Mannitol for intraoperative brain relaxation [Neurosurgery Wiki]

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====== 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
((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.)).
----
Although [[mannitol]] is widely used to facilitate [[brain retraction]] in cases of [[ruptured aneurysm]]s, there is no consensus about the intraoperative administration of mannitol in the case of unruptured aneurysms. Accordingly, this study was conducted to identify an intraoperative mannitol administration strategy.

Mannitol was routinely administered to patients (n = 90) from January 2015 to April 2016, and not administered to patients (n = 97) from May 2016 to June 2017. The patient groups with and without mannitol administration were then compared based on the patient medical records, radiological data, and digital recordings of the intraoperative microscope.

The patient groups with and without mannitol administration were comparable as regards patient age, number of elderly patients, sex, and aneurysm locations. No between-group difference was identified in terms of the intradural procedural time, retraction-induced cortical injury, postoperative electrolyte imbalance, symptomatic infarction, and postoperative epidural hematomas (EDHs). However, the patient group without mannitol administration showed a significantly lower incidence of chronic subdural hematomas (CSDHs) >50 mL (13.3% vs 3.1%, P = 0.010). Moreover, a multivariate analysis revealed that an advanced age (p = 0.019), male gender (p <0.001), and mannitol administration (p = 0.040) were all statistically significant risk factors for a postoperative CSDH >50 mL following unruptured aneurysm surgery.

Withholding the administration of mannitol during a pterional or modified procedure for unruptured aneurysms was found to reduce the postoperative occurrence of a CSDH without increasing the operative difficulties or other postoperative complications
((Park J, Kwak Y, Kim CH, Lee Y, Choi YJ, Kang DH, Ohk B. Intraoperative
Mannitol Administration Increases the Risk of Postoperative Chronic Subdural
Hemorrhage after Unruptured Aneurysm Surgery. World Neurosurg. 2019 Apr 5. pii:
S1878-8750(19)30977-5. doi: 10.1016/j.wneu.2019.03.296. [Epub ahead of print]
PubMed PMID: 30959258.
)).
----




Some clinicians 
((Wise BL. High-dose mannitol. J Neurosurg. 2004;101:566–567.))
((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.))
advocate high doses (>1.0 g/kg) of mannitol to effectively reduce intracranial pressure, while others recommend lower doses (<1.0 g/kg) 
((Myburgh JA, Lewis SB. Mannitol for resuscitation in acute head injury: effects on cerebral perfusion and osmolality. Crit Care Resusc. 2000;2:14–18))
((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.)).

Treatment [[guideline]]s 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 )
((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.
)).

===== References =====