Eight student-athletes at Texas Woman’s University were hospitalized over the weekend with symptoms of rhabdomyolysis, a breakdown of muscle tissue that can lead to kidney failure, the university announced Monday.
The university did not identify which sport the athletes play, citing privacy laws, but said all of them are in stable condition and improving. Star-Telegram content partner WFAA-TV reported that some of the athletes are on the university’s volleyball team.
“The university is assessing the situation and will take appropriate actions as necessary,” Monica Mendez-Grant, vice president for student life, wrote to students Monday.
Rhabdomyolysis happens when muscle tissue is damaged and broken down, and muscle fiber contents are released into the bloodstream, according to the U.S. National Library of Medicine. Severe exertion and dehydration can lead to the condition, which can cause kidney damage and, in some cases, lead to acute kidney failure and shock.
The Denton County health department was notified of patients suffering from “muscle weakness, pain and swelling consistent with a clinical diagnosis of rhabdomyolysis,” WFAA reported. The health department was investigating.
Case of the week 33/2016
Use of CytoSorb in mitral- and aortic valve endocarditis
Dr. med. Gerhard Valicek, Senior Physician Intensive Care Unit 2, University Hospital St.Pölten, Department for Anaesthesiology and Intensive Care Medicine, St. Pölten, Austria
This case study reports on a 63-year-old male patient with mitral and aortic valve endocarditis, who underwent two cardiac surgeries for valve replacement.
The patient had already been treated in the cardiologic intensive care unit for 17 days due to a Staph aureus sepsis
Due to a florid mitral valve endocarditis with large vegetations (2×2 cm in size) and consecutive mitral regurgitation as well as relevant risk of embolism, the decision was made to perform mitral valve replacement
Even prior to admission to the cardiosurgical operating theatre, the patient was already in dialysis-dependent renal failure, required low-dose vasoconstrictor support and was tracheostomized due to long-term ventilation
Relevant secondary diagnoses: IDDM, previous history of atrial flutter
During mitral valve replacement on cardiopulmonary bypass patient had high demand for vasoconstrictor support with norepinephrine, yet still displayed ongoing and insufficient perfusion pressures, even post cardiopulmonary bypass (a hyperdynamic circulatory situation)
After transfer to the anesthesiology ICU the patient exhibited signs of peripheral circulatory failure. Echocardiography confirmed hypovolemia and pulse contour analysis showed reduced peripheral vascular resistance
Therapy was extended to vasopressin and hydrocortisone, and later to epinephrine
After 48 hours with increasing hemodynamic stabilization, the vasopressin and epinephrine were discontinued, and norepinephrine reduced.
A follow-up echocardiogy showed that the mitral valve prosthesis was functionally regularly, however, there was a high-grade aortic regurgitation with suspicion for endocarditic vegetations and massive calcification of the non-coronary sail
On postoperative day 5 the patient underwent a second cardio-surgical revision followed by aortic valve replacement
In total two treatments with CytoSorb – treatments were performed postoperatively after mitral valve replacement (=1st treatment for 24 hours) and intra- and postoperatively during/after the aortic valve replacement procedure (=2nd treatment for 24 hours)
CytoSorb was used in conjunction with CRRT (Multifiltrate, Fresenius Medical Care) performed in CVVHD mode
CytoSorb adsorber position: pre-hemofilter
Hemodynamic parameters and demand for catecholamines
Inflammatory parameters (PCT, IL-1 beta,IL-6, IL-8,IL-10, IL-17, TNF alpha)
During the first treatment no relevant changes in hemodynamics were observed
Of the inflammatory mediators analyzed, the course of IL-6 showed a significant reduction when compared to the time prior to therapy initiation
The 2nd treatment, beginning with the revision surgery (aortic valve replacement) was associated with a hemodynamically and inflammatory stable course
The catecholamine demand remained virtually unchanged when comparing the intra- and postoperative with preoperative levels, hemodynamically there was no occurrence of vasoplegia, no significant increase in inflammatory mediators, and clinically no SIRS symptoms could be observed
The further stay in the anesthetics ICU proved stable, especially in the light of his pre-existing multi-organ failure
The longer-term follow-up care was carried out by the coronary care unit
The patient unfortunately died three weeks after his aortic valve replacement due to a repeated multiple organ failures
Lack of hemodynamic effects after the first treatment with CytoSorb may have been due to the delayed start of treatment (postoperatively) as well as the pre-existing and long-lasting inflammatory condition of the patient
The early use in acute endocarditis (early intraoperative start during the 2nd surgery) could possibly have contributed positively to the clinical course of the patient in terms of potential suppression of recurrence of an inflammatory surge, which might have helped stabilize the inflammatory and hemodynamic situation
Treatment with CytoSorb was safe and easy to use
In summary, treatment with ABT‐719 did not lower AKI incidence using the AKIN criteria, nor did it influence the elevation of novel markers of renal tubular injury or clinical outcomes through 90 days.
ABT-719 for the Prevention of Acute Kidney Injury in Patients Undergoing High-Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial.
McCullough PA, et al. J Am Heart Assoc. 2016.
Show full citation
BACKGROUND: Patients undergoing cardiac surgeries with cardiopulmonary bypass (on-pump) have a high risk for acute kidney injury (AKI). We tested ABT-719, a novel α-melanocyte-stimulating hormone analog, for prevention of AKI in postoperative cardiac surgery patients.
METHODS AND RESULTS: This phase 2b randomized, double-blind, placebo-controlled trial included adult patients with stable renal function undergoing high-risk on-pump cardiac surgery in the United States and Denmark. Participants received placebo (n=61) or cumulative ABT-719 doses of 800 (n=59), 1600 (n=61), or 2100 μg/kg (n=59). Primary outcome was development of AKI based on Acute Kidney Injury Network (AKIN) criteria, measured utilizing preoperative creatinine value and maximum value within 48 hours and urine output within the first 42 hours postsurgery. Secondary outcomes included incidence of AKI based on maximal changes from baseline in novel AKI biomarkers over a 72-hour period after clamp release and length of intensive care unit stays through 90 days postsurgery. A total of 65.5%, 62.7%, and 69.6% of patients in the 800-, 1600-, and 2100-μg/kg groups, respectively, developed AKI (stages 1, 2, and 3 combined) versus 65.5% in the placebo group (for each pair-wise comparison with placebo, P=0.966, 0.815, and 0.605, respectively). Adverse events occurred at a similar rate in all treatment groups.
CONCLUSIONS: ABT-719 treatment did not lower AKI incidence using AKIN criteria, influence the elevations of novel biomarkers, or change 90-day outcomes in patients after cardiac surgery.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01777165.
© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
PMID 27543797 [PubMed - as supplied by publisher]
Case of the week 32/2016
Use of CytoSorb to prevent acute renal failure during drug intoxication-associated rhabdomyolysis
Dr. med. Murad Alkhani, Dr. Michael Rennicke, Dr. Klotilda Jahaj, Dr. Anna Semyonova, Dr. Irina Veil, Dr. Karem Suleiman, Dr. Changguang Shan, Prof. Dr. Rüdiger Becker | Internal Intensive Care Unit of the Medical Clinic I, Hospital Wolfsburg
This case study reports on a 55-year-old female patient, found disoriented and poorly responsive at home who was subsequently brought to hospital by emergency ambulance.
In the emergency room it was found that the patient had ingested 8 g of ibuprofen and 25 g of metamizol (~ 50 tablets) as well as potassium bromatum (amount unknown) in a suicidal intent in chronic depression
On admission the patient had plasma levels of creatine kinase (CK) of 32,383 U/L, myoglobin 3,000 µg/L, CRP 48 mg/L and exhibited a drastically increased CK level 127,100 U / L (out of range) the next day, indicative for a drug-induced rhabdomyolysis
Patient was at any time hemodynamically and respiratory stable, renal function tests remained consistently within the normal range
Fluid Administration as well as of 8.4% sodium bicarbonate solution (~ 500 ml/day) to prevent myoglobin precipitation in the renal tubuli level
Due to massive elevation of serum CK and myoglobin very quick decision to use CytoSorb in combination with renal replacement therapy with the rationale for the treatment of rhabdomyolysis-associated complications even before acute renal failure could establish
Three consecutive CytoSorb treatments for a total treatment time of 72 hours (24 hours each)
CytoSorb was used in conjunction with a Octo Nova CRRT machine (Diamed; used hemofilter APS-18H from Asahi Kasei Medical Co., Ltd)
Anticoagulation: heparin (PTT guided administration)
CytoSorb adsorber position: pre-hemofilter
Rhabdomyolitic parameters (CK, myoglobin)
Inflammatory parameters (CRP)
After the last treatment CK plasma concentrations were at 51.111 U/L, myoglobin 1.045 µg/L, both continuing to decline
While receiving treatment, there were no signs of acute renal failure at any time, the patient always showed good excretion and normal creatinine levels
In the further course creatine kinase (4. 695 U/L) and myoglobin levels (936 µg/l) continued to decrease
Patient could be discharged in completely stable condition within a few days directly from intensive care to her home environment
The CytoSorb therapy proved as highly efficient in terms of the elimination of CK and myoglobin in this patient
According to the medical team, such patients with such a pronounced rhabdomyolysis are usually transferred to a university hospital, however due to the rapid response to CytoSorb therapy this was not necessary in the present case
An acute renal failure could be prevented by the early combined use of CytoSorb and renal replacement therapy
Safe, simple and extremely practical application of CytoSorb especially with the Octo Nova machine
More like 1.3 billion population .
I would say 5-10% would have access to CytoSorb treatment.
Case of the week 31/2016
Use of CytoSorb in severe refractory SIRS with multiple organ failure after post-resuscitation syndrome and cardiac surgery
Dr. Mike Strunden, Dr. A. Salhi*, PD Dr. M. Laß*, Prof. Thoralf Kerner | Asklepios Clinics Hamburg GmbH – Asklepios Clinics Harburg; Anaesthesiology, Intensive Care Medicine, Emergency medicine, Pain therapy | * Asklepios Kliniken Hamburg GmbH – Asklepios Klinikum Harburg; Abteilung für Herzchirurgie
This case study reports on a 71-year-old male patient, who was admitted to hospital in an intubated, ventilated and highly catecholamine-dependent condition after experiencing an infarction-related avulsion of a papillary muscle and associated free mitral valve insufficiency and prior successful cardiopulmonary resuscitation.
Mitral valve replacement emergency surgery with extended cardiopulmonary bypass time 2 hours on the day of admission
Post-operative transfer to ICU in intubated, ventilated, highly catecholamine-dependent condition and mechanical circulatory support with an intra-aortic balloon pump (IABP)
On the first postoperative day, development of multiple organ failure with kidney (anuric, creatinine 2.2 mg / dl) and circulatory failure
In addition, highly increased inflammatory parameters (IL-6 of 63 mg/l, CRP 167 mg/l, leukocytes 18,000/µl) and plasma myoglobin levels (2,001 µg/l)
Initiation of renal replacement therapy (CVVHDF)
Due to the high and stable catecholamine-dependency (norepinephrine 30 µg/min, adrenaline 4 µg/min), persistent renal failure, elevated inflammatory parameters, increased myoglobin plasma levels and condition after resuscitation and extended cardiopulmonary bypass time a CytoSorb adsorber was additionally installed into the CVVHDF circuit 12 hours after the start of renal replacement therapy
Three treatments with CytoSorb for a total treatment time of 72 hours (1st treatment for 12 hours, 2nd and 3rd treatment for 30 hours each)
CytoSorb was used in conjunction with CRRT (Prismaflex, Gambro) performed in CVVHDF mode
Blood flow rate: 100-140 ml/min
CytoSorb adsorber position: post-hemofilter
Demand for catecholamines
Renal function (creatinine, excretion)
Inflammatory parameters (IL-6, CRP, leucocytes)
Hemodynamic stabilization with significant reduction of catecholamines doses
Kidney function – excretion rate rising after starting the 2nd treatment (400 ml/day), creatinine after 2nd treatment back in the normal range at 1.1 mg/dl
On day 2 of treatment IL-6 fell to 21 ng/l – trend towards further decrease; leukocytes rose to 22,000/µL, however normalized to 13,000/µl two days after the last CytoSorb treatment
Two days after completion of CytoSorb therapy CRP was at 120 mg/l – trend towards further decrease
Termination of renal replacement therapy and extubation 5 days after the last CytoSorb treatment
Mobilization was possible still on intensive care unit
10 days after CytoSorb treatment the patient could be transferred to a normal ward
Transfer without any residuals to a cardiac rehabilitation unit
Treatment with CytoSorb was accompanied by an unexpectedly rapid and significant stabilization of hemodynamics and declining catecholamine dosages
Based on the clinical course of this patient the internal decision was made that CytoSorb should be used in the future already intraoperatively in combination with the heart-lung machine when conditions apply as in the present case (emergency cardiosurgery, severe post- resuscitation syndrome SIRS) and should be continued in the post-operative course
CytoSorb use should be further considered in septic patients not responding to conventional standard therapy within 12 hours
Treatment with CytoSorb was safe and easy to apply
Use of CytoSorb in a case of severe septic shock and MOF due to urosepsis
Dr. med. Hendrik Haake, Dr. med. Katharina Grün-Himmelmann & Prof. Jürgen vom Dahl | St. Franziskus-Hospital Mönchengladbach, Department of Cardiology and Intensive Care Medicine
This case study reports on a 75-year-old male patient who presented at the urology department for routine ambulatory elective single J- ureter splint exchange (condition after conduit installation with urostoma due to urothelial carcinoma) developing 40°C fever in the course of the following night and was hospitalized after re-presentation at the hospital with elevated infection parameters.
At previous ureter splint exchanges the patient regularly developed slight fever, however always without signs of generalized infection
Immediate initiation of antibiotic therapy with Unacid (ampicillin/sulbactam)
As a result of subsequent volume administration patient noticably reversed fever
Development of dyspnea after which the patient refractory decompensated and was transferred to IMC
Development of hypotension
Escalation of antibiotic therapy to piperacillin/tazobactam
Increasing respiratory insufficiency despite NIV therapy, followed by intubation and transfer to ICU with further escalation of antibiotic therapy to meropenem and fosfomycin, further increasing lactate levels
Highly increased inflammatory (PCT 64.74 ng/ml, leukocytes 20,000/µl, CRP 25 mg/dl, platelets 23,000/µl) and retention parameters (creatinine 1.6 mg/dl, urea 52 mg/dl, anuric)
Initiation of renal replacement therapy
Despite further massive volume resuscitation (9 l/24 h) patient remained unstable with increasing clinical deterioration (increase of lactate to a maximum of 14.3 mmol/l, norepinephrine 1 mg/h, dobutamine 15 mg/h – trending towards a refractory state), which led to the decision to implement CytoSorb into the CVVH circuit
All blood cultures which were taken during the course of the first few hours after admission later showed bacteremia with a multisensible E. coli
One treatment with CytoSorb for a total treatment time of 30 hours
CytoSorb was used in conjunction with CRRT (Multifiltrate, Fresenius Medical Care) performed in CVVHD mode
Blood flow rate: 150 ml/min
CytoSorb adsorber position: pre-hemofilter
Demand for catecholamines
Renal function (creatinine, urea, excretion)
Inflammatory parameters (CRP, PCT, leucocytes)
Hemodynamic stabilization with significant reduction of catecholamine dosages – dobutamine could be tapered after 3 hours, noradrenaline could be halved within the first 24 hours
Volume of initially 1,200 ml/h could be reduced to 600 ml/h after 3 hours, after 8 hours at 100 ml/h and could be completely discontinued after 24 hours
Lactate could be halved after 10 hours, after 24 hours lactate was at normal values (1.8 mmol/l)
Termination of renal replacement therapy and extubation 6 days after the last CytoSorb treatment
Within the following 48 hours after extubation, the patient could be mobilized into a chair, was awake and adequately contactable
14 days after CytoSorb treatment the patient could be transferred to a normal ward
Treatment with CytoSorb was accompanied by an unexpectedly rapid and significant stabilization of hemodynamics and declining catecholamine dosages within hours
Patient showed ever increasing needs volume and catecholamines, from the moment CytoSorb was implemented the patient clinically improved noticeably
According to the medical team patient would presumably not have survived without the absorber
Safe and easy application of CytoSorb
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.