A prospective randomized trial of the optimal dose of mannitol for intraoperative brain relaxation in patients undergoing craniotomy for supratentorial brain tumor resection

Abstract

OBJECTIVE Mannitol is used intraoperatively to induce brain relaxation in patients undergoing supratentorial brain tumor resection. The authors sought to determine the dose of mannitol that provides adequate brain relaxation with the fewest adverse effects. METHODS 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. RESULTS 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. CONCLUSIONS 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 ).

Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on electrolyte and acid‐base variables in dogs with suspected intracranial hypertension

“…22,38 In contrast to our study, people receiving MAN during intracranial tumor resection show prolonged increases in serum potassium concentrations up to 180 minutes postinfusion. However, the administered MAN doses were higher at 1.5 g/kg IV, 38 In the HTS group, plasma ionized calcium concentration did not differ significantly from baseline at any sampling time point, but decreased below RI after HTS administration. In the MAN group, plasma ionized calcium concentration decreased significantly but transiently by T 5 and then increased to concentrations higher than baseline, but this difference was not significant.…”

“…20,22,38 The most commonly cited mechanism for hyperkalemia development is cellular dehydration leading to increased intracellular potassium concentrations with a subsequent increase in passive potassium outflow from the intracellular space down its concentration gradient, and it is likely that it was also the primary mechanism at play in the dogs in our study. 22,38 In contrast to our study, people receiving MAN during intracranial tumor resection show prolonged increases in serum potassium concentrations up to 180 minutes postinfusion. However, the administered MAN doses were higher at 1.5 g/kg IV, 38 In the HTS group, plasma ionized calcium concentration did not differ significantly from baseline at any sampling time point, but decreased below RI after HTS administration.…”

Risk Factors Associated With Inadequate Brain Relaxation in Craniotomy for Surgery of Supratentorial Tumors

“…The incidence of satisfactory brain relaxation (≥3 points) was significantly higher with dosages of 1.0 and 1.5 g/kg than with 0.25 g/kg, but this was not the case with a dosage of 0.5 g/kg. The proportions of satisfactory brain relaxation were 32.3% and 51.6% in the groups receiving 0.25 and 0.5 g/kg of 20% mannitol, respectively [ 18 ].…”

“…One of the principal mechanisms of action of mannitol is the promotion of a reduction in the volume of cerebral cells by creating an osmotic gradient between the interstitial and intravascular compartments [ 13 ]. Research in animals has shown a significant increase in ICP and cortical water content after a reduction in osmolality of 13 mOsm/kg [ 19 ], and it has also been suggested that a significant correlation exists between BRS and serum osmolality after mannitol administration (correlation coefficient: 1.43) [ 18 ]. Thus, the lack of a difference in BRS in our study may be explained by the absence of a significant difference in osmolality between the groups.…”

Drug penetration in pediatric brain tumors: Challenges and opportunities

“…Osmotic BBBD has shown enhanceddelivery of therapeutic agents in other clinical trials 115–117,125,126 . Yet, challenges remain with this method that this is an invasive procedure requiring a multidisciplinary team to perform a complex technique and potential adverse effects can occur as seen in clinical studies are seizures, pulmonary edema, and renal failure 119,126–133 …”