Safety of Hypertonic Saline and Mannitol with HES in Supratentorial Brain Tumor Surgeries: A Comparative Study on Coagulation Parameters
Coagulation Effects of Osmotic Agents with HES in Brain Surgery
-
Sohrab Salimi
,
Shahram Sayadi
,
Dariush Abtahi
,
Mona Varzandeh
,
Arman Jami
,
Sepide Ghesmati Tabrizi
Abstract
Background: Managing intracranial pressure and brain swelling during supratentorial brain tumor surgery often involves hyperosmolar solutions like hypertonic saline and mannitol. However, using these solutions alongside hydroxyethyl starch (HES) could potentially affect blood clotting. This study aimed to compare the impact of hypertonic saline and mannitol, when combined with HES, on blood coagulation in patients undergoing these surgeries.
Materials and Methods: This clinical trial compared 20% mannitol and 3% hypertonic saline in patients undergoing brain tumor surgery. Patients were divided into two groups, each receiving one of these osmotic agents along with hydroxyethyl starch. The study focused on assessing any blood clotting abnormalities.
Results: The study included 30 patients (15 in each group). Their initial characteristics were similar. The study found no significant differences in blood coagulation tests between the groups. Additionally, osmolality levels and measures of brain tension were comparable in both groups. There were also no significant differences in intraoperative hemodynamic parameters.
Conclusion: Both hypertonic saline and mannitol, when used with HES, effectively manage intracranial pressure without significantly affecting blood clotting during supratentorial tumor surgeries. Further research is needed to refine fluid management strategies and minimize potential clotting risks in these procedures.
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[2] Oh S, Delic JJ. Hyperosmolar Therapy in the Management of Intracranial Hypertension. AACN Adv Crit Care. 2022; 33(1):5-10.
[3] Hinson HE, Stein D, Sheth KN. Hypertonic saline and mannitol therapy in critical care neurology. J Intensive Care Med. 2013;28(1):3-11.
[4] Gwak DS, Ko SB. Hyperosmolar therapy for regulation of cerebral edema and intracranial pressure. J Korean Med Assoc. 2023; 66(5):297–302.
[5] Kempski O. Hypertonic saline and stroke. Crit Care Med. 2005;33(1):259–60.
[6] Wang H, Cao H, Zhang X, Ge L, Bie L. The effect of hypertonic saline and mannitol on coagulation in moderate traumatic brain injury patients. Am J Emerg Med. 2017; 35(10):1404–7.
[7] Shao L, Wang B, Wang S, Mu F, Gu K. Comparison of 7.2% hypertonic saline - 6% hydroxyethyl starch solution and 6% hydroxyethyl starch solution after the induction of anesthesia in patients undergoing elective neurosurgical procedures. Clinics. 2013;68(3):323.
[8] Mousa SA, Ramadan TH, Kassem M. Brain relaxation and electrolyte balance during resection of posterior fossa tumors under sitting position: Mannitol versus placebo. Egypt J Anaesth. 2013; 29(3):255–65.
[9] Akcil EF, Dilmen OK, Tunali Y. Hypertonic saline versus mannitol for brain relaxation in supratentorial tumor surgery: a prospective randomized trial. Braz J Anesthesiol. 2025;75(6):844684.
[10] Li J, Wang B, Wang S, Mu F. Effects of hypertonic saline - hydroxyethyl starch and mannitol on serum osmolality, dural tension and hemodynamics in
patients undergoing elective neurosurgical procedures. Int J Clin Exp Med. 2014;7(8):2266.
[11] Fenger-eriksen C, Tønnesen E, Ingerslev J, Sørensen B. Mechanisms of hydroxyethyl starch-induced dilutional coagulopathy. J Thromb Haemost. 2009;7(7):1099–105.
[12] Azumaguchi R, Tokinaga Y, Kazuma S, Kimizuka M, Hamada K, Sato T, et al. Validation of the relationship between coagulopathy and localization of hydroxyethyl starch on the vascular endothelium in a rat hemodilution model. Sci Rep. 2021;11(1):10694.
[13] Golparvar M, Saghaei M, Hamidi H, Sajedi P, Kashefi P, Aghadavoudi O, et al. Comparative evaluation of the effects of hydroxyethyl starch on coagulation state of patients during brain tumor surgeries in comparison to crystalloids by thromboelastography. J Res Med Sci. 2014;19(1):8.
[14] Akay MO, Bilir A, Öge T, Kuş G, Mutlu FŞ. The Evaluation of Hydroxyethyl Starch (6% HES 130/0.4) Solution’s Potential Preventive Effects on Coagulation Status in Women with Gynecologic Malignancies Using Rotation Thromboelastography. Turk J Haematol. 2014; 31(3):261-5.
[15] Kang JG, Ahn HJ, Kim GS, Hahm TS, Lee JJ, Gwak MS, et al. The hemostatic profiles of patients with Type O and non-O blood after acute normovolemic hemodilution with 6% hydroxyethyl starch (130/0.4). Anesth Analg. 2006;103(6):1543–8.
[16] Porter SS, Goldberg RJ. Intraoperative allergic reactions to hydroxyethyl starch: a report of two cases. Can Anaesth Soc J. 1986;33(3 Pt 1):394–8.
[17] Bircher AJ, Harr T, Hohenstein L, Tsakiris DA. Hypersensitivity reactions to anticoagulant drugs: diagnosis and management options. Allergy. 2006; 61(12):1432–40.
[18] 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 [cited 2025;57(7):644–8.
[19] Hanke AA, Maschler S, Schöchl H, Flöricke F, Görlinger K, Zanger K, et al. In vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch. Scand J Trauma Resusc Emerg Med. 2011;19:12.
[20] Luostarinen T, Niiya T, Schramko A, Rosenberg P, Niemi T. Comparison of hypertonic saline and mannitol on whole blood coagulation in vitro assessed by thromboelastometry. Neurocrit Care. 2011; 14(2):238–43.
[21] Topçu I, Çivi M, Öztürk T, Keleş GT, Çoban S, Yentür EA, et al. Evaluation of hemostatic changes using thromboelastography after crystalloid or colloid fluid administration during major orthopedic surgery. Braz J Med. Biol Res. 2012; 45(9):869.
[22] Susanto M, Riantri I. Optimal Dose and Concentration of Hypertonic Saline in Traumatic Brain Injury: A Systematic Review. Medeni Med J. 2022;37(2):203.
[23] Kundu SK, Heilmann EJ, Sio R, Garcia C, Davidson RM, Ostgaard RA. Description of an in vitro platelet function analyzer--PFA-100. Semin Thromb Hemost. 1995;21 Suppl 2(SUPPL. 2):106–12.
[24] Mammen EF, Comp PC, Gosselin R, Greenberg C, Hoots WK, Kessler CM, et al. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost. 1998;24(2):195–202.
[25] Paniccia R, Priora R, Liotta AA, Abbate R. Platelet function tests: a comparative review. Vasc Health Risk Manag. 2015;11:133.
[26] Shao L, Hong F, Zou Y, Hao X, Hou H, Tian M. Hypertonic Saline for Brain Relaxation and Intracranial Pressure in Patients Undergoing Neurosurgical Procedures: A Meta-Analysis of Randomized Controlled Trials. PLoS One. 2015;10(1):e0117314.
[27] Alsharkasy M, Altouny A, Elshatoury H, Ewila H.
Comparison between Mannitol 20% and hypertonic saline 7.5% for cerebral resuscitation in severely head injured patients with intra-cranial hypertension. Int J Health Sci (Qassim). 2011;5(2 Suppl 1):36.
[28] Bhatnagar N, Bhateja S, Jeenger L, Mangal G, Gupta S. Effects of two different doses of 3% hypertonic saline with mannitol during decompressive craniectomy following traumatic brain injury: A prospective, controlled study. J Anaesthesiol Clin Pharmacol. 2021;37(4):523–8.
[29] El-Genaidy EMA, El-Medany SM, Abdelhalim AA, Beltagy RS, Rayan TA. Mannitol versus mannitol with hypertonic saline for brain relaxation during craniotomies using ultra-sonographic optic nerve sheath diameter. Alex J Med. 2025;61(1):88–95.
[30] Patil H, Gupta R. A Comparative Study of Bolus Dose of Hypertonic Saline, Mannitol, and Mannitol Plus Glycerol Combination in Patients with Severe Traumatic Brain Injury. World Neurosurg. 2019;125:e221–8./.
[2] Oh S, Delic JJ. Hyperosmolar Therapy in the Management of Intracranial Hypertension. AACN Adv Crit Care. 2022; 33(1):5-10.
[3] Hinson HE, Stein D, Sheth KN. Hypertonic saline and mannitol therapy in critical care neurology. J Intensive Care Med. 2013;28(1):3-11.
[4] Gwak DS, Ko SB. Hyperosmolar therapy for regulation of cerebral edema and intracranial pressure. J Korean Med Assoc. 2023; 66(5):297–302.
[5] Kempski O. Hypertonic saline and stroke. Crit Care Med. 2005;33(1):259–60.
[6] Wang H, Cao H, Zhang X, Ge L, Bie L. The effect of hypertonic saline and mannitol on coagulation in moderate traumatic brain injury patients. Am J Emerg Med. 2017; 35(10):1404–7.
[7] Shao L, Wang B, Wang S, Mu F, Gu K. Comparison of 7.2% hypertonic saline - 6% hydroxyethyl starch solution and 6% hydroxyethyl starch solution after the induction of anesthesia in patients undergoing elective neurosurgical procedures. Clinics. 2013;68(3):323.
[8] Mousa SA, Ramadan TH, Kassem M. Brain relaxation and electrolyte balance during resection of posterior fossa tumors under sitting position: Mannitol versus placebo. Egypt J Anaesth. 2013; 29(3):255–65.
[9] Akcil EF, Dilmen OK, Tunali Y. Hypertonic saline versus mannitol for brain relaxation in supratentorial tumor surgery: a prospective randomized trial. Braz J Anesthesiol. 2025;75(6):844684.
[10] Li J, Wang B, Wang S, Mu F. Effects of hypertonic saline - hydroxyethyl starch and mannitol on serum osmolality, dural tension and hemodynamics in
patients undergoing elective neurosurgical procedures. Int J Clin Exp Med. 2014;7(8):2266.
[11] Fenger-eriksen C, Tønnesen E, Ingerslev J, Sørensen B. Mechanisms of hydroxyethyl starch-induced dilutional coagulopathy. J Thromb Haemost. 2009;7(7):1099–105.
[12] Azumaguchi R, Tokinaga Y, Kazuma S, Kimizuka M, Hamada K, Sato T, et al. Validation of the relationship between coagulopathy and localization of hydroxyethyl starch on the vascular endothelium in a rat hemodilution model. Sci Rep. 2021;11(1):10694.
[13] Golparvar M, Saghaei M, Hamidi H, Sajedi P, Kashefi P, Aghadavoudi O, et al. Comparative evaluation of the effects of hydroxyethyl starch on coagulation state of patients during brain tumor surgeries in comparison to crystalloids by thromboelastography. J Res Med Sci. 2014;19(1):8.
[14] Akay MO, Bilir A, Öge T, Kuş G, Mutlu FŞ. The Evaluation of Hydroxyethyl Starch (6% HES 130/0.4) Solution’s Potential Preventive Effects on Coagulation Status in Women with Gynecologic Malignancies Using Rotation Thromboelastography. Turk J Haematol. 2014; 31(3):261-5.
[15] Kang JG, Ahn HJ, Kim GS, Hahm TS, Lee JJ, Gwak MS, et al. The hemostatic profiles of patients with Type O and non-O blood after acute normovolemic hemodilution with 6% hydroxyethyl starch (130/0.4). Anesth Analg. 2006;103(6):1543–8.
[16] Porter SS, Goldberg RJ. Intraoperative allergic reactions to hydroxyethyl starch: a report of two cases. Can Anaesth Soc J. 1986;33(3 Pt 1):394–8.
[17] Bircher AJ, Harr T, Hohenstein L, Tsakiris DA. Hypersensitivity reactions to anticoagulant drugs: diagnosis and management options. Allergy. 2006; 61(12):1432–40.
[18] 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 [cited 2025;57(7):644–8.
[19] Hanke AA, Maschler S, Schöchl H, Flöricke F, Görlinger K, Zanger K, et al. In vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch. Scand J Trauma Resusc Emerg Med. 2011;19:12.
[20] Luostarinen T, Niiya T, Schramko A, Rosenberg P, Niemi T. Comparison of hypertonic saline and mannitol on whole blood coagulation in vitro assessed by thromboelastometry. Neurocrit Care. 2011; 14(2):238–43.
[21] Topçu I, Çivi M, Öztürk T, Keleş GT, Çoban S, Yentür EA, et al. Evaluation of hemostatic changes using thromboelastography after crystalloid or colloid fluid administration during major orthopedic surgery. Braz J Med. Biol Res. 2012; 45(9):869.
[22] Susanto M, Riantri I. Optimal Dose and Concentration of Hypertonic Saline in Traumatic Brain Injury: A Systematic Review. Medeni Med J. 2022;37(2):203.
[23] Kundu SK, Heilmann EJ, Sio R, Garcia C, Davidson RM, Ostgaard RA. Description of an in vitro platelet function analyzer--PFA-100. Semin Thromb Hemost. 1995;21 Suppl 2(SUPPL. 2):106–12.
[24] Mammen EF, Comp PC, Gosselin R, Greenberg C, Hoots WK, Kessler CM, et al. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost. 1998;24(2):195–202.
[25] Paniccia R, Priora R, Liotta AA, Abbate R. Platelet function tests: a comparative review. Vasc Health Risk Manag. 2015;11:133.
[26] Shao L, Hong F, Zou Y, Hao X, Hou H, Tian M. Hypertonic Saline for Brain Relaxation and Intracranial Pressure in Patients Undergoing Neurosurgical Procedures: A Meta-Analysis of Randomized Controlled Trials. PLoS One. 2015;10(1):e0117314.
[27] Alsharkasy M, Altouny A, Elshatoury H, Ewila H.
Comparison between Mannitol 20% and hypertonic saline 7.5% for cerebral resuscitation in severely head injured patients with intra-cranial hypertension. Int J Health Sci (Qassim). 2011;5(2 Suppl 1):36.
[28] Bhatnagar N, Bhateja S, Jeenger L, Mangal G, Gupta S. Effects of two different doses of 3% hypertonic saline with mannitol during decompressive craniectomy following traumatic brain injury: A prospective, controlled study. J Anaesthesiol Clin Pharmacol. 2021;37(4):523–8.
[29] El-Genaidy EMA, El-Medany SM, Abdelhalim AA, Beltagy RS, Rayan TA. Mannitol versus mannitol with hypertonic saline for brain relaxation during craniotomies using ultra-sonographic optic nerve sheath diameter. Alex J Med. 2025;61(1):88–95.
[30] Patil H, Gupta R. A Comparative Study of Bolus Dose of Hypertonic Saline, Mannitol, and Mannitol Plus Glycerol Combination in Patients with Severe Traumatic Brain Injury. World Neurosurg. 2019;125:e221–8./.
| Files | ||
| Issue | Vol 12 No 3 (2026): May-Jun |
|
| Section | Research Article(s) | |
| DOI | https://doi.org/10.18502/aacc.v12i3.21310 | |
| Keywords | ||
| Blood coagulation disorder Hydroxyethyl Starch Derivatives Saline Solution Hypertonic mannitol neurosurgery Supratentorial Neoplasms | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Salimi S, Sayadi S, Abtahi D, Varzandeh M, Jami A, Ghesmati Tabrizi S. Safety of Hypertonic Saline and Mannitol with HES in Supratentorial Brain Tumor Surgeries: A Comparative Study on Coagulation Parameters. Arch Anesth & Crit Care. 2026;12(3):246-253.
