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 Table of Contents  
REVIEW
Year : 2020  |  Volume : 10  |  Issue : 1  |  Page : 50-53

Potential rules of anesthetic gases on glioma


Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China

Date of Submission08-Aug-2019
Date of Decision12-Aug-2019
Date of Acceptance12-Sep-2019
Date of Web Publication13-Mar-2020

Correspondence Address:
Jiang Wu
Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province
China
Zheng-Quan Yu
Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2045-9912.279984

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  Abstract 


Glioma is one of the most frequent primary brain tumors. Currently, the most common therapeutic strategy for patients with glioma is surgical resection combined with radiotherapy or/and adjuvant chemotherapy. However, due to the metastatic and invasive nature of glioma cells, the recurrence rate is high, resulting in poor prognosis. In recent years, gas therapy has become an emerging treatment. Studies have shown that the proliferation, metastasis and invasiveness of glioma cells exposed to anesthetic gases are obviously inhibited. Therefore, anesthetic gas may play a special therapeutic role in gliomas. In this review, we aim to collect existing research and summarize the rules of using anesthetic gases on glioma, providing potential strategies for further clinical treatment.

Keywords: anesthetic gases; glioma; invasion; isoflurane; metastasis; proliferation; sevoflurane


How to cite this article:
Chen X, Mao YG, Yu ZQ, Wu J, Chen G. Potential rules of anesthetic gases on glioma. Med Gas Res 2020;10:50-3

How to cite this URL:
Chen X, Mao YG, Yu ZQ, Wu J, Chen G. Potential rules of anesthetic gases on glioma. Med Gas Res [serial online] 2020 [cited 2020 Apr 8];10:50-3. Available from: http://www.medgasres.com/text.asp?2020/10/1/50/279984

Xiao Chen, Yi-Guang Mao These authors contributed equally to this work.





  Introduction Top


Tumors derived from neuroepithelial cell are collectively referred to glioma, which account for 50% to 60% of the primary central nervous system tumors and is the most common intracranial malignancies.[1] In terms of current treatment methods, surgical treatment is the primary treatment for patients with glioma. Although most postoperative patients receive follow-up radiotherapy and chemotherapy, the recurrence rate is still high and the prognosis is poor.[2],[3]

At present, gas gradually shows its enormous therapeutic potential in nervous system,[4],[5] cardiovascular diseases[6] and cancers.[7] Anesthetic gases are administered as the primary therapy for sedation in the perioperative setting and critical care. Compared with current intravenous sedation agents, anesthetic gases-induced sedation may provide superior awakening and extubation times. Although they have been widely used, the mechanism by which they induce and maintain anesthesia has not been clarified. On the one hand, they can reduce presynaptic excitation and neurotransmitter release through inhibition of sodium (Na+) and several isoforms of calcium (Ca2+) voltage-gated channels; on the other hand, they also reduce neurotransmitter activity in the postsynaptic membrane by γ-aminobutyric acid, glycine, nicotinic acetylcholine, serotonin type 3, glutamate, N-methyl-D-aspartate, and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid receptors.[8],[9]

Numerous studies have found that anesthetic gases may influence tumor recurrence, metastasis, and long-term survival.[10],[11] Due to the high degree of malignancy and recurrence rate of glioma, the application of anesthetics in glioma has also received more and more attention. In this article, we intend to summarize the previous studies and explain the effects of anesthetic gases on glioma, providing evidence for future gas therapy.

At present, sevoflurane and isoflurane are the two commonly used anesthetic gases in clinic. Due to research and space limitations, we only discuss the above two anesthetic gases in this review.


  Search Strategy Top


PubMed database was searched up to May 2019. The term “anesthetics” (including anesthetic gases, sevoflurane, or isoflurane) as a medical subject heading (MeSH) and key word, was combined with the term “glioma” as a medical subject heading (MeSH) and key word.


  Anesthetics Gases Top


Sevoflurane

Sevoflurane, a volatile anesthetic, is used to induce and maintain general anesthesia for outpatients and inpatients.[12] It has stable physical properties, rapid induction and minimal inhibitory effects on circulation. After being applied in more and more research, its special effects on cancer and tumors are discovered. For instance, it is well known that sevoflurane can play a protection for the lungs during surgery, and can also reduce the metastasis of cancer cells caused by surgery by promoting apoptosis of A549 cells (the human pulmonary adenocarcinoma cell line).[10] Fan et al.[13] have found that sevoflurane can reduce the metastasis and invasion of colorectal cancer cells.

Isoflurane

Isoflurane, a structural isomer to enflurane, is also a commonly used volatile anesthetic. But unlike enflurane, isoflurane carries a strong pungent odor that makes it difficult to use for inhalational induction of general anesthesia.[14] In addition to inducing anesthesia, isoflurane also shows the function of protecting organs from damage in hypoxic ischemic brain injury and myocardial ischemia-reperfusion injury.[15],[16] The study has found that isoflurane can inhibit the expression of phosphatidylinositol 3-kinase and protein kinase B (AKT) and reduce the activity of nuclear factor kappa-B to inhibit the metastasis and invasion of liver cancer cells, and also can induce caspase 3 activation in cancer cells to induce apoptosis.[17] In addition, it also has a role in soft nest cancer[18] and lupus nephritis.[19]


  Experimental Studies of Anesthetics Gases in Glioma Top


It is well known that a treatment must be verified by large number of basic experiments before being applied to clinic. However, different studies may show different results. We collect several experiments related to gliomas and anesthetic gases and summarize the outcomes in this article [Table 1]. Yi et al.[20] found that after sevoflurane treatment, the migration and invasion abilities of glioma cells were significantly reduced,[17] with increasing concentration. In another study, sevoflurane was found to inhibit the matrix metalloproteinase-2 (MMP-2) activity in glioma cells and reduced their metastasis and invasion.[21] Meuth et al.[22] and O’Leary et al.[23] found that isoflurane could promote the death of glioma cells. By comparing the effects of isoflurane, enflurane and sevoflurane on glioma cells, isoflurane is found to have the best anti-proliferative effect on C6 glioma, while sevoflurane has the worst. In addition to inhibition, some studies have the opposite conclusion. Shi et al.[24] found that sevoflurane promoted the production of hypoxia-inducible factors in a concentration-dependent manner and up-regulated the level of p-AKT, thereby promoting the proliferation of glioma stem cells. The same was true for isoflurane that exposure to isoflurane could promote the proliferation, survival and migration distance of human glioblastoma stem cells.[25] These conflicting results may be attributable to the heterogeneity of responses to the anesthetics gases depending on cell type, concentration, duration of exposure, or all.
Table 1: The effects of aesthetic gases in glioma

Click here to view



  Clinical Applications Top


Currently, most studies are limited to cellular levels. Although rats were used in one study, the anesthetic gas was not directly applied to rats with glioma.[25] Instead, the glioma cells were pretreated with anesthetic gas and injected into the right striatum to quantify the migratory potential capacity of cells in vivo. The results showed that the migration ability of glioma stem cells pre-exposed to 1.2% isoflurane was significantly enhanced. In addition to ethical reasons, one important reason is that the research is not yet mature. First, there are many types of gliomas, and the characteristics of each are different. Therefore, different anesthetic gases may have different effects on different types of tumors. Secondly, the gas concentration, exposure time and adverse reactions are difficult to control. Therefore, further relevant research is needed.


  Mechanisms of Anesthetics Gases in Glioma Top


Metastasis and invasion are main causes of poor prognosis and relapse in patients suffering from glioma, and are receiving more and more attention in scientific and clinical research.[26],[27] Anesthetics gases show an effective inhibitory effect on the survival, metastasis and invasion of glioma cells. However, due to the complexity of the processes, the molecular mechanisms have not been fully elucidated.

MicroRNAs (miRNAs) are a class of small noncoding RNAs with 21–25 nucleotides, which regulate the target gene expression by repressing translation or regulating mRNA degradation via binding to the 3′ untranslated region of their target genes.[28] They have important impacts on the progression of proliferation, migration and invasion.[29],[30],[31] A large number of studies have found that the effect of anesthetic gases on cancer cells is related to miRNAs.[13],[32] And the same is true for gliomas. MiR-637 is considered to be an inhibitor of hepatocellular carcinoma and pancreatic cancer.[33] AKT is a target protein of miR-637, and AKT phosphorylation may promote tumor development and progression.[34] Compared to normal brain tissue, the level of miR-637 in glioma cells is low, and the combination of miR-637 and AKT is reduced in gliomas.[35] After treatment with sevoflurane, miR-637 is significantly up-regulated, and the expression and activity of AKT are also inhibited.[20] At the same time, metastasis and invasion of glioma cells are also inhibited. Emerging evidence has suggested that the pathogenesis of anesthetic gases on cancer cells is related to a group of miRNAs, not individual. Therefore, there may be more miRNAs involved.

Besides AKT, considerable evidence suggests that MMP-2 plays an important role in the metastasis and invasion of glioma cells.[36] In addition, MMP-2 is involved in the degradation of the blood-brain barrier, which will cause hematogenous metastases of cancer cells to form new cancer foci that cannot be distinguished by naked eye.[37] Therefore, the high expression of MMP-2 is an indication of poor prognosis. Moreover, there is also a close relationship between MMP-2 and AKT in gliomas.[38] Many substances can upregulate the expressions of MMP-2 through AKT signaling pathway in gliomas.[39] However, whether sevoflurane can affect the expression of MMP-2 through the AKT pathway needs further verification.

In addition to targeting proteins, anesthetic gases can also act on glioma cells by inhibiting the channel.[40] It is well known that ion channels are also involved in the migration and proliferation of tumor cells.[41] So they have been identified as promising therapeutic targets of brain tumor. One of the most important glioma-related channels is Ca2+-activated K+ channels, being overexpressed in glioma patients.[42],[43] Currently, there are some drugs targeting this channel for the treatment of gliomas. For example, Oxaliplatin, a third-generation organoplatinum, can suppress the amplitude of glioma cell K+ currents by inhibiting Ca2+-activated K+ channels, thereby affecting cell activity.

The above mechanism is mainly to explain the beneficial aspects of anesthetic gases, while one study has found that anesthetic gas can stimulate the proliferation of glial stem cells by up-regulating the expression of AKT.[24],[25] And in addition to glioma, the effect on other tumors is not consistent. Therefore, the mechanism of anesthetic gases on glioma requires more types, more rigorous and more detailed research.


  Conclusion Top


Although anesthetic gases have been used for decades, most of them are used as anesthesia inducers. So far, most of the experiments on gliomas are limited to the cell stage, and the application to the living body has not been reported. Anesthetics may have side effects on brain function due to its toxicity.[44],[45],[46] For example, it may cause apoptosis of normal nerve cells and affect the learning and behavior of humans and animals.[14] Therefore, there are still great challenges in the application of living organisms. As far as current research is concerned, different anesthetic gases have different effects on different types of glioma cells.

Moreover, there is also no consensus on the optimal concentration of the application. Clinically, the choice of anesthetic dose is based on the minimum alveolar concentration. It is defined as the concentration of inhaled anesthetic within the alveoli at which 50% of people do not move in response to a surgical stimulus. Many variables can alter minimum alveolar concentration, such as age, temperature and pregnancy.[47],[48],[49] Therefore, the minimum alveolar concentration should be monitored and adjusted to the appropriate range during sedation. Since most of the current studies are still limited to the cellular level rather than the living body, a fixed concentration is given, which leads to differences in the dose of intervention and application in clinic.

Therefore, whether in vitro or in vivo, research will continue. Through the above introduction, anesthetic gas may become an emerging treatment of glioma. Although there are still many questions and problems at present, one day it will come to a conclusion.

Author contributions

Manuscript writing: XC; manuscript revision: YGM; review design: ZQY, JW, GC. All the authors read and approved the final version of the manuscript for publication.

Conflicts of interest

The authors have no conflicts of interest to declare.

Financial support

None.

Copyright license agreement

The Copyright License Agreement has been signed by all authors before publication.

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Checked twice by iThenticate.

Peer review

Externally peer reviewed.

Open access statement

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.



 
  References Top

1.
Chen X, Yang F, Zhang T, et al. MiR-9 promotes tumorigenesis and angiogenesis and is activated by MYC and OCT4 in human glioma. J Exp Clin Cancer Res. 2019;38:99-99.  Back to cited text no. 1
    
2.
Wang PG, Li YT, Pan Y, et al. Lower expression of Bax predicts poor clinical outcome in patients with glioma after curative resection and radiotherapy/chemotherapy. J Neurooncol. 2019;141:71-81.  Back to cited text no. 2
    
3.
Xue L, Lu B, Gao B, et al. NLRP3 promotes glioma cell proliferation and invasion via the interleukin-1β/NF-κB p65 signals. Oncol Res. 2019;27:557-564.  Back to cited text no. 3
    
4.
Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AMG. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci. 2007;8:766-775.  Back to cited text no. 4
    
5.
Zhang X, Bian JS. Hydrogen sulfide: a neuromodulator and neuroprotectant in the central nervous system. ACS Chem Neurosci. 2014;5:876-883.  Back to cited text no. 5
    
6.
Farah C, Michel LYM, Balligand JL. Nitric oxide signalling in cardiovascular health and disease. Nat Rev Cardiol. 2018;15:292-316.  Back to cited text no. 6
    
7.
He Q. Precision gas therapy using intelligent nanomedicine. Biomater Sci. 2017;5:2226-2230.  Back to cited text no. 7
    
8.
Jerath A, Parotto M, Wasowicz M, Ferguson ND. Volatile anesthetics. Is a new player emerging in critical care sedation? Am J Respir Crit Care Med. 2016;193:1202-1212.  Back to cited text no. 8
    
9.
Edgington TL, Maani CV. Sevoflurane. StatPearls. Treasure Island: StatPearls Publishing; 2019.  Back to cited text no. 9
    
10.
Wang L, Wang T, Gu JQ, Su HB. Volatile anesthetic sevoflurane suppresses lung cancer cells and miRNA interference in lung cancer cells. Onco Targets Ther. 2018;11:5689-5693.  Back to cited text no. 10
    
11.
Jose C, Hebert-Chatelain E, Dias Amoedo N, et al. Redox mechanism of levobupivacaine cytostatic effect on human prostate cancer cells. Redox Biol. 2018;18:33-42.  Back to cited text no. 11
    
12.
Brioni JD, Varughese S, Ahmed R, Bein B. A clinical review of inhalation anesthesia with sevoflurane: from early research to emerging topics. J Anesth. 2017;31:764-778.  Back to cited text no. 12
    
13.
Fan L, Wu Y, Wang J, He J, Han X. Sevoflurane inhibits the migration and invasion of colorectal cancer cells through regulating ERK/MMP-9 pathway by up-regulating miR-203. Eur J Pharmacol. 2019;850:43-52.  Back to cited text no. 13
    
14.
Hawkley TF, Maani CV. Isoflurane. StatPearls. Treasure Island: StatPearls Publishing. 2019.  Back to cited text no. 14
    
15.
Burchell SR, Dixon BJ, Tang J, Zhang JH. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury. J Investig Med. 2013;61:1078-1083.  Back to cited text no. 15
    
16.
Lang XE, Wang X, Jin JH. Mechanisms of cardioprotection by isoflurane against I/R injury. Front Biosci (Landmark Ed). 2013;18:387-393.  Back to cited text no. 16
    
17.
Hu J, Hu J, Jiao H, Li Q. Anesthetic effects of isoflurane and the molecular mechanism underlying isoflurane inhibited aggressiveness of hepatic carcinoma. Mol Med Rep. 2018;18:184-192.  Back to cited text no. 17
    
18.
Guo NL, Zhang JX, Wu JP, Xu YH. Isoflurane promotes glucose metabolism through up-regulation of miR-21 and suppresses mitochondrial oxidative phosphorylation in ovarian cancer cells. Biosci Rep. 2017;37:BSR20170818.  Back to cited text no. 18
    
19.
Yuan Y, Liu Z. Isoflurane attenuates murine lupus nephritis by inhibiting NLRP3 inflammasome activation. Int J Clin Exp Med. 2015;8:17730-17738.  Back to cited text no. 19
    
20.
Yi W, Li D, Guo Y, Zhang Y, Huang B, Li X. Sevoflurane inhibits the migration and invasion of glioma cells by upregulating microRNA-637. Int J Mol Med. 2016;38:1857-1863.  Back to cited text no. 20
    
21.
Hurmath FK, Mittal M, Ramaswamy P, Umamaheswara Rao GS, Dalavaikodihalli Nanjaiah N. Sevoflurane and thiopental preconditioning attenuates the migration and activity of MMP-2 in U87MG glioma cells. Neurochem Int. 2016;94:32-38.  Back to cited text no. 21
    
22.
Meuth SG, Herrmann AM, Ip CW, et al. The two-pore domain potassium channel TASK3 functionally impacts glioma cell death. J Neurooncol. 2008;87:263-270.  Back to cited text no. 22
    
23.
O’Leary G, Bacon CL, Odumeru O, et al. Antiproliferative actions of inhalational anesthetics: comparisons to the valproate teratogen. Int J Dev Neurosci. 2000;18:39-45.  Back to cited text no. 23
    
24.
Shi QY, Zhang SJ, Liu L, et al. Sevoflurane promotes the expansion of glioma stem cells through activation of hypoxia-inducible factors in vitro. Br J Anaesth. 2015;114:825-830.  Back to cited text no. 24
    
25.
Zhu M, Li M, Zhou Y, et al. Isoflurane enhances the malignant potential of glioblastoma stem cells by promoting their viability, mobility in vitro and migratory capacity in vivo. Br J Anaesth. 2016;116:870-877.  Back to cited text no. 25
    
26.
Ma B, Zhang L, Zou Y, et al. Reciprocal regulation of integrin β4 and KLF4 promotes gliomagenesis through maintaining cancer stem cell traits. J Exp Clin Cancer Res. 2019;38:23-23.  Back to cited text no. 26
    
27.
Bian EB, Chen EF, Xu YD, et al. Exosomal lncRNA ATB activates astrocytes that promote glioma cell invasion. Int J Oncol. 2019;54:713-721.  Back to cited text no. 27
    
28.
Ambros V. The functions of animal microRNAs. Nature. 2004;431:350-355.  Back to cited text no. 28
    
29.
Wang Z, Tong D, Han C, et al. Blockade of miR-3614 maturation by IGF2BP3 increases TRIM25 expression and promotes breast cancer cell proliferation. EBioMedicine. 2019;41:357-369.  Back to cited text no. 29
    
30.
Zhuang M, Zhao S, Jiang Z, et al. MALAT1 sponges miR-106b-5p to promote the invasion and metastasis of colorectal cancer via SLAIN2 enhanced microtubules mobility. EBioMedicine. 2019;41:286-298.  Back to cited text no. 30
    
31.
Sullivan TB, Robert LC, Teebagy PA, et al. Spatiotemporal microRNA profile in peripheral nerve regeneration: miR-138 targets vimentin and inhibits Schwann cell migration and proliferation. Neural Regen Res. 2018;13:1253-1262.   Back to cited text no. 31
    
32.
Liu J, Yang L, Guo X, et al. Sevoflurane suppresses proliferation by upregulating microRNA-203 in breast cancer cells. Mol Med Rep. 2018;18:455-460.  Back to cited text no. 32
    
33.
Xu RL, He W, Tang J, et al. Primate-specific miRNA-637 inhibited tumorigenesis in human pancreatic ductal adenocarcinoma cells by suppressing Akt1 expression. Exp Cell Res. 2018;363:310-314.  Back to cited text no. 33
    
34.
Xie L, Dai H, Li M, et al. MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K-AKT-β-catenin pathways. J Cell Mol Med. 2019;23:3386-3401.  Back to cited text no. 34
    
35.
Que T, Song Y, Liu Z, et al. Decreased miRNA-637 is an unfavorable prognosis marker and promotes glioma cell growth, migration and invasion via direct targeting Akt1. Oncogene. 2015;34:4952-4963.  Back to cited text no. 35
    
36.
Chen G, Yue Y, Qin J, Xiao X, Ren Q, Xiao B. Plumbagin suppresses the migration and invasion of glioma cells via downregulation of MMP-2/9 expression and inaction of PI3K/Akt signaling pathway in vitro. J Pharmacol Sci. 2017;134:59-67.  Back to cited text no. 36
    
37.
Zhang H, Ma Y, Wang H, Xu L, Yu Y. MMP-2 expression and correlation with pathology and MRI of glioma. Oncol Lett. 2019;17:1826-1832.  Back to cited text no. 37
    
38.
Bi Y, Li H, Yi D, et al. Cordycepin augments the chemosensitivity of human glioma cells to temozolomide by activating AMPK and inhibiting the AKT signaling pathway. Mol Pharm. 2018;15:4912-4925.  Back to cited text no. 38
    
39.
Liu M, Wang J, Huang B, Chen A, Li X. Oleuropein inhibits the proliferation and invasion of glioma cells via suppression of the AKT signaling pathway. Oncol Rep. 2016;36:2009-2016.  Back to cited text no. 39
    
40.
Tas PW, Kress HG, Koschel K. Volatile anesthetics inhibit the ion flux through Ca2+-activated K+ channels of rat glioma C6 cells. Biochim Biophys Acta. 1989;983:264-268.  Back to cited text no. 40
    
41.
Breuer EK, Fukushiro-Lopes D, Dalheim A, et al. Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling. Cell Death Dis. 2019;10:180.  Back to cited text no. 41
    
42.
Turner KL, Honasoge A, Robert SM, McFerrin MM, Sontheimer H. A proinvasive role for the Ca(2+) -activated K(+) channel KCa3.1 in malignant glioma. Glia. 2014;62:971-981.  Back to cited text no. 42
    
43.
Mohr CJ, Steudel FA, Gross D, et al. Cancer-associated intermediate conductance Ca(2+)-activated K+ channel K(Ca)3.1. Cancers (Basel). 2019;11:109.  Back to cited text no. 43
    
44.
Wang R, Zhang Z, Kumar M, Xu G, Zhang M. Neuroprotective potential of ketamine prevents developing brain structure impairment and alteration of neurocognitive function induced via isoflurane through the PI3K/AKT/GSK-3β pathway. Drug Des Devel Ther. 2019;13:501-512.  Back to cited text no. 44
    
45.
Hoffmann U, Sheng H, Ayata C, Warner DS. Anesthesia in experimental stroke research. Transl Stroke Res. 2016;7:358-367.  Back to cited text no. 45
    
46.
Duris K, Lipkova J, Splichal Z, Madaraszova T, Jurajda M. Early inflammatory response in the brain and anesthesia recovery time evaluation after experimental subarachnoid hemorrhage. Transl Stroke Res. 2018. doi: 10.1007/s12975-018-0641-z.  Back to cited text no. 46
    
47.
Liu X, Dingley J, Elstad M, Scull-Brown E, Steen PA, Thoresen M. Minimum alveolar concentration (MAC) for sevoflurane and xenon at normothermia and hypothermia in newborn pigs. Acta Anaesthesiol Scand. 2013;57:646-653.  Back to cited text no. 47
    
48.
Ni K, Cooter M, Gupta DK, et al. Paradox of age: older patients receive higher age-adjusted minimum alveolar concentration fractions of volatile anaesthetics yet display higher bispectral index values. Br J Anaesth. 2019;123:288-297.  Back to cited text no. 48
    
49.
Lee J, Lee J, Ko S. The relationship between serum progesterone concentration and anesthetic and analgesic requirements: a prospective observational study of parturients undergoing cesarean delivery. Anesth Analg. 2014;119:901-905.  Back to cited text no. 49
    



 
 
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