Background Sepsis is characterized by heterogeneous immune responses that may evolve during the course of illness. This study identified inflammatory immune responses in septic patients receiving vitamin C, hydrocortisone, and thiamine.
Methods This was a single-center, post-hoc analysis of 95 patients with septic shock who received the vitamin C protocol. Blood samples were drawn on days 1–2, 3–4, and 6–8 after shock onset. Group-based multi-trajectory modeling was used to identify immune trajectory groups.
Results The median age was 78 years (interquartile range, 70–84 years), and 56% were male. Clustering analysis identified group 1 (n=41), which was characterized by lower interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 levels, and these levels remained stationary or mildly increased until day 7. Conversely, group 2 (n=54) expressed initially higher IL-6, TNF-α, and IL-10 levels that decreased rapidly by day 4. There was a nonsignificant increase in lymphocyte count and a decrease in C-reactive protein level until day 7 in group 2. The intensive care unit mortality rate was significantly lower in group 2 (39.0% vs. 18.5%, P=0.03). Group 2 also had a significantly higher decrease in the mean (standard deviation) vasopressor dose (norepinephrine equivalent: –0.09±0.16 μg/kg/min vs. –0.23±0.31 μg/kg/min, P<0.001) and Sequential Organ Failure Assessment score (0±5 vs. –4±3, P=0.002) between days 1 and 4.
Conclusions There may be different subphenotypes in septic patients receiving the vitamin C protocol.
Background Rheumatoid arthritis (RA) is associated with increased risk of sepsis and higher infection-related mortality compared to the general population. However, the evidence on the prognostic impact of RA in sepsis has been inconclusive. We aimed to estimate the population-level association of RA with short-term mortality in sepsis. Methods: We used statewide data to identify hospitalizations aged ≥18 years in Texas with sepsis, with and without RA during 2014–2017. Hierarchical logistic models with propensity adjustment (primary model), propensity score matching, and multivariable logistic regression without propensity adjustment were used to estimate the association of RA with short-term mortality among sepsis hospitalizations. Results: Among 283,025 sepsis hospitalizations, 7,689 (2.7%) had RA. Compared to sepsis hospitalizations without RA, those with RA were older (aged ≥65 years, 63.9% vs. 56.4%) and had higher burden of comorbidities (mean Deyo comorbidity index, 3.2 vs. 2.7). Short-term mortality of sepsis hospitalizations with and without RA was 26.8% vs. 31.4%. Following adjustment for confounders, short-term mortality was lower among RA patients (adjusted odds ratio [aOR], 0.910; 95% confidence interval [CI], 0.856–0.967), with similar findings on alternative models. On sensitivity analyses, short-term mortality was lower in RA patients among sepsis hospitalizations aged ≥65 years and those with septic shock, but not among those admitted to intensive care unit (ICU; aOR, 0.990; 95% CI, 0.909–1.079). Conclusions: RA was associated, unexpectedly, with lower short-term mortality in septic patients. However, this “protective” association was driven by those patients without ICU admission. Further studies are warranted to confirm these findings and to examine the underlying mechanisms.
Background Sepsis and septic shock remain the leading causes of death in critically ill patients worldwide. Various biomarkers are available to determine the prognosis and therapeutic effects of sepsis. In this study, we investigated the effectiveness of presepsin as a sepsis biomarker. Methods: Patients admitted to the intensive care unit with major or minor diagnosis of sepsis were categorized into survival and non-survival groups. The white blood cell count and serum C-reactive protein, procalcitonin, and presepsin levels were measured in all patients. Results: The study included 40 patients (survival group, 32; non-survival group, 8; mortality rate, 20%). The maximum serum presepsin levels measured during intensive care unit admission were significantly higher in the non-survival group (median [interquartile range]: 4,205.5 pg/ml [1,155.8–10,094.0] vs. 741.5 pg/ml [520.0–1,317.5], P<0.05). No statistically significant intergroup differences were observed in the maximum, minimum, and mean values of the white blood cell count, as well as serum C-reactive protein, and procalcitonin levels. Based on the receiver operating characteristic curve, the area under the curve for presepsin as a predictor of sepsis mortality was 0.764. At a cut-off value of 1,898.5 pg/ml, the sensitivity and specificity of presepsin for prediction of sepsis-induced mortality were 75.0% and 87.5%, respectively. Conclusions: Early diagnosis of sepsis and prediction of sepsis-induced mortality are important for prompt initiation of treatment. Presepsin may serve as an effective biomarker for prediction of sepsis-induced mortality and for evaluation of treatment effectiveness.
Background Limited research has explored early mortality among patients presenting with septic shock. The objective of this study was to determine the incidence and factors associated with early death following emergency department (ED) presentation of septic shock.
Methods A prospective registry of patients enrolled in an ED septic shock clinical pathway was used to identify patients. Patients were compared across demographic, comorbid, clinical, and treatment variables by death within 72 hours of ED presentation.
Results Among the sample of 2,414 patients, overall hospital mortality was 20.6%. Among patients who died in the hospital, mean and median time from ED presentation to death were 4.96 days and 2.28 days, respectively. Death at 24, 48, and 72 hours occurred in 5.5%, 9.5%, and 11.5% of patients, respectively. Multivariate regression analysis demonstrated that the following factors were independently associated with early mortality: age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03–1.05), malignancy (OR, 1.53; 95% CI, 1.11–2.11), pneumonia (OR, 1.39; 95% CI, 1.02–1.88), urinary tract infection (OR, 0.63; 95% CI, 0.44–0.89), first shock index (OR, 1.85; 95% CI, 1.27–2.70), early vasopressor use (OR, 2.16; 95% CI, 1.60–2.92), initial international normalized ratio (OR, 1.14; 95% CI, 1.07–1.27), initial albumin (OR, 0.55; 95% CI, 0.44–0.69), and first serum lactate (OR, 1.21; 95% CI, 1.16–1.26).
Conclusions Adult septic shock patients experience a high rate of early mortality within 72 hours of ED arrival. Recognizable clinical factors may aid the identification of patients at risk of early death.
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Background In septic shock patients with cirrhosis, impaired liver function might decrease lactate elimination and produce a higher lactate level. This study investigated differences in initial lactate, lactate clearance, and lactate utility between cirrhotic and non-cirrhotic septic shock patients.
Methods This is a retrospective cohort study conducted at a referral, university-affiliated medical center. We enrolled adults admitted during 2012–2018 who satisfied the septic shock diagnostic criteria of the Surviving Sepsis Campaign: 2012. Patients previously diagnosed with cirrhosis by an imaging modality were classified into the cirrhosis group. The initial lactate levels and levels 6 hours after resuscitation were measured and used to calculate lactate clearance. We compared initial lactate, lactate at 6 hours, and lactate clearance between the cirrhosis and non-cirrhosis groups. The primary outcome was in-hospital mortality.
Results Overall 777 patients were enrolled, of whom 91 had previously been diagnosed with cirrhosis. Initial lactate and lactate at 6 hours were both significantly higher in cirrhosis patients, but there was no difference between the groups in lactate clearance. A receiver operating characteristic curve analysis for predictors of in-hospital mortality revealed cut-off values for initial lactate, lactate at 6 hours, and lactate clearance of >4 mmol/L, >2 mmol/L, and <10%, respectively, among non-cirrhosis patients. Among patients with cirrhosis, the cut-off values predicting in-hospital mortality were >5 mmol/L, >5 mmol/L, and <20%, respectively. Neither lactate level nor lactate clearance was an independent risk factor for in-hospital mortality among cirrhotic and non-cirrhotic septic shock patients.
Conclusions The initial lactate level and lactate at 6 hours were significantly higher in cirrhosis patients than in non-cirrhosis patients.
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Background Patients with sepsis are at risk for developing sepsis-induced cardiomyopathy (SIC). Previous studies offer inconsistent results regarding the association of SIC and mortality. This study sought to assess whether SIC is linked to mortality in patients with sepsis and to evaluate predictors of the development of SIC.
Methods In this retrospective study, patients admitted to the medical intensive care unit with a diagnosis of sepsis in the absence of acute coronary syndrome were included. SIC was identified using transthoracic echo and was defined by a new onset decline in left ventricular ejection fraction (LVEF) ≤50%, or ≥10% decline in LVEF compared to baseline in patients with a history of heart failure with reduced ejection fraction. Multivariable logistic regression analysis was performed using the R software program.
Results Of the 359 patients in the final analysis, 19 (5.3%) had SIC. Eight (42.1%) of the 19 patients in the SIC group and 60 (17.6%) of the 340 patients in the non-SIC group died during hospitalization. SIC was associated with an increased risk for all-cause in-hospital mortality (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.15–18.69; P=0.03). Independent predictors for the development of SIC were albumin level (OR, 0.47; 95% CI, 0.23–0.93; P=0.03) and culture positivity (OR, 8.47; 95% CI, 2.24–55.61; P=0.006). Concomitant right ventricular hypokinesis was noted in 13 (68.4%) of the 19 SIC patients.
Conclusions SIC was associated with an increased risk for all-cause in-hospital mortality. Low albumin level and culture positivity were independent predictors of SIC.
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Background Mortality rates associated with sepsis have increased progressively in Korea, but domestic epidemiologic data remain limited. The objective of this study was to investigate the characteristics, management and clinical outcomes of sepsis patients in Korea.
Methods This study is a multicenter retrospective cohort study. A total of 64,021 adult patients who visited an emergency department (ED) within one of the 19 participating hospitals during a 1-month period were screened for eligibility. Among these, patients diagnosed with sepsis based on the third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) were included in the study.
Results Using the Sepsis-3 criteria, 977 sepsis patients were identified, among which 36.5% presented with septic shock. The respiratory system (61.8%) was the most common site of infection. The pathogen involved was identified in 444 patients (45.5%) and multi-drug resistance (MDR) pathogens were isolated in 171 patients. Empiric antibiotic therapy was appropriate in 68.6% of patients, but the appropriateness was significantly reduced in infections associated with MDR pathogens as compared with non-MDR pathogens (58.8% vs. 76.0%, P<0.001). Hospital mortality was 43.2% and 18.5% in sepsis patients with and without shock, respectively. Of the 703 patients who survived to discharge, 61.5% were discharged to home and 38.6% were transferred to other hospitals or facilities.
Conclusions This study found the prevalence of sepsis in adult patients visiting an ED in Korea was 1.5% (15.2/1,000 patients). Patients with sepsis, especially septic shock, had a high mortality and were often referred to step-down centers after acute and critical care.
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Background Hemoglobin levels are a critical parameter for oxygen delivery in patients with shock. On comparing target hemoglobin levels upon transfusion initiation, the correlation between the severity of decrease in hemoglobin levels and patient outcomes remains unclear. We evaluated the association between initial hemoglobin levels and mortality in patients with septic shock treated with protocol-driven resuscitation bundle therapy at an emergency department.
Methods Data of adult patients diagnosed with septic shock between June 2012 and December 2016 were extracted from a prospectively compiled septic shock registry at a single academic medical center. Patients were classified into four groups according to initial hemoglobin levels: ≥9.0 g/dl, 8.0−8.9 g/dl, 7.0−7.9 g/dl, and <7.0 g/dl. The primary endpoint was 90-day mortality.
Results In total, 2,265 patients (male, 58.3%; median age, 70.0 years [interquartile range, 60 to 78 years]) with septic shock were included. For the four groups, 90-day mortality rates were as follows: 29.1%, 43.0%, 46.5%, and 46.9% for ≥9.0 g/dl (n=1,808), 8.0−8.9 g/dl (n=217), 7.0−7.9 g/dl (n=135), and <7.0 g/dl (n=105), respectively (P<0.001). Multivariate logistic regression showed that initial hemoglobin levels were an independent factor associated with 90-day mortality and mortality proportionally increased with decreasing hemoglobin levels (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.36 to 2.61 for 8.0−8.9 g/dl; OR, 1.97; 95% CI, 1.31 to 2.95 for 7.0–7.9 g/dl; and OR, 2.35; 95% CI, 1.52 to 3.63 for <7.0 g/dl).
Conclusions Low hemoglobin levels (<9.0 g/dl) were observed in approximately 20% of patients with septic shock, and the severity of decrease in these levels correlated with mortality.
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Jae Yeol Kim, Hwan Il Kim, Gee Young Suh, Sang Won Yoon, Tae-Yop Kim, Sang Haak Lee, Jae Young Moon, Jae-Young Kwon, Sungwon Na, Ho Geol Ryu, Jisook Park, Younsuck Koh
Acute Crit Care. 2019;34(1):30-37. Published online January 29, 2019
Background The 2016 Society of Critical Care Medicine (SCCM)/European Society of Intensive Care Medicine (ESICM) task force for Sepsis-3 devised new definitions for sepsis, sepsis with organ dysfunction and septic shock. Although Sepsis-3 was data-driven, evidence-based approach, East Asian descents comprised minor portions of the project population. Methods: We selected Korean participants from the fever and antipyretics in critically ill patients evaluation (FACE) study, a joint study between Korea and Japan. We calculated the concordance rates for sepsis diagnosis between Sepsis-2 and Sepsis-3 criteria and evaluated mortality rates of sepsis, sepsis with organ dysfunction, and septic shock by Sepsis-3 criteria using the selected data. Results: Korean participants of the FACE study were 913 (383 with sepsis and 530 without sepsis by Sepsis-2 criteria). The concordance rate for sepsis diagnosis between Sepsis-2 and Sepsis-3 criteria was 55.4%. The intensive care unit (ICU) and 28-day mortality rates of sepsis, sepsis with organ dysfunction, and septic shock patients according to Sepsis-3 criteria were 26.2% and 31.0%, 27.5% and 32.5%, and 40.8% and 43.4%, respectively. The quick Sequential Organ Failure Assessment (qSOFA) was inferior not only to SOFA but also to systemic inflammatory response syndrome (SIRS) for predicting ICU and 28-day mortality. Conclusions: The concordance rates for sepsis diagnosis between Sepsis-2 and Sepsis-3 criteria were low. Mortality rate for septic shock in Koreans was consistent with estimates made by the 2016 SCCM/ESICM task force. SOFA and SIRS were better than qSOFA for predicting ICU and 28-day mortality in Korean ICU patients.
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HYPOTENSION AT THE TIME OF SEPSIS RECOGNITION IS NOT ASSOCIATED WITH INCREASED MORTALITY IN SEPSIS PATIENTS WITH NORMAL LACTATE LEVELS Ji Hwan Kim, Yong Kyun Kim, Dong Kyu Oh, Kyeongman Jeon, Ryoung-Eun Ko, Gee Young Suh, Sung Yun Lim, Yeon Joo Lee, Young-Jae Cho, Mi-Hyeon Park, Sang-Bum Hong, Chae-Man Lim, Sunghoon Park Shock.2023; 59(3): 360. CrossRef
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Korean J Crit Care Med. 2016;31(2):140-145. Published online May 31, 2016
Severe hyperammonemia can occur as a result of inherited or acquired liver enzyme defects in the urea cycle, among which ornithine transcarbamylase deficiency (OTCD) is the most common form. We report a very rare case of a 45-year-old Korean male who was admitted to the intensive care unit (ICU) due to severe septic shock with acute respiratory failure caused by Pneumocystis jiroveci pneumonia. During his ICU stay with ventilator care, the patient suffered from marked hyperammonemia (>1,700 μg/dL) with abrupt mental change leading to life-threatening cerebral edema. Despite every effort including continuous renal replacement therapy and use of a molecular adsorbent recirculating system (extracorporeal liver support–albumin dialysis) to lower his serum ammonia level, the patient was not recovered. The lethal hyperammonemia in the patient was later proven to be a manifestation of acquired liver enzyme defect known as OTCD, which is triggered by serious catabolic conditions, such as severe septic shock with acute respiratory failure.
Although shock in sepsis is usually managed successfully by conventional medical treatment, a subset of cases do not respond and may require salvage therapies such as veno-arterial extracorporeal membrane oxygenation (VA ECMO) support as well as an attempt to remove endotoxins. However, there are limited reports of attempts to remove endotoxins in patients with septic shock on VA ECMO support. We recently experienced a case of septic shock with severe myocardial injury whose hemodynamic improvement was unsatisfactory despite extracorporeal membrane oxygenation (ECMO) support. Since the cause of sepsis was acute pyelonephritis and blood cultures grew gram-negative bacilli, we additionally applied polymyxin B direct hemoperfusion (PMX-DHP) to the ECMO circuit and were able to successfully taper off vasopressors and wean off ECMO support. To the best of our knowledge, this is the first adult case in which PMX-DHP in addition to ECMO support was successfully utilized in a patient with septic shock. This case indicates that additional PMX-DHP therapy may be beneficial and technically feasible in patients with septic shock with severe myocardial injury refractory to ECMO support.
The effects of direct hemoperfusion with polymyxin B immobilized fiber (PMX) treatment for septic shock have been recently reported. However, little evidence of a true benefit on clinical outcomes, including mortality, is available. Herein, we report three cases of intra-abdominal infection associated with refractory septic shock Case 1 was Escherichia coli peritonitis after a colectomy. PMX treatment improved the hemodynamic parameters and lactic acid levels of the patient. In case 2, secondary peritonitis was associated with septic or cardiogenic shock. Septic cardiomyopathy was assumed to be the cause of shock. 24 hours after the use of PMX, cardiac contractility assessed by echocardiography returned to baseline. In case 3, a patient with Burkitt’s lymphoma and neutropenia was found to be gastroenteritis and Klebsiella pneumoniae bacteremia. Intravenous meropenem was administered for 3 days. Hemodynamic parameters improve after the twice use of PMXOverall, the change of serial sequential organ failure assessment score (SOFA) was more significant in surgical cases as compared to the medical case at 72 hours after PMX administration. All patients were discharged from the hospital. In addition to early resuscitation efforts and infection source control, PMX treatment may be beneficial to patients with refractory intra-abdominal infection associated with septic shock.