Thyrotoxicosis and myxedema-Anesthetic implications

Thyrotoxicosis and Myxedema - Clinical features, Diagnosis, Treatment , Anesthetic MAnagement, Complications.

1. Thyrotoxicosis and Myxedema -Preoperative preparation and Intraoperative complications and Management R.Srihari

2. Topics for Discussion Thyrotoxicosis : Etiology Signs and Symptoms Diagnosis Treatment Management of Anesthesia Thyroid Storm Myxedema : Etiology Signs and Symptoms Diagnosis Treatment Management of Anesthesia Myxedema Coma

3. Thyrotoxicosis Introduction Thyrotoxicosis : State of thyroid hormone excess Hyperthyroidism: State of excessive thyroid function Major etiologies of thyrotoxicosis are hyperthyroidism caused by primary and secondary causes

4. Etiology Thyotoxicosis caused by hyperthyroidism: Graves Disease Toxic MNG Toxic adenoma Struma ovari TSH secreting pituitary adenoma Chorionic gonadotropin secreting tumours Iodine overdose Thyrotoxicosis caused by hypothyroidism: Drug induced thyroiditis Subacute thyroiditis

5. Clinical Manifestations Symptoms: Hyperactivtity and Irritability Palpitations Fatigue and Weakness Weight loss with increased appetite Diarrhoea Polyuria Oligomenorrhoea with loss of libido Signs: Tachycardia Atrial Fibrillation Tremors Goitre Warm, moist skin Muscle weakness Proximal myopathy Lid retraction Cardiomyopathy (severe)

6. Graves’ Disease: Associated with Graves’ ophthalmopathy and dermopathy Graves’ Ophthalmopathy : Dalrymple sign Von Grafe sign Joffroy sign Moebius sign

7. NO SPECS scheme – acronym derived from following eye changes: N – no changes O – only signs, no symptoms (lid retraction/lag) S – Soft tissue involvement ( Periorbital edema) P – Proptosis (>22m) E – Extraocular muscle involvement ( diplopia ) C – Corneal involvement S – Slight loss

8. Thyroid dermopathy : Almost always seen with Graves ophthalmopathy Overall incidence < 5% Although most frequent over anterior and lateral aspects of lower leg( aka pretibial myxedema ) Skin changes can occur at any site esp. after trauma Typical lesion – non inflamed, indurated plaque with deep purple/pink color and orange skin appearance Thyroid acropachy : Clubbing seen in Thyrotoxicosis pt (<1%) – strongly a/w Thyroid dermopathy

9. Investigations: CBC  Microcytic anemia with thrombocytopenia ECHO/ Ecg  if cardiac symptoms + S. Creatinine (if patient more 60 yrs) IDL  to r/o pre-existing vocal cord palsy CT scan of neck Flow volume loop Thyroid function tests

10. Treatment Hyperthyroidism of Graves’ Disease is treated by decreasing thyroid hormone synthesis Using antithyroid drugs OR Reducing the amount of thyroid tissue OR Thyroidectomy

11. Antithyroid drugs: Main drugs  Thionamides PTU/ Carbimazole / Methimazole Act by inhibiting TPO  decreasing oxidation and organification Decreasing Antithyroid antibody levels PTU also inhibits T4T3

12. Carbimazole / Methimazole : 10-20 mg Q8h-Q12h initially  once euthyroid 10-20mg OD  Duration of action- 6 hours PTU: 100-200mg Q6h-Q8h dose decreased as thyrotoxicosis improves TFTs and clinical manifestation are reviewed 3-4 weeks after starting treatment Euthyroid state seen 6-8 weeks following therapy Remission rates seen after 18-24 months following therapy

13. Common side effects of anti-thyroid drugs: Rash Urtacaria  May resolve spontaneously Fever or substituting with alternatives Arthralgia Rare but major side effects: Hepatitis SLE like vasculitis Agranulocytosis  confirmed with complete blood count

14. Propanolol : 20-40 mg Q6h Helps to control adrenergic symptoms especially in early stages brfore antithyroid drugs take effect Alternatives: atenolol Sodium ipodate / iopanoic acid: 500mg- 3g OD Mainly used in adequate response to treatment/relapse Progressive destruction of thyroid cells and can be used as initial treatment or for relapses after a trial of antithyroid drugs Pregnancy: Contraindicated

15. Iodine in high concentration inhibit release of hormones from hyperfunctioning gland  effect occurs immediately but lasts only for several weeks Hence preserved for preserved for preparing hyperthyroid patients for surgery Management of patients with thyrocardiac disease High concentrations of iodide reduce all phases of thyroid synthesis and release  result in decreased gland size and vascularity Admininistered orally as SSKI  3 drops Q8h  10-14 days

16. Surgery: Indicated only after patient returns to euthyroid state  Anithyroid drugs should be continued Anticoagulants/ Coumarins : Used if Atrial fibrillation present

17. Management of Anesthesia Preparation : Extremely important For elective surgery  all patients should be made euthyroid with course of antithyroid drugs for 6-8 weeks preoperatively Low TSH levels should not be a contraindication to surgery TSH levels remain suppressed from prolonged hyperthyroidism in patients who have normalised T3 and T4 levels SSKI – given 7-14 days prior to Sx Beta blockers to control heart rate perioperatively

18. For emergency surgery: Antithyroid drug should be administered even though it has limited effect if taken less than 2 weeks Antithyroid drugs should preceed iodide by 2-3 hours IV beta blockers ( Esmolol -0.5mg/kg  infusion  0.03-0.3mg/kg/min) Sodium ipodate 500mg BD Dexamethasone – 2mg q6h Euthyroid state usually achieved in 5-7 days

19. Preoperative Preparation: Premedication: Barbiturates/BZDs/Narcotics NO ATROPINE Monitoring: SpO2, BP, HR,eTCO2 and temperature IBP  in patients with uncontrolled thyroid condition Central line  if large amounts of blood loss anticipated

20. Induction: Thiopentone –preferred Ketamine –avoided Propofol - large doses to be given Muscle relaxants: the following can be used safely SCh Rocuronium Vecuronium

21. Maintenance of anesthesia: Should be kept in deeper plane of anesthesia MAC not affected Isoflurane and Sevoflurane - ideal with N20 + O2 Agents to correct hypotension: IVF Phenylephrine Eye protection- very important Reversal of anesthesia: Glyco + Neostigmine

22. Removal of thyrotoxic gland  does not mean immediate resolution of thyrotoxicosis T1/2 of T4 7-8 days Hence beta blocker therapy may be need to be continued post-operative period Antithyroid drug therapy can be discontinued

23. Thyroid Storm Introduction : Most serious compication of hyperthyroidism with mortality ranging from 10-75% of hospitalised patients Most common in patients with poorly controlled Graves’ Disease Clinical diagnosis  acute disruption of the normal steady state of circulating hormones

24. Precipitating Factors: Infection/Sepsis Withdrawal of anti-thyroid drugs Surgery/Trauma Parturition DKA Iodinated contrast dyes Hypoglycemia Excessive manipulation of thyroid gland Burns

25. Clinical features: Fever + Tachycardia  Most common Fever: Most characteristic  >41 C CVS: Tachycardia Atrial fibrillation, Ventricular arrhytmias Heart failure Hypertension with wide pulse pressure(early), Hypotension (late)

26. Neuromuscular: Tremors Encepalopathy Weakness Can progress to CVA/ Status epilepticus / Thyrotoxic myopathy / Rhabdomyolysis GI: Nausea/ Vomiting/ Diarhoea Jaundice (indicated hepatocellular injury- poor prognosis) Respiratory Dyspnea Increased eTCO2 and O2 consumption  Aggravated with pulmonary oedema / respiratory muscle weakness and tracheal obstruction from goitre

27. Lab testing: Increased FT3/FT4 Hyperglycemia Leucocytosis Abnormal LFT Reduced K/Mg ; Increased Ca  inc bone resorption

28. Management: Treatment aimed at: Control and relief of adrenergic symptoms Control of thyroid function abnormality Stopping Precipitating factor Investigation and treatment of underlying thyroid disease Supportive measures

29. Beta blockers: Mainstay of controlling adrenergic symptoms IV propanolol – 0.5-1mg increments over 10 minutes while monitoring CV response decreases sympathetic hyperactivity + Inhibits conversion of T4  T3 + Concurrent administration of enteral propanolol with doses of 60-120mg Q4h to Q6h to enhance elimination during thyroid crisis Esmolol  loading dose -250-500 mcg/kg  infusion  50-100mcg/kg/min  allows titration with minimal side effects

30. Thionamides : These drugs block de novo synthesis of thyroid hormones within 1-2 hours of administration  But no effect on release of preformed Glandular store of Thyroid Hormone PTU- Drug of choice – 200mg Q4h Methimazole -100mg stat foll by 20mg Q8h Iodine: Release of glandular store of thyroid hormone inhibited by administering Iodine/Lithium Should be given only after Thionamides given after 1 hour or it will exacerbate Storm SSKI -10 drops Q8h (8mg iodide/iodine per drop)

31. Amidarone : Blocks peripheral conversion of T4  T3 + Decreased concentration of T3 induced adrenoceptors in cardiac myocytes Bile acid sequesterants : Thyroid hormone are metabolised in the liver  where they are conjugated with glucoronide and sulfate excreted in bile which are reabsorbed in intestine Cholestyramine (4g Q6h) interferes the thyroid hormone reabsorption in enterohepatic circulation

32. Steroids: Decrease T4  T3 conversion Modulate auto-immune process during Thyroid crises Inj. Hydrocortisone 100mg Q8h or Inj. Dexa 4mg iv Q6h Supportive therapy: Fluid management Nutrition Drug therapy salicylates and Frusemide AVOIDED Precipitating factors Plasmapheresis  LAST RESORT

33. Myxedema Etiology: Primary: Iodine Deficiency Hasimoto’s Iatrogenic- ! odine 131 deficiency/ Total thyroidectomy Drugs: Iodine excess/ Amiodarone / Antothyroid drugs Infiltrative disorders: Amyloidosis / Sarcoidosis Secondary: Hypopituitarism Isolated TSH deficiency

34. Clinical Manifestations Symptoms: Tiredness, weakness Dry skin Feeling cold Difficulty concentrating/poor memory Constipation Weight gain with poor appetite Dypnea Hoarseness of voice Menorrhagia Hearing Loss Signs: Dry coarse skin Cool peripheral extremities Puffy face,palms Diffuse alopecia Peripheral edema Carpal tunnel syndrome Delayed tendon reflexes Myocardial contractility + decreased PR  decreased Stroke volume and bradycardia with increased peripheral vascular resistance

35. Non-pitting edema: seen due to accumulation of hydrophilic mucopolysaccharides in dermis and other areas : Tongue Vocal cords – hoarseness of voice

36. Investigations Findings in Hypothyroidism: Thyroid function test Increased CPK Elevated cholesterol and triglycerides Macrocytic anemia Adynamic ileus ECG: low amplitude P wave and QRS complexes + flattened/ inverted T waves + Sinus bradycardia

37. Treatment L- thyroxine - given for treatment of hypothyroidism consistent potency, reliably restores levels of T4 and T3 to normal and has prolonged duration of action Gradual onset with half life of 7-8 days If no residual thyroid function, daily replacement dose  1.6mcg/kg (~100-150mcg/day) In patients who develop hypothyroidism after treatment of Graves’ Disease necessary to replace with 75-125mcg/day

38. Adults <60 years without evidence of heart disease may be started on 50-100 mcg/day daily  Dose is adjusted on basis of TSH levels  goal of treatment being normal TSH / less than normal TSH responses are gradual and should be measured at 2 months after instituting therapy or after any subsequent change in levothyroxine dosage

39. Clinical effects  after initiation of therapy are slow to appear  Pts may not experience full relief from symptoms 3-6 months after TSH is normal Adjustments is made in 12.5 to 25 mcg increments if TSH is high Once full replacement is obtained and TSH stable- follow up – yearly Important component of therapy Compliance to Rx

40. For elderly or those with CAD starting dose of 25 mcg/kg  increasing monthly by 25 mcg till euthyroidism is achieved Patients with hypothyroid cardiomyopathy  improvement in cardiac function in 2-4 months on 100mcg /day of L- thyroxine Subclinical hypothyroidism treatment started only if TSH increased persistently for 3 months TSH>10 mU /l If TPO Ab+ve

41. Management of Anesthesia Preoperative Issues: Patients with overt hypothyoidism should be treated prior to elective surgery In emergency , if Surgery can be delayed for 24-48 hours  iv T3 can be given (peak action-24-38 hours) Because of increased adrenocortical insufficiency + decreased hormone response to stress  hypothyroid patients should receive hydrocortisone cover during periods of increased surgical stress

42. Hypothyroid patients may be at increased risk when receiving either general or regional anesthesia: Airway compromise secondary to swollen oral cavity with large tongue Edematous vocal cords Goitrous enlargement Decreased gastric emptying increasing risk of regurgitation and aspiration

43. Hypodynamic cardiovascular system: Low cardiac output/ Stroke volume/ heart rate/ baroreceptor reflexes and intravascular volume Compromised by surgical stress and cardiac depressant anesthetic agents Hypothermia occurs quickly and is difficult to prevent and treat

44. Hematological and Metabolic abnormalities: Anemia Platelet and coagulation factor abnormalities Hypoglycemia Hyponatremia Increased sensitivity to volatiles  dec CO PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM DO NOT PRESENT ANY ANESTHETIC PROBLEM

45. If pt is planned for emergency surgery Increased risk of cardiovascular instability intraoperatively Myxedema coma postoperatively Preoperative Sedation: Contraindicated in hypothyroid patients for elective surgery  increased sensitivity to sedative drugs

46. REGIONAL ANESTHESIA IS RECOMMENDED WHERE THERE ARE NO CONTRAINDICATIONS Monitoring: Routine Swan- Ganz  if severe hemodynamic impairment with TEE -> to assess intravascular volume IVF of choice  DNS

47. Induction agents: Ketamine Barbiturates and BZDs – in titrated doses Muscle relaxants: Sch Intermediate NDMR: Vecuronium and Rocuronium Opioids : Short acting  fentanyl and its derivatives

48. Maintenance: N20:O2 + Volatiles  carefully used esp. in hypovolemia  blunted barorecptor response Intraop monitoring: Temperature Electrolyte and Fluid status Invasive monitors in patients undergoing major surgery Peripheral nerve stimulator Warming: very important

49. Exaggerated hypotension: Common and should be treated with judicious fluid and inotropes and vasopressors Ephredrine Dopamine Epinephrine NO PURE ALPHA 1 AGONIST IF unresponsive  steroids should be given

50. Ventilation: Should be controlled – not spontaneous As hypoventilation seen due to increased sensitivity to anesthetic drugs Delayed recovery is common and postoperative ventilation may be required

51. Myxedema Coma Introduction: Myxedema coma  extreme manifestation of hypothyroidism  although rare Mortality  30-50% Term  misnomer Condition considered in patients presenting with reduced level of consciousness with hypothermia Most common in elderly women with long standing undiagnosed or undertreated hypothyroidism, in whom an additional significant stress is experienced

52. Precipitating Factors: Infections Cold environment Burns Stroke Surgery Trauma CHF Co2 retension

53. Clinical manifestation: Decreased mental status Hypothermia Clinical features of hypothyroidism CVS RS Airway GI Metabolic Though TBW is increased  intravascular volume decreased

54. Treatment: Mainstay of Rx: Thyroid replacement therapy Steroid replacement Supportive measures

55. Thyroid Replacement Therapy: All patients with suspected myxedema coma should receive presumptive treatment with thyroid hormones Severity of clinical presentation does not correlate with doses of replacement hormone required Rapid replacement: a/w life threatening myocardial ischemia and arrhythmias Delayed replacement: exposes prolonged risk of complication from crises

56. Loading doses  200-400 mcg iv  saturates binding proteins Followed by 50-100 mcg daily till conversion Steroid replacement: Corticosteroids  important part of treatment as relative/ absolute hypoadrenalism may occur concurrent with hypothyroid disease Inj. Hydrocortisone 100mg iv Q8h (or) Inj. Dexa 4mg iv Q6h  S.Cortisol level should be collected prior to starting therapy (Inj. Hydrocortisone)  if normal ..Rx stopped

57. Supportive Treatment: Hypothermia  warming where possible Cardiac output monitoring  guide fluid therapy Hyponatremia  reversible with thyroxine treatment If severe - fluid restriction + Hypertonic saline Hypoglycemia 25% Dextrose via central venous line Precipitating factor should be corrected DVT prophyllaxis Ulcer prophyllaxis Mechanical ventilation

58. Thank you