Recovery time after thyroid surgery may depend on several factors, such as postoperative
pain, nausea and vomiting, postoperative sore throat, phonation disorders associated with
recurrent laryngeal nerve palsy, and symptomatic postoperative hypocalcaemia associated with
postoperative hypoparathyroidism.
Glucocorticoids are well known for their analgesic, anti-inflammatory, immunomodulatory and
anti-emetic effects. However, there is little information in the literature on the
prophylactic use of glucocorticosteroids in patients undergoing thyroid surgery. In some
previous studies, preoperative intravenous dexamethasone supplementation was associated with
a reduced incidence of postoperative laryngeal nerve palsy, postoperative hypoparathyroidism,
and with less severe postoperative pain, postoperative sore throat, nausea and vomiting.
Patients receiving supplementation also had decreased levels of inflammatory biochemical
parameters and proinflammatory cytokines.
Vitamin D deficiency is widespread in Poland. Vitamin D status has an impact on the
postoperative complications in surgical patients. In previous study serum 25-hydroxyvitamin D
is also suggested as a negative acute phase reactant, which has implications for acute and
chronic inflammatory diseases. According to the authors, serum 25-hydroxyvitamin D level is
an unreliable biomarker of vitamin D status after acute inflammatory insult.
In the early stages of inflammation, phagocytic cells and endothelium secrete proinflammatory
cytokines, which include: interleukins: IL-1 α / β, IL-6, IL-8, TNF. The antagonistic group
is anti-inflammatory cytokines, which include interleukins: IL-4, -5, -10, -13, produced by
Th2 lymphocytes. These cytokines reduce the amount of interleukins secreted by Th1
lymphocytes.
Changes in the levels of proinflammatory and anti-inflammatory cytokines in the postoperative
period were found in studies related to the assessment of surgical trauma. Pro-inflammatory
interleukin 1 and interleukin 6 play an important role in many biological processes such as
inflammation, sepsis and wound healing. Interleukin 6 expression is proportional to the
extent of the surgical trauma. In turn, interleukin 10 is known as a cytokine that inhibits
cytokine synthesis. Is one of the strongest immunosuppressive agents.
The aim of my study is to evaluate the impact of preoperative oral dexamethasone
supplementation on the biochemical parameters and results of surgical treatment in patients
with nontoxic multinodular goiter undergoing total thyroidectomy.
Patients admitted to the Department of General and Oncological Surgery, Medical University of
Lodz with preoperative diagnosis of nontoxic multinodular goitre undergoing total
thyroidectomy will be inculded to the study.
After obtaining written informed consent from all participants during a preoperative visit,
they will be randomized to the supplementation group and the placebo group. The study will be
a prospective, placebo-controlled and double-blind (for patient and surgeon) research.
Intervention: In the supplementation group a single dose of 8mg of dexamethasone will be
given orally one hour before surgery (Dexamethasone Krka tablets (8mg), Warsaw, Poland). In
the placebo group patients will receive a single tablet of sweetener one hour before
operation (Clio tablets, sweetener with a dispenser, Instantina GES, Vienna, Austria).
Preoperatively in the group of all enrolled patients (in the supplementation group and in the
placebo group) following tests will be measured in serum: blood count, calcium, inorganic
phosphates, albumin, alkaline phosphatase, C reactive protein, procalcitonin,
25-hydroxyvitamin D, fibrinogen, parathormone, magnesium, interleukin 1β, interleukin 6,
interleukin 10, thyroid stimulating hormone, free thyroxine, free triiodothyronine.
Total thyroidectomies with routine identification of the recurrent laryngeal nerves and
parathyroid glands via a transverse cervicotomy under general anaesthesia will be performed
by 3 experienced surgeons.
During the total thyroidectomy the number of parathyroid glands found intraoperatively will
be registered.
At 6 hour after surgery in the group of all enrolled patients following tests will be
measured in serum: blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase,
C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium.
In addiction, at 6 hour after surgery the incidence and intensity of symptomatic
hypocalcaemia, postoperative pain (according to VAS scale), postoperative nausea and
vomiting, postoperative sore throat and hoarseness will be evaluated.
At 24 hour after surgery in the group of all enrolled patients following tests will be
measured in serum: blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase,
C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium,
interleukin 1β, interleukin 6, interleukin 10. Additionally, the level of interleukin 1β,
interleukin 6 and interleukin 10 will be evaluated in drainage fluid. In addiction, at 24
hour after surgery the incidence and intensity of symptomatic hypocalcaemia, postoperative
pain (according to Visual Analogue Scale - VAS scale), postoperative nausea and vomiting,
postoperative sore throat and hoarseness will be evaluated.
The laboratory parameters will be determined by electrochemiluminescence on the Cobas E411
analyzer and spectrophotometric method on the AU680, Beckman Coulter analyzer.
25-hydroxyvitamin D levels will be measured using the chemiluminescent microparticle
immunoassay (CMIA) (Architect 25-OHD). Interleukins levels will be determined by enzyme
immunoassay method (EIA) (DGR Medtek) on ElizaMat 2 X analyzer.
Hypocalcemic symptoms will be categorized as mild (a tingling sensation and numbness of the
hands or feet and perioral numbness) or severe (a positive Chvostek sign, Trousseau sign,
tetany, and carpopedal spasms).
Postoperative hypocalcaemia will be defined as corrected calcium levels <2.0 mmol/l, even if
recorded in one measurement only.
In both groups participants who will develop postoperative hypoparathyroidism (parathormone
level <1.6 pmol/l at 6 or 24 hour after surgery) or symptomatic hypocalcaemia during
hospitalisation will be treated with oral calcium (3 g/d - taken 1 g every 8 hours) and
vitamin D derivatives (1 ug/d alfacalcidol taken once).
Intravenous calcium gluconate will be administered if symptoms persist despite oral
supplementation.
Patients with symptomatic hypocalcaemia will receive supplementation until the symptoms
subside. The treatment will be extended to 6 weeks in patients with hypoparathyroidism on the
day of discharge.
The data will be statistically analysed. The main hypothesis of the study is that in patients
with supplementation postoperative discomfort and decrease in serum calcium and parathormone
level and hypocalcemic symptoms will be less severe and the levels of proinflammatory
substances will be decreased. Vitamin D deficiency is probably common in operated patients
and postoperative 25-hydroxyvitamin D levels are lower than those measured preoperatively.
The use of oral dexamethasone might be an effective strategy of prevention of complications
after total thyroidectomy.
To the best of our knowledge, this is a pioneering study assessing the usefulness of
preventive oral dexamethasone supplementation before total thyroidectomy in homogeneous group
of patients with nontoxic multinodular goiter undergoing total thyroidectomy.