The story of dexamethasone and how it became one of the most widely used drugs in neurosurgery

Sima Vazquez School of Medicine, New York Medical College, Valhalla, New York;

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Justin Gold School of Medicine, Cooper Medical School of Rowan University, Camden, New Jersey;

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Eris Spirollari School of Medicine, New York Medical College, Valhalla, New York;

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Sarfraz Akmal School of Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey; and

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Simon J. Hanft Department of Neurosurgery, Westchester Medical Center, Valhalla, New York

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Dexamethasone, a long-acting potent glucocorticoid, is one of the most widely used medications in neurosurgery. In this paper, the authors recount the history of dexamethasone’s rise in neurosurgery and discuss its use in brain tumors in the context of emerging neuro-oncological immunotherapies. In 1958, Glen E. Arth synthesized a 16-alpha-methylated analog of cortisone (dexamethasone) for treatment of rheumatoid arthritis. Joseph Galicich, a neurosurgery resident at the time, applied the rheumatological drug to neurosurgery. He gave doses to patients who had undergone craniotomy for tumor removal and saw their paresis improve, midline shift resolve, and mortality rates decrease. He advocated for clinical trials and the drug became a mainstay in neurosurgery. As neuro-oncological treatments evolve to include immunotherapy, the immunosuppressive effects of dexamethasone are becoming an unwanted effect. The question then becomes: how does one treat the patient’s symptoms if the only drug that has been used throughout history may become a detriment to their oncological treatment? Since its discovery, dexamethasone has maintained an impressive staying power in the field, acting as a standard drug for cerebral edema for more than 60 years. However, with the advent of immunotherapy, research is warranted to evaluate ways of treating symptomatic edema in the context of modern neuro-oncological therapies.

ABBREVIATIONS

ELSD = endolymphatic sac decompression; GBM = glioblastoma; SDH = subdural hematoma; VEGF = vascular endothelial growth factor.

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Paramedian and oblique transparietal approaches to meningiomas of the lateral ventricle provide operative corridors that avoid optic radiations and other white matter tracts. Artist: Kenneth X. Probst. Copyright John P. Andrews. Published with permission. See the article by Andrews et al. (pp 1001–1007).

  • 1

    World Health Organization. World Health Organization Model List of Essential Medicines—22nd list, 2021. Published September 30, 2021. Accessed October 9, 2023. https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2021.02

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Lorscheider M, Tsapis N, Ur-Rehman M, et al. Dexamethasone palmitate nanoparticles: an efficient treatment for rheumatoid arthritis. J Control Release. 2019;296:179189.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133(3):493499.

  • 4

    Jeong A, Wade K. Dexamethasone prescribing for cancer pain between palliative care and radiation oncology. Support Care Cancer. 2022;30(9):76897696.

  • 5

    Galicich JH, French LA. Use of dexamethasone in the treatment of cerebral edema resulting from brain tumors and brain surgery. Am Pract Dig Treat. 1961;12:169174.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Dietrich J, Rao K, Pastorino S, Kesari S. Corticosteroids in brain cancer patients: benefits and pitfalls. Expert Rev Clin Pharmacol. 2011;4(2):233242.

  • 7

    Hench PS, Kendall EC, Slocumb C, Polley HF. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone; compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis. Proc Staff Meet Mayo Clin. 1949;24(8):181197.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Arth GE, Johnston DBR, Fried J, Spooncer WW, Hoff DR, Sarett LH. 16-Methylated steroids. I. 16α-Methylated analogs of cortisone, a new group of anti-inflammatory steroids. J Am Chem Soc. 1958;80(12):31603161.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Oliveto EP, Rausser R, Weber L, et al. 16-Alkylated corticoids. II. 9α-Fluoro-16α-methylprednisolone 21-acetate. J Am Chem Soc. 1958;80(16):4431.

  • 10

    Shefrin AE, Goldman RD. Use of dexamethasone and prednisone in acute asthma exacerbations in pediatric patients. Can Fam Physician. 2009;55(7):704706.

  • 11

    Krogh C. "Compendium of pharmaceuticals and specialties.". Can Med Assoc J. 1983;129(9):928.

  • 12

    Zoorob RJ, Cender D. A different look at corticosteroids. Am Fam Physician. 1998;58(2):443450.

  • 13

    Cummings DM, Larijani GE, Conner DP, Ferguson RK, Rocci ML Jr. Characterization of dexamethasone binding in normal and uremic human serum. DICP. 1990;24(3):229231.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Rowland M. Protein binding and drug clearance. Clin Pharmacokinet. 1984;9(suppl 1):1017.

  • 15

    Dogra P, Vijayashankar NP. Dexamethasone suppression test. In: StatPearls [Internet]. StatPearls Publishing; 2023. Accessed October 9, 2023. http://www.ncbi.nlm.nih.gov/books/NBK542317/

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Bunim JJ, Black RL, Lutwak L, Peterson RE, Whedon GD. Studies on dexamethasone, a new synthetic steroid, in rheumatoid arthritis—a preliminary report. Arthritis Rheum. 1958;1(4):313331.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Black RL, Reefe WE, David JR, Bloch KJ, Ehrlich GE, Bunim JJ. Dexamethasone: antirheumatic properties, hormonal effects and adverse reactions (a 16 month study). Arthritis Rheum. 1960;3:112128.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Boland EW. Effectiveness of antacids in reducing digestive disturbances in patients treated with prednisone and prednisolone. Calif Med. 1958;89(4):262266.

  • 20

    Prados M, Strowger B, Feindel WH. Studies on cerebral edema; reaction of the brain to air exposure; pathologic changes. Arch Neurol Psychiatry. 1945;54:163174.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Grenell RG, McCawley EL. Central nervous system resistance; the effect of adrenal cortical substances on the central nervous system. J Neurosurg. 1947;4(6):508518.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Ingraham FD, Matson DD, McLaurin RL. Cortisone and ACTH as an adjunct to the surgery of craniopharyngiomas. N Engl J Med. 1952;246(15):568571.

  • 23

    Tytus JS, Seltzer HS, Kahn EA. Cortisone as an aid in the surgical treatment of craniopharyngiomas. J Neurosurg. 1955;12(6):555564.

  • 24

    Russek HI, Zohman BL, Russek AS. Cortisone in the immediate therapy of apoplectic stroke. J Am Geriatr Soc. 1954;2(4):216222.

  • 25

    Kofman S, Garvin JS, Nagamani D, Taylor SG III. Treatment of cerebral metastases from breast carcinoma with prednisolone. J Am Med Assoc. 1957;163(16):14731476.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Galicich JH, French LA, Melby JC. Use of dexamethasone in treatment of cerebral edema associated with brain tumors. J Lancet. 1961;81:4653.

  • 27

    Kaal ECA, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol. 2004;16(6):593600.

  • 28

    Stummer W. Mechanisms of tumor-related brain edema. Neurosurg Focus. 2007;22(5):E8.

  • 29

    French LA, Galicich JH. The use of steroids for control of cerebral edema. Clin Neurosurg. 1964;10(suppl 1):212-223.

  • 30

    Sørensen S, Helweg-Larsen S, Mouridsen H, Hansen HH. Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial. Eur J Cancer. 1994;30A(1):22-27.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Ryken TC, Kuo JS, Prabhu RS, Sherman JH, Kalkanis SN, Olson JJ. Congress of Neurological Surgeons systematic review and evidence-based guidelines on the role of steroids in the treatment of adults with metastatic brain tumors. Neurosurgery. 2019;84(3):E189E191.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693704.

  • 33

    Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022;97(8):10861107.

  • 34

    Fang Q, Qian X, An J, Wen H, Cope DK, Williams JP. Higher dose dexamethasone increases early postoperative cognitive dysfunction. J Neurosurg Anesthesiol. 2014;26(3):220225.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Jose R, Chakravarthy K, Nair S, Joseph M, Jeyaseelan V, Korula G. A randomized controlled trial studying the role of dexamethasone in scalp nerve blocks for supratentorial craniotomy. J Neurosurg Anesthesiol. 2017;29(2):150156.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Bojrab DI II, LaRouere MJ, Bojrab DI, et al. Endolymphatic sac decompression with intra-sac dexamethasone injection in Menière’s disease. Otol Neurotol. 2018;39(5):616621.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Mebberson K, Colditz M, Marshman LAG, Thomas PAW, Mitchell PS, Robertson K. Prospective randomized placebo-controlled double-blind clinical study of adjuvant dexamethasone with surgery for chronic subdural haematoma with post-operative subdural drainage: interim analysis. J Clin Neurosci. 2020;71:153157.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Zhao C, Zhang N, Shrestha N, Liu H, Ge M, Luo F. Dexamethasone as a ropivacaine adjuvant to pre-emptive incision-site infiltration analgesia in pediatric craniotomy patients: a prospective, multicenter, randomized, double-blind, controlled trial. Paediatr Anaesth. 2021;31(6):665675.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Canseco JA, Karamian BA, Bowles DR, et al. Updated review: the steroid controversy for management of spinal cord injury. World Neurosurg. 2021;150:18.

  • 40

    Iorgulescu JB, Gokhale PC, Speranza MC, et al. Concurrent dexamethasone limits the clinical benefit of immune checkpoint blockade in glioblastoma. Clin Cancer Res. 2021;27(1):276287.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    National Cancer Institute. Steroids May Limit the Effectiveness of Immunotherapy for Brain Cancer. Published December 28, 2020. Accessed October 9, 2023. https://www.cancer.gov/news-events/cancer-currents-blog/2020/brain-cancer-immunotherapy-steroids-limit-effectiveness

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Chiocca EA, Yu JS, Lukas RV, et al. Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: results of a phase 1 trial. Sci Transl Med. 2019;11(505):eaaw5680.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Giles AJ, Hutchinson MND, Sonnemann HM, et al. Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer. 2018;6(1):51.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Rinne ML, Lee EQ, Nayak L, et al. Update on bevacizumab and other angiogenesis inhibitors for brain cancer. Expert Opin Emerg Drugs. 2013;18(2):137153.

  • 45

    Liu S, Song Y, Zhang IY, et al. RAGE inhibitors as alternatives to dexamethasone for managing cerebral edema following brain tumor surgery. Neurotherapeutics. 2022;19(2):635648.

    • PubMed
    • Search Google Scholar
    • Export Citation

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