Adult Septic Shock Patients Research Articles

Troponin Testing for Assessing Sepsis-Induced Myocardial Dysfunction in Patients with Septic Shock.

(1) Background: Myocardial dysfunction in patients with sepsis is not an uncommon phenomenon, yet reported results are conflicting and there is no objective definition. Measurement of troponin may reflect the state of the heart and may correlate with echocardiographically derived data. This study aimed to evaluate the role of admission and peak troponin-I testing for the identification of sepsis-induced myocardial dysfunction (SIMD) by transthoracic echocardiography (TTE). (2) Methods: This was a retrospective cohort study using a prospective registry of septic shock at an Emergency Department from January 2011 and April 2017. All 1,776 consecutive adult septic shock patients treated with protocol-driven resuscitation bundle therapy and tested troponin-I were enrolled. SIMD was defined as left ventricular (LV) systolic/diastolic dysfunction, right ventricular (RV) diastolic dysfunction, or global/regional wall motion abnormalities (WMA). (3) Results: Of 660 (38.4%) septic shock patients with an elevated hs-TnI (≥0.04 ng/mL) at admission, 397 patients underwent TTE and 258 cases (65%) showed SIMD (LV systolic dysfunction (n = 163, 63.2%), LV diastolic dysfunction (n = 104, 40.3%), RV dysfunction (n = 97, 37.6%), and WMA (n = 186, 72.1%)). In multivariate analysis, peak hs-TnI (odds ratio 1.03, 95% confidence interval 1.01–1.06, p = 0.008) and ST-T wave changes in the electrocardiogram (odds ratio 1.82, 95% confidence interval 1.04–2.39, p = 0.013) were associated with SIMD, in contrast to hs-TnI level at admission. The area under the curve of peak hs-TnI was 0.668. When the peak hs-TnI cutoff value was 0.634 ng/mL, the sensitivity and specificity for SIMD were 58.6% and 59.1%, respectively. 4) Conclusions: About two-thirds of patients with an elevated hs-TnI level have various cardiac dysfunctions in terms of TTE. Rather than the initial level, the peak hs-TnI and ST-T change may be considered as a risk factor of SIMD.

Value of Central Venous to Arterial CO2 Difference after Early Goal-directed Therapy in Septic Shock Patients.

ABSTRACTBackground and aimsVenous to arterial difference of carbon dioxide (Pv–aCO2) tracks tissue blood flow. We aimed to evaluate if Pv–aCO2 measured from a superior central vein sample is a prognostic index (ICU length of stay, SOFA score, 28th mortality rate) just after early goal-directed therapy (EGDT)comparing its ICU admission values between patients with normal and abnormal (>6 mm Hg) Pv–aCO2. As secondary objectives, we evaluated the relationship of Pv–aCO2 with other variables of perfusion during the 24 hours that followed EGDT.Materials and methodsProspective observational study conducted in an academic ICU adult septic shock patients after a 6-hour complete EGTD. Hemodynamic measurements, arterial/central venous blood gases, and arterial lactate were obtained on ICU admission and after 6, 18 and 24 hours.ResultsSixty patients were included. Admission Pv–aCO2 values showed no prognostic value. Admission Pv–aCO2 (ROC curve 0.527 [CI 95% 0.394 to 0.658]) values showed low specificity and sensitivity as predictors of mortality. There was a difference observed in the mean Pv–aCO2 between nonsurvivors (NS) and survivors (S) after 6 hours. Central venous oxygen saturation (ScvO2) and Pv–aCO2 showed significant correlation (R2 = –0.41, P < 0.0001). Patients with normal ScvO2 (>70%) and abnormal Pv–aCO2 (>6 mm Hg) showed higher SOFA scores. Normal Pv–aCO2 group cleared their lactate levels in comparison to the abnormal Pv–aCO2 group.ConclusionIn septic shock, admission Pv–aCO2 after EGDT is not related to worse outcomes. An abnormal Pv–aCO2 along with a normal ScvO2 is related to organ dysfunction.How to cite this articleAraujo DT, Felice VB, Meregalli AF, Friedman G. Value of Central Venous to Arterial CO2 Difference after Early Goal-directed Therapy in Septic Shock Patients. Indian J Crit Care Med 2019;23(10):449–453.

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.

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.

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.

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

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.

Impact of Dobutamine in Patients With Septic Shock: A Meta-Regression Analysis.

Septic shock frequently requires vasopressor agents. Conflicting evidence exists for use of inotropes in patients with septic shock. Data from English studies on human adult septic shock patients were collected. A total of 83 studies were reviewed, while 11 studies with 21 data sets including 239 patients were pooled for meta-regression analysis. For VO2, pooled difference in means (PDM) was 0.274. For cardiac index (CI), PDM was 0.783. For delivery of oxygen, PDM was -0.890. For heart rate, PDM was -0.714. For left ventricle stroke work index, PDM was 0.375. For mean arterial pressure, PDM was -0.204. For mean pulmonary artery pressure, PDM was 0.085. For O2 extraction, PDM was 0.647. For PaCO2, PDM was -0.053. For PaO2, PDM was 0.282. For pulmonary artery occlusive pressure, PDM was 0.270. For pulmonary capillary wedge pressure, PDM was 0.300. For PVO2, PDM was -0.492. For right atrial pressure, PDM was 0.246. For SaO2, PDM was 0.604. For stroke volume index, PDM was 0.446. For SvO2, PDM was -0.816. For systemic vascular resistance, PDM was -0.600. For systemic vascular resistance index, PDM was 0.319. Meta-regression analysis was performed for VO2, DO2, CI, and O2 extraction. Age was found to be significant confounding factor for CI, DO2, and O2 extraction. APACHE score was not found to be a significant confounding factor for any of the parameters. Dobutamine seems to have a positive effect on cardiovascular parameters in patients with septic shock. Prospective studies with larger samples are required to further validate this observation.

The Effects of Atorvastatin on Inflammatory Responses and Mortality in Septic Shock: A Single-center, Randomized Controlled Trial.

Aim of the Study:Pleiotropic effect of statins can modulate inflammation in septic shock. We tested the hypothesis whether statins can reduce mortality in septic shock.Patients and Methods:We conducted a randomized double-blinded trial with treatment (40 mg dose of atorvastatin for 7 days) and control (placebo) arm in adult septic shock patients admitted to the Intensive Care Unit. Primary (28-day mortality) and secondary (vasopressor-, ventilation-, and renal replacement therapy-free days) outcomes, with lipid profile and adverse effects, were documented. Inflammatory biomarkers (interleukin [IL]-1, IL-6, tumor-necrosis-factor [TNF]-α, interferon [IFN], and C-reactive protein [CRP]), were also measured before (day 1 [D1]) and after start of trial drug (D4 and D7).Results:Seventy-three septic shock patients with 36 and 37 included in the atorvastatin and placebo group, respectively. Both groups were equally matched. Twenty-eight-day mortality, event-free days, lipid profile, and adverse effects were also not significantly different between groups. Reduced levels of IL-1, IL-6, TNF-α, IFN, and CRP were observed in the atorvastatin group. Also observed were significant day-wise changes in inflammatory biomarkers.Conclusions:Atorvastatin-induced changes in inflammatory biomarkers did not confer mortality benefit in septic shock (ClinicalTrials.govNCT02681653).

An observational study on the relationship between plasma vitamin C, blood glucose, oxidative stress, endothelial dysfunction and outcome in patients with septic shock

Background. Septic shock is associated with endothelial dysfunction and oxidative stress, against which vitamin C plays a protective role, possibly influencing clinical outcome. Hyperglycaemia may lower vitamin C. Objective. To study plasma vitamin C, oxidative stress, hyperglycaemia, endothelial dysfunction and outcome in septic shock. Methods. In a prospective, observational study of 25 adult septic shock patients, serial blood samples were analysed for vitamin C, thiobarbituric acid-reactive substances (TBARS) (a biomarker of oxidative stress), and soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (markers of endothelial dysfunction). Blood glucose, Sequential Organ Failure Assessment (SOFA) scores and fluid requirements were monitored. Results. Plasma vitamin C was low, while plasma TBARS were high throughout the 7-day study period. Endothelial dysfunction markers (sVCAM-1 and E-selectin) were high at the baseline. VCAM-1 decreased significantly on day 1 and normalised on day 7. E-selectin was unchanged on day 1 compared with baseline, but increased significantly on day 7. Oxidative stress and endothelial dysfunction were associated with increased SOFA score. Increased oxidative stress was associated with increased requirements for intravenous fluids and prolonged duration of vasoconstrictor support. Nine patients died in hospital. At baseline, levels of TBARS were significantly higher in non-survivors than in the survivors of septic shock. Conclusion. In septic shock, clinically relevant oxidative stress was associated with endothelial dysfunction, low vitamin C and high glucoseto- vitamin-C ratios. Markers of oxidative stress and endothelial damage were increased and correlated with resuscitation fluid requirements, vasoconstrictor use, organ failure and mortality.

Control groups in recent septic shock trials: a systematic review.

The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n=287 patients and 71% of eligible patients were randomized). Of the 24 studies, 14 (58%) presented baseline data on vasopressors and 58% the proportion of patients with elevated lactate values. Five studies (21%) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8%) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.