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Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis
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International Journal of Surgery xxx (2014) 1e4
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Original research
Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis Q2
Paolo Limongelli*, Salvatore Tolone, Adelmo Gubitosi, Gianmattia del Genio, Giuseppina Casalino, Vincenzo Amoroso, Landino Fei, Giampaolo Jannelli, Luigi Brusciano, Giovanni Docimo, Ludovico Docimo Department of General Surgery, Second University of Naples, Via Gino Doria 78, 80128 Naples, Italy
a r t i c l e i n f o
a b s t r a c t
Article history: Received 23 March 2014 Accepted 3 May 2014 Available online xxx
Introduction: The aim of the present study was to critically review the incidence of venous thromboembolism and postoperative hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis. Methods: A prospective electronic database of all patients undergoing total thyroidectomy over a six eyear period within August 2013 in our medical unit was analyzed. The incidence of postoperative bleeding and Venous thromboembolism (VTE) was reviewed by subgrouping all patients according to a risk factor score (RFS) for VTE as outlined in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Best Practice Guidelines. Results: An overall 1018 consecutive patients [244 men (24%, mean age 46 ± 13 years), 778 women (76%, mean age 44 ± 17 years)] underwent total thyroidectomy. Postoperative bleeding occurred in 8/1018 patients (0.8%). One out of 1018 (0.1%) patients also subcategorized according to the RFS had VTE. The incidence of VTE complication in the entire population was lower than the risk of postoperative bleeding (P < .0001). Conclusion: The risk of developing VTE in patients who undergo total thyroidectomy for benign and malignant diseases without preoperative prophylaxis is roughly 8-fold less than developing a potentially life threatening complication as postoperative bleeding. Until large well conducted prospective studies on the impact of preoperative prophylaxis on postoperative VTE and bleeding will clarify the issue, it is conceivable to propose the use of stockings and/or anticoagulants according to the individual patient risk factors. © 2014 Published by Elsevier Ltd on behalf of Surgical Associates Ltd.
1. Introduction Total thyroidectomy (TT) is a well recognized option to address benign and malignant thyroid diseases [1,2]. This surgical procedure is associated with different complications that may have an impact on perioperative surgical outcome [3,4]. During the last year the development of new technological advancement resulted in different surgical strategies for the treatment of patients affected by thyroid pathologies. Surgeons have changed their practice from a constant towards a tailored approach [5,6] and also improved the management of perioperative complications such as nerve damage * Corresponding author. E-mail address: [email protected] (P. Limongelli).
or bleeding [7e9]. A life-threatening bleeding complication is the main postoperative concern of most surgeons after thyroidectomy [10,11]. On the other hand, the American College of Chest Physicians (ACCP) guidelines recommend deep venous thrombosis (DVT) prophylaxis in all patients who undergo major surgical procedures such as thyroidectomy, regardless of anesthesia type [12]. A systematic review and metanalysis published in 2008 by Lloyd et al. provided evidence that anticoagulants conferred an absolute risk reduction in DVT formation, but a significantly greater risk of major bleeding compared to placebo [13]. The aim of the present study was to critically review the incidence of venous thromboembolism and postoperative hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis.
http://dx.doi.org/10.1016/j.ijsu.2014.05.009 1743-9191/© 2014 Published by Elsevier Ltd on behalf of Surgical Associates Ltd.
Please cite this article in press as: P. Limongelli, et al., Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis, International Journal of Surgery (2014), http://dx.doi.org/ 10.1016/j.ijsu.2014.05.009
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P. Limongelli et al. / International Journal of Surgery xxx (2014) 1e4
2. Methods
2.4. Statistics
2.1. Study design and patient selection
Data were analyzed using SPSS 17.0 for Windows (SPSS Inc, Chicago, IL). Results were expressed as mean ± SD. Differences in categorical data were analyzed using the chi square test. Results were considered statistically significant P value was less than 0.05.
A prospective electronic database of all patients undergoing total thyroidectomy over a six eyear period within August 2013 in our medical unit was analyzed. All had no history of prior thyroid or neck surgery. Patients requiring unilateral lobectomy or subtotal or completion thyroidectomy were excluded. All patients had normal renal function at the time of surgery and none had signs or symptoms indicating metabolic bone disease. No patient was on medications, such as oral calcium/vitamin D supplementation, antiresorptive agents, hormone replacement therapy for postmenopausal women, anabolic agents, thiazide type diuretics, or antiepileptic agents. Patients undergoing minimally invasive or video-assisted procedures were excluded from the study. 2.2. Surgical technique The TT procedure consists of a 3- to 5-cm skin incision 1e1.5 cm above the sternal notch. After division of the platysma, the cervical linea alba is opened without division of the strap muscles. The thyroid lobe is dissected progressively from the strap muscles. After identification of the recurrent laryngeal nerve and parathyroid glands, the vascular pedicles of the thyroid lobe are ligated with the Harmonic Ace/Focus scalpel (Ethicon Endo-Surgery Inc., Cincinnati, OH, USA), and the thyroid lobe is removed [8,9]. After a check for hemostasis, a drain is placed in the thyroid bed. The cervical linea alba and platysma are sutured with absorbable sutures, and the skin is closed by an intracutaneous running suture. Patients were asked to take oral calcium 2 g/d taken twice (1 g every 12 h) and vitamin D 1 g/d taken twice (0.5 g every 12 h) from the night of operation to post-operative day 14. Intravenous calcium gluconate was administered if significant symptomatic hypocalcaemia persisted after surgery despite oral supplementation. The medical and nursing notes were carefully examined for documentation of symptoms of hypocalcaemia. Postoperative hypocalcaemia was defined as either symptomatic or laboratory. Hypocalcaemia symptoms and signs, from perioral tingling and numbness to carpopedal spasms and tetany, were registered in detail. Laboratory hypocalcaemia was defined as serum total calcium concentrations of <8.0 mg/dL, even if recorded only in a single measurement. The time of administration of calcium, vitamin D analogues and intravenous fluids in relation to serum calcium and hypocalcaemia symptoms was also noted. Serum calcium, albumin, creatinine, and alkaline phosphatase were measured using automated assays. The reference ranges for serum calcium in our laboratory were 8.5e10.5 mg/dL. Vitamin K antagonists or antiplatelet drugs were discontinued at least 10 days before operation. 2.3. Parameters analyzed Postoperative bleeding was defined as bleeding after wound closure that required re-intervention on an Operating room (OR) basis or on a non-OR basis because of: rapid accumulation of blood, with more than 150 ml in the suction bottle; visible swelling of the neck; or symptoms of airway compression. Venous thromboembolism (VTE) was defined as either the occurrence of a pulmonary embolism (PE) or a deep venous thrombosis (DVT) within 3 months after total thyroidectomy. Patients were categorized with respect to the risk of VTE according to a risk factor score (RFS) as outlined in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Best Practice Guidelines [14e18].
3. Results An overall 1018 consecutive patients [244 men (24%, mean age 46 ± 13 years), 778 women (76%, mean age 44 ± 17 years)] underwent total thyroidectomy. The preoperative mean BMI was 26.5 (17e46). Pathologic indications for surgery are listed in Table 1. Operative time prolonged over 1 h in 285 patients. Patients course was characterized by several complications. Four patients developed 4 vocal cord paralysis. Permanent hypocalcaemia developed only in 11 patients (1%), whereas transient hypocalcaemia was recorded in 19% of patients (n ¼ 193). Ninety-eight out of 1018 patients developed experienced temporary laryngeal nerve injury after surgery, with longer lasting voice problems recorded in 48. Postoperative bleeding occurred in 8/1018 patients (0.8%). One out of 1018 (0.1%) patients also subcategorized according to risk factors for venous thromboembolism experienced DVT (Table 2). The incidence of VTE complication in the entire population was lower than the risk of postoperative bleeding (P < .0001) (Fig. 1). 4. Discussion The major finding from this study was that patients who underwent total thyroidectomy without preoperative prophylaxis had a very low incidence of postoperative VTE (1/1018). We also demonstrated that this cohort of patients had a significantly greater risk of developing bleeding complications as evidenced by the number of cases that required surgical reoperation (8/1018). Postoperative hemorrhage in the neck is likely to occur as an acute emergency that can put patients at major risk of airway compromise and death whether not quickly recognized and appropriately managed. It is true one-day surgery can expose patients to a predictable consistent risk of bleeding due to lack of postoperative surveillance carried out by trained health care personnel. In light of this, patients may not benefit from, but harmed by pharmacologic VTE prophylaxis. Indeed, VTE is viewed as a serious health care issue leading to longer hospital stays, increased mortality, and higher medical costs. Postoperative VTE is a leading cause of operation-related mortality and as suggested by the latest ACCP guidelines, pharmacoprophylaxis is recommended in all patients who undergo major surgical procedures as total thyroidectomy [19]. In the present study, none of the 1018 patients underwent preoperative VTE prophylaxis and only 0.1 percent of the entire cohort developed postoperative deep venous thrombosis without pulmonary embolism. Previous studies have reported the impact several risk factors may have on the rate of postoperative VTE after general and specialist surgery. Moreover, a number of studies have analyzed the association between cancer and a greater risk of postoperative VTE after surgery [20e29]. In recent studies, Reinke and coworkers have recommended tailoring VTE prophylaxis to the
Table 1 Preoperative diagnosis. Disease
Total N ¼ 1018
Multinodular goiter Carcinoma Basedow
865 (85%) 112 (11%) 41 (4%)
Please cite this article in press as: P. Limongelli, et al., Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis, International Journal of Surgery (2014), http://dx.doi.org/ 10.1016/j.ijsu.2014.05.009
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P. Limongelli et al. / International Journal of Surgery xxx (2014) 1e4 Table 2 Categorical risk factor scores for postoperative VTE after total thyroidectomy without preoperative prophylaxis. Total risk factor score
Risk level category per ACS NSQIP guidelines
Predicted incidence of VTE (%)
Postoperative incidence by RFS (%)
0e1 2 3e4 5
Low risk Moderate risk High risk Highest risk
<10 10e20 20e40 40e80
0.0 0.0 0.0 0.01
Fig. 1. Incidence of Postoperative Bleeding and Deep Vein Thromboembolism after total thyroidectomy.
specific type of malignancy for patients undergoing surgical procedures. Specifically, they found the absolute incidence of VTE ranged from nil to 11.9 per 1000 cases, with malignancies of the thyroid and parathyroid glands having the smallest (1 and 0 cases respectively). However, authors were not able to demonstrate thyroid cancer was independently associated with VTE in patients undergoing thyroidectomy [17,30]. In this study the only patient developing postoperative venous thrombosis had a multinodular goiter but the highest RFS as outlined in the ACS NSQIP venous thromboembolism guidelines for prophylaxis. The present study had several limitations. It is an observational study not comparing the incidence of postoperative VTE and bleeding in patients undergoing or not preoperative VTE prophylaxis. Another drawback is that patients included in this study had 3 distinct surgical diagnosis that each may carry different morbidity rates. Furthermore, based on the very low rate of patients with VTE, a lack of a proper power calculation could not allow any meaningful conclusions with regard to predictors of outcome. In conclusions, we provide evidence that the risk of developing VTE in patients who undergo total thyroidectomy for benign and malignant diseases without preoperative prophylaxis is roughly 8fold less than developing a potentially life threatening complication as postoperative bleeding. Until large well conducted prospective studies on the impact of VTE prophylaxis on postoperative VTE and bleeding will clarify the issue, it is conceivable to propose VTE prophylaxis (stockings and/or anticoagulants) according to the individual patient risk factors.
Q1
Ethical approval This is a retrospective study based only on the analyses of recorded data and then no Ethical Approval was necessary. Sources of funding All Authors have no source of funding.
3
Author contribution Paolo Limongelli: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Salvatore Tolone: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Adelmo Gubitosi: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Gianmattia del Genio: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Giuseppina Casalino: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Vincenzo Amoroso: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Landino Fei: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Giampaolo Jannelli: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Luigi Brusciano: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Giovanni Docimo: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Ludovico Docimo: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Conflicts of interest All Authors have no conflict of interests. References [1] A. Pezzolla, G. Docimo, R. Ruggiero, M. Monacelli, R. Cirocchi, D. Parmeggiani, et al., Incidental thyroid carcinoma: a multicentric experience, Recenti Prog. Med. 101 (5) (2010) 194e198. [2] C. Bellevicine, U. Malapelle, G. Docimo, G. Ciancia, G. Mossetti, G. Pettinato, et al., Multicentric encapsulated papillary oncocytic neoplasm of the thyroid: a case diagnosed by a combined cytological, histological, immunohistochemical, and molecular approach, Diagn. Cytopathol. 40 (5) (2012) 450e454. [3] G. Docimo, S. Tolone, D. Pasquali, G. Conzo, A. D'Alessandro, G. Casalino, et al., Role of pre and post-operative oral calcium and vitamin D supplements in prevention of hypocalcemia after total thyroidectomy, Giorn. Ital. Chir. 33 (2012) 374e378. [4] N. Avenia, A. Sanguinetti, R. Cirocchi, G. Docimo, M. Ragusa, R. Ruggiero, et al., Antibiotic prophylaxis in thyroid surgery: a preliminary multicentric italian experience, Ann. Surg. Innov. Res. 3 (2009) 10. [5] G. Conzo, G. Docimo, R. Ruggiero, S. Napolitano, A. Palazzo, C. Gambardella, et al., Surgical treatment of papillary thyroid carcinoma without lymph nodal involvement, G. Chir. 33 (2012) 339e342. [6] G. Docimo, S. Tolone, S. Gili, A. d’Alessandro, G. Casalino, L. Brusciano, et al., Minimally invasive thyroidectomy (MIT), Ann. Ital. Chir. 84 (2013) 617e622. [7] D. Parmeggiani, M. De Falco, N. Avenia, A. Sanguinetti, A. Fiore, G. Docimo, et al., Nerve sparing sutureless total thyroidectomy. Preliminary study, Ann. Ital. Chir. 83 (2012) 91e96.
Please cite this article in press as: P. Limongelli, et al., Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis, International Journal of Surgery (2014), http://dx.doi.org/ 10.1016/j.ijsu.2014.05.009
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[8] G. Docimo, R. Ruggiero, A. Gubitosi, G. Casalino, A. Bosco, S. Gili, et al., Ultrasound scalpel in thyroidectomy: prospective randomized study, Ann. Ital. Chir. 83 (2012) 491e496. [9] F. D'Ajello, R. Cirocchi, G. Docimo, A. Catania, G. Ardito, L. Rosato, et al., Thyroidectomy with ultrasonic dissector: a multicentric experience, G. Chir. 31 (2010) 289e292. [10] J. Fewins, C.B. Simpson, F.R. Miller, Complications of thyroid and parathyroid surgery, Otolaryngol. Clin. North Am. 36 (2003) 189e206. [11] G. Abbas, S. Dubner, K.S. Heller, Re-operation for bleeding after thyroidectomy and parathyroidectomy, Head. Neck 23 (2001) 544e546. [12] W.H. Geerts, D. Bergqvist, G.F. Pineo, J.A. Heit, C.M. Samama, M.R. Lassen, et al., Prevention of venous thromboembolism, Chest 133 (2008) 381Se453S. [13] N.S. Lloyd, J.D. Douketis, I. Moinuddin, W. Lim, M.A. Crowther, Anticoagulant prophylaxis to prevent asymptomatic deep vein thrombosis in hospitalized medical patients: a systematic review and meta-analysis, J. Thromb. Haemost. 6 (2008) 405e414. [14] M. Roy, V. Rajamanickam, H. Chen, R. Sippel, Is DVT prophylaxis necessary for thyroidectomy and parathyroidectomy? Surgery 148 (2010) 1163e1168 (discussion 1168e9). [15] C.E. Reinke, G.C. Karakousis, R.A. Hadler, J.A. Drebin, D.L. Fraker, R.R. Kelz, Incidence of venous thromboembolism in patients undergoing surgical treatment for malignancy by type of neoplasm: an analysis of ACS-NSQIP data from 2005 to 2010, Surgery 152 (2012) 186e192. [16] M. Raval, J. Caprini, N. Esnaola, ACS NSQIP Best Practices Guidelines: Prevention and Treatment of Venous Thromboembolism, 2009. Available from: http://reports.nsqip.facs.org/acsmain/private/documents/bestpractice/index. jsp. [17] S.F. Khuri, J. Daley, W. Henderson, et al., The department of veterans affairs' NSQIP: the first national, validated, outcome-based, risk-adjusted, and peercontrolled program for the measurement and enhancement of the quality of surgical care. National VA Surgical Quality Improvement Program, Ann. Surg. 228 (1998) 491e507. [18] S.F. Khuri, The NSQIP: a new frontier in surgery, Surgery 138 (2005) 837e843. [19] American College of Surgeons, ACS NSQIP data: Participant Use Data File. American College of Surgeons National Surgical Quality Improvement
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Program website, 2009. Available from: http://acsnsqip.org/puf/ PufRequestHomepage.aspx. N. Levitan, A. Dowlati, S.C. Remick, et al., Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data, Med. Baltim. 78 (1999) 285e291. D. Bergqvist, Venous thromboembolism and cancer: prevention of VTE, Thromb. Res. 102 (2001) V209eV213. A.Y. Lee, M.N. Levine, Venous thromboembolism and cancer: risks and outcomes, Circulation 107 (2003) I17eI21. J.W. Blom, C.J. Doggen, S. Osanto, F.R. Rosendaal, Malignancies, prothrombotic mutations, and the risk of venous thrombosis, J. Am. Med. Assoc. 293 (2005) 715e722. G. Agnelli, G. Bolis, L. Capussotti, et al., A clinical outcomebased prospective study on venous thromboembolism after cancer surgery: the @RISTOS project, Ann. Surg. 243 (2006) 89e95. G.H. Lyman, A.A. Khorana, A. Falanga, et al., American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer, J. Clin. Oncol. 25 (2007) 5490e5505. R.P. Merkow, K.Y. Bilimoria, M.D. McCarter, et al., Postdischarge venous thromboembolism after cancer surgery: extending the case for extended prophylaxis, Ann. Surg. 254 (2011) 131e137. R.H. White, H. Zhou, P.S. Romano, Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures, Thromb. Haemost. 90 (2003) 446e455. S.O. Rogers Jr., R.K. Kilaru, P. Hosokawa, et al., Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study, J. Am. Coll. Surg. 204 (2007) 1211e1221. F.A. Anderson Jr., F.A. Spencer, Risk factors for venous thromboembolism, Circulation 107 (2003) I9e16. C.E. Reinke, R.A. Hadler, G.C. Karakousis, D.L. Fraker, R.R. Kelz, Does the presence of thyroid cancer increase the risk of venous thromboembolism in patients undergoing thyroidectomy? Surgery 150 (2011) 1275e1285.
Please cite this article in press as: P. Limongelli, et al., Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis, International Journal of Surgery (2014), http://dx.doi.org/ 10.1016/j.ijsu.2014.05.009
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International Journal of Surgery xxx (2014) 1e4
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Original research
Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis Q2
Paolo Limongelli*, Salvatore Tolone, Adelmo Gubitosi, Gianmattia del Genio, Giuseppina Casalino, Vincenzo Amoroso, Landino Fei, Giampaolo Jannelli, Luigi Brusciano, Giovanni Docimo, Ludovico Docimo Department of General Surgery, Second University of Naples, Via Gino Doria 78, 80128 Naples, Italy
a r t i c l e i n f o
a b s t r a c t
Article history: Received 23 March 2014 Accepted 3 May 2014 Available online xxx
Introduction: The aim of the present study was to critically review the incidence of venous thromboembolism and postoperative hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis. Methods: A prospective electronic database of all patients undergoing total thyroidectomy over a six eyear period within August 2013 in our medical unit was analyzed. The incidence of postoperative bleeding and Venous thromboembolism (VTE) was reviewed by subgrouping all patients according to a risk factor score (RFS) for VTE as outlined in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Best Practice Guidelines. Results: An overall 1018 consecutive patients [244 men (24%, mean age 46 ± 13 years), 778 women (76%, mean age 44 ± 17 years)] underwent total thyroidectomy. Postoperative bleeding occurred in 8/1018 patients (0.8%). One out of 1018 (0.1%) patients also subcategorized according to the RFS had VTE. The incidence of VTE complication in the entire population was lower than the risk of postoperative bleeding (P < .0001). Conclusion: The risk of developing VTE in patients who undergo total thyroidectomy for benign and malignant diseases without preoperative prophylaxis is roughly 8-fold less than developing a potentially life threatening complication as postoperative bleeding. Until large well conducted prospective studies on the impact of preoperative prophylaxis on postoperative VTE and bleeding will clarify the issue, it is conceivable to propose the use of stockings and/or anticoagulants according to the individual patient risk factors. © 2014 Published by Elsevier Ltd on behalf of Surgical Associates Ltd.
1. Introduction Total thyroidectomy (TT) is a well recognized option to address benign and malignant thyroid diseases [1,2]. This surgical procedure is associated with different complications that may have an impact on perioperative surgical outcome [3,4]. During the last year the development of new technological advancement resulted in different surgical strategies for the treatment of patients affected by thyroid pathologies. Surgeons have changed their practice from a constant towards a tailored approach [5,6] and also improved the management of perioperative complications such as nerve damage * Corresponding author. E-mail address: [email protected] (P. Limongelli).
or bleeding [7e9]. A life-threatening bleeding complication is the main postoperative concern of most surgeons after thyroidectomy [10,11]. On the other hand, the American College of Chest Physicians (ACCP) guidelines recommend deep venous thrombosis (DVT) prophylaxis in all patients who undergo major surgical procedures such as thyroidectomy, regardless of anesthesia type [12]. A systematic review and metanalysis published in 2008 by Lloyd et al. provided evidence that anticoagulants conferred an absolute risk reduction in DVT formation, but a significantly greater risk of major bleeding compared to placebo [13]. The aim of the present study was to critically review the incidence of venous thromboembolism and postoperative hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis.
http://dx.doi.org/10.1016/j.ijsu.2014.05.009 1743-9191/© 2014 Published by Elsevier Ltd on behalf of Surgical Associates Ltd.
Please cite this article in press as: P. Limongelli, et al., Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis, International Journal of Surgery (2014), http://dx.doi.org/ 10.1016/j.ijsu.2014.05.009
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P. Limongelli et al. / International Journal of Surgery xxx (2014) 1e4
2. Methods
2.4. Statistics
2.1. Study design and patient selection
Data were analyzed using SPSS 17.0 for Windows (SPSS Inc, Chicago, IL). Results were expressed as mean ± SD. Differences in categorical data were analyzed using the chi square test. Results were considered statistically significant P value was less than 0.05.
A prospective electronic database of all patients undergoing total thyroidectomy over a six eyear period within August 2013 in our medical unit was analyzed. All had no history of prior thyroid or neck surgery. Patients requiring unilateral lobectomy or subtotal or completion thyroidectomy were excluded. All patients had normal renal function at the time of surgery and none had signs or symptoms indicating metabolic bone disease. No patient was on medications, such as oral calcium/vitamin D supplementation, antiresorptive agents, hormone replacement therapy for postmenopausal women, anabolic agents, thiazide type diuretics, or antiepileptic agents. Patients undergoing minimally invasive or video-assisted procedures were excluded from the study. 2.2. Surgical technique The TT procedure consists of a 3- to 5-cm skin incision 1e1.5 cm above the sternal notch. After division of the platysma, the cervical linea alba is opened without division of the strap muscles. The thyroid lobe is dissected progressively from the strap muscles. After identification of the recurrent laryngeal nerve and parathyroid glands, the vascular pedicles of the thyroid lobe are ligated with the Harmonic Ace/Focus scalpel (Ethicon Endo-Surgery Inc., Cincinnati, OH, USA), and the thyroid lobe is removed [8,9]. After a check for hemostasis, a drain is placed in the thyroid bed. The cervical linea alba and platysma are sutured with absorbable sutures, and the skin is closed by an intracutaneous running suture. Patients were asked to take oral calcium 2 g/d taken twice (1 g every 12 h) and vitamin D 1 g/d taken twice (0.5 g every 12 h) from the night of operation to post-operative day 14. Intravenous calcium gluconate was administered if significant symptomatic hypocalcaemia persisted after surgery despite oral supplementation. The medical and nursing notes were carefully examined for documentation of symptoms of hypocalcaemia. Postoperative hypocalcaemia was defined as either symptomatic or laboratory. Hypocalcaemia symptoms and signs, from perioral tingling and numbness to carpopedal spasms and tetany, were registered in detail. Laboratory hypocalcaemia was defined as serum total calcium concentrations of <8.0 mg/dL, even if recorded only in a single measurement. The time of administration of calcium, vitamin D analogues and intravenous fluids in relation to serum calcium and hypocalcaemia symptoms was also noted. Serum calcium, albumin, creatinine, and alkaline phosphatase were measured using automated assays. The reference ranges for serum calcium in our laboratory were 8.5e10.5 mg/dL. Vitamin K antagonists or antiplatelet drugs were discontinued at least 10 days before operation. 2.3. Parameters analyzed Postoperative bleeding was defined as bleeding after wound closure that required re-intervention on an Operating room (OR) basis or on a non-OR basis because of: rapid accumulation of blood, with more than 150 ml in the suction bottle; visible swelling of the neck; or symptoms of airway compression. Venous thromboembolism (VTE) was defined as either the occurrence of a pulmonary embolism (PE) or a deep venous thrombosis (DVT) within 3 months after total thyroidectomy. Patients were categorized with respect to the risk of VTE according to a risk factor score (RFS) as outlined in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Best Practice Guidelines [14e18].
3. Results An overall 1018 consecutive patients [244 men (24%, mean age 46 ± 13 years), 778 women (76%, mean age 44 ± 17 years)] underwent total thyroidectomy. The preoperative mean BMI was 26.5 (17e46). Pathologic indications for surgery are listed in Table 1. Operative time prolonged over 1 h in 285 patients. Patients course was characterized by several complications. Four patients developed 4 vocal cord paralysis. Permanent hypocalcaemia developed only in 11 patients (1%), whereas transient hypocalcaemia was recorded in 19% of patients (n ¼ 193). Ninety-eight out of 1018 patients developed experienced temporary laryngeal nerve injury after surgery, with longer lasting voice problems recorded in 48. Postoperative bleeding occurred in 8/1018 patients (0.8%). One out of 1018 (0.1%) patients also subcategorized according to risk factors for venous thromboembolism experienced DVT (Table 2). The incidence of VTE complication in the entire population was lower than the risk of postoperative bleeding (P < .0001) (Fig. 1). 4. Discussion The major finding from this study was that patients who underwent total thyroidectomy without preoperative prophylaxis had a very low incidence of postoperative VTE (1/1018). We also demonstrated that this cohort of patients had a significantly greater risk of developing bleeding complications as evidenced by the number of cases that required surgical reoperation (8/1018). Postoperative hemorrhage in the neck is likely to occur as an acute emergency that can put patients at major risk of airway compromise and death whether not quickly recognized and appropriately managed. It is true one-day surgery can expose patients to a predictable consistent risk of bleeding due to lack of postoperative surveillance carried out by trained health care personnel. In light of this, patients may not benefit from, but harmed by pharmacologic VTE prophylaxis. Indeed, VTE is viewed as a serious health care issue leading to longer hospital stays, increased mortality, and higher medical costs. Postoperative VTE is a leading cause of operation-related mortality and as suggested by the latest ACCP guidelines, pharmacoprophylaxis is recommended in all patients who undergo major surgical procedures as total thyroidectomy [19]. In the present study, none of the 1018 patients underwent preoperative VTE prophylaxis and only 0.1 percent of the entire cohort developed postoperative deep venous thrombosis without pulmonary embolism. Previous studies have reported the impact several risk factors may have on the rate of postoperative VTE after general and specialist surgery. Moreover, a number of studies have analyzed the association between cancer and a greater risk of postoperative VTE after surgery [20e29]. In recent studies, Reinke and coworkers have recommended tailoring VTE prophylaxis to the
Table 1 Preoperative diagnosis. Disease
Total N ¼ 1018
Multinodular goiter Carcinoma Basedow
865 (85%) 112 (11%) 41 (4%)
Please cite this article in press as: P. Limongelli, et al., Relationship between postoperative venous thromboembolism and hemorrhage in patients undergoing total thyroidectomy without preoperative prophylaxis, International Journal of Surgery (2014), http://dx.doi.org/ 10.1016/j.ijsu.2014.05.009
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P. Limongelli et al. / International Journal of Surgery xxx (2014) 1e4 Table 2 Categorical risk factor scores for postoperative VTE after total thyroidectomy without preoperative prophylaxis. Total risk factor score
Risk level category per ACS NSQIP guidelines
Predicted incidence of VTE (%)
Postoperative incidence by RFS (%)
0e1 2 3e4 5
Low risk Moderate risk High risk Highest risk
<10 10e20 20e40 40e80
0.0 0.0 0.0 0.01
Fig. 1. Incidence of Postoperative Bleeding and Deep Vein Thromboembolism after total thyroidectomy.
specific type of malignancy for patients undergoing surgical procedures. Specifically, they found the absolute incidence of VTE ranged from nil to 11.9 per 1000 cases, with malignancies of the thyroid and parathyroid glands having the smallest (1 and 0 cases respectively). However, authors were not able to demonstrate thyroid cancer was independently associated with VTE in patients undergoing thyroidectomy [17,30]. In this study the only patient developing postoperative venous thrombosis had a multinodular goiter but the highest RFS as outlined in the ACS NSQIP venous thromboembolism guidelines for prophylaxis. The present study had several limitations. It is an observational study not comparing the incidence of postoperative VTE and bleeding in patients undergoing or not preoperative VTE prophylaxis. Another drawback is that patients included in this study had 3 distinct surgical diagnosis that each may carry different morbidity rates. Furthermore, based on the very low rate of patients with VTE, a lack of a proper power calculation could not allow any meaningful conclusions with regard to predictors of outcome. In conclusions, we provide evidence that the risk of developing VTE in patients who undergo total thyroidectomy for benign and malignant diseases without preoperative prophylaxis is roughly 8fold less than developing a potentially life threatening complication as postoperative bleeding. Until large well conducted prospective studies on the impact of VTE prophylaxis on postoperative VTE and bleeding will clarify the issue, it is conceivable to propose VTE prophylaxis (stockings and/or anticoagulants) according to the individual patient risk factors.
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Ethical approval This is a retrospective study based only on the analyses of recorded data and then no Ethical Approval was necessary. Sources of funding All Authors have no source of funding.
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Author contribution Paolo Limongelli: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Salvatore Tolone: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Adelmo Gubitosi: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Gianmattia del Genio: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Giuseppina Casalino: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Vincenzo Amoroso: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Landino Fei: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript. Giampaolo Jannelli: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Luigi Brusciano: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Giovanni Docimo: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Ludovico Docimo: Participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data. Conflicts of interest All Authors have no conflict of interests. References [1] A. Pezzolla, G. Docimo, R. Ruggiero, M. Monacelli, R. Cirocchi, D. Parmeggiani, et al., Incidental thyroid carcinoma: a multicentric experience, Recenti Prog. Med. 101 (5) (2010) 194e198. [2] C. Bellevicine, U. Malapelle, G. Docimo, G. Ciancia, G. Mossetti, G. Pettinato, et al., Multicentric encapsulated papillary oncocytic neoplasm of the thyroid: a case diagnosed by a combined cytological, histological, immunohistochemical, and molecular approach, Diagn. Cytopathol. 40 (5) (2012) 450e454. [3] G. Docimo, S. Tolone, D. Pasquali, G. Conzo, A. D'Alessandro, G. Casalino, et al., Role of pre and post-operative oral calcium and vitamin D supplements in prevention of hypocalcemia after total thyroidectomy, Giorn. Ital. Chir. 33 (2012) 374e378. [4] N. Avenia, A. Sanguinetti, R. Cirocchi, G. Docimo, M. Ragusa, R. Ruggiero, et al., Antibiotic prophylaxis in thyroid surgery: a preliminary multicentric italian experience, Ann. Surg. Innov. Res. 3 (2009) 10. [5] G. Conzo, G. Docimo, R. Ruggiero, S. Napolitano, A. Palazzo, C. Gambardella, et al., Surgical treatment of papillary thyroid carcinoma without lymph nodal involvement, G. Chir. 33 (2012) 339e342. [6] G. Docimo, S. Tolone, S. Gili, A. d’Alessandro, G. Casalino, L. Brusciano, et al., Minimally invasive thyroidectomy (MIT), Ann. Ital. Chir. 84 (2013) 617e622. [7] D. Parmeggiani, M. De Falco, N. Avenia, A. Sanguinetti, A. Fiore, G. Docimo, et al., Nerve sparing sutureless total thyroidectomy. Preliminary study, Ann. Ital. Chir. 83 (2012) 91e96.
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