Septic Shock Publications (30143)


Septic Shock Publications

Free Radic. Biol. Med.
Free Radic Biol Med 2017 Jan 10. Epub 2017 Jan 10.
Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Stockholm, Sweden. Electronic address:

Thioredoxin (TRX), an endogenous anti-oxidant protein induced in inflammatory conditions, has been shown to increase in plasma and to be associated with outcome in septic patients. This biomarker has never been studied in a trauma setting. We hypothesized that TRX would be increased after trauma and associated with post-injury sepsis. Read More

Single-centre prospective observational study conducted at the intensive care unit (ICU) at the Karolinska University Hospital, Stockholm, Sweden, a level-1 trauma centre. Eighty-three severely injured trauma patients, 18 years or older, with an ICU stay of three days or more were included. Plasma samples were obtained on day 1 and 3 after informed consent. Clinical, physiological and outcome data were retrieved from the trauma and ICU research registries. Plasma samples were also obtained from 15 healthy subjects. In addition, a standardized porcine trauma model was conducted where a femur fracture followed by a controlled hemorrhage period were inflicted in four pigs.
In pigs, however not significant, there was a continuing increase in plasma-TRX after femur fracture and sequential hemorrhage despite near normalisation of cardiac index and lactate levels. In patients, median injury severity score was 29 and 48 patients developed sepsis during their ICU stay. A three-fold increase in initial TRX was seen in trauma patients when compared to healthy volunteers. Thioredoxin was significantly higher in patients in shock on admission, those subject to massive transfusion and in the most severely injured patients. No difference was seen between survivors and non-survivors. Plasma-TRX on day 1 was significantly increased in patients who later developed post-injury sepsis. In a logistic regression analysis including TRX, C-reactive protein, injury severity, massive transfusion, and admission blood pressure, TRX was the only variable independently associated with post-injury sepsis.
This study demonstrates that TRX is released into plasma in response to severe trauma and independently associated with post-injury sepsis. The use of TRX as a biomarker in trauma patients needs further evaluation in larger studies.
Retrospective cohort study, level III.

Am. J. Respir. Crit. Care Med.
Am J Respir Crit Care Med 2017 Jan;195(2):263-265
3 University of Cincinnati College of Medicine Cincinnati, Ohio and.
Immunol. Lett.
Immunol Lett 2017 Jan 9. Epub 2017 Jan 9.
Emergency Medicine Department, University of Sao Paulo, Sao Paulo, Brazil.

Antimicrobial peptides are key components of the innate immune system. They act as broad-spectrum antimicrobial agents against Gram-positive and -negative bacteria, viruses, and fungi. More recently, antimicrobial peptides have been ascribed immunomodulatory functions, including roles in wound healing, induction of cytokines, and altering host gene expression. Read More

Cathelicidins are a class of antimicrobial peptide found in humans, mice, and rats, among others. Known as LL-37 in humans and cathelin-related antimicrobial peptide (CRAMP) in rodents, cathelicidins are produced by many different cells, including macrophages, neutrophils, and epithelial cells. The role of cathelicidins is somewhat confounding, as they exhibit both pro-and anti-inflammatory activity. A major obstacle in the study of cathelicidins is the inability of exogenous LL-37 or CRAMP to mimic the activity of their endogenous counterparts. Nevertheless, studies have shown that LL-37 is recognized by multiple receptors, and may stabilize or modulate Toll-like receptor signaling. In addition, cathelicidins play a role in apoptosis, inflammasome activation, and phagocytosis. However, many studies are revealing the dual effects of cathelicidins. For example, CRAMP appears to be protective in models of group A Streptococcus skin infection, pneumonia, and meningitis, but detrimental in cases of severe bacterial infection, such as septic shock. It is becoming increasingly clear that the activity of cathelicidins is modulated by complex interactions with the microenvironment, as well as the disease background. This article reviews what is currently known about the activity of cathelicidins in an attempt to understand their complex roles in systemic diseases.

Crit. Care Med.
Crit Care Med 2017 Jan 10. Epub 2017 Jan 10.
1Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA. 2Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA. 3Department of Emergency Medicine, The Beth Israel Hospital, Harvard University, Boston, MA.

The Protocol-based Care for Early Septic Shock trial found no differences across alternative resuscitation strategies in all-cause mortality. A separate aim was to determine whether differences in resuscitation strategies affected trajectories of biomarkers of key pathways associated with downstream clinical outcomes of sepsis and whether there were differences in survival across treatment arms for patients with different baseline biomarker profiles.
Secondary analysis of a large randomized clinical trial. Read More

Thirty-one U.S. hospitals.
Six hundred twenty-eight patients with septic shock.
Two resuscitation protocols versus usual care.
We measured a panel of biomarkers representing four pathophysiologic domains: "inflammation" (tumor necrosis factor, interleukin-6, and -10); "coagulation" (D-dimers, thrombin-antithrombin complex); "oxidative stress" (urine isoprostane); and "tissue hypoxia" (lactate) at 0, 6, 24, and 72 hours after treatment. We analyzed whether alternative resuscitation strategies affected biomarker trajectories over 72 hours and whether effects on 90-day hospital mortality varied by baseline (time 0) biomarker profiles-both using regression models with interaction terms for treatment arms. For all baseline biomarkers, higher concentrations were associated with increased risk of death by 90 days. However, there was no significant effect of treatment assignment on subsequent biomarker trajectories. We did find evidence for heterogeneity of treatment effect of protocol-based care on mortality for patients with different baseline [interleukin-6] and [interleukin-6] × [interleukin-10] profiles, whereas patients with the lowest quartiles fared better with protocol-based care (odds ratios, 0.32 [0.13-075]; p = 0.01 and 0.32 [0.14-0.73]; p = 0.01, respectively).
In patients with septic shock, alterations in inflammation, coagulation, oxidative stress, and tissue hypoxia are common and associated with adverse outcomes but are not influenced by protocol-based resuscitation compared with usual care. However, contrary to expectation, protocol-based resuscitation appeared to be superior in patients with lower concentrations of inflammatory biomarkers. The mechanisms responsible for this effect are unclear.

Ceylon Med J
Ceylon Med J 2016 12;61(4):181-184
Sri Ramachandra University Research Institute, India.

Sepsis is the leading cause of intensive care unit (ICU) admissions and is associated with high mortality.
To identify the incidence, risk factors and outcome of patients with severe sepsis and septic shock.
A prospective observational study was done in a multidisciplinary ICU over a period of 18 months. Read More

We included all adult patients admitted to ICU with features of severe sepsis and septic shock as per SCCM/ACCP guidelines. Data related to demography, co-existing illnesses, parameters to assess Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, other relevant laboratory data, source of infection, organ failures and supportive measures given were recorded. Primary outcome data on mortality was collected and secondary outcome data on ventilator days, ICU length of stay (ALOS) and ventilator free days were recorded.
A total of 1162 patients were screened and 356 patients had severe sepsis. Incidence of severe sepsis was 30.6% and mortality rate was 51.6%. APACHEII (23.37 ± 9.47) and SOFA (7.58 ± 4.05) scores at admission were high. Most common source of infection was from the respiratory tract (37.2%) followed by urinary tract (10.3%) and intra-abdominal (9.5%) infections. About 63% of patients required ventilator support, 25.5% of patients required vasopressor support despite adequate fluid resuscitation and one third of patients required renal replacement therapy (35.7%). Haematocrit, total leucocyte count, serum bilirubin and SOFA scores were significantly higher among non-survivors.
Incidence of severe sepsis was high and was associated with a poor patient outcome in an ICU in India.

AJP Rep 2016 Oct;6(4):e436-e441
Department of Obstetrics and Gynecology, University of Rwanda, Rwanda; Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina; Department of Obstetrics and Gynecology, Yale University, New Heaven, Connecticut.

Background Gastric rupture is a rare, life-threatening condition during pregnancy. Case study We present three cases of gastric perforation during pregnancy and the puerperium. The first patient presented with gastric perforation 4 days following an uncomplicated cesarean delivery for obstetric indications. Read More

She initially complained of epigastric pain; however, those symptoms resolved. She later demonstrated worsening abdominal distension, intra-abdominal free fluid, and signs of peritonitis. At laparotomy, an ascariasis-associated gastric rupture was diagnosed. She died from sepsis 4 days following the laparotomy. The second patient presented 19 days following a normal vaginal delivery. She presented with hemodynamic instability and underwent emergent laparotomy due to suspected septic shock peritonitis. Gastric rupture was diagnosed intraoperatively. She improved clinically and was discharged home. The third patient underwent emergency cesarean delivery due to non-reassuring fetal status in the setting of preeclampsia. She was initially diagnosed with ascites and pulmonary edema as a result of preeclampsia. Later in her course, she developed features in favor of acute abdomen and signs of sepsis. At the time of emergent laparotomy, a gastric rupture was identified and repaired. She died 2 days later from sepsis. Conclusion We report the management and outcome of three cases of pregnancy-related gastric rupture. To our knowledge, these three cases represent the largest series of pregnancy-related gastric ruptures from a single institution.

J Intensive Care Med
J Intensive Care Med 2017 Jan 1:885066616686035. Epub 2017 Jan 1.
1 Department of Pharmacy, NYU Langone Medical Center, New York, NY, USA.
Anaesth Intensive Care
Anaesth Intensive Care 2017 Jan;45(1):12-20
Senior Lecturer, Nepean Clinical School, University of Sydney, Staff Specialist, Department of Intensive Care, Nepean Hospital, Sydney, New South Wales.

The current trend to treat hypotension in critically ill patients is to place a greater emphasis on inotropic support and less on fluid resuscitation in order to limit the potential harm from fluid overload. This combination may trigger left ventricular outflow tract obstruction (LVOTO) in susceptible patients. Although LVOTO is classically described in patients with hypertrophic cardiomyopathy it has been reported in other conditions including septic shock, apical ballooning syndrome, myocardial infarction, respiratory failure, and post valvular surgery. Read More

It is more common in the elderly, females, and in patients with hypertension, diabetes, and chronic vascular disease because of predisposing anatomical conditions such as left ventricular hypertrophy, small left ventricle size, sigmoid septum and alterations in the positions of the aortic and mitral valve annular planes. The onset of LVOTO is largely unpredictable due to a complex interplay between preload, afterload, heart rhythm and rate in susceptible patients. The consequences of missing this treatable condition may lead to life-threatening hypotension refractory to, or exacerbated by, a further increase in inotropic support. Dynamic LVOTO should be considered in any hypotensive intensive care patient. Echocardiography is perhaps the best tool to assess LVOTO and its underlying pathophysiology in the critically ill. Detection of LVOTO is a relatively simple task using a combination of two-dimensional, M-mode and spectral Doppler imaging by an operator alert to the possible diagnosis.

PLoS One 2017 10;12(1):e0169653. Epub 2017 Jan 10.
Department of Emergency and Critical Care Medicine, Aichi Medical University, Aichi, Japan.

Sepsis causes impairment of innate and adaptive immunity by multiple mechanisms, including depletion of immune effector cells and T cell exhaustion. Although lymphocyte dysfunction is associated with increased mortality and potential reactivation of latent viral infection in patients with septic shock, the relation between viral reactivation and lymphocyte dysfunction is obscure. The objectives of this study were 1) to determine the relation of lymphocyte dysfunction to viral reactivation and mortality, and 2) to evaluate recovery of lymphocyte function during septic shock, including T cell receptor (TCR) diversity and the expression of programmed death 1 (PD-1). Read More

In 18 patients with septic shock and latent cytomegalovirus (CMV) infection, serial blood samples were obtained on days 1, 3, and 7 after the onset of shock, and immune cell subsets and receptor expression were characterized by flow cytometry. TCR diversity of peripheral blood mononuclear cells was analyzed by Multi-N-plex PCR, and CMV DNA was quantified using a real-time PCR kit. A decrease of TCR diversity and monocyte HLA-DR expression were observed in the early stage of septic shock, while CD4+ T cells displayed an increase of PD-1 expression. Significant lymphopenia persisted for at least 7 days following the onset of septic shock. Normalization of TCR diversity and PD-1 expression was observed by day 7, except in patients who died. CMV reactivation was detected in 3 of the 18 patients during the first week of their ICU stay and all 3 patients died. These changes are consistent with the early stage of immune cell exhaustion and indicate the importance of normal lymphocyte function for recovery from septic shock. Ongoing lymphocyte dysfunction is associated with CMV reactivation and dissemination, as well as with unfavorable outcomes.

Pediatr Emerg Care
Pediatr Emerg Care 2017 Jan 9. Epub 2017 Jan 9.
From the *Department of Pediatrics, †Neonatal-Pediatric Research Group, ‡Division of Pediatric Critical Care, UCSF Benioff Children's Hospital Oakland, Oakland, CA; §Division of Pediatric Critical Care Medicine, University of Michigan, C.S. Mott Children's Hospital, Ann Arbor, MI; and ∥Division of Pediatric Critical Care, UCSF Benioff Children's Hospital San Francisco, San Francisco, CA.

The aim of the study was to assess the association of initial lactate (L0) with mortality in children with severe sepsis.
This prospective cohort study included 74 patients younger than 18 years with severe sepsis admitted to the pediatric intensive care unit (PICU) of a tertiary, academic children's hospital with lactate measured within 3 hours of meeting severe sepsis or septic shock. The primary outcome was in-hospital mortality. Read More

The secondary outcomes included PICU and hospital length of stay.
Although overall mortality was 10.5% (n = 18), patients with L0 measured (n = 72) had a higher mortality (16% vs 6%, P = 0.03) and higher median PRISM-III risk of mortality scores (P = 0.02) than those who did not. Median L0 was no different between nonsurvivors and survivors (3.6 mmol/L [interquartile range, 2.0-9.0] in nonsurvivors vs 2.3 mmol/L [interquartile range, 1.4-3.5] in survivors, P = 0.11). However, L0 was independently associated with PRISM-III score (coefficient, 1.12; 95% confidence interval, 0.4-1.8; P = 0.003) with an increase in mean PRISM-III score of 1.12 U for every 1 mmol/L increase in L0, with L0 accounting for 12% of the variability in PRISM-III scores between patients. There was no association between L0 and PICU or hospital length of stay.
Although our single center study did not demonstrate that an elevated early lactate is associated with mortality in pediatric severe sepsis, L0 did correlate strongly with PRISM-III, the most robust measure of mortality risk in pediatrics. Therefore, early lactate measurement may be important as an early biomarker of disease severity. These data should be validated in a larger, multicenter, prospective study.