Titrated hypertonic/hyperoncotic solution for hypotensive fluid resuscitation during uncontrolled hemorrhagic shock in rats

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/100 g 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 ≥ 70 mmHg). Liver dysoxia was monitored as increase in liver surface pCO ₂ 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). Conclusion: 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.