Resuscitation with centhaquin and 6% hydroxyethyl starch 130/0.4 improves survival in a swine model of hemorrhagic shock: a randomized experimental study

Abstract

Purpose: To investigate the effects of the combination of centhaquin and 6% hydroxyethyl starch 130/0.4 (HES 130/0.4) in a swine model of hemorrhagic shock.

Methods: Twenty Landrace-Large White pigs were instrumented and subjected to hemorrhagic shock. The animals were randomly allocated in two experimental groups, the control (group CO, n = 10) and the centhaquin groups (0.015 mg/kg, n = 10, group CH). Acute hemorrhage was induced by stepwise blood withdrawal (18 mL/min) from the internal jugular vein until MAP decreased to 40-45 mmHg, whereas anesthesia remained constant. All animals received HES 130/0.4 solution in the resuscitation phase until their mean arterial pressure (MAP) reached 90% of the baseline. The animals were observed for 60 min, during which no further resuscitation was attempted.

Results: The total amount of blood and the bleeding time did not differ significantly between group CO and group CH (120 ± 13 vs. 120 ± 14 mL, p = 0.6; 20 ± 2 vs. 20 ± 1 min, p = 0.62, respectively). During the hemorrhagic phase, only a difference in heart rate (97.6 ± 4.4 vs. 128.4 ± 3.6 beats/min, p = 0.038) was observed between the two groups. The time required to reach the target MAP was significantly shorter in the centhaquin group compared to controls (13.7 ± 0.4 vs. 19.6 ± 0.84 min, p = 0.012). During the resuscitation phase, a statistical significant difference was observed in MAP (75.2 ± 1.6 vs. 89.8 ± 2.1 mmHg, p = 0.02) between group CO and group CH. During the observation phase, a statistical significant difference was observed in SVR (1109 ± 32.65 vs. 774.6 ± 21.82 dyn s/cm⁵, p = 0.039) and cardiac output (5.82 ± 0.31 vs. 6.9 ± 0.78 L/min, p = 0.027) between the two groups. Two animals of group CO and seven animals of group CH survived for 24 h (p = 0.008). We observed a marked increase in microvascular capillary permeability in group CO compared to group CH, with the wet/dry weight ratio being significantly higher in group CO compared to group CH (4.8 ± 1.6 vs. 3.08 ± 0.6, p < 0.001).

Conclusions: The combination of centhaquin 0.015 mg/kg and HES 130/0.4 resulted in shorter time to target MAP, lower wet-to-dry ratio, and better survival rates after resuscitation from hemorrhagic shock.

Keywords: Acute care anesthesiology; Centhaquin; Emergency surgery; Hemorrhagic shock; Hydroxyethyl starch; Survival.