Thyroid Disease and Anesthetic Considerations 4/22/2017 Thyroid Disease and Anesthetic Considerations Jose Soliz, M.D. LBJ Grand Rounds February 2004

Basic Thyroid Gland Physiology 4/22/2017 Basic Thyroid Gland Physiology Hormones triiodothyronine (T3) and thyroxine (T4) are bound to proteins and stored in the thyroid gland. T3 is more potent and less protein bound, most T3 is made in peripheral tissues from the de-iodination of T4 Both hormones increase carbohydrate and fat metabolism, increasing metabolic rate, minute ventilation, heart rate and contractility, water / electrolyte balance, normal function of CNS.

Hyperthyroidism Causes 4/22/2017 Hyperthyroidism Causes Graves Disease-most common toxic multinodular goiter TSH hormone secreting pituitary tumors functioning thyroid adenomas overdose of thyroid replacement medication Garves disease is a systemic autoimmune disease where thyroid secreting antibodies promote hypersecretion of T4 and T3 Classically characterized by triad of hyperthyroidism, exopthalmos, and dermopathy

4/22/2017 Hyperthyroidism Diagnosis: made by abnormal TFT’s, elevated total and free T4, T3 low TSH, elevated free thyroxine index Medical Treatment consists of drugs that inhibit hormone synthesis (PTU-propylthiouracil, MMI-methimazole), inhibit hormone release (potassium, or sodium iodide) or mask the signs of adrenergic activity (Beta-blocker) While Beta blockade does not affect thyroid gland function, it does decrease the peripheral conversion of T4 to T3. Radioactive iodine and subtotal thyroidectomy are other alternatives to medical therapy Free thyroxine index: Total T4*thyroid binding ratio(T3 uptake) Amount of thyroid binding globulin increases with pregnancy, hepatic disease and estrogen therapy First line treatment are drugs that inhibit synthesis of thyroid hormones. Potassium iodide(Lugol solution) will inhibit the release of T3 and T4, and can inhibit new hormone synthesis by blocking organification Antithyroid drug therapy should precede the initiation of iodide since iodide alone can increase thyroid hormone stores. For patients allergic to iodine, lithium carbonate300mg PO Q6 will inhibit hormone release Radioablative therapy or surgery usually reserved for patients who antithyroid drugs are ineffective, toxic, or relapse occurs after 1-2 years of treatment

Hyperthyroidism Clinical Manifestations 4/22/2017 Hyperthyroidism Clinical Manifestations Weight loss heat intolerance muscle weakness diarrhea hyperactive reflexes nervousness / anxiety Physical: fine tremor, exophthalmos, goiter, warm clammy skin, fine brittle hair Cardiac: sinus tach, A Fib, increase in contractility, CO Signs and symptoms are that of a hypermetabolic state: tachycardia, palpitations, increased contractility and cardiac output, and possible cardiomegaly

Hyperthyroidism Anesthetic considerations-Preoperative 4/22/2017 Hyperthyroidism Anesthetic considerations-Preoperative Antithyroid medications and beta-blockers should be continued through the morning of surgery. Miller: Ideally patient should be rendered euthyroid prior to any elective procedure. Beginning pre-op antithyroid meds take 2-6weeks for effect, can use KI with Beta-blocker in addition, or alternative Benzodiazepines are good choice for pre-operative sedation Careful evaluation of patients airway Cardiac status must be evaluated adequately with ECG, and prior cardiac studies depending on the patient and procedure. There is direct correlation to severity of disease and intraoperative risk, mainly associated with cardiac status Patients should be rendered euthyroid prior to any elective surgery, Potassium iodide should be given 7-14 days prior to surgery. Hinders the secretion of thyroxine and peripheral conversion of T4 to T3. Though incidence of thyroid storm is extremely low, the preopertive use of KI dramitically decreased the incidince of thyroid storm. Anxiety has been shown to increase the severity of symptoms of hyperthyroidism, so benzos make a goof pre-op sedation choice. In addition to theusual pre-op evaluation and testing, careful attention should be given to the airway and patients may have a large goiter. Awake fiberoptic intubation may be necessary if there is a high suspecion of airway compromise

Hyperthyroidism Anesthetic considerations-Intraoperative 4/22/2017 Hyperthyroidism Anesthetic considerations-Intraoperative No controlled study suggest advantages of particular anesthetic drug or technique for hyperthyroid patients, however: Drugs that stimulate sympathetic nervous system should be avoided because of the possibility of large increases in blood pressure and heart rate. Ex. Ketamine. Pancuronium, atropine, ephedrine, epi Thiopental may be induction agent of choice as it possess antithyroid activity at high doses. Thiopental secondary to its thiourlene nucleus, inhibits the peripheral conversion of T4 to T3 regional anesthesia may be technique of choice because of its limiting of cardiovascular response

Hyperthyroidism Anesthetic considerations-Intraoperative 4/22/2017 Hyperthyroidism Anesthetic considerations-Intraoperative Close monitoring of cardiac function and body temperature is required. Need for invasive monitoring? Adequate anesthetic depth should be obtained prior to laryngoscopy or surgical stimulation to avoid tachycardia, hypertension, ventricular dysrhythmias Eye protection Thiopental secondary to its thiourlene nucleus, inhibits the peripheral conversion of T4 to T3 regional anesthesia may be technique of choice because of its limiting of cardiovascular response

Hyperthyroidism Anesthetic considerations-Intraoperative 4/22/2017 Hyperthyroidism Anesthetic considerations-Intraoperative Anticipate exaggerated hypotensive response during induction as patient may be hypovolemic Muscle relaxants can be given safely. Note patients with autoimmune thyrotoxicosis are associated with an increase risk of myopathies and myasthenia gravis. Reversal with glycopyrrolate instead of atropine Hyperthyroidism does NOT increase MAC requirements, volatile agents can be used safely

Hyperthyroidism Anesthetic considerations-Postoperative 4/22/2017 Hyperthyroidism Anesthetic considerations-Postoperative Thyroid storm is most serious post-op problem Characterized by: hyperpyrexia, tachycardia, altered consciousness, and hypertension Precipitating factors: infection, trauma, surgery Incidence is 10% in patients hospitalized for thyrotoxicosis Onset is usually 6-24 hours after surgery, but can happen intraoperatively mimicking malignant hyperthermia Unlike MH, not associated with muscle rigidity, elevated CPK, or marked degree or lactic or respiratory acidosis Is a life threatening exacerbation of hyperthyroidism precipitated by infection, emotional stress, parturition, or trauma. Historically lab values have been of little help to distinguish between uncomplicated thyrotoxicosis, and thyroid storm. No uniform diagnostic criteria have been formed to differentiate between the two. The severity of clinical signs and symptoms dictate the degree of aggressiveness

Hyperthyroidism Anesthetic considerations-Thyroid Storm 4/22/2017 Hyperthyroidism Anesthetic considerations-Thyroid Storm Treatment: ABC’s IV Hydration, cool patient IV propanolol (.5mg increments)/esmolol to control heart rate until less than 100. Propylthiouracil 250mg Q6 hours orally or by NG tube Sodium Iodide 1 gram over 12 hours correction of any precipitating events (infection) Cortisol is recommended if there is any coexisting adrenal gland suppression Mortality rate is approximately 20% Dehydration and hypoglycemia may require up to 3-5 liters a day of glucose containing crystalloid. Invasive hemodynamic monitoring should be considered in patients with known heart disease, as they are at risk of fluid overload If not clinically responding to medical treatment, plasmaphoresis, dialysis or chelators are an option to remove antibodies Clinical improvement generally occurs within 12-24 hours and is characterized by defervessence, decreased heart rate, and improved mental status

Anesthetic Considerations Subtotal Thyroidectomy 4/22/2017 Anesthetic Considerations Subtotal Thyroidectomy Associated with several complications: Recurrent laryngeal nerve palsy may cause hoarseness if unilateral, or stridor if bilateral Vocal cord function may be evaluated by DL after deep extubation if there is concern Hematoma formation may cause airway compromise. May require immediate opening of neck wound Hypoparathyroidism may result from unintentional removal of parathyroid glands. Hypocalcemia will result within 24-72 hours Pneumothorax Stridor from unopposed adduction of vocal cords. Immediate reintubation is required, though a very rare complication Symptoms of hypocalcemia: muscle stiffness, parathesias (oral or perioral) positive Chvostek or Trouseau’s sign prolonged QT interval - from delayed repolarization tachy, irreg HR, Afib(10%), heart failure(rare)

Hypothyroidism Causes 4/22/2017 Hypothyroidism Causes Primary hypothyroidism Autoimmune (Hashimoto’s thyroiditis) post thyroidectomy post radioactive iodine overdosage of antithyroid medication iodine deficiency secondary hypothyroidism (failure of the hypothalamic-pituitary axis) Primary hypothyroidism accounts for 95% of cases Its course is slow and insidous

4/22/2017 Hypothyroidism Incidence: 1% of adult population, ten times more prevalent in women Diagnosis: can be confirmed by low free thyroxine levels and elevated TSH (if primary) Medical Treatment: consist of oral replacement

Hypothyroidism Clinical Manifestations 4/22/2017 Hypothyroidism Clinical Manifestations Hypothyroidism in early neonatal development may result in cretinism. In adults, manifestations can be subtle: weight gain, cold intolerance, muscle fatigue, lethargy, constipation, hypoactive muscle reflexes, depression, periorbital or pretibial swelling Heart rate, contractility, stroke volume, and cardiac output decrease, extremities may be cold, hair may be coarse and brittle. Although plasma cathecholamine levels may be normal, end organ responses to catecholamines are altered CO may decrease by 30-50% in untreated hypothyroidism, hypoxic and hypercapnic ventilatory drive may be depressed. In advanced cases the heart is enlarged and a pericardial effusion may be present. Hyponatremia and free water excretion impairment is extremely common

Hypothyroidism Anesthetic considerations-Preoperative 4/22/2017 Hypothyroidism Anesthetic considerations-Preoperative Patients with uncorrected severe hypothyroidism (T4<1 ug/dL) or myxedema coma should not undergo elective surgery. Potential for severe cardiovascular instability intraoperatively and myxedema coma. If emergency surgery is necessary, in patients with overt disease or myxedema coma, IV thyroxine and steroid coverage. Euthyroid state is ideal, however, subclinical cases of hypothyroidism has not been shown to significantly increase risk of surgery Continue thyroid replacement meds on morning of surgery Assessing cardiac function is the most important clincal predictor of adverse perioperative ooutcome.

Hypothyroidism Anesthetic considerations-Preoperative 4/22/2017 Hypothyroidism Anesthetic considerations-Preoperative Airway eval: patients tend to be obese, large tongue, short neck, goiter, swelling of upper airway Pre-op sedation should be administered cautiously if at all, as patients are more prone to drug included respiratory depression from sedatives and narcotics Consider aspiration prophylaxis with Bicitra, Reglan as many hypothyroid patients have delayed gastric emptying times

Hypothyroidism Anesthetic considerations-Intraoperative 4/22/2017 Hypothyroidism Anesthetic considerations-Intraoperative Patients are more sensitive to hypotensive effects of anesthetic agents because decreased cardiac output, blunted baroreceptor reflexes, and decreased intravascular volume. Invasive monitoring on a per patient basis Ketamine or Etomidate may be induction agents of choice Succinylcholine and non-depolarizing muscle relaxants are generally safe for use. Monitor with peripheral nerve stim. Controlled ventilation is recommended as patients tend to hypoventilate

Hypothyroidism Anesthetic considerations-Intraoperative 4/22/2017 Hypothyroidism Anesthetic considerations-Intraoperative Hypothermia occurs quickly and difficult to prevent and treat MAC is essentially unchanged Hematological (anemia, platelet, coag dysfx), electrolyte imbalances, and hypoglycemia is common and require close monitoring intraoperatively Consider co-existed adrenal insufficiency in causes of refractory hypotension

Hypothyroidism Anesthetic considerations-Myxedema Coma 4/22/2017 Hypothyroidism Anesthetic considerations-Myxedema Coma Rare form of decompensated Hypothyroidism characterized by stupor or coma, hypoventilation, hypothermia, bradycardia, hypotension, and severe dilutional hyponatremia(SIADH), CHF Medical emergency with mortality rate of 15-20% Infection, trauma, cold, CNS depressants predispose hypothyroid patients, especially in elderly

Hypothyroidism Anesthetic considerations-Myxedema Coma 4/22/2017 Hypothyroidism Anesthetic considerations-Myxedema Coma Treatment IV thyroxine is indicated (L-thyroxine loading dose 300-500ug, followed by 50ug/day for 24-48hrs) IV hydration with dextrose containing crystalloid, correction of electrolyte abnormalities Support cardiovascular and pulmonary systems as necessary

Hypothyroidism Anesthetic considerations-Postoperative 4/22/2017 Hypothyroidism Anesthetic considerations-Postoperative Extubation/Emergence may be delayed secondary to hypothermia, respiratory depression, or slowed drug metabolism Awake extubation, try to maintain normothermia Cautiously administer opioids post-op, consider regional techniques or Ketorolac for post-op pain control Retrospective study showing of 59 mildly hypothyroid patients, had higher incidence of post op intubation 9 vs. 4 and bleeding complication versus controlled 4 vs 0. But not statistically significant

4/22/2017 References: 1. Graham, GW, Unger, BP, Coursin DB. Perioperative Management of Selected Endocrine Disorders. International Anesthesiology Clinics. 38(4) pp..31-67, 2000 2. Langley RW, Burch HB. Perioperative Management of the Thyrotoxic Patient. Endocrinology and Metabolism Clinics of North America. 32, 519-534, 2003 3. Miller, RD, Cucchiare RF, Miller ED, et al. Anesthesia, 5th ed. Churchiill-Livingston. New York, pp.927-933, 2000. 4. Morgan GE, Mikhail MS. Clinical Anesthesiology, New York, McGraw-Hill, 1996, 639-641 5. Murkin, JM. Anesthesia and Hypothyroidism: A Review of thyroxine physiology, pharmacology, and anesthetic complications. Anesthesia and Analgesia. Vol61(4) April 1982

4/22/2017 References:(cont.) 6. Nicoloff JT, LoPresti JS: Myxedema Coma: A Form of Decompensated Hypothyroidism. Endocrinology Clinics of North America, Philadelphia, WB Saunders, June 1993 279-290 7.Stathalos N, Wartofsky L. Perioperative Management of Patients with Hypothyroidism. Endocrinology Clinics of North America. 32, pp..503-518, 2003 8. Wall R. Unusual Endocrine Problems. Anesthesiology Clinics of North America 14, 471-493, 1996 9. Weinberg AD, Brennan MD, Gorman CA et al. Outcome of Anesthesia and Surgery in Hypothyroid patients. Arch Intern Med 143:893-897, 1983