Preventative and management strategies of hypocalcemia after thyroidectomy among surgeons: An international survey study

Journal Pre-proof Preventative and management strategies of hypocalcemia after thyroidectomy among surgeons: An international survey study

Anita Sulibhavi, Samuel J. Rubin, Jong Park, Sean Hashemi, Joseph DePietro, J. Pieter Noordzij PII:

S0196-0709(19)31130-5

DOI:

https://doi.org/10.1016/j.amjoto.2020.102394

Reference:

YAJOT 102394

To appear in:

American Journal of Otolaryngology--Head and Neck Medicine and Surgery

Received date:

28 December 2019

Please cite this article as: A. Sulibhavi, S.J. Rubin, J. Park, et al., Preventative and management strategies of hypocalcemia after thyroidectomy among surgeons: An international survey study, American Journal of Otolaryngology--Head and Neck Medicine and Surgery(2018), https://doi.org/10.1016/j.amjoto.2020.102394

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© 2018 Published by Elsevier.

Journal Pre-proof Preventative and Management Strategies of Hypocalcemia after Thyroidectomy Among Surgeons: An International Survey Study Authors: Anita Sulibhavi BA Department of Otolaryngology – Boston Medical Center One Boston Medical Center Place, Boston MA 02118

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[email protected]

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Samuel J Rubin MD, MPH

Department of Otolaryngology – Boston Medical Center

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830 Harrison Ave, 4th Floor, FGH Building, Boston MA 02118

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[email protected]

Jong Park, BS

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Department of Otolaryngology – Boston Medical Center

[email protected]

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One Boston Medical Center Place, Boston MA 02118

Sean Hashemi, MD Department of Otolaryngology – Boston Medical Center 830 Harrison Ave, 4th Floor, FGH Building, Boston MA 02118 [email protected]

Journal Pre-proof Joseph DePietro, MD Department of Otolaryngology – Boston Medical Center 830 Harrison Ave, 4th Floor, FGH Building, Boston MA 02118 [email protected] Corresponding Author:

Department of Otolaryngology – Boston Medical Center

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J. Pieter Noordzij MD

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830 Harrison Ave, 4th Floor, FGH Building, Boston MA 02118

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[email protected]

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Funding:

J. Pieter Noordzij MD

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Corresponding Author:

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No funding or grants were required for this project.

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Department of Otolaryngology – Boston Medical Center One Boston Medical Center Place, Boston MA 02118 781-385-1014 [email protected]

Journal Pre-proof Abstract: Objective: To determine international surgeon practice patterns for transient postoperative hypocalcemia in patients undergoing total thyroidectomy. Methods All member surgeons of the American Thyroid Association and the International Association of Thyroid Surgeons were contacted via email to complete a 20-question survey which included both questions about demographic information and preventing and managing

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postoperative hypocalcemia after thyroidectomy. Univariate analysis was performed to

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and/or PTH to assess for postoperative hypocalcemia.

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determine whether providers check preoperative vitamin D levels, postoperative calcium trends

Results:

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A total of 332 surgeons responded to the survey with 72.26% in practice for >10 years and

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82.18% performing >50 total thyroidectomies per year. 13.29% of surgeon’s surveyed reported

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that they routinely check preoperative vitamin D levels. Surgeon case volume, type of practice (academic vs non-academic practice), and geographic location in the US were significant

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predictors of whether surgeons check preoperative Vitamin D levels. International surgeons were

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significantly more likely to check both postoperative serum Ca and PTH compared to US based surgeons (p<0.01). There was no significance difference in practice patterns based on whether the surgeon was a General Surgeon or an Otolaryngologist. Conclusions: Using a questionnaire distributed to both General Surgeons and Otolaryngologists, we demonstrated that there is significant variation in practice patterns between surgeons practicing in the United States and surgeons practicing in other countries, and practice often differs from recommended guidelines.

Journal Pre-proof Key Words: Thyroidectomy, Hypocalcemia, Otolaryngology, Postoperative Complications,

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Outcomes

Journal Pre-proof Introduction: Hypocalcemia can develop post-operatively after thyroid and parathyroid surgery [1]. Hypocalcemia can be transient, or permanent secondary to hypoparathyroidism. Despite recent studies suggesting that the above procedures can be performed on an outpatient basis, most thyroidectomies continue to result in inpatient stays given the concern for post-operative hypocalcemia [2]. Hypocalcemia impacts up to 10-50% of patients after thyroidectomy and can

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be permanent in up to 2% of patients [3]. The ability to identify patients at risk for developing

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hypocalcemia and prompt implementation of treatment can reduce emergency room visits after

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surgery and prevent long-term sequelae for patients, which is why management of calcium and vitamin D status in the perioperative period has been a topic of interest [4].

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Risk factors for the development of transient post-operative hypocalcemia include low

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post-operative parathyroid hormone (PTH), age, female gender, vitamin D deficiency, and the

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presence of malignancy [5,6]. The American Thyroid Association suggests that development of post-operative hypocalcemia can be approximated using either a calculated slope between the 6-

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and 12-hour postoperative serum calcium levels or postoperative intact PTH levels [7,8]. At this

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time the gold standard management of transient hypocalcemia consists of repletion with calcium and/or calcitriol [7]. Despite these recommendations, providers are left to their own judgment when deciding whether to proceed with watchful waiting with treatment only of symptomatic patients, prophylactic treatment for all patients, or treating according to a protocol established by their institution [2,9]. One benefit of institution-established protocols is that these protocols have led to fewer postoperative procedures for patients, such as fewer blood draws [10]. Establishing protocols for the prediction and management of transient postoperative hypocalcemia is especially important given the interdisciplinary approach of thyroid and

Journal Pre-proof parathyroid surgery. Thyroid surgery is shared by Otolaryngologists and General Surgeons, which may lead to subtle differences in practice. There are few studies focusing on potential differences in incidence or management of post-operative hypocalcemia between these two fields. Current studies have evaluated differences in lymph node sampling techniques by surgical training type, stating that while surgical techniques varied significantly, they were independent of outcomes [11]. Given that physician training may impact management, it would be interesting

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to elucidate whether physician training-type impacts management decisions regarding

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United States and other surgeons internationally.

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hypocalcemia. This also goes for evaluating differences in practice between physicians in the

This study aims to determine whether surgeons routinely check preoperative vitamin D

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levels and whether calcium trends and PTH post-operatively are used in practice to assess for

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hypocalcemia. Furthermore, differences in approach to management based on type, level, and

Methods:

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geography of training will be explored.

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In this study, we included a population of General Surgeons and Otolaryngologists who

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regularly performed thyroidectomies and were members of the ATA or the International Association of Endocrine Surgeons (IAES). We sent a 20-question survey to all members (Figure 1). The survey questions included demographic information such as: years in practice, practice setting, geographic location of practice, type of specialty, fellowship training, and number of thyroidectomies performed per year. Data on age and sex were not collected in this survey. Questions relating to understanding of postoperative hypocalcemia included the estimated rate of temporary and permanent postoperative hypocalcemia. Questions relating to management of post-op calcium levels included percentage of cases that the surgeon performs

Journal Pre-proof auto-transplantation of a parathyroid gland, average length of hospital stay, whether the surgeon uses calcium trends and/or postoperative PTH level to evaluate for postoperative hypocalcemia, whether the surgeon uses rapid PTH levels, whether the surgeon administers prophylactic postoperative vitamin D or calcium supplements, does the surgeon routinely check a preoperative Vitamin D level, and whether the surgeon keeps the patient hospitalized until the calcium level plateaus.

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Variables are presented as mean plus or minus standard deviation for continuous

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variables and frequency (percentage of total) for categorical variables. Univariate analysis was

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performed using Analysis of Variance (ANOVA) for continuous variables and a chi-squared test for categorical variables. If n≤5 for a categorical variable then a Fisher’s exact test was used.

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Significance was determined if p<0.05. SAS version 9.4 (Cary, NC) was used for all statistical

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analysis.

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Results:

A total of 332 surgeons responded to the questionnaire, giving a response rate of 27%. At

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the time of response, 72.26% of respondents were in practice for an average of 18.92±11.05

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years (Table 1). Only 13.55% of respondents described themselves as working in a private practice while 62.35% describe themselves as working in an academic practice. Focusing on type of surgical training, 86.10% of respondents completed General Surgery training programs while only 13.55% of respondents completed Otolaryngology residency programs. A total of 70.69% of respondents received additional fellowship training. Of the respondents, 182 surgeons practice in the United States while 150 were from other countries. A majority of international respondents (45.33%) were from Europe and 33.33% of respondents were from Asia. Responses indicated that 42.42% of surveyed physicians routinely treat their postoperative total thyroidectomy

Journal Pre-proof patients with calcium supplementation, but 57.37% of respondents to the study survey felt that checking vitamin D levels when performing total thyroidectomy is not recommended (Table 2). The average length of stay after thyroidectomy reported by respondents was 2.32±1.60 days (Table 2). However, there was no significant difference in average length of stay by frequency of post-operative vitamin D level evaluation (p=0.64). Surgeons that performed >50 total thyroidectomies per year were more likely to check preoperative vitamin D levels compared

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to those surgeons that perform ≤50 total thyroidectomies per year (29.41% compared to 12.07%

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p=0.0226) (Table 3). Additionally, 29.52% of academic surgeons were likely to check

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preoperative vitamin D levels compared to 20.66% of non-academic surgeons (p=0.05). In addition to surgeon case volume and type of practice, geographic location in the US was

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suggestive of whether surgeons check preoperative vitamin D levels, with 43.48% of surgeons in

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the Northeast checking preoperative vitamin D levels, which was a significantly greater

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percentage than surgeons in other regions of the United States (p<0.01). Years in practice (p=0.74), whether the surgeon was considered a General Surgeon or Otolaryngologist (p=0.15)

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or if the surgeon practiced in the US compared to other countries (p=0.09) were not predictive of

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whether surgeons routinely checked preoperative Vitamin D levels. Only 13.29% of respondents routinely recommend that patients take prophylactic Vitamin D supplements in the postoperative period (Table 2).

With regards to postoperative hypocalcemia monitoring, 34.83% of surgeons routinely check postoperative serum calcium levels, while 13.21% of surgeons trend postoperative PTH levels, and 40.24% of surgeons check both. International surgeons were more likely to trend both serum Ca and PTH compared to US surgeons (50.67% vs 31.69%, p<0.01). However, there was

Journal Pre-proof no significant difference in practice pattern based on case volume, years in practice, surgical specialty, or type of practice (Table 4) Discussion: There were some differences in pre- and post-operative management in a variety of contexts. Variations in pre-operative vitamin D measurement were most impacted by casevolume, practicing in an academic center and practicing within the Northeast region of the

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United States. This is important, as vitamin D deficiency has been found to be a risk factor for

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the development of post-operative hypocalcemia and can be more prevalent in areas with

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significant winter seasons, such as the Northeast United States [12]. Surgeons with high yearly caseload of thyroidectomies were more likely to check preoperative vitamin D levels. This may

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be of significance because surgeon case-volume has been demonstrated to be a predictor of

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complication rates after thyroid surgery, and perhaps more experienced surgeons may be more

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likely to incorporate vitamin D evaluation into their practice [13]. Furthermore, average length of hospital stay did not vary based on surgeons and whether they checked preoperative vitamin D

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levels indicating that while practice may vary, outcomes and complications that would lengthen

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hospital stay do not appear to be impacted. Academic centers have also been found to more routinely evaluate preoperative vitamin D levels and this may be because studies have demonstrated increased adherence to practice guidelines in hospital and academic settings [14]. This could be a result of hospital settings having more hospital-wide practice guidelines that are required to be followed, along with greater access to guideline information through medical databases and libraries made accessible through the hospital [15]. Physicians in the private sector are less restricted by hospital policies and may choose to practice more individualized patient care, perceiving the rigidity of evidence-

Journal Pre-proof based medicine a threat to good clinic practice [15]. This individualized patient care could explain the rationale for not routinely checking preoperative vitamin D levels unless the physician perceives that a patient could be at increased risk for postoperative hypocalcemia. The northeast region of the United States was found to most regularly check preoperative vitamin D levels compared to other regions in the United States. This could be for a variety of reasons including that vitamin D deficiency is prevalent in the northeast US given the climate

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and weather. Studies have demonstrated that variation in northward latitude can decrease average

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vitamin D levels [6]. Increased concern in areas such as the northeast US may be contributing to

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more physician concern regarding vitamin D deficiency and its association with the development of post-operative hypocalcemia.

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With regards to international geography, postoperative evaluation of calcium and PTH

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levels was used more often by international surgeons compared to surgeons practicing in the

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United States to monitor hypocalcemia (p <0.01) but did not demonstrate variance with regards to any other practice variables. This is particularly interesting given that the ATA does

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recommend use of calcium and PTH levels for predicting post-operative hypocalcemia because

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studies have demonstrated that this information is useful and stratifying patients for short-term versus long-term stay [5]. This is all the more important given that it is becoming more common for thyroid surgeries to be performed in an outpatient setting, making monitoring for complications less convenient [16]. It becomes of greater value to have a measure to risk-stratify patients with. Furthermore, an international survey conducted in March 2017 claimed that although less than 10% of surgeons perform thyroid surgery in an outpatient setting, the majority that do so are surgeons in the US, particularly Otolaryngologists [17]. This may be due to lack of knowledge regarding the need for PTH assays, or that physicians performing thyroid surgery in

Journal Pre-proof an outpatient setting may have deemed these patients low-risk for post-operative complications. Given that outpatient thyroid surgery is most prevalent in the United States, it may be reasonable that the number of physicians checking PTH levels may be lower [17]. An interesting practical concern is whether our study found any differences in perioperative management of thyroidectomy patients between General Surgeons and Otolaryngologists that could lend itself to different outcomes. However, there was no suggested

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difference in evaluation of preoperative vitamin D levels between General Surgeons and

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Otolaryngologists, nor was there any difference in outcomes resulting in differences in length of

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hospital stay between physicians who check and do not check preoperative vitamin D (p = 0.64). Additionally, there was no significant difference in whether surgeons evaluated serum calcium or

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PTH levels between General Surgeons and Otolaryngologists.

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Despite the findings noted above, it is important to recognize that overall 67.06% of

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surgeons surveyed noted that they did not regularly check preoperative vitamin D levels, and 57.37% of surgeons did not believe it is recommended to check preoperative vitamin D levels.

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The ATA has indicated that vitamin D deficiency is a risk factor for transient hypocalcemia [7].

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Further specification regarding routine preoperative vitamin D measurement may be an additional measure that can be taken to reduce the risk of developing postoperative hypocalcemia, which could potentially lead to better short-term and long-term outcomes for patients as well as reduced hospital spending. Additionally, standardizing perioperative labs, including vitamin D, serum calcium, and intact PTH, between disciplines and practice settings can create a more uniform way of practice. A major strength of this study is the inclusion of surgeons from Asia, Europe and the United States, widening the applicability of these findings. Additional strengths include study

Journal Pre-proof size and anonymity of survey. There are few studies evaluating management decisions regarding post-operative hypocalcemia and differences between Otolaryngologists and General Surgeons who share this domain. Limitations include selection bias in that we had a response rate of 27%.. Secondly, recall bias may be present with regards to case volume per year along with frequency with which preoperative vitamin D levels are checked, as this data is based on self-reported information. It may also be difficult to accurately compare General Surgeons and

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Otolaryngologists through this study as the sample size of Otolaryngologists who responded was

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significantly smaller. The survey was also not created to assess patient outcomes beyond length

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of hospital stay, which can be influenced by multiple factors including comorbidities and other medical complications. Finally, there are variations in how hospitals define hypocalcemia and

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the definition each survey responder uses.

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these variations were not taken into account in this study and rather hypocalcemia was based on

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Conclusion

Using a questionnaire distributed to both General Surgeons and Otolaryngologists in both

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the United States and Internationally, we have demonstrated that there is significant variation in

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practice patterns when preventing and monitoring postoperative hypocalcemia in patients receiving total thyroidectomy that often times differ from recommended guidelines. Further research into absolute guidelines may lessen the incidence of post-operative hypocalcemia, and implementing set guidelines used to predict post-operative hypocalcemia can be an important step in standardizing the manner in which this complication is handled.

Journal Pre-proof References 1. Tredici P, Grosso E, Gibelli B, Massaro MA, Arrigoni C, Tradatini N. Identification of patients at high risk for hypocalcemia after total thyroidectomy . Acta Otorhinolaryngologica Italica. 2011;31(3):144-148. 2. Pechter, W. and Steward, D. (2010). PACU PTH Facilitates Safe Outpatient Total Thyroidectomy. Otolaryngology-Head and Neck Surgery, [online] 143(1), pp.43-47. Available

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at: https://pdfs.semanticscholar.org/f178/ae22a2c124b3d0162595bb6b704495fd3b13.pdf.

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3. Luo H, Yang H, Wei T, et al. Protocol for management after thyroidectomy: a retrospective

2017;13:635-641. doi:10.2147/TCRM.S129910.

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study based on one-center experience. Therapeutics and Clinical Risk Management.

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4. FitzGerald, R.A., Sehgal, A.R., Nichols, J.A. et al. Ann Surg Oncol (2015) 22(Suppl 3): 707. ./

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5. Noureldine SI, Genther DJ, Lopez M, Agrawal N, Tufano RP. Early Predictors of

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Hypocalcemia After Total ThyroidectomyAn Analysis of 304 Patients Using a Short-Stay Monitoring Protocol. JAMA Otolaryngol Head Neck Surg. 2014;140(11):1006–1013.

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doi:10.1001/jamaoto.2014.2435

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6. Falcone TE, Stein DJ, Jumaily JS, et al. Correlating pre-operative vitamin D status with postthyroidectomy hypocalcemia. Endocr Pract. 2015; 21: 348– 354. 7. Bahn, R., Burch, H., Cooper, D., Garber, J., Greenlee, M., Klein, I., Laurberg, P., Mcdougall, R., Montori, V., Rivkees, S., Scott, D., Sosa, J. and Stan, M. (2011). Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association on Clinical Endocrinologists. ATA/AACE Guidelines. 8. Husein M, Hier MP, Al-Abdulhadi K, Black M. Predicting calcium status post thyroidectomy with early calcium levels. Otolaryngol Head Neck Surg. 2002;127:289e293 9. Szubin L, Kacker A, Kakani R, Komisar A, Blaugrund S. The management of post-

Journal Pre-proof thyroidectomy hypocalcemia. Ear Nose Throat J . 75(9):612-4,616. https://www.ncbi.nlm.nih.gov/pubmed/8870367. 10. Patel NA, Blue RA, Adams S, et al. A clinical pathway for the postoperative management of hypocalcemia after pediatric thyroidectomy reduces blood draws. International Journal of Pediatric Otorhinolaryngology. 105:132-137. doi:https://doi.org/10.1016/j.ijporl.2017.12.011. 11. Takesuye R, Brethauer S, Thiringer JK, Riffenburgh RH, Johnstone PAS. Practice analysis:

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techniques of head and neck surgeons and general surgeons performing thyroidectomy for

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cancer. Qual Manag Health Care. 2006;15:257–62. doi: 10.1097/00019514-200610000-00007.

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12. Tripathi M, Karwasra RK, Parshad S. Effect of preoperative vitamin D deficiency on postoperative hypocalcemia after thyroid surgery. Thyroid Research. 2014;7:8.

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doi:10.1186/1756-6614-7-8.

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13. Basu S, Andrews J, Kishore S, Panjabi R, Stuckler D. Comparative Performance of Private

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and Public Healthcare Systems in Low- and Middle-Income Countries: A Systematic Review. Jenkins R, ed. PLoS Medicine. 2012;9(6):e1001244. doi:10.1371/journal.pmed.1001244.

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14. Hisham R, Ng CJ, Liew SM, Hamzah N, Ho GJ. Why is there variation in the practice of

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evidence-based medicine in primary care? A qualitative study. BMJ Open. 2016;6(3):e010565. doi:10.1136/bmjopen-2015-010565. 15. Leary PF, Zamfirova I, Au J, McCracken WH. Effect of latitude on vitamin D levels. J Am Osteopath Assoc. 2017;117(7):433–439. doi: 10.7556/jaoa.2017.089 16. Balentine CJ, Sippel RS. Outpatient Thyroidectomy: Is it Safe? Surgical oncology clinics of North America. 2016;25(1):61-75. doi:10.1016/j.soc.2015.08.003. 17. Maniakas A, Christopoulos A, Bissada E, Guertin L. Perioperative practices in thyroid surgery: An international survey. Head Neck. 2017;39(7):1296-1305. doi:10.1002/hed.24722.

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Table 1: Demographic Factors Total 310 331 272 23 86 224 332 76 207

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22.89% 62.35% 13.55% 1.20% 23.26% 62.84% 5.74% 7.85% .30% 37.91%

Australia Africa

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7.33% 0.66%

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19.23% 29.12% 7.69% 6.04%

Other Countries Asia Europe North America(Excluding the US) South America

35 53 14 11 150 50 68 16 4

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Southeast Midwest West Coast Southwest

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Region in the US Northeast

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Type of Training Program General Surgery Residency General Surgery Residency+fellowship Otolaryngology Residency Otolaryngology Residency+fellowship Other

45 4 331 77 208 19 26 1 182 69

27.74% 72.26%

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Private Practice Resident/Fellow

82.18%

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Practice Type Hospital Practice Academic Practice

18.92±11.05 years

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Years in practice Number of thyroid surgeries >50 cases/year Number of years in practice ≤10 years >10 years

33.33% 45.33% 10.66% 2.66%

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Table 2: Descriptive Statistics for Management of Postoperative Hypocalcemia 330 2.32±1.60 days Average length of stay 330 Do you routinely give your patients postop calcium Yes 140 42.42% No 155 46.97% Sometimes 35 10.61% 331 Do you routinely check a preoperative vitamin D level? yes 44 13.29% no 222 67.07% Sometimes 65 19.64% 324 Have you ever had a patient become hypercalcemic Yes 165 50.93% No 159 49.07% 309 Do you routinely place a drain in your total or completion thyroidectomy patients? Yes

26.20%

222 319

66.87%

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4.08%

57 34 183 29

17.87% 10.66% 57.37% 9.09%

44 222 65

13.29% 67.07% 19.64%

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No

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1 week 10 weeks Not Recommended Other

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When do you recommend checking a Vitamin D level prior to thyroidectomy? Preop holding area

Do you give all your thyroidectomy patients prophylactic vitamin D in the postoperative period? Yes No Sometimes

Journal Pre-proof Table 3: Factors Determining Whether Surgeons Routinely Check Vitamin D Levels Variable Yes No Sometimes p-value Average LOS 2.27±1.48 2.37±1.67 2.11±1.43 0.64 (days) Number of cases

Non-academic Surgeons in the US Surgeons from other countries Region in the US Northeast Southeast Midwest West Coast Southwest

21(21.42)

55(63.95)

10(11.63)

60(26.79)

144(64.29)

20(8.93)

72(25.35)

186(65.49)

26(9.15)

15(33.33)

23(51.11)

62(29.52)

123(58.57)

25(11.90)

25(20.66)

87(71.90)

9(7.44)

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26(9.56)

7(15.56)

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Practice Type Academic

166(61.03)

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Otolaryngology

80(29.41)

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Type of training General Surgery

8(13.79)

55(30.22)

106(58.24)

21(11.54)

104(69.80)

13(8.72)

31(44.93)

8(11.59)

25(71.43)

4(11.43)

8(15.09)

37(69.81)

8(15.09)

5(35.71)

8(57.14)

1(7.14)

6(54.55)

5(45.45)

0(0.0)

32(21.48) 30(43.48)

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>10 years

43(74.14)

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Years in practice ≤10 years

7(12.07)

6(17.14)

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≤50 cases/year >50 cases/year

0.02

0.74

0.15

0.05

0.09

<0.01

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Variable Number of cases ≤50 cases/year >50 cases/year

Serum Ca

PTH

Both

Neither

24 (40.68) 91(33.46)

4 (6.78) 40(14.71)

22(37.29) 111(40.81)

9(15.25)

26(30.23)

12(13.95)

35(40.70)

13(15.12)

80(35.71)

26(11.61)

94(41.96)

24(10.71)

97(34.04)

37(12.98)

117(41.05)

34(11.93)

17(37.78)

7(15.56)

16(35.56)

5(11.11)

71(33.65)

32(15.17)

87(41.23)

44(36.36)

12(9.92)

47(38.84)

64(34.97)

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Table 4: Factors Determining Whether Surgeons Routinely Check Postoperative PTH or Serum Calcium

30(16.39)

58(31.69)

18(14.88) 31(16.94)

14(9.33)

76(50.67)

8(5.33)

30(11.03)

p-value

0.26

Type of training General Surgery Otolaryngology

Surgeons from other countries

Figure 1: Survey

52(34.67)

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Surgeons in the US

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Non-academic

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Academic

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Practice Type

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>10 years

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≤10 years

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Years in practice 0.60

0.88

21(9.95 0.33

<0.01

Figure 1r1

Figure 1r2