Comparison of Effects of Intravenous 20% Mannitol versus Combination of 10% Mannitol and 10% Glycerol for Intraoperative Brain Relaxation in Neurosurgery

• Abstract
• Introduction
• Methods
• Statistics
• Results
• Discussion
• Conclusion
• References

Abstract

Background: Pharmacological reduction in intraoperative brain bulk is commonly achieved using mannitol. Other hyperoncotic agents like glycerol are less frequently used due to reported intravascular hemolysis and hyperglycemia. A combination of glycerol 10% and mannitol 10% may limit the adverse effects of both agents. The study's objective was to compare the impact of mannitol 20% and the combination on intraoperative brain relaxation and their adverse effects.

Methods: Sixty adult patients undergoing elective supratentorial tumor removal by craniotomy were randomized to receive either 2.5 mL /kg of 20% mannitol (group M) or 10% mannitol + 10% glycerol (group C). Brain relaxation was assessed on the four-point scale after craniotomy, and hemodynamics, electrolyte, and blood sugar were measured up to 1 hour after infusion.

Results: Seventy-nine percent of patients in group M and 93% in group C had adequate brain relaxation (scale1 and 2; p = 0.108) There was no significant difference in hemodynamic and electrolyte changes. There was a significant increase in blood glucose in group C (mean: 13.1 mg% (standard deviation: 4.4). There was no difference in the length of intensive care unit and hospital stay. None of the patients had hemolysis or clinical evidence of rebound edema. There was no mortality in the groups.

Conclusion: The combination of 10% mannitol and 10% glycerol provides a safe and effective alternative to 20% mannitol for intraoperative reduction in intracranial pressure and reduction in brain bulk for providing suitable conditions for the removal of supratentorial tumors.

Introduction

Pharmacological reduction in intraoperative intracranial volume by producing a shift of intracellular fluid into the intravascular compartment, thus reducing the brain bulk, is commonly achieved using the hyperosmotic agent, mannitol. However, mannitol infusion is associated with several adverse effects like electrolyte disturbances, initial hypervolemia followed by hypovolemia due to diuresis, and renal dysfunction.[1] Though alternatives to mannitol are desirable for intraoperative reduction of intracranial pressure (ICP), the only alternative agent clinically evaluated with a satisfactory outcome is hypertonic saline (HS). Glycerol is a hyperoncotic agent used in acute stroke[2] and encephalitis,[3] with reported adverse effects such as intravascular hemolysis and hyperglycemia.[3] [4] The adverse effects of both mannitol and glycerol are dose-dependent. A combination of 10% glycerol and 10% mannitol may limit the adverse effects of both agents while reducing brain bulk. The combination has been used to manage intracranial hypertension for conditions like stroke and head injury with satisfactory results.[5] However, its use in the intraoperative reduction of ICP has not been evaluated. So, we hypothesize that a combination of 10% mannitol and 10% glycerol is not inferior to 20% mannitol in providing intraoperative brain relaxation while minimizing the adverse effects associated with 20% mannitol.

The study's objective was to compare the effect of equivolemic solutions of 20% mannitol and a combination of 10% mannitol and 10% glycerol in adult patients undergoing elective craniotomy for supratentorial tumors. The primary outcome was a comparison of intraoperative brain relaxation using the four-point scale.[6] The secondary outcome measures were a comparison of electrolyte and blood glucose changes, changes in hemodynamic parameters, adverse events related to mannitol or glycerol, length of intensive care unit stay, and hospital stay.

Methods

After obtaining approval from the institutional ethics committee and informed consent from the patients, 60 adult patients aged between 20 and 60 years, weighing between 40 and 80 kg, belonging to either gender and American Society of Anesthesiologists physical status I and II, scheduled to undergo elective craniotomy under general anesthesia for supratentorial tumors were enrolled for this prospective, randomized double-blinded study. Patients were assigned to two groups using computer-generated randomization: Group M to receive 0.5 gm/kg of 20% mannitol (2.5 mL/kg) and group C to receive an equal volume (2.5 mL/kg) of the containing mixture of 10% mannitol and 10% glycerol solution (Neurotol, Venus Remidies, Haryana, India). Patients undergoing reoperation, urgent surgery, surgery in a position other than supine, patients with anemia (Hb%< 10gm/dL), with preoperative fluid or electrolyte disturbances (signs and symptoms of hypo or hypervolemia, preoperative hyponatremia or hypernatremia (serum Na <130 or >150mEq/L) hypokalemia (serum K+ <3 mEq/L) or hyperkalemia(S. K+ >5mEq/L), prior treatment with any hyperosmotic fluid (mannitol or HS) in the previous 24 hours, history of congestive heart failure or renal or hepatic disease, or patients having diabetes mellitus, patients with Glasgow Coma Scale less than 14, tumors > 6 cm patients with significant midline shift (>2.5mm), and pregnant and lactating patients were excluded from the study. Patients with surgical problems such as injury to major vessels or venous sinuses, requiring temporary vascular clamping, blood loss of more than 1,000 mL, or need for blood transfusion were excluded after initial inclusion.

All patients were anesthetized using the standard general anesthesia technique. It consisted of premedication with fentanyl (2 µg/ kg), induction with propofol (2 mg/kg), and vecuronium (0.1 mg/kg) for tracheal intubation with an appropriate-sized endotracheal tube. Anesthesia was maintained with 50% oxygen, 50% air, and isoflurane 1 minimal alveolar concentration (MAC). Intraoperative muscle relaxation was maintained with vecuronium 0.02 mg/kg as a bolus dose and analgesia with fentanyl 1 µg/kg/h infusion. All patients were monitored using electrocardiogram, pulse oximetry, capnography, invasive blood pressure using radial artery, and central venous pressure (CVP) using basilic vein. Mechanical ventilation was adjusted to maintain end-tidal carbon dioxide between 32 and 35mm Hg and partial pressure of carbon dioxide (PaCO₂) between 35 and 40 mm Hg; intravenous fluids (0.9% normal saline) were administered to maintain CVP at 5 to 10 mm Hg, and blood pressure was maintained within 20% of baseline. Core temperature was maintained using (nasopharyngeal: 36–37° C) forced air warming blankets. An infusion of 2.5 mL/ kg of study solution as per randomization was started at the beginning of the first burr hole and infused over 15 minutes. The labels of both the 100 mL solutions of the study drug were covered to blind the investigator for the study drug. Both surgeon and anesthesiologist were blinded to the nature of the solution infused. Dura was opened 15 minutes after the conclusion of infusion. The surgeon graded brain relaxation upon opening the dura on a four-point scale, 1: perfectly relaxed, 2: satisfactorily relaxed, 3: firm brain, 4: bulging brain over dura.[6] If the brain relaxation scale was three or more on dural opening, hyperventilation to a PaCO₂ of 30 mm Hg was initiated to provide relaxation for surgical access. If the surgeon requested further relaxation, the second bolus of 0.5 gm/kg of 20% mannitol was given. Patients requiring an additional dose of mannitol were excluded from hemodynamic and electrolyte measurement analysis. Patients whose blood glucose exceeded 160 mg/dL were administered insulin to titrate blood glucose between 120 and 160 mg/dL. The following parameters were measured: Hemodynamic variables, including mean arterial pressure, CVP; laboratory data—electrolytes (Na + , K + , CI), blood glucose, and urine output. The baseline data of all the above variables were recorded before administration of the study drug(T0) and 15 minutes (T15), 30 minutes (T30), and 60 minutes (T60) after the completion of infusion of the study drug. Urine was examined for color and free hemoglobin (macroscopic examination) 60 minutes after the study drug infusion. The occurrence of intraoperative brain bulge after craniotomy, which was not explainable by surgical or physiological changes, was noted as rebound edema. Postoperative recovery, length of intensive care unit stay (LOICUS), and hospital stay (LOHS) were noted. Patients who suffered neurological deterioration or required mechanical ventilatory support for more than 6 hours were excluded from LOICUS and LOHS. Postoperative mortality was noted.

Statistics

Sample size and power analysis were performed using power analysis for social studies. The sample size was determined based on the results of the pilot study of 12 patients per group. Sample sizes of 27 in each group achieve 82% power to detect a noninferiority margin difference between the group proportions of 0.15. The control group's proportion of satisfactory brain relaxation was 0.83. The significance level of the test was targeted at 0.05. The actual study had a 98% power to detect a noninferiority margin difference between the group proportions of 0.15, with the actual study group proportion being 0.78 and the treatment group proportion being 0.93.

Statistical analysis was performed using SPSS version 13 (Chicago, Illinois, United States). Data were presented as mean with standard deviation for the continuous variables and median with interquartile range (IQR) for ordered categorical variables. Categorical variables, that is, gender and brain relaxation scale, were presented as frequency and percentage of the occurrence. Appropriate parametric or nonparametric statistics were applied to determine the difference between the two groups based on the data distribution. Categorical data were compared between the groups using the chi-squared test with Fisher's exact test where applicable. Continuous variables distributed normally were compared between the groups using an independent t-test. Analysis of variance compared the change from the baseline within the groups, and post-hoc analysis was performed using the Dunnett test. A p-value less than 0.05 was considered significant for all tests.

Results

Of the total 60 patients enrolled in the study, 2 patients were excluded from the study. Twenty-eight patients who received 20% mannitol (group M) and 30 who received a combination of 10% glycerol and 10% mannitol (group C) were included in the study ([Fig. 1]). The age, gender, location, and lesion pathology were comparable in both groups ([Table 1]).

The median brain relaxation scales noted following craniotomy in group M was 2 (IQR: 1–2) and group C was 2 (IQR: 1.25-2) (p = 0.106). In group M, 75.6% of patients had adequate brain relaxation (scale 1 and 2), 21% had scale 3, and 3.4% had scale 4 relaxation. In group C, 93% had adequate brain relaxation, 7% had scale 3 relaxation, and none with scale 4 ([Fig. 2]). No statistically significant difference between the groups was observed in the scale of brain relaxation (p = 0.108). But the frequency of scale 1 was significantly higher (p = 0.02) in group C. There was no significant difference in the number of patients requiring additional intervention (scale 3 and 4) for brain relaxation (p = 0.138). Three patients in group M and one in group C received a second mannitol bolus (p = 0.28) and were excluded from further analysis of hemodynamic and electrolyte changes.

Twenty-five patients in group M and twenty-nine in group C were analyzed for electrolyte, blood glucose, and hemodynamic changes after the study drug infusion. There was no significant difference in mean arterial blood pressure and CVP between the groups at all measurement periods. There was no significant change in mean arterial pressure (group M p = 0.291, group C p = 0.34 and CVP (group M p = 0.859, group C p = 0.114) from the baseline in both the groups ([Fig. 3A] and [B]). The intravenous fluid administered during this 60 min was comparable. There was no significant difference in urine output ([Table 1]).

In group M, there was no significant change in the serum sodium, potassium, chloride, and blood glucose between pre- and postinfusion. In group C, there was a significant fall in serum sodium after 15 minutes of infusion (p = 0.043) from the baseline and no significant change in serum potassium or chloride after infusion ([Table 2]). There was a substantial increase in blood glucose in group C at 30- and 60-minute postinfusion ([Table 2]), but no blood sugar value exceeded 160 mg% requiring insulin. None of the patients had clinical signs suggestive of intravascular hemolysis, as evidenced by a change in urine color or hemoglobinuria. There was no clinical evidence of rebound cerebral edema. The LOICUS and LOHS were comparable between the groups ([Table 1]). There was no mortality in any of the patients.

Discussion

This study demonstrates that equal volumes of a single bolus of 20% mannitol and a combination of 10% glycerol and 10% mannitol at 2.5 mL/kg provide comparable brain relaxation without affecting hemodynamics or serum electrolytes.

Osmotherapy is essential in reducing brain volume during craniotomy.[7] Each osmotic agent, namely mannitol, glycerol, and HS, has its merits and drawbacks. Intravenous mannitol is commonly used, but in specific neuroanesthesia scenarios, alternatives are needed due to renal dysfunction or long-term use. Although HS is a well-studied alternative in the neurointensive care unit[8] and during surgery,[9] [10] [11] it has its limitations, such as elevated serum sodium levels,[12] and the risk of hyperchloremic metabolic acidosis and demyelination in hyponatremic patients.[12] [13] Despite being widely used by neurologists, the combination of mannitol and glycerol is not widely adopted in neuroanesthesia. Our study was designed to evaluate its impact on intraoperative brain relaxation during craniotomy.

Glycerol is a potent osmotic dehydrating agent with added effects on brain metabolism. It decreases ICP in numerous disease states, including head trauma,[14] stroke,[2] [15] encephalitis,[16] [17] meningitis,[18] and Reye's syndrome.[3] Intravenous glycerol is a safe alternative to mannitol for reducing cerebral edema.[10] [19] It may also improve short-term survival in ischemic stroke patients and has a longer therapeutic effect than mannitol.[2] Our study fills a gap by providing data on the use of intravenous glycerol during intraoperative craniotomy. In contrast to previous studies like Patil and Gupta's,[20] which focused on traumatic brain injury with elevated ICP, our goal was to optimize conditions for patients without significant ICP elevation. Patil and Gupta suggested HS as superior, but methodological limitations exist in their study. We observed a significantly higher proportion of patients achieving scale 1 brain relaxation with the mannitol–glycerol combination in our study, though no significant overall difference in brain bulge assessment or the need for an additional osmotic agent was noted.

There is a correlation between an increased serum osmolality and a decrease in ICP and brain water content.⁸ Though our study did not measure serum osmolality, the solution's osmolarity with a combination of 10% mannitol and 10% glycerol (osmolarity: 1, 635 mOsm/L) was higher than 20% mannitol (osmolarity: 1,098 mOsm/L). Concerns associated with osmotherapy, such as a rebound increase in ICP after drug withdrawal, electrolyte disturbances, and side effects related to renal and pulmonary failure,[10] were not evident in our patients. Notably, none of our patients experienced brain swelling or symptoms indicative of rebound ICP. While electrolyte disturbances have been reported with mannitol,[21] [22] [23] they were less pronounced with glycerol.[24] Importantly, no significant changes in serum electrolyte levels were observed in both groups when administered at a dose of 2.5 mL/kg in our study. Additionally, while mannitol does not interfere with glucose metabolism, glycerol impacts glucose metabolism,[25] resulting in elevated blood glucose levels in the given dose. However, none of the patients required intervention for hyperglycemia. It is important to consider the implications of this glucose increase, especially for diabetic patients.

The effect of a mannitol bolus on systemic arterial pressure can vary, resulting in a short but significant increase in pulse pressure and mean arterial blood pressure or a transient decrease in blood pressure, particularly in patients with relative volume depletion.[26] The rapid plasma volume expansion associated with mannitol use may precipitate congestive heart failure in patients with compromised cardiac or renal function. Glycerol-induced hemodynamic disturbances are fewer when compared to mannitol. In our study, patients remained hemodynamically stable following infusions of both mannitol and the mannitol–glycerol combination, attributable to the lower dose and slower rate of administration of these osmotic agents. Notably, rapid infusion of higher doses of glycerol has previously been associated with transient intravascular hemolysis.[3] However, in our study, there was no evidence of hemolysis when administering a combination of 10% mannitol and 10% glycerol at the specified dose.

Given that mannitol is primarily filtered through the kidneys and has a prolonged elimination from serum, especially in patients with renal insufficiency, it carries a risk of accumulation. In contrast, glycerol undergoes hepatic metabolism and is less likely to accumulate in patients with renal insufficiency. Since glycerol does not rely on renal excretion, adding it to mannitol can reduce the load of mannitol in patients with impaired renal function, reducing the potential for circulatory overload postmannitol administration. Importantly, our study found no statistically significant difference in urine output between the two groups.

The adverse effects of both mannitol and glycerol are dose and rate of administration-dependent, with glycerol generally exhibiting fewer side effects.[3] While it is reasonable to presume that the combination of mannitol and glycerol could help mitigate the adverse effects associated with each individual drug, our study did not directly address the benefits of this combination over individual drugs.

In addition to reducing ICP, glycerol offers neuroprotection through mechanisms such as the dilation of pial arterioles via nitric oxide release, stimulation of ATP-sensitive potassium (K ATP) channels, and prevention of microvascular alterations resulting from ischemia. Furthermore, glycerol increases cerebral blood flow to ischemic regions of the brain and provides an alternative energy source for compromised cerebral metabolism during hypoxic–ischemic states.[25]

Our study primarily focused on intraoperative outcomes, where we found no statistically significant differences in the length of ICU or hospital stays or in-hospital mortality. However, it is essential to acknowledge that long-term mortality, long-term outcomes, and quality of life are influenced by numerous factors beyond the scope of this study.

Several limitations should be considered when interpreting our findings. CVP measurements from the basilic vein may be less precise than those from the superior vena cava. Additionally, equal volumes of agents were employed in the study, and direct serum osmolarity measurements following drug administration were not conducted. Our primary outcome measure focused on brain relaxation, and while theoretically, the combination solution may result in fewer morbidities, our study lacked sufficient power to comprehensively assess morbidity related to the study drugs.

Conclusion

20% mannitol (2.5mL/kg) and a mixture of 10% mannitol and 10% glycerol 10% (2.5 mL/kg) provide comparable intraoperative brain relaxation during elective craniotomy without significant adverse hemodynamic or electrolyte abnormalities This suggests that the combination of 10% mannitol and 10% glycerol provides a safe and effective alternative to 20% mannitol for creating optimal conditions during the removal of supratentorial tumors.

Conflict of Interest

None declared.

• References

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• 14 Nara I, Shiogai T, Hara M, Saito I. Comparative effects of hypothermia, barbiturate, and osmotherapy for cerebral oxygen metabolism, intracranial pressure, and cerebral perfusion pressure in patients with severe head injury. Acta Neurochir Suppl (Wien) 1998; 71: 22-26
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  PubMedSearch in Google Scholar
• 21 Rozet I, Tontisirin N, Muangman S. et al. Effect of equiosmolar solutions of mannitol versus hypertonic saline on intraoperative brain relaxation and electrolyte balance. Anesthesiology 2007; 107 (05) 697-704
  CrossrefPubMedSearch in Google Scholar
• 22 Hassan ZU, Kruer JJ, Fuhrman TM. Electrolyte changes during craniotomy caused by administration of hypertonic mannitol. J Clin Anesth 2007; 19 (04) 307-309
  PubMedSearch in Google Scholar
• 23 Hirota K, Hara T, Hosoi S, Sasaki Y, Hara Y, Adachi T. Two cases of hyperkalemia after administration of hypertonic mannitol during craniotomy. J Anesth 2005; 19 (01) 75-77
  PubMedSearch in Google Scholar
• 24 Reinglass JL. Dose response curve of intravenous glycerol in the treatment of cerebral edema due to trauma. A case report. Neurology 1974; 24 (08) 743-747
  PubMedSearch in Google Scholar
• 25 Meyer JS, Itoh Y, Okamoto S. et al. Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction. Circulation 1975; 51 (04) 701-712
  PubMedSearch in Google Scholar
• 26 Sabharwal N, Rao GS, Ali Z, Radhakrishnan M. Hemodynamic changes after administration of mannitol measured by a noninvasive cardiac output monitor. J Neurosurg Anesthesiol 2009; 21 (03) 248-252
  CrossrefPubMedSearch in Google Scholar

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Article published online:
25 April 2025

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• References

• 1 Grande PO, Romner B. Osmotherapy in brain edema: a questionable therapy. J Neurosurg Anesthesiol 2012; 24 (04) 407-412
  PubMedSearch in Google Scholar
• 2 Righetti E, Celani MG, Cantisani T, Sterzi R, Boysen G, Ricci S. Glycerol for acute stroke. Review Cochrane Database Syst Rev 2004; 2004 (02) CD000096
  PubMedSearch in Google Scholar
• 3 MacDonald JT, Uden DL. Intravenous glycerol and mannitol therapy in children with intracranial hypertension. Neurology 1982; 32 (04) 437-440
  PubMedSearch in Google Scholar
• 4 Nau R. Osmotherapy for elevated intracranial pressure: a critical reappraisal. Clin Pharmacokinet 2000; 38 (01) 23-40
  CrossrefPubMedSearch in Google Scholar
• 5 Shankar A. Clinical efficacy of mannitol (10%) with glycerine (10%) versus mannitol (20%) in cerebral oedema. J Neurol Stroke 2019; 9 (04) 222-227
  PubMedSearch in Google Scholar
• 6 Li J, Gelb AW, Flexman AM, Ji F, Meng L. Definition, evaluation, and management of brain relaxation during craniotomy. Br J Anaesth 2016; 116 (06) 759-769
  CrossrefPubMedSearch in Google Scholar
• 7 Paczynski RP. Osmotherapy. Basic concepts and controversies. Crit Care Clin 1997; 13 (01) 105-129
  PubMedSearch in Google Scholar
• 8 Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med 2000; 28 (09) 3301-3313
  CrossrefPubMedSearch in Google Scholar
• 9 Harutjunyan L, Holz C, Rieger A, Menzel M, Grond S, Soukup J. Efficiency of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 versus mannitol 15% in the treatment of increased intracranial pressure in neurosurgical patients - a randomized clinical trial [ISRCTN62699180]. [ISRCTN62699180] Crit Care 2005; 9 (05) R530-R540
  CrossrefPubMedSearch in Google Scholar
• 10 Wang J, Ren Y, Wang SF. et al. Comparative efficacy and safety of glycerol versus mannitol in patients with cerebral oedema and elevated intracranial pressure: a systematic review and meta-analysis. J Clin Pharm Ther 2021; 46 (02) 504-514
  PubMedSearch in Google Scholar
• 11 Pasarikovski CR, Alotaibi NM, Al-Mufti F, Macdonald RL. Hypertonic saline for increased intracranial pressure after aneurysmal subarachnoid hemorrhage: a systematic review. World Neurosurg 2017; 105: 1-6
  PubMedSearch in Google Scholar
• 12 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 (01) 117314
  PubMedSearch in Google Scholar
• 13 Freeman N, Welbourne J. Osmotherapy: science and evidence-based practice. BJA Educ 2018; 18 (09) 284-290
  CrossrefPubMedSearch in Google Scholar
• 14 Nara I, Shiogai T, Hara M, Saito I. Comparative effects of hypothermia, barbiturate, and osmotherapy for cerebral oxygen metabolism, intracranial pressure, and cerebral perfusion pressure in patients with severe head injury. Acta Neurochir Suppl (Wien) 1998; 71: 22-26
  PubMedSearch in Google Scholar
• 15 Yu YL, Kumana CR, Lauder IJ. et al. Treatment of acute cerebral hemorrhage with intravenous glycerol. A double-blind, placebo-controlled, randomized trial. Stroke 1992; 23 (07) 967-971
  PubMedSearch in Google Scholar
• 16 Singhi S, Järvinen A, Peltola H. Increase in serum osmolality is possible mechanism for the beneficial effects of glycerol in childhood bacterial meningitis. Pediatr Infect Dis J 2008; 27 (10) 892-896
  PubMedSearch in Google Scholar
• 17 Gwer S, Gatakaa H, Mwai L, Idro R, Newton CR. The role for osmotic agents in children with acute encephalopathies: a systematic review. BMC Pediatr 2010; 10: 23
  PubMedSearch in Google Scholar
• 18 Wall EC, Ajdukiewicz KM, Heyderman RS, Garner P. Osmotic therapies added to antibiotics for acute bacterial meningitis. Cochrane Database Syst Rev 2013; 3 (03) CD008806
  PubMedSearch in Google Scholar
• 19 Biestro A, Alberti R, Galli R. et al. Osmotherapy for increased intracranial pressure: comparison between mannitol and glycerol. Acta Neurochir (Wien) 1997; 139 (08) 725-732 , discussion 732–733
  PubMedSearch in Google Scholar
• 20 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-e228
  PubMedSearch in Google Scholar
• 21 Rozet I, Tontisirin N, Muangman S. et al. Effect of equiosmolar solutions of mannitol versus hypertonic saline on intraoperative brain relaxation and electrolyte balance. Anesthesiology 2007; 107 (05) 697-704
  CrossrefPubMedSearch in Google Scholar
• 22 Hassan ZU, Kruer JJ, Fuhrman TM. Electrolyte changes during craniotomy caused by administration of hypertonic mannitol. J Clin Anesth 2007; 19 (04) 307-309
  PubMedSearch in Google Scholar
• 23 Hirota K, Hara T, Hosoi S, Sasaki Y, Hara Y, Adachi T. Two cases of hyperkalemia after administration of hypertonic mannitol during craniotomy. J Anesth 2005; 19 (01) 75-77
  PubMedSearch in Google Scholar
• 24 Reinglass JL. Dose response curve of intravenous glycerol in the treatment of cerebral edema due to trauma. A case report. Neurology 1974; 24 (08) 743-747
  PubMedSearch in Google Scholar
• 25 Meyer JS, Itoh Y, Okamoto S. et al. Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction. Circulation 1975; 51 (04) 701-712
  PubMedSearch in Google Scholar
• 26 Sabharwal N, Rao GS, Ali Z, Radhakrishnan M. Hemodynamic changes after administration of mannitol measured by a noninvasive cardiac output monitor. J Neurosurg Anesthesiol 2009; 21 (03) 248-252
  CrossrefPubMedSearch in Google Scholar