07/2017
Effect of extracorporeal cytokine removal on vascular barrier function in a septic shock patient.

David S1, Thamm K1, Schmidt BM1, Falk CS2, Kielstein JT1. 1 Department of Medicine, Division of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany. 2 Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany. J Intensive Care. 2017 Jan 21;5:12.

Summary:

This case study reports on a 32-year-old female patient with a 4-day history of fever, malaise, and cough who was found unconscious and hypoxic by the emergency team.

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Case presentation

  • The patient was successfully resuscitated and after initial treatment at a local hospital transferred to the authors institution for extracorporeal membrane oxygenation (ECMO) due to influenza pneumonia, which caused respiratory failure and severe ARDS
  • She also had an abscess of her left breast that grew Escherichia coli bacteria
  • Due to sepsis (peak CRP 222 mg/L; peak procalcitonin 81.2 μ g/L) and accompanying acute kidney injury (AKI), the patient required additional organ support by continuous veno-venous hemodialysis (CVVHD)
  • Sequential Organ Failure Assessment (SOFA) score was 18
  • The patient remained in refractory hypotension despite a broad anti-infective regimen, adequate fluid resuscitation, and high doses of inotropes and catecholamines
  • The severity of septic shock suggested an immense overwhelming host response assumingly accompanied by a notable cytokine storm such as that known from patients with toxic shock syndrome
  • Therefore, a CytoSorb adsorber was additionally installed into the CVVH circuit

Treatment

  • One treatment with CytoSorb for a total of 24 hours
  • CytoSorb was used in conjunction with CRRT performed in CVVHD mode

Measurements

  • Demand for catecholamines and hemodynamics
  • Cytokine, chemokine, and growth factor concentrations in serum (IL-1a, IL-6, IL-8, IL-9, IL-10, IL-13, FGF, GM-CSF, CXCL10 (IP-10), CCL2 (MCP-1), CCL4 (MIP-1b), PDGF-bb, RANTES, TNF-a, VEGF)
  • Creatinine, lactate
  • Removal of antibiotics
  • Stimulation of endothelial cells with plasma from healthy control and the septic shock patient (pre- and post CytoSorb therapy)
  • Transendothelial electrical resistance measurements to objectively quantify the functional permeability consequences of intercellular gaps

Results

  • Improved hemodynamic stability within the process of cytokine removal – after 24 h of treatment, the mean arterial pressure (MAP) could be maintained above 65 mmHg with markedly reduced need for vasopressors, even allowing the removal of excessive fluids by ultrafiltration
  • Noradrenalin doses could be reduced from 0.40 to 0.09 μg/kg/min after the 24 hour treatment (reduction to 0.11 μg/kg/min even within the first 12 hours)
  • During the course of the single treatment creatinine could be lowered from 242 to 70 μmol/L and lactate from 3.1 to 0.9 mmol/L
  • Significant removal of all cytokines and chemokines (except IL-13)
  • Pre- and post-CytoSorb drug levels of antibiotics yielded a marked reduction for meropenem and piperacillin and as well as a slight reduction for clindamycin
  • Treatment of endothelial cells challenged with serum from the septic patient pre CytoSorb treatment exhibited structural alterations with an increase in permeability, the cellular correlate for the clinical “ vascular leakage syndrome ”, while cells stimulated with serum from the same patient after CytoSorb treatment were comparable with cells from a healthy controls (in other words, the integrity of cell junctions was better preserved after CytoSorb)

Patient Follow-Up

  • Unfortunately, clinical and radiologic signs of severe hypoxic brain injury forced the authors to switch the therapeutic strategy to comfort care and the patient died the next dayfluid showed no malignant cells.

CONCLUSIONS

  • Extracorporeal cytokine removal using CytoSorb led to a stabilization of septic shock within hours
  • Due to the observed removal of antibiotics, the authors recommend thorough therapeutic drug monitoring in septic patients, as with the use of any other extracorporeal removal strategies
  • This is the first publication showing that a positive effect of CytoSorb on capillary integrity, and as a result, on microcirculation, can be assumed with a  high probability
  • There is no doubt that this report from a single patient is hypothesis generating in nature, so that a future systematic study is highly desirable