Abstract
Background
Several studies have demonstrated that magnesium (Mg) plays an important role in the prevention and treatment of central nervous system (CNS) insults. In this study, we tested the effect of intravenous magnesium sulfate (MgSO4) on the outcome of patients with brain tumors who underwent craniotomy. The outcome was defined clinically as the Barthel index score and paraclinically as blood levels of NSE (neuron-specific enloase) and S100Β protein.
Methods
Sixty patients were randomly divided into two groups of 30 patients: the treatment and control groups. In the treatment group, 5 g of MgSO4 in normal saline was infused in 6 h 2 days before surgery, and the same dosage was repeated the day before and during surgery. The control group received placebo. Serum S100Β and NSE concentrations were measured at baseline before administration of magnesium, before surgery, and on the 2nd postoperative day. The Barthel index score was evaluated and registered before surgery, 3, and 6 months after the operation.
Results
The study results showed a significant change in S100Β protein levels before and after surgery (p < 0.05), but we could not find similar results for NSE protein and the Barthel index score. There was a correlation between NSE protein and the Barthel index.
Conclusions
The results of this study revealed that administration of intravenous MgSO4 before and during surgery is safe and effective in reducing S100B protein levels in patients undergoing supratentorial craniotomy for brain tumors. Further studies to elucidate the pathophysiology of brain injuries and role of magnesium are warranted.
Similar content being viewed by others
References
Dhandapani S, Gupta A, Vivekanandhan S, Sharma B, Mahapatra A (2008) Randomized controlled trial of magnesium sulphate in severe closed traumatic brain injury. Indian J Neurotrauma 5:27–33
Kang SW, Choi SK, Park E, Chae SJ, Choi S, Jin Joo H, Lee GJ, Park HK (2011) Neuroprotective effects of magnesium-sulfate on ischemic injury mediated by modulating the release of glutamate and reduced of hyperreperfusion. Brain Res 1371:121–8
McLean RM (1994) Magnesium and its therapeutic uses: a review. Am J Med 96:63–76
Belfort MA, Anthony J, Saade GR, Allen JC Jr, Nimodipine Study G (2003) A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med 348:304–11
Temkin NR, Anderson GD, Winn HR, Ellenbogen RG, Britz GW, Schuster J, Lucas T, Newell DW, Mansfield PN, Machamer JE, Barber J, Dikmen SS (2007) Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial. Lancet Neurol 6:29–38
Cernak I, Savic VJ, Kotur J, Prokic V, Veljovic M, Grbovic D (2000) Characterization of plasma magnesium concentration and oxidative stress following graded traumatic brain injury in humans. J Neurotrauma 17:53–68
McIntosh TK, Faden AI, Yamakami I, Vink R (1988) Magnesium deficiency exacerbates and pretreatment improves outcome following traumatic brain injury in rats: 31P magnetic resonance spectroscopy and behavioral studies. J Neurotrauma 5:17–31
Bareyre FM, Saatman KE, Raghupathi R, McIntosh TK (2000) Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. J Neurotrauma 17:1029–39
Saatman KE, Bareyre FM, Grady MS, McIntosh TK (2001) Acute cytoskeletal alterations and cell death induced by experimental brain injury are attenuated by magnesium treatment and exacerbated by magnesium deficiency. J Neuropathol Exp Neurol 60:183–94
Lamers KJ, Vos P, Verbeek MM, Rosmalen F, van Geel WJ, van Engelen BG (2003) Protein S-100B, neuron-specific enolase (NSE), myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) and blood of neurological patients. Brain Res Bull 61:261–4
Hassan T, Nassar M, Elhadi SM, Radi WK (2012) Effect of magnesium sulfate therapy on patients with aneurysmal subarachnoid hemorrhage using serum S100B protein as a prognostic marker. Neurosurg Rev 35:421–7, discussion 427
Gonzalez-Garcia S, Gonzalez-Quevedo A, Fernandez-Concepcion O, Pena-Sanchez M, Menendez-Sainz C, Hernandez-Diaz Z, Arteche-Prior M, Pando-Cabrera A, Fernandez-Novales C (2012) Short-term prognostic value of serum neuron specific enolase and S100B in acute stroke patients. Clin Biochem 45:1302–7
Gradisek P, Osredkar J, Korsic M, Kremzar B (2012) Multiple indicators model of long-term mortality in traumatic brain injury. Brain Inj 26:1472–81
Hendoui N, Beigmohammadi MT, Mahmoodpoor A, Ahmadi A, Abdollahi M, Hasanpour M, Hadi F, Khazaeipour Z, Mousavi S, Mojtahedzadeh M (2013) Reliability of calcium-binding protein S100B measurement toward optimization of hyperosmolal therapy in traumatic brain injury. Eur Rev Med Pharmacol Sci 17:477–85
Martinez-Morillo E, Garcia Hernandez P, Begcevic I, Kosanam H, Prieto Garcia B, Alvarez Menendez FV, Diamandis EP (2014) Identification of novel biomarkers of brain damage in patients with hemorrhagic stroke by integrating bioinformatics and mass spectrometry-based proteomics. J Proteome Res 13:969–81
Wong GK, Poon WS, Chan MT, Boet R, Gin T, Ng SC, Zee BC, Investigators I (2010) Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage (IMASH): a randomized, double-blinded, placebo-controlled, multicenter phase III trial. Stroke 41:921–6
Apostol A, Apostol R, Ali E, Choi A, Ehsuni N, Hu B, Li L, Altura BT, Altura BM (2010) Cerebral spinal fluid and serum ionized magnesium and calcium levels in preeclamptic women during administration of magnesium sulfate. Fertil Steril 94:276–82
Fuchs-Buder T, Tramer MR, Tassonyi E (1997) Cerebrospinal fluid passage of intravenous magnesium sulfate in neurosurgical patients. J Neurosurg Anesthesiol 9:324–8
Jeremitsky E, Omert L, Dunham CM, Protetch J, Rodriguez A (2003) Harbingers of poor outcome the day after severe brain injury: hypothermia, hypoxia, and hypoperfusion. J Trauma 54:312–9
Manley G, Knudson MM, Morabito D, Damron S, Erickson V, Pitts L (2001) Hypotension, hypoxia, and head injury: frequency, duration, and consequences. Arch Surg 136:1118–23
Xiao G, Wei J, Yan W, Wang W, Lu Z (2008) Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care 12:R61
Livingston DH, Lavery RF, Mosenthal AC, Knudson MM, Lee S, Morabito D, Manley GT, Nathens A, Jurkovich G, Hoyt DB, Coimbra R (2005) Recovery at 1 year following isolated traumatic brain injury: a Western Trauma Association prospective multicenter trial. J Trauma 59:1298–304, discussion 1304
Mehta SS (2010) Biochemical serum markers in head injury: an emphasis on clinical utility. Clin Neurosurg 57:134–40
James ML, Blessing R, Phillips-Bute BG, Bennett E, Laskowitz DT (2009) S100B and brain natriuretic peptide predict functional neurological outcome after intracerebralhaemorrhage. Biomarkers 14:388–94
Wunderlich MT, Lins H, Skalej M, Wallesch CW, Goertler M (2006) Neuron-specific enolase and tau protein as neurobiochemical markers of neuronal damage are related to early clinical course and long-term outcome in acute ischemic stroke. Clin Neurol Neurosurg 108:558–63
Acknowledgments
This research was supported by Tehran University of Medical Sciences with grant no. 92-01-33-21641. The trial received no direct or indirect financial support from the companies named in the study.
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
Comment
Magnesium is an essential electrolyte involved in several basic cellular processes including preservation of membrane integrity, protein synthesis, energy metabolism, maintenance of ionic gradients, and regulation of calcium transport. The neuroprotective effect of magnesium sulfate has been attributed to the noncompetitive NMDA receptor antagonist activity of magnesium. In addition, magnesium modulates the ischemic brain injury cascade at other levels. These include the abilities to inhibit neurotransmitter release and cerebral vasospasm, to antagonize voltage-gated calcium ion channels, and to attenuate production of reactive oxygen species. Results on the use of magnesium sulfate (MgSO4) are however controversial: magnesium administration has been demonstrated to be safe and to improve short-term postoperative neurologic function after cardiac surgery, particularly in preserving short-term memory and cortical control over brainstem functions [1]. On the other hand, even though pilot studies have suggested the possible beneficial effects of MgSO4 infusion in treating patients with aneurysmal subarachnoid hemorrhage (SAH), an up-to-date systematic review and meta-analysis showed that MgSO4 administration does not reduce delayed ischemic deficits or improve neurological outcomes [2]. This same meta-analysis of six eligible studies with 875 patients suggests that a beneficial effect cannot, however, be ruled out because of sample size limitation.
In conclusion, although MgSO4 is a promising neuroprotective drug, studies involving hundreds of patients seem necessary to unequivocally demonstrate its clinical efficacy.
1. Bhudia SK, Cosgrove DM, Naugle RI, Rajeswaran J, Lam BK, Walton E, Petrich J, Palumbo RC, Gillinov AM, Apperson-Hansen C, Blackstone EH (2006) Magnesium as a neuroprotectant in cardiac surgery: a randomized clinical trial. J Thorac Cardiovasc Surg 131:853–861
2. Wong GK, Boet R, Poon WS, Chan MT, Gin T, Ng SC, Zee BC (2011) Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis. Crit Care 15:R52
Alfredo Conti,
Messina, Italy
In this prospective, randomized, double-blind and placebo-controlled study, Mirrahimi and colleagues assessed the effect of intravenous magnesium administration on the functional outcome and other parameters, such as the Barthel index score or duration of hospitalization, in 60 patients undergoing supratentorial brain tumor surgery. They found that the mean arterial pressure, heart rate, bleeding volume, and required dose of propofol were significantly lower in the treatment group.
Even though there are some limitations of the study, also seen by the authors themselves, in my opinion the study design warrants publication, and the results should encourage further studies.
Marcus Reinges
Giessen, Germany
Rights and permissions
About this article
Cite this article
Mirrahimi, B., Mortazavi, A., Nouri, M. et al. Effect of magnesium on functional outcome and paraclinical parameters of patients undergoing supratentorial craniotomy for brain tumors: a randomized controlled trial. Acta Neurochir 157, 985–991 (2015). https://doi.org/10.1007/s00701-015-2376-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00701-015-2376-x