C5-blocking antibody reduces fluid requirements and improves responsiveness to fluid infusion in hemorrhagic shock managed with hypotensive resuscitation.
Hypotensive resuscitation strategies and inhibition of complement may both be of benefit in hemorrhagic shock. We asked if C5-blocking antibody (anti-C5) could diminish the amount of fluid required and improve responsiveness to resuscitation from hemorrhage. Awake, male Sprague-Dawley rats underwent controlled hemorrhage followed by prolonged (3 h) hypotensive resuscitation with lactated Ringer's or Hextend, with or without anti-C5. Anti-C5 treatment led to an estimated 62.3 and 58.5% reduction in the volume of Hextend and lactated Ringer's, respectively. In the subgroup of animals with a positive mean arterial pressure (MAP) response to fluid infusion following prolonged hypotension, anti-C5 treatment led to an estimated 4.7- and 4.1-fold increase in mean arterial pressure response per unit Hextend and lactated Ringer's infused, respectively. We observed no significant postresuscitation metabolic differences between the anti-C5 groups and controls. Whether anti-C5 could serve as a volume-sparing adjunct that improves responsiveness to fluid administration in humans deserves further study.
Peckham
Russell M
RM
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA. russell.m.peckham@us.army.mil
Handrigan
Michael T
MT
Bentley
Timothy B
TB
Falabella
Michael J
MJ
Chrovian
Andrew D
AD
Stahl
Gregory L
GL
Tsokos
George C
GC
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001794:Blood Pressure / Q000502:physiology; D003182:Complement C5 / Q000276:immunology* / Q000502:physiology; D005440:Fluid Therapy / Q000379:methods*; D007023:Hypotension, Controlled / Q000379:methods*; D007261:Infusions, Intra-Arterial; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000628:therapy*
D000906:Antibodies; D003182:Complement C5; D007552:Isotonic Solutions; D000077325:Ringer's Lactate