PURPOSE: Owing to the recommendations of the Surviving Sepsis Campaign guidelines, protocol-based resuscitation or goal-directed therapy (GDT) is broadly advocated for the treatment of septic shock. However, the most recently published trials showed no survival benefit from protocol-based resuscitation in septic shock patients. Hence, we aimed to assess the effect of GDT on clinical outcomes in such patients. MATERIALS AND METHODS: We performed a systematic review that included a meta-analysis. We used electronic search engines including PubMed, Embase, and the Cochrane database to find studies comparing protocol-based GDT to common or standard care in patients with septic shock and severe sepsis. RESULTS: A total of 13269 septic shock patients in 24 studies were included [12 randomized controlled trials (RCTs) and 12 observational studies]. The overall mortality odds ratio (OR) [95% confidence interval (CI)] for GDT versus conventional care was 0.746 (0.631-0.883). In RCTs only, the mortality OR (95% CI) for GDT versus conventional care in the meta-analysis was 0.93 (0.75-1.16). The beneficial effect of GDT decreased as more recent studies were added in an alternative, cumulative meta-analysis. No significant publication bias was found. CONCLUSION: The result of this meta-analysis suggests that GDT reduces mortality in patients with severe sepsis or septic shock. However, our cumulative meta-analysis revealed that the reduction of mortality risk was diminished as more recent studies were added.
Humans ; *Observational Studies as Topic ; *Randomized Controlled Trials as Topic ; Resuscitation/*methods ; Shock, Septic/mortality/*therapy

BACKGROUNDPatients with septic shock have a high mortality. This study used the Surviving Sepsis Campaign (SSC) database to compare characteristics, treatments and outcomes of septic shock patients diagnosed in the emergency department (ED) to patients developing septic shock on hospital floors (HF).

METHODSThe studied population included patients admitted to the intensive care unit (ICU) of an urban tertiary care medical center over an 18-month period. Acute physiology and chronic health evaluation (APACHE II) scores, need for mechanical ventilation (MV), performance on four of the SSC resuscitation bundle indicators, ICU length of stay (LOS), hospital LOS and in-hospital mortality were ascertained.

RESULTSSixty-six ED and 27 HF septic shock patients were included in this study. Urinary tract infections (UTI) and pneumonia were the two most common sites of infection in the ED patients. The sources of infection for HF septic shock patients were fairly well distributed across etiologies. The time to achieve superior vena cava oxygen saturation (ScvO(2)) > 70% in HF patients ((10.8 ± 9.1) hours) was longer when compared to the ED patients ((6.6 ± 6.1) hours) (P < 0.05). Hospital mortality for the ED and HF patients were 25.8% and 59.3%, respectively (P < 0.05). Use of MV during the first 24 hours of shock was 44% in the ED patients and 70% in the HF patients (P < 0.05) and was linked to mortality.

CONCLUSIONSWhen compared to HF patients, ED septic shock patients have lower in-hospital mortality, there was less use of MV during the first 24 hours following onset of septic shock and the HF patients required a longer time to achieve target ScvO(2). The need for mechanical ventilation is independently associated with increased mortality.

Adult ; Aged ; Emergency Service, Hospital ; Female ; Hospital Mortality ; Humans ; Intensive Care Units ; Length of Stay ; Male ; Middle Aged ; Oxygen ; blood ; Respiration, Artificial ; Shock, Septic ; mortality ; therapy ; Treatment Outcome

PURPOSE: Recently, several studies for immature granulocyte proportion (IG%) in patients with sepsis have revealed its association with diagnosis and prognosis of patients with sepsis. In this study, we enrolled patients with severe sepsis and septic shock and compared IG% with other biologic markers as a predictor of 28-day mortality. METHODS: This was a retrospective study for patients with severe sepsis and septic shock who were admitted to the emergency department of a tertiary care hospital for four-months. The IG% measured using Sysmex XE-2100 and other inflammatory markers, including C-reactive protein, lactate, and procalcitonin were evaluated and compared for 28-day mortality. RESULTS: A total of 85 patients with septic shock and 45 patients with severe sepsis were enrolled. In the non-survivors group (n=32, 24.6%), APACHE II score (p=0.017), use of continuous renal replacement therapy (CRRT) (p=0.002), and septic shock (p=0.009) were statistically higher compared with thesurvivors group. APACHE II score (Odd ratio [OR] 1.099, p=0.008) and IG% (> or =0.5%) (OR 3.568, p=0.036) predicted the 28-day mortality independently after adjusting SOFA score, septic shock,disseminated intravascular coagulopathy, use of CRRT, and gender. However, IG (> or =0.5%) had low specificity of 33.7% and positive predictive value (PPV) of 30.1% for 28-day mortality. CONCLUSION: IG% could be a useful biologic marker for prediction of 28-day mortality in patients with severe sepsis or septic shock. However, the limitation of low specificity and PPV must be considered in clinical use.
APACHE ; Biomarkers ; C-Reactive Protein ; Diagnosis ; Emergency Service, Hospital ; Granulocytes* ; Humans ; Lactic Acid ; Mortality* ; Prognosis ; Renal Replacement Therapy ; Retrospective Studies ; Sensitivity and Specificity ; Sepsis* ; Shock, Septic* ; Tertiary Healthcare

OBJECTIVE: We evaluated the clinical characteristics and prognoses of patients with septic shock who transferred to the emergency department (ED) in a tertiary referral center. METHODS: This study was performed using a prospective, multi-center registry of septic shock, with the participation of 11 tertiary referral centers in the Korean Shock Society between October 2015 and February 2017. We classified the patients as a transferred group who transferred from other hospitals after meeting the inclusion criteria upon ED arrival and a non-transferred group who presented directly to the ED. Primary outcome was hospital mortality. We conducted multiple logistic regression analysis to assess variables related to in-hospital mortality. RESULTS: A total of 2,098 patients were included, and we assigned 717 patients to the transferred group and 1,381 patients to the non-transferred group. The initial Sequential Organ Failure Assessment score was higher in the transferred group than the non-transferred group (6; interquartile range [IQR], 4–9 vs. 6; IQR, 4–8; P < 0.001). Mechanical ventilator (29% vs. 21%, P < 0.001) and renal replacement therapy (12% vs. 9%, P=0.034) within 24 hours after ED arrival were more frequently applied in the transferred group than the non-transferred group. Overall hospital mortality was 22% and there was no significant difference between transferred and non-transferred groups (23% vs. 22%, P=0.820). Multivariable analysis showed an odds ratio for in-hospital mortality of 1.00 (95% confidence interval, 0.78–1.28; P=0.999) for the transferred group compared with the non-transferred group. CONCLUSION: The transferred group showed higher severity and needed more organ support procedures than the nontransferred group. However, inter-hospital transfer did not affect in-hospital mortality.
Emergencies* ; Emergency Service, Hospital* ; Hospital Mortality ; Humans ; Logistic Models ; Mortality ; Observational Study* ; Odds Ratio ; Prognosis ; Prospective Studies ; Renal Replacement Therapy ; Retrospective Studies* ; Sepsis ; Shock ; Shock, Septic* ; Tertiary Care Centers* ; Ventilators, Mechanical

Although the incidence of bleeding complications during extracorporeal membrane oxygenator (ECMO) support has decreased in various trials, bleeding is still the most fatal complication. We investigated the ideal dosage and efficacy of nafamostat mesilate for use with ECMO in patients with acute cardiac or respiratory failure. We assessed 73 consecutive patients who received ECMO due to acute cardiac or respiratory failure between January 2006 and December 2009. To evaluate the efficacy of nafamostat mesilate, we divided the patients into 2 groups according to the anticoagulants used during ECMO support. All patients of nafamostat mesilate group were male with a mean age of 49.2 yr. Six, 3, 5, and 3 patients were diagnosed with acute myocardial infarction, cardiac arrest, septic shock, and acute respiratory distress syndrome, respectively. The mean dosage of nafamostat mesilate was 0.64 mg/kg/hr, and the mean duration of ECMO was 270.7 hr. The daily volume of transfused packed red blood cells, fresh frozen plasma, and cryoprecipitate and the number of complications related to hemorrhage and thrombosis was lower in the nafamostat mesilate group than in the heparin group. Nafamostat mesilate should be considered as an alternative anticoagulant to heparin to reduce bleeding complications during ECMO.
Acute Disease ; Anticoagulants/*administration & dosage ; Dose-Response Relationship, Drug ; *Extracorporeal Membrane Oxygenation ; Female ; Guanidines/*administration & dosage ; Heart Failure/diagnosis/mortality/therapy ; Heparin/administration & dosage ; Humans ; Male ; Middle Aged ; Myocardial Infarction/diagnosis/mortality/therapy ; Respiratory Distress Syndrome, Adult/diagnosis/mortality/therapy ; Retrospective Studies ; Shock, Septic/diagnosis/mortality/therapy ; Survival Analysis

BACKGROUND: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. METHODS: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. RESULTS: The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. CONCLUSIONS: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.
Acute Kidney Injury ; Cooperative Behavior ; Critical Care ; Diet ; Epidemiology ; Glomerular Filtration Rate* ; Humans ; Inflammation ; Kidney ; Lipocalins* ; Mass Spectrometry ; Mortality ; Neutrophils* ; Plasma ; Prognosis ; Renal Insufficiency, Chronic ; Renal Replacement Therapy ; Sepsis* ; Shock, Septic

Sepsis is a systemic, deleterious host response to infection. The term "severe sepsis" is used when sepsis is complicated by acute organ dysfunction, and "septic shock" as sepsis complicated by either hypotension that is refractory to fluid resuscitation or by hyperlactatemia. The number of cases with severe sepsis exceeds 750,000 per year in the United States and the mortality is now closer to 20 to 30% in these days. The principles of the initial management bundle are to provide sufficient hemodynamic resuscitation and early initiation of appropriate antibiotics to mitigate uncontrolled infection. Initial resuscitation requires the use of intravenous fluids and vasopressors. It is very important to achieve the target of initial resuscitation. The supportive cares in ICU are also significant such as blood component transfusion, glucose control, renal replacement therapy, deep vein thrombosis prophylaxis and stress ulcer prophylaxis. The goals of care and prognosis including end-of-life care should be discussed with patients and families as early as feasible.
Anti-Bacterial Agents ; Blood Component Transfusion ; Evidence-Based Medicine ; Glucose ; Hemodynamics ; Humans ; Hypotension ; Mortality ; Patient Care Planning ; Prognosis ; Renal Replacement Therapy ; Resuscitation ; Sepsis* ; Shock, Septic ; Ulcer ; United States ; Venous Thrombosis

Etomidate and midazolam are the most popular drugs among the induction agents for emergent endotracheal intubation. The purpose of this study was to compare the incidence of adrenal insufficiency and mortality between the septic shock patients who received etomidate (ETM group) and those who received midazolam (MDZ group). Between November 2004 and September 2006, 65 patients were analyzed in this study. The hospital mortality rate was 36% in the ETM group (n=25) and 50% in the MDZ group (n=40), which was not statistically significant (p=0.269). The incidence of relative adrenal insufficiency was significantly higher in the ETM group than in the MDZ group (84% and 48%, respectively; p=0.003). On multivariate analysis, the use of etomidate was the only significant factor affecting the incidence of relative adrenal insufficiency (odds radio, 5.59; 95% confidence interval, 1.61- 19.4). In conclusion, we think that physicians who treat patients with septic shock should be aware that etomidate can cause adrenal insufficiency, and should start corticosteroids if etomidate is administered.
Adrenal Cortex Hormones/therapeutic use ; Adrenal Insufficiency/chemically induced/complications ; Aged ; Anesthetics, Intravenous/*adverse effects ; Etomidate/*adverse effects ; Female ; Humans ; *Intubation, Intratracheal ; Male ; Midazolam/*adverse effects ; Middle Aged ; Retrospective Studies ; Shock, Septic/complications/drug therapy/*mortality

OBJECTIVETo assess the value of central venous-to-arterial carbon dioxide difference [ P( cv-a) CO₂] in evaluation of disease severity and prognosis in children with septic shock who already had central venous oxygen saturation (ScvO₂) higher than 70% after early resuscitation.

METHODIn this prospective study, 48 septic shock children seen in Shanghai Children's Hospital, Shanghai Jiao Tong University were enrolled from Jun 2012 to May 2014. 36(75.0%) were male, 12 (25.0%) were female, the average age was (31.9 ± 24.5) months. The critically ill patients with septic shock were treated to achieve ScvO₂greater than 70% depending on early goal-directed therapy (EGDT). All patients were divided into two groups, based on P(cv-a)CO₂, low P(cv-a)CO₂group with P(cv-a)CO₂< 6 mmHg (1 mmHg = 0.133 kPa) and high P(cv-a)CO₂group with P(cv-a)CO₂≥ 6 mmHg. The parameters of hemodynamics including mean blood pressure (MAP), heart rate (HR), central venous pressure (CVP), perfusion-related parameters [ScvO₂, P(cv-a)CO₂, serum lactate (Lac), Lac clearance rate], pediatric critical illness score, PRISMIII score, and 28 days in-hospital mortality were recorded for all patients.

RESULTOf the 48 cases with septic shock whose ScvO₂was higher than 70%, 17 patients (35.4%) had high P(cv-a)CO₂( ≥ 6 mmHg) and 31 (65.6%) had lower P(cv-a)CO₂(<6 mmHg). There were no significant differences between the 2 groups of patients in age, PRISMIII score and PCIS (P > 0.05 ), but Lac and P(cv-a)CO₂values were significantly different ( P < 0.05). Low P(cv-a) CO₂group patients had lower 28 days mortality than high P(cv-a) CO₂group[11/17 vs. 32.3% (10/31), P < 0.05]; 24 h after resuscitation, compared with high P(cv-a) CO₂group, low P(cv-a) CO₂group patients had lower Lac values [(2.0 ± 1.3) vs.( 2.7 ± 1.2) mmol/L, P < 0.05]. Low P(cv-a) CO₂group patients had shorter duration of vasoactive drugs use [(16 ± 14) vs. (44 ± 21)h, P < 0.05], 24 h Lac clearance rate was significantly higher for low P(cv-a) CO₂group than for high P(cv-a) CO₂group[ (31 ± 10) % vs. (26 ± 6)%, P < 0.05].

CONCLUSIONWhen ScvO₂> 70% was achieved after early resuscitation in septic shock children, P(cv-a) CO₂is a sensitive biomarker to assess tissue perfusion, and high P(cv-a) CO₂group patients had poor outcome.

Arterial Pressure ; Blood Gas Analysis ; Carbon Dioxide ; blood ; Central Venous Pressure ; Child, Preschool ; China ; Critical Illness ; Female ; Heart Rate ; Hemodynamics ; Hospital Mortality ; Humans ; Infant ; Lactic Acid ; blood ; Male ; Oximetry ; Prognosis ; Prospective Studies ; Resuscitation ; Severity of Illness Index ; Shock, Septic ; blood ; therapy

OBJECTIVETo investigate the correlation between different Chinese medicine (CM) syndromes and variations in microcirculation in septic shock patients.

METHODSseventy Septic shock patients were divided into four groups: heat damaging qi-yin group (HDQY, 23 cases); yin exhaustion and yang collapse group (YEYC, 26 cases); excessive heat in Fu organ group (EHFO, 10 cases); and heat damaging nutrient-blood group (HDNB, 11 cases). Sublingual microcirculation parameters were observed by sidestream dark-field (SDF) imaging and scored by Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA), and parameters of microcirculation perfusion variations and prognoses were analyzed.

RESULTSCompared with those with qi-yin heat damage, perfused vessel density (PVD) in other groups decreased dramatically (P<0.05), and APACHE II scores increased significantly (P<0.05). In addition, the recovery time was prolonged substantially (P<0.05), and the mixed venous oxygen saturation (SVO2) decreased (P<0.05). Blood lactic acid increased significantly (P<0.05), and the mixed SVO decreased (P<0.05), in the YEYC group. Compared with the thermal injury camp blood group, sublingual microcirculation parameter variations showed no obvious difference in the YEYC and EHFO groups (P>0.05). There were significant positive correlations between CM syndromes and APACHE II scoring in different groups (r=0.512, P<0.05). There were negative correlations between PVD and APACHE II scoring (r=-0.378, P=0.043), the proportion of perfused vessels (PPV) and APACHE II scoring (r=-0.472, P=0.008), as well as between the microvascular flow index (MFI) and APACHE II scoring (r=-0.424, P=0.023) in different patients.

CONCLUSIONSublingual microcirculation may serve as a clinical diagnostic parameter of the patient condition, as well as being a prognostic indicator.

Aged ; Dopamine ; therapeutic use ; Dose-Response Relationship, Drug ; Female ; Hemodynamics ; Humans ; Male ; Medicine, Chinese Traditional ; Microcirculation ; physiology ; Middle Aged ; Mouth Floor ; blood supply ; physiopathology ; Perfusion ; Shock, Septic ; blood ; drug therapy ; mortality ; physiopathology ; Syndrome