In vitro effects of lactated Ringer's solution, hypertonic saline, hydroxyethyl starch, hypertonic saline/hydroxyethyl starch, and mannitol on thromboelastographic variables of canine whole blood.

Publisher: Blackwell Country of Publication: United States NLM ID: 101152804 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4431 (Electronic) Linking ISSN: 14764431 NLM ISO Abbreviation: J Vet Emerg Crit Care (San Antonio) Subsets: MEDLINE

Publication: <2005-> : Malden, MA : Blackwell
Original Publication: San Antonio, TX : Veterinary Emergency & Critical Care Society, [2001]-

Dogs/*blood ; Hydroxyethyl Starch Derivatives/*pharmacology ; Mannitol/*pharmacology ; Plasma Substitutes/*pharmacology ; Ringer's Lactate/*pharmacology ; Saline Solution, Hypertonic/*pharmacology; Animals ; Blood Coagulation/drug effects ; Male ; Thrombelastography/veterinary

Objective: To assess the in vitro effects of crystalloid and colloid IV fluids on the thromboelastographic (TEG) variables of canine whole blood.
Design: In vitro experimental study.
Setting: Veterinary teaching hospital.
Animals: Twenty-two healthy dogs.
Intervention: Citrated whole blood samples collected from healthy dogs were diluted with 3.4% hypertonic saline (HTS 3.4), 7% hypertonic saline (HTS 7), and 20% mannitol at 8% and 16% dilutions; hydroxyethyl starch 130/0.4 (HES 130/0.4) at 16% dilution; lactated Ringer's solution (LRS) at 16%, 33%, and 66% dilutions; and HTS 7-HES 130/0.4 at 25% and 50% dilutions. Kaolin-activated TEG analysis was concurrently performed on diluted and control (undiluted) samples.
Measurements and Main Results: Dilution of canine whole blood with LRS compared to control reduced α angle and MA at both 33% (P = 0.009 and P = 0.011, respectively) and 66% dilution (P < 0.001 and P < 0.001, respectively), and prolonged K time at 66% dilution (P = 0.003). At 16% dilution, HTS 3.4, prolonged R time (P = 0.007), while mannitol, a fluid iso osmolar to HTS 3.4, prolonged K time (P = 0.006), reduced α angle (P < 0.001), MA (P = 0.046), and LY60 (P = 0.015). At 8% dilution, HTS 7, a fluid of high osmolarity and tonicity, prolonged R time (P = 0.009) and reduced MA (P = 0.015), while all measured TEG variables were altered at the 16% dilution (P < 0.01 for all variables). HES 130/0.4 reduced α angle (P = 0.031) and MA (P = 0.001) and increased LY60 (P < 0.001) at 16% dilution. Comparing different fluid types, HES 130/0.4 and HTS 3.4 had no to minor, mannitol intermediate, and HTS 7 profound effects on TEG variables (P < 0.05) when compared to LRS at the same dilution.
Conclusions: In vitro dilution of canine whole blood with commonly used IV fluids leads to thromboelastographic changes consistent with hypocoagulability in a dose dependent manner for all fluid types tested. Viscoelastic changes are also influenced by fluid characteristics, specifically tonicity and osmolarity.
(© Veterinary Emergency and Critical Care Society 2020.)

Curry N, Davenport RA, Hunt BJ, Stanworth SJ. Transfusion strategies for traumatic coagulopathy. Blood Rev. 2012;26(5):223-232.
Cannon JW. Hemorrhagic shock. N Engl J Med. 2018;378:370-379.
Watts DD, Trask A, Soeken K, et al. Hypothermic coagulopathy in trauma: effect of varying levels of hypothermia on enzyme speed, platelet function, and fibrinolytic activity. J Trauma. 1998;44(5):846-854.
Martini WZ, Pusateri AE, Uscilowicz JM, et al. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J Trauma. 2005;58(5):1002-1009.
Meng ZH, Wolberg AS, Monroe DM III, Hoffman M. The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy of high-dose factor VIIa in hypothermic and acidotic patients. J Trauma. 2003;55:886-891.
Engstrom M, Schott U, Romner B, Reinstrup P. Acidosis impairs the coagulation: a thromboelastographic study. J Trauma. 2006;61:624-628.
Duan CY, Li T, Liu LM. Efficacy of limited fluid resuscitation in patients with hemorrhagic shock: a meta-analysis. Int J Clin Exp Med. 2015;8(7):11645-11656.
Wang CH, Hsieh WH, Chou HC, et al. Liberal versus restricted fluid resuscitation strategies in trauma patients: a systematic review and meta-analysis of randomized controlled trials and observational studies. Crit Care Med. 2014;42(4):954-961.
Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313:471-482.
Cannon JW, Khan MA, Raja AS, et al. Damage control resuscitation in patients with severe traumatic hemorrhage: a practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg. 2017;82:605-617.
Weiss G, Lison S, Spannagl M, Heindl B. Expressiveness of global coagulation parameters in dilutional coagulopathy. Br J Anaesth. 2010;105(4):429-436.
Ponschab M, Schochl H, Keibl C, et al. Preferential effects of low volume versus high volume replacement with crystalloid fluid in a hemorrhagic shock model in pigs. BMC Anesthesiol. 2015;15:10.
Maegele M, Lefering R, Yucel N, et al. Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury. 2007;38(3):298-304.
Hess JR, Brohi K, Dutton RP, et al. The coagulopathy of trauma: a review of mechanims. J Trauma. 2008;65(4):748-754.
de Jonge E, Levi M, Buller R, Berends F, Kesecioglu J: Decreased circulating levels of von Willebrand factor after intravenous administration of a rapidly degradable hydroxyethyl starch (HES 200/0.5/6) in healthy human subjects. J Intensive Care Med. 2001;27:1825-1829.
Deusch E, Gamsjager T, Kress HG, Kozek-Langenecker SA. Binding of hydroxyethyl starch molecules to the platelet surface. Anesth Analg. 2003;97(3):680-683.
Mittermayr M, Streif W, Haas T, et al. Effects of colloid and crystalloid solutions on endogenous activation of fibrinolysis and resistance of polymerized fibrin to recombinant tissue plasminogen activator added ex vivo. Br J Anaesth. 2008;100(3):307-314.
Smart L, Jandrey KE, Kass PH, et al. The effect of Hetastarch (670/0.75) in vivo on platelet closure time in the dog. J Vet Emerg Crit Care. 2009;19(5):444-449.
Griego-Valles M, Buriko Y, Prittie JE, Fox PR. An in vitro comparison of the effects of voluven (6% hydroxyethyl starch 130/0.4) and hespan (6% hydroxyethyl starch 670/0.75) on measures of blood coagulation in canine blood. J Vet Emerg Crit Care. 2017;27(1):44-51.
McBride D, Hosgood GL, Mansfield CS, Smart L. Effect of hydroxyethyl starch 130/0.4 and 200/0.5 solutions on canine platelet function in vitro. Am J Vet Res. 2013;74(8):1133-1137.
Falco S, Bruno B, Maurella C, et al. In vitro evaluation of canine hemostasis following dilution with hydroxyethyl starch (130/0.4) via thromboelastometry. J Vet Emerg Crit Care. 2012;22(6):640-645.
Wurlod VA, Howard J, Francey T, et al. Comparison of the in vitro effects of saline, hypertonic hydroxyethyl starch, hypertonic saline, and two forms of hydroxyethyl starch on whole blood coagulation and platelet function in dogs. J Vet Emerg Crit Care. 2015;25(4):474-487.
Morris BR, deLaforcade A, Lee J, et al. Effects of in vitro hemodilution with crystalloids, colloids, and plasma on canine whole blood coagulation as determined by kaolin-activated thromboelastography. J Vet Emerg Crit Care. 2016;26(1):58-63.
Adamik KN, Butty E, Howard J. In vitro effects of 3 % hypertonic saline and 20 % mannitol on canine whole blood coagulation and platelet function. BMC Vet Res. 2015;11:9.
Goggs R, Brainard B, de Laforcade AM, et al. Partnership on Rotational ViscoElastic Test Standardization (PROVETS): Evidence-based guidelines on rotational viscoelastic assays in veterinary medicine. J Vet Emerg Crit Care. 2014;24(1):1-22.
Micheal MM, Stephanie AS. Viscoelastic coagulation testing: technology, applications and limitations. Vet Clin Pathol. 2011;40(2):140-154.
Gonzalez E, Moore EE, Moore HB. Management of trauma-induced coagulopathy with thrombelastography. Crit Care Clin. 2017;33(1):119-134.
Bowbrick VA, Mikhailidis DP, Stansby G. Influence of platelet count and activity on thromboelastography parameters. Platelets. 2003;14(4):219-224.
Roche AM, James MFM, Bennett-Guerrero E, Mythen MG. A head-to-head comparison of in vitro coagulation effects of saline-based and balanced electrolyte crystalloid and colloid intravenous fluids. Anesth Analg. 2006;102(4):1274-1279.
Fries D, Innerhofer P, Klingler A, et al. The effect of the combined administration of colloids and lactated Ringer's solution on the coagulation system: an in vitro study using thrombelastograph (R) coagulation analysis (ROTEG (R)). Anesth Analg. 2002;94(5):1280-1287.
Hinson HE, Stein D, Sheth KN. Hypertonic saline and mannitol therapy in critical care neurology. J Intensive Care Med. 2013;28(1):3-11.
Banks CJ, Furyk JS. Review article: hypertonic saline use in the emergency department. Emerg Med Australas. 2008;20(4):294-305.
Hanke AA, Maschler S, Schochl H, et al. In vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch. Scand J Trauma Resusc Emerg Med. 2011;19:8.
Tan TS, Tan KHS, Ng HP, Loh MW. The effects of hypertonic saline solution (7.5%) on coagulation and fibrinolysis: an in vitro assessment using thromboelastography. Anaesthesia. 2002;57(7):644-648.
Reed RL, Johnston TD, Chen Y, Fischer RP. Hypertonic saline alters plasma clotting times and platelet aggregation. J Trauma. 1991;31(1):8-14.
Wilder DM, Reid TJ, Bakaltcheva IB. Hypertonic resuscitation and blood coagulation - In vitro comparison of several hypertonic solutions for their action on platelets and plasma coagulation. Thromb Res. 2002;107(5):255-261.
Luostarinen T, Niiya T, Schramko A, et al. Comparison of hypertonic saline and mannitol on whole blood coagulation in vitro assessed by thromboelastometry. Neurocrit Care. 2011;14(2):238-243.
Yozova ID, Howard J, Henke D, et al. Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on whole blood coagulation and platelet function in dogs with suspected intracranial hypertension - a pilot study. BMC Vet Res. 2017;13:9.
Glover PA, Rudloff E, Kirby R. Hydroxyethyl starch: A review of pharmokinetics, pharmodynamics, current products and potential clinical risks, benefits and use. J Vet Emerg Crit Care. 2014;24(6):642-661.
Kozek-Langenecker SA, Jungheinrich C, Sauermann W, Van der Linden P. The effects of hydroxyethyl starch 130/0.4 (6%) on blood loss and use of blood products in major surgery: a pooled analysis of randomized clinical trials. Anesth Analg. 2008;107(2):382-390.
Hartog CS, Reuter D, Loesche W, et al. Influence of hydroxyethyl starch (HES) 130/0.4 on hemostasis as measured by viscoelastic device analysis: a systematic review. Intensive Care Med. 2011;37(11):1725-1737.
Prough DS, Whitley JM, Taylor CL, et al. Small-volume resuscitation from hemorrhagic-shock in dogs - effect on the systemic hemodynamics and systemic blood-flow. Crit Care Med. 1991;19(3):364-372.
Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011;254(2):194-200.

U-VET Animal Hospital Internal Grant

Keywords: coagulation; dilutional coagulopathy; dogs; fluid therapy; viscoelastic testing

0 (Hydroxyethyl Starch Derivatives)
0 (Plasma Substitutes)
0 (Ringer's Lactate)
0 (Saline Solution, Hypertonic)
3OWL53L36A (Mannitol)

Date Created: 20200221 Date Completed: 20201005 Latest Revision: 20201005

20221213

10.1111/vec.12929

32077234