CytoSorb, a novel therapeutic approach for patients
with septic shock: a case report
Burkhard Hinz1
, Oliver Jauch1
, Toralf Noky1
, Sigrun Friesecke2
, Peter Abel2
, Rolf Kaiser3
1Department of Anesthesiology and Intensive Care Medicine, KMG Clinic Güstrow, Güstrow - Germany
2Department of Internal Medicine and Intensive Care Medicine, University Medicine Greifswald, Greifswald - Germany
3Department of Internal Medicine and Intensive Care Medicine, KMG Clinic Güstrow, Güstrow - Germany
Abstract
Introduction: Hemoadsorption using CytoSorb has gained attention as a potential immunotherapy to control
systemic inflammation and sepsis. We report on a patient with septic shock, successfully treated with CytoSorb
therapy.
Methods: A 72-year-old male with periodically recurring infectious episodes was admitted with the suspicion
of urosepsis. In the following hours his hemodynamic situation deteriorated markedly, exhibiting respiratorymetabolic
acidosis, elevated inflammatory marker plasma levels, a severely disturbed coagulation, increased
retention parameters, liver dysfunction, and confirmation of bacteria and leucocytes in urine. After admission
to the ICU in a state of septic shock the patient received renal support with additional hemoadsorption using
CytoSorb. Three CytoSorb sessions were run during the following days.
Results: The first and consecutive second session resulted in a reduction of procalcitonin, C-reactive protein and
bilirubin and a markedly reduced need for vasopressors while hemodynamics improved significantly (i.e., cardiac
index, extravascular lung water). Due to a recurring inflammatory “second hit” episode, another session with
CytoSorb was run, resulting in a marked decrease in leukocytosis and liver (dys)function parameters.
Conclusions: The rapid hemodynamic stabilization with reduction of vasopressor needs within hours and reduction
of the capillary leakage as well as a quick reduction in infection markers were the main conclusions drawn
from the use of CytoSorb in this patient. Additionally, treatment appeared to be safe and was well tolerated.
Despite the promising results of CytoSorb application in this patient, further studies are necessary to elucidate to
what extent these favorable consequences are attributable to the adsorber itself.
Keywords: Sepsis, Septic shock, Hemoadsorption, CytoSorb, Cytokine adsorption
Introduction
Reducing the mortality of systemic inflammation and
sepsis as leading causes of death in critical care units worldwide
still remains one of the most significant unmet medical
needs of our day (1). Notwithstanding numerous approaches
removing one specific mediator to interfere with the uncontrolled,
self-destructive inflammatory response, and despite
promising preclinical data, none of the therapies tested to
date has been able to truly regain control over inflammation
and to improve outcomes. In recent years, blood purification
techniques have evolved toward a more broad-spectrum,
nonselective removal of inflammatory mediators (2). In this
context, hemoadsorption using CytoSorb has gained attention
as a potential immunotherapy to control inflammation.
It is the only specifically CE-approved therapy to effectively
reduce key cytokines from the blood of critically ill patients.
To date, this therapy has shown promising early results in
single cases of patients with infectious (sepsis) as well as noninfectious
(postcardiac surgery SIRS, pancreatitis) diseases,
which regularly result in cytokine storm, organ failure, and
ultimately death. In this paper we report on a patient with
septic shock who was successfully treated with CytoSorb
therapy. Approval of the Institutional Review Board (IRB)/
Ethics Committee was not required for this study; informed
consent was obtained from the patient’s relatives.
Case presentation
A 72-year-old male was admitted to our hospital via the
emergency department with suspicion of urosepsis. Previously,
the patient underwent prostate surgery and suffered
from urinary incontinence with recurrent bladder infections
because of a nonclosing urethral sphincter. Prior medical
history further included periodically recurring infectious
episodes treated with different antibiotics and several other
medications (ramipril, etericoxib, ciprofloxacin, clindamycin,
amoxicillin/clavulan acid, and a neurologic substance). On admission,
the patient exhibited an impaired general condition,
however he was awake, responsive, oriented, and cooperative.
The hemodynamic situation was hypotonic but stable,
without any need for catecholamines, while spontaneous
breathing was sufficient.
In the following hours, the patient’s hemodynamic situation
manifestly deteriorated, making the administration
of noradrenaline necessary. Blood gas analysis revealed a
combined respiratory-metabolic acidosis (pH 7.22, pCO2
49 mmHg, base excess 9.1 mmol/l). Laboratory parameters
indicated elevated inflammatory marker plasma levels
(PCT>200 ng/ml, leucocytes 12.600/µl, neutrophils 970/µl,
CRP 92.7 mg/l), a severely disturbed coagulation (thrombocytes
72.000/µl, Quick 55%, PTT 40 s), increased retention
parameters (creatinine 297 µmol/l, urea 13.5 mmol/l), liver
dysfunction (ASAT 3.43 µmol/l, ALAT 3.15 µmol/l, bilirubin
42.5 µmol/l) as well as a proof of bacteria and leucocytes
in the patient’s urine. Body temperature was 36.5°C. Due to
the progressive hemodynamic instability and a gradual deterioration
of his general condition, the patient was admitted
to our interdisciplinary ICU. When he came under our
charge, the patient was already in septic shock with increasing
need for fluids (cumulative +17.400 ml during the first
2 days) and catecholamines (NE up to 0.8 µg/kg*min). Therefore,
an advanced hemodynamic monitoring system (PiCCO;
Pulsion Medical Systems, Feldkirchen, Germany) was applied.
The patient was treated according to the sepsis bundle
guidelines, including administration of hydrocortisone
dosages (100 mg/day on days 2-4; 25 mg/day on day 5).
Blood cultures verified the existence of only Proteus mirabilis,
however, a focus of infection could not be identified over
the entire course of the treatment at our hospital, despite
microbiologic and radiologic diagnostics.
Due to a further increase in retention parameters and decreasing
spontaneous diuresis despite the application of furosemide,
the patient received continuous renal replacement
therapy (Multifiltrate; Fresenius, Bad Homburg, Germany) for
the following 13 days. Criteria for acute kidney failure according
to RIFLE were met, with creatinine of 324 µmol/l (>1.5×),
GFR of 17 ml/min per m² (decrease >25% ) and a urine output
<0.3 ml/kg/h × 24 h.
Due to massive volume overload and an increase of extravascular
lung water index of 18.5 ml/kg per m² (normal range
3-7 ml/kg per m²), ultrafiltration was attempted and was successfully
established at 250 ml/h in order to reduce the positive
fluid balance. This was also supported by a progressive
improvement in the patient’s hemodynamic situation and a
simultaneous reduction of vasopressor dosage at this time.
As inflammatory markers remained high, the decision was
made to additionally install a CytoSorb hemoadsorption column
(CytoSorbents, Monmouth Junction, NJ, USA) into the
CVVHD circuit. The CytoSorb adsorber was placed in predialyzer
position. Blood flow rate was kept at 180 ml/min and
anticoagulation was achieved using heparin, targeting a partial
thromboplastin time (PTT) of 60 s to 80 s, controlled every
8 h. Three CytoSorb sessions were run during the following
days (first session 24 h, immediately followed by a second
session of 6 h, third session was 5 days later for 24 h).
The first and consecutive second sessions resulted in a drop
in PCT, C-reactive protein, and bilirubin (Tab. I). Mean arterial
pressure stabilized and the need for norepinephrine was reduced
from 0.8 µg/kg*min down to 0.13 µg/kg*min. It was
tapered out 48 h after termination of the second treatment.
Likewise, dobutamine infusion (10 mg/h) was stopped straight
after the second treatment. Hemodynamics improved significantly
with a cardiac index increasing from 3.22 l/min per m2
before the first treatment to 4.5 l/min per m2
after the second
treatment. Extravascular lung water as a measure of capillary
leak improved from 18.5 ml/kg to 7.8 ml/kg in the course of the
2 treatments (Fig. 1). Values for noradrenaline dosage, fluid
balance, and corresponding ultrafiltration rates throughout
the two treatments are depicted in (Tab. II). Notably, albumin
levels measured before and during both CytoSorb treatments
did not change, suggesting that albumin was not removed by
hemoadsorption using CytoSorb. After the second CytoSorb
session, hemoadsorption was paused for 5 days while the patient
received standard care treatment. Importantly, the second
session had to be terminated prematurely because of a
complete clotting of the CRRT filter and the CytoSorb adsorber.
Due to a recurring inflammatory “second hit” episode with
increasing infection markers, another session with CytoSorb
was run for 24 h, resulting in a marked decrease in leukocytosis,
CRP, and liver (dys)function parameters (ALT, AST, bilirubin).
During the entire treatment periods the patient received daptomycin
(10 mg/kg), clarithromycin (2 × 250 mg) and ceftazidim
(3 × 2 g) intravenously with no adaptation of dose at any
time.
After regaining clinical stability, the patient was transferred
to the University Hospital of Greifswald, Germany. The
transfer to Greifswald seemed reasonable due to their more
advanced diagnostic testing methods for the as-yet unsuccessful
focus search and because of their experience in the
use of CytoSorb hemoadsorption, in the event the patient
went on to develop further complications. Diagnostic testing
revealed a spondylodiscitis and the focus was surgically eradicated.
Probably due to the long previous antimicrobial therapy,
no underlying germ could be detected. During the next
days, organ functions and inflammatory status improved further,
accompanied by a considerable improvement in the patient’s
general condition. After discharge, the patient showed
no further infectious episodes during the follow-up period.
Conclusions
Sepsis syndromes represent the prototypical, most devastating
examples of uncontrolled inflammation, yet therapeutic
options remain sparse. In this patient with recurring
infectious episodes of unknown origin, eventually culminating
in a picture of full-blown septic shock, CytoSorb therapy
appeared to contribute to regaining control over the patient’s
inflammatory response. The rapid hemodynamic stabilization
with a reduction in vasopressor needs within hours and a reduction
in the capillary leakage as well as a quick reduction in
infection markers were the main conclusions drawn from the
use of CytoSorb in this particular patient. Additionally, treatment
appeared to be safe and was well tolerated.
Although cytokine levels were not measured in this patient,
the clinical course does suggest that CytoSorb had a considerable
effect on his inflammatory response and quite probably
on clinical improvement. In this context, the Cytosorb hemoadsorber
has been shown to remove various proinflammatory
as well as antiinflammatory cytokines in vitro and in animal
models of sepsis (3, 4). Furthermore, recent data derived from
case reports hint at clinical improvements in hemodynamics,
organ recovery, and suggest that clinical stabilization may
occur faster (5-9).
However, even though clinical experience from this patient
appears promising, it is hardly possible to make a valid statement
on the basis of a single case as to whether the effects
seen in this patient were a primary therapy effect of CytoSorb
or the consequence of an overall clinical improvement.
Therefore, further studies are necessary to elucidate to
what extent these favorable consequences are attributable
to the adsorber itself.
Disclosures
Financial support: There was no financial support for this study.
Conflict of interest: None of the authors have any conflicts of
interest associated with this report.
