Researchers develop low-volume resuscitative agent for prehospital treatment of severe hemorrhagic shock

Significant blood loss after injuries can be life-threatening and must be replaced as quickly as possible. Injections of relatively small volumes of solutions of a new star-shaped polymer could replace fluid loss without disrupting clotting, according to a new study published in the journal Applied Chemistry International Edition. This makes it particularly interesting for the preclinical treatment of hemorrhagic shock.

Traumatic injuries account for a large proportion of morbidity and mortality. In the United States, they are the leading cause of death in people under 46 years of age. In cases of significant blood loss, time is critical because shock can occur within minutes or hours of the injury, often before the patient reaches a clinic.

Blood pressure drops, tissues no longer receive enough blood. The lack of oxygen forces tissues to enter anaerobic respiration, which causes lactic acidosis. Cellular sodium pumps stop and water leaks from the blood vessels into the surrounding tissues. This further reduces blood volume and worsens the shock.

Additionally, inflammatory reactions occur, flooding tissues with toxic metabolites when blood flow later resumes, which can lead to multiple organ failure.

In such cases, the main intervention is to replace the volume of fluid lost with substances such as saline. This requires warming several liters of fluid to physiological temperature, which is not practical outside a clinic. The large volumes administered also dilute the clotting factors and increase blood pressure, which can lead to further bleeding.

This is why modern resuscitation strategies (Damage Control Resuscitation, DCR) deliberately limit the administration of fluids and instead rely on whole blood transfusions, which reduce clotting problems, inflammation and mortality rates. In the field, in an ambulance or in a rescue helicopter, this remains impractical, particularly due to the lack of supply.

Alternatives currently under development include synthetic low-volume resuscitators (LVRs), highly effective solutions in small quantities, such as polyethylene glycol PEG20K. These substances generate osmotic gradients that draw body fluids out of tissues and back into blood vessels. This reduces the volume needed for treatment and keeps blood pressure low. However, PEG20K disrupts blood clotting and can cause allergic reactions.

A team led by Nathan J. White and Suzie H. Pun from the University of Washington (Seattle, USA) has developed a new LVR. Using a special controlled polymerization process (RAFT), they were able to synthesize many variants of methacrylate-based polymers with different compositions, molecular weights, and properties. Among these, a radiating star-shaped polymer was found to be an effective LVR with no negative effects on blood clotting.

After a loss of about 60% of blood volume in rat models, using 10% of that volume of the new polymer solution filled the blood vessels enough to return blood pressure to the desired window and overcome shock.

Even high doses of the polymer produced no observable adverse effects on blood clotting or organs, demonstrating that the new starburst polymer is an improvement over colloidal resuscitators currently in development.