Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care.

INTRODUCTION: Although many sepsis biomarkers have shown promise in selected patient groups, only C-reactive protein and procalcitonin (PCT) have entered clinical practice. The aim of this study was to evaluate three promising novel sepsis biomarkers in unselected patients at admission to intensive care. We assessed the performance of pancreatic stone protein (PSP), soluble CD25 (sCD25) and heparin binding protein (HBP) in distinguishing patients with sepsis from those with a non-infective systemic inflammatory response and the ability of these markers to indicate severity of illness. METHODS: Plasma levels of the biomarkers, PCT and selected inflammatory cytokines were measured in samples taken from 219 patients during the first six hours of admission to intensive or high dependency care. Patients with a systemic inflammatory response were categorized as having sepsis or a non-infective aetiology, with or without markers of severity, using standard diagnostic criteria. RESULTS: Both PSP and sCD25 performed well as biomarkers of sepsis irrespective of severity of illness. For both markers the area under the receiver operating curve (AUC) was greater than 0.9; PSP 0.927 (0.887 to 0.968) and sCD25 0.902 (0.854 to 0.949). Procalcitonin and IL6 also performed well as markers of sepsis whilst in this intensive care unit (ICU) population, HBP did not: PCT 0.840 (0.778 to 0.901), IL6 0.805 (0.739 to 0.870) and HBP 0.607 (0.519 to 0.694). Levels of both PSP and PCT reflected severity of illness and both markers performed well in differentiating patients with severe sepsis from severely ill patients with a non-infective systemic inflammatory response: AUCs 0.955 (0.909 to 1) and 0.837 (0.732 to 0.941) respectively. Although levels of sCD25 did not correlate with severity, the addition of sCD25 to either PCT or PSP in a multivariate model improved the diagnostic accuracy of either marker alone. CONCLUSIONS: PSP and sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the time of admission to intensive or high dependency care. These markers warrant further assessment of their prognostic value. Whereas previously published data indicate HBP has clinical utility in the emergency department, it did not perform well in an intensive-care population.

How I manage haematology patients with septic shock.

Patients with a variety of haematological conditions are at risk of infection and its most serious complication: septic shock. Mortality for septic shock remains high and especially so in patients with haematological malignancy and following bone marrow transplantation. However, advances in the treatment of severe sepsis have improved mortality rates even though evidence for the management of severe sepsis in haematology patients is limited. Wherever possible this review will concentrate on evidence directly applicable to haematology patients but inevitably will have to extrapolate evidence from other patient groups. The Surviving Sepsis Guidelines 2008 provide information on best practice in the management of patients with severe sepsis and septic shock and are broadly applicable though not specific to haematology patients. This review summarizes a practical approach to the management of severe sepsis in haematology patients and highlights areas of research which may bring new treatments in the future. The review is limited to the management and initial resuscitation of septic shock in adult haematology patients and will not address the detailed intensive care management of these patients or the management of severe sepsis in children.

Thrombotic risk in COVID-19: a case series and case-control study.

BACKGROUND: A possible association between COVID-19 infection and thrombosis, either as a direct consequence of the virus or as a complication of inflammation, is emerging in the literature. Data on the incidence of venous thromboembolism (VTE) are extremely limited. METHODS: We describe three cases of thromboembolism refractory to heparin treatment, the incidence of VTE in an inpatient cohort, and a case-control study to identify risk factors associated with VTE. RESULTS: We identified 274 confirmed (208) or probable (66) COVID-19 patients. 21 (7.7%) were diagnosed with VTE. D-dimer was elevated in both cases (confirmed VTE) and controls (no confirmed VTE) but higher levels were seen in confirmed VTE cases (4.1 vs 1.2 µg/mL, p<0.001). CONCLUSION: Incidence of VTE is high in patients hospitalised with COVID-19. Urgent clinical trials are needed to evaluate the role of anticoagulation in COVID-19. Monitoring of D-dimer and anti-factor Xa levels may be beneficial in guiding management.

Perioperative goal directed haemodynamic therapy--do it, bin it, or finally investigate it properly?

The literature concerning the use of goal directed haemodynamic therapy (GDHT) in high risk surgical patients has been importantly increased by the study of Lopes and colleagues. Using a minimally invasive assessment of fluid status and pulse pressure variation monitoring during mechanical ventilation, improvements were seen in post-operative complications, duration of mechanical ventilation, and length of hospital and intensive care unit (ICU) stay. Many small studies have shown improved outcome using various GDHT techniques but widespread implementation has not occurred. Those caring for perioperative patients need to accept the published evidence base or undertake a larger, multi-centre study.

Circulating Plasma microRNAs can differentiate Human Sepsis and Systemic Inflammatory Response Syndrome (SIRS).

Systemic inflammation in humans may be triggered by infection, termed sepsis, or non-infective processes, termed non-infective systemic inflammatory response syndrome (SIRS). MicroRNAs regulate cellular processes including inflammation and may be detected in blood. We aimed to establish definitive proof-of-principle that circulating microRNAs are differentially affected during sepsis and non-infective SIRS. Critically ill patients with severe (n = 21) or non-severe (n = 8) intra-abdominal sepsis; severe (n = 23) or non-severe (n = 21) non-infective SIRS; or no SIRS (n = 16) were studied. Next-generation sequencing and qRT-PCR were used to measure plasma microRNAs. Detectable blood miRNAs (n = 116) were generally up-regulated in SIRS compared to no-SIRS patients. Levels of these 'circulating inflammation-related microRNAs' (CIR-miRNAs) were 2.64 (IQR: 2.10-3.29) and 1.52 (IQR: 1.15-1.92) fold higher for non-infective SIRS and sepsis respectively (p < 0.0001), hence CIR-miRNAs appeared less abundant in sepsis than in SIRS. Six CIR-miRNAs (miR-30d-5p, miR-30a-5p, miR-192-5p, miR-26a-5p, miR-23a-5p, miR-191-5p) provided good-to-excellent discrimination of severe sepsis from severe SIRS (0.742-0.917 AUC of ROC curves). CIR-miRNA levels inversely correlated with pro-inflammatory cytokines (IL-1, IL-6 and others). Thus, among critically ill patients, sepsis and non-infective SIRS are associated with substantial, differential changes in CIR-miRNAs. CIR-miRNAs may be regulators of inflammation and warrant thorough evaluation as diagnostic and therapeutic targets.