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.

• Authors: Zinais Kontouli, Chryssoula Staikou, Nicoletta Iacovidou, Ioannis Mamais, Evaggelia Kouskouni, Apostolos Papalois, Panagiotis Papapanagiotou, Anil Gulati, Athanasios Chalkias, Theodoros Xanthos
• Journal: European journal of trauma and emergency surgery : official publication of the European Trauma Society (Eur J Trauma Emerg Surg) Vol. 45 Issue 6 Pg. 1077-1085 (Dec 2019) ISSN: 1863-9941 [Electronic] Germany
• PMID: 30006694 (Publication Type: Journal Article)

Chemical References

• Hydroxyethyl Starch Derivatives
• Piperazines
• centhaquine

Topics

• Animals
• Blood Pressure (drug effects)
• Disease Models, Animal
• Hemodynamics (drug effects)
• Hydroxyethyl Starch Derivatives (administration & dosage, therapeutic use)
• Piperazines (administration & dosage, therapeutic use)
• Resuscitation (methods, mortality)
• Shock, Hemorrhagic (drug therapy, mortality, physiopathology, therapy)
• Swine
• Vascular Resistance (drug effects)