For Veterinarians

The VetResQ adsorber is composed of biocompatible porous polymer beads, each roughly the size of a grain of salt, which act like tiny sponges to remove substances from whole blood. Substances that are larger than the pores, such as blood cells, cannot get into the pores and go around the beads. Very small water soluble or charged substances, such as glucose, electrolytes, and other essential blood components, are also not captured.

Substances that are smaller than the pore size get trapped in the vast network of pores and channels in every bead, and are permanently eliminated from blood. The pores in the VetResQ beads were specifically designed to target the majority of cytokines and inflammatory mediators that cause many life-threatening conditions. VetResQ relies on size exclusion and hydrophobic adsorption and, in contrast to affinity-based sorbents, does not use antibodies, ligands, cells or drugs. Because of this, VetResQ is a broad-spectrum solution to cytokine storm and inflammation. Additionally, very small fat-soluble molecules, including many pharmacological agents, adsorb to the polymer surface and are efficiently eliminated, allowing for systemic drug removal in overdosed patients.

One unique aspect of VetResQ is that removal is concentration dependent. At high concentrations of a particular substance, VetResQ can remove large amounts very quickly. Conversely, at low concentrations, the clearance becomes negligible. This self-regulation helps prevent over-treatment, improving the safety of the therapy.

The main focus of VetResQ therapy is the removal of inflammatory mediators, particularly cytokines and chemokines, from the patient´s blood. Whereas standard high-flux dialysis or CRRT is only capable of removing substances generally below 15 kDa in size, the VetResQ adsorber removes a wide range of pro- and anti-inflammatory mediators up to ~60 kDa.

VetResQ’s broad spectrum removal is important because of the redundancy in function amongst different cytokines, PAMPs, and DAMPs of varying size. For example, in humans, therapies focused on reducing single cytokines or inflammatory mediators have not historically been effective in improving outcomes in critically ill patients, presumably because they target only one of many contributors to the immune response.

Because VetResQ targets the reduction of substances in a molecular weight range up to ~60 kDa, it can reduce other substances that play an important role outside the SIRS response.

Activated complement:  In a wide variety of illnesses, the activation of complement can lead to widespread cellular injury and tissue damage.  Activated C3a and C5a are removed by VetResQ.

Myoglobin: In rhabdomyolysis due to severe trauma, burn injury, muscle overuse, or statin usage, myoglobin (17 kDa) can be released in massive quantities, leading to fouling and damage of the renal tubules and acute kidney injury. Myoglobin can be efficiently removed from the blood using VetResQ.

Free hemoglobin: Hemolysis of red blood cells results in the release of free hemoglobin into the blood. Common causes of hemolysis in cats and dogs include immune mediated hemolytic anemia (IMHA), infections (e.g., malaria, Streptococcus, EHEC), genetic disorders (e.g., sickle cell anemia) and other causes. When levels of plasma free hemoglobin exceed the body’s natural haptoglobin scavenging system, it can accumulate and become toxic through free oxygen radical generation and endothelial injury, and via potent nitric oxide scavenging. VetResQ is capable of removing plasma free hemoglobin efficiently.

Bilirubin: Bilirubin and biliverdin are by-products of hemoglobin metabolism following breakdown of heme in the spleen and liver. They can be found in abnormally high levels in blood in hemolytic disorders, impaired liver function, and intra-hepatic and extra-hepatic cholestasis (e.g., bile duct obstruction). VetResQ can remove unconjugated bilirubin (0.6 kDa) and conjugated bilirubin (0.8 kDa), with binding confirmed by a gradual yellowing of the sorbent beads.

Bile acids: Bile acids, and their accumulation in the plasma, play an important, yet often underestimated role during critical illnesses such as sepsis, systemic inflammation, and liver failure. Because they are surfactants/detergents, they can cause injury to cellular membranes. VetResQ use has been associated with rapid reduction of plasma bile acids, potentially reducing their toxic effects.

VetResQ is capable of eliminating both free and protein-bound drugs, and can either be implemented as a stand-alone therapy or in conjunction with hemodialysis to augment drug removal capabilities. Most importantly, for most intoxications only a single treatment is required, allowing the patient to return home the following day.

These are just a sampling of drugs that can be removed with VetResQ. We are continually validating removal of other substances.

VetResQ is an adjunctive therapy. It is designed to be used alongside primary therapies to provide additional therapeutic benefits. VetResQ was developed to modulate the excessive immune response, thereby preventing organ injury and helping to stabilize critically ill animals, with the goal of ultimately increasing the chance of recovery.

VetResQ therapy is intended to improve patient outcomes by:

• Improving hemodynamic stability with a reduction in the need for vasopressors
• Removing a wide variety of inflammatory mediators that can destabilize the patient
• Rapidly reducing excessive levels of various pharmacological agents

VetResQ is compatible with both systemic heparin and regional citrate anti-coagulation. The adsorber is gamma sterilized and has a shelf-life of three years at room temperature.

Simple application: The VetResQ adsorber is a standard whole blood perfusion cartridge that can be used with conventional hemodialysis, continuous renal replacement therapy (CRRT), and extracorporeal membrane oxygenation (ECMO) machines, and as stand-alone therapy with hemoperfusion machines, including the VetSmart pump shown below. It takes only minutes to prime and set-up and can be used by itself or in series with a standard hemodialyzer or hemofilter.

VetResQ is designed for flexibility and ease-of-use, requiring minimal preparation prior to implementing into a stand-alone hemoperfusion circuit or dialysis circuit. To ensure successful use of VetResQ, the following criteria must be satisfied:

• The VetResQ device is saline filled and must NEVER be drained of fluid.
• Do not get air into the VetResQ device, which can result in poor performance and clotting
• Flushing and priming of VetResQ with sterile normal saline is done separately from the CRRT circuit, ensuring that air has been flushed from all tubing prior to VetResQ flushing
• The CRRT, hemodialysis, or hemoperfusion circuit is flushed with sterile normal saline separately from VetResQ. Once the main circuit and CytoSorb have been separately flushed, the two are connected together
• The VetResQ device must be oriented vertically, with the VetResQ label arrow pointing up, corresponding to the direction of blood flow (i.e., blood flows into the bottom of the device and out the top)
• The VetResQ device has been validated for up to 24 hours of use, at which point it should be changed
• Anticoagulation with systemic heparinization must be sufficient (aPTT 60-80s or ACT 160-210s) prior to commencing and throughout VetResQ treatment