DEVELOPMENT AND EVALUATION OF FREEZING RESISTANT INTRAVENOUS FLUID
Objectives: Hemorrhagic or hypovolemic shocks accounts for a large portion of civilian and military trauma deaths due to life-threatening blood loss which requires intravenous fluid infusion to prevent essential deficiencies of fluids. However, at low temperature (-150C) fluid bottles freeze out and can not be used in emergency. In view of that, objective of the present work is to develop a freezing resistant intravenous formulation (FRIV) and its in vivo safety and efficacy evaluation.
Methods: FRIV formulations were developed using standardized ringer lactate (RL) formulation protocol, in which varying concentrations of ethanol and glycerol were added to induce desired physiochemical properties. Efficacy of FRIV was evaluated in terms of survival percentage of hemorrhagic animal models (Swiss albino strain mice). Acute toxicity studies were carried out through an infusion at dose levels (0, 20 and 40 ml/Kg b. wt.).
Results: In vitro data showed that optimized FRIV (F-10) takes more time (360 Â± 21 min) for freezing and less time in thawing (50 Â± 4.50 min) in comparison to control which takes (110 Â± 15 min) in freezing and (80 Â± 7.25 min) in thawing. Formulations were found to be stable and sterile up to six months. In vivo efficacy data showed â‰¥ 75% survival in animals infused with FRIV as compared to control group in hemorrhagic animal models and no treatment related toxic effects of optimized formulation in terms of hematological, serum biochemistry and histopathological analysis.
Conclusion: Pre-clinical safety and efficacy data of the present study indicated that developed FRIV formulation could be used for fluid recovery during the hemorrhagic shocks conditions in the combat scenario.
2. Moore FA, McKinley BA, Moore EE. The next generation in shock resuscitation. Lancet 2004;363:1988-96.
3. Hak DJ, Smith WR, Suzuki T. Management of hemorrhage in life-threatening pelvic fracture. J Am Acad Orthop Surg 2009;17(7):447-57.
4. Gutierrez G, Reines HD, Wulf-Gutierrez ME. Clinical review: hemorrhagic shock. Crit Care 2004;8(5):373-81.
5. Letson HL, Dobson GP. Unexpected 100% survival following 60% blood loss using small-volume 7.5% NaCl with adenocaine and Mg++ in the rat model of extreme hemorrhagic shock. Shock 2011;36(6):586-94.
6. RÃ¶nn T, Lendemans S, de Groot H, Petrat F. A new model of severe hemorrhagic shock in rats. Comp Med 2011;61(5):419-26.
7. Wenzel V, Raab H, Dunser MW. Arginine vasopressin: a promising rescue drug in the treatment of uncontrolled haemorrhagic shock. Best Pract Res Clin Anaesthesiol 2008;22(2):299-16.
8. Committee on Trauma, Shock. Advanced Trauma Life Support, Student Course Manual, 6th ed. Chicago: American College of Surgeons; 1997. p. 87-107.
9. Jordan KS. Fluid resuscitation in acutely injured patients. J Intraven Nurs 2000;23(2):81-7.
10. Martel MJ, MacKinnon KJ, Arsenault MY. Arsenault, Hemorrhagic shock. J Obstet Gynaecol Can 2002;24(6):504-20.
11. Shires GT, Browder LK, Steljes TP, Williams SJ, Browder TD, Barber AE. The effect of shock resuscitation fluids on apoptosis. Am J Surg 2005;189:85-91.
12. Waitt C, Waitt C, Pirmohamed M. Intravenous therapy. PGD Med J 2004;80:1-6.
13. Tjon JA, Ansani NT. Transdermal nitroglycerin for the prevention of intravenous infusion failure due to phlebitis and extravasation. Ann Pharmacother 2000;34:1188-92.
14. Schrier RW. The science behind hyponatremia and its clinical manifestations. Pharmacotherapy 2011;31(5):9S-17S.
15. Cook LS. IV fluid resuscitation. J Infus Nurs 2003;26(5):296-303.
16. Tremblay LN, Rizoli SB, Brenneman FD. Advances in fluid resuscitation of hemorrhagic shock. Can J Surg 2001;44(3):172-9.
17. Kaplan LJ, Philbin N, Arnaud F, Rice J, Dong F, Freilich D. Resuscitation from hemorrhagic shock: fluid selection and infusion strategy drives unmeasured ion genesis. J Trauma 2006;61(1):90-8.
18. Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA, Nelson LS. Goldfrank's Toxicologic Emergencies, 8th ed. McGraw-Hill Professional; 2006.
19. Moore EE, Johnson JL, Cheng AM, Masuno T, Banerjee A. Insights from studies of blood substitutes in trauma. Shock 2005;24(3):197-205.
20. Olson H, Betton G, Robinson D. Concordance of the toxicity of pharmaceuticals in humans and animals. Regul Toxicol Pharmacol 2000;32(1):56-7.
21. Slaoui M, Fiette L. Histopathology procedures: from tissue sampling to histopathological evaluation. Methods Mol Biol 2011;691:69-82.
22. Kiernan JA. Histological and Histochemical Methods. Theory and Practice. 4th ed. Bloxham,UK: Scion; 2009. p. 12-73.
23. Hierholzer C, Billiar TR. Molecular mechanisms in the early phase of hemorrhagic shock. Langenbecks Arch Surg 2001;386(4):302-08.
24. Rhee P, Koustova E, Alam HB. Searching for the optimal resuscitation method: recommendations for the initial fluid resuscitation of combat casualties. J Trauma 2003;54(5):S52-S4.
25. Kumana CR, Chan GTC, Yu YL. Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol. Br J Clin Pharm 1994;29:347-53.
26. Nau R, Prins FJ, Kolenda H, Prange HW. Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol. Eur J Clin Pharmacol 1992;42(2):181-5.
27. Braun LJ, Tyagi A, Perkins S. Development of a freeze-stable formulation for vaccines containing aluminum salt adjuvants. Vaccine 2009;27:72-9.
28. Linker CA, McPhee SJ, Papadakis MA. (Eds.), Current Medical Diagnosis & Treatment. New York: Lange Medical Boods/ McGraw-Hill. 45th ed; 2006. p. 481-535.
29. Thompson RCC. Physiologic 0.9% saline in the fluid resuscitation of trauma. J R Army Med Corps 2005;151(3):146-51.
30. Baker AJ, Park E, Hare G, Liu, Mazer D. Effects of resuscitation fluid on neurological physiology after cerebral trauma and hemorrhage. J Trauma 2008;64(2):348-57.
31. Kiraley LN, Jerome A, Differding. Resuscitation with normal saline (ns) vs. lactated ringerâ€™s (lr). modulates hypercoagulability and leads to increased blood loss in an uncontrolled hemorrhagic shock swine model. J Trauma 2006;61:57-65.
32. Koustova E, Stanton K, Guschin V, Alam AB, Stegalkina S, Rhee PM. Effects of lactated Ringerâ€™s solutions on human leukocytes. J Trauma 2002;52:872-8.
33. Todd SR, Malinoski D, Muller PJ, Schreiber MA. Lactated ringerâ€™s is superior to normal saline in resuscitation of uncontrolled hemorrhagic shock. J Trauma 2007;62:636-9.
34. Waters JH, Gottlieb A, Schoenwald. Normal saline versus lactated ringerâ€™s solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Anesth Analg 2001;93:817-22.
35. Hayes AW. Principles and Methods of Toxicology. 5th ed. Informa Health care, New York; 2007.
36. Raza M, Al-Shabanah OA, El-Hadiyah TM. Effect of prolonged vigabatrin treatment on hematological and biochemical parameters in plasma, liver and kidney of swiss albino mice. Sci Pharm 2002;70:135-46.
37. Olsson J, Hahn RG. Glycine toxicity after high-dose I. V. infusion of 1.5% glycine in the mouse. Br J Anaesth 1999;82(2):250-4.