title: Resuscitation speed affects brain injury in a large animal model of traumatic brain injury and shock.
abstract: BACKGROUND
  Optimal fluid resuscitation strategy following combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remain controversial and the effect of resuscitation infusion speed on outcome is not well known. We have previously reported that bolus infusion of fresh frozen plasma (FFP) protects the brain compared with bolus infusion of 0.9% normal saline (NS). We now hypothesize reducing resuscitation infusion speed through a stepwise infusion speed increment protocol using either FFP or NS would provide neuroprotection compared with a high speed resuscitation protocol.
  
  
  METHODS
  23 Yorkshire swine underwent a protocol of computer controlled TBI and 40% hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for two hours prior to resuscitation with bolus FFP (n = 5, 50 ml/min) or stepwise infusion speed increment FFP (n = 6), bolus NS (n = 5, 165 ml/min) or stepwise infusion speed increment NS (n = 7). Hemodynamic variables over a 6-hour observation phase were recorded. Following euthanasia, brains were harvested and lesion size as well as brain swelling was measured.
  
  
  RESULTS
  Bolus FFP resuscitation resulted in greater brain swelling (22.36 ± 1.03% vs. 15.58 ± 2.52%, p = 0.04), but similar lesion size compared with stepwise resuscitation. This was associated with a lower cardiac output (CO: 4.81 ± 1.50 l/min vs. 5.45 ± 1.14 l/min, p = 0.03). In the NS groups, bolus infusion resulted in both increased brain swelling (37.24 ± 1.63% vs. 26.74 ± 1.33%, p = 0.05) as well as lesion size (3285.44 ± 130.81 mm(3) vs. 2509.41 ± 297.44 mm3, p = 0.04). This was also associated with decreased cardiac output (NS: 4.37 ± 0.12 l/min vs. 6.35 ± 0.10 l/min, p < 0.01).
  
  
  CONCLUSIONS
  In this clinically relevant model of combined TBI and HS, stepwise resuscitation protected the brain compared with bolus resuscitation.
authors.forename: Martin
authors.initials: M
authors.lastname: Sillesen
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.affiliation: Department of Surgery, University of Michigan Hospital, 2920 Taubman Center/5331, 1500 E, Medical Center Drive, Ann Arbor 48109, MI, USA. alamh@med.umich.edu.
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics; D008991:Monitoring, Physiologic / Q000379:methods; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000628:therapy*; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome