® CytoSorb

Case of the week 26/2019

Use of CytoSorb in severe traumatic

Dr. Hilde RH de Geus Department of Intensive Care, Erasmus University Medical Center Rotterdam, The Netherlands

This case reports on a 56-year-old male patient (known pre-existing medical conditions: intermittent claudication type symptoms however with no medical treatment or diagnosis), who was admitted to the hospital after he had suffered a severe traumatic of his lower extremities and abdomi- nal wall due to a with entrapment between a forklift and a wall.

Case presentation: • At the trauma scene, the patient was awake, however he was not able to move his left leg and complained about persistent numbness. Furthermore, he experienced tingling sensations in the upper right leg • He was tachycardic and hypotensive, a huge hematoma was noticed and a pelvis fracture was suspected. Initial at the scene consisted of intravenous fluid administration and pain management • After transfer to the hospital, subsequent examination in the emergency room (ER) revealed ischemic lower extremities with absent arterial pulse signals. Additionally, a huge degloving injury of both legs and a pelvic fracture of the ramus superior and inferior as well as a communicative acetabulum fracture were noted • The following CT-A examinations showed a traumatic dissection of the distal aorta and of both arteriae iliacae as well as a transection of the vena femoralis on both sides • Neurological examination further showed absence of sensory perceptions below T-12 and absent plantary and knee reflexes • In addition, laboratory diagnostics indicated severe ongoing rhabdomyolysis as indicated by myoglobin levels of 79,931 µg/l and CK levels of 15,032 U/l • After ER examination, the patient was transferred immediately to the operating theatre in an attempt to reconstruct the arterial supply to both lower extremities. On the left side, traumatic transection of the Arteria femoralis communis (AFC) and Arteria iliaca externa (AIE) was reconstructed with an expanded polytetrafluoroehtylene (ePTFE) interponat and on the right side a vascular crush injury was noticed. Recanalization of the left iliacal trajectory was attempted with a Gore excluder, which however was unsuccessful necessitating a femoral-femoral crossover construction with ePTFE from left to right. Although technically successful, functionality was not achieved due to persistent ischemia of >6 hours and stiff lifeless lower extremities, resulting in the indication for bilateral guillotine through the knees • Postoperatively, the patient was transferred to the intensive care unit (ICU) intubated, ventilated and highly catecholamine-dependent (norepinephrine >1.5 µg/kg/min) • Broad spectrum antibiotics were provided and continuous renal replacement therapy (CRRT) was initiated using a high cut-off EMIC-2 dialysis filter (Fresenius Medical Care) with the aim of removing excess myoglobin from the blood • Due to the inadequate myoglobin reduction, a CytoSorb hemoadsorber was additionally added to the circuit and run together with the EMIC-2 filter ® CytoSorb

Case of the week 26/2019

Treatment: • 3 consecutive treatments with CytoSorb for a total treatment duration of 2 days (1st treatment 16 hours, 2nd treatment 14 hours, 3rd treatment 6 hours) • CytoSorb was used in combination with CRRT (Multifiltrate Pro, Fresenius Medical Care) run in CVVHD mode using an ultra-high flux dialysis membrane (EMIC-2 Filter, Fresenius) • Blood flow rate: 200 ml/min • Dialysate flow rate: 4000 ml/h • Anticoagulation: None. Citrate was contra-indicated and as extremely elevated PTT levels were measured after application of 2500 IE heparin, the decision was made to perform CRRT without any anti-coagulation. During the CRRT treatment, no clotting related termination of the circuit was necessary • CytoSorb adsorber position: pre-hemofilter

Measurements: • Hemodynamics, and norepinephrine and enoximone demand • Fluid balance • Creatinkinase, myoglobin • Creatinine, urea

Results: • Norepinephrine demand remained stable throughout the first CytoSorb treatment. Between treatments 1 and 2, norepinephrine demand rebounded to a maximum of 1.75 µg/kg/min which was then successfully reduced to 1.1 µg/kg/min by the second hemoadsorption session. However, hemodynamic therapy had to be escalated with enoximone 1 µg/kg/min and amiodarone 600 mg/24 hrs. During the last treatment, norepinephrine could be again reduced from 1.5 µg/kg/min to 1.3 µg/ kg/min while enoximone and amiodarone had to be maintained at 1 µg/kg/min and 600 mg/24 hrs, respectively • Before application of CytoSorb, the patient had a positive fluid balance of 14 liters which could be reduced to 9.9 liters during the course of the second treatment and to 2.3 liters after the last treatment • Combined CRRT + CytoSorb therapy resulted in a reduction of the myoglobin levels from 110,000 µg/l to 90,000 µg/l within 4 hours of treatment. After replacement, levels could be further reduced to 70,000 µg/l. During the third treatment levels were reduced from 90,000 µg/l to 50,000 µg/l despite the unresolved source. Likewise, CK levels could be reduced from 130,000 to 45,000 U/l during the course of the three treatment cycles • Under combined CVVHD/CytoSorb therapy creatinine levels could be reduced from 115 to 95 µmol/l and urea levels from 4.2 to 1.5 mmol/l ® CytoSorb

Case of the week 26/2019

Patient Follow-Up • As vasopressor therapy could not be sufficiently lowered and due to persistent hyperkaliemia, a re-exploration of the amputated legs was performed, showing that all fascies had been correctly opened and that leg muscles were still vital. Therefore, a laparotomy was carried out revealing sigmoid ischemia followed by subsequent proctosigmoidectomy (Hartmann’s procedure). The next day, another exploration was performed due to persistent rectum stump ischemia in the context of worsening multiple organ failure and persisting deep vasoplegic shock with septic cardiomyopathy (cardiac index 1.9 l/min/m²) • Side stream dark field (SDF) measurements of the microcirculation showed a completely obstructed sublingual microcirculatory flow although macrocirculatory parameters were within a reasonable range • In search for the underlying root cause of persistent instability, another laparotomy was performed revealing completely avital rectus abdominus muscles for which no additional treatment was possible • The patient died after withholding and withdrawal of life-sustaining treatments

Conclusion:

• The use of CytoSorb in this patient with severe traumatic rhabdomyolysis was associated with a significant reduction in plasma concentrations of myoglobin and CK despite an unresolved source (bowel ischemia and unnoticed abdominal wall ischemia) as well as a considerable reduction of fluid balance • Of note, application of a high cut-off EMIC-2 dialysis filter alone with a high effluent volume (45 ml/kg/h) was unable to generate a sufficient effect on rhabdomyolysis parameters. In contrast, CytoSorb was able to reduce both myoglobin and CK levels and in this regard seems to be more powerful than EMIC-2 • In these severe cases of rhabdomyolysis, an adsorber change within 12 hours (or even earlier) seems advisable to reach persistent mediator reductions and to preempt adsorber saturation • The integration of CytoSorb into the running CRRT circuit was safe and easy