Is preoperative calcium and vitamin D supplementation effective in prevention of postoperative hypocalcaemia in thyroidectomised patients?

Abstract

Introduction Hypocalcaemia remains the most common postoperative complication after total thyroidectomy. The purpose of the study was to evaluate the clinical usefulness of routine preoperative oral calcium and vitamin D supplementation in the prevention of hypocalcaemia after total thyroidectomy. Material and methods One hundred fifty-three consecutive patients with nontoxic multinodular goitre were randomly assigned to routinely receive (group B) or not to receive (group A) calcium carbonate (3 g/d) and alfacalcidol (1 μg/d) on the day before surgery and calcium carbonate (1 g/d) and alfacalcidol (1 μg/d) taken once in the morning on the day of operation. Their preoperative 25-hydroxyvitamin D (25-OHD) levels, hypocalcemic symptoms, serum calcium and parathyroid hormone (iPTH) levels were determined 6 and 24 hour postoperatively and 6 weeks after surgery. Results Symptomatic hypocalcaemia was observed in 41/153(26.79%) patients. The incidence of symptomatic hypocalcaemia was significantly lower in the supplemented group than in the group not receiving supplementation: 10 of 77 participants (12.99%) versus 31 of 76 patients (40.79%) (p<0.05). The rates of laboratory and severe hypocalcaemia (corrected calcium <2.0 mmol/l) were 67.11% and 28.95% in group A and 50.65% and 9.09% in group B, respectively (p=0.04, p<0.05). There were no significant differences between groups A and B in corrected calcium levels after surgery and postoperative decreases in corrected calcium levels (p=0.06). 112(73.20%) participants had 25-OHD<20 ng/ml. Vitamin D levels did not influence corrected calcium level changes (p=0.98). Conclusions Oral supplementation of calcium and alfacalcidol may help in the prevention of postthyroidectomy hypocalcaemia. Vitamin D deficiency was widespread among operated patients. Powered by TCPDF (www.tcpdf.org) Pr pri t Introduction Thyroidectomy can lead to several complications, hypocalcaemia being one of them. Hypocalcaemia due to parathyroid gland insufficiency can be caused by factors such as: surgical injury causing devascularisation, inadvertent parathyroidectomy and hemodilution [1, 2]. Temporary hypocalcaemia appears from 19% to 38% of patients after thyroidectomy, while 0% to 3% of patients develop permanent hypoparathyroidism [3]. Risk factors for hypocalcaemia after total thyroidectomy were analysed. Vitamin D level is one of the most investigated. It has a pleiotropic health effect [4, 5, 6, 7]. Several studies have reported that preoperative vitamin D deficiency is a risk factor for postoperative hypocalcaemia [3, 8, 9]. Until now, mainly postoperative and perioperative calcium and vitamin D supplementation has been used to prevent postoperative hypocalcaemia [10 , 11, 12, 13, 14, 15, 16, 17]. Only in one study preoperative supplementation of calcium and vitamin D was used. It reduced the incidence of laboratory hypocalcaemia [18].However, only 32.61% of 92 participants had multinodular goitre. The rest of the patients were ill with cancer or toxic goitre – conditions where hypocalcaemia occurs more often after surgery [19]. The authors did not focus on a thorough analysis of laboratory assays (parathormone and calcium levels) nor hypocalcemic symptoms. Inactivated forms of vitamin D, used in the study with long time to onset of action, are unlikely to be beneficial in 24-hour preoperative supplementation [20]. In another retrospective study, perioperative calcium and calcitriol supplementation reduced laboratory and symptomatic hypocalcaemia more effectively than the postoperative supplementation Pr ep ri t [17]. However, only the efficacy of perioperative supplementation was evaluated in that study. The group of enrolled patients was not homogeneous some of them had carcinoma and they were performed additionally lymphadenectomy. The aim of this study was to evaluate the impact of preoperative prophylactic oral supplementation of calcium carbonate and alfacalcidol on the prevention of postoperative hypocalcaemia in thyroidectomised nontoxic multinodular goitre (NTG) patients. Material and Methods Patients 153 NTG patients were enrolled in this prospective single -blinded (for care providers) randomised controlled study. Total thyroidectomies with routine identification of the recurrent laryngeal nerves and parathyroid glands via a transverse cervicotomy under general anaesthesia were performed by 3 experienced surgeons at the Department of Surgery from April to December 2017. This study was performed with the informed consent of each patient. The approval of an appropriate local ethics committee (Bioethical Commission at the Medical University of Lodz – No. RNN/237/16/KE) was obtained. In our study exclusion criteria were as follows: a history of preoperative oral calcium or vitamin D supplement use, receiving medications affecting serum calcium metabolism ( i.e. antiresorptive agents, anabolic medicaments, thiazide -type diuretics, contraceptive drugs, hormone replacement therapy), metabolic bone disease, Pr ep rin t renal insufficiency, sarcoidosis, a history of prior thyroid or neck surgery or parathyroid diseases, prior neck radiation therapy, substernal thyroid disease, Graves’ disease, thyroid cancer, parathyroid autotransplantation. Study Design Preoperatively, the patients were randomly assigned (coin toss) to routinely receive (group B – 76 participants) or not to receive (group A – 77 participants) supplementation (Figure 1, Figure 2). All patients, in the supplementation group were administered 3 g/d oral calcium carbonate (Teva Pharmaceuticals Polska Sp. z o.o, Warsaw, Poland) taken 1 g every 8 hours from 9 a.m. and 1 μg/d alfacalcidol (GlaxoSmithKline Pharmaceuticals S.A., Poznań, Poland) taken once on the day before surgery, and 1 g/d oral calcium carbonate taken once and 1 μg /d alfacalcidol taken once in the morning on the day of operation. In the first twelve hours after the procedure, the participants received intravenously 500 ml of crystalloid . In both groups participants who developed postoperative hypoparathyroidism (parathormone (iPTH) <1.6 pmol/l at 6 or 24 hour after surgery) or symptomatic hypocalcaemia during hospitalisation were 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 was administered if symptoms persisted despite oral Pr ep rin t supplementation. Patients with symptomatic hypocalcaemia received supplementation until the symptoms subsided. The treatment was extended to 6 weeks in patients with hypoparathyroidism on the day of discharge. In both groups, anthropometric measurements and serum laboratory tests were performed on the day before surgery (Table I, Table II). Table I. Characteristics of the included patients . Table II. Preoperative levels of various parameters among groups. iPTH levels were measured with the electrochemiluminescence assay (ECLIA) and total calcium levels were determined with the colorimetric quantitative method (CA CALCIUM ARSENAZO III). Serum iPTH and total calcium levels were measured 6 and 24 hour postoperatively and 6 weeks after surgery. The total serum calcium level was adjusted for the serum albumin level. 25-hydroxyvitamin D (25-OHD) levels were measured using the chemiluminescent microparticle immunoassay (CMIA) (Architect 25 -OHD). Figure 1. Occurrence of symptomatic hypocalcaemia. Figure 2. Occurrence of hypoparathyroidism. All participants were clinically evaluated for symptoms of hypocalcaemia. Hypocalcemic symptoms were 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) [14]. Postoperative hypocalcaemia and severe hypocalcaemia were defined as corrected calcium levels 2.0 to 2.19 mmol/l and <2.0 mmol /l, respectively, even if recorded in one measurement only. P ep rin t Thresholds defining vitamin D status were determined on the basis of current guidelines [21]. The number of parathyroids found intraoperatively and noted in the histopathological examination protocol was also taken into consideration. Statistical Analysis Statistical analysis was performed using a commercially available statistical software package (Statistica 13.1 for Windows; Statsoft Poland Ltd.). Continuous variables were expressed as: mean ± SD, median and minimum –maximum values. The normal distribution was verified with the Shapiro -Wilk test. The data were compared for statistical analysis using Student ’s t-test to evaluate differences between quantitative variables following a Gaussian distribution. Variables following a non-parametric distribution were compared with the Mann -Whitney test. Categorical data analysis was done using the Chi 2 test or Fisher exact test. The Spearman rank correlation coefficient was calculated to evaluate correlations between iPTH levels and corrected calcium levels due to the non -occurrence of normal distribution. Serum calcium levels were plotted over time and analysed using a general linear model for repeated measurements. Alpha<0.05 was set as a threshold of statistical significance.