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Sepsis
Current Awareness Bulletin
April 2021
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Email: ruh-tr.library@nhs.netTitle: Emerging mechanisms of immunocoagulation in sepsis and septic shock
Citation: Trends in immunology; Apr 2021
Author(s): Tang D.; Wang H.; Billiar T.R.; Kroemer G.; Kang R.
Abstract: Sepsis and septic shock driven by microbial infections are still among the most
challenging health problems, causing 11 million deaths worldwide every year. How does the
host's response to pathogen infections effectively restore homeostasis instead of
precipitating pathogenic and potentially fatal feedforward reactions? Recently, there have
been significant new advances in our understanding of the interface between mammalian
immunity and coagulation ('immunocoagulation') and its impact on sepsis. In particular, the
release and activation of F3 (the main initiator of coagulation) from and on myeloid or
epithelial cells is facilitated by activating inflammasomes and consequent gasdermin D
(GSDMD)-mediated pyroptosis, coupled to signaling via high mobility group box 1 (HMGB1),
stimulator of interferon response CGAMP interactor 1 (STING1), or sequestosome 1
(SQSTM1). Pharmacological modulation of the immunocoagulation pathways emerge as
novel and potential therapeutic strategies for sepsis. Copyright © 2021 Elsevier Ltd. All
rights reserved.
Title: Septic Cardiomyopathy: From Basics to Management Choices
Citation: Current Problems in Cardiology; Apr 2021; vol. 46 (no. 4)
Author(s): Ravikumar N.; Sayed M.A.; Poonsuph C.J.; Sehgal R.; Shirke M.M.; Harky A.
Abstract: Septic cardiomyopathy (SCM) is increasingly recognized as a potential
complication of septic shock; it is understood to be a reversible left ventricular systolic
dysfunction. The presence of SCM in septic shock, in previous studies, infer a poorer
prognosis as it significantly increases the mortality rate of patients to 70%-90% and its
incidence varies from 18% to 40% of septic shock patients. The pathogenesis is unclear, but
believed to be a combination of bacterial toxins, cytokines, nitric oxide, and cardiac
mitochondrial dysfunction, that depresses intrinsic cardiac contractility. The presence of
SCM can be diagnosed in patients using a bedside transthoracic echocardiogram which
typically shows left ventricular ejection fractionrecover, but instead will go on to develop chronic critical illness (CCI) and experience dismal
long-term outcomes. The elderly and comorbid patient is highly susceptible to death or CCI
after sepsis. Here, we review aspects of the Persistent Inflammation, Immunosuppression,
and Catabolism Syndrome (PICS) endotype to explain the underlying pathobiology of a
dysregulated immune system in sepsis survivors who develop CCI; then, we explore targets
for immunomodulatory therapy. Copyright © 2021 by the authors. Licensee MDPI, Basel,
Switzerland.
Title: Review lipid and lipoprotein dysregulation in sepsis: Clinical and mechanistic
insights into chronic critical illness
Citation: Journal of Clinical Medicine; Apr 2021; vol. 10 (no. 8)
Author(s): Barker G.; Guirgis F.W.; Leeuwenburgh C.; Brusko T.; Moldawer L.; Reddy S.T.
Abstract: In addition to their well-characterized roles in metabolism, lipids and lipoproteins
have pleiotropic effects on the innate immune system. These undergo clinically relevant
alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL)
plays an important role in regulating the immune response by clearing bacterial toxins,
supporting corticosteroid re-lease, decreasing platelet aggregation, inhibiting endothelial cell
apoptosis, reducing the monocyte inflammatory response, and inhibiting expression of
endothelial cell adhesion molecules. It under-goes quantitative as well as qualitative
changes which can be measured using the HDL inflammatory index (HII). Pro-inflammatory,
or dysfunctional HDL (dysHDL) lacks the ability to perform these functions, and we have also
found it to independently predict adverse outcomes and organ failure in sepsis. Another
important class of lipids known as specialized pro-resolving mediators (SPMs) positively
affect the escalation and resolution of inflammation in a temporal fashion. These undergo
phenotypic changes in sepsis and differ significantly between survivors and non-survi-vors.
Certain subsets of sepsis survivors go on to have perilous post-hospitalization courses
where this inflammation continues in a low grade fashion. This is associated with
immunosuppression in a syndrome of persistent inflammation, immunosuppression, and
catabolism syndrome (PICS). The continuous release of tissue damage-related patterns and
viral reactivation secondary to immuno-suppression feed this chronic cycle of inflammation.
Animal data indicate that dysregulation of en-dogenous lipids and SPMs play important roles
in this process. Lipids and their associated path-ways have been the target of many clinical
trials in recent years which have not shown mortality benefit. These results are limited by
patient heterogeneity and poor animal models. Considerations of sepsis phenotypes and
novel biomarkers in future trials are important factors to be considered in future research.
Further characterization of lipid dysregulation and chronic inflammation during sepsis will aid
mortality risk stratification, detection of sepsis, and inform individualized pharmacologic
therapies. Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Title: Sepsis-Associated Acute Kidney Injury
Source: Critical Care Clinics; Apr 2021; vol. 37 (no. 2); p. 279-301
Author(s): Manrique-Caballero C.L.; Del Rio-Pertuz G.; Gomez H.
Abstract: Sepsis-associated acute kidney injury (S-AKI) is a common and life-threatening
complication in hospitalized and critically ill patients. It is characterized by rapid deterioration
of renal function associated with sepsis. The pathophysiology of S-AKI remains incompletely
understood, so most therapies remain reactive and nonspecific. Possible pathogenic
3mechanisms to explain S-AKI include microcirculatory dysfunction, a dysregulated
inflammatory response, and cellular metabolic reprogramming. In addition, several
biomarkers have been developed in an attempt to improve diagnostic sensitivity and
specificity of S-AKI. This article discusses the current understanding of S-AKI, recent
advances in pathophysiology and biomarker development, and current preventive and
therapeutic approaches. Copyright © 2020 Elsevier Inc.
Title: Key Challenges in Providing Effective Antibiotic Therapy for Critically Ill
Patients with Bacterial Sepsis and Septic Shock
Citation: Clinical Pharmacology and Therapeutics; Apr 2021; vol. 109 (no. 4); p. 892-904
Author(s): Landersdorfer C.B.; Nation R.L.
Abstract: Early initiation of effective antibiotic therapy is vitally important for saving the lives
of critically ill patients with sepsis or septic shock. The susceptibility of the infecting pathogen
and the ability of the selected dosage regimen to safely achieve the required antibiotic
exposure need to be carefully considered to achieve a high probability of a successful
outcome. Critically ill patients commonly experience substantial pathophysiological changes
that impact the functions of various organs, including the kidneys. Many antibiotics are
predominantly renally eliminated and thus renal function is a major determinant of the
regimen needed to achieve the required antibiotic exposure. However, currently, there is a
paucity of guidelines to inform antibiotic dosing in critically ill patients, including those with
sepsis or septic shock. This paper briefly reviews methods that are commonly used in
critically ill patients to provide a measure of renal function, and approaches that describe the
relationship between the exposure to an antibiotic and its antibacterial effects. Two common
conditions that very substantially complicate the use of antibiotics in critically ill patients with
sepsis, unstable renal function, and augmented renal clearance, are considered in detail and
their potential therapeutic implications are explored. Suggestions are provided on how
treatment of bacterial infections in critically ill patients with sepsis might be improved. Of high
potential are model-informed approaches that aim to individualize initial treatment regimens
based on patient and bacterial characteristics, with refinement of regimens during treatment
in response to monitoring antibiotic concentrations, responsive measures of renal function,
and other important clinical data.Copyright © 2021 The Authors. Clinical Pharmacology &
Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics
Title: Pathophysiology of sepsis
Citation: Current opinion in anaesthesiology; Apr 2021; vol. 34 (no. 2); p. 77-84
Author(s): Arina P.; Singer M.
Purpose Of Review: To provide a current overview of sepsis pathophysiology.
Recent Findings: The emphasis on sepsis pathophysiology has moved away from the
pathogen - the initiating factor - and instead is focussed upon the abnormal and exaggerated
host response. Instead of targeted eradication of the infection, the host response activates or
suppresses multiple downstream pathways, leading to multiple organ dysfunction.
Summary: Sepsis represents a dysregulated host response to infection leading to organ
dysfunction. Here, the pathogen triggers an initial exaggerated inflammatory-immune
response that leads to activation or suppression of multiple endothelial, hormonal,
bioenergetic, metabolic, immune, and other pathways. These, in turn, produce the circulatory
4and metabolic perturbations resulting in organ dysfunction. This review will provide an
overview of underlying mechanisms and propose that these processes, whereas superficially
viewed as dysfunctional, may actually be adaptive/protective in the first instance, though
spilling over into maladaptation/harm depending on the magnitude of the host response.
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Title: Epidemiology of sepsis and septic shock
Citation: Current opinion in anaesthesiology; Apr 2021; vol. 34 (no. 2); p. 71-76
Author(s): Chiu C.; Legrand M.
Purpose Of Review: The epidemiology of sepsis and septic shock has been challenging to
study for multiple reasons. These include changing diagnostic definitions, as well a high
concentration of sepsis-related studies published from high-income countries (HICs), despite
a large global burden. This section attempts to address the incidence of sepsis throughout
the years and worldwide.
Recent Findings: The incidence of sepsis and septic shock has continued to increase since
the first consensus definitions (Sepsis-1) were established in 1991, and the latest definitions
(Sepsis-3) provide a better reflection of mortality risk for a diagnosis of sepsis. Several
studies argue that the incidence of sepsis is overreported in HICs, based on billing and
coding practices, and may lead to overutilization of resources. However, recent estimates of
the true global burden of sepsis, including low-income countries, are likely much higher than
reported, with calls for better allocation of resources.
Summary: The true epidemiology of sepsis worldwide continues to be a highly debated
subject, and more research is needed among low-income countries and high-risk
subpopulations. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Title: Utilization of a Burn Sepsis Algorithm: A Five-Year Analysis.
Citation: Journal of Burn Care & Research; Apr 2021; vol. 42
Author(s): Williams ; Saraswat, Anju; Bailey, John K; Craig, Christopher K; Holmes, James
H
Introduction: After the first 24 hours, the major cause of death in burn patients is multiple
organ dysfunction/failure syndrome. It is preceded by an infection in 83% of burn patients,
with reported septic mortality up to 65%. Since the early recognition and treatment of
infection has been shown to decrease mortality from sepsis, we implemented a
multidisciplinary algorithm designed to rapidly identify septic adult burn patients.
Methods: Adult (≥18 y) admissions between 7/1/2014 – 6/30/2019 were identified from our
registry, and all initial sepsis screens were evaluated in the EMR. Patients were screened
clinically at least twice daily and were considered a "positive" screen if MAP < 65 mmHg
(SBP102.2F; HR >120; RR >28 (or RR >10% of ventilator set rate if set rate is >24 bpm). A
positive screen prompted lab work to include CBC, BMP, procalcitonin (PCT), and lactic acid
(LA), per protocol. If PCT >3.0 ng/ml or LA >2.0 mmol/L, or both thrombocytopenia and
hyperglycemia were present, a "Burn Code Sepsis" was initiated and included cultures, a
CXR, and empiric antibiotics. A patient was then formally considered "septic" (i.e. infected) if
the cultures were positive or the CXR demonstrated an infectious process.
Results: There were 1,523 admissions during the 5-year period, and 228 initial positive
screens. Of the 228 patients with positive screens, 159 (70%) were infected. There was a
5significant difference in PCT level between patients with and without infections, while no
difference was noted for LA, WBC, platelets, temperature, glucose, age, %TBSA burned, or
time to triggering a positive screen between the groups (Table). Defining PCT ≥3.0 ng/mL as
being positive for sepsis demonstrated a 76% PPV and a 36% NPV for PCT alone. Our
initial sepsis screening algorithm had a sensitivity of 64.8% and a specificity of 40.6% over
the five-year period.
Conclusions: Recognition of sepsis remains difficult in burn patients. PCT and the use of a
sepsis screening algorithm may have a role in the early detection of sepsis. Further research
is warranted.
Title: Biomarkers for the Early Diagnosis of Sepsis in Burns: Systematic Review and
Meta-analysis.
Citation: Journal of Burn Care & Research; Apr 2021; vol. 42
Author(s): Li ; Moussa, Anthony; Gus, Eduardo; Paul, Eldho; Yii, Erwin; Romero, Lorena;
Lo, Cheng H; Cleland, Heather J
Introduction: Early clinical diagnosis of sepsis in burns patients is notoriously difficult, and
many biomarkers have been proposed as adjuncts to clinical assessment. We aimed to
evaluate the diagnostic performance of all previously studied biomarkers for the early
diagnosis of sepsis in hospitalized patients with burns.
Methods: We conducted a systematic literature search to February 2020 of Medline,
Embase, Cochrane Central, Biosis Previews, Web of Science, and Medline In-Process. Only
diagnostic studies utilising a sepsis definition of positive blood cultures or a combination of
infection, systemic inflammation, and organ dysfunction were included. Where possible,
contingency tables were used as reported or constructed from original data using a cut-off
based on Youden's index. Pooled sensitivity and specificity estimates were derived for each
biomarker using random effects meta-analysis.
Results: We included 27 studies evaluating 56 different biomarkers. Procalcitonin was
moderately sensitive and specific for sepsis in patients with burns (sensitivity 72%, specificity
74%). CRP was also moderately sensitive and specific (74% and 64% respectively). White
cell count had poor sensitivity and specificity (46% and 59% respectively). All other
biomarkers had insufficient studies to include in a meta-analysis, however cell free DNA,
nuclear DNA, BDG, BNP, and SVI showed the most promise in single studies. There was
considerable heterogeneity between studies reflecting different definitions and cut-offs.
Conclusions: The most widely studied biomarkers are poorly predictive for sepsis in burn
patients. Several promising candidates have been reported which should be evaluated in
further studies. A standardized approach to the evaluation of diagnostic markers (including
time of sampling, approach to cut-offs and outcome) would be useful.
Title: Biomarkers in sepsis: can they help improve patient outcome?
Citation: Current Opinion in Infectious Diseases; Apr 2021; vol. 34 (no. 2); p. 126-134
Author(s): Kyriazopoulou ; Poulakou, Garyfallia; Giamarellos-Bourboulis, Evangelos J.
Purpose Of Review: Biomarkers, mainly procalcitonin, are commonly used in sepsis
diagnosis, prognosis and treatment follow-up. This review summarizes the potential benefit
of their use for the critically ill.
6Recent Findings: Increased clinical evidence from randomized clinical trials of biomarker-
guided treatment suggests a trend for appropriate but short antimicrobial treatment for the
critically ill. Procalcitonin (PCT) is the most studied biomarker; in the majority of randomized
clinical trials, the use of a stopping rule of antibiotics on the day when PCT is below 80%
from baseline or less than 0.5 ng/ml was proven effective to reduce length of antimicrobial
treatment, antibiotic-associated adverse events and infectious complications like infections
by multidrug-resistant organisms and Clostridium difficile. Survival benefit was also noted.
Summary: Biomarkers, mainly PCT, may help improve sepsis outcome by restriction of
injudicious antimicrobial use.
Title: Comparative Effectiveness of Heart Rate Control Medications for the Treatment
of Sepsis-Associated Atrial Fibrillation.
Citation: Chest; Apr 2021; vol. 159 (no. 4); p. 1452-1459
Author(s): Bosch ; Rucci, Justin M.; Massaro, Joseph M.; Winter, Michael R.; Quinn, Emily
K.; Chon, Ki H.; McManus, David D.; Walkey, Allan J.
Background: Atrial fibrillation (AF) with rapid ventricular response frequently complicates
the management of critically ill patients with sepsis and may necessitate the initiation of
medication to avoid hemodynamic compromise. However, the optimal medication to achieve
rate control for AF with rapid ventricular response in sepsis is unclear.
Research question: What is the comparative effectiveness of frequently used AF
medications (β-blockers, calcium channel blockers, amiodarone, and digoxin) on heart rate
(HR) reduction among critically ill patients with sepsis and AF with rapid ventricular
response?
Study design and methods: We conducted a multicenter retrospective cohort study among
patients with sepsis and AF with rapid ventricular response (HR > 110 beats/min). We
compared the rate control effectiveness of β-blockers to calcium channel blockers,
amiodarone, and digoxin using multivariate-adjusted, time-varying exposures in competing
risk models (for death and addition of another AF medication), adjusting for fixed and time-
varying confounders.
Results: Among 666 included patients, 50.6% initially received amiodarone, 10.1% received
a β-blocker, 33.8% received a calcium channel blocker, and 5.6% received digoxin. The
adjusted hazard ratio for HR of < 110 beats/min by 1 h was 0.50 (95% CI, 0.34-0.74) for
amiodarone vs β-blocker, 0.37 (95% CI, 0.18-0.77) for digoxin vs β-blocker, and 0.75 (95%
CI, 0.51-1.11) for calcium channel blocker vs β-blocker. By 6 h, the adjusted hazard ratio for
HR < 110 beats/min was 0.67 (95% CI, 0.47-0.97) for amiodarone vs β-blocker, 0.60 (95%
CI, 0.36-1.004) for digoxin vs β-blocker, and 1.03 (95% CI, 0.71-1.49) for calcium channel
blocker vs β-blocker.
Interpretation: In a large cohort of patients with sepsis and AF with rapid ventricular
response, a β-blocker treatment strategy was associated with improved HR control at 1 h,
but generally similar HR control at 6 h compared with amiodarone, calcium channel blocker,
or digoxin.
Keywords: atrial fibrillation; comparative effectiveness; rate control; sepsis.
Title: Comparison of shock reversal with high or low dose hydrocortisone in intensive
care unit patients with septic shock: A retrospective cohort study
Citation: Journal of Critical Care; Apr 2021; vol. 62 ; p. 111
7Author(s): Bonnin, Sophia; Radosevich, John J; Yong Gu Lee; Feldman, Jeremy P;
Barletta, Jeffrey F
Purpose: This study aims to describe differences in shock reversal between hydrocortisone
200 mg and 300 mg per day dosing regimens in patients with septic shock.
Methods: This is a multi-center retrospective study including patients admitted to intensive
care units with septic shock receiving vasopressors and hydrocortisone between 2013 and
2018. We compared patients who received low dose hydrocortisone (50 mg every 6 h)
versus high dose hydrocortisone (100 mg every 8 h) on the primary outcome of shock
reversal.
Results: 319 patients (low dose group, n = 134 and high dose group, n = 185) were
included. In the multivariate regression model, high-dose steroids were associated with
shock reversal [OR (95% CI) = 2.278 (1.063–4.880), p = 0.034]. This was not confirmed in
the propensity score matched analysis [OR (95% CI) =2.202 (0.892–5.437), p = 0.087]. High
dose steroids were associated with a lower need for additional vasopressor therapy (22% vs.
34%, p = 0.012) and lower shock recurrence (6.7% vs. 16%, p = 0.013), which was
confirmed with propensity score matching.
Conclusions: Low and high dose hydrocortisone have similar rates of shock reversal in
septic shock patients. Hydrocortisone 100 mg every 8 h may reduce rates of recurrence of
shock and reduce the need for additional vasopressors.
Title: Dantrolene repurposed to treat sepsis or septic shock and COVID-19 patients.
Citation: European review for medical and pharmacological sciences; Apr 2021; vol. 25 (no.
7); p. 3136-3144
Author(s): Wei, H; Liang, G; Vera, R M
Objective: Disruption of intracellular Ca2+ homeostasis via excessive and pathological
Ca2+ release from the endoplasmic reticulum (ER) and/or sarcoplasmic reticulum (SR)
through ryanodine receptor (RyRs) Ca2+ channels play a critical role in the pathology of
systemic inflammatory response syndrome (SIRS) and associated multiple organ
dysfunction syndrome (MODS) in sepsis or septic shock. Dantrolene, a potent inhibitor of
RyRs, is expected to ameliorate SIRS and MODS and decrease mortality in sepsis or septic
shock patients. This review summarized the potential mechanisms of therapeutic effects of
dantrolene in sepsis or septic shock at molecular, cell, and organ levels and provided
suggestions and strategies for future clinical studies.
Title: Early Recognition and Management of Sepsis in the Elderly
Citation: Critical Care Nursing Quarterly; 2021; vol. 44 (no. 2); p. 175
Author(s): Onawola, Alice M
Abstract: Sepsis is a life-threatening and debilitating sickness in the elderly. This case study
explores the importance of adequate assessment of patients on their initial presentation to
the emergency department, during hospitalization, and before discharge. The clinical
evaluation, recognition, and management of sepsis continue to be essential for patient
survival to prevent and decrease the mortality rate. Some changes go on in the elderly organ
systems and can lead to delay in identifying and treatment implementation. The use of the
8Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3) to
anticipate outcomes in septic patients and the use of the Survival Sepsis Campaign for
treatment guidelines promptly to improve outcomes are crucial. This article aims to inform
clinicians and nurses of the importance of early recognition of subtle signs and symptoms
and the management of sepsis in the elderly.
Title: Implementation of an Automated Sepsis Screening Tool in a Community
Hospital Setting
Citation: Journal of Nursing Care Quality; 2021; vol. 36 (no. 2); p. 132
Author(s): Cooper, Penny B; Hughes, Bobbi J; Verghese, George M; Scott, Just J;
Markham, Amy J
Background: Early identification of sepsis remains the greatest barrier to compliance with
recommended evidence-based bundles.
Purpose: The purpose was to improve the early identification and treatment of sepsis by
developing an automated screening tool.
Methods: Six variables associated with sepsis were identified. Logistic regression was used
to weigh the variables, and a predictive model was developed to help identify patients at risk.
A retrospective review of 10 792 records of hospitalizations was conducted including 339
cases of sepsis to retrieve data for the model.
Results: The final model resulted an area under the curve of 0.857 (95% CI, 0.850-0.863),
suggesting that the screening tool may assist in the early identification of patients developing
sepsis.
Conclusion: By using artificial intelligence capabilities, we were able to screen 100% of our
inpatient population and deliver results directly to the caregiver without any manual
intervention by nursing staff.
Title: Implementation of the Surviving Sepsis Campaign one-hour bundle in a short
stay unit: A quality improvement project
Citation: Intensive & Critical Care Nursing; Apr 2021; vol. 63
Author(s): Gripp, Lauren; Raffoul, Melanie; Milner, Kerry A
Objective: To improve timely sepsis care by implementing the 2018 Surviving Sepsis
Campaign one-hour interventions.
Design: Ten-month prospective quality improvement project.
Setting: A 38-bed short stay unit within an 800-bed hospital in New York City.
Participants: Patients admitted to the short stay unit who screened positive for sepsis.
Intervention: A sepsis implementation tool was created from the 2018 Surviving Sepsis
Campaign guidelines. Sepsis champions delivered education on sepsis recognition,
treatment, and management, and the sepsis implementation tool to the healthcare staff.
Process and Outcome Measures: Time to first lactate, blood cultures × 2, antibiotic
administration, length of stay and mortality were tracked weekly for five months.
Results: From May 6, 2019 to October 1, 2019, 32 patients were diagnosed with sepsis.
Initial lactate and blood cultures were completed on every patient within 1one-hour of sepsis
9diagnosis. Administration of antibiotics within one-hour reached 100% after week four and
was sustained.
Conclusion: Use of a registered nurse-initiated sepsis implementation tool in a short stay
unit led to the completion of blood cultures, initial lactate, and antibiotic administration within
one-hour. Key factors to support this practice improvement were increasing registered nurse,
physician and physician assistant sepsis knowledge, registered nurse and
physician/physician assistant early collaboration, increased staffing and intravenous access
equipment.
Title: Improvement in Activities of Daily Living during a Nursing Home Stay and One-
Year Mortality among Older Adults with Sepsis.
Citation: Journal of the American Geriatrics Society; Apr 2021; vol. 69 (no. 4); p. 938-945
Author(s): Downer ; Pritchard, Kevin; Thomas, Kali S.; Ottenbacher, Kenneth
Background/Objective: To describe the recovery of activities of daily living (ADLs) during a
skilled nursing facility (SNF) stay and the association with 1-year mortality after SNF
discharge among Medicare beneficiaries treated in intensive care for sepsis. DESIGN
Retrospective cohort study.
Setting: Skilled nursing facilities in the United States.
Participants: Medicare fee-for-service beneficiaries admitted to an SNF within 3 days of
discharge from a hospitalization that included an intensive care unit (ICU) stay for sepsis
between January 1, 2013, and September 30, 2015 (N = 59,383).
Measurements: Data from the Minimum Data Set (MDS) were used to calculate a total
score for seven ADLs. Improvement was determined by comparing the total ADL scores
from the first and last MDS assessments of the SNF stay. Proportional hazard models were
used to estimate the association between improvement in ADL function and 1-year mortality
after SNF discharge.
Results: Approximately 58% of SNF residents had any improvement in ADL function.
Residents who had improvement in ADL function had 0.72 (95% confidence interval (CI) =
0.69–0.74) lower risk for mortality following SNF discharge than residents who did not
improve. Residents who improved 1–3 points (hazard ratio (HR) = 0.82, 95% CI = 0.79–
0.84) and four or more points (HR = 0.57, 95% CI = 0.55–0.60) in ADL function had
significantly lower mortality risk than residents who did not improve.
Conclusion: Older adults treated in an ICU with sepsis can improve in ADL function during
an SNF stay. This improvement is associated with lower 1-year mortality risk after SNF
discharge. These findings provide evidence that ADL recovery during an SNF stay is
associated with better health outcomes for older adults who have survived an ICU stay for
sepsis.
Title: Independent predictors for 90-day readmission of emergency department
patients admitted with sepsis: a prospective cohort study.
Citation: BMC Infectious Diseases; Apr 2021; vol. 21 (no. 1); p. 1-10
Author(s): Stenholt ; Abdullah, S. M. Osama Bin; Sørensen, Rune Husås; Nielsen, Finn
Erland
10Background: The primary objective of our study was to examine predictors for readmission
in a prospective cohort of sepsis patients admitted to an emergency department (ED) and
identified by the new Sepsis-3 criteria.
Method: A single-center observational population-based cohort study among all adult
(≥18 years) patients with sepsis admitted to the emergency department of Slagelse Hospital
during 1.10.2017–31.03.2018. Sepsis was defined as an increase in the sequential organ
failure assessment (SOFA) score of ≥2. The primary outcome was 90-day readmission. We
followed patients from the date of discharge from the index admission until the end of the
follow-up period or until the time of readmission to hospital, emigration or death, whichever
came first. We used competing-risks regression to estimate adjusted subhazard ratios
(aSHRs) with 95% confidence intervals (CI) for covariates in the regression models.
Results: A total of 2110 patients were admitted with infections, whereas 714 (33.8%)
suffered sepsis. A total of 52 patients had died during admission and were excluded leaving
662 patients (44.1% female) with a median age of 74.8 (interquartile range: 66.0–84.2) years
for further analysis. A total of 237 (35,8%; 95% CI 32.1–39.6) patients were readmitted
within 90 days, and 54(8.2%) had died after discharge without being readmitted. We found
that a history of malignant disease (aSHR 1,61; 1.16–2.23), if previously admitted with
sepsis within 1 year before the index admission (aSHR; 1.41; 1.08–1.84), and treatment with
diuretics (aSHR 1.51; 1.17–1.94) were independent predictors for readmission. aSHR (1.49,
1.13–1.96) for diuretic treatment was almost unchanged after exclusion of patients with heart
failure, while aSHR (1.47, 0.96–2.25) for malignant disease was slightly attenuated after
exclusion of patients with metastatic tumors.
Conclusions: More than one third of patients admitted with sepsis, and discharged alive,
were readmitted within 90 days. A history of malignant disease, if previously admitted with
sepsis, and diuretic treatment were independent predictors for 90-day readmission.
Title: Interleukin-27 as a Diagnostic Biomarker for Patients with Sepsis: A Meta-
Analysis.
Citation: BioMed Research International; Apr 2021 ; p. 1-7
Author(s): Wang ; Zhao, Jingyi; Yao, Yinhui; Zhao, Dan; Liu, Shiquan
Background: The present study was aimed to investigate the value of blood interleukin-27
(IL-27) as a diagnostic biomarker of sepsis.
Methods: We searched PubMed, EMBASE, the Cochrane Library, and the reference lists of
relevant articles. All studies published up to October 21, 2020, which evaluated the accuracy
of IL-27 levels for the diagnosis of sepsis were included. All the selected papers were
assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). We
used a bivariate random effects model to estimate sensitivity, specificity, diagnostic odds
ratios (DOR), and a summary receiver operating characteristic curve (SROC). Deeks' funnel
plot was used to illustrate the potential presence of publication bias.
Results: This meta-analysis included seven articles. The pooled sensitivity, specificity, and
DOR were 0.85 (95% CI, 0.72-0.93), 0.72 (95% CI, 0.42-0.90), and 15 (95% CI, 3-72),
respectively. The area under the summary receiver operating characteristic curve was 0.88
(95% CI, 0.84-0.90). The pooled I 2 statistic was 96.05 for the sensitivity and 96.65 for the
specificity in the heterogeneity analysis. Deeks' funnel plot indicated no publication bias in
this meta-analysis (P = 0.07).
Conclusions: The present results showed that IL-27 is a reliable diagnostic biomarker of
sepsis, but it should be investigated in combination with other clinical tests and results.
11Title: Machine learning methods to improve bedside fluid responsiveness prediction
in severe sepsis or septic shock: an observational study.
Citation: BJA: The British Journal of Anaesthesia; Apr 2021; vol. 126 (no. 4); p. 826-834
Author(s): Bataille ; de Selle, Jade; Moussot, Pierre-Etienne; Marty, Philippe; Silva, Stein;
Cocquet, Pierre
Title: Management of sepsis and septic shock in the emergency department.
Citation: Internal and emergency medicine; Apr 2021
Author(s): Gavelli, Francesco; Castello, Luigi Mario; Avanzi, Gian Carlo
Abstract: Early management of sepsis and septic shock is crucial for patients' prognosis. As
the Emergency Department (ED) is the place where the first medical contact for septic
patients is likely to occur, emergency physicians play an essential role in the early phases of
patient management, which consists of accurate initial diagnosis, resuscitation, and early
antibiotic treatment. Since the issuing of the Surviving Sepsis Campaign guidelines in 2016,
several studies have been published on different aspects of sepsis management, adding a
substantial amount of new information on the pathophysiology and treatment of sepsis and
septic shock. In light of this emerging evidence, the present narrative review provides a
comprehensive account of the recent advances in septic patient management in the ED.
Title: Metabolic responses in neonatal sepsis - a systematic review of human
metabolomic studies.
Citation: Acta paediatrica (Oslo, Norway : 1992); Apr 2021
Author(s): Bjerkhaug, Aline Uhirwa; Granslo, Hildegunn Norbakken; Klingenberg, Claus
Aim: To systematically review human metabolomic studies investigating metabolic
responses in septic neonates.
Methods: A systematic literature search was performed in the databases MEDLINE,
EMBASE and Cochrane library up to the 1st of January 2021. We included studies that
assessed neonatal sepsis and the following outcomes; (1) change in the metabolism
compared to healthy neonates and/or (2) metabolomics compared to traditional diagnostic
tools of neonatal sepsis. The screened abstracts were independently considered for
eligibility by two researchers.
Prospero ID: CRD42020164454.
Results: The search identified in total 762 articles. Fifteen articles were assessed for
eligibility. Four studies were included, with totally 78 neonates. The studies used different
diagnostic criteria and had between 1 and 16 sepsis cases. All studies with bacterial sepsis
found alterations in the glucose and lactate metabolism, reflecting possible redistribution of
glucose consumption from mitochondrial oxidative phosphorylation to the lactate and
pentose phosphate pathway. We also found signs of increased oxidative stress and fatty
acid oxidation in sepsis cases.
Conclusion: We found signs of metabolomic signatures in neonatal sepsis. This may lead
to better understanding of sepsis pathophysiology and detection of new candidate
biomarkers. Results should be validated in large-scale multicentre studies.
12Title: Micronutrients in Sepsis and COVID-19: A Narrative Review on What We Have
Learned and What We Want to Know in Future Trials.
Citation: Medicina (Kaunas, Lithuania); Apr 2021; vol. 57 (no. 5)
Author(s): Rossetti, Matteo; Martucci, Gennaro; Starchl, Christina; Amrein, Karin
Abstract: Sepsis remains the leading cause of mortality in hospitalized patients, contributing
to 1 in every 2-3 deaths. From a pathophysiological view, in the recent definition, sepsis has
been defined as the result of a complex interaction between host response and the infecting
organism, resulting in life-threatening organ dysfunction, depending on microcirculatory
derangement, cellular hypoxia/dysoxia driven by hypotension and, potentially, death. The
high energy expenditure driven by a high metabolic state induced by the host response may
rapidly lead to micronutrient depletion. This deficiency can result in alterations in normal
energy homeostasis, free radical damage, and immune system derangement. In critically ill
patients, micronutrients are still relegated to an ancillary role in the whole treatment, and
always put in a second-line place or, frequently, neglected. Only some micronutrients have
attracted the attention of a wider audience, and some trials, even large ones, have tested
their use, with controversial results. The present review will address this topic, including the
recent advancement in the study of vitamin D and protocols based on vitamin C and other
micronutrients, to explore an update in the setting of sepsis, gain some new insights
applicable to COVID-19 patients, and to contribute to a pathophysiological definition of the
potential role of micronutrients that will be helpful in future dedicated trials.
Title: Optimal combination of early biomarkers for infection and sepsis diagnosis in
the emergency department: The BIPS study.
Citation: Journal of Infection; Apr 2021; vol. 82 (no. 4); p. 11-21
Author(s): Velly ; Volant, Steven; Fitting, Catherine; Ghazali, Daniel Aiham; Salipante,
Florian; Mayaux, Julien; Monsel, Gentiane; Cavaillon, Jean-Marc; Hausfater, Pierre
Title: Outcomes of new-onset atrial fibrillation in patients with sepsis: A systematic
review and meta-analysis of 225,841 patients.
Citation: The American journal of emergency medicine; Apr 2021; vol. 42 ; p. 23-30
Author(s): Xiao, Fang-Ping; Chen, Ming-Yue; Wang, Lei; He, Hao; Jia, Zhi-Qiang; Kuai, Lin;
Zhou, Hai-Bo; Liu, Meng; Hong, Mei
Background: The outcomes of new-onset atrial fibrillation (AF) during sepsis are
inconsistent and inconclusive. This meta-analysis aims to provide a comprehensive
description of the impact of new-onset AF on the prognosis of sepsis.
Methods: Three electronic databases (PubMed, Embase, and the Cochrane Library) were
searched for relevant studies. Meta-analysis was performed using odds ratios (OR) and 95%
confidence intervals (CI) as effect measures.
Results: A total of 225,841 patients from 13 individual studies were incorporated to the
meta-analysis. The summary results revealed that new-onset AF during sepsis was
associated with increased odds of in-hospital mortality (pooled OR: 2.09; 95% CI: 1.53-2.86;
p < 001), post-discharge mortality (pooled OR: 2.44; 95% CI: 1.81-3.29; p < .001), and
stroke (pooled OR:1.88; 95% CI: 1.13-3.14; p < .05). Results also indicated that the
13incidence of new-onset AF varied from 1.9% for mild sepsis to 46.0% for septic shock.
Furthermore, compared to those without AF, people with new-onset AF had longer ICU and
hospital stays, as well as a higher recurrence of AF.
Conclusions: New-onset AF is frequently associated with adverse outcomes in patients
with sepsis. This is a clinical issue that warrants more attention and should be managed
appropriately to prevent poor prognosis.
Title: Physiological machine learning models for prediction of sepsis in hospitalized
adults: An integrative review.
Citation: Intensive & critical care nursing; Apr 2021 ; p. 103035
Author(s): Kausch, Sherry L; Moorman, J Randall; Lake, Douglas E; Keim-Malpass, Jessica
Background: Diagnosing sepsis remains challenging. Data compiled from continuous
monitoring and electronic health records allow for new opportunities to compute predictions
based on machine learning techniques. There has been a lack of consensus identifying best
practices for model development and validation towards early identification of sepsis.
Objective: To evaluate the modeling approach and statistical methodology of machine
learning prediction models for sepsis in the adult hospital population.
Methods: PubMed, CINAHL, and Cochrane databases were searched with the Preferred
Reporting Items for Systematic Reviews guided protocol development. We evaluated studies
that developed or validated physiologic sepsis prediction models or implemented a model in
the hospital environment.
Results: Fourteen studies met the inclusion criteria, and the AUROC of the prediction
models ranged from 0.61 to 0.96. We found a variety of sepsis definitions, methods used for
event adjudication, model parameters used, and modeling methods. Two studies tested
models in clinical settings; the results suggested that patient outcomes were improved with
implementation of machine learning models.
Conclusion: Nurses have a unique perspective to offer in the development and
implementation of machine learning models detecting patients at risk for sepsis. More work
is needed in developing model harmonization standards and testing in clinical settings.
Title: Post–Sepsis Syndrome
Citation: Critical Care Nursing Quarterly; 2021; vol. 44 (no. 2); p. 182
Author(s): Leviner Sherry
Abstract: Sepsis is both common and costly. Successful implementation of guidelines in the
acute care setting has decreased mortality and increased the number of sepsis survivors.
However, patients returning to the community continue to experience complications related
to sepsis and many are poorly prepared to manage these long-term complications. These
long-term complications are collectively referred to as post–sepsis syndrome. The purpose
of this review is to increase knowledge about post–sepsis syndrome and to compare post–
sepsis syndrome with post–intensive care unit syndrome.
14Title: Predictive value of geriatric-quickSOFA in hospitalized older people with sepsis. Citation: BMC Geriatrics; Apr 2021; vol. 21 (no. 1); p. 1-7 Author(s): Remelli ; Castellucci, Federico; Vitali, Aurora; Mattioli, Irene; Zurlo, Amedeo; Spadaro, Savino; Volpato, Stefano Title: Preventing sepsis; how can artificial intelligence inform the clinical decision- making process? A systematic review. Citation: International journal of medical informatics; Apr 2021; vol. 150 ; p. 104457 Author(s): Hassan, Nehal; Slight, Robert; Weiand, Daniel; Vellinga, Akke; Morgan, Graham; Aboushareb, Fathy; Slight, Sarah P Background and Objectives: Sepsis is a life-threatening condition that is associated with increased mortality. Artificial intelligence tools can inform clinical decision making by flagging patients at risk of developing infection and subsequent sepsis. This systematic review aims to identify the optimal set of predictors used to train machine learning algorithms to predict the likelihood of an infection and subsequent sepsis. Methods: This systematic review was registered in PROSPERO database (CRD42020158685). We conducted a systematic literature review across 3 large databases: Medline, Cumulative Index of Nursing and Allied Health Literature, and Embase. Quantitative primary research studies that focused on sepsis prediction associated with bacterial infection in adults in all care settings were eligible for inclusion. Results: Seventeen articles met our inclusion criteria. We identified 194 predictors that were used to train machine learning algorithms, with 13 predictors used on average across all included studies. The most prevalent predictors included age, gender, smoking, alcohol intake, heart rate, blood pressure, lactate level, cardiovascular disease, endocrine disease, cancer, chronic kidney disease (eGFR
production of reactive oxygen species (ROS), and disorder of calcium regulation have been
involved in SIMD. Mitophagy has potential role in protecting myocardial cells in sepsis,
especially in survivors.
Conclusion: In the current review, we focus on the role of mitochondrial dysfunction and
other mitochondria-related mechanisms including immunologic imbalance, energetic
reprogramming, mitophagy, and pyroptosis in the mechanisms of SIMD.
Title: Signs and symptoms of sepsis: raising awareness in the learning disability
community.
Citation: Learning Disability Practice; Apr 2021 ; p. 27-32
Author(s): Doherty ; Barksby, Justine; McCorkindale, Melissa
Abstract: In sepsis, prompt diagnosis and immediate treatment are vital to avoid
deterioration, organ failure and death. Sepsis is challenging to recognise because there is no
one single presenting sign and because it may initially present similarly to conditions such as
influenza, gastroenteritis or a chest infection. Sepsis has been shown to be an important
cause of mortality in people with learning disabilities, in whom recognising sepsis in a timely
manner presents its own challenges. Improving awareness of sepsis in the learning disability
community, including by providing easy-read information on this life-threatening condition, is
important to assist in reducing the number of avoidable deaths from sepsis among people
with learning disabilities. This article discusses sepsis in people with learning disabilities and
describes a leaflet developed as part of a student assignment at De Montfort University to
inform people with learning disabilities about sepsis.
Title: Skin and sepsis: contribution of dermatology to a rapid diagnosis.
Citation: Infection; Apr 2021
Author(s): Pulido-Pérez, A; Bergón-Sendín, M; Suárez-Fernández, R; Muñoz-Martín, P;
Bouza, E
Abstract: In patients who develop sepsis, whether due to primary, secondary or metastatic
lesions, the skin is frequently affected. However, there are unresolved aspects regarding the
general clinical manifestations in the skin or the prognosis and/or therapeutic implications.
The main challenge in the approach to sepsis is its early diagnosis and management. In this
review, we address the sepsis-skin relationship and the potential impact of early
dermatological intervention on the septic patient through ten basic questions. We found little
evidence of the participation of the dermatologist in sepsis alert programs. There are early
skin changes that may alert clinicians on a possible sepsis, such as skin mottling or
variations in acral skin temperature. In addition, the skin is an accessible and highly cost-
effective tissue for etiological studies of some forms of sepsis (e.g., meningococcal purpura)
and its involvement defines the prognosis of certain patients (e.g., infective endocarditis).
Title: The Surviving Sepsis Campaign: Fluid Resuscitation and Vasopressor Therapy
Research Priorities in Adult Patients.
Citation: Critical Care Medicine; Apr 2021; vol. 49 (no. 4); p. 623-635
16Author(s): Lat ; Coopersmith, Craig M.; De Backer, Daniel; Deutschman, Clifford S.; Evans,
Laura; Ferrer-Roca, Ricard; Hellman, Judith; Jog, Sameer; Kesecioglu, Jozef; Machado,
Flavia; Martin, Greg; Martin-Loeches, Ignacio; Nunnally, Mark E.; Rhodes, Andrew
Objective: To expand upon the priorities of fluid resuscitation and vasopressor therapy
research priorities identified by a group of experts assigned by the Society of Critical Care
Medicine and the European Society of Intensive Care Medicine.
Data Sources: Original paper and literature search.
Study Selection: Several members of the original task force with expertise specific to the
area of fluid resuscitation and vasopressor therapy.
Data Extraction: None.
Data Synthesis: None.
Conclusion: In the second of a series of manuscripts subsequent to the original paper,
members with expertise in the subjects expound upon the three identified priorities related to
fluid resuscitation and vasopressor therapies. This analysis summarizes what is known and
what were identified as ongoing and future research.
Title: The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease
2019 in Critical Illness.
Citation: Critical Care Medicine; Apr 2021; vol. 49 (no. 4); p. 598-622
Author(s): Coopersmith ; Antonelli, Massimo; Bauer, Seth R.; Deutschman, Clifford S.;
Evans, Laura E.; Ferrer, Ricard; Hellman, Judith; Jog, Sameer; Kesecioglu, Jozef; Kissoon,
Niranjan; Martin-Loeches, Ignacio; Nunnally, Mark E.; Prescott, Hallie C.; Rhodes, Andrew;
Talmor, Daniel; Tissieres, Pierre; De Backer, Daniel
Objectives: To identify research priorities in the management, pathophysiology, and host
response of coronavirus disease 2019 in critically ill patients.
Design: The Surviving Sepsis Research Committee, a multiprofessional group of 17
international experts representing the European Society of Intensive Care Medicine and
Society of Critical Care Medicine, was virtually convened during the coronavirus disease
2019 pandemic. The committee iteratively developed the recommendations and subsequent
document.
Methods: Each committee member submitted a list of what they believed were the most
important priorities for coronavirus disease 2019 research. The entire committee voted on 58
submitted questions to determine top priorities for coronavirus disease 2019 research.
Results: The Surviving Sepsis Research Committee provides 13 priorities for coronavirus
disease 2019. Of these, the top six priorities were identified and include the following
questions: 1) Should the approach to ventilator management differ from the standard
approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be
modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe
acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early
data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide
therapies?, 5) What is the role of prone positioning and noninvasive ventilation in
nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use
for viral load modulation and when should they be given?
Conclusions: Although knowledge of both biology and treatment has increased
exponentially in the first year of the coronavirus disease 2019 pandemic, significant
17knowledge gaps remain. The research priorities identified represent a roadmap for
investigation in coronavirus disease 2019.
Title: Trajectories of depression in sepsis survivors: an observational cohort study.
Citation: Critical Care; Apr 2021; vol. 25 (no. 1); p. 1-11
Author(s): Boede ; Gensichen, Jochen S.; Jackson, James C.; Eißler, Fiene; Lehmann,
Thomas; Schulz, Sven; Petersen, Juliana J.; Wolf, Florian P.; Dreischulte, Tobias; Schmidt,
Konrad F. R.
Background: Advances in critical care medicine have led to a growing number of critical
illness survivors. A considerable part of them suffers from long-term sequelae, also known
as post-intensive care syndrome. Among these, depressive symptoms are frequently
observed. Depressive symptom trajectories and associated factors of critical illness survivors
have rarely been investigated. Study objective was to explore and compare different
trajectories of depressive symptoms in sepsis survivors over 1 year after discharge from
ICU.
Methods: Data of a randomized controlled trial on long-term post-sepsis care were analyzed
post hoc. Depressive symptoms were collected at 1, 6 and 12 months post-ICU discharge
using the Major Depression Inventory (MDI), among others. Statistical analyses comprised
descriptive analysis, univariate and multivariate, linear and logistic regression models and
Growth Mixture Modeling.
Results: A total of 224 patients were included into this analysis. We identified three latent
classes of depressive symptom trajectories: Over the course of 1 year, 152 patients
recovered from mild symptoms, 27 patients showed severe persistent symptoms, and 45
patients recovered from severe symptoms. MDI sum scores significantly differed between
the three classes of depressive symptom trajectories at 1 and 6 months after ICU discharge
(p < 0.024 and p < 0.001, respectively). Compared with other classes, patients with the mild
recovered trajectory showed lower levels of chronic pain (median sum score of 43.3 vs.
60.0/53.3 on the Graded Chronic Pain Scale, p < 0.010) and posttraumatic stress (4.6% with
a sum score of ≥ 35 on the Posttraumatic Stress Scale 10 vs. 48.1%/33.3%, p < 0.003); and
higher levels of health-related quality of life (HRQOL) using the Short Form-36 scale within
1 month after ICU discharge (p < 0.035).
Conclusions: In the first year after discharge from ICU, sepsis survivors showed three
different trajectories of depressive symptoms. Course and severity of depressive symptoms
were associated with chronic pain, posttraumatic stress and reduced HRQOL at discharge
from ICU. Regular screening of sepsis survivors on symptoms of depression, chronic pain
and posttraumatic stress within 1 year after ICU may be considered.
Sources Used: The following databases are used in the creation of this bulletin: CINAHL,
EMBASE & Medline.
Disclaimer: The results of your literature search are based on the request that you made,
and consist of a list of references, some with abstracts. Royal United Hospital Bath
Healthcare Library will endeavour to use the best, most appropriate and most recent sources
available to it, but accepts no liability for the information retrieved, which is subject to the
content and accuracy of databases, and the limitations of the search process. The library
assumes no liability for the interpretation orapplication of these results, which are not
intended to provide advice or recommendations on patient care.
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