Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
European Journal of Trauma and Emergency Surgery
Published in: European Journal of Trauma and Emergency Surgery 6/2019

01-12-2019 | Original Article

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

Published in: European Journal of Trauma and Emergency Surgery | Issue 6/2019

Login to get access

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.
Literature
1.
Mtaweh H, Trakas EV, Su E, Carcillo JA, Aneja RK. Advances in monitoring and management of shock. Pediatr Clin N Am. 2013;60:641–4.
2.
3.
4.
Bunn F, Alderson P, Hawkin V. Colloid solution for fluid resuscitation. Cochrane database Syst Rev. 2000;2:CD001319.
5.
Perel P, Roberts I. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2012;6:CD000567.
6.
Naig CM, Win DK. Do colloids in comparison to crystalloids for fluid resuscitation improve mortality? Trans R Soc Trop Med Hyg. 2010;104:311–2.
7.
Burns JW, Baer LA, Darlington DN, Dubick MA, Wade CE. Screening of potential small volume resuscitation products using a severe hemorrhage sedated swine model. Int J Burn Trauma. 2012;2:59–67.
8.
Rizolli SB. Crystalloids and colloids in trauma resuscitation: a brief overview of the current debate. J Trauma. 2003;54:82–8.
9.
Finfer S, Liu B, Taylor C, Bellomo R, Billot L, Cook D, et al. Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care. 2010;14:R185.PubMedPubMedCentral
10.
Dubin A, Pozo MO, Casabella CA, Murias G, Pálizas F Jr, Moseinco MC, et al. Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for resuscitation of the microcirculation during the early goal-directed therapy of septic patients. J Crit Care. 2010;25:659.e1–8.
11.
Feldheiser A, Pavlova V, Bonomo T, Jones A, Fotopoulou C, Sehouli J, et al. Balanced crystalloid compared with balanced colloid solution using a goal-directed haemodynamic algorithm. Br J Anaesth. 2013;110:231–40.PubMed
12.
Srimal RC, Gulati K, Nityanand S, Dhawan BN. Pharmacological studies on 2-(2-(4-(3-methhylphenyl)-1-piperazinyl)ethyl) quinoline (centhaquin). I. Hypotensive activity. Pharmacol Res. 1990;22:319–29.PubMed
13.
Bhatnagar Z, Pande M, Dubey MP, Dhawan BN. Effect of centhaquin on spontaneous and evoked norepinephrine release from isolated perfused rabbit heart. Arzneimittelforschung. 1985;35:693–7.PubMed
14.
Lavhale MS, Havalad S, Gulati A. Resuscitative effect of centhaquin after hemorrhagic shock in rats. J Surg Res. 2013;179:115–24.PubMed
15.
Papapanagiotou P, Xanthos T, Gulati A, Chalkias A, Papalois A, Kontouli Z, et al. Centhaquin improves survival in a swine model of hemorrhagic shock. J Surg Res. 2016;200:227–35.PubMed
16.
Zornow MH, Prough DS. Fluid management in patients with traumatic brain injury. New Horiz. 1995;3:488–98.PubMed
17.
Xanthos TT, Balkamou XA, Stroumpoulis KI, Pantazopoulos IN, Rokas GI, Agrogiannis GD, et al. A model of hemorrhagic shock and acute lung injury in Landrace–Large White swine. Comp Med. 2011;61:158–62.PubMedPubMedCentral
18.
Xanthos T, Bassiakou E, Koudouna E, Rokas G, Goulas S, Dontas I, et al. Combination pharmacotherapy in the treatment of experimental cardiac arrest. Am J Emerg Med. 2009;27:651–9.PubMed
19.
Balkamou X, Xanthos T, Stroumpoulis K, Moutzouris DA, Rokas G, Agrogiannis G, et al. Hydroxyethyl starch 6% (130/0.4) ameliorates acute lung injury in swine hemorrhagic shock. Anesthesiology. 2010;113:1092–8.PubMed
20.
Shires GT, Cunningham JN, Backer CR, Reeder SF, Illner H, Wagner IY, et al. Alterations in cellular membrane function during hemorrhagic shock in primates. Ann Surg. 1972;176:288–95.PubMedPubMedCentral
21.
Chatrath V, Khetarpal R, Ahuja J. Fluid management in patients with trauma: restrictive versus liberal approach. J Anaesthesiol Clin Pharmacol. 2015;31:308–16.PubMedPubMedCentral
22.
Ross SW, Christmas AB, Fischer PE, Holway H, Walters AL, Seymour R, et al. Impact of common crystalloid solutions on resuscitation markers following class I hemorrhage: a randomized control trial. J Trauma Acute Care Surg. 2015;79:732–40.PubMed
23.
Mitra B, Gabbe BJ, Kaukonen KM, Olaussen A, Cooper DJ, Cameron PA. Long-term outcomes of patients receiving a massive transfusion after trauma. Shock. 2014;42:307–12.PubMed
24.
Delano MJ, Rizoli SB, Rhind SG, Cuschieri J, Junger W, Baker AJ, et al. Prehospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsens Hypocoagulation and Hyperfibrinolysis. Shock. 2015;44:25–31.PubMedPubMedCentral
25.
Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2013;2:CD000567.
26.
Annane D, Siami S, Jaber S, Martin C, Elatrous S, Declère AD, et al. CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013;310:1809–17.PubMed
27.
Vives M, Callejas R, Duque P, Echarri G, Wijeysundera DN, Hernandez A, et al. Modern hydroxyethyl starch and acute kidney injury after cardiac surgery: a prospective multicentre cohort. Br J Anaesth. 2016;117:458–63.PubMed
28.
Schindler AW, Marx G. Evidence-based fluid management in the ICU. Curr Opin Anaesthesiol. 2016;29:158–65.PubMed
29.
Kheirabadi BS, Miranda N, Terrazas IB, Gonzales MD, Grimm RC, Dubick MA. Does small-volume resuscitation with crystalloids or colloids influence hemostasis and survival of rabbits subjected to lethal uncontrolled hemorrhage? J Trauma Acute Care Surg. 2017;82:156–64.PubMed
30.
Roger C, Muller L, Deras P, Louart G, Nouvellon E, Molinari N, et al. Does the type of fluid affect rapidity of shock reversal in an anaesthetized-piglet model of near-fatal controlled haemorrhage? A randomized study. Br J Anaesth. 2014;112:1015–23.PubMed
31.
Garnacho-Montero J, Fernández-Mondéjar E, Ferrer-Roca R, Herrera-Gutiérrez ME, Lorente JA, Ruiz-Santana S, et al. Crystalloids and colloids in critical patient resuscitation. Med Intensiva. 2015;39:303–15.PubMed
32.
Gulati A, Hussain G, Srimal RC. Effect of repeated administration of centhaquin, a centrally acting hypotensive drug, on adrenergic, cholinergic (muscarinic), dopaminergic, and serotonergic receptors in brain-regions of rat. Drug Dev Res. 1991;23:307–23.
33.
Gulati A, Hussain G, Srimal RC. Effect of repeated administration of clonidine on adrenergic, cholinergic (muscarinic), dopaminergic, and serotonergic receptors in brain-regions of rat. Drug Dev Res. 1991;22:141–52.
34.
Lavhale MS, Briyal S, Parikh N, Gulati A. Endothelin modulates the cardiovascular effects of clonidine in the rat. Pharm Res. 2010;62:489–99.
35.
Gulati A, Srimal RC. Endothelin antagonizes the hypotension and potentiates the hypertension induced by clonidine. Eur J Pharmacol. 1993;230:293–300.PubMed
36.
Gondos T, Marjanek Z, Ulakcsai Z, Szabó Z, Bogár L, Károlyi M, et al. Short-term effectiveness of different volume replacement therapies in postoperative hypovolaemic patients. Eur J Anaesthesiol. 2010;27:794–800.PubMed
37.
Rooke GA, Schwid HA, Shapira Y. The effect of graded hemorrhage and intravascular volume replacement on systolic pressure variation in humans during mechanical and spontaneous ventilation. Anesth Analg. 1995;80:925–32.PubMed
38.
Funk DJ, Jacobsohn E, Kumar A. Role of the venous return in critical illness and shock: part II-shock and mechanical ventilation. Crit Care Med. 2013;41:573–9.PubMed
39.
Shen T, Baker K. Venous return and clinical hemodynamics: how the body works during acute hemorrhage. Adv Physiol Educ. 2015;39:267–71.PubMed
40.
Wang P, Li Y, Li J. Hydroxyethyl starch 130/0.4 prevents the early pulmonary inflammatory response and oxidative stress after hemorrhagic shock and resuscitation in rats. Int Immunopharmacol. 2009;9:347–53.PubMed
41.
Michelet P, Lambert D, Papazian L, Auffray JP, Carpentier JP. Comparison of lung injury after normal or small volume optimized resuscitation in a model of hemorrhagic shock. Intensive Care Med. 2007;33:1645–54.PubMed
42.
Feng X, Yan W, Liu X, Duan M, Zhang X, Xu J. Effects of hydroxyethyl starch 130/0.4 on pulmonary capillary leakage and cytokines production and NF-κB activation in CLP-induced sepsis in rats. J Surg Res. 2006;135:129–36.PubMed
43.
Lv R, Zhou W, Chu C, Xu J. Mechanism of the effect of hydroxyethyl starch on reducing pulmonary capillary permeability in a rat model of sepsis. Ann Clin Lab Sci. 2005;35:174–83.PubMed
44.
Tian J, Lin X, Guan R, Xu JG. The effects of hydroxyethyl starch on lung capillary permeability in endotoxic rats and possible mechanisms. Anesth Analg. 2004;98:768–74.PubMed
45.
Di Filippo A, Ciapetti M, Prencipe D, Tini L, Casucci A, Ciuti R, et al. Experimentally-induced lung injury: the protective effect of hydroxyethyl starch. Ann Clin Lab Sci. 2006;36:345–52.PubMed
46.
Feng X, Yan W, Wang Z, Liu J, Yu M, Zhu S, et al. Hydroxyethyl starch, but not modified fluid gelatin, affects inflammatory response in a rat model of polymicrobial sepsis with capillary leakage. Anesth Analg. 2007;104:624–30.PubMed
47.
Chen G, You G, Wang Y, Lu M, Cheng W, Yang J, et al. Effects of synthetic colloids on oxidative stress and inflammatory response in hemorrhagic shock: comparison of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin. Crit Care. 2013;17:R141.PubMedPubMedCentral
48.
Silva PL, Güldner A, Uhlig C, Carvalho N, Beda A, Rentzsch I, et al. Effects of intravascular volume replacement on lung and kidney function and damage in nonseptic experimental lung injury. Anesthesiology. 2013;118:395–408.PubMed
Metadata
Title
Resuscitation with centhaquin and 6% hydroxyethyl starch 130/0.4 improves survival in a swine model of hemorrhagic shock: a randomized experimental study
Publication date
01-12-2019
Published in
European Journal of Trauma and Emergency Surgery / Issue 6/2019
Print ISSN: 1863-9933
Electronic ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-018-0980-1

Other articles of this Issue 6/2019

European Journal of Trauma and Emergency Surgery 6/2019 Go to the issue

Review Article

Displaced distal radius fractures in children, cast alone vs additional K-wire fixation: a meta-analysis

Original Article

Efficacy and safety of TEVAR with debranching technique for blunt traumatic aortic injury in patients with severe multiple trauma

Original Article

Health-related quality of life in trauma patients at 12 months after injury: a prospective cohort study

Original Article

Validation study of 3D-printed anatomical models using 2 PLA printers for preoperative planning in trauma surgery, a human cadaver study

Original Article

Non-invasive cardiac output monitoring device “ICON” in trauma patients: a feasibility study

Original Paper

Anteromedial femoral neck plate with cannulated screws for the treatment of irreducible displaced femoral neck fracture in young patients: a preliminary study