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Essential trace elements and micronutrients are critical in eliciting an effective immune response to combat sepsis, with selenium being particularly noteworthy. The objective of this investigation is to analyze and the levels of serum selenium in neonates within sepsis and control groups.
Methodology:
In 2023, a case–control study was carried out involving 66 hospitalized infants – 33 diagnosed with sepsis forming the case group and 33 free from sepsis constituting the control group – along with their mothers, at Children’s and Shariati Hospitals in Bandar Abbas. The serum selenium concentrations (expressed in micrograms per deciliter) were quantified utilizing atomic absorption spectrometry. Subsequently, the data were processed and analyzed using IBM SPSS statistical software, version 22.
Results:
The average serum selenium level in neonates with sepsis (42.06 ± 20.40 µg/dL) was notably lower compared to the control group (55.61 ± 20.33 µg/dL), a difference that was statistically significant (p-value = 0.009). The levels of serum selenium were comparable between neonates and mothers across both study groups.
Conclusion:
The findings of this research indicate that selenium levels in the sepsis group were reduced compared to the control group, despite similar selenium levels in the mothers and neonates in both groups, suggesting that sepsis could be associated with a decrease in selenium levels.
Organ dysfunction often occurs in the perioperative setting and in sepsis. Alterations in systemic hemodynamics may play a role, but even when these are within therapeutic goals, organ dysfunction may still occur. Microcirculatory alterations, a key determinant of tissue perfusion and of mitochondrial dysfunction, may play a role in the development of organ dysfunction. In this chapter, we discuss the evidence for alterations in microcirculatory and mitochondrial functions and their relevance, in circulatory failure and in the perioperative setting.
Infections cause direct maternal morbidity and remain a leading cause of maternal morbidity in the United States and globally. In this chapter, we will discuss the physiologic considerations of infectious diseases in pregnancy, alterations in pregnancy response to infections, changes in immune cell populations, and fetal immune response. Pregnancy is a state of relative immunosuppression order for the maternal “host” to not reject fetus and this immunosuppression has consequences in the setting of infectious illness. The pathophysiology, epidemiology, obstetric management, antibiotic therapy, and anesthetic management of the most frequent bacterial and viral infections in the obstetric patient including chorioamnionitis, sepsis, human immunodeficiency virus (HIV), group A streptococcus, and TORCH infections. Additionally, we will present the obstetric and anesthetic management of uncommon bacterial, viral, and parasitic infections. This chapter provides nuanced understanding of peripartum immunologic physiology, an overview of common obstetrical infections, and a quick resource for uncommon as well as tropical infections, such as tuberculosis and malaria as they relate to pregnancy for obstetrics anesthesia providers. Management pearls included in this chapter can improve maternal and fetal outcomes for pregnant patients with infections illnesses.
Sepsis is currently defined as life-threatening organ dysfunction caused by dysregulated host response to infection. Septic shock is sepsis with persistent hypotension requiring vasopressor to maintain mean arterial pressure (MAP) ≥ 65 mmHg and having a serum lactate > 2 mmol/dL despite adequate fluid resuscitation.
There is wide variation in test characteristics for screening scores such as systemic inflammatory response syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA), National Early Warning Score (NEWS) and Modified Early Warning Score (MEWS). A qSOFA score of ≥ 2 or a change in SOFA score of ≥ 2 can promptly identify these patients; however, qSOFA is not recommended as a single screening tool over comparable scores such as SIRS, NEWS, or MEWS.
Shock is a pathological state resulting from inadequate delivery, increased demand or poor utilization of metabolic substrates (i.e., oxygen and glucose), which leads to cellular dysfunction and cell death. This then leads to progressive acidosis, endothelial dysfunction and inflammatory cascade that results in end-organ injury. Early in the course of shock, compensatory mechanisms may attempt to augment cardiac output (CO) and/or systemic vascular resistance (SVR) in an effort to improve tissue perfusion. Without treatment, those compensatory mechanisms are overwhelmed, leading to decompensated shock, multiorgan failure (MOF) and death.
This study aimed to determine the impact of current hepatitis B virus (HBV) infection on patients hospitalised with sepsis. This was a retrospective cohort study. Patients from three medical centres in Suzhou from 10 January 2016 to 23 July 2022 participated in this study. Demographic characteristics and clinical characteristics were collected. A total of 945 adult patients with sepsis were included. The median age was 66.0 years, 68.6% were male, 13.1% presented with current HBV infection, and 34.9% of all patients died. In the multivariable-adjusted Cox model, patients with current HBV infection had significantly higher mortality than those without (hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.11–2.02). A subgroup analysis showed that being infected with HBV significantly increased in-hospital mortality in patients younger than 65 years old (HR 1.74, 95% CI 1.16–2.63), whereas no significant impact was observed in patients ≥65 years. The propensity score-matched case–control analysis showed that the rate of septic shock (91.4% vs. 62.1%, P < 0.001) and in-hospital mortality (48.3% vs. 35.3%, P = 0.045) were much higher in the propensity score-matched HBV infection group compared with the control group. In conclusion, current HBV infection was associated with mortality in adults with sepsis.
The early recognition of patients with sepsis is difficult and the initial assessment outside of hospitals is challenging for ambulance clinicians (ACs). Indicators that ACs can use to recognize sepsis early are beneficial for patient outcomes. Research suggests that elevated point-of-care (POC) plasma glucose and serum lactate levels may help to predict sepsis in the ambulance service (AS) setting.
Study Objective:
The aim of this study was to test the hypothesis that the elevation of POC plasma glucose and serum lactate levels may help to predict Sepsis-3 in the AS.
Methods:
A prospective observational study was performed in the AS setting of Gothenburg in Sweden from the beginning of March 2018 through the end of September 2019. The criteria for sampling POC plasma glucose and serum lactate levels in the AS setting were high or intermediate risk according to the Rapid Emergency Triage and Treatment System (RETTS), as red, orange, yellow, and green if the respiratory rate was >22 breaths/minutes. Sepsis-3 were identified retrospectively. A primary and secondary analyses were carried out. The primary analysis included patients cared for in the AS and emergency department (ED) and were hospitalized. In the secondary analysis, patients who were only cared for in the AS and ED without being hospitalized were also included. To evaluate the predictive ability of these biomarkers, the area under the curve (AUC), sensitivity, specificity, and predictive values were used.
Results:
A total of 1,057 patients were included in the primary analysis and 1,841 patients were included in the secondary analysis. In total, 253 patients met the Sepsis-3 criteria (in both analyses). The AUC for POC plasma glucose and serum lactate levels showed low accuracy in predicting Sepsis-3 in both the primary and secondary analyses. Among all hospitalized patients, regardless of Sepsis-3, more than two-thirds had elevated plasma glucose and nearly one-half had elevated serum lactate when measured in the AS.
Conclusions:
As individual biomarkers, an elevated POC plasma glucose and serum lactate were not associated with an increased likelihood of Sepsis-3 when measured in the AS in this study. However, the high rate of elevation of these biomarkers before arrival in hospital highlights that their role in clinical decision making at this early stage needs further evaluation, including other endpoints than Sepsis-3.
Sepsis is a clinical syndrome characterised by a severe disorder of pathophysiology caused by infection of pathogenic micro-organisms. The addition of antioxidant micronutrient therapies such as thiamine to sepsis treatment remains controversial. This study explored the effect of thiamine on the prognosis of patients with sepsis. This study was a retrospective study involving patients with sepsis from the Medical Information Mart for Intensive Care IV. Patients were divided into two groups, the thiamine received group (TR) and the thiamine unreceived group (TUR), according to whether they were supplemented with thiamin via intravenous while in the intensive care unit (ICU). The primary outcome was ICU mortality. The association between thiamine and outcome was analysed using the Cox proportional hazards regression model, propensity score matching (PSM), generalised boosted model-based inverse probability of treatment weighting (IPTW) and doubly robust estimation. A total of 11 553 sepsis patients were enrolled in this study. After controlling for potential confounders using Cox regression models, the TR group had a statistically significantly lower ICU mortality risk than the TUR group. The hazard ratio of ICU mortality for the TR group was 0·80 (95 % CI 0·70, 0·93). We obtained the same results after using PSM, IPTW and doubly robust estimation. Supplementation with thiamine has a beneficial effect on the prognosis of patients with sepsis. More randomised controlled trials are needed to confirm the effectiveness of thiamine supplementation in the treatment of sepsis.
Sepsis is a complex clinical syndrome triggered by an inflammatory host response to an infection. It is usually complicated to detect and diagnose, and has severe consequences in human and veterinary health, especially when treatment is not started early. Therefore, efforts to detect sepsis accurately are needed. In addition, its proper diagnosis could reduce the misuse of antibiotics, which is essential fighting against antimicrobial resistance. This case is a particular issue in farm animals, as antibiotics have been traditionally given massively, but now they are becoming increasingly restricted. When sepsis is suspected in animals, the most frequently used biomarkers are acute phase proteins such as C-reactive protein, serum amyloid A and haptoglobin, but their concentrations can increase in other inflammatory conditions. In human patients, the most promising biomarkers to detect sepsis are currently procalcitonin and presepsin, and there is a wide range of other biomarkers under study. However, there is little information on the application of these biomarkers in veterinary species. This review aims to describe the general concepts of sepsis and the current knowledge about the biomarkers of sepsis in pigs, horses, and cattle and to discuss possible advances in the field.
A 25-year-old female last menstrual period approximately eight weeks ago presents to the emergency department with fever and pelvic pain. She is a recent immigrant without health insurance who sought care for a termination of pregnancy from an unknown provider. She took several pills seven days ago and had subsequent heavy bleeding and cramping. She has continued bleeding and worsening cramping. She describes subjective fever for the last 24 hours. She has not obtained pain relief with acetaminophen. She feels light-headed and has not eaten today due to nausea. She denies vomiting, diarrhea, or any urinary symptoms. She is sexually active with one partner for the last six months. Her gynecologic history is significant for one full-term vaginal delivery and a history of chlamydia. She has no significant past medical or surgical history and has no known drug allergies.
1. The hypothalamic–pituitary–adrenal axis plays a key role in the stress response to critical illness.
2. Critical illness-related corticosteroid insufficiency (CIRCI) is thought to occur when this response is inadequate to the severity of the metabolic stress encountered.
3. CIRCI should be distinguished from other forms of primary hypoadrenalism encountered in critical care.
4. There is currently no agreed definition nor diagnostic criteria for diagnosing CIRCI.
5. Supplemental corticosteroids should be considered for those patients thought to have CIRCI, with refractory hypotension in the context of sepsis, despite conflicting evidence of any benefit in clinical trials.
Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown.
Methods:
We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health record review. The 48 unique criteria were rated by anonymous electronic survey tools, and the results were fed back to the expert panel participants. Consensus was achieved to either retain or remove each criterion.
Results:
After 3 rounds, 22 unique criteria remained as part of the opt-out safety checklist. These criteria included high-risk comorbidities, signs of severe illness, lack of cultures during sepsis work-up or antibiotic use prior to blood cultures, or ongoing signs and symptoms of infection.
Conclusions:
The modified Delphi approach is a useful method to achieve expert-level consensus in the absence of evidence suifficient to provide validated guidance. The Delphi approach allowed for flexibility in development of an opt-out trial protocol for sepsis antibiotic de-escalation. The utility of this protocol should be evaluated in a randomized controlled trial.
Our study was conducted to assess the sepsis-associated hospitalisations and antimicrobials prescribed for sepsis inpatients in Hong Kong. Demographic, diagnostic and antimicrobial prescription data were analysed for patients admitted to public hospitals with a diagnosis of septicaemia from 2000 to 2015. A total of 223 250 sepsis hospitalisations were recorded in Hong Kong from 2000 to 2015 during which the hospitalisation rate increased by 85.6%. The majority of the sepsis hospitalisations occurred in adults ≥65 years and children aged 0–4 years. Adults with a secondary diagnosis of sepsis were often admitted with a primary diagnosis of urological conditions or pneumonia; whereas diabetes mellitus was the most common secondary diagnosis among those with primary sepsis. Paediatric sepsis patients aged 0–4 years were often diagnosed with disorders relating to short gestation and low birthweight. Antimicrobial prescriptions increased by 51.1% and 34.4% for primary and secondary sepsis patients, respectively. β-Lactam and β-lactamase inhibitor combinations were the most used antibiotics whereas the usage of carbapenems increased more than 10 times over the study period. A substantial burden of hospitalisations was attributable to sepsis in Hong Kong, particularly in the extremes of age. Broad-spectrum and last-resort antibiotics had been increasingly dispensed for sepsis inpatients.
Although abundant evidence exists that adverse events during pregnancy lead to chronic conditions, there is limited information on the impact of acute insults such as sepsis. This study tested the hypothesis that impaired fetal development leads to altered organ responses to a septic insult in both male and female adult offspring. Fetal growth restricted (FGR) rats were generated using a maternal protein-restricted diet. Male and female FGR and control diet rats were housed until 150–160 d of age when they were exposed either a saline (control) or a fecal slurry intraperitoneal (Sepsis) injection. After 6 h, livers and lungs were analyzed for inflammation and, additionally, the amounts and function of pulmonary surfactant were measured. The results showed increases in the steady-state mRNA levels of inflammatory cytokines in the liver in response to the septic insult in both males and females; these responses were not different between FGR and control diet groups. In the lungs, cytokines were not detectable in any of the experimental groups. A significant decrease in the relative amount of surfactant was observed in male FGR offspring, but this was not observed in control males or in female animals. Overall, it is concluded that FGR induced by maternal protein restriction does not impact liver and lung inflammatory response to sepsis in either male or female adult rats. An altered septic response in male FGR offspring with respect to surfactant may imply a contribution to lung dysfunction.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
Prognosis and disposition among older emergency department (ED) patients with suspected infection remains challenging. Frailty is increasingly recognized as a predictor of poor prognosis among critically ill patients; however, its association with clinical outcomes among older ED patients with suspected infection is unknown.
Methods
We conducted a multicenter prospective cohort study at two tertiary care EDs. We included older ED patients (≥75 years) with suspected infection. Frailty at baseline (before index illness) was explicitly measured for all patients by the treating physicians using the Clinical Frailty Scale (CFS). We defined frailty as a CFS 5–8. The primary outcome was 30-day mortality. We used multivariable logistic regression to adjust for known confounders. We also compared the prognostic accuracy of frailty with the Systemic Inflammatory Response Syndrome (SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) criteria.
Results
We enrolled 203 patients, of whom 117 (57.6%) were frail. Frail patients were more likely to develop septic shock (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.08–2.51) and more likely to die within 30 days of ED presentation (aOR 2.05; 95% CI, 1.02–5.24). Sensitivity for mortality was highest among the CFS (73.1%; 95% CI, 52.2–88.4), compared with SIRS ≥ 2 (65.4%; 95% CI, 44.3–82.8) or qSOFA ≥ 2 (38.4; 95% CI, 20.2–59.4).
Conclusions
Frailty is a highly prevalent prognostic factor that can be used to risk-stratify older ED patients with suspected infection. ED clinicians should consider screening for frailty to optimize disposition in this population.