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Therapeutic Plasma Exchange in Adults Patients With Severe Sepsis

2019-08-20 20:17:10 | BioPortfolio

Summary

The incidence of sepsis (severe infection) has increased over the last four decades. Severe sepsis and septic shock are among the leading causes of death for patients admitted to critical care units with mortality ranging from 20-70% depending on totality of organ dysfunction. Outside of antibiotics and good bedside care, little has changed in the management of this life-threatening problem.

Therapeutic plasma exchange (TPE) involves the separation of plasma from whole blood. The removed plasma is 'exchanged or replaced' with either IV fluids, albumin, blood products or a combination thereof.

The purpose of this study is to assess the safety and feasibility of using plasma exchange in adult patients with septic shock. TPE is now a well-established program at the South Health Campus for neuro-muscular disorders. Since starting in May 2018, the investigators have performed over 150 runs making the SHC ICU one of the most experienced centers in Canada.

Description

The incidence of sepsis has increased over the last four decades. Severe sepsis and septic shock are among the leading causes of death for patients admitted to critical care units with mortality ranging from 20-70% depending on totality of organ dysfunction . The literature is replete with initial promising phase 2 therapies failing in definitive randomized trails. The most recent guidelines have tried to redefine sepsis as a 'syndrome' since neither validated criterion nor do standard diagnostic tests exist. Most of the clinical manifestations of severe infections are caused by an intense, generalized inflammatory response in the host mediated by a multitude of interrelated cellular and humoral factors.

Plasmapheresis or therapeutic plasma exchange (TPE) involves the separation of plasma from whole blood. The removed plasma is 'exchanged or replaced' with either crystalloids, albumin, fresh frozen plasma or a combination thereof. TPE use is well established in many neurological disorders including Guillain-Barre syndrome, Myasthenia Gravis and antibody mediated syndromes . It is considered the standard of care for Thrombotic thrombocytopenic purpura (TTP).

The rationale for the use of TPE in sepsis, a non-selective intervention, is to remove multiple toxic mediators including endotoxins, activated complement, pro-inflammatory cytokines and procoagulant factors. If fresh-frozen plasma is used as replacement fluid, consumed plasma factors are substituted, thereby possibly restoring the opsonic capacity and improving the coagulation abnormalities and microcirculation

Plasma exchange has been reported since the late 1970s as a potential adjunctive or salvage therapy in severe sepsis in both pediatric and adult patients . These case reports, retrospective reviews and observational studies suggest a survival advantage when compared to historical controls. However, the obvious bias limits any meaningful interpretation. A literature review found only 4 studies with a reasonable attempt at randomization.

The use of plasma exchange in severe sepsis is graded by the American Society for Apheresis as category III with grade 2C indications, indicating that there lack of reliable trials to support TPE use in the general condition. The purpose of this pilot study is to assess the safety and feasibility of using plasma exchange in adult patients with septic shock. TPE is now a well-established program at the South Health Campus for neuro-muscular disorders. Since starting in May 2018, the investigators have performed over 125 runs making the SHC ICU one of the the most experienced centers in Canada.

1. Adult patients with a documented or strong clinical suspicion of infection and meet the definition of septic shock as per the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The investigators will identify the subset with a hospital mortality in excess of 40%:

a. >30mls/kg fluid resuscitation b. Noradrenaline >0.1 ug/kg/min to maintain mean arterial pressure (MAP)> 65 mmHg for at least 4 consecutive hours and present at initiation of TPE c. Lactate >2 mmol/l.

1. All resuscitation, investigation, source-control and anti-microbial therapy will be performed at the discretion of treating ICU team.

2. Initiate TPE within 24 hours of diagnosis.

3. TPE can be repeated, once within 48h of diagnosis of septic shock, if the clinical condition does not improve, or in whom the clinical condition deteriorates, as judged by the presence or progression of hemodynamic instability and/or the development of further organ dysfunction.

4. The plasma exchange will be 1.5 x plasma volume

5. 1:1:1 combination of FF, albumin, crystalloid (max of 5000mls)

6. Informed consent by patient or proxy

7. Demographic and clinical characteristics at baseline will be collected

8. Patients will be followed until ICU discharge and be assessed:

1. >50% vasopressor decrease within 24hours of (each)TPE use

2. Improvement in Sepsis-related Organ Failure Assessments(SOFA) Score of at least 1 point in each of the 5 domains of SOFA score within 24hour and 7 days after TPE use

3. Days on ventilator if applicable,

4. Days in ICU (censored to day ready for discharge)

5. Mortality,

6. Need for renal replacement therapy (RRT),

9. This cohort will be compared to matched controls within previous year admitted to same ICU. Cohort will be matched and same outcomes, as above, will be compared.

Study Design

Conditions

Septic Shock

Intervention

Therapeutic plasma exchange

Status

Not yet recruiting

Source

Alberta Health Services, Calgary

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-08-20T20:17:10-0400

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Medical and Biotech [MESH] Definitions

Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions.

Condition of low SYSTEMIC VASCULAR RESISTANCE that develops secondary to other conditions such as ANAPHYLAXIS; SEPSIS; SURGICAL SHOCK; and SEPTIC SHOCK. Vasoplegia that develops during or post surgery (e.g., CARDIOPULMONARY BYPASS) is called postoperative vasoplegic syndrome or vasoplegic syndrome.

Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.

Increase in blood LACTATE concentration often associated with SEPTIC SHOCK; LUNG INJURY; SEPSIS; and DRUG TOXICITY. When hyperlactatemia is associated with low body pH (acidosis) it is LACTIC ACIDOSIS.

A ubiquitous membrane transport protein found in the plasma membrane of diverse cell types and tissues, and in nuclear, mitochondrial, and Golgi membranes. It is the major integral transmembrane protein of the erythrocyte plasma membrane, comprising 25% of the total membrane protein. It exists as a dimer and performs the important function of allowing the efficient transport of bicarbonate across erythrocyte cell membranes in exchange for chloride ion.

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