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A single centre experience with CytoSorb® as an adjunct therapy in critically ill patients with sepsis: a case series
IJMDAT 2023; 6: e398
DOI: 10.32113/ijmdat_20236_398
Topic: Infectious disease Category: Original Article
Gajera H., Gohil S., Chhatravala A. J.
Abstract
Objective: Sepsis is an immune response to infections that are caused by bacteria, viruses, fungi, or parasites. This potentially life-threatening condition is associated with high mortality and morbidity that causes a major global health burden and hence requires intense therapeutic support and close monitoring. As a result, substantial work has been done to enhance outcomes by focusing on alternate treatment strategies. One such approach is CytoSorb®, an extracorporeal blood purification therapy that is used for elevated cytokines levels in patients admitted to ICU suffering from sepsis and septic shock, cytokine release syndrome, COVID-19, ARDS, etc. We present authors’ experience of using CytoSorb® therapy as an adjuvant in six critically ill patients from India with sepsis or septic shock.
Patients and Methods: In this case series, we report the outcomes of six severely ill Indian adults with sepsis or septic shock who were treated by CytoSorb® as an adjuvant therapy.
Results: All patients across wide age groups demonstrated significantly reduced inflammatory mediators and vital parameters when CytoSorb® therapy was initiated within 24 hours of admission in ICU. It was also found to be effective and safe in patients with COVID-19 and associated post-COVID symptoms. The present case series showed rapid hemodynamic stability and enhanced survival in all patients except one, as a consequence of hemoadsorption utilizing CytoSorb®, especially in individuals for whom therapy was initiated early.
Conclusions: CytoSorb® treatment is efficient in cases where elevated levels of cytokines lead to hyperinflammation. It not only resolves excessive inflammation, but also improves organ dysfunction and provides further clinical benefits in severely ill patients.
https://www.ijmdat.com/article/398
Case of the Month
Literature Database
Successful use of extracorporeal life support and hemadsorption in the context of venlafaxine intoxication requiring cardiopulmonary resuscitation: a case report
Matthias Hoffmann1, Samira Akbas1, Rahel Kindler2, Dominique Bettex1 | 1 Institute of Anesthesiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland | 2 Institute of Intensive Care Medicine, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland | J Artif Organs 2023; epub
07/05/2023
New!Case of the Week / Month
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Summary
CoM 07/2023 – This case reports on a 17-year-old female patient who was admitted to a regional hospital for mixed intoxication with a presumed intake of 24 g of venlafaxine (both immediate and extended-release preparations) and unknown amounts of oxycodone, zolmitriptan and itinerol B6.
Case presentation
The patient had been treated with venlafaxine by her outpatient psychiatrist for severe depression with suicidal ideation for two weeks prior to the event. An inpatient psychiatric stay had already been planned
Approximately five hours after taking the medication, the patient was found somnolent and brought to the hospital by ambulance
Due to the severity of the intoxication with the risk of developing hemodynamic instability, the patient was immediately transferred to the intensive care unit
Shortly after that, the patient went into status epilepticus
Because of this the patient was then analgosedated and intubated
After tracheal intubation, progressive hemodynamic deterioration occurred with sinus tachycardia up to 140 bpm, hypotension with systolic blood pressure of 70 mmHg and vasoconstriction (prolonged capillary refill time > 3 s)
ECG on the day of admission showed sinus tachycardia and a prolongation of cQT-time
Furthermore, echocardiography revealed severely impaired left ventricular function (Ejection Fraction – EF 10–15%) with hypokinetic left ventricle, apical and midventricular akinesia with normal right ventricular function. Pericardial effusion was excluded
Arterial blood gas analysis showed metabolic acidosis (pH 7.28) and a serum lactate of 7.8 mmol/l
Despite extended catecholamine therapy with high-dose norepinephrine, dobutamine and epinephrine, the patient could not be stabilized and cardiopulmonary resuscitation due to cardiac arrest had to be initiated
After 2.5 h (150 min) of mechanical resuscitation, extracorporeal life support (ECLS) system was established on-site with subsequent air-ambulance transfer to a tertiary hospital
Shortly after arrival at the tertiary hospital, a large volume of tablets (filling one-third of the stomach) was removed during primary decontamination via gastroscopy. The gastric mucosa was slightly hemorrhagic
A total of 55 g of activated charcoal was applied for additional adsorption. Because of her distended abdomen with subileus, repeated administration was withheld
Laboratory chemistry revealed disseminated intravascular coagulation (DIC) and acute liver failure with transaminase elevation, drop in coagulation factor V (Factor V: < 10%), INR elevation (max. INR 5.9) and lactic acidosis (lactate max. 9.8 mmol/l, pH min. 7.27), leading to the administration of N-acetylcysteine following Prescott schema for four days despite negative paracetamol serum levels
Sonographically, the liver was well perfused without obstructive intra- or extrahepatic cholestasis
Balanced hemodynamic management using volume and low-dose epinephrine (0.1 µg/kg/min) to promote inotropy, as well as high ECLS blood flow (maximum 5 l/min), were used to maintain sufficient
mean arterial pressure
Toxicological screening in urine and blood detected the metabolites of oxycodone, tramadol, nicotine and lidocaine, venlafaxine, metoprolol, metoclopramide, naloxone, and caffeine. In addition, iatrogenic amoxicillin, midazolam and levetiracetam metabolites were found
The initial compound venlafaxine plasma concentration was markedly elevated (maximum 52.53 µmol/l, therapeutic range of 0.7–1.44 µmol/l)
Therefore, a CytoSorb adsorber was initiated 6 h after admission to support drug removal
Treatment
Hemoadsorption treatment with CytoSorb was run for a total of 72 h with three adsorber changes during that time
The adsorber was integrated into a bypass within the running ECLS circuit
Blood flow rate: 300 ml/min
Measurements
Venlafaxine systemic plasma concentration
Left ventricular ejection fraction (LV-EF)
Results
Venlafaxine plasma concentrations were reduced significantly from a maximum of 52.53 µmol/l to 9.60 µmol/l within the first 12 hours. On day 2, it was 7.17 µmol/l and decreased further to 3.74 µmol/l
LV-EF increased steadily reaching ~22% at discontinuation of CytoSorb and ~36% on day 7
Patient Follow-Up
A 900 ml serous left pleural effusion was drained following the correction of coagulation on day four
The patient was anuric with acute kidney injury (AKIN stage 3, max. creatinine 331 µmol/l) and required continuous hemodiafiltration from day five
Already on admission, microbiological sampling was performed after documented aspiration and the established antimicrobial therapy with amoxicillin/clavulanic acid was continued
Despite negative bacterial detection, antimicrobial therapy was escalated to piperacillin/tazobactam on day eight due to respiratory deterioration and increasing inflammatory parameters (C-reactive protein peak level 154 mg/l)
The patient’s health condition progressively improved over the next few days
In addition to an increased blood pressure amplitude over 20 mmHg, serial transthoracic echocardiograms documented improved cardiac function and sufficient ejection fraction
Electrocardiographically, cQT peaked at 507 ms with no arrhythmias
Three days post-admission, levosimendan (0.1mcg/kg/min) intravenously (25 mg) facilitated weaning and removal of the ECLS system
Hepatic function recovered and after 7 days of high-volume hemodiafiltration, acid–base and fluid hemostasis were restored
The patient was transferred back to the peripheral hospital on day 11 post symptom onset and completely recovered neurologically and cardiopulmonarily
The discharge to inpatient psychiatric treatment was organized 31 days after the initial intoxication due to persistent suicidality
Conclusions
The combination of hemadsorption with CytoSorb with ECLS, along with traditional decontamination strategies, resulted in the intact neurological survival of the highest venlafaxine intoxication reported in the literature to date
The authors state this case supports the evidence that hemadsorption with CytoSorb might help to reduce blood serum levels of venlafaxine, and that swift clearance of toxic blood levels may support cardiovascular recovery after life-threatening intoxications.
New on PubMed
Extracorporeal liver support techniques: a comparison
Ivano Riva et al. J Artif Organs. 2023.
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J Artif Organs
. 2023 Jun 19.
doi: 10.1007/s10047-023-01409-9. Online ahead of print.
Authors
Ivano Riva 1 , Antonella Marino 2 , Tino Martino Valetti 3 , Gianmariano Marchesi 3 , Fabrizio Fabretti 3
Affiliations
1 General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy. iriva@asst-pg23.it.
2 General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy. antonellamar@gmail.com.
3 General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy.
PMID: 37335451
DOI: 10.1007/s10047-023-01409-9
Cite
Abstract
ExtraCorporeal Liver Support (ECLS) systems were developed with the aim of supporting the liver in its detoxification function by clearing the blood from hepatic toxic molecules. We conducted a retrospective comparative analysis on patients presenting with liver failure who were treated with different extracorporeal techniques in our intensive care unit to evaluate and compare their detoxification abilities. To verify the effectiveness of the techniques, mass balance (MB) and adsorption per hour were calculated for total bilirubin (TB), direct bilirubin (DB), and bile acids (BA) from the concentrations measured. MB represents the total amount (mg or mcMol) of a molecule removed from a solution and is the only representative parameter to verify the purification effectiveness of one system as it is not affected by the continuous production of the molecules, released in the circulation from the tissues, as it is the case for the reduction rate (RR). The total adsorption per hour is calculated by the ratio between MB and the time duration and shows the adsorption ability in an hour. Our comparative study shows the superior adsorption capability of CytoSorb system regarding TB, DB, and BA, evaluated through the MB and adsorption per hour, in comparison with CPFA, MARS, Prometheus, and PAP. In conclusion, as extracorporeal purification in liver failure could be considered useful for therapeutic purposes, Cytosorb, being more performing than other systems considered, could represent the device of first choice.
Keywords: Extracorporeal support; Liver failure; Liver support.
Intraoperative ticagrelor removal via hemoadsorption during on-pump coronary artery bypass grafting
Hassan K, Geidel S, Zamvar V, Tanaka K, Knezevic-Woods Z, Wendt D, Deliargyris EN, Storey RF, Schmoeckel M. JTCVS 2023; epub
05/2023
This three centre study prospectively included 11 patients on ticagrelor undergoing urgent coronary artery bypass graft (CABG) surgery. CytoSorb hemoadsorption was incorporated in the cardiopulmonary bypass (CPB) circuit and remained there for the duration of the pump run. Blood samples were collected pre and post CPB so that mean ticagrelor levels could be measured. The time interval between surgery and last ticagrelor dose was £48 hrs and the mean intraoperative hemoadsorption duration was 97 minutes with a mean flow rate through the device of 422 mL/min. Mean ticagrelor levels pre-CPB were 103±63.8 ng/mL compared to mean post CPB levels of 34.0±17.5 ng/mL (significant reduction of 67.1%, p< 0.001). There were no re-operations performed for bleeding and no BARC-4 bleeding events occurred. Median chest tube drainage over 24 hours was 520mL (375mL-930mL). Intraoperative integration of CytoSorb into the CPB circuit was simple and safe without any device related adverse events reported. This is the first in vivo report showing that the intraoperative use of CytoSorb can efficiently remove ticagrelor and significantly reduce circulating drug levels. As the authors state, whether this active removal can reduce serious postoperative bleeding in patients undergoing urgent cardiac surgery is currently being evaluated in the double blinded randomized Safe and Timely Antithrombotic Removal – Ticagrelor (STAR-T) trial.
No opinion at this time
Cost-Effectiveness and Budget Impact of a Novel Antithrombotic Drug Removal System to Reduce Bleeding Risk in Patients on Preoperative Ticagrelor Undergoing Cardiac Surgery
Benjamin G Cohen et al. Am J Cardiovasc Drugs. 2023.
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Am J Cardiovasc Drugs
. 2023 May 19.
doi: 10.1007/s40256-023-00587-4. Online ahead of print.
Authors
Benjamin G Cohen 1 , Francine Chingcuanco 2 , Jingwei Zhang 3 , Natalie M Reid 2 , Victoria Lee 3 , Jonathan Hong 4 , Efthymios N Deliargyris 3 , William V Padula 5 6 7
Affiliations
1 Stage Analytics, Duluth, GA, USA. benjamin.cohen@stageanalytics.com.
2 Stage Analytics, Duluth, GA, USA.
3 CytoSorbents Corporation, Princeton, NJ, USA.
4 St. Boniface Hospital, University of Manitoba, Winnipeg, MB, Canada.
5 Stage Analytics, Duluth, GA, USA. padula@usc.edu.
6 Department of Pharmaceutical and Health Economics, School of Pharmacy, University of Southern California, Los Angeles, CA, USA. padula@usc.edu.
7 The Leonard D. Schaeffer Center for Health Policy and Economics, University of Southern California, USC Schaeffer Center, 635 Downey Way (VPD), Los Angeles, CA, 90089, USA. padula@usc.edu.
PMID: 37204675
DOI: 10.1007/s40256-023-00587-4
Cite
Abstract
Background: Antithrombotic drugs, including the P2Y12 inhibitor ticagrelor, increase the risk of perioperative bleeding in patients requiring urgent cardiac surgery. Perioperative bleeding can lead to increased mortality and prolong intensive care unit and hospital stays. A novel sorbent-filled hemoperfusion cartridge that intraoperatively removes ticagrelor via hemoadsorption can reduce the risk of perioperative bleeding. We estimated the cost-effectiveness and budget impact of using this device versus standard practices to reduce the risk of perioperative bleeding during and after coronary artery bypass grafting from the US healthcare sector perspective.
Methods: We used a Markov model to analyze the cost-effectiveness and budget impact of the hemoadsorption device in three cohorts: (1) surgery within 1 day from last ticagrelor dose; (2) surgery between 1 and 2 days from last ticagrelor dose; and (3) a combined cohort. The model analyzed costs and quality-adjusted life years (QALYs). Results were interpreted as both incremental cost-effectiveness ratios and net monetary benefits (NMBs) at a cost-effectiveness threshold of $100,000/QALY. We analyzed parameter uncertainty using deterministic and probabilistic sensitivity analyses.
Results: The hemoadsorption device was dominant for each cohort. Patients with less than 1 day of washout in the device arm gained 0.017 QALYs at a savings of $1748 (USD), for an NMB of $3434. In patients with 1-2 days of washout, the device arm yielded 0.014 QALYs and a cost savings of $151, for an NMB of $1575. In the combined cohort, device gained 0.016 QALYs and a savings of $950 for an NMB of $2505. Per-member-per-month cost savings associated with device was estimated to be $0.02 for a one-million-member health plan.
Conclusion: This model found the hemoadsorption device to provide better clinical and economic outcomes compared with the standard of care in patients who required surgery within 2 days of ticagrelor discontinuation. Given the increasing use of ticagrelor in patients with acute coronary syndrome, incorporating this novel device may represent an important part of any bundle to save costs and reduce harm.
Case of the Month
Literature Database
Use of CytoSorb for bilirubin removal in ischemic hepatitis and multiple organ failure due to uterine rupture with massive postpartum hemorrhage
Henry Kai Wing Chan, Kenny King Chung Chan | Department of Anesthesia and Intensive Care, Tuen Mun Hospital, Hong Kong, China
05/03/2023
New!Other indicationsBilirubinCase of the Week / MonthCase reportCritical CareCRRT pre filterLiver failure
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Summary
CoM 05/2023 – This case reports on a 43-year-old pregnant woman, who was hospitalized for an anticipated complicated delivery.
Case presentation
The patient had hypothyroidism and was additionally on antihypertensive medication (methyldopa). She had also suffered from persistent liver impairment with hyperbilirubinemia from admission to hospital
Due to her medical condition, she was transferred to the Department of Anesthesia and Intensive Care for further management and induction of labor was performed at the 39-weeks gestation
Postpartum, the patient suddenly developed pulseless electrical activity (PEA) which resulted in a cardiac arrest for 20 minutes. An uterine rupture was noted and treated by emergency hysterectomy with embolization of the right internal iliac artery and ligation of left internal iliac artery. During the operation, the patient developed abdominal compartment syndrome with hypoxemia and so she was eventually connected to veno-venous extracorporeal membrane oxygenation (VV-ECMO) therapy
In addition to fluid substitution given her hypovolemic shock state high dose inotropic support was initiated
In the postoperative period, she required mass blood transfusions to manage her postpartum hemorrhage
Although the patient could eventually be weaned from ECMO, she developed signs of ischemic hepatitis accompanied by massive liver failure with serum bilirubin levels increasing to over 64 mg/dL on day 10 after ICU admission
Simultaneously, she developed acute renal failure, resulting in the initiation of continuous renal replacement therapy (CRRT)
Moreover, she was noted to be in atrial fibrillation with short pause intervals, followed by severe bradycardia (heart rate 40-50 bpm) and asystole for 2 minutes. Therefore, transvenous pacing (TVP) was inserted by the cardiologist for severe bradycardia
With the rationale to reduce her elevated bilirubin levels, a CytoSorb adsorber was integrated into the CRRT circuit
Treatment
A total of three treatment sessions of CytoSorb were run consecutively for a total of 52 hours
The CytoSorb absorber was installed pre-hemofilter into the CRRT circuit (AV1000S, multiFiltrate, Fresenius)
Blood flow rate: 80-100 ml/min
Measurements
Bilirubin serum levels
Results
CytoSorb treatment led to a reduction in serum bilirubin levels from 64 to 33 mg/dL within 12 hours of initialization. A slight rebound of bilirubin was observed and a second CytoSorb treatment was started. The patient’s serum bilirubin remained stable during CytoSorb treatment and continued to decrease over time
Patient Follow-Up
The patient was eventually weaned from TVP two days after discontinuation of CytoSorb treatment as her heart rate returned to normal sinus rhythm
Over time, her clinical condition further stabilized and liver as well as renal function progressively improved, both returning to normal values
She was discharged home four months later after a prolonged course of rehabilitation with her healthy baby
Conclusion
To the best of the authors knowledge, this is the first case that describes the use of CytoSorb for bilirubin removal in multiple organ failure, including cardiac arrest, ischemic hepatitis and renal failure following severe postpartum hemorrhage postpartum with uterine rupture
In this complex and multifactorial scenario, implementation of CytoSorb treatment successfully reduced the patient’s serum bilirubin level and was associated with improved liver and cardiac function, and eventually enabled weaning-off from transvenous pacing within a short time period
These data further support the use of hemoadsorption for bilirubin removal while treatment with CytoSorb was safe and feasible without technical problems.
Case of the Month
Use of CytoSorb in a case of hyperinflammation in the context of severe acute necrotizing pancreatitis
José O. Castro Abteilung für Intensivmedizin, Pacifica Salud Hospital, Panama-Stadt, Panama
04/04/2023
New!PancreatitisReduction in catecholaminesSafetyStandalone (HP)Improv. fluid balanceAnticoagulation HeparinCase of the Week / MonthCase reportCritical CareInflammatory parameters
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Summary
CoM 04/2023 – This case reports on a 34-year-old male patient with a history of heavy alcohol intake (1 bottle of wine per day for the past 15 years) but no other comorbidities, who was transferred to the emergency department due to an acute onset of epigastric abdominal pain, 24 h prior to admission.
Case presentation
Following initial physical and laboratory examinations, he was transferred to the general ward with severe pain and nausea, but without hemodynamic instability or respiratory failure
Over the next 48 hours, the patient showed progressive abdominal distention, tachypnea (36/min) and otherwise poor respiratory mechanics while already on a non-rebreather mask (15 L/min)
As a trial, high flow nasal cannula did not ameliorate his clinical picture, so he was finally intubated and mechanically ventilated. His hypoxemic respiratory failure was seen to be primarily attributed to volume overload due to aggressive fluid resuscitation (cumulative fluid-balance: 5 liters) as well as abdominal distention interfering with respiratory mechanics
After intravenous administration of furosemide and following initiation of positive pressure ventilation, a PaO2/FiO2 ratio >200 mmHg could be achieved
During his stay, the patient was extremely difficult to sedate, most probably due to high benzodiazepine tolerance and alcohol withdrawal
24 hours after intubation, a new onset of fever was noticed, accompanied by increasing vasopressor requirements and abdominal hypertension (intraabdominal pressure 16-18 mmHg)
Abdominal CT confirmed suspicion of pancreatic necrosis (around 80%) without any fluid collection, and bi-basal infiltrates (serum lipase on admission 1,718 U/L, amylase 389 U/L)
Moreover, methicillin-sensitive Staphylococcus aureus (MSSA) was isolated from his sputum and bacteremia with Streptococcus agalactiae was confirmed in the blood, resulting in the initiation of antibiotic therapy with meropenem
Despite antibiotic therapy and supportive care, his condition deteriorated further, with persistent fever, tachycardia (130/min), norepinephrine requirements up to 0.4 µg/kg/min, increasing leucocytes, C-reactive protein (CRPI 648 mg/l) and elevated procalcitonin (PCT) levels (4.2 ng/ml)
Given his worsening clinical condition and with the rationale to control the ongoing hyperinflammatory response, CytoSorb hemoadsorption was commenced in a stand-alone configuration (in the absence of renal failure)
Treatment
Two consecutive treatments with CytoSorb were performed for an overall treatment duration of 48 hours
CytoSorb was used in a stand-alone configuration (hemoperfusion mode) using a conventional dialysis machine (Aferetica)
Blood flow rate: 200 ml/min
Anticoagulation: 400-600 IU/h
Measurements
Hemodynamics and catecholamine requirements
Inflammatory response
Renal function
Cumulative fluid-balance
Results
Treatment resulted in an immediate improvement in his clinical condition. Within the first 6 hours of therapy, the dose of vasopressors could be reduced significantly (norepinephrine 0.1 µg/kg/min) accompanied by control of his hyperdynamic state (heart rate 95-100/min). He remained hemodynamically stable on low-dose vasopressor therapy over the following days. Norepinephrine administration was finally stopped on day 8 after admission
Additionally, there was control of the hyperinflammatory condition indicated by a clear reduction in inflammatory mediators (procalcitonin 2.69 ng/ml, CRP 559 mg/l) during the course of hemoadsorption therapy. This was accompanied by decreasing fever and an overall improvement in his clinical condition
Renal function remained normal throughout the entire period
The cumulative fluid balance (+7 liters at 48 hours) also decreased over time without any necessity for initiation of renal replacement therapy or ultrafiltration treatment
Patient Follow-Up
Following discontinuation of CytoSorb treatment, the patient remained on mechanical ventilation and medical management of the abdominal hypertension for 10 more days
In the follow-up period, the patient suffered an episode of severe acute respiratory distress syndrome (ARDS) in the context of ventilator-associated pneumonia, which was treated with prone positioning, steroids (dexamethasone) and intravenous antibiotics
Tracheostomy was performed and weaning from mechanical ventilation was started as well as adjustments to his nutrition and physical therapy
The patient was transferred to the normal ward after a total of 30 days
At the time of documentation, the patient is able to perform active exercises in the rehab center, is managing a low-fat diet by mouth with no assistance, requires only minimal oxygen support (nasal cannula 3L/min) and is planned for discharge in a stable clinical condition
Conclusion
In this patient with hyperinflammation in the context of severe acute necrotizing pancreatitis the use of CytoSorb led to hemodynamic stabilization and control of hyperinflammation
According to the authors, application of CytoSorb contributed to an overall reduction in morbidity and potentially rescued the patient from more severe long-term sequelae
In this case, CytoSorb was safe and easy to apply.
Case of the Month
Use of CytoSorb in a patient with urosepsis and septic shock
Dr. Zsolt Rausch Department for Anesthesia, Surgical Intensive Care Medicine, Emergency Medicine and Pain Therapy, SLK Clinics Heilbronn, Heilbronn, Germany
03/01/2023
New!Reduction in catecholaminesSafetySeptic ShockAnticoagulation CitrateCase of the Week / MonthCase reportCRRT pre filterInflammatory parameters
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Summary
CoM 03/2023 – This case reports on a 56-year-old female patient who was admitted to hospital by ambulance with fever (up to 42°C) that had been persisting for 4 days, lower abdominal pain and progressive deterioration of her general condition.
Case presentation
Pre-existing medical conditions included morbid obesity (body mass index 46), arterial hypertension and chronic back pain
On admission, her vital signs were as follows: blood pressure 90/70 mmHg, tachycardia up to 180/min, SpO291%, respiratory rate 28/min and a Glasgow Coma Scale (GCS) score of 7
While still in the shock room, a FAST sonography, blood gas analysis and a CT from head to abdomen were performed. In addition, the patient was intubated and ventilated, and an arterial line inserted
The CT showed a grade II renal obstruction with an inflamed imbibed ureter on the right side as the only pathological findings
With the working diagnosis of urosepsis and septic shock, urine status and blood cultures were taken
Following admission to the intensive care unit (ICU), the patient was analgosedated (propofol, sufentanil), tachycardic up to 110/min with high catecholamine requirements
Advanced hemodynamic PiCCO monitoring was established. Septic shock was treated according to guidelines including volume resuscitation, catecholamine administration and initiation of empiric anti-infective therapy with piperacillin/tazobactam (for 5 days). After the detection of Klebsiella bacteria in blood cultures, urine and tracheal secretions, antibiotic therapy was changed to cefotaxime in accordance with the antibiogram
Over time, the patient’s right leg and left arm became cold following increasing doses of catecholamines and vasopressin (norepinephrine 0.67 µg/kg/min, argipressin 2.1 IU), accompanied by livid marbling of her toes and fingers. Consequently, administration of argipressin was stopped
Initially, urine was sterile and the focus of the infection not clear. However, a cerebrospinal fluid (CSF) puncture was performed to exclude meningitis in the presence of neck stiffness
Later that day, ultrasound-guided Shaldon catheter insertion was performed into the left internal jugular vein without any problems. Given the sepsis-associated hyperinflammatory picture and in order to stabilize the hemodynamic situation, renal replacement therapy in combination with CytoSorb hemoadsorption was started. At that time, the patient was anuric despite massive volume substitution
During the night of the second day, spasticity and a drop in blood pressure to 30 mmHg occurred during repositioning, most likely due to a leakage of the catecholamine line. After administration of epinephrine, she developed ventricular fibrillation, followed by 1x defibrillation and brief period of cardiopulmonary resuscitation (30 s) and return of spontaneous circulation. After subsequent administration of amiodarone 300 mg i.v., sinus rhythm was restored.
Treatment
CytoSorb treatment was started 14 hours after hospital admission and a total of 3 consecutive treatments with CytoSorb were performed over a period of 54 hours (change of the 1st adsorber after 12 hours, the 2nd and 3rdtreatment were performed for 27 and 18 hours, respectively)
CytoSorb was used in combination with CRRT (Fresenius, Mulitfiltrate CiCa) run in continuous veno-venous hemodialysis (CVVHD) mode
Blood flow rate: 170 ml/min, with a calculated blood purification volume of 6.12 L/kgBW*
Anticoagulation: citrate
CytoSorb adsorber position: pre-hemofilter
Measurements
Hemodynamics and need for vasoactive substances
Inflammatory parameters (interleukin 6, C-reactive protein, procalcitonin, leukocytes)
Lactate
Fluid balance
Renal function
Results
Following initially stable catecholamine requirements, vasoactive therapy with norepinephrine and vasopressin could be significantly reduced on the second day (from 0.67 µg/kg/min to 0.3 µg/kg/min) and both were completely discontinued on the fourth day. At the end of CytoSorb treatment (after 54 hours, on the third day), norepinephrine dosage was 0.05 µg/kg/min. Due to a recurring septic event (bilateral pneumonia), catecholamine requirements had to be increased again for a short time, but could be completely discontinued after 24 hours
The hyperinflammatory situation could also be well controlled during the use of CytoSorb therapy, as evidenced by a reduction in interleukin 6 levels from 344 to 66 pg/ml within 32 hours, with subsequently decreasing values thereafter. Plasma concentrations of procalcitonin and C-reactive protein also decreased significantly during and after hemoadsorption therapy. Leukocytes initially remained at normal levels during the course of CytoSorb therapy, rose progressively after the end, before spontaneously turning back to normal values in the following 2 weeks under appropriate therapy
Lactate levels significantly decreased under volume resuscitation and CytoSorb therapy and were back within the normal range (4.6 vs 1.05 mmol/L) at cessation of hemoadsorption therapy after 54 hours
After stabilization of the hemodynamic situation and a cumulative positive fluid balance of 30 litres, consistent negative balancing could be achieved from day 6 onwards
Furthermore, combined treatment with CRRT and CytoSorb was associated with a significant improvement in renal function with good diuresis as of day 4
Patient Follow-Up
Tracheotomy was performed 12 days after admission given the ongoing need for invasive ventilation and difficult weaning (morbid obesity, bilateral pneumonia and massive positive fluid balance)
The patient was successfully weaned off ventilation and decannulation was performed 21 days after her initial admission
Sonography confirmed that the right kidney was no longer congested and according to the urological consultation, urological intervention was not necessary at this time
The patient could be transferred to the normal ward after 24 days of intensive care in a good general clinical condition, awake, oriented, mobile and hemodynamically stable
The bladder catheter as well as the central venous cannula were removed due to the patient’s significantly improved laboratory results and favorable clinical condition
The patient was given physiotherapy for muscle weakness and fatigue, and after consultation with a neurologist, mild critical illness polyneuropathy and myopathy was diagnosed, and neurological rehabilitation was organized.
32 days after admission, the patient could finally be discharged from the hospital
Conclusions
In this patient with hyperinflammatory syndrome due to urosepsis with septic shock, combined treatment consisting of guideline-based sepsis therapy, CRRT and CytoSorb resulted in hemodynamic stabilization, control of the hyperinflammation and rapid recovery in renal function
According to the treating physicians, in this case CytoSorb therapy contributed to faster hemodynamic stabilization, shortened catecholamine therapy and faster improvement of renal function
Application of CytoSorb in combination with CRRT was safe and easy to perform
* Footnote
ABP = (CD × BF)/BW × 0,001
ABP = amount of blood purified (l/kg), CD = duration of treatment with CytoSorb® (min), BF = blood flow through the extra-corporeal circuit (ml/min) and BW = actual body weight (kg)
Reference: Schultz P, Schwier E, Eickmeyer C, Henzler D, Köhler T. High-dose CytoSorb hemoadsorption is associated with improved survival in patients with septic shock: A retrospective cohort study. J Crit Care. 2021 Aug;64:184-192.
Case of the Month
Literature Database
Use of CytoSorb in a patient with hyperinflammatory syndrome following extensive 3-vessel coronary surgery
Dr. Angelika Oblin | Department of Cardiology, Cardiological Intensive Care Unit, Floridsdorf Hospital, Vienna, Austria
02/01/2023
New!Post-OpReduction in catecholaminesSafetyImprov. fluid balanceAortic SurgeryAnticoagulation CitrateCardiac surgeryCase of the Week / MonthCase reportCritical CareCRRT pre filterInflammatory parameters
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Summary
CoM 02/2023 – This case reports on a 60-year-old male patient who presented to hospital for elective aortocoronary bypass surgery.
Case presentation
His extensive cardiac medical history included chronic ischemic (3-vessel) heart disease, post-aortocoronary bypass, post-endovascular aortic repair for abdominal aortic aneurysm, peripheral arterial occlusive disease with serial high-grade stenosis of the left femoral artery, cerebral arterial occlusive disease, left ventricular hypertrophy, arterial hypertension, post-nephrectomy left, chronic nicotine abuse and hyperlipidemia
The operation was initially performed without complications and included a triple LIMA and LAD, RIMA and CX and vein [brachial left] and RCA. Repeated administration of low doses of norepinephrine was required for hemodynamic stabilization. The intraoperative cumulative fluid balance was +7400 ml (8800 in, 1400 out)
On postoperative transfer to the intensive care unit (ICU), the patient was deeply sedated (Richmond Agitation Sedation Scale [RASS] -5) and hemodynamically stable with still only low catecholamine requirements
During the night, however, catecholamine requirement increased (norepinephrine >1 µg/kg/min, additional administration of vasopressin) with simultaneously increasing lactate values (3.7 mmol/l). Hydrocortisone therapy was also started
Continuous renal replacement therapy (CRRT) was initiated 18 hours after postoperative transfer to the ICU because of progressively increasing retention parameters and to compensate for the metabolic acidosis (pH 7.3)
Given the simultaneously increasing inflammatory parameters (leukocytes 13.6×10³/µl, C-reactive protein [CRP] 37.45 mg/dl, interleukin-6 [IL-6] 16,586 pg/ml) in the context of a hyperinflammatory post-cardiopulmonary bypass syndrome and with the aim to hemodynamically stabilize the patient, a CytoSorb hemoadsorber was additionally integrated into the CRRT circuit
Treatment
A total of 10 treatments with CytoSorb were performed over a period of 96 hours (change of adsorber every 8 hours on day 1, and every 12 hours thereafter)
CytoSorb was used in combination with CRRT (Fresenius, Mulitfiltrate CiCa) run in continuous veno-venous hemodialysis (CVVHD) mode
Blood flow rate: 100 ml/min
Anticoagulation: Citrate
Position of the CytoSorb adsorber: pre-hemofilter
Measurements
Hemodynamics and norepinephrine requirements
Inflammatory parameters (leukocytes, CRP, IL-6)
Lactate
Fluid balance
Renal function
Results
Initially, blood pressure values fluctuated and he exhibited intermittent tachycardia as well as slightly increasing norepinephrine values (as part of the attempt to reduce volume). Catecholamine therapy with norepinephrine and vasopressin could then be significantly reduced from the second day onwards while vasopressin was discontinued after only 48 hours. Norepinephrine dosage was 0.43 µg/kg/min (under generous volume administration) on postoperative day 3. On the 4th postoperative day, only a low maintenance dose of norepinephrine (0.1 µg/kg/min) was required, which could be discontinued over the following days
In addition, the hyperinflammatory situation was well controlled during treatment, as evidenced by a reduction in IL-6 plasma levels to 360 pg/ml within 48 hours and further decreases thereafter. Leukocytes and CRP initially remained at an elevated level, but progressively decreased over time
Lactate values also reached normal ranges on the 4th postoperative day
After stabilization of his hemodynamic condition and a cumulative positive fluid balance of 18 litres, continuous negative fluid balancing could be achieved from day 3 onwards
Furthermore, the combined treatment with CRRT and CytoSorb was associated with a significant improvement in renal function with good diuresis from day 5 onwards
Patient Follow-Up
Successful extubation on postoperative day 5, initially without problems. However, over time he became tachypneic and stressed. This was followed by the start of a non-invasive high-flow ventilation regime
Removal of pleural drains on postoperative day 6
Also, discontinuation of renal replacement therapy after 2 therapy cycles 6 days after surgery
Transfer of the patient with non-invasive O2 application to the general ward after a total of 12 days of intensive care
Conclusions
In this patient with profound cardiac history with hyperinflammatory syndrome secondary to extensive 3-vessel coronary surgery, the postoperative combined use of CRRT and CytoSorb resulted in hemodynamic stabilization, control of hyperinflammation, resolution of metabolic acidosis, improvement in renal function and the possibility of a negative fluid balance
According to the authors, CytoSorb therapy helped to rapidly reduce the inflammatory parameters and thus stabilize the hyperinflammatory situation in this complex case
In this challenging setting, application of CytoSorb in combination with CRRT was safe and easy.
Case of the Week
Use of CytoSorb in a patient with severe polytrauma and ARDS following a motorbike accident
Dr. med. Christoph Busjahn Clinic and Polyclinic for Anesthesiology and Intensive Care, Rostock University Medical Centre, Rostock, Germany
01/04/2023
MyoglobinNew!Reduction in catecholaminesSafetyTraumaImprov. fluid balanceAnticoagulation HeparinARDSCase of the Week / MonthCase reportCritical CareECMO-VVInflammatory parameters
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Summary
CoM 01/2023 – This case reports on a 20-year-old patient with no relevant medical history, who was admitted to the emergency room with severe polytrauma after hitting a stationary car whilst on his motorbike.
Case presentation
In the shock room, while he was still breathing spontaneously, rapid pulmonary deterioration occurred so that emergency intubation was performed immediately
The main injuries diagnosed in the course of the initial assessment included: avulsion of the left main bronchus with bilateral hemato-pneumothorax, extensive pulmonary contusions with hemorrhages, cervical soft tissue emphysema and soft tissue hematoma, various rib fractures, right clavicle fracture, left scapula fracture, fracture of the manubrium sterni, left tripod fracture, dislocated multi-fragmentary fractures of the left maxillary sinus walls, right petrous bone longitudinal fracture, fractures of the left proc. transversi, non-displaced fracture of the proc. spinosus, multi-fragmentary fractures of the left pelvic scapula, left distal ulnar shaft fracture, suspected rupture of the anterior cruciate ligament and medial collateral ligament of the left knee joint, contusio cordis (contusion of the heart in the context of the thoracic trauma), splenic laceration (grade II), a craniocerebral trauma as well as a subcapsularly dorsal liver contusion/hematoma in the right liver lobe and also diffuse intraparenchymal hematoma in the right liver lobe
Subsequently, veno-venous extracorporeal membrane oxygenation (vv-ECMO) therapy was commenced due to his actively bleeding bronchus injury and the patient was transferred to the perioperative intensive care unit (ICU) intubated and ventilated in a controlled ventilation mode, already requiring high catecholamines (0.6 µg/kg/min)
The bronchus injury was treated with a thoracotomy with resection of the left upper lobe by colleagues from the thoracic surgical team
Diagnostic laparoscopy and gastroscopy were performed in the same time without further therapeutic consequences
In addition, mass transfusions were necessary in the context of his hemorrhagic shock with anemia (a total of 19 red cell concentrates, 19 units of fresh frozen plasma, 9 platelet concentrates)
Already intraoperatively, increased lactate levels were noted. Postoperatively, the patient then exhibited increased volume and catecholamine requirements with ongoing increases in lactate levels
Due to pronounced acute respiratory distress syndrome (ARDS), proning therapy was required and maintained for 4 days
After postoperative transfer to the ICU, CytoSorb therapy was started to control the hyperinflammatory situation, to achieve hemodynamic stabilization and to potentially avoid pulmonary hyperhydration and edema through reduced volume requirements
Treatment
Consecutive use of 2 CytoSorb adsorbers over a period of 41 hours (1st adsorber 15 hours, 2nd adsorber 26 hours)
Integration of the adsorber as bypass into the vv-ECMO circuit (Xenios console, Fesenius Medical Care) via the ECMO connections offered by CytoSorbents
Anticoagulation: initially without, then in the second treatment 200 IU/h heparin, with a target pTT of 40 – 45 sec
Measurements
Hemodynamics and catecholamine requirements
Inflammatory parameters
Metabolic parameters
Fluid balance
Myoglobin
Results
Under combined CytoSorb and vv-ECMO therapy, catecholamine requirements could be clearly reduced. Within 24 hours, norepinephrine demand was lowered to 0.09 µg/kg/min and could be stopped already on the first post op day
Treatment also led to a control of the hyperinflammatory situation as evidenced by a rapid reduction in interleukin-6 plasma levels and a normalization in leukocyte levels after the start of the hemoadsorption therapy
Already 5 hours after initiation of CytoSorb therapy, serum lactate had decreased from 9.8 to 4.8 mmol/l. Levels trended downwards over time reaching normal values 26 hours after the start of Cytosorb therapy
In parallel, the pH value normalized already during the first CytoSorb treatment
In addition, total fluid balance for the first 24 hours was only 1.5 litres and 2.6 litres for the first 48 hours. On day 3, this increased again by 2.3 litres. Afterwards, a negative fluid balance could be achieved throughout
Furthermore, therapy was associated with a rapid and sustained reduction in myoglobin and creatine kinase plasma levels
Patient Follow-Up
Bronchoscopies were repeatedly required due to viscous secretions and diffuse bleeding tendencies. HSV-1 was detected in the tracheal secretions, so that anti-viral therapy with aciclovir was started
Due to wide-complex tachycardia following contusio cordis, continuous amiodarone therapy was started, which was terminated after he converted back to sinus rhythm
As the duration of ventilation was expected to be long, a dilatative tracheotomy was performed on day 5 in the ICU. During the subsequent weaning period, the patient could tolerate spontaneous breathing trials and was able to breath adequately with stable gas exchange on Continuous Positive Airway Pressure (CPAP)
With sufficient improvement of pulmonary gas exchange and an increasing bleeding tendency in the context of an acquired von Willebrand syndrome, vv-ECMO therapy was discontinued after a total of 8 days
The last tracheal cannula change was performed on day 10 after admission to the ICU
Surgical treatment of the ulna fracture was performed by the trauma surgery team one week later
Given his pronounced stress reaction and agitation, sedation was extended until the patient could finally be weaned
At the time of transfer, the patient was awake, fully oriented, normotensive, catecholamine-free and breathing 3 x 2 hours a days using a heat and moisture exchanger
Conclusions
In this patient with severe polytrauma, hemorrhagic shock, traumatic brain injury and ARDS, the use of CytoSorb in combination with other therapeutic measures was associated with hemodynamic stabilization, control of the hyperinflammatory response, resolution of metabolic acidosis and reduction in myoglobin and creatine kinase levels
According to the authors, CytoSorb was helpful in this particular case for rapid control of the hyperinflammation in the setting of trauma and for achieving hemodynamic stability without massive volume overload. Contrary to all expectations, the use of CytoSorb prevented a significant positive fluid balance and thus an additional burden, especially to the lungs
The use of CytoSorb in combination with vv-ECMO proved to be safe and simple.
Case of the Week
The Sequential Use of Extracorporeal Cytokine Removal Devices in an Adolescent With COVID-19 Receiving Continuous Renal Replacement Therapy
Wun Fung Hui1, Renee Wan Yi Chan2,3,4,5 , Chun Kwok Wong6, Ka Hang Andy Kwok1, Wing Lum Cheung1, Fung Shan Chung1, Karen Ka Yan Leung1, Kam Lun Hon1, Shu Wing Ku1 1Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong. 2Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. 3Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong. 4Laboratory for Paediatric Respiratory Research, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. 5CUHK-UMCU Joint Research Laboratory of Respiratory Virus & Immunobiology, Department of Paediatrics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. 6Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. ASAIO J 2022; 68(12):e230-e234
12/21/2022
New!Peer Reviewed Published DataViral infectionCase of the Week / MonthCase reportCOVID-19Critical CareCRRT post filterInflammatory parameters
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Summary
CoW 43/2022 – This case reports on an a 14-year-boy (43 kg) without any respiratory symptoms, who was admitted to a regional hospital with a fever of one day associated with vomiting and breakthrough seizures.
Summary
A 14-year-old male (43kg) developed multisystem inflammatory syndrome in children (MIS-C) after acquiring the SARS-CoV-2 infection. He deteriorated rapidly requiring inotropic and ventilatory support as well as continuous renal replacement therapy (CRRT) due to rhabdomyolysis-associated acute kidney injury. CytoSorb was first incorporated into the post-CRRT filter circuit for myoglobin and cytokine removal (hour 18 – 40), which was followed by sequential use of Oxiris (hour 40 – 80), followed by another CytoSorb adsorber (hour 85 – 110), giving a total of 100 hours of extracorporeal blood purification [EBP] therapy. There were no major complications related to the EBP therapy including hemodynamic compromise. Cytokine profile revealed a marked reduction of levels of several cytokines including tumor necrosis factor-alpha (TNFa), interleukin (IL)-6, IL-8, and IL-10 after the EBP therapy. It was noted that both pro-inflammatory and anti-inflammatory cytokines were removed, and the removal efficacy varied between different devices. The authors note that the two devices appeared to complement each other’s adsorption capacity. His condition improved and the serum ferritin, C-reactive protein, and procalcitonin levels also dropped gradually, which correlated well with his clinical progress and the trend of cytokine levels. The authors conclude that this case demonstrates that extracorporeal cytokine removal can be safely applied in children with MIS-C and can be considered as adjunctive therapy in selected patients with critically ill conditions.
Case presentation
Known medical history included a de novo G-Protein Subunit Alpha O1 (GNAO1)-mutation with movement disorder, epilepsy, and severe intellectual disability receiving baclofen, tetrabenazine, carbamazepine, and clobazam
On admission, his temperature was 40.1°C, heart rate 150/min, blood pressure 90/50 mmHg, and desaturation requiring oxygen supplementation
He exhibited vigorous involuntary movements and developed a status dystonicus
Blood tests on admission showed a white blood cell count of 9.1×109/L (neutrophil and lymphocyte count of 7.7×109/L and 0.9 × 109/L, respectively), urea 2.9 mmol/L, creatinine 41 µmol/L (baseline creatinine level was 31 µmol/L) and creatine kinase (CK) level of 117575 IU/L. Moreover, he was also found to pass brownish-red (myoglobin-positive) urine
He went on to develop disseminated intravascular coagulation with thrombocytopenia with an abnormal clotting profile (INR 1.7, aPTT >120 s, D-dimer 5072.9 ng/ml and fibrinogen 2.24 g/L)
The nasopharyngeal swab proved positive for SARS-CoV-2
He was started on hyperhydration, empirical piperacillin/tazobactam and one dose of remdesivir
Oral chloral hydrate was used for sedation
Urine output was maintained at 2–3 ml/kg/hour but the persistent fever and tachycardia continued, as did the excessive movements
He later developed stage 2 acute kidney injury (AKI) with an estimated glomerular filtration rate (eGFR) of 75 ml/min/1.73 m2 and was therefore transferred to the pediatric intensive care unit (PICU) for further management
His CK level rose sharply to the peak level of 449,100 IU/L with hypernatremia (sodium level of 155 mmol/L) and metabolic acidosis (pH 7.33, bicarbonate level of 13.8, and base excess of -11.8 mmol/L)
The lactate level was 2.3 mmol/L, troponin-T level was 170 ng/L and the eGFR reduced to 66 ml/min/1.73m2
He developed abnormal liver function tests with serum levels of alanine aminotransferase (ALAT) 1469 IU/L, aspartate aminotransferase (ASAT) 6577 IU/L, and ammonia 52 µmol/L
There were also elevated levels of inflammatory markers including ferritin 5842 pmol/L, procalcitonin 13.63 ng/ml, and C-reactive protein (CRP) 130 mg/L
The clinical diagnosis was multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection triggering status dystonicus and subsequent rhabdomyolysis-associated AKI
After his transfer to the PICU, his blood pressure dropped to 60/40mmHg and SpO2 was 90%
A bedside echocardiogram showed impaired septal motion and mildly impaired left ventricular contractility with fractional shortening of 25%
He subsequently required intubation for respiratory failure, and a norepinephrine infusion was started at 0.03 µg/kg/min for hemodynamic support
Multiple sedative medications were used for sedation and control of his dystonia and dyskinesia in addition to his usual medications
Remdesivir was not continued due to his impaired liver function. Tocilizumab was starter later
He was started on continuous renal replacement therapy (CRRT) due to rhabdomyolysis-associated AKI
Ten hours after CRRT initiation, a CytoSorb hemoadsorption column was integrated into the CRRT circuit to enhance myoglobin and cytokine removal
Treatment
CytoSorb was first incorporated into the CRRT circuit for myoglobin and cytokine removal (hour 18 – 40), which was followed by sequential use of Oxiris (hour 40 – 80), followed by another CytoSorb adsorber (hour 85 – 110), giving a total of 100 hours of extracorporeal blood purification [EBP] therapy
CytoSorb was used in conjunction with CRRT run in high-volume continuous veno-venous hemodiafiltration (HF CVVHDF) mode using the Prismaflex system
Position of the adsorber: post-CRRT filter
Measurements
Hemodynamics and catecholamine requirements
Inflammatory parameters
Creatine kinase
Results
Initially, he continued to deteriorate with persistent hypotension requiring escalation of inotropes. However, there were no major complications related to the EBP therapy including hemodynamic compromise
Cytokine profile revealed a marked reduction of levels of several cytokines including tumor necrosis factor-alpha (TNFa), interleukin (IL)-6, IL-8, and IL-10 after the EBP therapy. His condition improved under both EBP therapies and the serum ferritin, C-reactive protein, and procalcitonin levels also dropped gradually, which correlated well with his clinical progress and the trend of cytokine levels
The serum levels of CK gradually decreased
Patient Follow-Up
A dose of intravenous immunoglobulin (IVIG) and dexamethasone were added during therapy
It was possible to stop all inotropes 4 days after PICU admission
Extubation was possible on 8th day of PICU admission
The CRRT doses were gradually reduced, and it was possible to stop CRRT support 8 days after admission
The clinical course was complicated by secondary Pseudomonas aeruginosa pneumonia requiring an additional course of antibiotics for two weeks
The patient was finally discharged from the PICU to his original hospital one month after admission
Conclusions
In this case of an adolescent with MIS-C following SARS-CoV-2 infection as well as rhabdomyolysis-associated acute kidney injury, the application of extracorporeal blood purification therapy was associated with pronounced hemodynamic stabilization, as well as a marked reduction in levels of several cytokines and creatine kinase
It was noted that both pro-inflammatory and anti-inflammatory cytokines were removed, and the removal efficacy varied between different devices. However, the authors note that the two devices (CytoSorb + Oxiris) appeared to complement each other’s adsorption capacity
The authors conclude that this case demonstrates that extracorporeal cytokine removal can be safely applied in children with MIS-C and can be considered as adjunctive therapy in selected patients with critically ill conditions.
New on PubMed
Case Reports
A rare case of acute liver failure with intrahepatic cholestasis due to dengue hemorrhagic fever: CytoSorb® and plasma exchange aided in the recovery: case report
Arosha Minori Gunasekera et al. BMC Infect Dis. 2022.
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BMC Infect Dis
. 2022 Dec 13;22(1):938.
doi: 10.1186/s12879-022-07933-y.
Authors
Arosha Minori Gunasekera 1 , Udeshan Eranthaka 2 , Dilshan Priyankara 2 , Ranjith Kalupahana 2
Affiliations
1 National Hospital of Sri Lanka, Colombo, Sri Lanka. arosha.minorig@gmail.com.
2 National Hospital of Sri Lanka, Colombo, Sri Lanka.
PMID: 36514003
DOI: 10.1186/s12879-022-07933-y
Cite
Abstract
Background: Dengue haemorrhagic fever is a severe form of acute dengue infection characterized by leakage of plasma through capillaries into body spaces resulting in circulatory insufficiency leading to shock. Despite varying degrees of liver involvement occurring in acute dengue infection, intrahepatic cholestasis is very rare in the literature with only two cases reported so far. We report a challenging case of a middle-aged woman with DHF complicated by acute liver failure, coagulopathy, acute renal failure and prolonged intrahepatic cholestasis. She was successfully managed in the intensive care unit with supportive therapy, Cytosorb® and therapeutic plasma exchange.
Case presentation: A 54-year-old Sri Lankan obese woman with multiple comorbidities presented with fever, headache, vomiting and generalized malaise for 3 days and was diagnosed with dengue haemorrhagic fever. Despite the standard dengue management, she clinically deteriorated due to development of complications such as, acute liver injury, intrahepatic cholestasis and acute renal injury. Acute liver failure was evidenced by transaminitis, lactic acidosis, coagulopathy with pervaginal bleeding and severe encephalopathy necessitating elective intubation and mechanical ventilation. She was immediately transferred to intensive care facilities where she underwent supportive management for liver failure, continuous renal replacement therapy coupled with cytosorb and therapeutic plasma exchange with which she made a remarkable recovery.
Conclusion: Acute liver failure with a prolonged phase of intrahepatic cholestasis is a very rare complication of acute dengue illness which is sparsely documented in medical literature so far. This patient was managed successfully with supportive therapy, aided by cytoSorb hemo-adsorption and therapeutic plasma exchange.
Keywords: Acute liver failure; Cholestasis; Cytosorb®; Dengue fever; Dengue haemorrhagic fever; Therapeutic plasma exchange.
Case of the Week
Literature Database
Use of hemadsorption in pediatric meningococcal sepsis, Waterhouse-Friderichsen-Syndrome, and multiple organ failure
Guido Mandilaras, Simone Katrin Dold, Robert Dalla Pozza Division of Pediatric Cardiology and Pediatric Intensive Care, University Hospital, LMU Munich, Munich, Germany. Open Journal of Clinical & Medical Case Reports 2022; 8(12):1889
12/13/2022
New!PediatricsReduction in catecholaminesSafetySeptic ShockAnticoagulation HeparinCase of the weekCase reportCritical CareCRRT (pre or post filter)Inflammatory parameters
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Summary
CoW 42/2022 – This case reports on an 18-year-old male without relevant medical history, who presented at the emergency room of a peripheral primary care hospital with nausea and headaches.
Summary
Community-acquired bacterial meningitis still represents one of the most important infectious diseases worldwide and remains a substantial cause of mortality and morbidity, particularly in both the very young and the elderly patients. The disease is characterized by a hyperinflammatory response with a rapid and excessive production of inflammatory mediators, accompanied by disseminated intravascular coagulation (DIC) and development of Waterhouse–Friderichsen syndrome. Extracorporeal blood purification therapies represent a new therapeutic approach since they seem to be able to attenuate this detrimental process by lowering systemic cytokine levels. We herein report on an 18-year-old previously healthy male who had to be intubated and mechanically ventilated shortly after hospital admission followed by confirmation of Neisseria meningitidis infection. Antibiotic as well as catecholamine and volume therapy were initiated. Over time he developed excessive hyperinflammation, Waterhouse-Friderichsen-syndrome with purpura fulminans, hyperlactatemia and progressive renal failure, leading to the initiation of combined renal replacement and CytoSorb hemoadsorption therapy. This resulted in significant decrease in inflammatory parameters and a progressive reduction in catecholamine and lactate levels while peripheral perfusion was restored preventing any loss of extremities. The patient could be extubated 10 days after PICU admission. No adverse or unwanted device-related side effects were documented. In conclusion, this case report is supporting other promising results in this highly sensitive patient cohort, by showing rapid hemodynamic stabilization and control of hyperinflammation being associated with the use of CytoSorb, however, evidence on the application of the CytoSorb adsorber in pediatrics remain rather sparse and more clinical data are needed.
Case presentation
During the hospital admission process, the patient rapidly developed petechiae over his entire body, resulting in the preliminary diagnosis of meningococcal sepsis
Following initiation of antibacterial therapy with cefotaxime (2 x 4g iv) and ampicillin (3 x 5g iv) as well as administration of dexamethasone (3 x 10 mg iv), the patient had to be intubated due to respiratory insufficiency and a central venous and arterial catheters were inserted
Subsequently, catecholamine (norepinephrine 0.8 mg/h) and volume therapy (2 l isotonic saline, 2000 IE prothrombin complex, 2x fresh frozen plasma, 1x platelet concentrate) were started due to progressive hemodynamic instability
Microbiological analysis of the liquor puncture confirmed presence of Neisseria Meningitidis type B bacteria
The mechanically ventilated patient was then transferred under ongoing catecholamine therapy to the pediatric intensive care (PICU) unit for further diagnosis and therapy
At this time, clinically the patient was exhibiting a picture of full-blown Waterhouse-Friderichsen-syndrome with purpura fulminans accompanied by ubiquitous petechial hemorrhages and hyperlactatemia (max. 10.8 mmol/l)
Hydrocortisone administration was started according to the guidelines (50 mg/m² body surface) along with sedation with midazolam, and sufentanyl, which was later complemented by propofol and dexmedetomidine
Antibiotic therapy was supplemented by tobramycin and his disseminated intravascular coagulopathy (DIC) was treated by means of repeated doses of fresh frozen plasma, platelet concentrates, and vitamin K
Echocardiography revealed a restricted cardiac function with an ejection fraction of 31% and inotropic therapy was extended by epinephrine and milrinone, accordingly
Mechanical ventilation had to be intensified because of increasing bronchial secretions and left atelectasis (max positive end-expiratory pressure [PEEP] 10 mbar)
Due to progressive renal failure with elevated retention parameters, continuous renal replacement therapy (CRRT) was started five hours after PICU admission and approximately twelve hours later a CytoSorb hemoadsorber was additionally added to the circuit to control excessive hyperinflammation (Interleukin – IL-6 >200,000 pg/ml)
Treatment
Two CytoSorb treatment sessions were performed for a total duration of approximately 50 hours
CytoSorb was used in combination with CRRT run in continuous veno-venous hemodiafiltration (CVVHDF) mode
Blood flow rate: 120 ml/min
Anticoagulation: heparin
Measurements
Hemodynamics and catecholamine requirements
Inflammation
Lactate
Respiratory status
Cardiac function
Sequelae of DIC
Results
Therapy resulted in early and rapid hemodynamic stabilization accompanied by a prompt decrease in norepinephrine and epinephrine doses. The epinephrine infusion could already be tapered off at the end of the second hemoadsorption session
During combined CVVHDF and hemoadsorption treatment, there was also a significant decrease in inflammatory parameters noted, pointing towards control of the hyperinflammatory state. IL-6 levels reduced from >200,000 to 770 pg/ml within the first 48 hours of combined therapy
Lactate levels also reduced progressively
The respiratory situation stabilized during treatment and cardiac function started to improve
Additionally, there were no further petechial hemorrhages, and no peripheral ischemia observed with no loss of extremities in the follow-up period
Patient Follow-Up
Continuous hemodiafiltration was switched to intermittent dialysis as renal function consecutively improved as evidenced by a normalization in retention parameters and return of spontaneous diuresis
The pulmonary situation slowly improved with inhalation and repeated bronchoscopy with bronchial lavage, so that the patient could be extubated 10 days after PICU admission
Ongoing follow-up was characterized by mild delirium and development of critical illness neuropathy with pronounced tremors, which, however, resolved during his stay
Two weeks after admission to the PICU, the patient was transferred to the general pediatric ward in a stable clinical condition with a normal cardiac function (EF 70%) and was discharged from the hospital shortly afterwards
Conclusions
Treatment in this adolescent patient with meningococcal sepsis, Waterhouse-Friderichsen-Syndrome, and multiple organ failure was associated with a rapid and significant reduction in plasma cytokine levels, accompanied by improved hemodynamics, normalization of plasma lactate levels and restored peripheral perfusion preventing any loss of extremities
As such, this case report supports other promising results in this highly sensitive patient cohort
The very positive clinical course in our case does not imply that there was relevant removal of any of the antibiotics used
No adverse or device-related side effects were documented during or after the treatment sessions and the combination was practical, technically feasible and appeared to be highly beneficial for the patient.
New on PubMed
Hemoadsorption in Complex Cardiac Surgery-A Single Center Experience
Murali Manohar et al. J Clin Med. 2022.
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J Clin Med
. 2022 Nov 27;11(23):7005.
doi: 10.3390/jcm11237005.
Authors
Murali Manohar 1 , Vivek Jawali 1 2 , Siddu Neginahal 3 , Sudarshan Gt 1 , Geetha Muniraj 4 , Murali Chakravarthy 4
Affiliations
1 Cardiac Surgery Department, Fortis Hospital, Bengaluru 560076, India.
2 Cardiac Sciences Board, Fortis Hospital, Bengaluru 560076, India.
3 Cardiac Surgery Perfusion Department, Fortis Hospital, Bengaluru 560076, India.
4 Anaesthesia Department, Fortis Hospital, Bengaluru 560076, India.
PMID: 36498579
DOI: 10.3390/jcm11237005
Cite
Abstract
(1) Background: Cardiac surgery may evoke a generalized inflammatory response, typically magnified in complex, combined, redo, and emergency procedures with long aortic cross-clamp times. Various treatment options have been introduced to help regain control over post-cardiac surgery hyper-inflammation, including hemoadsorptive immunomodulation with CytoSorb®. (2) Methods: We conducted a single-center retrospective observational study of patients undergoing complex cardiac surgery. Patients intra-operatively treated with CytoSorb® were compared to a control group. The primary outcome was the change in the vasoactive-inotropic score (VIS) from pre-operatively to post-operatively. (3) Results: A total of 52 patients were included in the analysis, where 23 were treated with CytoSorb® (CS) and 29 without (controls). The mean VIS increase from pre-operative to post-operative values was significantly lower in the CS group compared to the control group (3.5 vs. 5.5, respectively, p = 0.05). In-hospital mortality in the control group was 20.7% (6 patients) and 9.1% (2 patients) in the CS group (p = 0.26). Lactate level changes were comparable, and the median intensive care unit and hospital lengths of stay were similar between groups. (4) Conclusions: Despite notable imbalances between the groups, the signals revealed point toward better hemodynamic stability with CytoSorb® hemoadsorption in complex cardiac surgery and a trend of lower mortality.
Keywords: aortic surgery; blood purification; complex cardiac surgery; cytokines; cytosorb; hemoadsorption; hyperinflammation; redo.
Case of the Week 41
Hemadsorption: A New Therapeutic Option for Selected Cases of Bromazepam Intoxication
Mekeirele M, Verheyen S, Van Lancker R, Wuyts S, Balthazar T. Case Reports in Nephrology and Dialysis 2022; 12(3):163-166
12/06/2022
New!Peer Reviewed Published DataCase reportCritical CareCRRT (pre or post filter)Drug removalIntoxicationLiver failure
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Summary
CoW 41/2022 – This case reports on an a 67-year-old woman with CHILD-C liver cirrhosis, who was admitted to the tertiary intensive care unit (ICU) after intoxication with bromazepam.
Benzodiazepine ingestion can account for around 21% of all intoxications requiring admission to Intensive Care (IC). Management is normally with a supportive approach and with the use of flumazenil, an antidote for benzodiazepines, however, flumazenil does not influence elimination. In this case report, a 67 yr old patient with impaired liver function (CHILD-C cirrhosis) was admitted after intoxication with the benzodiazepine, bromazepam. The initial plasma concentration was very high (874 mg/L, upper limit of normal 170 mg/L). She became increasingly drowsy with respiratory insufficiency so a flumazenil infusion was started resulting in her becoming more alert, however, the infusion rate could not be decreased due to her repeatedly relapsing into stupor. Due to her liver failure (and consequent slow metabolism), it was calculated that the half-life of bromazepam would be 10 days rather than 10 hrs, requiring a stay of 23 days on the ICU, so CytoSorb hemoadsorption was initiated using continuous venovenous hemofiltration (CVVHF). Pre and post CytoSorb adsorber blood levels were taken. Results showed that elimination of bromazepam by CytoSorb was quick and efficient (-31% after 1 h, -56% after 11 h). After the first 11 hrs there was a quick decline in adsorbing capacity suggesting saturation, however, by this time the patient was in the upper limit of normal for bromazepam, so no second hemoadsorber was needed and the flumazenil infusion could be quickly tapered off within 1 day. The authors conclude that hemadsorption is a viable option to reduce length of IC stay or need for intubation in slow metabolizers. They state that the cost of a prolonged stay in the intensive care unit is significantly higher than the cost of an adsorber.
Case presentation
The initial plasma concentration was 874 µg/L (upper limit of normal 170 µg/L)
The patient developed respiratory failure due to decreased consciousness
Given the expected slow decrease in plasma levels of bromazepam due to cirrhosis and the inherent risk of a prolonged need for mechanical ventilation, an infusion of flumazenil was initiated to avoid intubation
The patient regained consciousness and remained stable, but the flumazenil infusion rate could not be decreased due to a relapse in stupor following this intervention
As expected, only a very slow decrease in bromazepam titer was observed
Based on the decline in titer, the half-life of bromazepam was calculated to be 10 days rather than the expected 10 h. This implied that a reduction of the bromazepam titer to 170 µg/L could only be expected after 23 days of ICU admission, warranting a search for further therapeutic options
Hence hemadsorption was initiated in combination with continuous renal replacement therapy (CRRT)
Treatment
CytoSorb was used in conjunction with CRRT run in continuous veno-venous hemofiltration (CVVHF) mode using the Prismax® (Baxter, IL, USA) system
Measurements
Sequential quantifications of bromazepam levels from blood taken pre and post CytoSorb adsorber
Results
Application of CytoSorb resulted in the quick and efficient elimination of bromazepam (-31% after 1 h, -56% after 11 h). There was no rebound in plasma titer after cessation of the hemadsorption therapy and the patient attained the target level of bromazepam 13 days earlier than predicted without the hemoadsorber
Patient Follow-Up
After the first 11 hrs there was a quick decline in adsorbing capacity suggesting saturation. However, by this time the patient was in the upper therapeutic limit for bromazepam, so no second hemoadsorber was needed
The flumazenil infusion could be quickly tapered off within 1 day
Conclusions
The application of CytoSorb proved to be effective in eliminating bromazepam in a patient with CHILD-C cirrhosis
The authors conclude that hemoadsorption is a viable option to reduce length of ICU stay or need for intubation in slow metabolizers
They state that the cost of a prolonged stay in the intensive care unit is significantly higher than the cost of an adsorber.
Case of the Week
Hemoadsorption as part of a multimodal therapy concept to treat Capnocytophaga sepsis with thrombocytopenia and multiple organ failure
Kreutz J, Choukeir M, Chatzis G, Schieffer B, Markus B. Int Journal Art Organs 2022; epub
11/30/2022
MyoglobinNew!Other indicationsPeer Reviewed Published DataRhabdomyolysisSafetySeptic ShockAnticoagulation CitrateCase of the weekCase reportCritical CareCRRT (pre or post filter)Inflammatory parameters
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Summary
CoW 40/2022 – This case reports on a 68-year-old male with known arterial hypertension, who presented at the hospital by ambulance following severe deterioration of his general condition including fever up to 39°C, oliguria and repeated vomiting over the recent days.
In this case report a 68-year-old presented at the hospital following a severe deterioration in his general condition, including fever up to 39°C, oliguria and repeated vomiting for a couple of days following a dog bit to his right foot whilst on holiday. On admission, the patient showed pronounced marbling and cyanosis to all extremities and ears. The reddened bite wound to the second toe did not appear infected so there was no medical or surgical intervention at this time. Despite standard therapy including antibiotics and multiple blood products he developed septic shock with acute renal failure, liver dysfunction, cognitive dysfunction and respiratory deterioration so was started on continuous renal replacement therapy (CRRT), and eventually intubated and ventilated. Given the patients hyperinflammatory condition a CytoSorb hemoadsorber was additionally integrated into the CRRT circuit. In total 4 adsorbers were used during this 1st therapy interval (changed every 12 hrs). CytoSorb was then stopped for 24 hrs as he improved clinically, however, due to a relapse in his clinical condition, CytoSorb was then restarted for another 5 treatment sessions for 24 hours each (2nd therapy interval). All of the applied therapeutic measures led to rapid clinical stabilization, control of the hyperinflammatory situation, and improvement in his neurological status. The therapy was well tolerated with no complications encountered. The patient was able to be extubated after 3 days of mechanical ventilation and he was finally able to be transferred to a rehabilitation unit in a stable condition after a total hospital stay of 32 days. This is the first clinical case describing the successful application of a multimodal treatment approach including extracorporeal blood purification therapy in a patient with septic shock, acute renal failure and severe thrombocytopenia with signs of DIC and TMA due to Capnocytophaga infection following a dog bite.
Case presentation
Two days previously, he had returned from a vacation where he had had a dog bite to his right foot and subsequently complained of chills, sweating, tachycardia, and general malaise
On admission, the patient showed pronounced marbling to all extremities and ears with cyanosis of his extremities. The reddened bite wound to the second toe did not appear infected so there was no need for any medical or surgical intervention at this time
Subsequent chest X-ray examination for a focus proved inconclusive
Echocardiography revealed a mild to moderately reduced systolic function, which was consistent with septic cardiomyopathy
In addition, an infection-triggered atrial fibrillation was detected during this acute phase
Laboratory diagnostics revealed clearly elevated infection parameters (leucocytes 33 G/l, procalcitonin (PCT) >100 µg/l, C-reactive protein (CRP) 298 mg/l, interleukin (IL)-6 1866 pg/ml) and in light of all of these findings, the patient was diagnosed with sepsis progressing to septic shock
In addition, his coagulation status was markedly deranged (thrombocytes 6 G/l, Quick 22%, International Normalized Ratio [INR] 3.1, activated Partial Thromboplastin Time [aPTT] 112 sec) consistent with disseminated intravascular coagulopathy (DIC) and thrombotic microangiopathy (TMA), resulting in the administration of fresh frozen plasma (FFP) and platelet concentrates to stabilize his coagulopathy
Also, over time, a red blood cell transfusion was needed due to considerable volume administration of blood products leading to dilution, low hemoglobin (13.8 g/dl) and signs of hemolysis as evidenced by clearly increased levels of lactate dehydrogenase (3164 U/l)
Following detection of intracellular and extracellular rod-shaped bacteria in the initial differential blood count and in the blood smear with suspected Capnocytophaga canimorsus infection, anti-infective therapy was initiated with ampicillin/sulbactam and clarithromycin. The antibiotic regimen was then escalated to piperacillin/tazobactam (18 g/24h) and levofloxacin (500 mg twice daily). As infection parameters continued to increase further, antibiotic therapy was again escalated to imipenem (4 g per day) on day 2
Additionally, the patient received 2 units of FFP every 6 hours
In the context of increasing retention parameters (creatinine 4.34 mg/dl) and oliguria (24 hours diuresis 150 ml) under ongoing volume resuscitation, the decision was made to initiate continuous renal replacement therapy (CRRT)
Furthermore, high-flow oxygen therapy was started because of assumed cardiac decompensation with incipient pulmonary edema and his significantly reduced general condition
Radiological examination, however, only revealed a slight congestion with bilateral pulmonary infiltrates
The patient also exhibited signs of liver dysfunction (aspartate aminotransferase [AST] 1094 U/l, alanine aminotransferase [ALT] 365 U/l, lactate dehydrogenase [LDH] 3164 U/l, bilirubin 2.89 mg/dl) as well as increased creatine kinase (418 U/l) and myoglobin levels (1674 µg/l)
Laboratory diagnostics further revealed severe hyperlactatemia (6.3 mmol/l)
Over time, the patient showed progressive respiratory deterioration whilst on high-flow oxygen therapy and so he was switched to non-invasive oxygen therapy
However, due to clearly reduced vigilance (Glasgow Coma Scale [GCS] 8) and incipient respiratory insufficiency with progressive metabolic acidosis (pH 7.34), the patient eventually had to be intubated and mechanically ventilated on the same day
During this episode of respiratory decompensation, norepinephrine and dobutamine infusions were required briefly
Given the patients hyperinflammatory condition in the context of septic shock, a CytoSorb hemoadsorber was additionally integrated into the CRRT circuit
After clinical improvement under CytoSorb treatment, therapy was discontinued. However, due to a recurrence in clinical deterioration, hemoadsorption therapy had to be reinstituted for a second therapy interval
Treatment
The patient received a total of 9 CytoSorb hemoadsorption therapy sessions over the following 8 days (4 adsorbers during the first two days changed every 12 hours [1st therapy interval], pause interval of 24 hours, thereafter another 5 treatment sessions for 24 hours each [2nd therapy interval])
CytoSorb was used in conjunction with CRRT run in continuous veno-venous hemodiafiltration (CVVHDF) mode
Blood flow rate: 100 ml/min
Anticoagulation: citrate
Measurements
Inflammatory parameters
Myoglobin
Lactate
Neurologic status
Results
During the course of combined hemoadsorption and renal replacement therapy treatment, stabilization in his overall clinical condition was noticed accompanied by clear control of the hyperinflammatory situation as evidenced by a significant decrease in inflammatory parameters by the end of the treatment cycle (e.g. PCT from >100 to 1.2 µg/L after CytoSorb treatment, CRP from 298 to 94 mg/L. IL- 6 levels decreased from 1866 to 833 pg/ml within one day of CytoSorb initiation)
Plasma concentrations of myoglobin could be reduced from 1674 to 108 µg/L
Lactate decreased from 6.3 to 0.9 mmol/L during the course of the 9 therapy sessions
Combined CRRT+CytoSorb therapy was further associated with neurological improvement finally resulting in swift extubation after 3 days of mechanical ventilation
Patient Follow-up
On the 7th day on the intensive care unit, blood cultures, which have already been preserved at the time of admission, yielded the Gram-negative bacillus Capnocytophaga canimorsus
Markers of inflammation increased after discontinuation of imipenem most probably in the context of a concomitant pneumonia, requiring escalation of antimicrobial therapy to vancomycin plus ceftazidime
His reduced left ventricular function recovered during his inpatient stay
With improved urinary output, CRRT was discontinued
Of note, during his hospital stay, the patient received prednisolone (100 mg/d) for 3 days as additional therapy as well as a total of 51 units of FFP
He was finally transferred to a rehabilitation unit in a cardio-respiratory stable general condition after a total hospital stay of 32 days
At the time of discharge, the patient still had dry necroses on two toes of both feet which will probably lead to amputation over time
Conclusion
This is the first clinical case describing the successful application of a multimodal treatment approach including extracorporeal blood purification therapy in a patient with septic shock, acute renal failure, and severe thrombocytopenia with signs of DIC and TMA due to Capnocytophaga infection following a dog bite
Application of therapeutic measures including antibiotic therapy, mass transfusions, CRRT and CytoSorb hemoadsorption therapy was associated with rapid clinical stabilization, control of the hyperinflammatory situation, and improvement in his neurological status
The therapy was well tolerated with no complications encountered
This case supports the clinical recognition of severe Capnocytophaga infection that can lead to critical conditions even in immunocompetent patients.
Case of the Week
Literature Database
A New Apheresis Device for Antithrombotic Drug Removal during Off-Pump Coronary Artery Bypass Surgery
Helmut Mair 1, Norman Micka1, Ferdinand Vogt1,2, Dow Rosenzweig1, Frank Vogel3, Benedikt Baumer1 , Stephanie Ulrich4 and Peter Lamm1 | 1Department of Cardiac Surgery, Artemed Klinikum München Süd, 81379 Munich, Germany | 2Department of Cardiac Surgery, Paracelsus Medical University, 40791 Nuremberg, Germany | 3Department of Anesthesiology, Artemed Klinikum München Süd, 81379 Munich, Germany | 4Department of Cardiology, Benedictus Krankenhaus Tutzing, 82327 Tutzing, Germany | Medicina 2022; 58(10):1427
10/19/2022
New!Case of the week
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Summary
CoW 35/2022 – This case reports on an a 74-year-old male patient who was admitted to Artemed Klinikum Munich South, for urgent coronary artery bypass grafting (CABG) for severe three-vessel disease (occluded right coronary artery, severe stenosis of the left descending artery, and severe stenosis of the circumflex artery).
Case presentation
The patient was treated with Dual Antiplatelet Therapy (DAPT) (ticagrelor 2×90 mg/day plus aspirin 100 mg/day) for the acute coronary syndrome and non-ST elevated myocardial infarction (NSTEMI) after an acute occlusion of the right coronary artery
Additional medical history included hypothyroidism, moderate diverticulitis, hypercholesterolemia, and hypertension
In addition to DAPT, the patient was treated with rosuvastatin, bisoprolol and L-thyroxin
Ticagrelor was stopped the day before surgery
After the initiation of standard anesthetic care, tubes were connected to a 12 F, 3-lumen high-flow catheter, which was implanted into the right cervical vein of the patient. This enabled treatment with the CytoSorb intended to remove residual ticagrelor throughout the operation
The off-pump coronary artery bypass (OPCAB) procedure included harvesting the left internal thoracic artery (LITA), myocardial revascularization using an Octopus tissue stabilizer with the LITA to the left anterior descending artery and venous grafts to the circumflex artery and to the right coronary artery. The procedure was then finished using standard techniques while the graft showed good flow rates
Treatment
Adsorption was initiated with the skin incision and was continued for 221 min
CytoSorb was run in conjunction with a new apheresis platform, PUR-01 (Nikkisio Co., Ltd., Tokyo, Japan)
Blood flow rate: 150-200 ml/min. The blood volume that had circulated through the CytoSorb during the 221 min treatment phase was 39.04 L
Anticoagulation: with start, 5000 I.E. single injection of heparin. Prior to the bypass anastomosis, another 10,000 units of heparin were administered (activated coagulation time > 300 s)
Measurements
Hemodynamics and norepinephrine requirements
Chest drain volume
Hemoglobin
Creatine kinase levels
Results
Mid-range doses of norepinephrine could be reduced and finally stopped by the end of the first postoperative day
The chest tubes delivered 440 mL in 24 h
Hemoglobin (Hb) dropped from 13.1 g/dL preoperatively to 9.3 g/dL postoperatively so that perioperatively, 2 units of red blood cells were infused
Postoperatively, the maximum creatine kinase level was 232 U/L (normal range, < 190 U/L), and the creatine kinase MB (CKMB) isoenzyme was 6.5 µg/L (normal range, < 5.2 µg/L)
Patient Follow-up
Postop the patient was transferred to the intensive care unit and was extubated the same day
Chest tubes were removed on the second postoperative day
On discharge, the Hb was 12.4 g/dL
The further postoperative course was uneventful, with good recovery of the patient
At the 6 weeks follow-up, the patient demonstrated a normal left ventricular function and sinus rhythm, with no cardiac symptoms
Conclusion
This is the first report on the intraoperative use of a PUR-01 apheresis pump in combination with a CytoSorb adsorption column to remove ticagrelor during an OPCAB procedure
The treatment resulted in good control of the peri- and postoperative bleeding risk and hemodynamic stabilization, with a concomitant reduction in norepinephrine requirements as well as an overall satisfactory clinical outcome
This is the first publication showing that the setup is feasible and safe with no device-related adverse events occurring
Note from CytoSorbents: The setting to use CytoSorb for ticagrelor removal outside cardiopulmonary bypass, however, is not covered in the current Instructions for Use.
A New Apheresis Device for Antithrombotic Drug Removal during Off-Pump Coronary Artery Bypass Surgery
Mair H, Micka N, Vogt F, Rosenzweig D, Vogel F, Baumer B, Ulrich S, Lamm P. Medicina 2022; 58(10):1427
10/12/2022
New!Observational studyPeer Reviewed Published DataSafetyStandalone (HP)TransfusionsAnti throm. removalRe-thoracotomyCardiac surgeryCase seriesDrug removalIntra-Op
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Summary
In this report, the first reference case on the use of CytoSorb with the direct hemoperfusion pump PUR-01 (Nikkisio) is reported, during urgent off-pump cardiac surgery (OPCAB) in a 74 yr old on concomitant Dual Antiplatelet Therapy (DAPT) with ticagrelor and aspirin. The hemoperfusion device ran for 221 mins to eliminate ticagrelor with a total blood volume through the CytoSorb of 39.04 L. The patient’s care postoperatively was uneventful and he made a good recovery with no cardiac symptoms at six week follow up. Since this initial case a further 3 patients on DAPT requiring OPCAB surgery have been operated on using this system. In all patients the intraoperative surgical procedure has not been complicated by any remarkably enhanced bleeding, no patient has required a reoperation, and the postoperative course has been uneventful. In summary, in this study the use of CytoSorb with a hemoperfusion pump during OPCAB surgery for the removal of the antiplatelet drug ticagrelor has proved successful, with no device related adverse events occurring. Treatment has resulted in good control of the peri- and postoperative bleeding risk, hemodynamic stabilization, and satisfactory clinical outcome.
Case of the Week
Literature Database
Intraoperative use of CytoSorb in a mitral valve replacement redo procedure due to infective endocarditis
Darío Andrade1, David Orozco-Vinasco2 | 1Department of Cardiac Surgery, Clínica Colsubsidio Calle 100, Bogota, Colombia | 2Department of Cardiovascular Anesthesia, Clínica Colsubsidio Calle 100, Bogota, Colombia
10/05/2022
Reduction in catecholaminesAnticoagulation HeparinCardiac surgeryCase of the weekCase reportCPBEndocarditisInflammatory parametersIntra-Op
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Summary
CoW 34/2021 – This case reports on a 18-year-old male patient, who was admitted to a secondary hospital due to febrile symptoms (38.5-39°C) and headache with deterioration of his neurological status (bradypsychia, deviation of gaze and vomiting) after outpatient antibiotic management following suspected neuro-infection.
Case presentation
Known medical history included Marfan syndrome, bacterial endocarditis at the age of 16 as well as mitral valve replacement with a mechanical prosthesis 8 months before the current hospitalization
Antibiotic therapy at this time point consisted of vancomycin (870 mg every 12 hours), rifampicin (300 mg every 8 hours) and gentamicin (60 mg iv every 8 hours)
Following admission, he was evaluated and after diagnostic brain CT imaging and laboratory analysis, initial working diagnosis was either endocarditis and/or septic embolism in the brain
Due to his medical history, he was then referred to the Clínica Colsubsidio Calle 100, Bogota, being a tertiary referral centre
Subsequent transesophageal echocardiography showed preserved contractility and systolic function, with a left ventricular ejection fraction (LVEF) of 58%, mechanical prosthesis in mitral position with elevated transvalvular gradients, echo-dense mass described in anterior portion of prosthetic ring compatible with a vegetation, and at least moderate anterior paravalvular leak
Over the following 4 days, the patient was evaluated for potential surgical treatment. However, due to the unknown etiology of his cerebrovascular event, additional studies were performed including checks for potential infectious diseases (e.g. COVID-19), and more advanced laboratory tests
Contrast magnetic resonance imaging (MRI) then confirmed an ischemic event in the late subacute evolutionary phase of probable embologenic etiology (septic) being the most likely cause, however micro-abscesses were also considered as differential diagnosis
Four days later, further neurological examinations reconfirmed an ischemic acute cerebrovascular event without hemorrhagic transformation and micro-abscesses. The antimicrobial management was deemed appropriate and was proposed to be continued for at least 4 weeks
Prior to surgery, the patient showed profound hemodynamic instability with a decreased systemic vascular resistance index (SVRI, 620 dyn*s*cm5*m²) requiring massive doses of vasopressors (vasopressin 3 IU/h, norepinephrine 0.5 µg/kg/min)
Additionally, hemodynamic disturbances translated into profound lactic acidosis (4.4 mmol/l)
As there were no contraindications for surgery nor for the use of anticoagulants, the redo procedure was scheduled for the next day and consisted of mitral valve replacement (MVR) with a mechanical prosthesis and tricuspid annuloplasty
Given the young age of the patient, his extensive medical history, the infectious profile as well as the hemodynamic instability, a CytoSorb hemoadsorber was integrated into the cardiopulmonary bypass (CPB) circuit with the rationale to stabilize hemodynamics and to reduce the hyperinflammatory response, which was anticipated would be triggered by this major procedure in a patient with considerable cardiac history
Treatment
CytoSorb was used in conjunction with the cardiopulmonary bypass machine (SARNS 8.000, Terumo. Additionally BP-80 Centrifugal pump, Medtronic) for a period of 100 minutes, cross clamp time was 90 min
Anticoagulation: heparin
Blood flow rate: 500 ml/min
ACT: 418 – 527 – 483 – 144 sec
Total heparin: 32,500 IU
Protamine: 30,000 IU
Ultrafiltration rate: 2.200 cc
Administered blood components during surgery: 2x fresh frozen plasma, 6x cryoprecipitate, 1x red blood cell concentrate
Measurements
Hemodynamics and catecholamine requirements
Lactate values
Inflammatory parameters
Postoperative bleeding rate
Results
Perioperatively, his vasopressor demand increased transiently and dobutamine had to be added. However, already 60 minutes after completion of the procedure, dosages of vasopressors could be decreased considerably (vasopressin 1 IU/h, norepinephrine: 0.05 µg/kg/min). Six hours after the procedure, vasopressin and norepinephrine infusion could be stopped and dobutamine was kept at 2.5 µg/kg/min to support contractility
This was accompanied by a decrease in plasma lactate concentrations from 4 mmol/l pre-treatment to 2.9 mmol/l during CPB and 2.5 mmol/l post CPB
Also levels of C-reactive protein (CRP) decreased under CytoSorb therapy: CRP pre 77 mg/l, CRP during CPB 3.3 mg/l, CRP post CPB 2.8 mg/l
Patient Follow-Up
Extubation 12 hours after leaving the operating theatre
Clinical evidence of good peripheral perfusion
No bleeding complications occurred and surgical drains were removed after 48 hours
Examination of valve cultures later confirmed colonization with S. hominis so it was decided to maintain antibiotic treatment with vancomycin for another 6 weeks
The patient developed a complete AV block postoperatively, and the electrophysiology department opted for permanent pacemaker implantation, while neurology recommended continuation of treatment initially in the intensive care unit
Transfer of the patient to the normal ward 6 days after the procedure and back home 9 days later with continued antibiotic and anticoagulation therapy
Conclusion
The intraoperative use of CytoSorb incorporated into the CPB circuit in this patient with infective endocarditis undergoing a mitral valve replacement redo procedure was associated with an improvement of the perioperative hemodynamic situation accompanied by resolution of lactic acidosis and control of the anticipated hyperinflammatory response
Due to the excellent results both in modulation of the inflammatory response and in the postoperative bleeding rate, the surgical team now routinely consider the intraoperative use of CytoSorb in patients with a diagnosis of infective endocarditis
Integration into the CPB circuit was easy and safe. No adverse events were recorded.
Case report: Cytokine hemoadsorption in a case of hemophagocytic lymphohistiocytosis secondary to extranodal NK/T-cell lymphoma
Juan Carlos Ruiz-Rodríguez et al. Front Med (Lausanne). 2022.
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Front Med (Lausanne)
. 2022 Aug 15;9:925751.
doi: 10.3389/fmed.2022.925751. eCollection 2022.
Authors
Juan Carlos Ruiz-Rodríguez 1 2 3 , Luis Chiscano-Camón 1 2 3 , Adolf Ruiz-Sanmartin 1 2 3 , Clara Palmada 1 2 , Ivan Bajaña 1 2 , Gloria Iacoboni 3 4 , Camilo Bonilla 1 2 , Alejandra García-Roche 1 2 , Erika Paola Plata-Menchaca 1 2 3 , Carolina Maldonado 1 2 , Marcos Pérez-Carrasco 1 2 3 , Mónica Martinez-Gallo 3 5 6 7 , Clara Franco-Jarava 5 6 , Manuel Hernández-González 5 6 7 , Ricard Ferrer 1 2 3
Affiliations
1 Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
2 Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
3 Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
4 Hematology Department, Vall d'Hebron Hospital Universitari, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
5 Immunology Division, Vall d'Hebron University Hospital, Barcelona, Spain.
6 Diagnostic Immunology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
7 Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Barcelona, Spain.
PMID: 36045925
PMCID: PMC9423101
DOI: 10.3389/fmed.2022.925751
Cite
Abstract
We discuss a single case of Hemophagocytic lymphohistiocytosis (HLH) due to NK-type non-Hodgkin lymphoma and Epstein-Barr virus reactivation with multiorgan dysfunction and distributive shock in which we performed cytokine hemoadsorption with Cytosorb ®. A full microbiological panel was carried out, including screening for imported disease, standard serologies and cultures for bacterial and fungal infection. A liver biopsy and bone marrow aspirate were performed, confirming the diagnosis. The patients fulfilled the HLH-2004 diagnostic criteria, and according to the 2018 Consensus Statements by the HLH Steering Committee of the Histiocyte Society, dexamethasone and etoposide were started. There was an associated hypercytokinemia and, due to refractory distributive shock, rescue therapy with cytokine hemoadsorption was performed during 24 h (within day 2 and 3 from ICU admission). After starting this procedure, rapid hemodynamic control was achieved with a significant reduction in vasopressor support requirements. This case report highlights that cytokine hemoadsorption can be an effective since rapid decrease in IL-10 levels and a significant hemodynamic improvement was achieved.
New on PubMed
Use of Cytokine Filters During Cardiopulmonary Bypass: Systematic Review and Meta-Analysis
Vinci Naruka et al. Heart Lung Circ. 2022.
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Heart Lung Circ
. 2022 Aug 27;S1443-9506(22)01038-1.
doi: 10.1016/j.hlc.2022.07.015. Online ahead of print.
Authors
Vinci Naruka 1 , Mohammad Yousuf Salmasi 2 , Arian Arjomandi Rad 2 , Nandor Marczin 2 , George Lazopoulos 3 , Marco Moscarelli 2 , Roberto Casula 4 , Thanos Athanasiou 5
Affiliations
1 Department of Surgery and Cancer, Imperial College, London, UK; Department of Cardiothoracic Surgery, Hammersmith Hospital, London, UK.
2 Department of Surgery and Cancer, Imperial College, London, UK.
3 Department of Cardiothoracic Surgery, University Hospital of Heraklion, Crete, Greece.
4 Department of Cardiothoracic Surgery, Hammersmith Hospital, London, UK.
5 Department of Surgery and Cancer, Imperial College, London, UK; Department of Cardiothoracic Surgery, Hammersmith Hospital, London, UK. Electronic address: t.athanasiou@imperial.ac.uk.
PMID: 36041987
DOI: 10.1016/j.hlc.2022.07.015
Cite
Abstract
Introduction: Cardiac surgery involving cardiopulmonary bypass (CPB) activates an inflammatory response releasing cytokines that are associated with less favourable outcomes. This study aims to compare i) CPB during cardiac surgery (control) versus ii) CPB with haemoadsorption therapy; and assess the effect of adding this therapy in reducing the inflammatory cytokines burden.
Methods: A systematic literature review with metanalysis was conducted regarding the main outcomes (operative mortality, ventilation duration, intensive care unit [ICU] and hospital stays) and day-1 inflammatory markers levels post-surgery. Fifteen (15) studies were included for final analysis (eight randomised controlled trials, seven observational studies) with no evidence of publication bias.
Results: Subgroup analysis of non-elective surgeries across observational studies (emergency and infective endocarditis) significantly favoured cytokine filters in terms of 30-day mortality (OR 0.40, 95% CI 0.20, 0.83; p=0.01) and shorter ICU stay (MD -42.36, 95% CI -68.07, -16.65; p=0.001). At day-1 post-surgery, there was a significant difference favouring the cytokine filter group in c-reactive protein (CRP) (MD -0.71, 95% CI -0.84, -0.59; p<0.001) with no differences in white blood count (WBC), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-a), IL-6, IL-8 and lactate. When comparing cytokine filters and control across all studies there was no significant difference in operative mortality, ventilation duration, hospital stay and ICU length of stay. Also, there were no statistical differences in randomised controlled trials (RCTs) using haemadsorption filters.
Conclusions: A significant reduction in 30-day mortality and ICU stay could be obtained by using haemadsorption therapy during non-elective cardiac surgery, especially emergency surgery and in patients with higher inflammatory burden such as infective endocarditis.
Case of the Week
Literature Database
The successful application of hemoadsorption for extracorporeal liver support in a child with acute liver failure
Wun Fung Hui, Wing Lum Cheung, Fung Shan Chung, Karen Ka Yan Leung and Shu Wing Ku | Department of Paediatrics and Adolescent Medicine, Hong Kong Children’s Hospital, Kowloon, Hong Kong | Int J Artif Organs 2022; epub
08/17/2022
New!PediatricsPeer Reviewed Published DataSafetyBilirubinCase of the weekCase reportCritical CareCRRT (pre or post filter)Improv. hep. encephalopathy
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Summary
CoW 33/2022 – This case reports on a 6-year-old boy, who was admitted to the hospital due to prolonged dyskinetic movements resulting in rhabdomyolysis and acute kidney injury.
Summary
The following case report describes the use of CytoSorb in a pediatric patient for the reduction of hyperbilirubinemia and elevated serum bile acids in acute liver failure. A 6-year-old boy was admitted to hospital due to prolonged dyskinetic movements resulting in rhabdomyolysis and acute kidney injury. Over the following 10 days he was given multiple antibiotics for various infections and five days later developed acute liver failure with hepatic coma due to drug rash with eosinophilia and systemic symptoms (DRESS). He had hyperbilirubinemia, elevated serum bile acids and hyperammonemia as well as raised liver enzymes. Despite standard therapies his condition deteriorated, and he was admitted to the Pediatric Intensive Care Unit (PICU) for ongoing management. In addition to the use of systemic steroids and other supportive therapies, he was started on continuous renal replacement therapy (CRRT), into which a CytoSorb column was added as an extracorporeal liver support to try and reduce the bilirubin and bile acids. Three adsorbers were used for a total duration of 75 hrs (28, 22 and 25 hrs). Serum levels of total bilirubin reduced from 418 to 119 µmol/L, bile acids to from 174 to 58 µmol/L and ammonia reduced from 172 to 55 µmol/L. His conscious level gradually improved, as did his liver function. Except for mild, non-symptomatic thrombocytopenia and mild electrolyte disturbances, the therapy was well tolerated with no major complication encountered. He was finally able to be discharged from the PICU after 20 days. The authors state that hemoadsorption may have the merits of a faster initial rate of bilirubin removal and ease of set up compared to albumin dialysis. In summary this case demonstrates that hemoadsorption with CytoSorb can be safely employed as an adjunctive extracorporeal liver support modality in children with acute liver failure as it can efficiently remove bilirubin and bile acids. The potential role and technical concerns of applying such technique in pediatric patients requires further evaluation in future studies.
Case presentation
He was initially given ceftriaxone for potential central venous system infection. Later, his course was complicated by streptococcus mitis pneumonia resulting in the administration of vancomycin for 7 days. In the subsequent 10 days of hospitalization, he was given amoxicillin and clavulanic acid as well as piperacillin/tazobactam as empirical therapy for recurrence of fever, while all microbiological investigations showed no positive bacterial growth
Five days after stopping all antibiotics, he again developed low grade fever. He also had hepatomegaly, ascites and a generalized erythematous maculopapular rash associated with tender cervical lymphadenopathy
Blood tests revealed leukocytosis with white blood cell count 12.4×109/L, lymphocyte count 4.72×109/L, eosinophil count 0.37 × 109/L, and the presence of atypical lymphocytes
He also showed increased liver enzymes (serum levels of alanine aminotransferase [ALT] 1241 IU/L, alkaline phosphatase [ALP] 220 IU/L, aspartate aminotransferase [AST] 839 IU/L and gamma-glutamyl transferase [GGT] 160 IU/L), hypoalbuminemia (29 g/L), hyperbilirubinemia (25 µmol/L), and coagulopathy (international normalized ratio [INR] 1.49 and activated partial thromboplastin time [aPTT] 34.6 s). The ammonia level was <20 µmol/L
Ultrasound of the hepatobiliary system showed no focal hepatic lesions and no dilated biliary system
He was started on cefotaxime empirically, which was changed to meropenem 4 days later
Supportive treatment with vitamin K, albumin and fresh frozen plasma (FFP) was also commenced
However, serial investigations revealed evolving hepatic failure and he was subsequently transferred to the Pediatric Intensive Care Unit (PICU) for further management
Upon PICU admission, he was still arousable and his Glasgow Coma Scale (GCS) was 15, but he soon started to desaturate requiring high flow oxygen of 15 L/min
Multiple investigations were performed to try and determine the underlying cause of his acute hepatic failure. Finally, he was diagnosed with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome (most probably due to previous exposure to multiple antibiotics, in particularly the beta-lactams) based on the RegiSCAR (Registry of Severe Cutaneous Adverse Reaction) criteria, with Wilson’s disease being an important differential diagnosis
Hence, all antibiotics were stopped after PICU admission
He was then given ursodeoxycholic acid and vitamin supplements for his cholestasis and lactulose to limit enteral ammonia absorption. His protein intake was limited to <1 g/kg/day
One dose of intravenous immunoglobulin was administered for potential Epstein-Barr virus infection
Methylprednisolone was also started 3 days after admission as a treatment for DRESS syndrome
Despite that, he continued to deteriorate with reduced conscious level (GCS dropped to 10) suggesting the development of grade three hepatic encephalopathy. Serum total bilirubin was 418 µmol/L, direct bilirubin 328 µmol/L, bile acids 174 µmol/L and ammonia levels had increased to 172 µmol/L, while INR increased to 3.12
There was also evolving bradycardia suggestive of bile acid-associated cardiac toxicity. The bedside echocardiogram showed normal contractility with a left ventricular fractional shortening of 37%
His highest Pediatric End-stage Liver Disease (PELD) score was 30 and he had a work up for potential liver transplant
Therefore, continuous renal replacement therapy (CRRT) was started for hyperammonemia 4 days after admission. In order to accelerate removal of bilirubin and bile acids, a CytoSorb hemoadsorption column was additionally integrated into the CRRT circuit
Treatment
Three adsorbers were used for a total duration of 75 hrs (28, 22 and 25 hrs)
Measurements
Bilirubin, bile acids, ammonia
Liver function
Level of consciousness
Coagulation profile
Platelets, electrolytes
Results
Under combined CRRT+CytoSorb treatment, serum levels of total bilirubin reduced from 418 to 119 µmol/L, bile acids to from 174 to 58 µmol/L and ammonia reduced from 172 to 55 µmol/L
His liver function showed gradual improvement following therapy initiation. Of note, one day after commencing combined CRRT+CytoSorb he was started on penicillamine based on the provisional diagnosis of Wilson’s Disease
His conscious level also improved and returned to his baseline level 2 days after CRRT+CytoSorb initiation
The coagulation profile improved and there was reduced requirement for FFP infusion
Except for mild, non-symptomatic thrombocytopenia and mild electrolyte disturbances, the therapy was well tolerated with no major complications encountered
Patient Follow-up
One dose of carglumic acid and regular sodium benzoate were started as a bridging therapy to prevent rebound of hyperammonemia upon CRRT termination
Sodium benzoate administration was stopped one week after CRRT termination
A drug challenge test was arranged and blood tests on day 20 of PICU admission showed serum levels of ammonia 37 µmol/L, total bilirubin 102 µmol/L, ALT 91 IU/L, ALP 170 IU/L, AST 43 IU/L, GGT 208 IU/L, INR was 0.95
He was finally discharged from the PICU 20 days after admission
Conclusion
In summary, this case demonstrates that hemoadsorption with CytoSorb can be safely employed as an adjunctive extracorporeal liver support modality in children with acute liver failure as it can efficiently remove bilirubin and bile acids
The authors state that hemoadsorption may have the advantages of a faster initial rate of bilirubin removal and ease of set up compared to albumin dialysis
The potential role of applying such technique in pediatric patients requires further evaluation in future studies.
Management of perioperative bleeding risk in patients on antithrombotic medications undergoing cardiac surgery – a systematic review
Matejic-Spasic M, Hassan K, Thielmann M, Geidel S, Storey RF, Schmoeckel M, Adamson H, Deliargyris EN, Wendt D. J Thorac Disease 2022; epub
08/2022
The aim of this review was to evaluate perioperative bleeding complications in patients on dual antiplatelet therapy (DAPT) or direct-acting oral anticoagulants (DOACs) undergoing high-bleeding risk cardiovascular surgery and to present currently available potential solutions to mitigate antithrombotic therapy-related bleeding complications. Relevant articles on bleeding complications in cardiac surgery from last 10 years in Medline (PubMed) were screened. An additional search evaluating potential solutions to mitigate bleeding complications was also performed. From all reviewed studies, a total of 19 articles could be included evaluating the risk for bleeding in cardiac surgery related to DAPT or DOACs, and 10 papers evaluating antithrombotic drug reversal or removal in this setting. Reported bleeding rates ranged between 18% and 41%, a remarkably wide variability. New costly reversal agents are available but have not been sufficiently tested in this setting. Antithrombotic removal by innovative intraoperative hemoadsorption has been shown to be associated with a significant decrease in re-thoracotomy rate, overall procedure duration, administered transfusion volumes, chest-tube drainage, and length of hospitalization. Results from ongoing trials should provide more informed insights concerning the efficacy and safety of several potential solutions.
Case of the Week
Literature Database
Hemoadsorption for severe MIS-C in critically ill children, should we consider it as a therapeutic opportunity?
Gabriella Bottari1, Flavia Severini2, Anna Hermine Markowich2, Giulia Lorenzetti2, Juan Carlos Ruiz Rodriguez3,4, Ricard Ferrer3,4, Paola Francalanci5, Antonio Ammirati6, Paolo Palma7 and Corrado Cecchetti1 |1 Pediatric Intensive Care Unit, Pediatric Emergency Department, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy | 2 Department of Pediatrics, University of Rome Tor Vergata, Residency School of Pediatrics, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy | 3 Intensive Care Department, Vall d’Hebron University Hospital, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain | 4 Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Research, Institute (VHIR), Barcelona, Spain | 5 Unit of Pathology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy | 6 Pediatric Emergency Unit, Pediatric Emergency Department, Bambino Gesù Children’s Hospital, IRCSS, Rome, Italy Int J Artif Organs 2022; epub
08/10/2022
New!PediatricsPeer Reviewed Published DataReduction in catecholaminesReviewSafetyViral infectionCase of the weekCase reportCOVID-19Critical CareCRRT (pre or post filter)Inflammatory parameters
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Summary
CoW 32/2022 – This case reports on a 13 year old boy (weight 60 kg, height 160 cm) who presented with fever, rash, abdominal pain, and vomiting.
Summary
Multisystem inflammatory syndrome (MIS-C) is a new severe clinical condition that has emerged during the COVID-19 pandemic and affects children and the young usually after a mild or asymptomatic COVID-19 infection. Symptoms commonly include cardiovascular dysfunction for which support is required in the majority of cases. In the case report a 13 yr old boy with refractory shock secondary to left ventricular dysfunction (LVD) in the context of MIS-C, the use of hemoadsorption with CytoSorb is described. The therapeutic strategy resulted in hemodynamic and clinical stabilization (reduction then cessation of vasopressors) as well as control of the hyperinflammatory response (including C-Reactive Protein, interleukin – IL-6 and IL-10). The patient received in total 5 adsorbers over 72 hrs. with the first 2 adsorbers for 12 hours each, and a further 3 adsorbers for 24 hours each inserted into the continuous renal replacement circuit. Treatment appeared to be safe and feasible. The authors then compare this case with two more published cases where CytoSorb has been used as an adjuvant therapy in similarly critically ill children with severe forms of MIS-C. All three patients responded with a prompt improvement in their myocardial function (within the first 24 h) following the start of hemadsorption. The authors state that using this blood purification strategy could be a therapeutic opportunity in severe LVD due to MIS-C, sparing the need for extracorporeal membrane oxygenation (ECMO) and other mechanical cardiocirculatory supports, with the advantage of it being less invasive. They also state that CytoSorb does not appear to interfere with most common immunomodulatory therapies although further evidence is required.
Case presentation
Blood tests revealed elevated leukocytes with neutrophilia, high C-reactive protein (CRP) (29.31 mg/gL), procalcitonin (3.32 ng/mL), and hyperferritinemia (1529 ng/mL)
He had a positive history for SARS-CoV-2 infection 6 weeks previously with positive serology
Within 24 h he developed diarrhea, poor pallor, and hypotension
Cardiac markers were elevated, and 2D-echocardiogram showed left ventricular (LV) dysfunction (Ejection Fraction EF 35%)
Supportive care with milrinone and dopamine was started and, as multisystem inflammatory syndrome in children (MIS-C) was suspected, he received immunoglobulins and corticosteroids
The following day he deteriorated, with an 2D-echocardiogram showing a LVEF of 25%, therefore he was referred to the pediatric intensive care unit (PICU) requiring endotracheal intubation and invasive mechanical ventilation (IMV) due to cardiogenic shock
Given the increase in troponin I (high sensitivity troponin, hs-TnI) levels from 75 to 1200 pg/ml in 12 h, infectious myocarditis was suspected and an endomyocardial biopsy (EMB) was taken
Considering the clinical picture of hyperinflammation associated severe shock due to left ventricular dysfunction (LVD) and high lactate (7.9 mmol/l) with the need for high inotropic and vasopressor support (epinephrine 0.35 µ/kg/min, norepinephrine 0.06 µ/kg/min, and milrinone 0.5 µ/kg/min), hemoadsorption with CytoSorb was started in combination with continuous kidney replacement therapy (CKRT)
Of note, even though the patient fulfilled the diagnostic criteria of MIS-C, the authors could not completely rule out the development of fulminant myocarditis due to Parvovirus B19 (PVB19) positivity after suffering from COVID-19, which is why corticosteroids were withheld and immunoglobulins and anakinra were maintained
Treatment
The patient received in total 5 adsorbers over 72 hrs with the first 2 adsorbers for 12 hours each, and a further 3 adsorbers for 24 hours each inserted into the continuous renal replacement circuit
Anticoagulation protocol: citrate-calcium
Measurements
Hemodynamics and requirements for vasoactive substances
Inflammatory parameters
Left ventricular ejection fraction
Cardiac enzymes
Safety
Results
The therapeutic strategy resulted in hemodynamic stabilization with a rapid reduction followed by the cessation of vasopressors at the time of discontinuation of CytoSorb therapy
Treatment was also associated with control of the hyperinflammatory response as evidenced by a reduction in inflammatory parameters including CRP, interleukin – IL-6 and IL-10
After the first 24 h of combined hemoadsorption and CKRT therapy, an improvement in the LVEF to 50% was observed
Troponin I levels decreased from 1200 pg/ml to around 375 pg/ml within 12 hours of treatment with decreasing levels thereafter, reaching ~100 pg/ml by the end of blood purification therapy
No adverse events were noted
Patient Follow-up
CKRT was discontinued at the same time of hemoperfusion after 72 h (day 3)
He was weaned off invasive mechanical ventilation on day 6 and discharged from the PICU on day 8
After 2 weeks his cardiac function had completely restored and the patient was discharged from the hospital on day 20 requiring only the diuretic, spironolactone
Conclusion
In this adolescent with refractory shock secondary to LV dysfunction in the context of MIS-C, treatment with hemoadsorption in combination with immunomodulatory therapies resulted in hemodynamic and clinical stabilization as well as control of the hyperinflammatory response with the treatment appearing safe and feasible
The authors compare this case with two more published cases where CytoSorb has been used as an adjuvant therapy in similarly critically ill children with severe forms of MIS-C. All three patients responded with prompt improvements in their myocardial function (within the first 24 h) following the start of hemoadsorption
The authors state that using this blood purification strategy could be a therapeutic opportunity in severe LVD due to MIS-C, sparing the need for extracorporeal membrane oxygenation (ECMO) and other mechanical cardiocirculatory supports, with the advantage of it being less invasive. They also state that CytoSorb does not appear to interfere with most common immunomodulatory therapies although further evidence is required.
Extracorporeal hemoadsorption with the CytoSorb device as a potential therapeutic option in severe intoxications: Review of the rationale and current clinical experiences
Darko Mitrovic et al. J Clin Pharm Ther. 2022.
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J Clin Pharm Ther
. 2022 Aug 3.
doi: 10.1111/jcpt.13724. Online ahead of print.
Authors
Darko Mitrovic 1 , Daan W Huntjens 2 , Elisabeth A J de Vos 3 , Martijn van Tellingen 4 , Eric J F Franssen 2
Affiliations
1 Hospital Pharmacy, Tjongerschans Hospital Heerenveen, Heerenveen, The Netherlands.
2 Department of Clinical Pharmacy, OLVG Hospital, Amsterdam, The Netherlands.
3 Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands.
4 Intensive Care, Tjongerschans Hospital Heerenveen, Heerenveen, The Netherlands.
PMID: 35924306
DOI: 10.1111/jcpt.13724
Cite
Abstract
What is known and objective: Many severe intoxications occur with substances with no specific antidote, which is why methods of extracorporeal elimination represent a particularly useful and even critical component in their management. The purpose of this review is to summarize the accumulating evidence and clinical results from the application of CytoSorb hemoadsorption therapy in patients with severe intoxications.
Comment: The technology represents a promising technique with an increasing number of publications in a variety of severe intoxication scenarios suggesting that early intervention might provide rapid substance removal with subsequent overall clinical improvement.
What is new and conclusion: Given the tremendous challenges in performing prospective, randomized trials in this field, the strong safety profile of the device and the high acuity of these life-threatening situations, CytoSorb should be considered as a therapeutic option in severe intoxications, particularly when direct antidotes are not available. However, further clinical data are desirable to provide precise recommendations.
Keywords: CytoSorb; blood purification; drug; hemoadsorption; intoxication.
Case of the Week
Literature Database
First Hemoadsorption during Cardiopulmonary Bypass in Neonate with Complex Cardiac Malformation
Christophel-Plathier E, Mendes V, Verdy F, Mauron S, Mury C. Annals of Clinical Case Reports 2022; 7:2257
08/03/2022
New!PediatricsPeer Reviewed Published DataReduction in catecholaminesReduction in length of staySafetyImprov. resp functionImpact on organ supportCardiac surgeryCase of the weekCase reportCPBInflammatory parametersIntra-Op
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Summary
CoW 31/2022 – This case reports on a 5 day old male full term newborn with congenital hypoplastic left heart syndrome who was scheduled for a corrective procedure.
Case presentation
His left heart syndrome involved an absent mitral valve and exceedingly small aortic annulus, ascending aorta and aortic arch. Perfusion of the aortic arch was retrograde through a persistent patent ductus arteriosus. Right ventricular systolic function was normal
Shortly after birth, the neonate required continuous positive airway pressure (CPAP) and then invasive ventilation with permissive hypercapnia
He received levosimendan 12 h before surgery, and maintenance with a prostaglandin E1 infusion
Five days after birth, the patient underwent a Norwood stage I palliation with interatrial septum resection, aortic arch reconstruction and the creation of a Blalock-Taussig shunt
Cardiopulmonary bypass (CPB) duration was 227 min, aortic cross-clamping duration 180 min. Selective cerebral perfusion was 27 min at a central core temperature of 27.8° Celsius
In order to reduce the pre-operative and intra-operative inflammatory process, a CytoSorb hemoadsorption device was pre-emptively integrated into the CPB circuit
Treatment
The CytoSorb cartridge was inserted between the oxygenator outlet (QUADROX-i neonatal HMO 11000® MAQUET) and the venous line, assisted by a roller pump slave to the blood pump
The minimum flow rate through the cartridge was 100 ml/min. The servo control was 14% of the patient’s theoretical flow, indexed to 3.0 l/min/m2 to compensate for the drop induced by CytoSorb and to ensure a flow rate of 2.4 l/min/m2 to the patient
Priming was performed using “ventilated reconstituted whole blood” to ensure homeostatic conditions at CPB initiation requiring 385 ml of blood, of which 120 ml were used for priming the CytoSorb
Measurements
Hemodynamics and requirements for vasoactive substances
Overall clinical course
Results
The patient returned to the intensive care unit (ICU) intubated with infusions of norepinephrine, dopamine and milrinone. Thereafter, hemodynamic adaptation was good, with rapid weaning off all amine infusions and definitive weaning off norepinephrine on post-operative day 5
Surgery was successful and correction was adequate, with unobstructed flow through the interatrial communication and inside the aortic arch, and with good ventricular function. Despite the severity of his condition, the baby had anuneventful post-operative course, without renal, digestive, or infectious complications
Patient Follow-up
The patient was extubated on post-operative day 6
He left the ICU on day 22 and was discharged home on day 45
Conclusion
The authors describe the clinical course post-operatively as remarkable with shortened ICU and hospital lengths of stay due to the lack of (anticipated) complications. They state that previous similar cases have required much longer support on ventilation and longer ICU stays. They also believe the expected benefits to the anti-inflammatory processes are worth the large homologous blood use
As the use of CytoSorb was the only differentiating factor, its use likely helped to reduce the pre-operative and intra-operative inflammatory process, and thereby helped with the positive clinical course and outcome. The authors conclude with stating that by reducing cytokine levels, CytoSorb may have significantly reduced catecholamine infusion time, intubation time, and ICU stay.
Comparison of the CytoSorb ® 300 mL and Jafron HA380 hemoadsorption devices: an in vitro study
Axel Nierhaus et al. Minim Invasive Ther Allied Technol. 2022.
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Minim Invasive Ther Allied Technol
. 2022 Aug 1;1-8.
doi: 10.1080/13645706.2022.2104617. Online ahead of print.
Authors
Axel Nierhaus 1 2 , Jesus Morales 3 , Daniel Wendt 3 4 , Jörg Scheier 3 , Dominik Gutzler 3 , Dominik Jarczak 1 2 , Frank Born 5 , Christian Hagl 5 , Efthymios Deliargyris 3 , Yatin Mehta 6
Affiliations
1 Clinic for Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg, Hamburg, Germany.
2 Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
3 CytoSorbents, Princeton, NJ, USA.
4 Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, Essen, Germany.
5 Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany.
6 Medanta Institute of Critical Care and Anesthesiology, Gurgaon, India.
PMID: 35913784
DOI: 10.1080/13645706.2022.2104617
Cite
Abstract
Introduction: We performed an analysis of two blood purification systems to determine their performance for removing interleukins (ILs)-6 and 10, tumor necrosis factor (TNF)-a and monocyte chemoattractant protein (MCP)-1 from blood.
Material and methods: An in vitro hemoperfusion blood recirculation circuit was used to compare the CytoSorb® 300 mL (CytoSorbents Inc., Princeton, NJ) and Jafron HA 380 (Jafron Biomedical Co., Ltd., Zhuhai City, China) devices. The removal of purified recombinant human IL-6, IL-10, TNFa and MCP-1 by the adsorbers was compared at various timepoints. Three runs were completed and removal was evaluated as the mean area under the curve (AUC).
Results: Both devices showed effective removal of the tested cytokines. IL-6, IL-10, TNFa and MCP-1 were removed faster and to a higher extent by the CytoSorb® 300 mL device. At maximal time of 12 h, overall removal according to AUC of remaining concentrations was significantly lower with CytoSorb® 300 mL compared with HA 380 (IL-6: 1075.5 ± 665.9 vs. 4345.1 ± 1499.3 (p = 0.01), IL-10: 5065.7 ± 882.5 vs. 11,939.7 ± 4523.1 (p = 0.03), TNF-a: 6519.9 ± 997.6 vs. 10,303.7 ± 2347.0 (p = 0.03) and MCP-1: 278.9 ± 40.7 vs. 607.3 ± 84.4 (p = 0.001)).
Conclusions: Both the CytoSorb® and the Jafron HA 380 devices are capable of removing cytokines from blood in a benchtop model. The CytoSorb® 300 device was significantly more efficient achieving the bulk of the removal in the first 120 min.
Literature Database
Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation
Ghaidan H, Stenli M, Niroomand A, Mittendorfer M, Hirdman G, Gvazava N, Edström D, Silva IAN, Broberg E, Hallgren O, Olm F, Wagner DE, Pierre L, Hyllén S, Lindstedt S. Nature Communications 2022; 13:4173
07/27/2022
New!Peer Reviewed Published DataSafetyTransplantImprov. resp functionAnimal modelsARDSExperimental setupInflammatory parameters
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Summary
Despite improvements, lung transplantation for end-stage disease remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lung utilization, this study investigated the use of CytoSorb cytokine adsorption as a means of treating ARDS donor lungs. Ex-vivo lung perfusion (EVLP) was used to assess the donor lungs. Mild to moderate ARDS was induced via lipopolysaccharide (LPS) in 16 donor pigs. The non-treated group received EVLP and underwent transplantation without cytokine adsorption. The treated groups were subdivided between a ‘two step’ group (lungs were treated with CytoSorb both during EVLP (4 hours) and for 12 hours post transplantation) and a ‘one step’ group (use of CytoSorb only for 12 hrs postop). The primary endpoint of lung function was the PaO2/FiO2 ratio. Results showed that treatment with CytoSorb significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. The effects of CytoSorb seemed to increase when used at two times points. In summary, CytoSorb cytokine adsorption in the context of ARDS injured lungs (i) reduced inflammation and restored pulmonary function during EVLP, (ii) restored pulmonary function and decreased inflammation following transplantation, and (iii) reduced the incidence of PGD in transplanted recipients. The authors suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.
Case of the Week
Literature Database
Use of CytoSorb hemoadsorption column during prolonged cardiopulmonary bypass in complex cardiac surgery patient
Marianne Alarie*, Maggie Savelberg, Danika Vautour and Igo B. Ribeiro | Kingston Health Sciences Centre, Kingston, ON, Canada | J Cardiothorac Surg 2022 Jul 7;17(1):172
07/27/2022
New!Peer Reviewed Published DataReduction in catecholaminesSafetyCardiac surgeryCase of the weekCase reportCPBIntra-Op
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Summary
CoW 30/2022 – This case reports on a 61-year-old male, who was assessed by cardiac surgery in consideration for mitral valve surgery following presentation for congestive heart failure.
Summary
In this report a 61-year-old male with congestive heart failure was assessed for cardiac surgery, and was found to require mitral valve replacement, aortic valve replacement, tricuspid valve repair, single coronary artery bypass grafting and a left atrial appendage clip. Given the complexity of the surgery, the anticipated prolonged length of cardiopulmonary bypass, the associated risk of significant vasoplegia and his preoperative kidney dysfunction, the decision was made to integrate the CytoSorb cartridge into the cardiopulmonary bypass (CPB) circuit. One CytoSorb hemoadsorber was used intraoperatively throughout the CPB time (154 min). Despite an initial rise in vasopressor requirements, the mean arterial pressure (MAP) gradually improved during the time on by-pass whilst vasopressors could be weaned off completely. However, ten minutes post-bypass (i.e. after discontinuation of CytoSorb), the patient once again required multiple vasopressors to support his MAP. Despite the presence of postoperative thrombocytopenia, postoperative platelet counts did not significantly differ from baseline. Treatment was safe and feasible while integration into the cardiopulmonary bypass circuit was uncomplicated with no device-related complications. In this complex cardiac surgery patient, the authors state that the application of CytoSorb during cardiopulmonary bypass contributed to a decreased need for vasoactive support during and after surgery as well as improved postoperative outcomes, rendering it a promising therapeutic option in critically ill patients at risk of significant postoperative vasoplegia and multiorgan injury following prolonged and complex cardiac surgery.
Case presentation
Transthoracic echocardiography showed significant mitral valve calcification resulting in severe mitral regurgitation and moderate mitral stenosis. The right and left ventricles both had mild dysfunction with an ejection fraction of 46%. Further evaluation with transesophageal echocardiography revealed moderate aortic cusp calcification with moderate stenosis. Moderate tricuspid regurgitation was also noted. Coronary angiography revealed the presence of significant coronary artery disease with second diagonal ostial stenosis
The patient’s medical history included end-stage renal disease requiring intermittent hemodialysis, autoimmune cytopenia (severe thrombocytopenia, neutropenia) with mild responsiveness to preoperative steroids, New York Heart Association class III heart failure, hypertension, chronic obstructive pulmonary disease, severe untreated sleep apnea, previous Graves` disease diagnosis and atrial fibrillation
The patients’ preoperative blood work included a platelet count of 74?×?109/L, hemoglobin 91 g/L and hematocrit 29%. Preoperative creatinine was 598 µmol/L and glomerular filtration rate (GFR) was 8 mL/min/1.73 m2
The procedure included mitral valve replacement, aortic valve replacement, tricuspid valve repair, single coronary artery bypass grafting and left atrial appendage clip. Total cardiopulmonary bypass (CPB) time was 154 min, with a cross-clamp time of 115 min
Following induction of anesthesia and prior to commencement of the CPB, the patient required norepinephrine at 2 µg/min for hemodynamic support
A total of 3 units of packed red blood cells (pRBC), 2 units of platelets and 1 unit of prothrombin complex concentrate were administered to treat his perioperative anemia and coagulopathy
Given the complexity of the surgery (triple valve surgery), the anticipated prolonged length of cardiopulmonary bypass, the associated risk of significant vasoplegia and the preoperative kidney dysfunction, the decision was made to integrate the CytoSorb cartridge into the cardiopulmonary bypass circuit in this critically ill patient
Treatment
One CytoSorb hemoadsorber was used intraoperatively throughout the CPB time (154 min)
The CytoSorb device was inserted between the recirculation line (high-pressure line) and the venous reservoir of the CPB circuit. The cartridge was placed in a parallel fashion with the hemoconcentrator. The cartridge was primed and flushed with one liter of Ringer’s Lactate
Estimated blood flow rates through the CytoSorb: 200-230 mL/min
Anticoagulation: heparin with target activated clotting times (ACT) greater than 400 s, monitored every 20 to 30 min
Measurements
Hemodynamics and requirements for vasoactive substances
Total chest tube drainage volume
Ultrafiltration rate
Thrombocytes
Safety
Results
Following initiation of CPB and CytoSorb, norepinephrine infusion was increased to 5 µg/min for the first half hour of the bypass run under which the mean arterial pressure (MAP) could be sustained at around 45–50 mmHg. At the 40 min mark, MAP increased to a mean of 65–70 mmHg and the norepinephrine dose was reduced to 2 µg/min. After one hour on bypass, MAP increased to 70–75 mmHg and norepinephrine was discontinued. MAP levels above 60 mmHg were sustained for the remainder of the bypass run and there was no additional need for vasoactive support. Ten min post-bypass (i.e. after discontinuation of CytoSorb), the patient required dobutamine 5 µg/kg/min, norepinephrine 4 µg/min, epinephrine 5 µg/min and vasopressin 0.04 units/min for support. The patient was transferred to the cardiac intensive care unit on 5 µg/kg/min of dobutamine, 6 µg/min of norepinephrine, 5 µg/min of epinephrine and 0.04 units/min of vasopressin. Dobutamine was discontinued within the first postoperative hour. Vasopressin was stopped 24 h postoperatively. Norepinephrine was discontinued by the end of the 2nd postoperative day while epinephrine was eventually discontinued 48 h postoperatively
Total chest tube drainage was measured to be 1080 mL
Zero balance ultrafiltration was performed during bypass, with a total of 2.2 L of dialysate solution administered and 5.2 L of fluid removed via the hemoconcentrator
Postoperative platelet counts did not significantly differ from baseline
No adverse or any device-related side effects were documented during or after CytoSorb treatment
Patient Follow-up
Early postoperative blood work showed somewhat improved kidney function, with a creatinine of 394 umol/L and a GFR of 13 mL/min/1.73 m2
Lactate levels peaked at 3.4 mmol/L on the 6th postoperative hour and quickly normalized over the next 24 hours
Following the first postoperative day, the patient received an additional 3 units of pRBC, 2 units of fresh frozen plasma and 1 unit of platelets
Surgical drains were removed on the second postoperative day
The patient was extubated 48 h post-surgery
Hemodialysis treatments were resumed on the third postoperative day
The patient was transferred to the normal ward on the 6th postoperative day and discharged on the 11th postoperative day
Conclusion
In this complex cardiac surgery patient, application of CytoSorb during cardiopulmonary bypass contributed to a decreased need for vasoactive support during and after surgery as well as improved postoperative outcomes, rendering it a promising therapeutic option in critically ill patients at risk of significant postoperative vasoplegia and multiorgan injury following prolonged and complex cardiac surgery
The authors do not believe that CytoSorb therapy significantly impacted on the platelet concentrations or perioperative transfusion requirements
Treatment was safe and feasible while integration into the cardiopulmonary bypass circuit was uncomplicated with no device-related complications observed.
Case of the Week
Literature Database
Use of CytoSorb in a post kidney transplant pediatric patient with acute respiratory failure and sepsis
Dr. Rajiv Sinha | Paediatric Nephrology, Apollo Multispeciality Hospital, Kolkata, India
07/20/2022
New!PediatricsReduction in catecholaminesSafetySeptic ShockImprov. resp functionCase of the weekCase reportCritical CareIHD / SLEDInflammatory parameters
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Summary
CoW 29/2022 – This case reports on a 13-year-old girl from Bangladesh, who was admitted to the hospital with incipient renal failure and hypertension.
Case presentation
At the age of 9 months, she had been diagnosed with steroid resistant nephrotic syndrome secondary to WT1 mutation. She slowly progressed to end-stage renal disease and underwent bilateral nephrectomy and initiation of chronic peritoneal dialysis. Kidney transplantation was performed within 6 months (February, 2014), where the donor was the child’s mother. The patient was then on regular follow-ups in India until the current renal deterioration happened
On admission, the patient was found to have a creatinine of 2.5 mg/dl along with severe hypertension for which the patient was put on multiple anti-hypertensive drug therapy. A transplant renal biopsy was performed suggesting thrombotic microangiopathy. In view of her deteriorating renal function, the patient was prepared for renal replacement therapy (Perma-catheter insertion for hemodialysis)
Following admission, the patient’s condition deteriorated including epistaxis, dyspnoea, tachycardia, desaturation on room air and altered sensorium with increasing respiratory distress
Laboratory investigations revealed a leucocyte count of 13,700/µl, 91% neutrophils, platelets 0.85 lacs/cumm, C-reactive protein (CRP) 29.7mg/dl, INR of 4, aPTT of 120 secs, urea 142 mg/dl, and creatinine 4.1mg/dl
A subsequent chest X-ray showed patchy consolidations in the right perihilar region
She went on to develop hemodynamic instability with a drop in mean arterial pressure to 60 mmHg requiring initiation of vasopressor therapy (norepinephrine 0.8 µg/kg/min, epinephrine 0.5 µg/kg/min)
Additionally, the patient was intubated and put on mechanical ventilation with high ventilator settings including a positive end-expiratory pressure (PEEP) of 13 cmH2O, a peak inspiratory pressure (PIP) of 42 cmH2O, an FiO2 of 100% and a tidal volume of 5 ml/kg
Intravenous antibiotics were administered
Hemodialysis was initiated but had to be discontinued due to hypotension and the renal replacement therapy (RRT) modality was switched to Sustained Low Efficiency Dialysis (SLED)
As the patient was unresponsive to standard therapy and due to the ongoing clinical deterioration along with increased inflammatory markers (D-Dimer 2524.6 ng/ml, IL-6 5000 pg/ml), the decision was made to additionally integrate a CytoSorb hemoadsorber in order to control the hyperinflammatory response and to stabilize the patient hemodynamically
Treatment
One CytoSorb therapy session was performed for 8 hours on day 1
CytoSorb was used in conjunction with SLED therapy
Measurements
Hemodynamics and vasopressor requirements
Inflammatory markers
Ventilation invasiveness and oxygenation
Results
CytoSorb treatment resulted in a considerable improvement in the patient’s hemodynamic situation. 24 hours after initiation of therapy, norepinephrine had already decreased to 0.5 µg/kg/min and epinephrine to 0.1 µg/kg/min and continued to decrease also after cessation of CytoSorb therapy
Treatment with CytoSorb was further associated with a marked reduction in IL-6 (decrease from >5000 pg/ml to 44 pg/ml over the following 24 hours), indicating a clear control of the hyperinflammatory situation
Moreover, ventilation invasiveness decreased, and oxygenation improved
Patient Follow-up
RRT was continued for several consecutive days along with other supportive management
As the patient improved clinically, she was extubated on day 4 and kept on high flow oxygen therapy via nasal cannula
Antibiotic therapy was initiated for 14 days as the blood cultures were positive for Staphylococcus epidermidis(Coagulase-Negative Staphylococci)
The patient was finally discharged in a clinically stable condition with a follow-up plan for intermittent hemodialysis
Conclusion
In this case of a post kidney transplant pediatric patient with acute respiratory failure and sepsis, the use of CytoSorb hemoadsorption in combination with renal replacement therapy and standard therapeutic measures resulted in rapid hemodynamic stabilization, control of the hyperinflammatory response as well as improvement in ventilation invasiveness and oxygenation
Hemoadsorption therapy may therefore be a potentially important advance in the control of such conditions, if instituted early and judiciously. The presented case successfully adds to the growing experience from eastern India as the first case of pediatric hemoadsorption therapy
Use of CytoSorb in combination with SLED was safe and easy.
Hemoadsorption for severe MIS-C in critically ill children, should we consider it as a therapeutic opportunity?
Gabriella Bottari et al. Int J Artif Organs. 2022.
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Int J Artif Organs
. 2022 Jul 13;3913988221111179.
doi: 10.1177/03913988221111179. Online ahead of print.
Authors
Gabriella Bottari 1 , Flavia Severini 2 , Anna Hermine Markowich 2 , Giulia Lorenzetti 2 , Juan Carlos Ruiz Rodriguez 3 4 , Ricard Ferrer 3 4 , Paola Francalanci 5 , Antonio Ammirati 6 , Paolo Palma 7 , Corrado Cecchetti 1
Affiliations
1 Pediatric Intensive Care Unit, Pediatric Emergency Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
2 Department of Pediatrics, University of Rome Tor Vergata, Residency School of Pediatrics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
3 Intensive Care Department, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
4 Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron Research, Institute (VHIR), Barcelona, Spain.
5 Unit of Pathology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
6 Pediatric Emergency Unit, Pediatric Emergency Department, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy.
7 Clinical Immunology and Vaccinology Unit, Pediatric Academic Department (DPUO), Bambino Gesù Children's Hospital, IRCSS, Rome, Italy.
PMID: 35822878
DOI: 10.1177/03913988221111179
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Abstract
Multisystem inflammatory syndrome (MIS-C) is a new severe clinical condition that has emerged during the COVID-19 pandemic. MIS-C affects children and the young usually after a mild or asymptomatic COVID-19 infection. MIS-C has a high tropism for the cardiovascular system with need for inotropes and vasopressor support in 62% of cases. As of today a mortality from 1.5% to 1.9% related to MIS-C is reported. Hemoadsorption via the inflammatory mediator adsorber CytoSorb (CytoSorbents Europe, Berlin Germany) has been used as adjunctive therapy with the aim to restore the host response in septic shock and other hyper-inflammatory syndromes. We present the clinical experience of an adolescent boy with a refractory shock secondary to left ventricular dysfunction (LVD) in the context of MIS-C, treated with hemoadsorption, and continuous kidney replacement therapy (CKRT) in combination with immunomodulatory therapies. The therapeutic strategy resulted in hemodynamic and clinical stabilization as well as control of the hyperinflammatory response. Treatment appeared to be safe and feasible. Our findings are in line with previously published clinical cases on Cytosorb use in MIS-C showing the beneficial role of the hemoperfusion with Cytosorb in severe MIS-C to manage the cytokine storm. We provide an analysis and comparison of recent evidence on the use of hemoadsorption as an adjuvant therapy in critically ill children with severe forms of MIS-C, suggesting this blood purification strategy could be a therapeutic opportunity in severe LVD due to MIS-C, sparing the need for extracorporeal membrane oxygentation (ECMO) and other mechanical cardiocirculatory supports.
Keywords: Coronavirus; cytokines; left venticular failure (LVEF); multisystem inflammatory syndrome in children (MIS-C); myocarditis; pediatric critical care; shock.
Case of the Week 28
Literature Database
Use of CytoSorb in splenic abscessand septic shock due to intestinal ischemia following portal vein thrombosis and extensive small bowel resection
Dr. Klaus Kogelmann | Interdisciplinary Intensive Care Medicine, Emden Hospital, Germany
07/13/2022
New!Case of the week
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Summary
CoW 28/2022 – This case reports on a 37-year-old male patient with known type 1 diabetes mellitus, who was admitted to the hospital with nausea, multiple vomiting and abdominal pain.
Case presentation
The patient had already complained of nausea, vomiting, abdominal pain and multiple loose bowel movements about 10-12 days previously. After initial improvement after taking ibuprofen (1-2 times daily), the patient’s condition worsened again, leading to the current hospital admission
Initially, the patient presented with limited vigilance, tachycardia, tachypnoea, pale skin and cold sweats
On rectal digital examination pale blood was found
Additionally, sonography revealed dilated loops of the small intestine, which was clinically compatible with the diagnosis of peritonism
Consequently, there was an immediate indication for emergency surgery including median laparotomy, opening and draining of a splenic abscess found intraoperatively and application of a vacuum dressing to the open abdomen
Postoperatively, the patient was now in septic shock and transferred to the intensive care intubated and ventilated
Due to pronounced hemodynamic instability, a differentiated, protocol-based sepsis therapy (volume, catecholamines and calculated antibiotic therapy – with piperacillin/sulbactam as well as lung-protective ventilation) was started immediately
In addition, high-dose hydrocortisone administration (10 mg/h for 7 days) was initiated
On the following day and in the context of increasing intra-abdominal pressure and protracted septic shock, which was most likely due to the splenic abscess with consecutive portosplenomesenteric thrombosis and circulatory disturbances of the jejunum (mesenteric infarction), the patient underwent a re-operation and resection of the entire small intestine up to 10 cm from the oral and aboral ending, with creation of a jejunostoma and blind closure of the terminal ileum
Given a postoperative increase in catecholamine requirements (initial norepinephrine 0.22 µg/kg/min), infection markers (procalcitonin [PCT] 2 pg/ml, C-reactive protein [CRP] 145.9 mg/l), lactate levels (4.2 mmol/L), leukocytosis (42.5 thousand/µl) and anuria, combined continuous renal replacement therapy (CRRT) and adjunctive CytoSorb therapy were initiated with a CytoScore of 7 points
Behandlung
A total of 3 consecutive treatments with CytoSorb were performed over the following 3 days (each treatment for 24 hours)
CytoSorb was used in combination with CRRT (Multifiltrate, Fresenius Medical Care) run in continuous veno-venous hemodialylis (CVVHD) mode
Blood flow rate: 100 ml/min
Anticoagulation: Citrate
CytoSorb adsorber position: pre-hemofilter
Measurements
Hemodynamics and catecholamine requirements
Inflammatory parameters
Lactate
Results
Catecholamine therapy could already be discontinued after the 2nd treatment cycle
Treatment was further associated with a control of the hyperinflammatory response with clear reductions in inflammatory parameters (leukocytes 16.2/nl and PCT 0.47 pg/ml 24 h after the last treatment)
Lactate also returned to normal values (1.3 mmol/L) 24 h after the last treatment
Patient Follow-up
Discontinuation of dialysis and CytoSorb treatment on day 3
Invasive ventilation was also terminated after 3 days and the patient could be successfully extubated
Transfer from intensive care to the normal ward after a total of 7 days
Discharge from the hospital into his home environment after 21 days of total hospital stay
Currently the patient is permanently dependent on a daily parenteral fluid and nutrient supply. Thus, the patient appears to be a possible candidate for a small bowel transplant and has been referred to an appropriate centre
Conclusions
In this patient with septic shock, the combined treatment consisting of standard therapy, CytoSorb hemoadsorption and renal replacement therapy resulted in a marked stabilization in hemodynamics with rapid reduction of norepinephrine requirements as well as control of the hyperinflammatory situation
According to the authors, CytoSorb quickly and effectively helped to stabilize a critical condition
A CytoScore above 6 points represents a refractory shock state. The score may therefore help in the initiation of CytoSorb therapy
Treatment with CytoSorb was safe and feasible without technical problems.
Case of the Week 27
Literature Database
Use of CytoSorb hemoadsorption for the management of acute liver failure
Dr. Vinod Singh | Institute of Critical Care Medicine, Sir Gangaram Hospital, New Delhi, India
07/06/2022
New!Reduction in catecholaminesSafetyImprov. resp functionBilirubinCase of the weekCase reportCritical CareCRRT pre filterImprov. hep. encephalopathyLiver failure
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Summary
CoW 27/2022 – This case reports on a 28-year-old female patient who was referred intubated and ventilated from an intensive care unit (ICU) of another tertiary care hospital to Sir Gangaram Hospital, Delhi, with a confirmed diagnosis of acute liver failure with grade II hepatic encephalopathy and coagulopathy.
Case presentation
Before her initial admission to the peripheral hospital, the patient had a history of fever associated with chills and rigors for 7 days and was also suffering from abdominal pain. She also had a history of taking ayurvedic medicine for jaundice
Following hospitalization at the Sir Gangaram hospital, the patient’s vitals were recorded. Blood pressure and respiratory rate were 120/82 mmHg and 16/min, respectively
Subsequently, she was transferred to the intensive care unit (ICU) with impaired oxygenation and a PaO2/FiO2 ratio of 195 mmHg
Lab investigations showed a total leukocyte count of 13.9×103/µl as well as a platelet count of 67×103/µl. Coagulation tests revealed a grossly elevated International Normalized Ratio (INR) of 4.07
Her liver function tests were markedly abnormal (bilirubin 19.2 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT) 164 U/L, serum glutamic-pyruvic transaminase (SGPT) 140 U/L) indicating pronounced and already established liver failure while she was also suffering from intermittent episodes of altered sensorium
Furthermore, she had elevated serum lactate levels (3.37 mmol/L)
However, serum creatinine level was normal at 1.19 mg/dl and urinary output was 4185 ml/day
The patient’s Glasgow Coma Scale (GCS) score was 6 while Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were 13 and 12, respectively
Model for End-Stage Liver Disease (MELD) score was estimated to be 40
She also exhibited hemodynamic instability requiring norepinephrine support up to 3 µg/min
Abdominal ultrasound examination showed an enlarged liver and a contracted bladder with moderate free fluid in the peritoneal cavity, all signs suggestive of acute liver failure
The decision was made to perform 4 cycles of plasma exchange therapy
Given the patient’s critical condition and in order to accelerate liver toxin removal, but also to control the septic/hyperinflammatory condition, a CytoSorb hemoadsorption cartridge was additionally integrated into the plasma exchange therapy cycle
Rotational thromboelastometry (ROTEM) was used throughout the treatment interval to control for any changes in the coagulatory status. Accordingly, four units of fresh frozen plasma (FFP) and albumin had to be administered over this time
Measurements
Hemodynamics
Liver function
Lactate
Renal function
Respiratory parameters
GCS
SOFA score
Treatment
One CytoSorb therapy session was performed for a duration of 24 hours
The CytoSorb device was run in conjunction with plasma exchange therapy (Prismaflex, Baxter)
Blood flow rate: 150 ml/min
Anticoagulation: none
Results
Mean arterial pressure remained stable during CytoSorb therapy. Norepinephrine could be weaned off 2 hours after CytoSorb therapy completion
Treatment was associated with a rapid and sustained decline in bilirubin plasma levels with a concomitant decrease in liver transaminases
There also was a reduction in serum lactate under hemoadsorption treatment
Renal function improved as evidenced by an increase in urinary output
Lung function/oxygenation remained stable with a PaO2/FiO2 of 198 mmHg
GCS showed a slight improvement
SOFA score could be reduced
Parameters Before CytoSorb therapy After CytoSorb therapy
Mean arterial pressure (mmHg) 90 90
Bilirubin (mg/dL) 19.2 7.97
SGOT (U/L) 140 115
SGPT (U/L) 164 81
Serum lactate (mmol/L) 3.37 2.70
Urinary output (ml/day) 4185 4600
PaO2/FiO2 195 198
GCS Score 6 7
SOFA score 13 12
Patient Follow-Up
On suspecting autoimmune related acute liver failure the patient was put on steroids, and her acute kidney injury was managed conservatively. The patient was extubated as her condition improved and she was transferred to a high-dependency unit
Later, transjugular liver biopsy showed features of chronic venous hepatic congestion, and ultrasound doppler flow axis examination revealed hepatomegaly with bilateral mild pleural effusion and moderate ascites
As the steroids were not showing any effect on the patient’s condition, they were stopped. She was managed with IV antibiotics, anti-hepatic encephalopathy (HE) measures, diuretics, and other supportive measures
The patient’s family was informed about the need for liver transplantation based on above mentioned medical conditions
Patient was referred to a surgical gastroenterologist for evaluation of a liver transplant, and she decided to undergo cadaveric liver transplantation while simultaneously opting for discharge. Hence, she was discharged from hospital after 28 days of hospitalization in a stable condition and advised to follow-up with a liver clinic
Conclusions
In this case of a patient with acute liver failure, CytoSorb hemoadsorption in combination with plasma exchange and standard of care therapy resulted in a stabilization of her liver function including a rapid decrease in plasma bilirubin levels as well as a reduction in serum lactate levels and an overall improvement in the patient’s clinical condition
According to the authors, in this special case CytoSorb contributed towards controlling the hyperinflammation, and it also acted as an effective means of controlling the hyperbilirubinemia
CytoSorb in combination with plasma exchange therapy was safe and easy to apply.
Use of CytoSorb® hemoadsorption column during prolonged cardiopulmonary bypass in complex cardiac surgery patient
Marianne Alarie et al. J Cardiothorac Surg. 2022.
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J Cardiothorac Surg
. 2022 Jul 7;17(1):172.
doi: 10.1186/s13019-022-01922-7.
Authors
Marianne Alarie 1 , Maggie Savelberg 2 , Danika Vautour 2 , Igo B Ribeiro 2
Affiliations
1 Kingston Health Sciences Centre, Kingston, ON, Canada. marianne.alarie@kingstonhsc.ca.
2 Kingston Health Sciences Centre, Kingston, ON, Canada.
PMID: 35799205
DOI: 10.1186/s13019-022-01922-7
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Abstract
Background: Complex cardiac surgery and prolonged cardiopulmonary bypass are associated with significant activation of the systemic inflammatory response system. Pro-inflammatory cytokines, oxygen free radicals and complement activation products contribute to postoperative complications and multiorgan injury. CytoSorb® hemoadsorption therapy has been suggested to alleviate the hyperinflammatory response triggered by cardiopulmonary bypass during cardiac surgery.
Case presentation: We describe the use of CytoSorb® hemoadsorption therapy in a 61-year-old male presenting for aortic valve replacement, mitral valve replacement, tricuspid valve repair, coronary artery bypass grafting and left atrial appendage clip.
Conclusion: We were able to demonstrate that CytoSorb® use during cardiopulmonary bypass may be a safe and feasible adjunct therapy that may contribute to improved postoperative outcomes in a patient with complex cardiac disease.
Keywords: Bypass; Case report; CytoSorb; Cytokines; Hemoadsorption; Inflammation.
Literature Database
Sepsis Management in Southeast Asia: A Review and Clinical Experience
Mehta Y, Paul R, Rabbani R, Acharya SP, Withanaarachchi UK. Journal of Clinical Medicine 2022; 11(13);3635
06/27/2022
New!Peer Reviewed Published DataReviewSeptic Shock
Link to source
Summary
This review summarizes the literature that focuses on the diagnosis and treatment of sepsis, issues with colistin resistance, the increasing use of chloramphenicol, antibiotic abuse, resource constraints and finally the association of sepsis with COVID-19 in Southeast Asia. A panel of five experts discussed the literature and made the following recommendations:
Data on the incidence of sepsis in this region be collected and shared
The management of sepsis be personalized
Use of conventional approaches and innovative therapeutic alternatives to sepsis management be employed
In particular a personalized approach and innovative therapeutic alternatives such as CytoSorb are highlighted as potential options for the treatment of patients with sepsis in Southeast Asia. CytoSorb is described in detail, along with all the publications on these patients from this region. It is noted that it is now well established that absence of evidence is not evidence of absence. Therefore, adopting a personalized treatment approach wherever and whenever desirable and embracing novel extracorporeal blood purification technologies could further enhance patient outcomes and alleviate the burden of sepsis. In support of this, the authors state that instead of randomized control trials, that real-world evidence be used to show the benefit in determining the potential of CytoSorb for the management of sepsis.
Case of the Week
Literature Database
CytoSorb as adjuvant therapy in refractory ARDS and ECMO support in COVID-19
Dr. med. Martin Schmölz, Dr. med. T. Gröbl, Dr. med. A. Schirner, Dr. med. L. Wagner | Department for Anesthesiology, Intensive Care and Emergency Medicine, Immenstadt Clinic - Klinikverbund Allgäu gGmbH, Germany
06/29/2022
New!Reduction in catecholaminesSafetyViral infectionImprov. resp functionAnticoagulation OthersARDSCase of the weekCase reportCOVID-19Critical CareECMO (VV or VA)
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Summary
CoW 26/2022 – This case reports on a 55-year-old male patient who was transferred from an external hospital to Immenstadt hospital due to progressive respiratory deterioration with confirmed COVID-19 pneumonia.
Case presentation
Prior to this, he was admitted to a peripheral hospital following a deterioration in his general condition including fever. At this hospital he initially received oxygen therapy via nasal cannula and dexamethasone therapy for a total of 16 days. However, respiratory wise he continued to deteriorate with subsequent transfer to the intensive care unit (ICU). Hence, high-flow oxygen/non-invasive ventilation therapy was started, but there was a continuous clinical deterioration with O2 requirements of 90-100% via non-invasive ventilation. Finally, endotracheal intubation was performed and the patient was subsequently transferred to Immenstadt hospital
His vaccination status was as follows: vaccinated 3x COVID-19 (2x Biontech, 1x Moderna), but no titer response to the first two vaccinations, but only to the 3rd vaccination
The patient’s medical history further included follicular lymphoma, post-radiotherapy, current chemotherapy, nicotine abuse, hypercholesterolaemia and obesity
On admission to Immenstadt hospital, the patient was intubated with the following settings: paO2 59 mmHg, paCO2 46 mmHg, FiO2 of 1.0, positive end-expiratory pressure (PEEP) 14 cmH2O; his blood pressure was 89/52 mmHg under ongoing norepinephrine therapy (2.2 mg/h)
Due to the highly critical acute situation of refractory acute respiratory distress syndrome (ARDS) and the rapid dynamics of deterioration, veno-venous (vv) extracorporeal membrane oxygenation (ECMO) therapy was implanted immediately after admission. Given a difficult puncture attempt of the right internal jugular vein and status after port implantation in the right subclavian vein, a bifemoral insertion technique was chosen, with the reflow cannula via the femoral vein on the left side
After initiation of the extracorporeal circuit, lung-protective ventilation could be performed. The patient was then prone-positioned several times. Subsequently, FiO2 could be reduced to 0.5. PaO2/FiO2 at that time was 133 mmHg
To measure the transpulmonary pressure, a PESO catheter was placed and the PEEP was adjusted according to the measured values which varied considerably with positioning
Computed tomography showed severe COVID changes, but also pneumonic consolidations. Calculated antibiotic therapy was started with meropenem; in addition, voriconazole was administered in a calculated manner due to radiological suspicion of COVID-19-associated pulmonary aspergillosis. This was later confirmed in the bronchoalveolar lavage. Over time, the patient developed recurrent severe infections, partly with multi-resistant pathogens and also with herpes simplex Virus
Due to a pronounced hyperinflammatory state with markedly elevated plasma concentrations of C-reactive protein (CRP 347 mg/l), a CytoSorb hemoadsorber was additionally integrated into the vvECMO circuit with the aim of controlling the hyperinflammatory situation
Treatment
One treatment with CytoSorb was performed for a total treatment duration of 24 hours
The CytoSorb adsorber was directly integrated into the vvECMO circuit as a bypass
Anticoagulation was performed according to internal standard with Argatroban controlled via PTT and ECA-test
Measurements
Hemodynamics and norepinephrine requirements
Inflammatory parameters
Results
The catecholamine dose (norepinephrine 2.1 mg/h) initially required to maintain an adequate mean arterial pressure could be significantly reduced under adsorber therapy and fluid substitution. After 24 h, norepinephrine requirement was 0.5 mg/h with subsequent further decreasing values
A decrease in the elevated CRP levels (347 mg/l) was not observed during the treatment period
Patient Follow-Up
Over time, continuous renal replacement therapy (CRRT) using continuous veno-venous hemodialysis (CVVHD) was indicated due to the development of acute renal failure
Initially, the patient had a protracted course with septic multi-organ failure and a difficult sedation regime (inhalative sedation)
He also suffered from diffuse hemorrhages and microthrombi in his extremities with severe necrosis of all fingers of the left hand as a result of severe disseminated intravascular coagulation
Repeated initiation of broad-spectrum antibiotic therapy with evidence of partly multi-resistant pathogens in the bronchial secretions as well as in the bloodstream
Weaning was difficult and prolonged in the context of the underlying disease
A CT scan performed because of ongoing drowsiness that showed acute subdural bilateral hematomas with a slight midline shift. Anticoagulation in the context of the extracorporeal ECMO circuit was immediately discontinued and vvECMO therapy had to be stopped
Initially, pulmonary stabilization was only partially successful without ECMO and ventilation pressures outside the lung-protective range had to be tolerated for a short time
After infection control though, there was a steady improvement in compliance with consecutive pulmonary stabilization, and the patient could be switched to discontinuous weaning
Ventilation intervals via the nasal cannula with intermittent relief could be steadily increased
After 8 weeks of intensive therapy, the patient could be decannulated with good vigilance, respiratory mechanics and good pulmonary gas exchange
Unfortunately, the patient was still COVID-19 positive after several months. A mutation analysis revealed the virus type to be Omicron (BA.2-like). Antiviral triple therapy with Remdesivir, Paxlovir and Sotrovimab was therefore initiated
Early neurological rehabilitation has been organised and is expected to start soon
Conclusions
In this patient with COVID-19, refractory ARDS and vvECMO support, the combination of extracorporeal oxygenation, adsorber therapy and volume/catecholamine therapy resulted in clear clinical stabilization both in regards to his hemodynamic and respiratory parameters during the highly critical phase
A hyperinflammatory state could be controlled initially, but severe septic episodes occurred repeatedly later on
Treatment with CytoSorb was safe and use of the adsorber together with vvECMO therapy was feasible without technical problems.
Case of the Week
Literature Database
Use of the CytoSorb® filter for elimination of residual therapeutic argatroban concentrations during heparinized cardiopulmonary bypass for heart transplantation
Andreas Koster1, Helmuth Warkentin1, Vera von Dossow1, and Michiel Morshuis2 | 1 Institute of Anesthesiology and Pain Therapy, Bad Oeynhausen, Germany | 2 Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum NRW, Bad Oeynhausen, Ruhr-University Bochum, Germany Perfusion 2022; epub
06/08/2022
New!Peer Reviewed Published DataTransplantCardiac surgeryCase of the weekCase reportCPBDrug removalIntra-Op
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Summary
CoW 25/2022 – This case reports on a 34-year-old male patient with a medical history of a correction of Fallot tetralogy, who was scheduled for heart transplantation.
Summary
This is a case report about a 34-year-old patient who, after a five week wait in hospital, was offered a donor heart that had to be transplanted within 2 hours. Because of a history of heparin-induced thrombocytopenia (HIT), the patient had been placed preoperatively on the anticoagulation drug argatroban for which there is currently no reversal agent. Despite ceasing the continuous infusion of argatroban immediately, concentration only declined from 0.60 mug/ml to 0.58 mug/ml before surgery, with the activated clotting time (ACT) value remaining very high (223 s). Microvascular bleeding was observed on chest incision, therefore a CytoSorb column was integrated into the system of the heparin-anticoagulated cardiopulmonary bypass (CPB) circuit, with a flow of 400 mL/min provided during the 150 mins of extracorporeal circulation. The argatroban concentration after weaning from CPB was 0.04 mug/ml and satisfying hemostasis was achieved after protamine administration. Despite severe bleeding within the context of perioperative use of argatroban having been described, the 12-h postoperative blood loss was only 580 mL. The authors note that the availability of a technology for quick elimination of high therapeutic concentrations of argatroban may have a significant impact on the safety profile of this drug, and that the use of CytoSorb might be an effective tool that has the potential to fulfil these criteria.
Comment from CytoSorbents
Argatroban is a direct thrombin inhibitor used instead of heparin for anticoagulation in cases of heparin-induced thrombocytopenia. This is the first published clinical case report that suggests a potential relevant removal of argatroban, but there are a number of other published papers (case reports / case series) that confirm the feasibility of argatroban anticoagulation without the need for additional precautions. Relevant in-vitro removal of argatroban has been shown, however, with the exception of this case report, there has been no signal towards clinically important removal from the published literature. Based on the currently available, inconclusive data, we recommend regular monitoring of aPTT when argatroban is used as anticoagulant during CytoSorb application.
Case presentation
The patient further revealed severe biventricular dysfunction requiring moderate inotropic support as well as multiorgan dysfunction (Model of End Stage Liver Disease excluding International Normalized Ratio [INR] (MELD XI) score of 12.3)
Due to a previous history of heparin-induced thrombocytopenia (HIT), systemic anticoagulation with argatroban was initiated and monitoring of the drug was performed with a target plasma concentration of 0.4–1.0 µg/ml
After a five week wait in hospital, a donor organ was finally offered, which, however, had to be transplanted within 2 hours due to logistical reasons
The infusion of argatroban was immediately stopped and blood samples taken to measure the actual argatroban plasma concentration
Despite ceasing the continuous infusion of argatroban immediately, concentration only declined from 0.60 µg/ml to 0.58 µg/ml within 2 hours before surgery, with the activated clotting time (ACT) value remaining very high (223 s)
With chest incision, 1 g of tranexamic acid was given to the patient and 0.5 g added to the cardiopulmonary bypass (CPB) system
During sternotomy, massive coagulopathy was evident and, as dialysis or continuous hemofiltration do not result in significant clearance of argatroban plasma levels, it was decided to incorporate a CytoSorb hemoadsorption column into the CPB circuit for possible enhanced extracorporeal elimination of argatroban
Treatment
One CytoSorb hemoadsorber was provided during the 150 mins of extracorporeal circulation
The CytoSorb column was integrated into the system of the heparin-anticoagulated CPB circuit. No hemofiltration was performed. During CPB, two units of red blood cell (RBC) concentrates were transfused
Blood flow rate: 400 mL/min
Measurements
Hemodynamics and need for inotropes
Argatroban plasma concentrations
Hemostasis as well as perioperative blood loss
Results
Weaning from CPB was possible with moderate inotropic support
Argatroban concentration declined from 58 µg/ml to 0.04 µg/ml during hemoadsorption
This was associated with a satisfying hemostasis after protamine administration with only modest microvascular bleeding observed in the operation field. The 12-h postoperative blood loss was only 580 mL
Patient Follow-up
The chest could be closed 1 hour after the end of CPB and the patient was transferred to the intensive care unit
Conclusion
This is the first report about the use of the CytoSorb column to eliminate high therapeutic concentrations of argatroban
The authors note that the availability of a technology for quick elimination of high therapeutic concentrations of argatroban may have a significant impact on the safety profile of this drug, and that the use of CytoSorb might be an effective tool that has the potential to fulfil these criteria.
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Corona, Acute Ischemic Stroke, Malignant Cerebral Edema, and Hemo-adsorption: A Case Report
Mehul Shah et al. Indian J Crit Care Med. 2022 Feb.
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Indian J Crit Care Med
. 2022 Feb;26(2):235-238.
doi: 10.5005/jp-journals-10071-24116.
Authors
Mehul Shah 1 , Zakaria Kaidawala 1 , Arun Shah 2 , Rushi Desphande 3
Affiliations
1 Department of Critical Care Medicine, Sir HN Reliance Foundation Hospital and Research Centre, Mumbai, Maharashtra, India.
2 Department of Neurosciences, Sir HN Reliance Foundation Hospital and Research Centre, Mumbai, Maharashtra, India.
3 Department of Nephro Critical Care, Sir HN Reliance Foundation Hospital and Research Centre, Mumbai, Maharashtra, India.
PMID: 35712732
PMCID: PMC8857715
DOI: 10.5005/jp-journals-10071-24116
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Abstract
Background: COVID-19 infection can be associated with systemic hyperinflammation, hypercoagulable state, vasculitis, and cardiomyopathy leading to multiorgan failure. Use of extracorporeal blood purification has been shown to mitigate the cytokine storm, improving hemodynamic stability and pulmonary function.
Case summary: We report a case of a young patient with malignant cerebral edema due to acute cerebrovascular accident, with COVID-19. He was taken up for life-saving decompression craniotomy amidst the cytokine storm and multiorgan failure, and was treated with steroids, antibiotics, and Cytosorb® therapy for the cytokine storm. IL-6 and PCT levels were reduced by 99.5 and 98.6%, respectively. Vasopressors were stopped on day 4 and successfully weaned off ventilator support by 2 weeks of tracheostomy. He was de-cannulated and discharged neurologically stable on day 32.
Conclusion: Timely detection of COVID-19 and anti-inflammatory and hemo-adsorption measures may be helpful in modulating cytokine storm, thereby reducing morbidity and mortality.
How to cite this article: Shah M, Kaidawala Z, Shah A, Desphande R. Corona, Acute Ischemic Stroke, Malignant Cerebral Edema, and Hemo-adsorption: A Case Report. Indian J Crit Care Med 2022;26(2):235-238.
Keywords: Acute ischemic stroke; COVID-19; Corona; Cytosorb;
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Use of CytoSorb in a patient with hemorrhagic shock and multiple organ failure due to complicated secondary cesarean section
Dr. Mirko Brenni und Dr. Julien Marrel | Department for Anesthesiology, Intensive Care and Emergency Medicine, See-Spital Horgen, Horgen, Switzerland
06/15/2022
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Summary
CoW 24/2024 – This case reports on a 31-year-old previously healthy female patient, who was admitted post-operatively to the intensive care unit (ICU) with hemorrhagic shock and dilutional/ disseminated intravascular coagulopathy following secondary cesarean section with uterine atony, after already two revisions and ultimately an emergency hysterectomy.
Case presentation
On admission to the ICU, the patient was ventilated (pressure-controlled ventilation, with an FiO2 of 0.8), hemodynamically unstable with high catecholamine requirements. For hemodynamic stabilization, the patient was given norepinephrine up to 70 µg/min and dobutamine up to 300 µg/min in addition to fluid resuscitation. Moreover, the intravascular oncotic pressure was increased by an albumin infusion. While in shock, lactate levels were 10 mmol/l accompanied by severe metabolic acidosis
Also, following perioperative mass transfusion (including 9 red cell concentrates, 12 litres of Ringer’s solution) in postpartum hemorrhagic shock, she had dilutional and disseminated intravascular In accordance with repeated rotational thromboelastometry (ROTEM) measurements and a confirmed decrease in hemoglobin and platelet levels, as well as an increased bleeding tendency with prolonged aPTT, increased INR and fibrinogen deficiency, she received coagulation factors (a total of 15 g fibrinogen, 4500 IU human prothrombin complex (PPSB), 6000 IU blood coagulation factor XIII, 2000 mg tranexamic acid, 6 g calcium) as well as two platelet concentrates. As a result, her coagulative state was largely normalized intraoperatively under ROTEM control, and there were no further indications of post-operative bleeding
Chest X-ray examination showed bilateral pleural effusions and evidence of pulmonary hyperhydration, most probably due to the initial massive volume replacement therapy with increased capillary leakage, however without signs of pulmonary infiltrates
There was also a marked increase in troponin and creatine kinase values. Given the hemorrhagic shock situation, it was assumed that there was ischemic myocardial damage in the context of a type 2 acute coronary syndrome
Several hours post-operatively, inflammatory markers were clearly elevated: leukocytes 18.4 G/l, C-Reactive Protein [CRP] 62.5 mg/l and Interleukin [IL-6] 119 ng/l
Due to a confirmed nitrite-positive urinary tract infection, antibiotic therapy with co-amoxicillin was started for a total of 7 days. Repeated urine cultures, however, were negative on all measurements, while no bacterial growth could be detected in subsequent microbiological examinations
On the first postoperative day, there was also a marked increase in aminotransferases (aspartate aminotransferase [AST] 779 U/l, alanine aminotransferase [ALT] 132 U/l) indicating a shock-induced ischemic hepatopathy
Moderate ascites with anasarka was also found in the context of the pronounced fluid resuscitation. During the post-operative course, 1000-3000 mls of wound drainage per day was recorded
Due to acute anuric renal failure with hyperkalemia and hyperphosphatemia, continuous renal replacement therapy (CRRT) was started early, i.e. about 2 hours after admission to the ICU
Given the pronounced hemodynamic instability with progressive multi-organ failure in the context of severe hyperinflammation following mass transfusion, a CytoSorb cytokine adsorber was started simultaneously with CRRT
Treatment
Treatment with CytoSorb was performed for a period of about 48 hours
CytoSorb was used in combination with CRRT (Prismaflex, Baxter) run in CVVHDF mode
Anticoagulation: regional citrate. After the onset of citrate accumulation in the context of the most severe shock state with severe lactic acidosis, continuous veno-venous hemodiafiltration (CVVHDF) could be continued without problems following adjustment of hemodiafiltration settings
Position of the CytoSorb adsorber: post-hemofilter
Measurements
Hemodynamics and norepinephrine requirements
Lactate
Inflammatory parameters (CRP, Procalcitonin [PCT], ferritin, IL-6)
Fluid balance (colloids and crystalloids)
Oxygenation/ventilation
Results
Catecholamine therapy with norepinephrine could already be reduced to 3-5 µg/min 24 hours after initiation of combined CRRT/CytoSorb therapy after generous fluid substitution including album administration
Lactate levels also normalized on the first postoperative day
One day post-operatively, leukocytes were 14.1 G/l, CRP 72.5 mg/l, PCT 1.7 ng/ml, ferritin 787.7 µg/l and IL-6 86.4 ng/l
Following hemodynamic stabilization, consistent negative balancing could be achieved from day 4 onwards
The clinical pulmonary hyperhydration improved daily under negative balancing while chest X-ray examination showed that the pleural effusions had regressed. There was no evidence of transfusion-associated acute lung injury (TRALI). Weaning was also unproblematic, extubation was performed after neurological improvement on day 7
Patient Follow-Up
Due to a recurrent febrile episode in the antibiotic window, another sampling was performed, confirming the growth of Pseudomonas aeruginosa and Enterococcus faecium in the abdominal wound discharge. Consequently, antibiotic therapy was initially changed to piperacillin/tazobactam and daptomycin (for acute renal failure), and was then, according to the resistogram, switched from piperacillin/tazobactam to meropenem and continued for a total of 14 days. Following another recurrence of fever and ultrasound-guided puncture of an intra-abdominal hematoma, Candida albicans was detected in the collected sample After initiating antifungal therapy with fluconazole, inflammatory parameters decreased over time
After a total of 7 days of CVVHDF with an increase in diuresis, a first discontinuation attempt was started a few days later, which resulted in a renewed increase in creatinine and urea plasma levels. Therefore, intermittent hemodialysis was started and continued until transfer of the patient to a rehabilitation unit
Following an initial delayed recovery phase (despite reduced sedation, vigilance was still reduced), extubation was finally achieved without complications after a total of 7 days of invasive ventilation. Gas exchange was unproblematic. Due to persistent dyspnoea, a lung scintigraphy was performed without evidence of pulmonary embolism
After extubation, the patient was temporarily disoriented with hallucinations, which was interpreted as multifactorial delirium. The symptoms improved rapidly and there were no cognitive impairments. In the course of the patient’s stay, she developed loss of vision in the right eye, which, after magnetic resonance and ophthalmological examination, was interpreted as ischemic optic neuropathy in the context of the severe shock event
During the entire intensive care stay, the patient required a total of 7 units of red blood cells. Substrates remained within the normal range and erythropoietin was administered weekly in the presence of dialysis-dependent renal insufficiency with hyporegenerative anemia. At discharge, severe anemia persisted with an Hb of 63 g/l, however with measurable reticulocytosis.
The patient was discharged to a rehabilitation facility after a total hospital stay of 31 days
Conclusions
In this patient with hemorrhagic shock and multiple organ failure due to complicated secondary cesarean section, the post-operative use of CytoSorb, in addition to correcting hypoalbuminemia, led to hemodynamic stabilization by controlling hyperinflammation
According to the authors, CytoSorb therapy in this complex case presumably contributed to gaining control over the hyperinflammation triggered by the initial mass transfusion within a few hours
Hemoadsorption with CytoSorb in combination with CRRT was safe and easy to perform in this challenging setting.