Hyperthyroidism in the surgical patient may significantly alter surgical risk by imposing additional burden on the cardiovascular system.78,79 Angina pectoris, atrial fibrillation, and cardiac failure may be precipitated, and other abnormalities include hypercalcemia, glucose intolerance, anorexia, myopathy, impaired drug absorption, and coagulation defects.
Preoperative preparation of a hyperthyroid patient includes deferral of elective surgery and optimization of thyroid function where possible. Most patients with hyperthyroidism have Graves disease and should be treated with a combination of antithyroid drugs (such as propylthiouracil and methimazole), iodide solutions, and possibly glucocorticoids to protect against adrenal insufficiency that may be associated with thyrotoxicosis.80
Surgical options for the treatment of a patient with Graves disease include subtotal or total thyroidectomy. A recent retrospective analysis of over 1200 patients over a 40-year period suggests that total thyroidectomy is the preferred surgical option for the treatment of Graves disease.81
If the surgery is emergent, the mainstay of treatment is perioperative β-blockade to reduce adrenergic thyroxine effects. Traditionally, propranolol has been recommended. However, esmolol may be preferred because of the rapid action and elimination, particularly when hemodynamic instability occurs.82
Thyroid storm is fortunately a rare event because of β-blockade prophylaxis, but when it occurs there is still a 40% mortality rate. Tachydysrhythmias, frequently atrial fibrillation, are seen. Cardioversion is usually unsuccessful. Hyperthermia, hypertension, leukocytosis, and evidence of adrenal insufficiency may occur. Treatment with β-blockade should begin once the diagnosis is suspected. Invasive hemodynamic monitoring should be instituted to guide fluid and electrolyte therapy in the intensive care environment where possible.
The incidence of hypothyroidism in the general population is 0.5% to 0.8%, increasing to 1% to 3% in patients over 65 years of age. Treatment with lithium or amiodarone, drugs not uncommonly associated with drug-induced hypothyroidism, may alert the clinician to this diagnosis.
Although there are many physical signs of hypothyroidism, the only sign statistically correlated with biochemical abnormalities is the presence of delayed ankle reflexes. Retrospective analysis suggests that postoperative complications are not increased in patients with mild to moderate hypothyroidism, but patients with severe hypothyroidism undergoing surgery are more prone to periods of hypotension, neuropsychiatric disturbance, and intestinal hypomotility.83 Clinical assessment in addition to serum T3, T4, and thyrotropin levels should be used to assess thyroid status.84
Patients receiving regular thyroxine replacement, without signs and symptoms of hypothyroidism, can safely withhold oral thyroxine perioperatively for the majority of operations, as the half-life of levothyroxine is 1 week. If parenteral administration is required, thyroxine can safely be given intravenously at half the oral daily dose. Overtly hypothyroid patients undergoing emergency surgery should be treated with thyroxine replacement in addition to hydrocortisone 100 to 300 mg every 8 hours. Elderly patients with a clinical history or suspicion of coronary artery disease require cautious thyroxine replenishment and coadministration of nitrates.85
General anesthesia may be associated with profound cardiovascular depression in hypothyroid patients. Special consideration needs to be taken to titrate anaesthetic drugs to avoid this known effect. The use of newer anesthetic monitoring techniques such as bispectral index analysis may help titrate anaesthetic medications.86
Diabetes mellitus is the most common endocrine disorder encountered in the perioperative period, since it occurs in almost 5% of the general population.87 Traditionally, diabetics presented for surgery for limb amputation and wound débridement, but owing to surgical advances in vitrectomy, cataract extraction, renal transplantation, and peripheral vascular repairs, diabetic patients are frequently presenting for preoperative assessment. Type I (insulin-dependent diabetes mellitus) comprises approximately 25% of the diabetic population, and affects a younger population (<35 years) which is prone to perioperative hyperglycemia and ketoacidosis because of inability to secrete insulin. Type II (non-insulin-dependent diabetes mellitus) patients are older and often obese and have a decrease in the number or responsiveness of insulin receptors, together with impaired insulin secretion, features which are accentuated in the perioperative period.88,89
The aim of therapy is to avoid excess morbidity and mortality which may be caused or exacerbated by extremes in blood glucose levels, undue protein catabolism, and fluid and electrolyte disturbances.
Although one study showed no difference in mortality and morbidity in vascular surgical patients, it is generally accepted that diabetics encounter increased perioperative morbidity and mortality.90–92
A perioperative myocardial infarction rate of 5.2% is reported in diabetics undergoing abdominal aortic reconstruction compared to 2.1% of nondiabetic patients. Inadequate control of blood glucose can lead to ketosis, acidemia, and dehydration. Decreased wound healing occurs at glucose levels greater than 200 mg/dL. Glucose concentrations greater than 250 mg/dL have been shown to impair leukocyte function and exacerbate ischemic brain damage. In addition to the effects of abnormal blood glucose levels, diabetics are at particular risk of atherosclerotic vascular disease, hypertension, and coronary artery disease.
Preoperative clinical markers for increased perioperative complications have been suggested. The presence of congestive cardiac failure, diabetic end-organ failure commonly associated with diabetes, valvular heart disease, and peripheral vascular disease associated with infection are statistically associated with increased mortality. Autonomic neuropathy is found in over 40% of patients presenting for surgery and may alter hemodynamic responses to intubation and surgery.93,94
Apart from anesthesia for cataract extraction, choice of anesthetic technique has not been associated with altered outcome.95 Thoracic epidural and spinal anesthesia techniques are associated with reduced intraoperative catecholamine release. However, to date, no study of exclusively diabetic patients has compared outcome between regional and general anesthesia techniques.
Preoperative evaluation should include thorough clinical assessment for cardiac, neurologic, and peripheral vascular abnormalities. A careful history for the presence of ischemic heart disease or prior myocardial infarction should be supported by cardiac investigations where appropriate. Glycosylated hemoglobin (HbA1c) levels less than 10% suggest satisfactory glycemic control. Renal failure may be present in up to 35% of diabetic patients upon presentation,110 and plasma creatinine, urinary sediment examination, and urine analysis for infection should be assessed. Recent evidence that intensive insulin therapy to achieve strict control of blood sugar (80 to 110 mg/dL) improves outcome in nondiabetic surgical ICU patients suggests that general practice (to maintain a blood sugar <200 mg/dL) may be inadequate in the postoperative diabetic.96
Nondiabetic patients recovering from surgery commonly show transient hyperglycemia and diminished insulin secretion and end-organ responsiveness in response to increased circulating catecholamines.97 However, these patients secrete sufficient insulin to suppress lipolysis and ketogenesis. Diabetics present with decreased or absent preoperative insulin secretion and a pre-existing insulin resistance, which serves to worsen the hyperglycemic response to surgery. Decreased peripheral use of glucose results in lipolysis, ketogenesis, possible acidemia, glycosuria, and dehydration.98
A variety of insulin regimens have been suggested for the routine perioperative management of diabetics undergoing surgery. No single regimen has proved markedly superior. Currently, perioperative intravenous glucose infusions are recommended, and insulin may be administered via a variety of dosages and routes. Subcutaneous administration of half the regular daily dose before surgery, using a variable-rate glucose infusion to maintain normoglycemia, has proved successful.99 Mixing insulin, potassium, and 5% or 10% glucose has also been suggested.100,101 Most authors suggest a variable-rate insulin infusion using an automated syringe device with a simultaneous glucose infusion through an alternative intravenous access.102,103
Insulin requirements vary widely in the perioperative patient. The normal state (approximately 0.25 unit of insulin per gram of glucose) is influenced by many factors such as obesity, concomitant glucocorticoid administration, and the septic state, which may increase insulin requirements to as high as 0.4 to 0.8 unit of insulin per gram of glucose. The highest insulin requirements have been observed in patients undergoing CABG (0.8 to 1.2 U/g of glucose).104
Recommendations for glucose infusion to prevent catabolism suggest between 5 and 10 g of glucose per hour,105 although the optimal dose of glucose necessary for prevention of fat and protein catabolism has not been clearly determined. However, clinical experience suggests that most surgical diabetics can be maintained within the normal blood glucose range with an insulin infusion set between 1 and 2 U/h.
Patients receiving total parenteral nutrition, which is generally up to 25% dextrose, usually require an additional 2 to 3 units of insulin per hour. Apart from careful monitoring of blood glucose levels, the patient's overall clinical status (particularly neurologic and hemodynamic) should be closely observed. Avoidance of hypoglycemic episodes while allowing mild hyperglycemia without ketosis is prudent in the diabetic whose blood sugar is extremely difficult to control.
What emerges from all the studies dealing with perioperative diabetes management is that the most important factor in optimal perioperative glycemic control is frequent measurement of blood sugar and appropriate therapeutic interventions by trained staff. Perioperative metabolic management should be planned and coordinated by surgeons, anesthetists, and diabetic care teams in conjunction with the patient when possible. With the exception of type II diabetic patients presenting for minor surgery, all diabetic patients should receive intravenous infusions of glucose with appropriate insulin to achieve normoglycemia until the preoperative regimen is resumed.
Glucocorticoid Supplementation in Chronic Glucocorticoid Users
Perioperative glucocorticoid supplementation for patients receiving steroid therapy is common. The rationale for its use is the avoidance of hypoadrenalism, resulting in a variety of clinical signs including fever, nausea, dehydration, abdominal pain, hypotension, and shock. Other evidence of hypoadrenalism includes low-voltage complexes on the ECG, hypoglycemia, and eosinophilia. Despite the common use of steroids in hospital patients, the incidence of perioperative adrenal insufficiency is low (0.01% to 0.1%).106
Retrospective and prospective data suggest that routine steroid supplementation for all glucocorticoid-treated patients may not be necessary.107–109. Well-known adverse effects of exogenous glucocorticoids include immunosuppression, exacerbation of osteoporosis, avascular necrosis of the femur, diabetes, peptic ulcer disease, diminished wound healing, and neuropsychiatric disorders.
Daily endogenous cortisol release in normal adults approximates 25 to 30 mg per day at rest. Stressors such as major surgery or critical illness increase endogenous production to 75 to 100 mg per day because of increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. Increased cortisol secretion returns to normal within 24 hours of skin incision in uncomplicated minor surgery.110
The clinical rationale for steroid supplementation in the perioperative period is based on the known protracted recovery of the hypothalamus-pituitary-adrenal (HPA) axis following prolonged glucocorticoid administration.111 However, the stress response observed in perioperative patients results in ACTH levels far in excess of that required for maximal adrenocortical stimulation.112 A number of studies113–115 have suggested that patients on chronic steroid therapy undergoing elective major surgery may not require perioperative steroid supplementation in addition to their regular steroid regimen. In a study of 40 renal transplant recipients on chronic prednisone therapy, none of the patients received more than baseline glucocorticoid therapy during admission for surgery or critical illness. Despite biochemical evidence of decreased adrenal response to exogenous ACTH in 67% of the patients, none of the patients exhibited clinically overt hypoadrenalism, and 97% of all patients excreted normal or increased urinary cortisol concentrations during their hospital stay. This suggested that cortisol concentrations were sufficient to meet requirements during the time of stress.109
Identification of patients at risk for perioperative hypoadrenalism by history alone is difficult.113 Functional status of the adrenal gland may be assessed quickly and easily using the 30-minute ACTH test. This is the most effective and convenient tool for perioperative evaluation of HPA function.116
Baseline cortisol measurements are taken immediately prior to the intravenous administration of 250 μg of synthetic ACTH. Adequate adrenal function is diagnosed by baseline levels usually above 200 nmol/L, which rises above 500 nmol/L 30 minutes following ACTH administration (see Chap. 79).
Patients who exhibit a subnormal response to ACTH should receive supplemental steroids. Since endogenous cortisol secretion in normal individuals rarely exceeds 200 mg/d, exogenous steroid supplementation should range from 75 to 150 mg per day. To date, no data suggest that supplemental glucocorticoid therapy exceeding this amount is beneficial. Patients on chronic steroid therapy undergoing minor surgery should have their regular steroid dose on the morning of surgery and no additional doses if surgery is uncomplicated. Candidates for major surgery should receive 25 mg hydrocortisone intravenously on induction of anesthesia, and 100 to 150 mg per day over the following 24 to 72 hours. If a patient presenting for surgery is already receiving a maintenance steroid dose greater than the estimated requirement, additional steroid coverage is not necessary.115
Clinical and biochemical preoperative assessment of patients on chronic steroid therapy is invaluable in the identification of patients at risk for adrenal insufficiency in the perioperative period. Published recommendations for supplemental steroid coverage should be followed by dosing to physiologic levels. If doubt exists, a preoperative 30-minute ACTH test will clarify the need for perioperative supplemental glucocorticoid administration.