Patients and methodsA decision analytic model was developed to compare expected costs and outcomes associated with the standard technique vs a novel, faster technique for rapid fluid resuscitation in adult patients with severe sepsis or septic shock.ResultsUse of an innovative fluid delivery device (LifeFlow) resulted in lower expected mortality compared to standard intravenous fluid delivery methods (reduction of 10 fewer deaths per 500 cases). Compared to standard methods, use of the innovative rapid fluid delivery device also resulted in lower expected hospital costs (US$1,569,131 cost reduction per 500 cases), a lower required use of mechanical ventilation (24% vs 31%), decreased average length of stay (11 vs 13 days), decreased average intensive care unit length of stay (2 vs 3 days), and decreased use of vasopressors (17% vs 21%). A sensitivity analysis showed that utilization of the rapid fluid delivery device is more cost-effective than standard methods, even under the most conservative assumptions.ConclusionBased on existing data supporting the importance of early, controlled fluid resuscitation in septic shock patients, the analytical model developed in this study demonstrated the benefit of a novel device that facilitates earlier fluid bolus completion and better adherence to sepsis bundles.

Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis.

This study aimed to compare the effects on mortality of albumin and crystalloid, used for fluid resuscitation among adult patients with septic shock, through conducting a meta-analysis and trial sequential analysis (TSA). Meta-analysis and TSA conducted at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Data were collected from several major databases including MEDLINE, EMBASE, Clinical Trials.gov and Cochrane Central Register of Controlled Trials. Studies that compared the effects of albumin therapy versus crystalloid therapy on mortality among adult septic shock patients were eligible for inclusion in the analyses. The study name, year of publication, country of the trial, albumin concentration, type of crystalloid and all reported mortalities at different follow-up endpoints were extracted. Compared with crystalloid, albumin did not decrease all-cause mortality at the final follow-up. However, in TSA, the required information size was not achieved in all groups, which means that the effect size was not definitive and further RCTs are needed to confirm or deny these findings. Compared with crystalloid solutions, albumin was unable to decrease all-cause mortality. However, TSA indicated that these results could be false-negative. Additional randomized controlled trials are needed to clarify this discrepancy.

Clinical Outcomes of Minimized Hydrocortisone Dosage of 100 Mg/Day on Lower Occurrence of Hyperglycemia in Septic Shock Patients.

The current international guideline recommended 200 mg/day of hydrocortisone intravenously to treat septic shock. However, a subsequent study on cortisol metabolism actually showed an increase in cortisol level during sepsis. Hence, the smaller hydrocortisone dose of 100 mg/day might be sufficient and reduce steroid-associated complications. We aimed to compare the clinical outcomes of minimized hydrocortisone dose of 100 mg to the currently recommended dose in the treatment of septic shock patients. A double-blinded randomized controlled trial included 80 septic shock patients with hemodynamic instability despite fluid and vasopressive therapy. Participants were divided equally into two groups to treat with 100 mg/day or 200 mg/day of hydrocortisone, then stepwise down titrated and discontinued on day 8. The outcome of interest was the hyperglycemic rate. Vital status, time to shock reversal, superinfection and gastrointestinal bleeding rates were also compared. Patients with 100 mg hydrocortisone had significantly lower hyperglycemic rate compared with 200 mg, 63.9% versus 86.5% (the adjusted hazard ratio [HR], 0.08; 95% confidence interval [CI], 0.02-0.41, P = 0.002). Time to shock reversal was shorter in patients with 100 mg hydrocortisone, 2 days vs. 4 days, P = 0.031. The 28-day mortality rate when adjusted for Simplified Acute Physiology Score II showed no significant difference (HR, 0.68; 95% CI, 0.37-1.24, P = 0.209). The reinfection and gastrointestinal bleeding rates were comparable between groups. Minimized daily hydrocortisone dosage of 100 mg could lower the occurrence of hyperglycemia without increasing mortality in septic shock, compared with the currently recommended dosage of 200 mg/day.

Challenges and Opportunities for Emergency Department Sepsis Screening at Triage

Feasibility of ED triage sepsis screening, before diagnostic testing has been performed, has not been established. In a retrospective, outcome-blinded chart review of a one-year cohort of ED adult septic shock patients (“derivation cohort”) and three additional, non-consecutive months of all adult ED visits (“validation cohort”), we evaluated the qSOFA score, the Shock Precautions on Triage (SPoT) vital-signs criterion, and a triage concern-for-infection (tCFI) criterion based on risk factors and symptoms, to screen for sepsis. There were 19,670 ED patients in the validation cohort; 50 developed ED septic shock, of whom 60% presented without triage hypotension, and 56% presented with non-specific symptoms. The tCFI criterion improved specificity without substantial reduction of sensitivity. At triage, sepsis screens (positive qSOFA vital-signs and tCFI, or positive SPoT vital-signs and tCFI) were 28% (95% CI: 16–43%) and 56% (95% CI: 41–70%) sensitive, respectively, p < 0.01. By the conclusion of the ED stay, sensitivities were 80% (95% CI: 66–90%) and 90% (95% CI: 78–97%), p > 0.05, and specificities were 97% (95% CI: 96–97%) and 95% (95% CI: 95–96%), p < 0.001. ED patients who developed septic shock requiring vasopressors often presented normotensive with non-specific complaints, necessitating a low threshold for clinical concern-for-infection at triage.

Do low-dose corticosteroids improve survival or shock reversal from septic shock in adults? Meta-analysis with trial sequential analysis.

ObjectiveThis meta-analysis with trial sequential analysis (TSA) was performed to determine whether low-dose corticosteroids (LDCs) can improve survival or shock reversal from septic shock in adults.MethodsA literature search was performed using several databases (Medline, Cochrane Library, Embase, and Chinese Biological Medical Database) until 23 October 2017. The systematic review was registered in PROSPERO.ResultsNine randomized controlled trials (RCTs) (n = 1182) were included. LDC intervention improved 7-day shock reversal compared with the control group (relative risk, 1.36; TSA-adjusted 95% confidence interval, 1.20–1.54). LDCs had no statistically significant effects on gastrointestinal bleeding or superinfection. LDCs did not reduce 28-day mortality from septic shock (relative risk, 0.96; TSA-adjusted 95% confidence interval, 0.74–1.24). The TSA indicated that RCTs of about 3000 patients would be needed to draw definitive conclusions; similar results were obtained in a subgroup analysis of nonresponders.ConclusionsLDCs improve 7-day shock reversal. However, whether LDCs improve 28-day survival from septic shock in adults remains unclear. The results of well-designed larger RCTs are needed.

A Non-Comparative Prospective Pilot Study of Ketamine for Sedation in Adult Septic Shock.

Sedation and analgesia in the intensive care unit (ICU) for patients with sepsis can be challenging. Opioids and benzodiazepines can lower blood pressure and decrease respiratory drive. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that provides both amnesia and analgesia without depressing respiratory drive or blood pressure. The purpose of this pilot study was to assess the effect of ketamine on the vasopressor requirement in adult patients with septic shock requiring mechanical ventilation. We conducted a two-phase study in a multi-disciplinary adult ICU at a tertiary medical center. The first phase was a retrospective chart review of patients admitted with septic shock between July 2010 and July 2011; 29 patients were identified for a historical control group. The second phase was a prospective, non-randomized, open-label pilot study. Patients were eligible for inclusion if they were 18-89 yr of age with a diagnosis of septic shock, who also required mechanical ventilation for at least 24 h, concomitant sedation, and vasopressor therapy. Pregnant patients, patients in the peri-operative timeframe, and patients with acute coronary syndrome were excluded. Patients enrolled in the phase two pilot study received ketamine as the primary sedative. Ketamine was administered as a 1-2 mg/kg IV bolus, then as a continuous infusion starting at 5 mcg/kg/min, titrated 2 mcg/kg/min every 30 min as needed to obtain a Richmond Agitation Sedation Scale (RASS) goal of -1 to -2. If continuous sedation was still required after 48 h, patients were transitioned off ketamine and sedative strategy reverted to usual ICU sedation protocol. The primary outcome was the dose of vasopressor required at 24, 48, 72 and 96 h after enrollment. Secondary outcomes included cumulative ketamine dose, additional sedative and analgesics used, cumulative sedative and analgesic dosing at all time periods, corticosteroid use, days of mechanical ventilation, ICU LOS, hospital LOS, and mortality. Contiguous data were analyzed with unpaired t-tests and categorical data were analyzed with two-tailed, Fisher's exact test. This study was approved by our Institutional Review Board. From January 2012 to April 2015, a total of 17 patients were enrolled. Patient characteristics were similar in the control and study group. Ketamine was discontinued in one patient due to agitation at 36 h. There was a trend towards decreased norepinephrine and vasopressin use in the study group at all time periods. Regarding secondary outcomes, the study group received less additional analgesia with fentanyl at 24 and 48 h (p < 0.001), and less additional sedation with lorazepam, midazolam or dexmedetomidine at 24 h (p = 0.015). This pilot study demonstrated a trend towards decreased vasopressor dose, and decreased benzodiazepine and opiate use when ketamine is used as the sole sedative. The limitations to our study include a small sample size and those inherent in using a retrospective control group. Our findings should be further explored in a large, randomized prospective study.

Is Heparin-Binding Protein Inhibition a Mechanism of Albumin's Efficacy in Human Septic Shock?

Our objectives were to determine first whether albumin prevents heparin-binding protein-induced increased endothelial cell permeability and renal cell inflammation and second, whether a plasma heparin-binding protein-to-albumin ratio predicts risk of acute kidney injury, fluid balance, and plasma cytokine levels in septic shock. In vitro human endothelial and renal cell model and observation cohort of septic shock. Research laboratory and multicenter clinical trial (Vasopressin and Septic Shock Trial). Adult septic shock (norepinephrine dose > 5 μg/min for > 6 hr). In vitro: heparin-binding protein (or thrombin) was added with or without albumin to 1) human endothelial cell monolayers to assess permeability and 2) to human renal tubular epithelial cells to assess inflammation. Transendothelial electrical resistance-a marker of permeability-of human endothelial cells was measured using a voltohmmeter. We measured plasma heparin-binding protein-to-albumin ratio and a panel of cytokines in septic shock patients (n = 330) to define an heparin-binding protein-to-albumin ratio that predicts risk of acute kidney injury. Albumin inhibited heparin-binding protein (and thrombin-induced) increased endothelial cell permeability at a threshold concentration of 20-30 g/L but increased renal tubular cell interleukin-6 release. Patients who developed or had worsened acute kidney injury had significantly higher heparin-binding protein-to-albumin ratio (1.6 vs 0.89; p < 0.001) and heparin-binding protein (38.2 vs 20.8 ng/mL; p < 0.001) than patients without acute kidney injury. The highest heparin-binding protein-to-albumin ratio (> 3.05), heparin-binding protein quartiles (> 69.8), and heparin-binding protein > 30 ng/mL were significantly associated with development or worsening of acute kidney injury (p < 0.001) in unadjusted and adjusted analyses and were robust to sensitivity analyses for death as a competing outcome. Heparin-binding protein and heparin-binding protein-to-albumin ratio were directly associated with positive fluid balance (p < 0.001) and with key inflammatory cytokines. Increasing quartiles of heparin-binding protein-to-albumin ratio and heparin-binding protein (but not albumin) were highly significantly associated with days alive and free of acute kidney injury and renal replacement therapy (p < 0.001), vasopressors (p < 0.001), ventilation (p < 0.001), and with 28-day mortality. Albumin inhibits heparin-binding protein-induced increased human endothelial cell permeability and heparin-binding protein greater than 30 ng/mL and heparin-binding protein-to-albumin ratio greater than 3.01-but not serum albumin-identified patients at increased risk for acute kidney injury in septic shock.

Clinical Outcomes of Weight-Based Norepinephrine Dosing in Underweight and Morbidly Obese Patients: A Propensity-Matched Analysis.

Weight-based dosing strategy for norepinephrine in septic shock patients with extremes of body mass index has been lesser studied. This historical study of adult septic shock patients was conducted from January 1, 2010, to December 31, 2015, at all intensive care units (ICUs) in Mayo Clinic, Rochester. Patients with documented body mass index were classified into underweight (body mass index <18.5 kg/m2), normal weight (18.5-24.9 kg/m2), and morbidly obese (≥40 kg/m2) patients. Patients with repeat ICU admissions, ICU stay <1 day, and body mass index 25 to 39.9 kg/m2 were excluded. The primary outcome was in-hospital mortality, and secondary outcomes included cumulative norepinephrine exposure acute kidney injury, cardiac arrhythmias, and 1-year mortality. Two-tailed P < .05 was considered statistically significant. From 2010 to 2015, 2016 patients met inclusion-145, 1406, and 466 patients, respectively, in underweight, normal weight, and morbidly obese cohorts. Underweight patients used the highest peak dose and absolute exposure was greatest for morbidly obese patients. In-hospital mortality decreased with increasing log10 body mass index: 41.4% (underweight), 28.4% (normal weight), and 24.7% (morbidly obese), respectively (P < .001); however, this relationship was not noted at 1 year. Unadjusted log10 norepinephrine cumulative exposure (mg) was associated with higher in-hospital mortality, acute kidney injury, cardiac arrhythmias, and 1-year mortality. After adjustment for demographics, body mass index, comorbidity, and illness severity, log10 norepinephrine exposure was an independent predictor of in-hospital mortality (odds ratio 2.4 [95% confidence interval, 2.0-2.8]; P < .001) and 1-year mortality (odds ratio 1.7 [95% confidence interval, 1.5-2.0]; P < .001). In a propensity-matched analysis of 1140 patients, log10 norepinephrine was an independent predictor of in-hospital mortality (odds ratio 2.2 [95% confidence interval, 1.8-2.6]; P < .001). Morbidly obese patients had lower in-hospital mortality but had higher 1-year mortality compared to normal weight and underweight patients. Cumulative norepinephrine exposure was highest in morbidly obese patients. Total norepinephrine exposure was an independent mortality predictor in septic shock.

Extracorporeal life support for adults with refractory septic shock

ObjectiveAlthough the use of extracorporeal membrane oxygenation (ECMO) in shock patients is increasing worldwide, studies concerning this treatment for adult septic shock are limited. This study aimed to analyze the outcome of venoarterial ECMO in adult patients with septic shock refractory to conventional treatment. MethodsA total of 71 consecutive patients who presented with septic shock and underwent venoarterial ECMO were reviewed. Clinical parameters were compared between survivors and nonsurvivors. Weaning and survival outcomes of these patients were compared with the control group of 253 patients who received venoarterial ECMO for cardiogenic shock. ResultsThe mean age was 56.0 ± 12.3 years. Of the 71 septic shock patients, 11 (15.5%) were successfully weaned from ECMO after a median of 7.9 [interquartile range (IQR), 6.3-10.2] days, 5 of whom (7.0%) survived to discharge. Pre- and 6 hours post-procedural lactate levels were significantly higher in the nonsurvivors (11.6 [IQR, 7.5-15.0] vs 5.8 [IQR, 4.3-5.9], P = .036; 15.0 [IQR, 11.1-15.0] vs 5.2 [IQR, 4.7-5.4], P = .002). Rates of successful weaning from venoarterial ECMO (15.5% vs 45.5%), and of survival up to hospital discharge (7.0% vs 28.9%) were significantly lower in septic shock than in cardiogenic shock patients (n = 253; P < .001). ConclusionsOutcomes of ECMO in refractory septic shock patients were poor with a very low probability of survival. This finding raises questions concerning the utility of applying ECMO for medically refractory septic shock. Elevated arterial lactate levels pre- and post-ECMO were associated with risk of in-hospital death. Further large-scale studies are needed to validate the results of this study.

Septic Shock Shapes B Cell Response toward an Exhausted-like/Immunoregulatory Profile in Patients.

Septic shock is accompanied by the development of immune dysfunctions whose intensity and duration are associated with increased risk of secondary infections and mortality. Although B lymphocytes play a pivotal role in the immune response to infections, no comprehensive exploration of circulating B cell status has been performed during the immunosuppressive phase of septic shock. Thus, our aim was to extensively characterize the phenotype and function of B cells in septic shock, including IL-10 production. Circulating B lymphocyte phenotype and function were evaluated by flow cytometry on fresh whole blood and after ex vivo stimulation in adult septic shock patients sampled at day 1, 3, and 6 after the onset of shock. The circulating B cell number was reduced in septic shock patients, whereas the B cell proportion among total lymphocytes was increased. The remaining circulating B lymphocytes presented with decreased MHC class II expression and increased CD21low CD95high exhausted-like phenotype but showed no change in maturation status. Circulating B cell functions were markedly altered after sepsis with reduced ex vivo activation and proliferation capacities. Finally, B cell response after septic shock was characterized by a clear plasmacytosis and an increased IL-10 production in remaining B cells from patients after ex vivo stimulation. During the sepsis-induced immunosuppression phase, B cell response is altered and is oriented toward an exhausted-like/immunoregulatory profile. Further studies are now needed to confirm the immunoregulatory properties of B lymphocytes and evaluate their role in sepsis-induced immunosuppression.

Lactate clearance cut off for early mortality prediction in adult sepsis and septic shock patients

Previous lactate clearance cut off for early mortality prediction in sepsis and septic shock patient was determined by consensus from small sample size-study. We investigated the best lactate clearance cut off and its ability to predict early mortality in sepsis and septic shock patients. This cohort study was conducted in Intensive Care Unit of CiptoMangunkusumo Hospital in 2013. Patients’ lactate clearance and eight other resuscitationendpoints were recorded, and theoutcome was observed during the first 120 hours. The clearance cut off was determined using receiver operating characteristic (ROC) analysis, and its ability was investigated with Cox’s proportional hazard regression analysis using other resuscitation endpoints as confounders. Total of 268 subjects was included, of whom 70 (26.11%) subjects died within the first 120 hours. The area under ROC of lactate clearance to predict early mortality was 0.78 (95% % confidence interval [CI] 0.71-0.84) with best cut off was <7.5% (sensitivity and specificity 88.99% and 81.4% respectively). Compared with group achieving lactate clearance target, group not achieving lactate clearance target had to increase early mortality risk (adjusted hazard ratio 13.42; 95%CI 7.19-25.07). In conclusion, the best lactate clearance cut off as anearly mortality predictor in sepsis and septic shock patients is 7.5%.

Elevated central venous pressure is associated with increased mortality in pediatric septic shock patients

BackgroundCentral venous pressure (CVP) is an important factor affecting capillary blood flow, and it is associated with poor outcomes in adult septic shock patients. However, whether a similar association exists in pediatric patients remains unclear.MethodsWe retrospectively analyzed data from patients admitted to our pediatric intensive care unit (PICU) between February 2009 and July 2015. Patients were divided into two groups—survivors and nonsurvivors—according to 28-day mortality. The associations between (a) mortality and CVP at 6, 24, 48, and 72 h after initiating treatment for established septic shock was analyzed and (b) initial serum lactic acid levels and 6-h CVP.ResultsTwo hundred twenty-six patients were included in this study, and the mortality rate was 29.6% (67 deaths, nonsurvivor group). Initial serum lactic acid levels, Pediatric Risk of Mortality (PRISM) III score, and Vasoactive–Inotropic Score (VIS) within 24 h after PICU admission were significantly higher in the nonsurvivors than in survivors (1.3 [0.9, 2.4] vs. 3.9 [1.6, 8.0] mmol/l, 11.0 [7.0, 15.0] vs. 17.0 [10.0, 21.5], 12.0 [7.0, 25.0] vs. 22.5 [8.0, 55.0], respectively with p-values < 0.001, < 0.001, and 0.009, respectively). In addition, compared to survivors, a greater percentage of nonsurvivors required mechanical ventilation (92.5% vs. 51.6%, p < 0.001) and showed a greater extent of fluid overload at 48 h after admission (3.9% vs. 1.9%, p = 0.006), along with higher 6-h CVP (10.0 [7.0, 16.0] vs. 8.0 [5.0, 11.0] mmHg, p < 0.001). Patient survival according to levels of CVP (CVP < 8 mmHg, CVP 8–12 mmHg, or CVP > 12 mmHg) showed that the CVP > 12-mmHg group had significantly greater mortality rates (50.0%, p = 0.002) than the other groups (21.3% and 27.5%). Furthermore, multivariate analysis identified significant associations of CVP > 12 mmHg, serum lactic acid levels, and the need for mechanical ventilation with mortality (OR: 2.74, 1.30, and 12.51, respectively; 95% CI: 1.11–6.72, 1.12–1.50, and 4.12–37.96, respectively).ConclusionsElevated CVP is an independent risk factor for mortality in pediatric septic shock patients.

Patterns and Outcomes Associated With Timeliness of Initial Crystalloid Resuscitation in a Prospective Sepsis and Septic Shock Cohort.

The objectives of this study were to 1) assess patterns of early crystalloid resuscitation provided to sepsis and septic shock patients at initial presentation and 2) determine the association between time to initial crystalloid resuscitation with hospital mortality, mechanical ventilation, ICU utilization, and length of stay. Consecutive-sample observational cohort. Nine tertiary and community hospitals over 1.5 years. Adult sepsis and septic shock patients captured in a prospective quality improvement database inclusion criteria: suspected or confirmed infection, greater than or equal to two systemic inflammatory response criteria, greater than or equal to one organ-dysfunction criteria. The primary exposure was crystalloid initiation within 30 minutes or lesser, 31-120 minutes, or more than 120 minutes from sepsis identification. We identified 11,182 patients. Crystalloid initiation was faster for emergency department patients (β, -141 min; CI, -159 to -125; p < 0.001), baseline hypotension (β, -39 min; CI, -48 to -32; p < 0.001), fever, urinary or skin/soft-tissue source of infection. Initiation was slower with heart failure (β, 20 min; CI, 14-25; p < 0.001), and renal failure (β, 16 min; CI, 10-22; p < 0.001). Five thousand three hundred thirty-six patients (48%) had crystalloid initiated in 30 minutes or lesser versus 2,388 (21%) in 31-120 minutes, and 3,458 (31%) in more than 120 minutes. The patients receiving fluids within 30 minutes had lowest mortality (949 [17.8%]) versus 31-120 minutes (446 [18.7%]) and more than 120 minutes (846 [24.5%]). Compared with more than 120 minutes, the adjusted odds ratio for mortality was 0.76 (CI, 0.64-0.90; p = 0.002) for 30 minutes or lesser and 0.76 (CI, 0.62-0.92; p = 0.004) for 31-120 minutes. When assessed continuously, mortality odds increased by 1.09 with each hour to initiation (CI, 1.03-1.16; p = 0.002). We observed similar patterns for mechanical ventilation, ICU utilization, and length of stay. We did not observe significant interaction for mortality risk between initiation time and baseline heart failure, renal failure, hypotension, acute kidney injury, altered gas exchange, or emergency department (vs inpatient) presentation. Crystalloid was initiated significantly later with comorbid heart failure and renal failure, with absence of fever or hypotension, and in inpatient-presenting sepsis. Earlier crystalloid initiation was associated with decreased mortality. Comorbidities and severity did not modify this effect.

Norepinephrine Dosing in Obese Patients: Impact of Weight-Based Dosing on Short- and Long-Term Mortality

SESSION TITLE: Sepsis & Septic Shock SESSION TYPE: Original Investigation Slide PRESENTED ON: Sunday, October 29, 2017 at 01:30 PM - 03:00 PM PURPOSE: Obesity is thought to be protective in septic shock. Norepinephrine (NE) is frequently dosed by a weight-based regimen, and potentially higher doses of NE are used in the obese population. The interaction of body mass index (BMI) with NE dosing and their influence on clinical outcomes has been only limitedly explored. METHODS: Historical cohort study of all adult septic shock patients requiring NE admitted between 2010 through 2015 to all intensive care units (ICU) at Mayo Clinic Rochester. Patients with BMI 25-39.9 kg/m2 were classified into overweight (25-29.9 kg/m2), obesity class I (30-34.9 kg/m2) and obesity class II (35-39.9 kg/m2). Patients with normal BMI (18.5-24.9 kg/m2) formed the control group. Patients with chronic respiratory failure, repeat ICU admissions, ICU stay <1day, lactate <2 mmol/L and BMI <18.5 and ≥ 40 kg/m2 were excluded. The primary outcome was in-hospital mortality and secondary outcomes included new cardiac arrhythmias, acute kidney injury (AKI) and one-year mortality. Odds ratios (OR) [95% confidence intervals (CI)] were used to represent univariate and multivariate outcomes respectively. A two-tailed p<0.05 was considered significant. RESULTS: During this 6-year period, 4774 patients met our study criteria - BMI 18.5-24.9, 25-29.9, 30-34.9 and 35-39.9 kg/m2 had 1406 (29%), 1608 (34%), 1151 (24%) and 609 (13%) patients respectively. The baseline characteristics revealed significant inter-group differences in age, race, gender and baseline creatinine, but no differences in comorbidity burden, severity of illness or use of corticosteroids in the ICU. Median NE dose increased linearly with increase in BMI cohorts - 5 gm (interquartile range [IQR] 1-13) (BMI 18.5-24.9 kg/m2), 5.3 gm (IQR 2-14) (BMI 25-29.9 kg/m2), 6 gm (IQR 2-16) (BMI 30-34.9 kg/m2) and 7 gm (IQR 2-18) (BMI 35-39.9 kg/m2), p<0.001. There was no difference in number, type or total doses of additional vasoactive medications. In-hospital (29%, 24%, 22%, 22%; p<0.001) and one-year mortality (46%, 53%, 53%, 51%; p=0.001) were significantly different between patients with BMI 18.5-24.9, 25-29.9, 30-34.9 and 35-39.9 kg/m2 respectively. Unadjusted log10NE levels were associated with higher in-hospital mortality (OR 2.9 [95%CI 2.6-3.3]; p<0.001), AKI (OR 1.8 [95% CI 1.6-1.9]; p<0.001), cardiac arrhythmias (OR 1.4 [95% CI 1.3-1.5]; p<0.001) and one-year mortality (OR 1.8 [95% CI 1.6-2]; p<0.001). After adjusting for age, gender, BMI, comorbidity burden, severity of illness, cardiac injury, AKI, cardiac arrhythmia and use of mechanical ventilation, log10NE was an independent predictor of in-hospital (OR 2.2 [95% CI 1.9-2.7]; p<0.001) and one-year mortality (OR 1.4 [95% CI 1.2-1.7]; p<0.001). CONCLUSIONS: Total NE use was independently associated with worse short and long-term mortality, AKI and cardiac arrhythmias in patients independent of BMI. CLINICAL IMPLICATIONS: Alternative strategies to weight-based NE dosing are recommended in obese patients. DISCLOSURE: The following authors have nothing to disclose: Aditya Kotecha, Saraschandra Vallabhajosyula, Dinesh Apala, Erin Frazee, Vivek Iyer No Product/Research Disclosure Information

Respiratory extracorporeal membrane oxygenation for severe sepsis and septic shock in adults: a propensity score analysis in a multicenter retrospective observational study.

AimThis multicenter retrospective observational study aimed to evaluate the efficacy of extracorporeal membrane oxygenation (ECMO) support for septic patients with severe respiratory failure using propensity score analyses.MethodsThe data of severe sepsis patients from 42 intensive care units between January 2011 and December 2013 were retrospectively collected. Propensity score matching analyses were undertaken for severe respiratory failure patients with/without veno‐venous ECMO support. The main outcome was in‐hospital all‐cause mortality.ResultsOf 3195 patients with severe sepsis, 570 had severe respiratory failure. Forty patients in the ECMO group were matched with 150 patients in the control group. A survival time analysis revealed no difference in the in‐hospital survival (hazard ratio, 0.854; 95% confidence interval, 0.531–1.373; P = 0.515). Two‐hundred and eighty‐five patients had severe respiratory failure induced by lung infection. Twenty‐five ECMO group patients were matched with 89 patients in the control group. In the ECMO group, the survival time was longer than in the control group (hazard ratio, 0.498; 95% confidence interval, 0.279–0.889; P = 0.018). The number of renal replacement therapy‐ and vasopressor‐free days improved. The ECMO group received more red blood cells transfused than the control group, but there was no significant difference in the rate of severe bleeding complications between the groups.ConclusionsThere was no difference in the in‐hospital survival between the ECMO group and control group among overall septic patients with severe respiratory failure. However, in sepsis patients with severe respiratory failure induced by lung infection, ECMO support may improve their survival time.

Intestinal fatty acid-binding protein level as a predictor of 28-day mortality and bowel ischemia in patients with septic shock: A preliminary study

PurposeWe sought to evaluate the levels of intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, as a predictor of 28-day mortality and bowel ischemia in septic shock patients. Material and methodsIn this preliminary prospective observational study, 57 adult septic shock patients under mechanical ventilation were enrolled. Serum I-FABP levels and prognostic biomarkers were recorded upon intensive care unit (ICU) admission. ResultsThe overall 28-day mortality rate of participants was 23% (13/57). Non-survivors displayed significantly higher lactate (p=0.009), I-FABP (p=0.012), and N-terminal pro-B-type natriuretic peptide (p=0.039) levels compared to survivors. Only I-FABP was associated with 28-day mortality (odds ratio, 1.036; 95% confidence interval, 1.003–1.069; p=0.031) in a multiple logistic regression analysis adjusted for the Acute Physiology and Chronic Health Evaluation II score. When divided into low and high I-FABP groups based on the optimum cut-off value of 19.0ng/mL for predicting 28-day mortality, high-I-FABP patients had a significantly higher incidence of non-occlusive mesenteric ischemia (NOMI) (2% [1/43] vs 29% [4/14]; p=0.011). ConclusionsI-FABP level at ICU admission can serve as a predictor of 28-day mortality in septic shock patients and is associated with the incidence of NOMI.

WITHDRAWN: Pulse-induced contour cardiac output (PiCCO) combined with passive leg raising test predicting fluid resuscitation in adult patients with septic shock

To investigate the clinical value of pulse-induced contour cardiac output (PiCCO) monitoring combined with passive leg raising (PLR) test in predicting fluid responsiveness so as to guide fluid resuscitation in adult septic shock patients managed by rehydration test. One hundred and forty five adult septic shock patients, who were informed to receive PLR tests and rehydration tests. Patients were divided into two groups based on the observation of fluid responsiveness in the rehydration test. Parameters including heart rate (HR), central venous pressure (CVP), systolic blood pressure (SAP), mean arterial pressure (MAP), pulse pressure (PP), pulse indicates cardiac index (PCCI), central venous blood saturation in oxygen (ScvO2) and stroke fluid (SV) were monitored. By PLR test, CVP, SAP, MAP, PP, PCCI and ScvO2 were all increased significantly in the responding group; CVP, SAP, MAP, PP, PCCI and ScvO2 were all upregulated in the responding and nonresponding groups after PLR test (all P < 0.05). By rehydration test, CVP, MAP, PCCI, ScvO2 and SV were elevated in the responding group; and CVP, MAP and PCCI improved significantly both in both groups after rehydration test (all P < 0.05). PLR-ΔSV and PLR-ΔPP (PLR induced changes in stroke fluid) were both positively correlated with ΔSV (the rate of change of stroke fluid induced by fluid infusion test) (both P < 0.05). PLR combined with PiCCO may predict the fluid responsiveness in adult patients with septic shock by monitoring PLR-ΔSV associated with PLR-ΔPP, thereby contribute effectively to the guidance of fluid resuscitation.

Concomitant vasopressin and hydrocortisone therapy on short-term hemodynamic effects and vasopressor requirements in refractory septic shock

PurposeThe objective of this study was to evaluate the short-term hemodynamic effects as well as vasopressor requirements with concomitant vasopressin (AVP) and hydrocortisone (HCT) compared to either agent alone in refractory septic shock. Materials and methodsThis was a retrospective, cohort study conducted in adult septic shock patients. Patients received continuous infusion AVP at 0.04units/min and/or HCT 200–300mg intravenous daily in divided doses for refractory septic shock. Refractory septic shock was defined as systolic or mean blood pressure (MAP) of <90mmHg or <70mmHg, respectively, despite fluid resuscitation and requiring norepinephrine. ResultsA total of 300 patients were evaluated. The rate of achieving a “response” (norepinephrine dose reduction by ≥50% without any decrease in MAP) at 4h from baseline was significantly higher in patients receiving concomitant AVP/HCT (88.5%) compared to HCT alone (62.3%) or AVP alone (72.9%) (p=0.0005). The AVP/HCT group had higher “response” rates over the HCT and AVP monotherapy groups at 12 (p=0.052) and 24h (p=0.036). Multivariate regression showed combination therapy to be independently associated with response at 4h. ConclusionsConcomitant AVP and HCT was associated with an immediate, additive catecholamine-sparing effect over either agent alone in patients with refractory septic shock.