<< Therapeutic Uses Of Hypertonic Saline In The Critically Ill Emergency Department Patient (Trauma CME)


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Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study, will be included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, will be noted by an asterisk (*) next to the number of the reference.

  1. Sauaia A, Moore FA, Moore EE, et al. Epidemiology of trauma deaths: a reassessment. J Trauma. 1995;38(2):185-193.
  2. Rocha-e-Silva M, Poli de Figueiredo LF. Small volume hypertonic resuscitation of circulatory shock. Clinics. 2005;60(2):159-172. (Review)
  3. Rizoli SB, Rhind SG, Shek PN, et al. The immunomodulatory effects of hypertonic saline resuscitation in patients sustaining traumatic hemorrhagic shock: a randomized, controlled, double-blinded trial. Ann Surg. 2006;243(1):47-57. (Prospective randomized controlled trial; 27 patients)
  4. Hirsh M, Dyugovskaya L, Bashenko Y, et al. Reduced rate of bacterial translocation and improved variables of natural killer cell and T-cell activity in rats surviving controlled hemorrhagic shock and treated with hypertonic saline. Crit Care Med. 2002;30(4):861-867. (Laboratory)
  5. Loomis WH, Namiki S, Hoyt DB, et al. Hypertonicity rescues T cells from suppression by trauma-induced anti-inflammatory mediators. Am J Physiol Cell Physiol. 2001;281(3):C840-C848. (Laboratory)
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  7. Homma H, Deitch EA, Feketeova E, et al. Small volume resuscitation with hypertonic saline is more effective in ameliorating trauma-hemorrhagic shock-induced lung injury, neutrophil activation and red blood cell dysfunction than pancreatitic protease inhibition. J Trauma. 2005;59(2):266-272. (Laboratory)
  8. Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med. 2000;28(9):3301-3313. (Review)
  9. Suarez JI. Hypertonic saline for cerebral edema and elevated intracranial pressure. Cleve Clin J Med. 2004;71 Suppl 1:S9-S13. (Review)
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  14. Horn P, Munch E, Vajkoczy P, et al. Hypertonic saline solution for control of elevated intracranial pressure in patients with exhausted response to mannitol and barbiturates. Neurol Res. 1999;21(8):758-764. (Prospective; 10 patients)
  15. Khanna S, Davis D, Peterson B, et al. Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury. Crit Care Med. 2000;28(4):1144-1151. (Prospective; 10 children)
  16. Munar F, Ferrer AM, de Nadal M, et al. Cerebral hemodynamic effects of 7.2% hypertonic saline in patients with head injury and raised intracranial pressure. J Neurotrauma. 2000;17(1):41-51. (Prospective; 14 patients)
  17. Schatzmann C, Heissler HE, Konig K, et al. Treatment of elevated intracranial pressure by infusions of 10% saline in severely head injured patients. Acta Neurochir Suppl. 1998;71:31-33. (Prospective randomized controlled trial)
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  20. Fisher B, Thomas D, Peterson B. Hypertonic saline lowers raised intracranial pressure in children after head trauma. J Neurosurg Anesthesiol. 1992;4(1):4-10. (Prospective double-blind crossover trial; 18 patients)
  21. Simma B, Burger R, Falk M, et al. A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer’s solution versus hypertonic saline. Crit Care Med. 1998;26(7):1265-1270. (Prospective randomized controlled trial; 35 pediatric patients)
  22. * Roberts I, Schierhout G, Wakai A. Mannitol for acute traumatic brain injury. Cochrane Database Syst Rev. 2003;(2):CD001049. (Cochrane systematic review and meta-analysis; 4 trials)
  23. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. J Neurotrauma. 2007;24 Suppl 1:S1-S2. (Evidence-based guideline)
  24. Ware ML, Nemani VM, Meeker M, et al. Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study. Neurosurgery. 2005;57(4):727-736. (Retrospective; 13 patients)
  25. Oddo M, Levine JM, Frangos S, et al. Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension. J Neurol Neurosurg Psychiatry. 2009;80(8):916-920. (Prospective; 12 patients)
  26. * Kamel H, Navi BB, Nakagawa K, et al. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med. 2011;39(3):554-559. (Meta-analysis; 5 trials, 112 patients)
  27. * Wakai A, Roberts I, Schierhout G. Mannitol for acute traumatic brain injury. Cochrane Database Syst Rev. 2007;(1):CD001049. (Cochrane systematic review and meta-analysis; 4 trials)
  28. Vialet R, Albanese J, Thomachot L, et al. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med. 2003;31(6):1683-1687.
  29. Cottenceau V, Masson F, Mahamid E, et al. Comparison of effects of equiosmolar doses of mannitol and hypertonic saline on cerebral blood flow and metabolism in traumatic brain injury. J Neurotrauma. 2011;28(10):2003-2012. (Prospective; 47 patients)
  30. * Bunn F, Tasker R, Daksha T. Hypertonic versus near isotonic crystalloid for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2008;(4):CD002045. (Cochrane systematic review and meta-analysis; 956 patients)
  31. * Cooper DJ, Myles PS, McDermott FT, et al. Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury: a randomized controlled trial. JAMA. 2004;291(11):1350-1357. (Prospective randomized controlled trial; 229 patients)
  32. * Bulger EM, May S, Brasel KJ, et al. Out-of-hospital hypertonic resuscitation following severe traumatic brain injury: a randomized controlled trial. JAMA. 2010;304(13):1455-1464. (Prospective randomized controlled trial; 1331 patients)
  33. Tan PG, Cincotta M, Clavisi O, et al. Review article: prehospital fluid management in traumatic brain injury. Emerg Med Australas. 2011;23(6):665-676. (Review article)
  34. Vassar MJ, Fischer RP, O’Brien PE, et al. A multicenter trial for resuscitation of injured patients with 7.5% sodium chloride. The effect of added dextran 70. The Multicenter Group for the Study of Hypertonic Saline in Trauma Patients. Arch Surg. 1993;128(9):1003-1011. (Prospective randomized controlled trial; 194 patients)
  35. Wade CE, Grady JJ, Kramer GC, et al. Individual patient cohort analysis of the efficacy of hypertonic saline/dextran in patients with traumatic brain injury and hypotension. J Trauma. 1997;42(5 Suppl):S61-S65. (Cohort analysis; 223 patients)
  36. * Committee on Fluid Resuscitation for Combat Casualties, Institute of Medicine. State of the Science for Treating Combat Casualties and Civilian Injuries. Washington DC: National Academies Press: 1999. (Textbook)
  37. de Felippe J Jr, Timoner J, Velasco IT, et al. Treatment of refractory hypovolaemic shock by 7.5% sodium chloride injections. Lancet. 1980;2(8202):1002-1004. (Case report; 12 patients)
  38. Velasco IT, Pontieri V, Rocha e Silva M Jr, et al. Hyperosmotic NaCl and severe hemorrhagic shock. Am J Physiol. 1980;239(5):H664-H673. (Laboratory)
  39. Younes RN, Aun F, Ching CT, et al. Prognostic factors to predict outcome following the administration of hypertonic/hyperoncotic solution in hypovolemic patients. Shock. 1997;7(2):79-83. (Prospective randomized controlled trial; 212 patients)
  40. Mattox KL, Maningas PA, Moore EE, et al. Prehospital hypertonic saline/dextran infusion for post-traumatic hypotension. The U.S.A. Multicenter Trial. Ann Surg. 1991;213(5):482-491. (Multicenter prospective randomized controlled trial; 422 patients).
  41. Vassar MJ, Perry CA, Holcroft JW. Prehospital resuscitation of hypotensive trauma patients with 7.5% NaCl versus 7.5% NaCl with added dextran: a controlled trial. J Trauma. 1993;34(5):622-632. (Prospective randomized controlled trial; 258 patients)
  42. Alpar EK, Killampalli VV. Effects of hypertonic dextran in hypovolaemic shock: a prospective clinical trial. Injury. 2004;35(5):500-506. (Prospective randomized controlled trial; 180 patients)
  43. Maningas PA, Mattox KL, Pepe PE, et al. Hypertonic saline-dextran solutions for the prehospital management of traumatic hypotension. Am J Surg. 1989;157(5):528-533; discussion 533-524. (Prospective randomized controlled trial; prehospital; 48 patients)
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  45. Bulger EM, Jurkovich GJ, Nathens AB, et al. Hypertonic resuscitation of hypovolemic shock after blunt trauma: a randomized controlled trial. Arch Surg. 2008;143(2):139-148. (Prospective randomized controlled trial; 209 patients)
  46. Younes RN, Aun F, Accioly CQ, et al. Hypertonic solutions in the treatment of hypovolemic shock: a prospective, randomized study in patients admitted to the emergency room. Surgery. 1992;111(4):380-385. (Prospective randomized trial; 105 patients)
  47. Holcroft JW, Vassar MJ, Turner JE, et al. 3% NaCl and 7.5% NaCl/dextran 70 in the resuscitation of severely injured patients. Ann Surg. 1987;206(3):279-288. (Prospective, randomized controlled trial; 32 patients)
  48. * Bulger EM, May S, Kerby JD, et al. Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial. Ann Surg. 2011;253(3):431-441. (Prospective randomized controlled trial; 853 patients)
  49. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. 2006;119(7 Suppl 1):S30-S35. (Review)
  50. Widdess-Walsh P, Sabharwal V, Demirjian S, et al. Neurologic effects of hyponatremia and its treatment. Cleve Clin J Med. 2007;74(5):377-383. (Case report)
  51. * Sterns RH, Cappuccio JD, Silver SM, et al. Neurologic sequelae after treatment of severe hyponatremia: a multicenter perspective. J Am Soc Nephrol. 1994;4(8):1522-1530. (Retrospective; 56 patients)
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  72. Gross D, Landau EH, Klin B, et al. Treatment of uncontrolled hemorrhagic shock with hypertonic saline solution. Surg Gynecol Obstet. 1990;170(2):106-112. (Laboratory)
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  76. Hannemann L, Reinhart K, Korell R, et al. Hypertonic saline in stabilized hyperdynamic sepsis. Shock. 1996;5(2):130-134. (Prospective; 14 patients)
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