Mannitol for intraoperative brain relaxation

The risk of brain edema after dural opening is high in patients with midline shift undergoing supratentorial tumor surgery. Brain swelling may result in intracranial hypertension, impeded tumor exposure, and adverse outcomes. Mannitol is recommended as a first-line dehydration treatment to reduce brain edema and enable brain relaxation during neurosurgery. Research has indicated that mannitol enhanced brain relaxation in patients undergoing supratentorial tumor surgery; however, these results need further confirmation, and the optimal mannitol dose has not yet been established 1).

Some clinicians 2) 3) advocate high doses (>1.0 g/kg) of mannitol to effectively reduce intracranial pressure, while others recommend lower doses (<1.0 g/kg) 4) 5).

Treatment guidelines for using mannitol in patients with traumatic brain injury and stroke have been published and provide recommendations regarding the dose and timing of mannitol. However, there is still controversy concerning dehydration treatment with mannitol in patients with preoperatively increased intracranial pressure during brain tumor surgery.


Seo et al. sought to determine the dose of mannitol that provides adequate brain relaxation with the fewest adverse effects.

A total of 124 patients were randomized to receive mannitol at 0.25 g/kg (Group A), 0.5 g/kg (Group B), 1.0 g/kg (Group C), and 1.5 g/kg (Group D). The degree of brain relaxation was classified according to a 4-point scale (1, bulging; 2, firm; 3, adequate; and 4, perfectly relaxed) by neurosurgeons; Classes 3 and 4 were considered to indicate satisfactory brain relaxation. The osmolality gap (OG) and serum electrolytes were measured before and after mannitol administration.

The brain relaxation score showed an increasing trend in patients receiving higher doses of mannitol (p = 0.005). The incidence of satisfactory brain relaxation was higher in Groups C and D than in Group A (67.7% and 64.5% vs 32.2%, p = 0.011 and 0.022, respectively). The incidence of OG greater than 10 mOsm/kg was also higher in Groups C and D than in Group A (100.0% in both groups vs 77.4%, p = 0.011 for both). The incidence of moderate hyponatremia (125 mmol/L ≤ Na+ < 130 mmol/L) was significantly higher in Group D than in other groups (38.7% vs 0.0%, 9.7%, and 12.9% in Groups A, B, and C; p < 0.001, p = 0.008, and p = 0.020, respectively). Hyperkalemia (K+ > 5.0 mmol/L) was observed in 12.9% of patients in Group D only.

The higher doses of mannitol provided better brain relaxation but were associated with more adverse effects. Considering the balance between the benefits and risks of mannitol, the authors suggest the use of 1.0 g/kg of intraoperative mannitol for satisfactory brain relaxation with the fewest adverse effects. Clinical trial registration no.: NCT02168075 ( clinicaltrials.gov ) 6).

1)

Peng Y, Liu X, Wang A, Han R. The effect of mannitol on intraoperative brain relaxation in patients undergoing supratentorial tumor surgery: study protocol for a randomized controlled trial. Trials. 2014 May 10;15:165. doi: 10.1186/1745-6215-15-165. PubMed PMID: 24884731; PubMed Central PMCID: PMC4018619.
2)

Wise BL. High-dose mannitol. J Neurosurg. 2004;101:566–567.
3)

Cruz J, Minoja G, Okuchi K, Facco E. Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial. J Neurosurg. 2004 Mar;100(3):376-83. PubMed PMID: 15035271.
4)

Myburgh JA, Lewis SB. Mannitol for resuscitation in acute head injury: effects on cerebral perfusion and osmolality. Crit Care Resusc. 2000;2:14–18
5)

Sorani MD, Morabito D, Rosenthal G, Giacomini KM, Manley GT. Characterizing the dose–response relationship between mannitol and intracranial pressure in traumatic brain injury patients using a high-frequency physiological data collection system. J Neurotrauma. 2008;25:291–298. doi: 10.1089/neu.2007.0411.
6)

Seo H, Kim E, Jung H, Lim YJ, Kim JW, Park CK, Se YB, Jeon YT, Hwang JW, Park HP. A prospective randomized trial of the optimal dose of mannitol for intraoperative brain relaxation in patients undergoing craniotomy for supratentorial brain tumor resection. J Neurosurg. 2017 Jun;126(6):1839-1846. doi: 10.3171/2016.6.JNS16537. Epub 2016 Aug 19. PubMed PMID: 27540904.

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