Table 1.
Treatable traits in septic patients.
| Treatable Trait | Description | Biomarker | Treatment |
|---|---|---|---|
| Hyperinflammatory phenotype | High endotoxemic phenotype | EAA 0.6 – 0.9 | Endotoxin HA devices (e.g.: Toraymixin ®) |
| High cytokine phenotype | IL-6 plasmatic concentration, (however there is still no threshold plasma cytokine level used for beginning or closure of therapy) | Cytokine HA devices (e.g.: Cytosorb ®) | |
| High EAA and high cytokine phenotype | Same tresholds as above |
Sequential HA Endotoxin HA with PMX, Toraymixin ®, and subsequent cytokine HA with Cytosorb® has been applied in highly selected patients. Sequential HA is intended to remove the primary stimulus that induces the dysregulated inflammatory response. |
|
| Macrophage activation-like syndrome (MALS) | Ferritin > 4,420 ng/mL | Anti-IL1 (Anakinra) Anti-TNFα |
|
| Hypoinflammatory phenotype | Hypogammaglobulinemia | IgG < 500 mg/dL or 2 standard deviations below reference values for age IgM < 35mg/dl |
Polivalent IVIG IgM and IgA-enriched polyclonal IVIG dose of 250 mg/kg/d by a 10-h infusion, for 3 consecutive days |
| Immunoparalysis T-cell exhaustion syndrome |
HLA-DR expression in circulating monocytes <5,000 antibodies bound/cell Ferritin < 4,420 ng/mL |
rhIFNγ Monoclonal antibodies (Nivolumab) |
|
| Catecholamine resistant hypotension (CRH) | Defined as a decreased vascular responsiveness to catecholamine independently of the administered NE dose (5) | Isolated NE > 0.5 μg/kg/min for a minimum of 6 h, to maintain a MAP between 55–70 mmHg. | 1) Corticosteroids [Hydrocortisone (200 mg/day)] 2) Vasopressin (VP) infusion and titration 3) Metabolic resuscitation [Ascorbic acid 1,500 mg/6h (15 doses) plus Thiamine 200 mg/12h] |
| CED*> 0.25 μg/kg/min and high Renin plasmatic concentrations (n.v. = 2.13–58.78 pg/ml) | Angiotensin-II (AT-II) infusion and titration | ||
| Low-Flow phenotype | Patients with septic cardiomyopathy exhibiting signs of inadequate perfusion despite the administration and titration of vasoactive drugs (Dobutamine) and receiving supportive treatment guided to other phenotypes. | Lactate plasmatic concentrations and ΔLactate SvcO2 < 70 mmHg ΔAvCO2 > 6mmHg Echocardiographic parameters of cardiac dysfunction, mainly biventricular failure |
Veno-arterial ECMO |
| Endothelial dysfunction | Endothelial cells amplify the immune response and activate the coagulation system. They are both a target and source of inflammation and serve as a link between local and systemic immune responses. | BioADM (>108 pg/mL) MR-proADM (decline in blood plasma concentration to 1.65 nmol/L within 48 h of admission) sTREM-1 (>532 pg/mL) |
Adrecizumab Future research (high-dose Nangibotide) |
AT-II, angiotensin II; BioADM, circulating bioactive adrenomedullin; CED, catecholamine equivalent dose; CRH, catecholamine resistant hypotension; E, epinephrine; EAA, endotoxin activity assay; ECMO, extracorporeal membrane oxygenation; HA, hemoadsorption IL. IL; Ig, immunogloblulin; IVIG, intravenous immunoglobulin; MALS, macrophage activation-like syndrome; MAP, median arterial pressure; MR-proADM, mid-region proadrenmedullin; NE, norepinephrine; n.v., normal values; PMX, polimyxin; rhIFNγ, recombinant human inferteron-gamma; Soluble Triggering Receptor Expressed on Myeloid Cells 1 (sTREM-1); VP, vasopressin. *CED (catecholamine equivalent dose); E = NE = 0.1 μg/kg/min; VP 0.04 U/min = NE 0.1 μg/kg/min.