Determining the effect of long-term dexamethasone and prednisolone treatment on sugammadex
Determining the effect of long-term dexamethasone and prednisolone treatment on sugammadex
Background/aim: We aimed to investigate the effect of long-term use of dexamethasone and prednisolone on the reversal effect ofsugammadex.Materials and methods: TTwenty-four male Wistar albino rats were divided into three groups. Dexamethasone (600 µg/kg) was given togroup D, prednisolone (10 mg/kg) was given to group P, and an equivalent volume of saline per day was administered intraperitoneally togroup S for 14 days, respectively. The left hemidiaphragm with attached phrenic nerve was maintained in Krebs solution. Sugammadex(30 µmol/L) was applied while rocuronium (10 µmol/L) was present in an organ bath and a single twitch was obtained. The righthemidiaphragm was used for both adult (ɛ-subunit) and fetal nicotinic acetylcholine receptor (AChR) (ɣ-subunit) determination usingpolymerase chain reaction.Results: All animals lost weight, except group S. The mean baseline single-twitch tension was lower in both group D (14.4 ± 1.7 g) andgroup P (12.68 ± 0.05 g) than group S (16.8 ± 0.5 g) (P < 0.001). When sugammadex was added to the organ bath while rocuronium waspresent, the single twitch was measured to be lower in both group D (11.7 ± 0.7 g) and group P (11.5 ± 0.78 g) than group S (16.5 ± 0.24g) (P < 0.001). ɣ-AChR expression was higher in both dexamethasone and prednisolone than in saline.Conclusion: Long-term medication with dexamethasone and prednisolone caused muscle weakness, resistance to neuromuscularblockers, and upregulation of immature γ-AChR and reduced the neuromuscular reversal effect of sugammadex.
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- Behbehani NA, Al Mane F, D’yachkova Y, Pare P, FitzGerald
JM. Myopathy following mechanical ventilation for acute
severe asthma: the role of muscle relaxants and corticosteroids.
Chest 1999; 115: 1627-1631.
- Arts WF, Oosterhuis HJ. Long-term effect of glucocorticoids
on neuromuscular blocking in mice. J Neurol Neurosurg
Psychiatry 1977; 40: 675-677.
- Shin YS, Fink H, Khiroya R, Ibebunjo C, Martyn J.
Prednisolone-induced muscle dysfunction is caused more by
atrophy than altered acetylcholine receptor expression. Anesth
Analg 2000; 91: 322-328.
- Veldsema-Currie RD, Wolters ECMJ, Leeuwin RS. The effect
of corticosteroids and hemicholinium-3 on choline uptake
and incorporation into acetylcholine in rat diaphragm. Eur J
Pharmacol 1976; 35: 399-402.
- Leeuwin RS, Veldsema-Currie RD, Van Wilgenburg H,
Ottenhof M. Effects of corticosteroids on neuromuscular
blocking actions of d-tubocurarine. Eur J Pharmacol 1981; 69:
165-173.
- Braun S, Askanas V, Engel WK, Ibrahim EN. Long-term
treatment with glucocorticoids increases synthesis and stability
of junctional acetylcholine receptors on innervated cultured
human muscle. J Neurochem. 1993; 60: 1929-1935.
- Soltész S, Mencke T, Mey C, Röhrig S, Diefenbach C, Molter
GP. Influence of a continuous prednisolone medication on the
time course of neuromuscular block of atracurium in patients
with chronic inflammatory bowel disease. Br J Anaesth 2008;
100: 798-802.
- Soltész S, Mencke T, Stunz M, Diefenbach C, Zıegeler S, Molter
GP. Attenuation of a rocuronium-induced neuromuscular
block in patients receiving prednisolone. Acta Anaesthesiol
Scand 2009; 53: 443-448.
- Fischbach GD, Schuetze SM. A post-natal decrease in
acetylcholine channel open time at rat end-plates. J Physiol
1980; 303: 125-137.
- Kim C, Fuke N, Martyn JA. Burn injury to rat increases nicotinic
acetylcholine receptors in the diaphragm. Anesthesiology
1988; 68: 401-406.
- Martyn JAJ, Fagerlund MJ, Eriksson LI. Basic principles of
neuromuscular transmission. Anaesthesia 2009; 64: 1-9.
- Martyn JAJ, Richtsfeld M. Succinylcholine-induced
hyperkalemia in acquired pathologic states: etiologic factors and
molecular mechanisms. Anesthesiology 2006; 104: 158-169.
- Fagerlund MJ, Eriksson LI. Current concepts in neuromuscular
transmission. Br J Anaesth 2009; 103: 108-114.
- Maestrone E, Lagostena L, Henning RH, Hertog AD, Nobile
M. Functional aspects of dexamethasone upregulated nicotinic
acetylcholine receptors in C2C12 myotubes. Pharmacol Res
1995; 32: 305-308.
- Chen D, Yang MR, Huang LN, Qiu YW, Li ST. Different
magnitude of resistance to non-depolarizing muscle relaxants
in dexamethasone-treated rat diaphragm associated with
altered acetylcholine receptor expression. Genet Mol Res 2014;
13: 5892-5900.
- Chen D, Yang MR, Huang LN, Qiu YW, Lİ ST. Dexamethasoneinduced hyposensitivity to rocuronium in rat diaphragm
associated with muscle-fiber transformation. Mol Med Res
2014; 9: 527-534.
- Choi ES, Oh AY, Koo BW, Hwang JW, Han JW, Seo KS, Ahn
SH, Jeong WJ. Comparison of reversal with neostigmine of
low-dose rocuronium vs. reversal with sugammadex of highdose rocuronium for a short procedure. Anaesthesia 2017; 72:
1185-1190.
- Nicholson S, Cambell E, Torrellas A, Beckford U, Altaher R,
Sandford R, Scraggs R, Gillham B, Jones M. Recovery of the
hypothalamo-pituitary-adrenocortical axis in the rat after
long-term dexamethasone treatment. Neuroendocrinology
1984; 39: 343-349.
- Cea LA, Balboa E, Puebla C, Vargas AA, Cisterna BA, Escamilla
R, Saez JC. Dexamethasone-induced muscular atrophy
is mediated by functional expression of connexin-based
hemichannels. Biochim Biophys Acta 2016; 1862: 1891-1899.
- Van Balkom RH, Zhan WZ, Prakash YS, Dekhuijzen PN, Sieck
GC. Corticosteroid effects on isotonic contractile properties of
rat diaphragm muscle. J Appl Physiol 1997; 83: 1062-1067.
- Martyn JA. Basic and clinical pharmacology of the acetylcholine
receptor: implications for the use of neuromuscular relaxants.
Keio J Med 1995; 44: 1-8.
- Ma K, Mallidis C, Bhasin S, Mahabadi V, Artaza J, GonzalezCadavid N, Arias J, Salehian B. Glucocorticoid-induced skeletal
muscle atrophy is associated with upregulation of myostatin gene
expression. Am J Physiol Endocrinol Metab 2003; 285: 363-371.
- Wang X, Engisch KL, Teichert RW, Olivera BM, Pinter MJ,
Rich MM. Prolongation of evoked and spontaneous synaptic
currents at the neuromuscular junction after activity blockade
is caused by the upregulation of fetal acetylcholine receptors. J
Neurosci 2006; 26: 8983-8987.
- Hall ED. Glucocorticoid effects on the electrical properties of
spinal motor neurons. Brain Res 1982; 240: 109–116.
- Veldsema-Currie RD, Wolters E, Leeuwin RS. The effect of
corticosteroids and hemicholinium-3 on choline uptake
and incorporation into acetylcholine in rat diaphragm. Eur J
Pharmacol 1976; 35: 399-402.
- Dalkara T, Onur R. Facilitatory effects of dexamethasone on
neuromuscular transmission. Exp Neurol 1987; 95: 116-125.
- Wilson RW, Ward MD, Johns TR. Corticosteroids: a direct
effect at the neuromuscular junction. Neurology 1974; 24:
1091-1095.
- Rezonja K, Lorenzon P, Mars T. Opposing effects of
dexamethasone, agrin and sugammadex on functional
innervation and constitutive secretion of IL-6 in in vitro
innervated primary human muscle cells. Neurosci Lett 2013; 9:
1861-1890.
- Kindler CH, Verotta D, Gray AT, Gropper MA, Yost S.
Additive inhibition of nicotinic acetylcholine receptors
by corticosteroids and the neuromuscular blocking drug
vecuronium. Anesthesiology 2000; 92: 821-832.
- Rezonja K, Sostaric M, Vidmar G, Mars T. Dexamethasone
produces dose-dependent inhibition of sugammadex reversal
in in vitro innervated primary human muscle cells. Anesth
Analg 2014; 118: 755-763.
- Bom AH, Thomson K. Effect of high doses of sugammadex on
mouse hemi-diaphragm contractions during TOF stimulation.
Anesthesiology 2006; 105: A110.
- Epemolu O, Bom A. The concept behind sugammadex. Rev
Esp Anestesiol Reanim 2014; 61: 272-276.
- Kelly FJ, McGrath JA, Goldspink DF, Cullen MJ. A
morphological/biochemical study on the actions of
corticosteroids on rat
- Dropcho EJ, Soong SJ. Steroid-induced weakness in patients
with primary brain tumors. Neurology 1991; 41: 1235-1239.