CC BY-NC-ND 4.0 · J Neuroanaesth Crit Care 2017; 04(03): 138-146
DOI: 10.4103/jnacc-jnacc-31.17
Review Article
Thieme Medical and Scientific Publishers Private Ltd.

Understanding the physiological changes induced by mannitol: From the theory to the clinical practice in neuroanaesthesia

Wilson Fandino
1   Department of Neuronaesthesia, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
08 May 2018 (online)

Abstract

In this narrative review, the current evidence for the use of mannitol in neuroanaesthesia is presented, with focus on its pharmacokinetics and its main physiologic effects. Mannitol is a naturally occurring polyol that undergoes no biotransformation and is freely filtered in the kidney. Due to its strong osmotic effects, it induces key physiological changes, mainly in the cardiovascular system, the kidney and the brain. While it is clear that hypertonic solutions are effective in the treatment of intracranial hypertension in patients with acute brain injury, the role of mannitol in the context of intracranial haemorrhage, acute stroke and brain relaxation remains controversial. Furthermore, it possesses important side effects including acute kidney injury and electrolyte imbalances, particularly related to high doses in predisposing patients. Other aspects including the capability to modify neurological outcomes, the impact on mortality, the utility in patients with disrupted blood–brain barrier and the alternative use of hypertonic saline are also discussed. Further research is needed to make clear recommendations on these aspects.

 
  • REFERENCES

  • 1 Smith WW, Finkelstein N, Smith HW. Renal excretion of hexitols (sorbitol, mannitol, and dulcitol) and their derivatives (sorbitan, isomannide, and sorbide) and of endogenous creatinine-like chromogen in dog and man. J Biol Chem 1940; 135: 231-50
  • 2 Better OS, Rubinstein I, Winaver JM, Knochel JP. Mannitol therapy revisited (1940-1997). Kidney Int 1997; 52: 886-94
  • 3 Nissenson AR, Weston RE, Kleeman CR. Mannitol. West J Med 1979; 131: 277-84
  • 4 Shawkat H, Westwood MM, Mortimer A. Mannitol: A review of its clinical uses. Contin Educ Anaesth Crit Care Pain 2012; 12: 82-5
  • 5 WHO. WHO Model Lists of Essential Medicines. WHO; 2015. Available from: http://www.who.int/medicines/publications/essentialmedicines/en/ [Last accessed on 2017 May 06].
  • 6 Song SH, Vieille C. Recent advances in the biological production of mannitol. Appl Microbiol Biotechnol 2009; 84: 55-62
  • 7 Lin SY, Tang SC, Tsai LK, Yeh SJ, Shen LJ, Wu FL. et al. Incidence and risk factors for acute kidney injury following mannitol infusion in patients with acute stroke: A retrospective cohort study. Medicine (Baltimore) 2015; 94: e2032
  • 8 White H, Cook D, Venkatesh B. The use of hypertonic saline for treating intracranial hypertension after traumatic brain injury. Anesth Analg 2006; 102: 1836-46
  • 9 Nomani AZ, Nabi Z, Rashid H, Janjua J, Nomani H, Majeed A. et al. Osmotic nephrosis with mannitol: Review article. Ren Fail 2014; 36: 1169-76
  • 10 Rabetoy GM, Fredericks MR, Hostettler CF. Where the kidney is concerned, how much mannitol is too much?. Ann Pharmacother 1993; 27: 25-8
  • 11 Rudehill A, Lagerkranser M, Lindquist C, Gordon E. Effects of mannitol on blood volume and central hemodynamics in patients undergoing cerebral aneurysm surgery. Anesth Analg 1983; 62: 875-80
  • 12 Coté CJ, Greenhow DE, Marshall BE. The hypotensive response to rapid intravenous administration of hypertonic solutions in man and in the rabbit. Anesthesiology 1979; 50: 30-5
  • 13 Quentin C, Charbonneau S, Moumdjian R, Lallo A, Bouthilier A, Fournier-Gosselin MP. et al. A comparison of two doses of mannitol on brain relaxation during supratentorial brain tumor craniotomy: A randomized trial. Anesth Analg 2013; 116: 862-8
  • 14 Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, Joint Section on Neurotrauma and Critical Care, AANS/CNS. Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF. et al. Guidelines for the management of severe traumatic brain injury. II. Hyperosmolar therapy. J Neurotrauma 2007; 24 Suppl (Suppl. 01) S14-20
  • 15 Fink ME. Osmotherapy for intracranial hypertension: Mannitol versus hypertonic saline. Continuum (Minneap Minn) 2012; 18: 640-54
  • 16 Doi K, Ogawa N, Suzuki E, Noiri E, Fujita T. Mannitol-induced acute renal failure. Am J Med 2003; 115: 593-4
  • 17 Kim MY, Park JH, Kang NR, Jang HR, Lee JE, Huh W. et al. Increased risk of acute kidney injury associated with higher infusion rate of mannitol in patients with intracranial hemorrhage. J Neurosurg 2014; 120: 1340-8
  • 18 Berry AJ, Peterson ML. Hyponatremia after mannitol administration in the presence of renal failure. Anesth Analg 1981; 60: 165-7
  • 19 Tsai SF, Shu KH. Mannitol-induced acute renal failure. Clin Nephrol 2010; 74: 70-3
  • 20 Dziedzic T, Szczudlik A, Klimkowicz A, Rog TM, Slowik A. Is mannitol safe for patients with intracerebral hemorrhages? Renal considerations. Clin Neurol Neurosurg 2003; 105: 87-9
  • 21 Hassan ZU, Kruer JJ, Fuhrman TM. Electrolyte changes during craniotomy caused by administration of hypertonic mannitol. J Clin Anesth 2007; 19: 307-9
  • 22 Fanous AA, Tick RC, Gu EY, Fenstermaker RA. Life-threatening mannitol-induced hyperkalemia in neurosurgical patients. World Neurosurg 2016; 91: 672.e5-9
  • 23 Flynn BC. Hyperkalemic cardiac arrest with hypertonic mannitol infusion: The strong ion difference revisited. Anesth Analg 2007; 104: 225-6
  • 24 Sharma J, Salhotra R. Mannitol-induced intraoperative hyperkalemia, a little-known clinical entity. J Anaesthesiol Clin Pharmacol 2012; 28: 546-7
  • 25 Seto A, Murakami M, Fukuyama H, Niijima K, Aoyama K, Takenaka I. et al. Ventricular tachycardia caused by hyperkalemia after administration of hypertonic mannitol. Anesthesiology 2000; 93: 1359-61
  • 26 Tisherman SA. Mannitol: It is not just for intracranial pressure any more! Maybe. Crit Care Med 2015; 43: 2267-8
  • 27 Ravussin P, Archer DP. The uses of mannitol in neuro-anaesthesia and neuro-intensive care. Eur J Anaesthesiol 2000; 17: 89-91
  • 28 Schrot RJ, Muizelaar JP. Mannitol in acute traumatic brain injury. Lancet 2002; 359: 1633-4
  • 29 Winkler SR, Munoz-Ruiz L. Mechanism of action of mannitol. Surg Neurol 1995; 43: 59
  • 30 Boone MD, Oren-Grinberg A, Robinson TM, Chen CC, Kasper EM. Mannitol or hypertonic saline in the setting of traumatic brain injury: What have we learned?. Surg Neurol Int 2015; 6: 177
  • 31 Hemphill 3rd JC, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M. et al. Guidelines for the management of spontaneous intracerebral hemorrhage: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015; 46: 2032-60
  • 32 Dastur CK, Yu W. Current management of spontaneous intracerebral haemorrhage. Stroke and Vascular Neurology. 2017. (PMID: e000047)
  • 33 Gigliuto CM, Stone KE, Algus M. The use of mannitol in intracerebral bleeds in the medical ICU. N J Med 1991; 88: 48-51
  • 34 Kalita J, Misra UK, Ranjan P, Pradhan PK, Das BK. Effect of mannitol on regional cerebral blood flow in patients with intracerebral hemorrhage. J Neurol Sci 2004; 224: 19-22
  • 35 Misra UK, Kalita J, Ranjan P, Mandal SK. Mannitol in intracerebral hemorrhage: A randomized controlled study. J Neurol Sci 2005; 234: 41-5
  • 36 Wang X, Arima H, Yang J, Zhang S, Wu G, Woodward M. et al. Mannitol and outcome in intracerebral hemorrhage: Propensity score and multivariable intensive blood pressure reduction in acute cerebral hemorrhage trial 2 results. Stroke 2015; 46: 2762-7
  • 37 Shah M, Rasmussen J, Birnbaum L, Moomaw C, Sekar P, Osborne J. et al. Effect of hyperosmolar therapy on outcome following spontaneous intracerebral hemorrhage: The ERICH study (S25.007). Neurology 2014; 82 (Suppl. 10) Suppl S25.007
  • 38 Jauch EC, Saver JL, Adams Jr. HP, Bruno A, Connors JJ, Demaerschalk BM. et al. Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44: 870-947
  • 39 Bereczki D, Mihálka L, Szatmári S, Fekete K, Di Cesar D, Fülesdi B. et al. Mannitol use in acute stroke: Case fatality at 30 days and 1 year. Stroke 2003; 34: 1730-5
  • 40 Videen TO, Zazulia AR, Manno EM, Derdeyn CP, Adams RE, Diringer MN. et al. Mannitol bolus preferentially shrinks non-infarcted brain in patients with ischemic stroke. Neurology 2001; 57: 2120-2
  • 41 Li J, Gelb AW, Flexman AM, Ji F, Meng L. Definition, evaluation, and management of brain relaxation during craniotomy. Br J Anaesth 2016; 116: 759-69
  • 42 Sharma S, Grover VK, Mathew PJ. Mannitol versus hypertonic saline for intra-operative brain relaxation during aneurysm surgery. J Neuroanaesth Crit Care 2015; 2: 23-7
  • 43 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. pii: (PMID: S0967-586831498-9)
  • 44 Wu CT, Chen LC, Kuo CP, Ju DT, Borel CO, Cherng CH. et al. A comparison of 3% hypertonic saline and mannitol for brain relaxation during elective supratentorial brain tumor surgery. Anesth Analg 2010; 110: 903-7
  • 45 Schilte C, Bouzat P, Millet A, Boucheix P, Pernet-Gallay K, Lemasson B. et al. Mannitol improves brain tissue oxygenation in a model of diffuse traumatic brain injury. Crit Care Med 2015; 43: 2212-8
  • 46 Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ. et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2017; 80: 6-15
  • 47 Wakai A, McCabe A, Roberts I, Schierhout G. Mannitol for acute traumatic brain injury. Cochrane Database Syst Rev 2013; 8 DOI: CD001049.
  • 48 Helmy A, Vizcaychipi M, Gupta AK. Traumatic brain injury: Intensive care management. Br J Anaesth 2007; 99: 32-42
  • 49 Li M, Chen T, Chen SD, Cai J, Hu YH. Comparison of equimolar doses of mannitol and hypertonic saline for the treatment of elevated intracranial pressure after traumatic brain injury: A systematic review and meta-analysis. Medicine (Baltimore) 2015; 94: e736
  • 50 Kamel H, Navi BB, Nakagawa K, Hemphill 3rd JC, Ko NU. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: A meta-analysis of randomized clinical trials. Crit Care Med 2011; 39: 554-9
  • 51 Vialet R, Albanèse J, Thomachot L, Antonini F, Bourgouin A, Alliez B. 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: 1683-7
  • 52 Francony G, Fauvage B, Falcon D, Canet C, Dilou H, Lavagne P. et al. Equimolar doses of mannitol and hypertonic saline in the treatment of increased intracranial pressure. Crit Care Med 2008; 36: 795-800
  • 53 Oddo M, Levine JM, Frangos S, Carrera E, Maloney-Wilensky E, Pascual JL. 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: 916-20
  • 54 Cottenceau V, Masson F, Mahamid E, Petit L, Shik V, Sztark F. 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: 2003-12
  • 55 Sakellaridis N, Pavlou E, Karatzas S, Chroni D, Vlachos K, Chatzopoulos K. et al. Comparison of mannitol and hypertonic saline in the treatment of severe brain injuries. J Neurosurg 2011; 114: 545-8
  • 56 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