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Impact of different haemodynamic resuscitation strategies on brain perfusion and tissue oedema markers in a model of severe haemorrhagic shock

Introduction

This study aimed to compare the cerebral effects of terlipressin (TERLI) with conventional prehospital fluid resuscitation with lactated Ringer's solution (LR) in a model of haemorrhagic shock (HS).

Methods

Pigs (20 to 30 kg) were randomized into one of the groups: Sham (n = 2), HS (n = 9), LR (3× volume bled; n = 9) or TERLI (2 mg bolus; n = 9). HS induced to target MAP of 40 mmHg was maintained for 30 minutes. Brain tissue oxygen pressure (PbtO2), intracranial pressure (ICP), cerebral perfusion pressure (CPP), haemodynamics and blood gas analyses were assessed prior to HS (baseline) up to 120 minutes after treatment. Tissue markers of brain oedema (aquaporin-4 (AQP4) and Na-K-Cl cotransporter-1 (NKCC1)), apoptosis (pre-apoptotic protein (Bax)) and oxidative stress (thiobarbituric acid reactive substances (TBARS)) were also measured.

Results

Sham animals had no significant changes in the variables assessed. HS resulted in a significant decrease in CPP (mean varied from 36 to 39 mmHg), PbtO2 (from 23.6 to 26.6 mmHg), ICP (from 1 to 2 mmHg) and haemodynamics (MAP from 38 to 40 mmHg; CI from 1.8 to 2.1 l/minute/m2), and a significant increase in blood lactate (from 6.7 to 8.9 mmol/l) and cerebral AQP4 (mean ± SE; 167 ± 54% of sham), NKCC1 (237 ± 47% of sham), Bax (167 ± 44% of sham) and TBARS. Fluid resuscitation was followed by an increase in ICP (from 7 to 9 mmHg) and a decrease in CPP (from 41 to 52 mmHg), with an increased expression of cerebral AQP4 (210 ± 56% of sham), NKCC1 (163 ± 32% of sham) and Bax (137 ± 24% of sham). Only TERLI restored baseline values of CPP (from 54 to 61 mmHg) and did not change the cerebral expression of AQP4 (100 ± 6% of sham), NKCC1 (100 ± 1% of sham), Bax (102 ± 6% of sham) and TBARS. Both TERLI and LR recovered baseline levels of PbtO2 (TERLI from 30.0 to 34.2 mmHg; LR from 29.4 to 40.7 mmHg) and MAP (TERLI from 53 to 64 mmHg; LR: 48 to 61 mmHg). Blood lactate levels were not recovered in any group (TERLI from 5.7 to 8.1 mmol/l; LR from 4.5 to 7.7 mmol/l).

Conclusion

TERLI recovered cerebral perfusion and oxygenation with no significant changes in ICP and cerebral markers of oedema, apoptosis and oxidative stress. LR did not recover CPP probably due to a significant increase in ICP caused by brain oedema, which may have contributed to the cerebral apoptosis. None of the treatments caused cerebral oxidative stress.

References

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Correspondence to KK Ida.

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Ida, K., Otsuki, D., Castro, L. et al. Impact of different haemodynamic resuscitation strategies on brain perfusion and tissue oedema markers in a model of severe haemorrhagic shock. Crit Care 17, P218 (2013). https://doi.org/10.1186/cc12156

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Keywords

  • Blood Lactate
  • Brain Oedema
  • Cerebral Perfusion Pressure
  • Fluid Resuscitation
  • Lactate Ringer