Download PDF
CC BY 4.0 · J Neuroanaesth Crit Care 2023; 10(01): 012-020
DOI: 10.1055/s-0043-1763264
Review Article

Use of Hypertonic Saline in Neuroanesthesia and Neurocritical Care Practice: A Narrative Review

Amiya K. Barik 
1   Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
,
Priya Thappa
1   Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
,
Kiran Jangra 
1   Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
,
Hemant Bhagat
1   Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
,
Kirandeep Kaur
1   Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Hypertonic saline (HTS) is a group of fluids containing sodium and chloride in a higher concentration as compared to physiological saline. The authors have conducted this review to evaluate the use of HTS in neuroanesthesia and neurocritical care. The articles for this narrative review on HTS were searched on databases like PubMed Central, EMBASE, and Google Scholar using the Medical Subject Headings keywords “Hypertonic Saline,” “Neuroanesthesia,” and “Neurocritical Care.” The review focuses on the mechanisms of HTS and its in routine clinical practice. The results of various comparative studies between HTS and mannitol and guidelines regarding the use of HTS have also been reviewed. HTS can be used to treat hyponatremia, reduce intracranial pressure, provide intraoperative relaxed brain, and aid in resuscitation during cardiogenic, neurogenic, and septic shock. Its side effects include renal toxicity in the case of hypernatremia, rebound intracranial hypertension, volume overload, dyselectrolytemia, phlebitis, local tissue damage, and osmotic demyelination syndrome in the case of rapid correction of serum sodium concentration.

Keywords

hypertonic saline - neuroanesthesia - neurocritical care


Publication History

Article published online:
24 April 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Freeman N, Welbourne J. Osmotherapy: science and evidence-based practice. BJA Educ 2018; 18 (09) 284-290
    CrossrefPubMedSearch in Google Scholar
  • 2 Weed LH, McKibben PS. Experimental alteration of brain bulk. Am J Physiol-Legacy Content 1919; 48: 531-558
    CrossrefPubMedSearch in Google Scholar
  • 3 Strandvik GF. Hypertonic saline in critical care: a review of the literature and guidelines for use in hypotensive states and raised intracranial pressure. Anaesthesia 2009; 64 (09) 990-1003
    CrossrefPubMedSearch in Google Scholar
  • 4 de Carvalho WB. Hypertonic solutions for pediatric patients [in Portuguese]. J Pediatr (Rio J) 2003; 79 (Suppl 2): S187-S194
    CrossrefPubMedSearch in Google Scholar
  • 5 Hochwald GM, Wald A, DiMattio J, Malhan C. The effects of serum osmolarity on cerebrospinal fluid volume flow. Life Sci 1974; 15 (07) 1309-1316
    CrossrefPubMedSearch in Google Scholar
  • 6 Shackford SR, Schmoker JD, Zhuang J. The effect of hypertonic resuscitation on pial arteriolar tone after brain injury and shock. J Trauma 1994; 37 (06) 899-908
    CrossrefPubMedSearch in Google Scholar
  • 7 Finberg L. Dangers to infants caused by changes in osmolal concentration. Pediatrics 1967; 40 (06) 1031-1034
    CrossrefPubMedSearch in Google Scholar
  • 8 Tyagi R, Donaldson K, Loftus CM, Jallo J. Hypertonic saline: a clinical review. Neurosurg Rev 2007; 30 (04) 277-289
    CrossrefPubMedSearch in Google Scholar
  • 9 Joseph B, Aziz H, Snell M. et al. The physiological effects of hyperosmolar resuscitation: 5% vs 3% hypertonic saline. Am J Surg 2014; 208 (05) 697-702
    CrossrefPubMedSearch in Google Scholar
  • 10 Gemma M, Cozzi S, Piccoli S, Magrin S, De Vitis A, Cenzato M. Hypertonic saline fluid therapy following brain stem trauma. J Neurosurg Anesthesiol 1996; 8 (02) 137-141
    CrossrefPubMedSearch in Google Scholar
  • 11 Thompson R, Greaves I. Hypertonic saline–hydroxyethyl starch in trauma resuscitation. J R Army Med Corps 2006; 152 (01) 6-12
    CrossrefPubMedSearch in Google Scholar
  • 12 Oliveira RP, Velasco I, Soriano FG, Friedman G. Clinical review: hypertonic saline resuscitation in sepsis. Crit Care 2002; 6 (05) 418-423
    CrossrefPubMedSearch in Google Scholar
  • 13 Rhind SG, Crnko NT, Baker AJ. et al. Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients. J Neuroinflammation 2010; 7: 5
    CrossrefPubMedSearch in Google Scholar
  • 14 Huang LQ, Zhu GF, Deng YY. et al. Hypertonic saline alleviates cerebral edema by inhibiting microglia-derived TNF-α and IL-1β-induced Na-K-Cl cotransporter up-regulation. J Neuroinflammation 2014; 11: 1-20
    CrossrefPubMedSearch in Google Scholar
  • 15 Choi DW. Calcium: still center-stage in hypoxic-ischemic neuronal death. Trends Neurosci 1995; 18 (02) 58-60
    CrossrefPubMedSearch in Google Scholar
  • 16 Huang SJ, Chang L, Han YY, Lee YC, Tu YK. Efficacy and safety of hypertonic saline solutions in the treatment of severe head injury. Surg Neurol 2006; 65 (06) 539-546 , discussion 546
    CrossrefPubMedSearch in Google Scholar
  • 17 Qureshi AI, Suarez JI, Castro A, Bhardwaj A. Use of hypertonic saline/acetate infusion in treatment of cerebral edema in patients with head trauma: experience at a single center. J Trauma 1999; 47 (04) 659-665
    CrossrefPubMedSearch in Google Scholar
  • 18 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 (01) 41-51
    CrossrefPubMedSearch in Google Scholar
  • 19 Cooper DJ, Myles PS, McDermott FT. et al; HTS Study Investigators. Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury: a randomized controlled trial. JAMA 2004; 291 (11) 1350-1357
    CrossrefPubMedSearch in Google Scholar
  • 20 Vialet R, Albanèse 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 (06) 1683-1687
    CrossrefPubMedSearch in Google Scholar
  • 21 Saltarini M, Massarutti D, Baldassarre M, Nardi G, De Colle C, Fabris G. Determination of cerebral water content by magnetic resonance imaging after small volume infusion of 18% hypertonic saline solution in a patient with refractory intracranial hypertension. Eur J Emerg Med 2002; 9 (03) 262-265
    CrossrefPubMedSearch in Google Scholar
  • 22 Ware ML, Nemani VM, Meeker M, Lee C, Morabito DJ, Manley GT. Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study. Neurosurgery 2005; 57 (04) 727-736
    CrossrefPubMedSearch in Google Scholar
  • 23 Berger-Pelleiter E, Émond M, Lauzier F, Shields JF, Turgeon AF. Hypertonic saline in severe traumatic brain injury: a systematic review and meta-analysis of randomized controlled trials. CJEM 2016; 18 (02) 112-120
    CrossrefPubMedSearch in Google Scholar
  • 24 Han C, Yang F, Guo S, Zhang J. Hypertonic saline compared to mannitol for the management of elevated intracranial pressure in traumatic brain injury: a meta-analysis. Front Surg 2022; 8: 765784
    CrossrefPubMedSearch in Google Scholar
  • 25 Shi J, Tan L, Ye J, Hu L. Hypertonic saline and mannitol in patients with traumatic brain injury: a systematic and meta-analysis. Medicine (Baltimore) 2020; 99 (35) e21655
    CrossrefPubMedSearch in Google Scholar
  • 26 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
    CrossrefPubMedSearch in Google Scholar
  • 27 Huang X, Yang L, Ye J, He S, Wang B. Equimolar doses of hypertonic agents (saline or mannitol) in the treatment of intracranial hypertension after severe traumatic brain injury. Medicine (Baltimore) 2020;99(38):e22004. [published correction appears in Medicine (Baltimore) 2021; 100: e25953]
    PubMedSearch in Google Scholar
  • 28 Ichai C, Payen JF, Orban JC. et al. Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured patients: a randomized controlled trial. Intensive Care Med 2013; 39 (08) 1413-1422
    CrossrefPubMedSearch in Google Scholar
  • 29 Jagannatha AT, Sriganesh K, Devi BI, Rao GS. An equiosmolar study on early intracranial physiology and long term outcome in severe traumatic brain injury comparing mannitol and hypertonic saline. J Clin Neurosci 2016; 27: 68-73
    CrossrefPubMedSearch in Google Scholar
  • 30 Mangat HS, Chiu YL, Gerber LM, Alimi M, Ghajar J, Härtl R. Hypertonic saline reduces cumulative and daily intracranial pressure burdens after severe traumatic brain injury. J Neurosurg 2015; 122 (01) 202-210
    CrossrefPubMedSearch in Google Scholar
  • 31 Sakellaridis N, Pavlou E, Karatzas S. et al. Comparison of mannitol and hypertonic saline in the treatment of severe brain injuries. J Neurosurg 2011; 114 (02) 545-548
    CrossrefPubMedSearch in Google Scholar
  • 32 Adelson PD, Bratton SL, Carney NA. et al; American Association for Surgery of Trauma, Child Neurology Society, International Society for Pediatric Neurosurgery, International Trauma Anesthesia and Critical Care Society, Society of Critical Care Medicine, World Federation of Pediatric Intensive and Critical Care Societies. Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 11. Use of hyperosmolar therapy in the management of severe pediatric traumatic brain injury. Pediatr Crit Care Med 2003; 4 (3, Suppl): S40-S44
    CrossrefPubMedSearch in Google Scholar
  • 33 Simma B, Burger R, Falk M, Sacher P, Fanconi S. 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 (07) 1265-1270
    CrossrefPubMedSearch in Google Scholar
  • 34 Fisher B, Thomas D, Peterson B. Hypertonic saline lowers raised intracranial pressure in children after head trauma. J Neurosurg Anesthesiol 1992; 4 (01) 4-10
    CrossrefPubMedSearch in Google Scholar
  • 35 Kochanek PM, Adelson PD, Rosario BL. et al; ADAPT Investigators. Comparison of intracranial pressure measurements before and after hypertonic saline or mannitol treatment in children with severe traumatic brain injury. JAMA Netw Open 2022; 5 (03) e220891
    CrossrefPubMedSearch in Google Scholar
  • 36 Cook AM, Morgan Jones G, Hawryluk GWJ. et al. Guidelines for the acute treatment of cerebral edema in neurocritical care patients. Neurocrit Care 2020; 32 (03) 647-666
    CrossrefPubMedSearch in Google Scholar
  • 37 Bentsen G, Breivik H, Lundar T, Stubhaug A. Predictable reduction of intracranial hypertension with hypertonic saline hydroxyethyl starch: a prospective clinical trial in critically ill patients with subarachnoid haemorrhage. Acta Anaesthesiol Scand 2004; 48 (09) 1089-1095
    CrossrefPubMedSearch in Google Scholar
  • 38 Bentsen G, Breivik H, Lundar T, Stubhaug A. Hypertonic saline (7.2%) in 6% hydroxyethyl starch reduces intracranial pressure and improves hemodynamics in a placebo-controlled study involving stable patients with subarachnoid hemorrhage. Crit Care Med 2006; 34 (12) 2912-2917
    CrossrefPubMedSearch in Google Scholar
  • 39 Tseng MY, Al-Rawi PG, Pickard JD, Rasulo FA, Kirkpatrick PJ. Effect of hypertonic saline on cerebral blood flow in poor-grade patients with subarachnoid hemorrhage. Stroke 2003; 34 (06) 1389-1396
    CrossrefPubMedSearch in Google Scholar
  • 40 Al-Rawi PG, Zygun D, Tseng MY, Hutchinson PJ, Matta BF, Kirkpatrick PJ. Cerebral blood flow augmentation in patients with severe subarachnoid haemorrhage. Acta Neurochir Suppl (Wien) 2005; 95 (Suppl 95): 123-127
    CrossrefPubMedSearch in Google Scholar
  • 41 Al-Rawi PG, Tseng MY, Richards HK. et al. Hypertonic saline in patients with poor-grade subarachnoid hemorrhage improves cerebral blood flow, brain tissue oxygen, and pH. Stroke 2010; 41 (01) 122-128
    CrossrefPubMedSearch in Google Scholar
  • 42 Schwarz S, Georgiadis D, Aschoff A, Schwab S. Effects of hypertonic (10%) saline in patients with raised intracranial pressure after stroke. Stroke 2002; 33 (01) 136-140
    CrossrefPubMedSearch in Google Scholar
  • 43 Chugh AJ, Maynard M, Sunshine K. et al. Role of continuous hypertonic saline in acute ischemic infarcts: a systematic literature review. J Neurocrit Care 2021; 14: 1-7
    CrossrefPubMedSearch in Google Scholar
  • 44 Harutjunyan L, Holz C, Rieger A, Menzel M, Grond S, Soukup J. Efficiency of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 versus mannitol 15% in the treatment of increased intracranial pressure in neurosurgical patients - a randomized clinical trial [ISRCTN62699180]. Crit Care 2005; 9 (05) R530-R540
    CrossrefPubMedSearch in Google Scholar
  • 45 Koenig MA, Bryan M, Lewin III JL, Mirski MA, Geocadin RG, Stevens RD. Reversal of transtentorial herniation with hypertonic saline. Neurology 2008; 70 (13) 1023-1029
    CrossrefPubMedSearch in Google Scholar
  • 46 Toung TJK, Tyler B, Brem H, Traystman RJ, Hurn PD, Bhardwaj A. Hypertonic saline ameliorates cerebral edema associated with experimental brain tumor. J Neurosurg Anesthesiol 2002; 14 (03) 187-193
    CrossrefPubMedSearch in Google Scholar
  • 47 Hernández-Palazón J, Fuentes-García D, Doménech-Asensi P. et al. A dose-response relationship study of hypertonic saline on brain relaxation during supratentorial brain tumour craniotomy. Br J Neurosurg 2018; 32 (06) 619-627
    CrossrefPubMedSearch in Google Scholar
  • 48 Rozet I, Tontisirin N, Muangman S. et al. Effect of equiosmolar solutions of mannitol versus hypertonic saline on intraoperative brain relaxation and electrolyte balance. Anesthesiology 2007; 107 (05) 697-704
    CrossrefPubMedSearch in Google Scholar
  • 49 Singla A, Mathew PJ, Jangra K, Gupta SK, Soni SL. A comparison of hypertonic saline and mannitol on intraoperative brain relaxation in patients with raised intracranial pressure during supratentorial tumors resection: a randomized control trial. Neurol India 2020; 68 (01) 141-145
    CrossrefPubMedSearch in Google Scholar
  • 50 Barik AK, Agrawal S, Gupta P, Kumari R. Evaluation of equiosmolar 20% mannitol, 3% hypertonic saline and 8.4% sodium bicarbonate on intraoperative brain relaxation and hemodynamic parameters in patients undergoing craniotomy for supratentorial tumors: a prospective randomized study. Minerva Anestesiol 2021; 87 (09) 997-1005
    CrossrefPubMedSearch in Google Scholar
  • 51 Ali A, Tetik A, Sabanci PA. et al. Comparison of 3% hypertonic saline and 20% mannitol for reducing intracranial pressure in patients undergoing supratentorial brain tumor surgery: a randomized, double-blind clinical trial. J Neurosurg Anesthesiol 2018; 30 (02) 171-178
    CrossrefPubMedSearch in Google Scholar
  • 52 Sokhal N, Rath GP, Chaturvedi A, Singh M, Dash HH. Comparison of 20% mannitol and 3% hypertonic saline on intracranial pressure and systemic hemodynamics. J Clin Neurosci 2017; 42: 148-154
    CrossrefPubMedSearch in Google Scholar
  • 53 Ramesh GH, Uma JC, Farhath S. Fluid resuscitation in trauma: what are the best strategies and fluids?. Int J Emerg Med 2019; 12 (01) 38
    CrossrefPubMedSearch in Google Scholar
  • 54 Younes RN, Birolini D. Hypertonic/hyperoncotic solution in hypovolemic patients: experience in the emergency room. Rev Hosp Clin Fac Med Sao Paulo 2002; 57 (03) 124-128
    CrossrefPubMedSearch in Google Scholar
  • 55 Vassar MJ, Perry CA, Gannaway WL, Holcroft JW. 7.5% sodium chloride/dextran for resuscitation of trauma patients undergoing helicopter transport. Arch Surg 1991; 126 (09) 1065-1072
    CrossrefPubMedSearch in Google Scholar
  • 56 Alpar EK, Killampalli VV. Effects of hypertonic dextran in hypovolaemic shock: a prospective clinical trial. Injury 2004; 35 (05) 500-506
    CrossrefPubMedSearch in Google Scholar
  • 57 Goertz AW, Mehl T, Lindner KH. et al. Effect of 7.2% hypertonic saline/6% hetastarch on left ventricular contractility in anesthetized humans. Anesthesiology 1995; 82 (06) 1389-1395
    CrossrefPubMedSearch in Google Scholar
  • 58 Gayatri P, Misra S, Menon G, Arulvelan A, Thulaseedharan JV. Transesophageal echocardiographic evaluation of left ventricular systolic and diastolic function in response to 20% mannitol and 3% hypertonic saline infusion in neurosurgical patients undergoing craniotomy. J Neurosurg Anesthesiol 2014; 26 (03) 187-191
    CrossrefPubMedSearch in Google Scholar
  • 59 Frithiof R, Eriksson S, Bayard F, Svensson T, Rundgren M. Intravenous hypertonic NaCl acts via cerebral sodium-sensitive and angiotensinergic mechanisms to improve cardiac function in haemorrhaged conscious sheep. J Physiol 2007; 583 (Pt 3): 1129-1143
    CrossrefPubMedSearch in Google Scholar
  • 60 Licata G, Di Pasquale P, Parrinello G. et al. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Am Heart J 2003; 145 (03) 459-466
    CrossrefPubMedSearch in Google Scholar
  • 61 Zampieri FG, Caruso P. Acute treatment of uncompensated heart failure with 10% hypertonic saline and its subsequent effect on respiratory patterns. Clinics (São Paulo) 2011; 66 (04) 717-718
    CrossrefPubMedSearch in Google Scholar
  • 62 Järvelä K, Kööbi T, Kauppinen P, Kaukinen S. Effects of hypertonic 75 mg/ml (7.5%) saline on extracellular water volume when used for preloading before spinal anaesthesia. Acta Anaesthesiol Scand 2001; 45 (06) 776-781
    CrossrefPubMedSearch in Google Scholar
  • 63 Nout YS, Mihai G, Tovar CA, Schmalbrock P, Bresnahan JC, Beattie MS. Hypertonic saline attenuates cord swelling and edema in experimental spinal cord injury: a study utilizing magnetic resonance imaging. Crit Care Med 2009; 37 (07) 2160-2166
    CrossrefPubMedSearch in Google Scholar
  • 64 Oliveira RP, Weingartner R, Ribas EO, Moraes RS, Friedman G. Acute haemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis. Intensive Care Med 2002; 28 (11) 1574-1581
    CrossrefPubMedSearch in Google Scholar
  • 65 Hannemann L, Reinhart K, Korell R, Spies C, Bredle DL. Hypertonic saline in stabilized hyperdynamic sepsis. Shock 1996; 5 (02) 130-134
    CrossrefPubMedSearch in Google Scholar
  • 66 Effat HS, Ramadan SS, Mokhtar MS, Ibrahim MM. Hypertonic saline versus isotonic saline in septic shock (effects on morbidity, mortality, and clinical outcome). Egypt J Crit Care Med 2021; 8: 43-50
    PubMedSearch in Google Scholar
  • 67 The Brain Trauma Foundation, The American Association of Neurological Surgeons, The Joint Section on Neurotrauma and Critical Care. Initial management. J Neurotrauma 2000; 17 (6-7): 463-469
    CrossrefPubMedSearch in Google Scholar
  • 68 Huang PP, Stucky FS, Dimick AR, Treat RC, Bessey PQ, Rue LW. Hypertonic sodium resuscitation is associated with renal failure and death. Ann Surg 1995; 221 (05) 543-554
    CrossrefPubMedSearch in Google Scholar
  • 69 Kumar AB, Shi Y, Shotwell MS, Richards J, Ehrenfeld JM. Hypernatremia is a significant risk factor for acute kidney injury after subarachnoid hemorrhage: a retrospective analysis. Neurocrit Care 2015; 22 (02) 184-191
    CrossrefPubMedSearch in Google Scholar
  • 70 Videen JS, Michaelis T, Pinto P, Ross BD. Human cerebral osmolytes during chronic hyponatremia. A proton magnetic resonance spectroscopy study. J Clin Invest 1995; 95 (02) 788-793
    CrossrefPubMedSearch in Google Scholar
  • 71 Häussinger D, Laubenberger J, vom Dahl S. et al. Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy. Gastroenterology 1994; 107 (05) 1475-1480
    CrossrefPubMedSearch in Google Scholar
  • 72 Lien YH, Shapiro JI, Chan L. Study of brain electrolytes and organic osmolytes during correction of chronic hyponatremia. Implications for the pathogenesis of central pontine myelinolysis. J Clin Invest 1991; 88 (01) 303-309
    CrossrefPubMedSearch in Google Scholar
  • 73 Olson JE, Goldfinger MD. Amino acid content of rat cerebral astrocytes adapted to hyperosmotic medium in vitro. J Neurosci Res 1990; 27 (02) 241-246
    CrossrefPubMedSearch in Google Scholar
  • 74 Peterson B, Khanna S, Fisher B, Marshall L. Prolonged hypernatremia controls elevated intracranial pressure in head-injured pediatric patients. Crit Care Med 2000; 28 (04) 1136-1143
    CrossrefPubMedSearch in Google Scholar
  • 75 Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med 2000; 28 (09) 3301-3313
    CrossrefPubMedSearch in Google Scholar
  • 76 Knapp JM. Hyperosmolar therapy in the treatment of severe head injury in children: mannitol and hypertonic saline. AACN Clin Issues 2005; 16 (02) 199-211
    CrossrefPubMedSearch in Google Scholar
  • 77 Tan TS, Tan KH, 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 (07) 644-648
    CrossrefPubMedSearch in Google Scholar