LAUSR

Colloids, known as volume expanders, have been used as resuscitation fluids for hypovolemic shock for decades, as they increase plasma oncotic pressure and expand intravascular volume. However, recent studies show that commonly used synthetic colloids have adverse interactions with human biological systems. In this work, a low‐fouling amine(N)‐oxide‐based zwitterionic polymer as an alternative volume expander with improved biocompatibility and efficacy is designed. It is demonstrated that the polymer possesses antifouling ability, resisting cell interaction and deposition in major organs, and is rapidly cleared via renal filtration and hepatic circulation, reducing the risk of long‐term side effects. Furthermore, in vitro and in vivo studies show an absence of adverse effects on hemostasis or any acute safety risks. Finally, it is shown that, in a head‐to‐head comparison with existing colloids and plasma, the zwitterionic polymer serves as a more potent oncotic agent for restoring intravascular volume in a hemorrhagic shock model. The design of N‐oxide‐based zwitterionic polymers may lead to the development of alternative fluid therapies to treat hypovolemic shock and to improve fluid management in general.