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

  • Zinais Kontouli
  • Chryssoula Staikou
  • Nicoletta Iacovidou
  • Ioannis Mamais
  • Evaggelia Kouskouni
  • Apostolos Papalois
  • Panagiotis Papapanagiotou
  • Anil Gulati
  • Athanasios ChalkiasEmail author
  • Theodoros Xanthos
Original Article



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.


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.


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).


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.


Hemorrhagic shock Centhaquin Hydroxyethyl starch Acute care anesthesiology Emergency surgery Survival 



This study was supported by the Experimental-Research Center ELPEN Pharmaceuticals (E.R.C.E), Athens, Greece by providing the research facilities for this project. We would like to thank, A. Zacharioudaki, E. Karampela, K. Tsarea, M. Karamperi, N. Psychalakis, A. Karaiskos, S. Gerakis and E. Gerakis, staff members of the E.R.C.E., for their assistance during the experiments.

Compliance with ethical standards

Conflict of interest

Zinais Kontouli, Chryssoula Staikou, Nicoletta Iacovidou, Ioannis Mamais, Evaggelia Kouskouni, Apostolos Papalois, Panagiotis Papapanagiotou, Anil Gulati, Athanasios Chalkias, and Theodoros Xanthos declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed consent

Non-applicable. We did not include patients in this study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Zinais Kontouli
    • 1
  • Chryssoula Staikou
    • 2
  • Nicoletta Iacovidou
    • 1
    • 3
    • 4
  • Ioannis Mamais
    • 5
    • 6
    • 7
  • Evaggelia Kouskouni
    • 1
    • 8
  • Apostolos Papalois
    • 9
  • Panagiotis Papapanagiotou
    • 4
  • Anil Gulati
    • 10
  • Athanasios Chalkias
    • 4
    • 11
    • 13
    Email author
  • Theodoros Xanthos
    • 12
  1. 1.Postgraduate Study Program (MSc) “Cardiopulmonary Resuscitation”, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  2. 2.Department of Anesthesiology, Medical School, Aretaieio HospitalNational and Kapodistrian University of AthensAthensGreece
  3. 3.Department of Neonatology, Medical School, Aretaieio HospitalNational and Kapodistrian University of AthensAthensGreece
  4. 4.Hellenic Society of Cardiopulmonary ResuscitationAthensGreece
  5. 5.Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  6. 6.Department of Health SciencesEuropean University CyprusNicosiaCyprus
  7. 7.Department of Life SciencesEuropean University CyprusNicosiaCyprus
  8. 8.Department of Biopathology, Medical School, Aretaieio HospitalNational and Kapodistrian University of AthensAthensGreece
  9. 9.Experimental-Research Centre ELPENAthensGreece
  10. 10.Department of Pharmaceutical Sciences, Chicago College of PharmacyMidwestern UniversityDowners GroveUSA
  11. 11.Department of Anesthesiology and Perioperative Medicine, Faculty of Medicine, School of Health SciencesUniversity of ThessalyLarisaGreece
  12. 12.School of MedicineEuropean University CyprusNicosiaCyprus
  13. 13.LarisaGreece

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