Can procalcitonin levels indicate the need for adjunctive therapies in sepsis?

Abstract

a b s t r a c tAfter decades of extensive experimental and clinical research, septic shock and the related multiple organ dysfunction still remain the leading cause of mortality in intensive care units (ICUs) worldwide. Defining sepsis is a difficult task, but what is even more challenging is differentiating infection-induced from non-infection-induced systemic inflammatory response-related multiple organ dysfunction. As conventional signs of infection are often unreliable in intensive care, biomarkers are used, of which one of the most frequently investigated is procalcitonin. Early stabilisation of vital functions via adequate supportive therapy and antibiotic treatment has resulted in substantial improvements in outcome over the last decades. However, there are certain patients who may need extra help, hence modulation of the immune system and the host's response may also be an important therapeutic approach in these situations. Polyclonal intravenous immunoglobulins have been used in critical care for decades. A relatively new potential approach could be attenuation of the overwhelming cytokine storm by specific cytokine adsorbents. Both interventions have been applied in daily practice on a large scale, with firm pathophysiological rationale but weak evidence supported by clinical trials. The purpose of this review is to give an overview on the pathophysiology of sepsis as well as the role and interpretation of biomarkers and their potential use in assisting adjunctive therapies in sepsis in the future.

Cytokine removal in human septic shock: Where are we and where are we going?

“…Detecting persistent ‘cytokine storm’—despite adequate resuscitation and source control—could be an alarming signal that cytokine removal may be beneficial. PCT as one of the most studied inflammatory biomarker in sepsis could be added as a biomarker to determine in which patient to start therapy [87, 88]. It is difficult to determine the absolute cutoff values above which treatment may be indicated, but there is some evidence, that PCT kinetics, i.e.…”

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study)

“…Subsets with a high mortality delta (defined as the difference between the percentage of patients who received trimodulin and died, and the percentage of patients who received placebo and died) were considered for further analyses (if the subsets were of sufficient size). Markers were selected taking into account the possible targeting of the inflammatory response or immunomodulatory capacity of trimodulin [ 23 ]. C-reactive protein (CRP) and IgM cutoff values were chosen to identify maximal differences between the trimodulin and placebo groups (Supplementary Figs.…”

The Use of CytoSorb Therapy in Critically Ill COVID-19 Patients: Review of the Rationale and Current Clinical Experiences

“…However, at the present time, there is no welldefined threshold for biomarkers to inform the start of CytoSorb therapy and it is unclear whether such thresholds will be established in the future since biomarker levels are affected by several factors and most importantly by the individual host response. is is similar to the huge scatter in inflammatory biomarker distribution in other disease states such as septic shock, ARDS, pancreatitis, or trauma where clear thresholds for diagnosis and treatment have also not been defined [67]. Nevertheless, it seems that relatively lower levels of inflammatory biomarkers in COVID-19 patients do not exclude the presence of cytokine storm; hence, patient selection remains a challenge in whom and when to commence cytokine adsorption as an adjuvant therapy.…”