title: Titrated hypertonic/hyperoncotic solution for hypotensive fluid resuscitation during uncontrolled hemorrhagic shock in rats.
abstract: BACKGROUND
  In volume- or pressure-controlled hemorrhagic shock (HS) a bolus intravenous infusion of hypertonic/hyperoncotic solution (HHS) proved beneficial compared to isotonic crystalloid solutions. During uncontrolled HS in animals, however, HHS by bolus increased blood pressure unpredictably, and increased blood loss and mortality. We hypothesized that a titrated i.v. infusion of HHS, compared to titrated lactated Ringer's solution (LR), for hypotensive fluid resuscitation during uncontrolled HS reduces fluid requirement, does not increase blood loss, and improves survival.
  
  
  METHODS
  We used our three-phased uncontrolled HS outcome model in rats. HS phase I began with blood withdrawal of 3 ml/100g over 15 min, followed by tail amputation. Then, hydroxyethyl starch 10% in NaCl 7.2% was given i.v. to the HHS group (n=10) and LR to the control group (n=10), both titrated to prevent mean arterial pressure (MAP) from falling below 40 mmHg during HS time 20-90 min. At HS 90 min, resuscitation phase II of 180 min began with hemostasis, return of all the blood initially shed, plus fluids i.v. as needed to maintain normotension (MAP>or=70 mmHg). Liver dysoxia was monitored as increase in liver surface pCO2 during phases I and II. Observation phase III was to 72 h.
  
  
  RESULTS
  During HS, preventing a decrease in MAP below 40 mmHg required HHS 4.9+/-0.6 ml/kg (all data mean+/-S.E.M.), compared to LR 62.2+/-16.6 ml/kg (P<0.001), with no group difference in MAP. Uncontrolled blood loss during HS from the tail stump was 13.3+/-1.9 ml/kg with HHS infusion, versus 12.6+/-2.5 ml/kg with LR infusion (P=0.73). Serum sodium concentrations were moderately elevated at the end of HS in the HHS group (149+/-3 mmol/l) versus the LR group (139+/-1 mmol/l) (P=0.001), and remained elevated throughout. Liver pCO2 increased during HS in both groups equally (P<0.001 versus baseline), and tended to return to baseline levels at the end of HS. Blood gas and lactate values throughout did not differ between groups. During HS, 2 of 10 rats in the HHS group versus 0 of 10 in the LR group died (P=0.47). There was no difference between HHS and LR groups in survival rates to 72 h (3 of 10 in the HHS group versus 2 of 10 in the LR group) (P=1.0). Survival times, by life table analysis, were not different (P=0.75).
  
  
  CONCLUSIONS
  In prolonged uncontrolled HS, a titrated i.v. infusion of HHS can maintain controlled hypotension with only one-tenth of the volume of LR required, without increasing blood loss. This titrated HHS strategy may not increase the chance of long-term survival.
authors.affiliation: Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, 3434 Fifth Avenue, Pittsburgh, PA 15260, USA.
authors.forename: Rainer
authors.initials: R
authors.lastname: Kentner
authors.forename: Peter
authors.initials: P
authors.lastname: Safar
authors.forename: Stephan
authors.initials: S
authors.lastname: Prueckner
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Behringer
authors.forename: Xianren
authors.initials: X
authors.lastname: Wu
authors.forename: Jeremy
authors.initials: J
authors.lastname: Henchir
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruemelin
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Tisherman
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis; D001794:Blood Pressure; D004195:Disease Models, Animal; D005440:Fluid Therapy / Q000379:methods*; D006470:Hemorrhage / Q000209:etiology; D007022:Hypotension / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D007262:Infusions, Intravenous; D007552:Isotonic Solutions / Q000008:administration & dosage; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000503:physiopathology / Q000628:therapy*; D016019:Survival Analysis; D017186:Titrimetry; D016896:Treatment Outcome
chemical_list: D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic