Case of the week 28/2016
CytoSorb in septic shock after infection of a knee endoprosthesis
Dr. med. Burkhard Hinz, Head of Interdisciplinary ICU, KMG Clinic Güstrow Dr. med Oliver Jauch, Senior Physician, Department of Anesthesiology and Intensive Care Medicine, KMG Clinic Güstrow Dr. med. Rolf Kaiser, Head of Department of Internal Medicine, Cardiology and Intensive Care Medicine, KMG Clinic Güstrow
This case study reports on a 55-year-old male patient (pre-existing conditions: obesity, insulin dependent type 2 diabetes mellitus, arterial hypertension), who was admitted to hospital with signs of sepsis due to an infection of his knee endoprosthesis implanted 1 year before, after an ambulatory puncture of the knee.
On admission the patient exhibited high temperature and poorly detectable blood pressure, with an immediately identifiable infection focus (knee endoprosthesis)
Immediate surgical removal of the knee endoprosthesis and insertion of a Palacos spacer
Postoperative transfer to ICU. From this time the patient was already in septic anuric renal failure, including septic cardiomyopathy, lactic acidosis, and infection-related anemia (Hb 5.2 mmol/l, hematocrit 0.26, thrombocytes 127 Gpt/l, ATIII 46%)
Greatly increased inflammatory (leukocytes 8.3 Gpt/l, PCT 42.5 µg/l, CRP 450.8 mg/l) and retention parameters (creatinine 633 mol/l, urea 27.3 mmol/l)
Patient had ongoingcirculatory instability (norepinephrine 1.1 µg/kg/min) with progressive clinical deterioration
PiCCO-guided volume therapy with Ringers-Acetate (12 l/24 h) with which norepinephrine doses could be decreased to 0.99 µg/kg/min
Antibiotic treatment: Rifampicin/ciprofloxacin later changed to rifampicin/ceftriaxone
Due to the high and ongoing demand for catecholamines with persisting renal failure, CytoSorb therapy was initiated in combination with CRRT
Three consecutive CytoSorb sessions for a total treatment time of 80 hours (two sessions for 24 hours each, one session for 32 hours)
CytoSorb was used in conjunction with a Multifiltrate CRRT machine (Fresenius Medical Care) in CVVHD mode
Blood flow rate: 180 ml/min
CytoSorb adsorber position: pre-hemofilter
Demand for catecholamines
Inflammatory parameters (CRP, PCT, leucocytes)
Renal function (creatinine, urea)
During the first treatment the hemodynamic condition of the patient could be stabilized considerably and the demand for catecholamines (noradrenaline) could be reduced from an initial dose of 0.99 µg/kg/min to 0.6 µg/kg/min, and in the course of the second treatment to 0.12 µg/kg/min and after the last treatment to 0.03 µg/kg/min
Rapid reduction of inflammatory parameters within the first five postoperative days (POD): PCT 10.76 µg/l (1. POD), 4.67 µg/l (2. POD), 4.1 µg/l (3. POD), 0.43 µg/l (5. POD); CRP 371.2 mg/l (1. POD), 148 mg/l (2. POD), 223 mg/l (3. POD), 94 mg/l (5. POD)
Equally quick decrease of retention parameters under CVVHD within the first five postoperative days (POD): creatinine 387 µmol/l (1. POD), 148 µmol/l (2. POD), 117 µmol/l (3. POD), 98 µmol/l (5. POD); urea 21 mmol/l (1. POD), 10 mmol/l (2. POD), 9.5 mmol/l (3. POD), 8.0 µmol/l (5. POD)
Ongoing rapid and sustained stabilization of hemodynamics and organ functions
Extubation 1 day after the last CytoSorb treatment
Transfer to normal ward possible within a few days
Fast decision and the early start of treatment with CytoSorb in this patient led to a rapid stabilization of the clinical situation within the first 24 hours
According to the medical team, the patient would presumably not have survived without the CytoSorb treatment
Significant stabilization and consolidation of hemodynamic and inflammatory parameters under CytoSorb
The application of CytoSorb therapy was easy and safe without any complications during or after the procedure
Case of the week 27/2016
Improvement of hemodynamic and inflammatory parameters by combined hemoadsorption and hemodiafiltration in septic shock
Steffen R. Mitzner, Martin Gloger, Jörg Henschel, Sebastian Koball, Divisions of Nephrology and Pulmonology and Internal Intensive Care, Department of Internal Medicine, University of Rostock, Germany
This case study reports on a 80-year-old male patient stable on chronic hemodialysis for more than 12 months who was admitted to emergency department after he collapsed at the end of a regular dialysis session. button_EN
Past history included coronary artery disease with a myocardial infarction 14 months ago, end-stage renal disease due to nephrosclerosis, arterial hypertension and diabetes mellitus type II
On examination, patient had fever (39.2°C), moist rales in bilateral lungs, O2-saturation 79%, BP 126/60 mmHg, HR 130 beats/min, lactic acidosis with pH 7.1, APACHE II 33, SAPS II 48
Later blood cultures remained negative, however, bronchoalveolar lavage was positive for Staph aureus
Upon further deterioration of the circulatory situation, patient was diagnosed of having pneumogenic septic shock
Intubation for mechanical ventilation and admission to ICU
Immediate start on Ceftriaxone and Clarithromycin and 0.2 µg/kg/min noradrenaline
On day 3 of the ICU stay the patient was in clinical need for renal replacement therapy
Interleukin (IL) 6 level was elevated to 665 pg/m
Due to clinical need for renal replacement therapy, a sharp increase of inflammatory markers, high need for catecholamines and septic shock with multiple organ failure CytoSorb was additionally installed into the CRRT circuit
One CytoSorb treatment session for 24 hours
CytoSorb was used in conjunction with citrate dialysis (Multifiltrate; Fresenius Medical Care) in CVVHD mode
CytoSorb adsorber position: pre-hemofilter
Demand for catecholamines
Inflammatory parameters (IL-6, PCT, CRP, leucocytes)
Renal function (creatinine)
Noradrenaline could be reduced from a maximum of 3.0 to 0.4 µg/kg/min while MAP remained stable
Values of IL-6, CRP, creatinine, procalcitonin, and leukocytes decreased during treatment
Antibiotic therapy was perforemd without necessity to adjust doses at any time during CytoSorb treatment
Values of inflammatory markers continued to decrease in the following days
Clear stabilization and consolidation of hemodynamics and inflammatory mediators under CytoSorb
Treatment appeared to be safe and was well tolerated by the patient
We invite you to CytoSorbents Symposium!
Thursday, 15.09.2016, 13:45 to 15:15
in room 5 | 2nd Floor
"CytoSorb: treatment option for systemic hyperinflammation - an update"
Chair: H. Gerlach, Berlin I C. Krenn, Vienna
The new sepsis definition: Andert something? H. Gerlach, Berlin
The international CytoSorb register: An interim analysis F. Brunkhorst, Jena
CytoSorb and rhabdomyolysis: New aspects and clinical case reports C. Krenn, Vienna
Influencing the postoperative hemodynamics by CytoSorb K. Carrier, Ulm
First report of cytokine removal using CytoSorb in severe noninfectious inflammatory syndrome after liver transplantation
Tomescu DR, Dima SO, Ungureanu D, Popescu M, Tulbure D, Popescu I
In this report the authors present the case of a 46-year-old man with primary graft nonfunction after liver transplantation who underwent emergency retransplantation with an ABO-incompatible graft.
46-year-old man who underwent deceased donor liver transplantation (LT) for Hepatitis-B-Virus (HBV) and alcoholic cirrhosis
Postoperatively, the patient remained neurologically unresponsive, could not be extubated, and there was a massive increase in serum transaminases and bilirubin
Hyperdynamic hemodynamic status with a high cardiac index (CI) and low systemic vascular resistance index (SVRI) requiring vasopressor support was noted immediately after surgery
Laboratory results showed disseminated intravascular coagulopathy and one session of plasma exchange was performed for severe coagulopathy and cholestasis
Acute graft dysfunction was diagnosed on the 1st postoperative day with emergency retransplantation (ABO incompatible) 36 hours after the first LT
CytoSorb was used in conjunction with CVVH during retransplantation for the entire duration of surgery (total treatment time of 7 hours) and on the first postoperative day with a treatment time of 12 hours
CytoSorb was installed into the CVVH circuit (multiFiltrate® using an Ultraflux® AV 600S hemofilter, Fresenius Medical Care)
Blood flow rates were 150 ml/min
Anticoagulation was achieved using heparin
Intraoperative immunosuppression consisted of 500 mg methylprednisolone and 20 mg basiliximab
Cytokine levels were measured at the beginning of surgery (T1), after graft reperfusion (T2), at the end of surgery (T3) and before (T4) and after (T5) the second CytoSorb treatment
Hemodynamic parameters, biochemical assays and vasopressor support were noted
During the first treatment pro-inflammatory cytokines IL-1b, TNF-a, IL-6 and IL-8 levels decreased, anti-inflammatory cytokines IL-4, IL-13 were constant within the normal range, IL-10 and MCP-1 levels decreased 10-fold to about normal levels
Improvement in hemodynamics with a stabilized MAP and a continuous decrease in vasopressor support (NE) during surgery (NE discontinued at the end of surgery)
The use of CytoSorb during the second session was associated with an improvement in cardiac output and SVRI
Lactate levels and central venous oxygen saturation (ScvO2) returned to normal values
A decrease in platelet count was observed during both treatments (attributed to a multifactorial etiology: CVVH procedure, use of heparin, intraoperative blood loss, and possibly to the use of CytoSorb)
The treatment was well tolerated with no obvious adverse effects
Patient was extubated 12 hours after re-transplantation
Liver function returned to normal within the next 5 days
Discharge from the Post Anaesthesia Care Unit 7 days after retransplantation
Discharge from hospital on the 35th postoperative day
At the 4 months follow-up the patient was in good clinical state with normal liver function
A normal liver function was also recorded at the 1-year follow-up
First use of CytoSorb during CVVH in a patient undergoing re-transplantation with AB0 incompatible graft for Acute Graft Dysfunction
The use of CytoSorb was associated with an excellent outcome in terms of improved hemodynamic parameters, rebalancing pro-inflammatory and anti-inflammatory cytokines and patient survival
Hemoadsorption with CytoSorb may represent an approach to bridge patients with acute liver failure or Acute Graft Dysfunction to liver transplantation
When George Badame started complaining about stomach pain after a big Italian Easter dinner three years ago, his wife, Mary, chalked it up to a little agita.
He vomited that night, and his stomach still hurt the next morning. The couple figured he had a virus, and Mary went to work as usual.
Back at their South Philadelphia home by midafternoon, she found George on the bedroom floor shivering.
Less than 24 hours after Easter dinner, he was in the intensive-care unit at the Hospital of the University of Pennsylvania. Doctors told Mary that her husband, 69, was in septic shock. His body's immune system had reacted so fiercely to an infection in his bloodstream that his organs were in peril.
"I looked at them perplexed," recalled Mary, 56. "I was so unaware. I didn't know a thing."
On June 13, just two months later, he died of the condition. And as in many sepsis cases, the cause of the terrible infection is unknown.
Every year, more than 1.6 million Americans - about one person every 20 seconds - are diagnosed with sepsis or septic shock, and 258,000 die, according to the Sepsis Alliance. That's more than die from prostate cancer, breast cancer, and AIDS combined, but other experts believe even that high figure is an understatement.
Sepsis is deadly because it is so difficult to diagnose in its early stages. Now researchers are working with data from millions of patients to tease apart the mystery of how to diagnose it sooner, before it turns deadly.
Some progress has been seen. While the number of sepsis cases is rising, the mortality rate is falling to a national rate of 15 percent to 20 percent, says Clifford S. Deutschman, a critical-care specialist who has studied sepsis for 30 years. But the mortality rate for patients such as George Badame who progress to septic shock is still more than 50 percent.
"We don't know enough about the underlying biology to be able to say, 'This is how septic shock is different from sepsis,' " Deutschman said.
In 2014, Deutschman cochaired a task force of 16 international experts from the Society of Critical Care Medicine in America and Canada and the European Society of Intensive Care Medicine with the goal of revealing the early symptoms of sepsis and distilling that information into a practical diagnosis tool.
The team took information from six million patients and came up with the Third Consensus Definitions for Sepsis and Septic Shock, published in February in the Journal of the American Medical Association.
"The new definition is that sepsis is life-threatening organ dysfunction caused by a disregulated host response to infection," Deutschman said.
The first attempt to identify the symptoms using clinical data was in 1991. A decade later, that work was updated and defined sepsis as a presumed infection with an inflammatory response that elevated two of four measures - heart rate, respiratory rate, white blood cell count, and temperature - or the Systemic Inflammatory Response Syndrome (SIRS) criteria.
"The problem with SIRS is it's good at identifying septic patients, but it's also good at identifying everybody who has a bad cold or a minor infection," Deutschman said.
Researchers knew that organs start to become dysfunctional in patients with sepsis and that the body's response is disproportionate. But that definition was too vague to help an emergency-room doctor making a diagnosis.
So two years ago the task force enlisted the help of Christopher W. Seymour, an assistant professor of emergency medicine at the University of Pittsburgh. Analyzing records from six million infected patients, Seymour identified those who died, or who survived after spending three or more days in intensive care.
"Then he started looking at what we would be able to measure early on that would identify those patients as rapidly as possible," Deutschman said. "What Chris did was a stroke of genius."
Seymour took every variable that anybody had ever looked at when considering sepsis and the early symptoms of sepsis.
"You can get a terrific predictive value with something as simple as an elevated respiratory rate greater than 22, a systolic blood pressure, or top number, of less than 100 [normal is 120], and a change in mental status," Deutschman said. "If you have two out of three of those, you have a very high likelihood of ending up in the ICU or dying with suspected infection."
To identify septic shock, task force member Manu Shankar-Hari from University College London looked at the sickest patients in the group and found that they had elevated serum lactate and needed drugs to bring up their low blood pressure.
"The combination of those two things identified a cohort of patients with mortality in excess of 50 percent," Deutschman said.
Since its publication, the study has been downloaded from JAMA's website more than 180,000 times and has had in excess of 875,000 hits. Most of the feedback has been positive, but the study has stirred controversy among those reluctant to switch from the old criteria.
"There are a lot of people who have concerns about the requirement for both blood pressure and lactate for septic shock," he said, adding that the task force's work needed more study. "That said, I think we now have better tools."
Case of the week 25/2016
CytoSorb in septic shock and multi organ failure after burn injury
Dr. Markus Engel Senior Consultant Medical ICU, Hospital Bogenhausen
This case study reports on a 27-year-old patient who was admitted to emergency department in status post burn injury (25% TBSA) button_EN
Burn injury of face, arms, hands and lower legs on both sides after flash fire during work as craftsman. Primary care by emergency physician on site including intubation and analgosedation and subsequent transport to hospital by helicopter
On admission intubated and ventilated and with stable circulation requiring low dose catecholamine administration. Primary wound care and vacuseal dressing of both hands
On day 3 uneventful extubation with stable pulmonary and circulatory functions not requiring catecholamine administration
Here after debridement and closure of arm and leg wounds with Suprathel
In the following, however worsening of the cardiopulmonary and renal functions and after the pressure supported NIV approach had failed the indication for intubation was given. In the course of that further deterioration of circulatory instability requiring high dose administration of norepinephrine. Decreasing diuresis despite high doses of furosemide.
Chest x-ray diagnosis showed progressive pulmonary alterations in terms of ARDS. Echocardiography showed only low grade reduced left ventricular function and no real cardiac dysfunction.
Due to multiple organ failure because of the massive inflammatory reaction as well as the persisting high doses of catecholamines needed (norepinephrine up to 5mg/h) treatment with CytoSorb was started after renal failure had also required CRRT.
One CytoSorb treatment sessions for a total period of 24 hours
CytoSorb was used in conjunction with CRRT (multiFiltrate, Fresenius Medical Care) in CVVHD mode
CytoSorb adsorber position: pre-hemofilter
Demand for catecholamines
IL – 6 levels
Quick hemodynamic stabilization of the patient with significantly decreased needs for catecholamines initially and complete tapering of catecholamines after 48 hrs.
Effective reduction of lactate and IL-6 levels during the CytoSorb sessions
Proof of 3MRGN Pseudomonas as well as diagnosis of HIT
In the further course end of CRRT and extubation of (tracheotomized) patient
Finally discharge with stable overall situation and plain wound conditions
Treatment with CytoSorb resulted in a significant and quick stabilization of hemodynamics as well as an effective reduction of lactate and IL-6 plasma levels
Treatment was easy to apply and safe
TORONTO, ONTARIO--(Marketwired - Jun 27, 2016) - Spectral Medical Inc. ("Spectral" or the "Company"), (EDT.TO)(EDTXF), a Phase III Company advancing a precision treatment targeting specific patients at high risk of death from endotoxemic septic shock, today announced that the U.S. Food and Drug Administration (FDA) has accepted its protocol for Expanded Access of Toraymyxin™, the Company's investigational therapeutic device that removes endotoxin from the bloodstream.
The Expanded Access program, sometimes referred to as Compassionate Use, can now begin at certain of the 29 U.S. hospitals that had participated in the recently completed Phase III EUPHRATES clinical trial and have agreed to be part of this program. Patients who meet the clinical criteria for septic shock, are in multiple organ failure and who have elevated levels of endotoxin in the blood, as measured by the Company's FDA cleared Endotoxin Activity Assay (EAA™), would be eligible for the treatment. A similar program is planned for Canada, where there were 12 hospitals engaged in the clinical trial.
"As we move to complete our PMA submission for Toraymyxin™ with the FDA later this year, physicians in our clinical trial locations can now have immediate access to a therapy that has been used on more than 150,000 patients outside of North America for more than a decade," said Dr. Paul Walker, President and CEO of Spectral. "Prior clinical research has demonstrated that removing endotoxin from the blood with Toraymyxin™ can result in positive patient outcomes and a reduction in mortality."
A novel therapy for certain patients in septic shock, Toraymyxin™ is a medical device specifically targeted at those with elevated levels of endotoxin in the blood. Toraymyxin™ is a direct hemoperfusion adsorption column that has been shown to be highly effective in removing endotoxin. Studies have shown that Toraymyxin™ can remove up to 90 percent of an endotoxemic patient's circulating endotoxin when administered twice within a 24 hour period.
Cytosorbents (NASDAQ:CTSO), an immunotherapy developer, reported that strategic partner Fresenius Medical Care (FMS) is initiating sales efforts for its flagship product, the CytoSorb blood purification cartridge, in France, Poland, Sweden, Denmark, Finland, and Norway. Cytosorbents said Fresenius, a German healthcare company, has deployed a team of sales, marketing, and medical experts to work with nationally recognized key opinion leaders, to market CytoSorb at intensive care conferences and symposiums, and to promote CytoSorb to customers in the field.
Dr. Phillip Chan, Cytosorbents CEO, said: “Our collaboration with FMC has been excellent to date. We have been particularly impressed by the effort of their people and attention to detail that they have brought to the partnership. With their large installed base of dialysis machines, ability to rapidly access Intensive Care Units physicians, and the high quality of their marketing and sales organization, we believe FMC has set the stage for a strong CytoSorb market launch and potential future expansion.” The CytoSorb cartridge is designed to reduce the “cytokine storm” or “cytokine release syndrome” that could otherwise cause massive inflammation, organ failure and death in common critical illnesses such as sepsis, burn injury, trauma, lung injury, and pancreatitis, as well as in cancer immunotherapy.
The stock is down 0.47% or $0.02 after the news, hitting $4.27 per share. About 11,853 shares traded hands. Cytosorbents Corp (NASDAQ:CTSO) has declined 29.32% since October 23, 2015 and is downtrending. It has underperformed by 30.38% the S&P500.
CytoSorbents Corporation, a critical care focused immunotherapy company, engages in the research, development, and commercialization of medical devices with its platform blood purification technology incorporating a proprietary adsorbent polymer technology. Its principal product is CytoSorb device, an extracorporeal cytokine filter designed for the adjunctive therapy in the treatment of sepsis; for the adjunctive therapy in other critical care applications; the prevention of post-operative complications of cardiopulmonary bypass surgery and damage to organs donated by brain-dead donors prior to organ harvest; the treatment of cancer cachexia; the prevention of transfusion reactions caused by contaminants in transfused blood products; and the prevention of contrast induced nephropathy, the treatment of drug overdose, and the treatment of chronic kidney failure.
The company is also developing HemoDefend blood purification technology platform to reduce contaminants in the blood supply that can cause transfusion reactions or disease when administering blood and blood products to patients; and ContrastSorb for the removal of IV contrast in blood administered during CT imaging, an angiogram, or during a vascular interventional radiology procedure to reduce the risk of contrast-induced nephropathy. In addition, it is developing BetaSorb device for the prevention and treatment of health complications caused by the accumulation of metabolic toxins in patients with chronic renal failure; and DrugSorb, an extracorporeal hemoperfusion cartridge designed to remove toxic chemicals from the blood. The company was formerly known as MedaSorb Technologies Corporation and changed its name to CytoSorbents Corporation in May 2010. CytoSorbents Corporation was founded in 1997 and is based in Monmouth Junction, New Jersey.
First description of single-pass albumin dialysis combined with cytokine adsorption in liver failure and hemophagocytic syndrome resulting from generalized herpes simplex virus 1 infection
Frimmel S, Schipper J, Henschel J, Tsui TY, Mitzner SR, Koball S. Division of Nephrology, Department of Medicine, Rostock University Medical Center, Rostock, Germany
This case study reports on a 50-year-old immunocompetent woman who was admitted to hospital for acute hepatitis with acute liver failure.
Liver biopsy revealed acute liver cell necrosis due to herpes simplex virus type 1 (HSV-1)
Despite antiviral therapy liver failure progressed and patient was transferred to ICU
Rapid development of MOF with hepatic coma, severe coagulopathy, acute anuric renal failure, respiratory insufficiency and arterial hypotension
Patient was listed for highly urgent liver transplantation
Additional diagnosis of hemophagocytic lymphohistiocytosis (HLH), secondary to HSV-1-infection
Hemodialysis and extracorporeal liver support were initiated using MARS ® -therapy (6 hours 1 st day, 19 hours 2 nd day)
Increasing need for NE and excessively elevated concentrations of inflammatory markers indicated ongoing severe SIRS
Hence extracorporeal therapy was changed to CVVHD with SPAD (12 hours of treatment)
One session of CytoSorb treatment was performed with a treatment duration of 20 hours
CytoSorb was integrated in a predialyzer position
Regional anticoagulation was performed using sodium citrate
Need for vasopressors
IL-6 levels fell from 81059 pg/ml to 17177 pg/ml after 12 hours of treatment
Noradrenaline dosage was reduced to 0.25 µg/kg/min
No further clinical deterioration of the patient
Antiinfective therapy was conducted with Acyclovir, with no reported adaption of dosage during CytoSorb treatment
Reduction of the moderately elevated bilirubin with SPAD + CytoSorb
Successful OLT on 4th day on ICU
Further improvement after OLT
First report of the combined use of CytoSorb with SPAD in a patient suffering from ALF and probable HLH with severe SIRS listed for liver transplantation
Major results of the intervention were a marked decrease of IL-6, and bilirubin, as well as a reduction of vasopressor need
Treatment was safe and well-tolerated, without any adverse events
Existing liver support technique (MARS ® treatment) had no effect on the reduction of bilirubin
CytoSorb might be a useful tool for patients with acute liver failure and severe hyperinflammatory syndromes
Renal replacement therapy neutralizes elevated MIF levels in septic shock.
Pohl J1, Papathanasiou M1, Heisler M1, Stock P1, Kelm M2, Hendgen-Cotta UB1, Rassaf T1, Luedike P1.
1West-German Heart and Vascular Center Essen, Department of Cardiology and Department ofVascular Medicine, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany.
2Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Macrophage migration inhibitory factor (MIF) is known to amplify the immune response in septic animal models. Few clinical data support this pro-inflammatory role in septic patients. Renal replacement therapy (RRT) as adjuvants in the complex therapy of sepsis has been proposed as a possible approach to eliminate elevated circulating cytokines. Since recent data suggest that MIF can be effectively removed from the circulating blood pool in patients with chronic kidney disease, we here aimed to investigate whether RRT in septic shock can lower plasma levels of this pro-inflammatory cytokine in septic shock patients.
An observational single-center study on an internist intensive care unit (ICU) was conducted. MIF plasma levels and mortality of n = 25 patients with septic shock were assessed with a previously validated method for reliable MIF values. The effect of continuous renal replacement therapy (CRRT) on daily MIF levels and mortality was assessed by comparing patients with and without need for CRRT due to acute kidney injury (AKI).
MIF plasma levels in patients undergoing CRRT due to septic AKI were steadily decreased compared to those from patients without CRRT hinting at a MIF removal by hemodialysis. MIF release during ICU stay as assessed by MIFAUC was lower in patients undergoing CRRT, and Kaplan-Meier analysis revealed a distinctly lower mortality in patients undergoing CRRT. Analysis of daily MIF levels showed that patients who did not survive septic shock exhibited steadily higher MIF plasma levels and higher MIFAUC compared to those surviving sepsis. Low MIF levels were closely associated with improved survival.
This is the first study investigating the effect of efficient MIF removal from the plasma pool of patients with septic shock. Reduction of high circulating MIF by CRRT therapy was accompanied by improved survival. Thus, targeted removal of MIF from the circulating blood pool might be a promising approach to reduce mortality in severe sepsis.
CytoSorb in septic shock after perforated Ulcus ventriculi
Dr. Markus Teipel, head physician, Interdisciplinary Intensive Care, Nordwest-Krankenhaus Sanderbusch GmbH
This case study reports on a 43-year-old male patient, who was transferred to hospital via emergency boat and ambulance service from Langeoog island with initially belt-shaped and then diffuse radiating acute pain in the upper abdomen, dark vomitus, diarrhea and dyspnea.
Diagnosis: perforated ulcus ventriculi at the small curvature
Immediate emergency laparoscopy and laparotomy within 2 hours after admission followed by surgical suturing and covering of the perforation
The patient was transferred to ICU intubated and ventilated
At this time the patient was hemodynamically unstable, hypotonic, tachycardic with high requirement for catecholamines (noradrenaline 0.5 ug / kg / min)
Significantly increased inflammatory parameters: PCT 200 ng/ml, leukocytes 6.900/µL, CRP 27 mg/dl
Advanced hemodynamic monitoring showed septic shock with high volume requirements (SVRI 1500 dyn*s*cm-5*m², ELWI 5.6 ml/kg, GEDI 496 ml/m²)
High loading volumes (positive fluid balance 12 liters) with poor and further decreasing spontaneous diuresis (200 ml/day), creatinine 5.8 mg/dl, GFR 11.3 ml/min, urea 95 mg/dl
Initiation of antibiotic therapy with ertapenem followed by additional calculated antifungal treatment with caspofungin
Hydrocortisone 200 mg/day, continuous Amiodarone with 300 mg loading dose (maintenance dose 900 mg/d)
Insertion of a Shaldon catheter and initiation of continuous veno-venous hemodiafiltration (CVVHDF)
Due to acute renal failure, sharp increase in inflammatory markers, progressive need for vasopressors and septic shock, CytoSorb was started 24 hours after initiation of CVVHDF
Two consecutive CytoSorb treatment sessions for 24 hours each
CytoSorb was used in conjunction with citrate dialysis (Prismaflex; Gambro) in CVVHDF mode
Blood flow rate: 150 ml/min
CytoSorb adsorber position: post-hemofilter
Demand for catecholamines
Advanced hemodynamic monitoring parameters (SVRI, GEDI)
Inflammatory parameters (PCT, CRP)
Renal function (excretion)
Clear stabilization of hemodynamics during the course of the two CytoSorb treatments (GEDI 840 ml/m², SVRI 2600 dyn*s*cm-5*m²)
With installation of the adsorber the norepinephrine dose could be reduced significantly to around 1/5 of the initial dose after completion of the first CytoSorb treatment and a further reduction to 0.08µg/kg/min after completion of the second treatment. Five days after the first treatment norepinephrine could be completely tapered off
Reduction of inflammatory parameters during the two treatments: PCT to 45 ng/ml after the first and to 23 ng/ml after the second treatment, CRP at 27 mg/dl after the first treatment and 7.4 mg/dl after the second treatment
Two days after completion of CytoSorb therapy increasing spontaneous diuresis
Antibiotic dosages did not have to be adjusted at any time
Cessation of renal replacement therapy 5 days after last CytoSorb treatment
Extubation on postoperative day 11
Antibiotic treatment with ertapenem could be discontinued 10 days and the antifungal treatment 14 days after admission
After extubation, patient had ongoing delirium which normalized over the next 4 days
No neuropathic sequelae
Transfer to IMC 16 days after initial admission and 4 days later to the normal ward
Clear stabilization and consolidation of hemodynamic and inflammatory mediators with CytoSorb within 48 hours
Conventional therapy using the sepsis bundle was not enough to hemodynamically stabilize the patient during his acute septic phase, however, after using the CytoSorb adsorber this could be achieved in a short period of time
The application of CytoSorb therapy was simple, safe with no problems installing the adsorber in a post-hemofilter position
During his life, Muhammad Ali did many great things for a great many people. But he may still have another contribution to make to the public, or in this case, for the public’s health.
The cause of Ali’s death has been given as septic shock, not from Parkinson’s Disease, the condition that had stalked him the last 30 years of his life.
Sepsis is one of the deadliest killers of Americans. More people die of sepsis in the U.S. every year than AIDS, breast cancer and colon cancer combined. According to a federal study, it’s also the most expensive cause for hospitalizations in the U.S.
Sepsis can occur in anyone with a weakened immune system when a pathogen, either a fungus or bacteria, enters the bloodstream and sends the body’s major organs into shock. This could happen through a cut in the skin, an internal rupture of an organ or even through a patient’s PIC line in the hospital. Unable to fend off the infection, the pathogen overwhelms the blood, and the patient’s organs begin to basically shut down.
Sepsis spreads very rapidly through the body, so it is critical to identify the cause in a patient, whether fungal or bacterial, and administer the appropriate response before the sepsis is completely out of control for any chance of saving the patient.
Every hour of delay of the correct treatment increases mortality by 8%.
When patients present with sepsis, most physicians’ first move is to prescribe a broad spectrum of antibiotics while the patient’s blood culture test is processed, which could take one to five days. But if the sepsis is not caused by bacteria, the antibiotic treatment is utterly useless, and wastes precious hours as the infection rages on.
And, because giving an antifungal at the same time as an antibacterial could be toxic for the patient, the physician will have to wait hours, maybe days, before administering an antifungal drug.
Meanwhile you’ve just given a sick patient powerful antibiotics needlessly, increasing the potential for future resistance against a true bacterial infection.
According to the CDC, over one million Americans will be affected by sepsis, and 1.6 million will be hospitalized with the condition. Sepsis claims 258,000 lives each year. Nearly one third to one half of all hospital deaths in the U.S. are related to sepsis. There is evidence that more and more American lives are being claimed by sepsis each year. In fact, you are more likely to die of sepsis in America than you are to even encounter Ebola, Zika, West Nile virus, malaria or dengue fever combined.
The technology most hospitals rely on in their pathology labs to run blood culture tests are close to 90 years old and can take days to process. However, some hospitals are already beginning to utilize newer, faster technology like a platform device called the T2Dx.
Made by T2 Biosystems, Inc., the T2Dx is an FDA-cleared device that can rapidly detect and identify a blood infection in three to five hours, with rapid pinpoint screening of fungus-caused infections. That’s important because approximately 15% of healthcare-associated infections are caused by fungi, and 70-90% of all those infections are due to a family of fungus called Candida, which the T2 Biosystems device tests for. Eventually, T2’s device should be cleared to discern between various types of infections, including a test for detecting sepsis due to a bacterial infection.
American healthcare leadership is focused on the rise of drug-resistant bacteria and the ineffectiveness of antibiotics; antifungal medications have also been losing their potency. Later today, in fact, the U.S. Congressional Committee of Energy and Commerce is holding a hearing on the issue of combating drug resistance. They should also be asking about the increasing weakness of standard anti-fungal infection medications, which are also becoming more vulnerable to superbugs.
We have helped create superbugs because we misidentify infections and grossly misuse antibiotics and antifungals. Given the number of infections per year and the amount of drugs prescribed wantonly to treat patients, it is essential that the guesswork be taken out of the process of treating infections that cause sepsis. While there are several efforts to develop novel antibiotic and antifungal drugs, we still need to place better diagnostics in our hospitals to use our current arsenal accurately and wisely.
When patients receive the correct treatment quickly, they stand a better chance to survive and receive further treatment through the healthcare continuum. The benefits to the patient are obvious, but it also benefits all players in the market, including pharmaceutical giants like Merck and Pfizer, two of the largest manufacturers of antifungals and antibiotics.
The right drug utilized at the right time also means that there is less chance of exposing pathogens needlessly to critical drugs, thereby potentially decreasing their potency. Today, entire classes of antibiotic and antifungal drugs are losing their effectiveness because of their overuse in both humans and animals in the livestock industry.
What makes this striking is the fact that many of the major pharmaceutical companies have abandoned antibiotic and antifungal R&D.
After WWII, Pfizer was the established leader in antibiotic drug development, having provided penicillin for our troops. While Pfizer still makes several important antibiotic drugs, the company shut down its gram-negative antibiotic drug development campus in 2011. Sanofi, Eli Lilly and Bristol-Myers Squibb haven’t conducted significant R&D on antibiotics since the 90s. Instead, big pharma has focused resources on newer areas of medicine like immunotherapy (just as they did in the 1940s with antibiotics), along with other mainstays like statins, antidepressants and newer autoimmune/anti-inflammatory drugs. Antibiotics and antifungals are not as appealing financially, nor are they treatments for chronic diseases. For Big Pharma, that means an unsteady stream of income, and so most large drugmakers have bailed on those drug classes.
Today, smaller biotech companies are the major players aggressively developing newer antibiotics and antifungal medications.
When Muhammad Ali entered the hospital two weeks ago, the reported cause was respiratory problems. Within a couple days, he was gone; cause, septic shock.
We will probably never know what caused Muhummad Ali’s sepsis–or when it set in–but his death has brought momentary attention long overdue to an illness that has reached epidemic proportions in the U.S. Anyone who has seen a loved one suffer through septic shock knows how sudden and dreadful it can be.
Once it takes hold, sepsis can be very difficult to reverse, making it even more important to utilize the best technologies modern science can provide. In the future, that may include a combination of rapid-fire diagnostics like T2’s device and more conventional blood culture studies for a fuller view of the patient’s condition.
Hopefully during today’s congressional hearing, the panel will enter the ring and cover the broader issues we face with superbugs, and realize that part of dealing with this issue is to for the government to encourage adoption of modernized diagnostic technologies, and for hospitals to embrace them to better meet the needs of their patients.
05-25-2016 4 Current version
10-22-2015 3 Update
01-28-2014 2 Update
07-17-2013 1 First version
Recruitment Status: Recruiting complete, follow-up complete
Study Closing (LPLV): 2015/12/31
Great interest in CytoSorb at the Euroelso Congress 2016 in Glasgow - from left to right Dominik Gutzler, Stefan Baudis, Prof. Robert Bartlett
Dominik Gutzler -Great to see that CytoSorb is in the mind of many experts. Synergetic effects are seen on base of the current experiences. Traffic at our booth was high over the whole conference.
Around 160 interested people attended the symposium "CytoSorb® – Neues zur Therapie von Sepsis und schwerem SIRS" at the annual meeting of the German and Austrian intensive care medical societies that now takes place in Berlin. Prof Kluge from Hamburg talked about "Sepsis 3.0 – Was gibt es Neues? (Sepsis 3.0-what's new?) and Dr Friesecke from Greifswald presented new promising data.
Three-time world heavyweight boxing champion Muhammad Ali died of septic shock "due to unspecified natural causes," a family spokesperson told reporters on Saturday.
He was hospitalized last Monday with respiratory issues. Ali was 74.
According to the Centers for Disease Control and Prevention, sepsis is the body's overwhelming response to an infection. It can lead to tissue damage, organ failure, and death.
"If you have a splinter in your hand, you get a local inflammatory response. You get inflammation and pus, but you don't get sick. Now, say you get a big infection, you have that same local response, but then you also have a whole body response," Dr. Fredrick Moore, chief of acute care surgery at University of Florida Health and Director of the UF Sepsis and Critical Illness Research Center, explained to CBS News.
The CDC reports there are over 1 million cases of sepsis each year in the U.S. It kills more than 258,000 Americans annually, making it the ninth leading cause of disease-related deaths.
If caught early, sepsis can be treatable with fluids and antibiotics. But it progresses quickly and if not treated, a patient's condition can deteriorate at a rapid pace. Septic shock occurs when someone has all of these symptoms plus extremely low blood pressure that doesn't respond to fluid replacement.
Anyone can get sepsis as a reaction to an infection, but the risk is higher in older adults, babies and very young children, and people with weakened immune systems.
Ali's daughter Hana described her father's last moments in a tweet. She said that although all of his organs had failed in the end, "his heart would not stop beating."
"For 30 minutes... his heart just kept beating," she wrote. "No one had ever seen anything like it. A true testament to the strength of his spirit and will."
Taipei, June 6 (CNA) A Taiwanese research team has discovered a molecule in human cells that can regulate inflammation when infections caused by invasive pathogenic germs occur and help protect the body from systemic inflammation, known as sepsis.
Every year, about 110,000 patients in Taiwan die from sepsis triggered by terminal cancer or surgical inflections, said Kuo Cheng-chin (郭呈欽), an associate researcher at the Institute of Cellular and System Medicine under the National Health Research Institutes (NHRI), when presenting the findings on Monday.
Kuo said patients become weaker after undergoing an operation or chemotherapy and are particularly vulnerable at those times to pathogenic germs that invade patients' circulation systems and reproduce in big quantities.
The germs can trigger acute infections throughout the body, causing systemic inflammation that can induce multi-organ failure.
There is currently no drug that can protect patients against the phenomenon, Kuo added, but the team's research may offer a path to a solution.
The research team Kuo worked with spent three years studying endothelium, which plays a critical role in maintaining cellular and inflammatory balance and controlling systemic inflammation and the progress of inflammatory diseases, Kuo said.
Endothelium is the tissue which forms a single layer of cells lining various organs and cavities of the body, especially the blood vessels, heart and lymphatic vessels.
During the study, the team found that endothelium produces and releases a defending molecule, called 5-methoxytryptophan (5-MTP), that acts to restrain inflammatory responses in the body, Kuo said.
During laboratory trials, they found the molecule increased the survival rate of sepsis-affected mice by 80 percent, he said.
The 5-MPT molecule can be acquired through the process of chemical synthesis at a small cost of several hundred Taiwan dollars, according to Kuo.
"It's fairly cheap," he said, noting that if the technology is successfully transferred and commercialized, a drug for sepsis could be developed and produced in five years. Patents for the process are now being applied for in many countries, he said.
The study has been published in international journal "Circulation Research" in May.
Members of the research team include Kuo, former NHRI President Kenneth Wu (伍焜玉) and two physicians at Tri-Service General Hospital, Hsu Yu-juei (許育瑞) and Yang Ya-sung (楊雅頌).
CytoSorb in pneumogenic septic shock after mitral valve reconstruction
Dr. Bastian Huschens, Dr. Ender Demircioglu, Department of Thoracic and Cardiovascular Surgery, University Hospital Essen
This case study reports on a 45-year-old female patient with mitral valve regurgitation III° and tricuspid valve regurgitation I-II° who underwent elective mitral valve reconstruction and then gradually deteriorated during her postoperative intensive care course.
On the 3rd postoperative day (POD) development of a ventilator-associated pneumonia culminating in pneumogenic sepsis with accompanying ARDS
Increased plasma levels of inflammatory parameters: PCT 29.4 ng/ml, CRP 21.2 mg/dl, elevated lactate 6.1 mmol/l
Antibiotic regimen: ciprofloxazin, tazobactam/piperacillin
Septic shock with multiple organ failure: hemodynamics (norepinephrine dose on the 2nd POD 1.5 µg/kg/min), lung, kidney, liver
Development of sepsis-associated liver dysfunction (bilirubin 3.9 mg/dl on the 1st POD and further increasing levels with a peak value on the 6th POD of 20 mg/dl)
Further deterioration of renal function, initially oliguric but trending towards decreasing excretion culminating in anuria and initiation of continuous renal replacement therapy (CVVH) on POD 5
Pre-ECMO therapy: kinetic positioning for 4 days
Initial stabilization of the circulatory situation (epinephrine dose on the 7th POD 0.05 µg/kg/min)
Second septic insult along with hemodynamic deterioration on POD 8 with 0.2 µg/kg/min and worsening liver failure (plasma bilirubin levels with peak value of 38.5 mg/dl, quick 24%, hepatic encephalopathy), lactate at 3.1 mmol/l
Escalation of antibiotic therapy from ciprofloxazin, tazobactam/piperacillin to imipenem/cilastatin
Due to acute renal- and respiratory failure, sharp increase in inflammatory markers and progressive need for vasopressors as well as further increase in bilirubin levels indicative of progressive liver failure, CytoSorb was installed into the CVVH circuit on the 8th POD
8 CytoSorb treatment sessions for 24 hours each and a total treatment period of 8 days
CytoSorb was used in conjunction with citrate dialysis (Multifiltrate; Fresenius Medical Care) in CVVHDF mode
Blood flow rate: 100 ml/min
Anticoagulation: initially heparin, after recovery of liver function change to citrate
CytoSorb adsorber position: pre-hemofilter
Demand for catecholamines
Inflammatory parameters (PCT, CRP)
Renal function (excretion)
After implementation of CytoSorb there was an initial deterioration of the hemodynamic situation with increasing needs for catecholamines from 0.2 to 0.6 µg/kg/min for the first 24 hours, however there was a significant stabilization of hemodynamics in the further course of combined CVVH-CytoSorb treatment with a clear reduction in norepinephrine requirements. After 48 hours norepinephrine could be significantly reduced and was completely tapered off on the 12th POD
Reduction of inflammatory parameters during the course of treatments: PCT from 43.5 ng/ml on the first treatment day to 7.42 ng/ml on the 2nd and 1.35 ng/ml on the last treatment day; CRP from 31.8 mg/dl on the first treatment day to 21.3 mg/dl on the 2nd and 14.7 mg/dl on the last treatment day
Lactate from 1.3 mmol/l on the first treatment day to 4.6 mmol/l on the 2nd and 2.0 mmol/l on the last treatment day
Bilirubin from 25.6 mg/dl on the first treatment day to 17.2 mg/dl on the 2nd and 4.7 mg/dl on the last treatment day
Ammonia from 64 µg/dl on the first treatment day to 55 µg/dl on the 2nd, 135 µg/dl on the 4th, 201 µg/dl on the 5th and 6th treatment day and 47 µg/dl after the last treatment
No recovery of renal function
Patient still dialysis-dependent on POD 24
Regressive hepatic encephalopathy along with significant neurological improvement (vigilance)
Patient is free of catecholamines, complete regeneration of liver function including stabilization of coagulation disorder even without substitution
CPAP without pressure support, alternated with nightly BiPAP training
Transfer of the patient to a weaning clinic while awake, oriented and hemodynamically stable
The most obvious effect was the significant and rapid stabilization of liver function and neurological improvement
Acute phase of septic shock could be overcome surprisingly quickly
Clear stabilization and consolidation of hemodynamics and inflammatory mediators with CytoSorb
Handling of the adsorber was easy and safe
We had about 10 investors last year. All total about 20-25 ,Dr Steiner will be at the meeting.plus board members and management. Where you coming from. I am from CT. They will be servicing Coffee an.
I have been to other Annual meetings. Try to get there early 9:30.
Any other info needed email me at email@example.com