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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 10  |  Issue : 2  |  Page : 167-172

The staggering hypothyroidism in head-and-neck cancer patients after combined multimodality treatment: Dealing with the anesthetic dilemma


1 Department of Anesthesia, Bendigo Health, Victoria, Australia
2 Department of Anaesthesiology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
3 Department of Anaesthesia, Manchester University NHS Foundation Trust, London, United Kingdom

Date of Submission06-Sep-2022
Date of Acceptance25-Sep-2022
Date of Web Publication15-Dec-2022

Correspondence Address:
Sunil Rajan
Department of Anaesthesiology, Amrita Institute of Medical Sciences, Kochi, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jhnps.jhnps_57_22

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  Abstract 


Background and Aims: Hypothyroidism is common following treatment of head-and-neck malignancy. We aimed to assess the incidence of hypothyroidism in patients posted for operations with a history of radical neck surgeries with or without adjuvant chemoradiotherapy, their requirement of induction agents, hemodynamic changes, and recovery time following general anesthesia. Methods: This was a prospective, nonrandomized single-arm study conducted in 100 patients aged 18–85 years, who were posted for surgery under general anesthesia after 3 months of radical neck surgery with or without adjuvant therapy. All patients received a standardized general anesthesia protocol. Patients were grouped into those having either hypothyroidism or those in the euthyroid state. Results: Seventy-two percent of patients had varying degrees of hypothyroidism. There was significant reduction in heart rate (HR) and mean arterial pressure (MAP) from preinduction values at 1, 3, 5, and 10 min after intubation in patients with hypothyroidism. The reduction in both HR and MAP was significantly pronounced throughout postintubation period in the hypothyroid patients as compared to the patients with normal thyroid function. The mean induction dose of propofol was significantly lesser for hypothyroid patients compared with euthyroid (0.85 ± 0.17 mg/kg vs. 1.62 ± 2.52 mg/kg), with prolonged recovery time. The incidence of hypotension was significantly high among the hypothyroid patients. Conclusion: The incidence of hypothyroidism in patients after radical neck surgery with or without adjuvant chemo-radiotherapy is as high as 72%. These patients required less anesthetic agents for the induction of general anesthesia and developed profound hypotension after induction which persisted after intubation and had a prolonged recovery time.

Keywords: General anesthesia, hypothyroidism, induction, malignancy, recovery


How to cite this article:
Vasu BK, Rajan S, Sasikumar NK, Babu SC, Sudevan M, Paul J. The staggering hypothyroidism in head-and-neck cancer patients after combined multimodality treatment: Dealing with the anesthetic dilemma. J Head Neck Physicians Surg 2022;10:167-72

How to cite this URL:
Vasu BK, Rajan S, Sasikumar NK, Babu SC, Sudevan M, Paul J. The staggering hypothyroidism in head-and-neck cancer patients after combined multimodality treatment: Dealing with the anesthetic dilemma. J Head Neck Physicians Surg [serial online] 2022 [cited 2023 Feb 1];10:167-72. Available from: https://www.jhnps.org/text.asp?2022/10/2/167/363928




  Introduction Top


Anesthesia for onco-surgical patients is often challenging and demanding in terms of its timely requirements, and it is a developing subspecialty with new vigor. Head-and-neck malignancy is managed with radical surgeries and other combination therapies. These patients have high risk for developing clinical or subclinical hypothyroidism as an undesirable sequela of the treatment. The risk increases 3 − 6 months after surgery and is found to be higher among those who had preoperative radiotherapy.[1],[2] Even though on-going monitoring of the thyroid function is recommended after laryngectomies and other advanced surgeries in the region, many patients return for repeat surgical procedures for the correction of the delayed surgical complications or disease recurrence without thyroid function assessment or monitoring and the necessary appropriate management. The delayed complications needing surgical interventions were for recurrence, node clearance, wound dehiscence, flap necrosis, or fistula formation.

The primary objective of our study was to find the incidence of hypothyroidism in patients with history of nonthyroid radical neck surgeries with or without adjuvant chemotherapy and/or radiotherapy requiring related repeat surgeries. The secondary objectives were to find the quantity of propofol used for induction, the hemodynamic changes during induction, and the recovery time following general anesthesia in this cohort of patients.


  Methods Top


This was a prospective, nonrandomized, single arm, observational study conducted over a period of 2 years in a nonprofitable charity hospital, a tertiary care referral center in South India, with a major head and neck onco-surgical unit. After obtaining approval from the Institutional Review Board and Ethics Committee and registration in Clinical Trials Registry-India (CTRI/2020/01/022948), the trial was conducted in 100 patients, aged 18–85 years, after obtaining their written informed consent. Patients were recruited from the semi-elective surgical list for general anesthesia with a history of radical neck surgery with or without adjuvant therapy more than 3 months before their subsequent surgery. Onco-surgical patients with a history of thyroid disorder at the time of their primary surgery, total thyroidectomy, panhypopituitarism; postlaryngectomy patients, and those on tracheostomy or known history of difficult airway requiring fiberoptic bronchoscope-assisted intubations were excluded from the study.

The patient population in the study was from the various geographic and remote locations with diverse socioeconomic backgrounds. Their thyroid function tests during the preanesthetic visit or within 1 week before the surgery if available were noted for the study. Thyroid dysfunction, if present, was stabilized within 1 week preceding the surgery in consultation with endocrinologist, since delaying surgeries for longer periods were feared to affect the overall outcome of the patient adversely. Patients of severe hypothyroidism with features such as bradycardia and thyroid-stimulating hormone (TSH) values > 50 mIU/L in whom optimization within 1 week were deemed impossible were not taken for the study.

Patients on thyroxine supplements were required to continue the medication preoperatively. All patients received standardized general anesthesia with universally accepted safety measures and monitoring as per the protocol. Patients were hydrated with Ringer lactate at 10 mL/kg body weight per hour before surgery. After preoxygenating for 3 min, fentanyl 2 μg/kg and glycopyrrolate 0.2 mg were given intravenously. Propofol 20 mg every 10 s titrated to the loss of response to verbal commands was used for induction of general anesthesia and direct laryngoscopy was facilitated with suxamethonium 2 mg/kg. After 1 min of mask ventilation with 1 minimum alveolar concentration (MAC) of inhalational agent in oxygen, laryngoscopy and tracheal intubation was performed with 7.0 or 6.5 mm cuffed endotracheal tube for male and female patients, respectively. Correct placement of endotracheal tube was confirmed by auscultation and by confirming the appearance of regular square wave end-tidal carbon dioxide waveforms.

Anesthesia was maintained with 1 MAC of the inhalation agent in air oxygen mixture (1:1) with mechanical ventilation by monitoring respiratory gases, continuous pulse oximetry, and end-tidal capnography with end-tidal gas analysis for the depth of anesthesia. As the availability of processed electroencephalogram was not possible for every patient, the bispectral index (BIS) monitoring was not used. Atracurium 0.5 mg/kg was used as the muscle relaxant in all patients after intubation. Heart rate and mean arterial blood pressure were recorded before induction of and at 1, 3, 5, and 10 min (s) after intubation. The dose of propofol required for induction and the recovery time were also noted. The recovery time was calculated from the time of discontinuing inhalational agent to extubation after reversing neuromuscular blockade when the patient was awake with return of protective airway reflexes. Any increase in mean arterial pressure (MAP) by ≥20% intraoperatively was managed with a bolus of 20–30 mg propofol. Tachycardia and hypertension from surgical stimuli were managed with 0.5 μg/kg of fentanyl; fall in MAP by >20% was managed with a bolus of 250 mL of intravenous fluid initially followed by incremental doses of 3–6 mg of ephedrine or 50 μg of phenylephrine as necessary. Noradrenaline infusion was started in patients with persistent hypotension. The incidence of hypotension requiring interventions, fluids, and medication was noted.

The categorical variables were presented as number and percentage and continuous variables as mean with standard deviation. The comparison of observed means was done using the independent samples t-test and Chi-squared test was used for the comparison of proportions. MedCalc Software Ltd. version 20.110 (Acacialaan 22 8400 Ostend, Belgium) was used for the statistical analysis.


  Results Top


One hundred and eight patients were considered for recruitment for the trial. Anesthesia was deferred in eight patients as they had overt features of severe hypothyroidism such as bradycardia with TSH values >50 mIU/L. The data of 100 patients were available for the analysis. Twenty-eight patients were euthyroid (Group N) and 72 patients had varying degrees of hypothyroidism [Group H, [Table 1]] despite 65 patients among them being already on thyroid supplements when scheduled for surgery.
Table 1: Thyroid function tests Group H (n=72)

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The mean age of patients was 68 ± 6.5 years, weight 56 ± 8.3 kg, preinduction heart rate (HR) 68 ± 22/min, and MAP 106 ± 13 mmHg. There was significant reduction in HR and MAP from preinduction values at 1, 3, 5, and 10 min after intubation [Table 2] in patients with hypothyroidism. The hypothyroid patients had a significantly lower baseline HR than the euthyroid patients as expected; but it was not very low, and the lowest HR was 58/min before induction. Hypothyroid patients had marginally higher but statistically insignificant baseline MAP than the euthyroid patients (112 ± 13 and 108 ± 9 mmHg, respectively). The reduction in both HR and MAP was significantly more pronounced throughout the postintubation period in the hypothyroid group of patients compared to the patients with normal thyroid function [Table 2] and [Figure 1], [Figure 2].
Table 2: Comparison of heart rate and mean arterial pressure between preinduction and postinduction within hypothyroid group (Group H) and between hypothyroid group (Group H) and euthyroid group (Group N) of patients

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Figure 1: Changes in mean heart rate

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Figure 2: Changes in mean arterial pressure

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The mean induction dose of propofol was lesser by half with 0.85 ± 0.17 mg/kg for hypothyroid patients while it was 1.62 ± 2.52 mg/kg for patients with normal thyroid function. The difference was statistically significant (P = 0.018). The mean recovery time was 15.62 ± 5.43 min in the hypothyroid patients while euthyroid patients had the recovery time reduced by two and a half times to 6.24 ± 1.38 min, which was significantly low [P < 0.0001, [Table 3]]. The incidence of hypotension was significantly high among the hypothyroid patients, with 86% of them requiring ephedrine, phenylephrine, or noradrenaline soon after induction while hypotension occurred in 40% of patients with normal thyroid function (P < 0.001).
Table 3: Comparison of propofol dose, recovery time and the need for vasopressors or inotropes

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  Discussion Top


Head-and-neck cancers constitute one-third of cancers in India, which are mostly a heterogeneous cluster of malignancies arising from the upper aero-digestive tract.[3] Cancer surgeries require meticulous follow-up and timely appropriate management to have the best outcome. Lack of satisfactory follow-up due to poor understanding of the natural course of cancers and the need for surveillance, socioeconomic constraints, and remoteness of home from the cancer centers are some of the factors affecting the outcome adversely in the head-and-neck cancers in India.[4] This in turn influences the optimization of these patients, especially when they have to undergo further surgeries for surgical inadequacies or complications or disease recurrence.

Thyroid dysfunction is a major problem that is often overlooked which may have serious implications in the health and response to subsequent surgeries of these patients. The disease itself and all modalities of therapy can affect the thyroid function adversely. Hypothyroidism is one of the late adverse effects after radiation therapy (RT) or combination therapies for head-and-neck cancers. The incidence of hypothyroidism depends on the absorbed dose of radiation by the thyroid gland.[5] Sinard et al. assessed the incidence of posttreatment hypothyroidism in 198 patients who underwent surgery with or without radiotherapy for nonthyroid head-and-neck cancer.[6] Eighty percent of these patients had advanced stage (III or IV) or recurrent cancer. It was observed that approximately 15% of patients treated for advanced head-and-neck cancers with surgery and radiotherapy developed hypothyroidism within a mean follow-up of 12 months. Those treated with total laryngectomy, including thyroid lobectomy, followed by radiotherapy were at the greatest risk, with 61% of patients having developed hypothyroidism while it was 12% among those who had surgeries for nonlaryngeal cancers and radiotherapy.

Hypothyroidism with associated advanced tumor stage, flap reconstruction, and postoperative hypokalcemia is implicated interfering with wound healing and leading to fistula formation.[7] Cancer chemotherapy and immunotherapy can cause hypothyroidism. Sunitinib, a targeted therapeutic agent, was reported causing hypothyroidism in 20%–70% of patients.[8],[9],[10],[11] Other antineoplastic agents are also implicated in causing thyroid dysfunction, mostly hypothyroidism and rarely hyperthyroidism as well.[11]

Life-long TSH screening is recommended for patients undergoing RT to the neck owing to the increased incidence of radiation-induced hypothyroidism and the importance of early thyroid hormone replacement therapy in patients becoming hypothyroid for maintaining optimal quality of their life.[12] However, due to several reasons, many patients fail to comply for elective surveillance[4] and return for follow-up when it is inevitable. In our cohort of patients, varying degrees of hypothyroidism was identified in 72% of patients during the preoperative assessment for their re-operations.

Hypothyroidism can lead to many adverse events during the conduct of general anesthesia. Increased sensitivity to cardio-depressant effects of anesthetics in hypothyroidism could be due to decreased intravascular volume, decreased preload, blunted baroreceptor response, and decreased cardiac output. The degree of hemodynamic instability correlates with the degree of thyroid dysfunction.[13] Subclinical hypothyroidism is associated with an increased risk of congestive heart failure among older adults with a TSH level of 7.0 mIU/L or more, but not with other cardiovascular events and mortality.[14] TSH value of up to 15 mIU/L is considered safe for head-and-neck cancer surgeries in carefully selected asymptomatic patients with subclinical hypothyroidism.[15] However, there has been no randomized control trials on or regarding the optimal minimum duration of optimization required for hypothyroid patients undergoing semi-elective surgeries.

Postlaryngectomy patients have been found showing minimal or absent hemodynamic stress response to endotracheal intubation and developing profound hypotension following induction of general anesthesia that persisted despite intubation.[16] Decreased intravascular volume due to preoperative dehydration, hypertension, and baroreceptor failure might have contributed to the postinduction hypotension in these patients. Cancer chemotherapy can induce cardiac, pulmonary, renal, hepatic, gastrointestinal, bone marrow, and neurological damages. Some toxic effects can be long-lasting like the pulmonary fibrosis induced by bleomycin potentially aggravated by the administration of high concentration of oxygen. The myocardial depressant effects of anesthetic agents can exacerbate the chemotherapy-induced cardiotoxicity.[17]

The mean induction dose of propofol was 0.85 ± 0.17 mg/kg in our study in patients with hypothyroidism. It can be assumed that the effects of hypothyroidism rendered them more susceptible to the depressant effects of anesthetic drugs on the central nervous and cardiovascular systems. The presence of hypoalbuminemia secondary to catabolic states or malnutrition in cancer patients could be a factor contributing to the accelerated anesthetic effects of propofol as it is 97%–99% protein bound. The effects of hypothyroidism and the enhanced effects of depressant actions of the anesthetic drugs could be the reasons for the prolonged recovery time (15.62 ± 5.43 min) and high incidence of hypotension which was observed in up to 86% of our patients after induction of general anesthesia, which required inotropic/vasopressor administration.

The causes of the reduced requirements of propofol for the induction of anesthesia and the prolongation of recovery time could be far beyond the reduced thyroid function alone. Nutritional status could be deteriorated due to the functional disturbances in speech, swallowing, hearing, breathing, and associated social interaction besides the disease status and the treatment itself.[18],[19],[20] Facial disfigurements, rarely even dependence on enteral tube feeding, lowered self-esteem, lack of initiative in socializing and competing with peers, limitations in employment opportunities and growth at work place are the important factors impeding their quality of life and psychological status besides financial constraints coming in the way of their surgical course and cancer surveillance.

The result of the study reinforces the recommendation of preoperative thyroid function assessment and optimization when patients with history of radical neck surgeries with or without adjuvant chemo-radiotherapy need further surgical interventions. Surgery may be postponed in those having severe hypothyroidism who are symptomatic for better tolerance to anesthesia and optimal surgical outcome. Even when anesthetizing those with asymptomatic hypothyroidism extra care should be taken to identify and treat untoward complications promptly during conduct of general anesthesia.

Limitations of the study

Detailed assessment of socioeconomic and nutritional statuses was not uniformly obtained preoperatively in these patients due to the various reasons including financial constraints. These might have given further insights into the differences in the hemodynamic behavior among the groups and possibly the linkage with the patients' background.


  Conclusion Top


The incidence of hypothyroidism in patients after radical neck surgery with or without adjuvant chemo-radiotherapy was as high as 72%. These patients required a reduced amount of anesthetic agents for the induction of general anesthesia, showed pronounced postinduction hypotension that persisted after intubation, and had a prolonged recovery time.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Disclosure

This material has never been published and is not currently under evaluation in any other peer reviewed publication.

Ethical approval

The permission was taken from Institutional Ethics Committee before starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.



 
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Dutta S, Biswas KD, Ghatak S, Haldar D, Sen I, Sinha R. Postoperative hypofunctioning of the thyroid gland after total laryngectomy. Ear Nose Throat J 2016;95:E23-7.  Back to cited text no. 1
    
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Cinar U, Yiğit O, Alkan S, Uslu B, Topuz E, Unsal O, et al. The effect of laryngectomy and postoperative radiotheraphy on thyroid gland functions. Kulak Burun Bogaz Ihtis Derg 2003;10:226-30.  Back to cited text no. 2
    
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Dandekar M, Tuljapurkar V, Dhar H, Panwar A, DCruz AK. Head and neck cancers in India. J Surg Oncol 2017;115:555-63.  Back to cited text no. 3
    
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Prakash Saxena PU, Unnikrishnan B, Rathi P, Kotian H, Reshmi B. Survival analysis of head and neck cancer: Results from a hospital based cancer registry in southern Karnataka. Clin Epidemiol Glob Health 2019;7:346-50.  Back to cited text no. 4
    
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Fujiwara M, Kamikonya N, Odawara S, Suzuki H, Niwa Y, Takada Y, et al. The threshold of hypothyroidism after radiation therapy for head and neck cancer: A retrospective analysis of 116 cases. J Radiat Res 2015;56:577-82.  Back to cited text no. 5
    
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Sinard RJ, Tobin EJ, Mazzaferri EL, Hodgson SE, Young DC, Kunz AL, et al. Hypothyroidism after treatment for nonthyroid head and neck cancer. Arch Otolaryngol Head Neck Surg 2000;126:652-7.  Back to cited text no. 6
    
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Rosko AJ, Birkeland AC, Bellile E, Kovatch KJ, Miller AL, Jaffe CC, et al. Hypothyroidism and wound healing after salvage laryngectomy. Ann Surg Oncol 2018;25:1288-95.  Back to cited text no. 7
    
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Mahipal A, Tijani L, Chan K, Laudadio M, Mastrangelo MJ, Sato T. A pilot study of sunitinib malate in patients with metastatic uveal melanoma. Melanoma Res 2012;22:440-6.  Back to cited text no. 8
    
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Rutkowski P, Bylina E, Klimczak A, Switaj T, Falkowski S, Kroc J, et al. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure – One institution study. BMC Cancer 2012;12:107.  Back to cited text no. 9
    
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Del Fabbro E, Dev R, Cabanillas ME, Busaidy NL, Rodriguez EC, Bruera E. Extreme hypothyroidism associated with sunitinib treatment for metastatic renal cancer. J Chemother 2012;24:221-5.  Back to cited text no. 10
    
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Hamnvik OP, Larsen PR, Marqusee E. Thyroid dysfunction from antineoplastic agents. J Natl Cancer Inst 2011;103:1572-87.  Back to cited text no. 11
    
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Sudha P, Koshy RC, Pillai VS. Undetected hypothyroidism and unexpected anesthetic complications. J Anaesthesiol Clin Pharmacol 2012;28:276-7.  Back to cited text no. 13
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Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med 2005;165:2460-6.  Back to cited text no. 14
    
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Galloway T, Amdur RJ. Management and prevention of complications during initial treatment of head and neck cancer. UpToDate 2022. Available from: https://www.uptodate.com/contents/management-and-prevention-of-complications-during-initial-treatment-of-head-and-neck-cancer. [Last accessed on 2022 Sep 01].  Back to cited text no. 20
    


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