Continuous Hemodiafiltration with a Cytokine-Adsorber During Sepsis

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Continuous Hemodiafiltration with a Cytokine-Adsorber During Sepsis Department of Plastic and Hand Surgery, Burn Unit, Bergmannstrost Halle, Germany Director: Professor Frank Siemers Khosrow Houschyar, MD 19.04.17

Disclosure Speaker contract with CytoSorbents Europe 2

Introduction Sepsis is a well-recognized worldwide healthcare issue, ultimately resulting in significant mortality, morbidity and resource utilization during and after critical illness Although mortality related to severe sepsis and septic shock have reduced slightly in the past decade, it remains more than 20% 3

Causes of Sepsis Bacterial infections are the most common cause of sepsis, but sepsis can also be caused by fungal, parasitic, or viral infections The infection can originate from anywhere in the body 4

Causes of Sepsis 5

Risk factors for developing sepsis Elderly Newborn Chronic illnesses such as Diabetic, cancer Immunocompromised such as after organ transplant, Splenectomy or those with HIV or AIDS Patients receiving immunosuppresive therapy such as chemotherapy Malnourished Debilitated patients 6

Systemic Inflammatory Response Syndrome 7

CytoSorb- Adsorber 1. Extracorporeal cytokine adsorber, approved in the European Union and broadly indicated for use in any clinical situation where cytokines are elevated 2. Represents a potentially major advance in the control of deadly inflammation in critically-ill patients and those undergoing complex cardiac surgery 8

CytoSorb-Adsorber 9

CytoSorb-Adsorber 10

Case Study 1 Admission of a 72-year-old patient on March 19, 2016: Scalding during cooking Diagnosis: 2a-2b gradual scalding of 8% body surface Affected areas: Thorax on the right, back, thigh on both sides, Buttocks on both sides, right foot, lower left leg 11

Secondary diagnoses - Parkinson's disease of the akinetically-rigid type stage III with dysarthrophonia - Omarthrosis on both sides - Coronary heart disease 12

Operations Day 2: Tangential debridement of the left thigh grafted with split skin graft Day 5: Puncture tracheotomy 13

Course of IL-6 ng/l 300 250 200 150 100 50 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 14

Course of IL-10 pg/ml 60 50 40 30 20 10 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 15

Case Study 2 Admission of a 47-year-old patient on March 11, 2014: Pneumococcal sepsis with intravascular coagulation Diagnosis: Waterhouse Friderichsen syndrome after dental treatment in pneumococcal sepsis Condition after splenectomy after two-time splenic rupture after traffic accident 1989 Affected areas: Both feet and lower legs, right hand Khosrow Houschyar 19.04.17 16

History diagnostics - Catecholamine-compulsorily circulatory insufficiency - Pneumonia (3 MRGN Pseudomonas) - Transfusion-related anemia and thrombocytopenia in disseminated intravascular coagulation - Herpes Simplex Infection 17

Operations Day 7: Amputation in the area of both lower limbs in the middle third with septic microembolism of both feet and lower limbs Day 10: Debridement in the area of the right lower limb Day 20: Revision of both stumps and defect cover with split-thickness skin graft, amputation of the right thumb 18

Operations Day 28: Debridement of the right hand and secondary closure Day 35: Debridement, residual defect cover on both lower limb stumps with split-thickness skin graft 19

Course of IL-6 ng/l 500 450 400 350 300 250 200 150 100 50 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 20

Course of IL-10 120 pg/m 100 80 60 40 20 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 21

Case Study 3 Admission of a 21-year-old patient on 06.03.2014, 0.30 am: Apartment fire with explosion Diagnosis: 2b-3 graded burn of 60% body surface Affected areas: Arms on both sides, face, thorax, back, thigh on both sides, genitalia Inhalation trauma second grade (bronchoscopically secured) Khosrow Houschyar 19.04.17 22

Secondary diagnoses - Depression - Epilepsy - Well-known drug abuse (Crystal Meth) History diagnostics -Thigh thrombosis left -Heparin-induced thrombocytopenia (HIT) 23

Operations Day 2: Epifascial debridement, MEEK 1:6/1:4 Abdomen and upper arm on both sides, ventral thorax and lower arms on both sides Day 4: Epifascial debridement back, lower arms on both sides and MEEK transplant 1:4 on the back and 1:3 lower arms on both sides Day 7: Tangential debridement of both hands, split-thickness skin graft 1: 1.5, tangential debridement, thigh left with split-thickness skin graft 1:5, tangential debridement thigh right with MEEK transplant 1:4/1:3, splitthickness skin graft 1:1.5 24

Operations Day 16: Epifascial necrectomy neck, groin region on the right, covering with 1:1 split-thickness skin graft Day 22: Tangential debridement back, shoulders on both sides, thorax, axillae on both sides, left upper arm and cover by cultivated keratinocytes Day 27: Tangential debridement of the remaining necrosis on both arms Day 31: Tangential debridement back, shoulder, arms on both sides, splitthickness skin graft 1:3 25

Germ spectrum Day 6 Day 16 Day 16 Day 19 Day 19 Day 19 Day 36 Day 36 Day 48 Candida albicans Stenotrophomonas maltophilia Enterobacter cloacae Acinetobacter baumannii (4MRGN) Green Streptococci Coagulase negative staphylococci Staphylococcus aureus Klebsiella pneumoniae (3MRGN) Klebsiella pneumoniae (4MRGN) Acinetobacter baumannii Klebsiella pneumoniae 26

Course of cytokines Measured cytokines: 1. Proinflammatory: IL-6 2. Anti-inflammatory: IL-10 27

ng/l Interleukin 6 4000 3500 3000 2500 2000 1500 1000 500 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 28

pg/ml Interleukin 10 400 350 300 250 200 150 100 50 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 29

Use of the CytoSorb-Adsorber 30

Discussion CytoSorb seems effective in reducing postoperative systemic inflammatory response syndrome In the present study, a successful outcome in a case of septic shock and multiorgan failure where CytoSorb was used as an adjuvant therapy is reported CytoSorb therapy in septic shock patients with multi-organ failure might be an option as rescue therapy However, further studies with prospective randomized control design would be necessary to establish the benefit of this therapy as an adjuvant treatment in septic shock 31

Conclusion Treatments have been considered safe and well-tolerated CytoSorb significantly reduced IL-6, a predictor of mortality in sepsis and surrogate for cytokine storm Improved hemodynamics as evidenced by a reduction in noradrenaline and a significant impact on the patients survival time 32

References 1. Hetz H, Berger R, Recknagel P, et al. Septic shock secondary to ß-hemolytic streptococcus-induced necrotizing fasciitis treated with a novel cytokine adsorption therapy. Int J Artif Organs. 2014;37(5):422-6. 2. Basu R, Pathak S, Goyal J, et al. Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septic shock with multi-organ dysfunction: A case study. Indian J Crit Care Med. 2014;18(12):822-4. 3. Mitzner SR, Gloger M, Henschel J, et al. Improvement of hemodynamic and inflammatory parameters by combined hemoadsorption and hemodiafiltration in septic shock. A case report. Blood Purif. 2013;35:314-5. 4. Hinz B, Jauch O, Noky T, et al. CytoSorb, a novel therapeutic approach for patients with septic shock: a case report. Int J Artif Organs. 2015;38(8):461-4. 5. Linden K, Scaravilli V, Kreyer SF, et al. Evaluation of the Cytosorb Hemoadsorptive Column in a PIG Model of Severe Smoke and Burn Injury. Shock 2015; 44(5):487-95. 6. Träger K, Fritzler D, Fischer G, et al. Treatment of post-cardiopulmonary bypass SIRS by hemoadsorption: a case series. Int J Artif Organs. 2016 May 16;39(3):141-6. 7. Gehling M, Tryba M. Is the time ripe for CytoSorb. Dtsch Med Wochenschr. 2016 Mar;141(6):428-9. 8. Houschyar KS, Nietzschmann I, Siemers F. The Use of a Cytokine Adsorber (CytoSorb) in a Patient with Septic Shock and Multi-Organ Dysfunction (MODS) after a Severe Burn Injury. Handchir Mikrochir Plast Chir. 2016. 33

Thank you! 34