title: Targeted resuscitation improves coagulation and outcome.
abstract: BACKGROUND
  Acute trauma coagulopathy in seriously injured casualties may be initiated by tissue hypoperfusion. A targeted (or novel hybrid [NH]) resuscitation strategy was developed to overcome poor tissue oxygen delivery associated with prolonged hypotension.
  
  
  METHODS
  Under the Animals (Scientific Procedures) Act 1986, terminally anesthetized large white pigs were divided into four groups (n = 6). Groups 1 and 2 received blast injury and 3 and 4 no blast (sham). All were given a controlled hemorrhage (35% blood volume) and an uncompressed grade IV liver injury. Five minutes later, all were resuscitated with 0.9% saline to a systolic arterial pressure (SAP) of 80 mm Hg. After 60 minutes, the NH groups (1 and 3) were resuscitated to a SAP (110 mm Hg), whereas hypotensive groups (2 and 4) continued with SAP 80 mm Hg for up to 8 hours from onset of resuscitation.
  
  
  RESULTS
  Mean survival time was shorter in group 2 (258 minutes) compared with groups 1, 3, and 4 (452 minutes, 448 minutes, and 369 minutes). By the end of the study, hypotension was associated with a significantly greater prothrombin time (1.73 ± 0.10 and 1.87 ± 0.15 times presurgery, groups 2 and 4) compared with NH (1.44 ± 0.09 and 1.36 ± 0.06, groups 1 and 3, p = 0.001). Blast versus sham had no significant effect on prothrombin time (p = 0.56). Peak levels of interleukin 6 were significantly lower in NH groups. Arterial base excess was significantly lower with hypotension (-18.4 mmol/L ± 2.7 mmol/L and -12.1 mmol/L ± 3.2 mmol/L) versus NH (-3.7 mmol/L ± 2.8 mmol/L and -1.8 mmol/L ± 1.8 mmol/L, p = 0.0001). Hematocrit was not significantly different between groups (p = 0.16).
  
  
  CONCLUSIONS
  Targeted resuscitation (NH) attenuates the development of acute trauma coagulopathy and systemic inflammation with improved tissue perfusion and reduced metabolic acidosis in a model of complex injury. This emphasizes the challenge of choosing a resuscitation strategy for trauma patients where the needs of tissue perfusion must be balanced against the risk of rebleeding during resuscitation.
authors.affiliation: Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Birmingham, United Kingdom.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Doran
authors.forename: Callie A
authors.initials: CA
authors.lastname: Doran
authors.forename: Tom
authors.initials: T
authors.lastname: Woolley
authors.forename: Alun
authors.initials: A
authors.lastname: Carter
authors.forename: Keith
authors.initials: K
authors.lastname: Male
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Midwinter
authors.forename: Peter F
authors.initials: PF
authors.lastname: Mahoney
authors.forename: Sarah
authors.initials: S
authors.lastname: Watts
authors.forename: Emrys
authors.initials: E
authors.lastname: Kirkman
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000097:blood / Q000150:complications / Q000628:therapy; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000097:blood / Q000209:etiology* / Q000628:therapy; D004195:Disease Models, Animal; D058734:Exsanguination / Q000097:blood / Q000150:complications / Q000628:therapy; D007022:Hypotension / Q000097:blood / Q000209:etiology / Q000628:therapy; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000293:injuries; D011517:Prothrombin Time; D012151:Resuscitation / Q000379:methods*; D013552:Swine; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications / Q000628:therapy*
chemical_list: D015850:Interleukin-6