Adult Septic Shock Patients Research Articles

The Effect of Early Goal-Directed Therapy on Outcome in Adult Severe Sepsis and Septic Shock Patients: A Meta-Analysis of Randomized Clinical Trials.

Whether early goal-directed therapy (EGDT) improves outcome in severe sepsis and septic shock remains unclear. We performed a meta-analysis of existing clinical trials to examine whether EGDT improved outcome in the resuscitation of adult sepsis patients compared with control care. We searched for eligible studies using MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials, and Web of Science databases. Studies were eligible if they compared the effects of EGDT versus control care on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Data including mortality, sample size of the patients with severe sepsis and septic shock, and resuscitation end points were extracted. Data were analyzed using methods recommended by the Cochrane Collaboration Review Manager 4.2 software. Random errors were evaluated by trial sequential analysis (TSA). Nine studies compared EGDT with control care, and 5202 severe sepsis and septic shock patients were included. A nonsignificant trend toward reduction in the longest all-cause mortality was observed in the EGDT group compared with control care (relative risk, 0.89; 99% confidence interval, 0.74-1.07; P = 0.10). However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients (relative risk, 0.72; 99% confidence interval, 0.57-0.90; P = 0.0002). TSA indicated lack of firm evidence for a beneficial effect. In this meta-analysis, a nonsignificant trend toward reduction in the longest all-cause mortality in patients resuscitated with EGDT was noted. However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients. TSA indicated a lack of firm evidence for the results. More powered, randomized controlled trials are needed to determine the effects.

Cytochrome C in Patients with Septic Shock.

Cytochrome c is an essential component of the electron transport chain, and circulating cytochrome c might be an indicator of mitochondrial injury. The objective of this study was to determine whether cytochrome c levels are elevated in septic patients, whether there is an association between cytochrome c levels and lactate/inflammatory markers, and whether elevated levels of cytochrome c are associated with poor outcomes. This was a single-center, prospective, observational, pilot study within a randomized, placebo-controlled trial. We enrolled adult patients in septic shock and with an elevated lactate (>3 mmol/L). Blood was collected at enrollment and at 12 and 24 h thereafter. Cytochrome c was measured in plasma using an electrochemiluminescence immunoassay. We included 77 patients. Plasma cytochrome c levels were significantly higher in septic patients than in healthy controls (0.70 ng/mL [quartiles: 0.06, 1.99] vs. 0.19 ng/mL [quartiles: 0.03, 1.32], P = 0.008). Cytochrome c levels at enrollment were positively correlated with lactate levels (r(s) = 0.40, P < 0.001) but not with inflammatory markers. Patients who died before hospital discharge had significantly higher cytochrome c levels than survivors (0.99 ng/mL [quartiles: 0.36, 4.09] vs. 0.58 ng/mL [quartiles: 0.03, 1.64], P = 0.01). When analyzed over time, the difference between survivors and nonsurvivors remained significant (P < 0.001). Cytochrome c levels are higher in septic patients than in controls. In unadjusted analysis, septic nonsurvivors had higher cytochrome c levels than survivors.

Comparing transesophageal Doppler corrected systolic flow time versus central venous pressure as a guide for fluid resuscitation in septic shock

BackgroundAortic corrected flow time (FTc) is easily measured by Doppler techniques. Recent data using transesophageal Doppler suggest that it may predict fluid responsiveness in critical care. This use of FTc has not previously been evaluated in septic shock, and only one preliminary study has incorporated transcutaneously measured FTc, denoting its importance in prediction of fluid responsiveness in septic patient. Furthermore, no comparison has been made between transesophageal FTc and central venous pressure (CVP).ObjectiveThe aim of our study was to compare the impact of using FTc versus CVP as a guide for fluid resuscitation in septic shock on stroke volume denoting cardiac responsiveness for fluid administration.MethodsThis was a prospective study of 46 consecutive adult septic shock patients (in sinus rhythm). 44 patients were mechanically ventilated, treated with intravenous fluid challenge (500 mL over 15 min), guided with CVP in control group and guided by FTC in Doppler group assessment incorporating transesophageal aortic Doppler (CardioQ®) measurements in a surgical tertiary intensive care unit. Stroke volume (SV), mechanical ventilation days, length of stay and mortality of both groups were recorded.ResultsFourty one patients demonstrated an increase in stroke volume (SV) by more than 10% (fluid responders) while five patients were non responders. There were statistically significant increases in SV after 1 h post resuscitation in the Doppler group as the values were 63.87 ± 25.87 & 81.39 ± 35.02 in the control group and the Doppler group respectively (p value = 0.034). There were statistically significant differences in FTc values after 1 h [397.00 (390.00–404.00) & 362.00 (351.00–377.00)] between non-responders and responders respectively (p value was 0.003) and after 6 h [377.00 (376.00–378.00) & 330.00 (314.00–353.00)] between non-responders and responders respectively (p value was 0.007).ConclusionTransesophageal aortic Doppler is a simple, non-invasive tool of guiding fluid therapy in patients with severe sepsis and septic shock. FTC change was a better predictor of fluid responsiveness than CVP in septic shock. There was higher significant difference in SV after resuscitation when using FTC as guidance.

The effect of atrial natriuretic peptide infusion on intestinal injury in septic shock.

Background and Aims:The aim of this study is to assess the effect of atrial natriuretic peptide (ANP) on intestinal ischemia-reperfusion injury in septic shock.Material and Methods:A prospective randomized controlled, observer-blinded study was carried out in surgical Intensive Care Unit (ICU), University Hospital. Forty adult patients in septic shock were randomly divided into two groups, control group (Group C) received normal saline and ANP group (Group A) patients received ANP in the form of 1.5 mg vial added to 250 ml solvent in plastic bag (1 ml = 6 micg) given at 2 mcg/kg intravenous bolus over 1 min followed by 0.01 mcg/kg/min for 24 h. The primary outcome measurements were blood marker of intestinal hypoperfusion in form of intestinal fatty acid binding protein (I-FABP), malondialdehyde (MDA), myloperoxidase enzyme activity (MPO), protein carbonyl (PC), and glutathione peroxidase activity (GPA) measured before start of ANP infusion, 6 h, 12 h, and 24 h after start of infusion. The secondary outcome measurements were the duration of noradrenaline infusion, duration of ICU stay, hospital mortality rate, and complications related to ANP.Results:In comparison with Group C, Group A showed a significant decrease (P < 0.05) in serum level of MPO, MDA, PC, and I-FABP, with a significant increase (P < 0.05) in serum level of GPA, 6 h, 12 h, and 24 h after the start of ANP infusion. There was significant decrease (P < 0.05) in mean duration of noradrenaline infusion, the length of ICU stay and mortality rate in Group A in comparison with Group C. In Group A, seven patients had mean arterial blood pressure < 65 mmHg but respond to volume resuscitation, three patients serum sodium was 125–130 mmol/L.Conclusion:In cases of septic shock, concomitant administration of ANP with noradrenaline may have a protective effect against intestinal injury through a decrease in the level of intestinal hypoperfusion owing to its anti-inflammatory and antioxidant effect.

Does vasopressin improve the mortality of septic shock patients treated with high-dose NA.

Aim of Study:In Surviving Sepsis Campaign Guidelines 2012, noradrenalin (NA) is recommended as a first choice vasopressor. Although vasopressin (VP) is recommended for the treatment of NA-resistant septic shock, the optimal parameters for its administration remain unclear.Materials and Methods:We conducted a retrospective study to evaluate the clinical outcomes of the administration of VP to adult septic shock patients who were undergoing high-dose NA (≥0.25 μg/kg/min) therapy in our Intensive Care Unit between January 2010 and December 2013. We defined high-dose NA as a dose of >0.25 μg/kg/min, based on the definition of low-dose NA as a dose of 5–14 μg/min because the average body weight of the patients in this study was 53.0 kg.Results:Among 29 patients who required the administration of high-dose NA, 18 patients received VP. Although the patient background physiological conditions and NA dose did not differ between the two groups, the survival rate of the VP-treated patients was significantly lower (33%) than that of the patients who were managed with a high-dose of NA-alone (82%) (P = 0.014). The lactate clearance did not change after the administration of VP, whereas it improved when in NA treatment alone.Conclusion:The results suggest that the administration of VP did not improve the mortality among septic shock patients when administered in addition to high-dose NA.

The Effect of Early Goal-Directed Therapy On Outcome in Adult Severe Sepsis And Septic Shock Patients: A Meta-Analysis of Randomised Clinical Trials

The Effect of Early Goal-Directed Therapy On Outcome in Adult Severe Sepsis And Septic Shock Patients: A Meta-Analysis of Randomised Clinical Trials

Sepsis-associated pulmonary complications in emergency department patients monitored with serial lactate: An observational cohort study

PurposePatients with severe sepsis and septic shock are at high risk for development of pulmonary complications, including acute respiratory distress syndrome (ARDS). Serial lactate monitoring is a useful tool to gauge global tissue hypoxia in emergency department (ED) patients with sepsis. We hypothesized that patients undergoing serial lactate monitoring (SL) would demonstrate a decreased incidence of pulmonary complications. MethodsThis is a retrospective observational cohort study of adult severe sepsis and septic shock patients with elevated lactate presenting to a large academic ED. A total of 243 patients were assigned to SL (n = 132) or no serial lactate monitoring (NL; n = 111). The primary outcome was a composite of pulmonary complications: (1) ARDS development and (2) respiratory failure. ResultsTwenty-eight patients (21%) in the SL group and 37 patients (33%) in the NL group developed the primary outcome (P = .03). Multivariate analysis demonstrated an association between the NL group and development of pulmonary complications (adjusted odds ratio [aOR], 2.1; confidence interval [CI], 1.15-3.78). Emergency department mechanical ventilation was independently associated with development of ARDS (aOR, 3.5; 1.8-7.0). In the a priori subgroup of patients mechanically ventilated in the ED (n = 97), those who developed ARDS received higher tidal volumes compared to patients who did not develop ARDS (8.7 mL/kg predicted body weight [interquartile range, 7.6-9.5] vs 7.6 [interquartile range, 6.8-9.0]; P < .01). ConclusionsSerial lactate monitoring is associated with a decrease in major pulmonary complications in severe sepsis and septic shock. Acute respiratory distress syndrome incidence is also influenced by ED-based mechanical ventilation. These results provide 2 potentially modifiable variables to be targeted in future studies to prevent pulmonary complications in this patient subset.

Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database.

The Surviving Sepsis Campaign guidelines recommend obtaining a serum lactate measurement within 6 hours of presentation for all patients with suspected severe sepsis or septic shock. A lactate greater than 4 mmol/L qualifies for administration of early quantitative resuscitation therapy. We evaluated lactate elevation (with special attention to values > 4 mmol/L) and presence or absence of hypotension as a marker of clinical outcome. The Surviving Sepsis Campaign developed a database to assess the overall effect of the sepsis bundles as a performance improvement tool for clinical practice and patient outcome. This analysis focuses on one element of the Surviving Sepsis Campaign's resuscitation bundle, measuring serum lactate in adult severe sepsis or septic shock patients and its interaction with hypotension. This analysis was conducted on data submitted from January 2005 through March 2010. Data from 28,150 subjects at 218 sites were analyzed. None. Unadjusted analysis of the 28,150 observations from the Surviving Sepsis Campaign database demonstrated a significant mortality increase with the presence of hypotension in conjunction with serum lactate elevation greater than 2 mmol/L. On multivariable analysis, only lactate values greater than 4 mmol/L, in conjunction with hypotension, significantly increased mortality when compared with the referent group of lactate values less than 2 mmol/L and not hypotensive. Mortality was 44.5% in patients with combined lactate greater than 4 mmol/L and hypotension when compared with 29% mortality in patients not meeting either criteria. Serum lactate was commonly measured within 6 hours of presentation in the management of severe sepsis or septic shock in this subset analysis of the Surviving Sepsis Campaign database in accordance with the Surviving Sepsis Campaign guidelines. Our results demonstrate that elevated lactate levels are highly associated with in-hospital mortality. However, only patients who presented with lactate values greater than 4 mmol/L, with and without hypotension, are significantly associated with in-hospital mortality and is associated with a significantly higher risk than intermediate levels (2-3 and 3-4 mmol/L). This supports the use of the cutoff of greater than 4 mmol/L as a qualifier for future clinical trials in severe sepsis or septic shock in patient populations who use quantitative resuscitation and the Surviving Sepsis Campaign bundles as standard of care.

Early versus delayed administration of norepinephrine in patients with septic shock.

IntroductionThis study investigated the incidence of delayed norepinephrine administration following the onset of septic shock and its effect on hospital mortality.MethodsWe conducted a retrospective cohort study using data from 213 adult septic shock patients treated at two general surgical intensive care units of a tertiary care hospital over a two year period. The primary outcome was 28-day mortality.ResultsThe 28-day mortality was 37.6% overall. Among the 213 patients, a strong relationship between delayed initial norepinephrine administration and 28-day mortality was noted. The average time to initial norepinephrine administration was 3.1 ± 2.5 hours. Every 1-hour delay in norepinephrine initiation during the first 6 hours after septic shock onset was associated with a 5.3% increase in mortality. Twenty-eight day mortality rates were significantly higher when norepinephrine administration was started more than or equal to 2 hours after septic shock onset (Late-NE) compared to less than 2 hours (Early-NE). Mean arterial pressures at 1, 2, 4, and 6 hours after septic shock onset were significantly higher and serum lactate levels at 2, 4, 6, and 8 hours were significantly lower in the Early-NE than the Late-NE group. The duration of hypotension and norepinephrine administration was significantly shorter and the quantity of norepinephrine administered in a 24-hour period was significantly less for the Early-NE group compared to the Late-NE group. The time to initial antimicrobial treatment was not significantly different between the Early-NE and Late-NE groups.ConclusionOur results show that early administration of norepinephrine in septic shock patients is associated with an increased survival rate.

Septic Shock and Adequacy of Early Empiric Antibiotics in the Emergency Department

BackgroundAntibiotic resistance is an increasing concern for Emergency Physicians. ObjectivesTo examine whether empiric antibiotic therapy achieved appropriate antimicrobial coverage in emergency department (ED) septic shock patients and evaluate reasons for inadequate coverage. MethodsRetrospective review was performed of all adult septic shock patients presenting to the ED of a tertiary care center from December 2007 to September 2008. Inclusion criteria were: 1) Suspected or confirmed infection; 2) ≥ 2 Systemic Inflammatory Response Syndrome criteria; 3) Treatment with one antimicrobial agent; 4) Hypotension requiring vasopressors. Patients were dichotomized by presentation from a community or health care setting. ResultsEighty-five patients with septic shock were identified. The average age was 68 ± 15.8 years. Forty-seven (55.3%) patients presented from a health care setting. Pneumonia was the predominant clinically suspected infection (n = 38, 45%), followed by urinary tract (n = 16, 19%), intra-abdominal (n = 13, 15%), and other infections (n = 18, 21%). Thirty-nine patients (46%) had an organism identified by positive culture, of which initial empiric antibiotic therapy administered in the ED adequately covered the infectious organism in 35 (90%). The 4 patients who received inadequate therapy all had urinary tract infections (UTI) and were from a health care setting. ConclusionIn this population of ED patients with septic shock, empiric antibiotic coverage was inadequate in a small group of uroseptic patients with recent health care exposure. Current guidelines for UTI treatment do not consider health care setting exposure. A larger, prospective study is needed to further define this risk category and determine optimal empiric antibiotic therapy for patients.

ABSTRACT 685

Background and aims: Septic shock remains a leading cause of morbidity and mortality. Whilst mortality has reduced with improvements in critical care management, there is evidence from adult septic shock patients that early diagnosis and aggressive treatment (‘goal directed therapy’) improves outcome. Best practice guidelines for adult and paediatric septic shock include early intervention with fluid resuscitation, ventilator and circulatory support and correction of metabolic disturbances3. Aims: We set out to determine the level of compliance to current guidelines in children admitted to Addenbrooke’s Hospital PICU with a clinical diagnosis of septic shock, and to investigate variables that were related to clinical outcome. Methods: A retrospective audit was undertaken from May 2011 to September 2013 to identify children admitted with a clinical diagnosis of septic shock using criteria defined by the surviving sepsis campaign. The need for ethics approval was waived by the institution, and instead the study was registered as a clinical audit. Results: We found that there is generally good compliance to the guidelines. Bivariate correlation analysis demonstrated that PIM2 severity scores calculated on retrieval had an association with the length of PICU stay (p<0.05), which we took as our primary outcome. We also found that the worst lactate and worst bicarbonate values on retrieval had some correlation with our primary outcome (p=0.053 and p=0.061 respectively) but were not statistically significant. Conclusions: In conclusion, compliance to current guidelines is good and there is potential for retrieval lactate and bicarbonate to be used as markers in the management of septic shock.

Changes in Plasma Kynurenic Acid Concentration in Septic Shock Patients Undergoing Continuous Veno-Venous Haemofiltration

Kynurenic acid (KYNA) is one of the end products of tryptophan metabolism. The aim of this study was to analyse plasma KYNA concentration in septic shock patients (SSP) with acute kidney injury (AKI) undergoing continuous veno-venous haemofiltration (CVVH). Changes in KYNA content were compared to alterations in the levels of procalcitonin (PCT), C-reactive protein and lactate. Adult SSP with AKI were examined. Measurements were conducted at seven time points: before beginning CVVH and at 6, 12, 24, 48, 72 and 96 h after the beginning of CVVH. Based on clinical outcomes, the data were analysed separately for survivors and non-survivors. Twenty-seven patients were studied. CVVH was associated with reduced plasma KYNA concentration only in survivors. Plasma KYNA concentration correlated with the levels of lactate and PCT only in survivors. (1) CVVH reduced plasma KYNA concentration only in survivors; (2) lack of this reduction may predict fatal outcomes in SSP.

Extracorporeal membrane oxygenation resuscitation in adult patients with refractory septic shock

Experience with extracorporeal membrane oxygenation for adult patients with refractory septic shock remains limited. We aimed to study the clinical features and outcomes of this patient group in an extracorporeal membrane oxygenation referral center in Taiwan. From January 2005 to December 2010, all adult patients in refractory septic shock and requiring venoarterial extracorporeal membrane oxygenation for circulatory support were included in the present study. The variables analyzed included patient demographics; comorbidities; smoking status; hemodynamic, ventilatory, and laboratory parameters just before extracorporeal membrane oxygenation support; clinical course; extracorporeal membrane oxygenation details; complications; microbiology results; and outcomes. The primary endpoint was survival to hospital discharge. A total of 52 patients, 39 men and 13 women, were included during a 6-year period. Their median age and body mass index was 56.8 years and 24.1 kg/m(2), respectively. Of the 52 patients, 39 (75%) had failure of at least 3 organ systems and 21 (40%) had developed cardiac arrest and received cardiopulmonary resuscitation at extracorporeal membrane oxygenation implantation. Of these 52 patients, 8 (15%) survived to hospital discharge. The nonsurvivors were significantly older than the survivors (59.3 vs 43.8 years; P=.009), and all 20 patients (38%) aged 60 years or older died. In our single-center experience with extracorporeal membrane oxygenation for adults with refractory septic shock, the outcomes of these patients remain unsatisfactory. From our findings, we suggest that if extracorporeal membrane oxygenation were to be used in this patient population, age 60 years or older might be a contraindication. Also, central extracorporeal membrane oxygenation could possibly be beneficial according to the favorable pediatric experience in published studies.

Human protein C concentrate to restore physiological values in adult septic shock patients: effects on microcirculation

We investigated whether human protein C (PC) concentrate to restore physiological values in adult septic shock patients can influence microcirculatory blood flow.

133 Sepsis and Empiric Antibiotics: Should We Consider “Health Care Associated” Urinary Tract Infections?

The objective of this study was to examine whether empiric antibiotic choices achieved adequate antimicrobial coverage in septic shock patients based on ultimate culture data. A retrospective medical record review of adult septic shock patients who presented to the emergency department (ED) of a tertiary care, academic medical center from December 2007- September 2008 was performed. Inclusion criteria consisted of: 1) Suspected or confirmed infection 2) > 2 SIRS criteria 3) Treatment with at least 1 antimicrobial agent in the ED 4) Hypotensive requiring vasopressor use. Patients were excluded if they were immunocompromised or had known active cancer. Data collected included demographics, initial vital signs and laboratory data, culture results, as well as empiric antimicrobial therapies administered in the ED. Patients were classified as presenting from either a community or health care setting. Initial empiric therapy was classified as adequate if at least 1 of the agents administered displayed in vitro activity against a culture-identified pathogen. Simple descriptive statistics including means and standard deviations (for continuous data) and frequency with percentages (for categorical data) were used to describe the study population where appropriate. A total of 112 patients were identified during the study period. Of these, 85 patients met all inclusion criteria and none of the exclusion criteria and were included in the analysis. The average age of patients was 68±15.8, and 44 (52%) were male. Thirty-eight (45%) patients in the study group presented from a health care setting. Pneumonia was the predominant infection type (38/85; 45%), followed by urinary tract infection (16/85; 19%), other (skin, soft tissue, bone, meningitis, etc; 18/85; 21%), and intra-abdominal infection (13/85; 15%). Thirty-nine patients (46%) ultimately had a positive culture. Patients presenting with pneumonia as their suspected infection source had fewer positive cultures (13/38, 34%) in comparison with UTI (9/16, 56%), intra-abdominal (8/13, 62%), or other infection (9/18, 50%) patients. Of the 39 patients, initial empiric antibiotic therapy administered in the ED adequately covered the infecting organism in 90% of patients (35/39). All patients presenting with pneumonia with positive cultures received adequate antibiotic therapy (13/13, 100%). Four (4/39; 10%) patients received empiric antimicrobial therapy in the ED which was inadequate to treat the infecting organism; in this group, all (4/4; 100%) of these patients presented with UTI, and all were classified as being from a health care setting. All resistant strains were extended spectrum beta-lactam producers (ESBLs). In this population of ED patients with septic shock, empiric antibiotic therapy was adequate for most sources of infection, such as pneumonia or intra-abdominal infection. However, inadequate empiric antimicrobial therapy occurred in a small group of uroseptic patients who were all categorized as health care exposed. Current guidelines for urinary tract infection treatment do not take into account health care setting exposure or the possibility of ESBLs. A larger, prospective study is needed to further define this risk category and determine optimal empiric antibiotics for patients with urospesis and health care setting exposure.

Low‐dose hydrocortisone treatment for patients with septic shock: A pilot study comparing 3 days with 7 days

Although there is controversy regarding the benefit of low-dose corticosteroid therapy in patients with septic shock, the Surviving Sepsis Campaign has advocated that low-dose intravenous hydrocortisone be used to treat adult septic shock patients. This study investigated the effect of the duration of a stress dose of hydrocortisone on survival of septic shock patients with relative adrenal insufficiency. One hundred and thirty consecutive patients who met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock were included in the study. An additional inclusion criterion was vasopressor support after fluid resuscitation. The primary end-point was 28-day mortality, and the secondary end-points were shock reversal and mortality in the intensive care unit and hospital. All eligible patients were prospectively randomized to receive hydrocortisone treatment for 3 or 7days. Hydrocortisone treatment was started at a dose of 50mg every 6h. Baseline data at recruitment did not differ between the two groups. After 28days, mortality did not differ between the 3- and 7-day treatment groups (33.8% vs 36.9%, P=0.629). Mortality rates in the intensive care unit and hospital did not differ significantly between the two groups. The median time to withdrawal of vasopressor therapy was 5.0days in the 3-day treatment group and 6.4days in the 7-day treatment group (P=0.102). This pilot study showed that in patients with septic shock and relative adrenal insufficiency, 28-day mortality did not differ between those treated with low-dose hydrocortisone for 3 or 7days.

Thenar Oxygen Saturation and Invasive Oxygen Delivery Measurements in Critically Ill Patients in Early Septic Shock

This prospective study was aimed to test the hypothesis that tissue hemoglobin oxygen saturation (StO₂) measured noninvasively using near-infrared spectroscopy is a reliable indicator of global oxygen delivery (DO₂) measured invasively using a pulmonary artery catheter (PAC) in patients with septic shock. The study setting was a 26-bed medical-surgical intensive care unit at a university hospital. Subjects were adult patients in septic shock who required PAC hemodynamic monitoring for resuscitation. Interventions included transient ischemic challenge on the forearm. After blood pressure normalization, hemodynamic and oximetric PAC variables and, simultaneously, steady-state StO₂ and its changes from ischemic challenge (deoxygenation and reoxygenation rates) were measured. Fifteen patients were studied. All the patients had a mean arterial pressure above 65 mmHg. The DO₂ index (iDO₂) range in the studied population was 215 to 674 mL O₂/min per m. The mean mixed venous oxygen saturation value was 61% ± 10%, mean cardiac index was 3.4 ± 0.9 L/min per m, and blood lactate level was 4.6 ± 2.7 mmol/L. Steady-state StO₂ significantly correlated with iDO₂, arterial and venous O₂ content, and O₂ extraction ratio. A StO₂ cutoff value of 75% predicted iDO₂ below 450, with a sensitivity of 0.9 and a specificity of 0.9. In patients in septic shock and normalized MAP, low StO₂ reflects extremely low iDO₂. Steady-state StO₂ does not correlate with moderately low iDO₂, indicating poor sensitivity of StO₂ to rule out hypoperfusion.

81: Increased Outcome Effectiveness of the Surviving Sepsis Campaign Severe Sepsis Resuscitation Bundle With the Addition of Lactate Clearance as a Bundle Element: A Multi-National Evaluation for the ATLAS Investigators

81: Increased Outcome Effectiveness of the Surviving Sepsis Campaign Severe Sepsis Resuscitation Bundle With the Addition of Lactate Clearance as a Bundle Element: A Multi-National Evaluation for the ATLAS Investigators

12: Implementation of Early Goal-Directed Therapy and the Surviving Sepsis Campaign Resuscitation Bundle In Asia Is Associated With Decreased Mortality: Analysis of a Team Versus Non-Team Model of Care for the ATLAS Investigators

Evidence from America and Europe suggests that successful implementation of the Surving Sepsis Campaign severe sepsis resuscitation bundle including early goal-directed therapy is associated with significant outcome benefit. This study examines the impact of implementing such bundle in multiple Asian countries having team versus non-team models of care. The study is a multi-national, prospective interventional cohort of adult severe sepsis or septic shock patients presenting to the emergency department (ED) of 8 hospitals in Korea, Singapore, India, Taiwan, and China. Implementation of the bundle was divided into six quartiles from July 1, 2008 to December 31, 2009: Baseline, Education, and four Quality Improvement quartiles. Components of the bundle included: 1) lactate measured; 2) blood cultures prior to antibiotics; 3) fluid bolus given; 4) antibiotics by 3 hours; 5) achieve CVP > 8 mm Hg by 6 hours; and 6) achieve ScvO2 > 70% by 6 hours. Three hospitals with team model were championed by intensive care medicine, with initiation of the bundle in the ED and completion in the ICU setting by a focused multi-disciplinary team. Five hospitals with non-team model were championed by emergency medicine, with completion of the bundle in the ED as part of standard care. Five-hundred and fifty-seven patients were enrolled with age 61+/-18 yrs, APACHE II 22+/-8, lactate 4.7+/-3.2 mmol/L, 72% septic shock, 50% mechanical ventilation, and 31% Inhospital mortality. ED length of stay was 13+/-32 hours and hospital length of stay 13+/-14 days. Compliance to all items of the bundle was 13, 27, 38, 46, 49, and 55% (p=0.01) over the six quartiles of implementation. Comparing compliance in the first quartile to 6th quartile, hospitals with team increased from 38 to 76%, whereas hospitals with non-team increased from 3 to 29% (p<0.001). Throughout the study period, patients who received the entire bundle had mortality of 25%, compared to 34% mortality in patients who only received some components of the bundle (p=0.03). Baseline compliance to the severe sepsis resuscitation bundle is low in Asia and similar to other published data in Europe and America. Through education and quality improvement efforts, improved compliance and outcome benefit was achieved. A team model was more effective compared to a non-team model of implementation in achieving compliance.

Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients: Results of a three-year follow-up quasi-experimental study*

To describe the effectiveness of the Surviving Sepsis Campaign bundles with regard to both implementation and outcome in patients with septic shock and to determine the contribution of the various elements of the bundles to the outcome. Quasi-experimental study with a historical comparison group. The three medical-surgical intensive care units of an academic tertiary care center. A total of 384 adult patients in septic shock were enrolled after the educational intervention (September 2005-August 2008) and 96 patients in the historical group (June 2004-May 2005). A hospital-wide quality improvement program based on the implementation of the Surviving Sepsis Campaign guidelines performed between June 2005 and August 2005. In-hospital mortality was reduced from 57.3% in the historical group to 37.5% in the intervention group (p = .001). This difference remained significant after controlling for confounding factors (odds ratio, 0.50; 95% confidence interval, 0.28-0.89). The intervention group had also lower length of stay for survivors in the hospital (36.2 +/- 34.8 days vs. 41.0 +/- 26.3 days; p = .043) and in the intensive care units (8.4 +/- 9.8 days vs. 11.0 +/- 9.5 days; p = .004). Improvements in survival were related to the number of bundle interventions completed (p for trend <.001). Compliance with six or more interventions of the 6-hr resuscitation bundle was an independent predictor of survival (adjusted odds ratio, 0.30; 95% confidence interval, 0.17-0.53; p <.001). The only single intervention with impact on mortality was the achievement of ScvO2 > or =70% (adjusted odds ratio, 0.62; 95% confidence interval, 0.38-0.99; p = .048). The implementation of the Surviving Sepsis Campaign guidelines was associated with a significant decrease in mortality. The benefits depend on the number of interventions accomplished within the time limits. The 6-hr resuscitation bundle showed greater compliance and effectiveness than the 24-hr management bundle.