© 2003 WebMD Inc. All rights reserved.                                                   ACS Surgery: Principles and Pract...
© 2003 WebMD Inc. All rights reserved.                                                           ACS Surgery: Principles a...
© 2003 WebMD Inc. All rights reserved.                                                                ACS Surgery: Princip...
© 2003 WebMD Inc. All rights reserved.                                                           ACS Surgery: Principles a...
© 2003 WebMD Inc. All rights reserved.                                                             ACS Surgery: Principles...
© 2003 WebMD Inc. All rights reserved.                                                                                ACS ...
© 2003 WebMD Inc. All rights reserved.                                                                              ACS Su...
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Acs0810 Endocrine Problems


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Acs0810 Endocrine Problems

  1. 1. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 10 Endocrine Problems — 1 10 ENDOCRINE PROBLEMS Robert H. Bartlett, M.D., and Preston B. Rich, M.D. Patients scheduled for operation may be receiving treatment glucose levels should be carefully monitored in patients taking this with insulin, oral hypoglycemics, corticosteroids, thyroid hor- medication who have experienced injury or undergone operation. mone, or estrogen. The presence of any state calling for such treatment must be taken into consideration in planning opera- Laboratory Studies tive management and perioperative care. In addition, glucose The degree of control of diabetes can be assessed by recording intolerance may develop in otherwise normal patients after oper- blood glucose measurements at frequent intervals during fasting ation, and this possibility must be taken into account as well. In and at other times during the day and by determining what per- what follows, we describe an approach to preventing and man- centage of total hemoglobin is combined with carbohydrate (i.e., aging common endocrine conditions that occur as complicating glycosylated). Normally, glycosylated hemoglobin (commonly factors in the perioperative period. We do not, however, address called HbA1c) accounts for 4% to 7% of total hemoglobin. HbA1c perioperative problems related to operations for primary levels increase when hyperglycemia occurs, and the increases are endocrine disease. cumulative over time. The value of measuring HbA1c in a preop- erative patient known to be diabetic is that it gives the attending physicians some idea of how well hyperglycemic episodes are Diabetes Mellitus being controlled by insulin or oral hypoglycemics. Monthly mea- Diabetics have a 50% chance of undergoing a surgical proce- surements yield a good picture of the adequacy of glucose control dure during their lifetime.1 In the past, operation in these over extended periods. HbA1c percentages higher than 10% to patients was associated with a mortality of 4% to 13%,2 usually 20% indicate that the hyperglycemic aspect of diabetes has been attributed to cardiovascular complications—clearly a significant poorly controlled. Chronic diabetic complications are reduced operative risk. Any subsequent improvement in diabetes-related when good control of blood glucose is maintained; diabetic operative mortality has probably been offset by the increasing patients are advised to measure their blood glucose levels fre- age of patients with diabetes and the larger variety of procedures quently, which should result in normal HbA1c levels. HbA1c per- they undergo. centages higher than 15% suggest that the diabetes is quite brit- Perioperative management of diabetic patients [see Figure 1] is tle and that more frequent monitoring of blood glucose levels and complicated both by the metabolic abnormalities of the disease closer control of insulin administration are indicated during and and by the effects of any diabetic complications that may be pres- after operation. As long as the patient is carefully monitored, ent. There is also an increased risk of postoperative surgical site there is no evidence that high levels of HbA1c are associated with infection (SSI). any increased risk of impaired glucose control or complications after operation. EVALUATION OF THE DIABETIC PATIENT The other important laboratory study in diabetic patients is measurement of serum creatinine levels (or, perhaps, creatinine History and Physical Examination clearance) as an indicator of renal function. Renal insufficiency In taking a preoperative history from a diabetic patient, atten- is a common complication of diabetes that may not be recog- tion should be directed to any recent fluctuation in blood glu- nized during normal preoperative testing. cose level as well as to the type of therapy used to control the PREOPERATIVE MANAGEMENT condition. The timing and dosage of medication should be con- sidered, especially if the patient is taking long-acting insulin or an oral hypoglycemic.The extent to which diabetes is controlled Metabolic Monitoring and Medications in the perioperative period, which has a significant impact on All diabetic patients who are candidates for elective surgical postoperative recovery, may be affected by certain medications procedures should undergo careful preoperative assessment, (e.g., antihypertensive agents). The presence of diabetic compli- including metabolic monitoring. Ideally, glycemic control is cations (e.g., atherosclerotic disease, diabetic nephropathy, and achieved before a diabetic patient is admitted to the hospital. autonomic neuropathy) should be documented because these More realistically, however, admission may have to be scheduled conditions may have serious effects during and after operation. for the day before the operation to allow time for optimizing Medications used to control diabetes include the various forms metabolic control in all insulin-dependent patients as well as in of insulin as well as oral hypoglycemic agents. The most com- non–insulin-dependent patients who have inadequate metabolic monly used oral hypoglycemics are sulfonylurea, which acts by control. As a rule, target blood glucose levels before operation stimulating insulin secretion, and metformin, which acts by should be less than 125 mg/dl (6.9 mmol/L) during fasting and decreasing intestinal absorption. Patients should stop taking oral less than 180 mg/dl (10.0 mmol/L) postprandially. If emergency hypoglycemics before major operations, and their blood glucose operation is required in patients with severe metabolic derange- should be controlled with insulin if necessary. Because sudden ments (e.g., diabetic ketoacidosis or hyperosmolar nonketotic discontinuance of sulfonylurea can lead to hypoglycemia, blood states), 6 to 8 hours of intensive treatment with insulin infusion
  2. 2. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Car 10 Endocrine Problems — 2 Diabetic patient is undergoing Diabetic patient is scheduled mone) increase in nondiabetic as well as diabetic patients. emergency procedure for elective procedure Increased secretion of these hormones in the setting of low insulin levels stimulates hepatic production of glucose. In non- Give insulin and glucose as Evaluate for cardiovascular and diabetic persons, major procedures are frequently associated needed to control blood glucose, renal complications. with blood glucose levels of 150 to 200 mg/dl (8.3 to 11.1 ketoacidosis, and blood volume. Measure HbA1c to assess degree mmol/L). In diabetic persons, the metabolic abnormality varies of glucose control (10%–20% according to the extent and duration of the surgical procedure suggests poor control). and the degree to which insulin secretion is impaired. Give insulin and glucose as needed to control blood glucose. A study in patients with stable type 1 (insulin-dependent) dia- betes mellitus showed that blood glucose levels rose from about 180 mg/dl (10.0 mmol/L) to about 270 mg/dl (15.0 mmol/L) postoperatively.3 Ketone body levels increased by about 100%, as compared with levels in nondiabetic control subjects. Similar During operation metabolic findings were reported even in patients with type 2 diabetes mellitus who underwent minor procedures that gener- Monitor blood glucose. ated relatively little stress: blood glucose levels rose to 180 mg/dl Give insulin and glucose as needed. (10.0 mmol/L), with higher than normal levels of ketone bodies Consider potential effects of and free fatty acids.4 diabetic complications. Autonomic neuropathy can cause severe hypotension during induction of anesthesia. Diabetic nephropathy complicates fluid management and usually results in electrolyte abnormalities. All diabetic patients are at high risk for postoperative myocardial infarction, which is often asymptomatic. Poor nutrition and After operation: diabetic patient After operation: nondiabetic impaired phagocytosis make diabetic patients more susceptible patient with acquired glucose to infection and slower to heal. Control blood glucose with intolerance glucose and intermittent insulin. Insulin and Glucose Administration If blood glucose is labile, give Suspect infection, the presence insulin by continuous infusion. of necrotic tissue, or steroid use. Emergency procedures Diabetic patients may be more If patient is on TPN, give no Control blood glucose with likely than nondiabetic patients to undergo emergency opera- additional glucose. insulin. If patient is on TPN, give tion, which can cause rapid metabolic decompensation with Consider possible postoperative no additional glucose. dehydration, hyperglycemia, and ketoacidosis. In addition, a SSI. surgical emergency can precipitate uncontrolled diabetes in Assess renal function, and perform serial ECGs in patients patients with no history of diabetes. Appropriate management at risk for cardiac complications. depends, to a large extent, on the patient’s metabolic condition. When one is faced with a so-called surgical abdomen, it is cru- Figure 1 Shown is an algorithm outlining preoperative and cial to determine whether there is a metabolic abnormality that postoperative management of the diabetic surgical patient. may be causing the condition. Given this possibility, it is sensi- ble to manage the patient conservatively at first, with an empha- sis on metabolic correction. If the underlying problem is in fact and volume restoration usually improves their general condi- metabolic, it should resolve or improve in 3 to 4 hours; if the tion. This brief period permits clarification of the diagnosis in problem is surgical, it should remain the same or worsen over patients with acute abdominal pain, which may be the conse- this period. quence of diabetic ketoacidosis rather than a so-called surgical abdomen. Elective major procedures In a patient undergoing gen- In preparing diabetic patients for operation, all long-acting eral anesthesia, regardless of the duration of the operation, infu- insulins (i.e., Ultralente preparations) should be replaced with sion of insulin and glucose is recommended if the patient is tak- intermediate-acting insulins (i.e., neutral protamine Hagedorn ing insulin for diabetes or is using drugs or diet therapy (or both) [NPH] or Lente preparations). If the patient has type 2 (non– without achieving satisfactory control of type 2 diabetes mellitus. insulin-dependent) diabetes mellitus, use of long-acting sulfony- Several methods of insulin administration may be used dur- lureas (e.g., chlorpropamide and glyburide) should be stopped ing the perioperative period. Most of the protocols include I.V. because of the risk of hypoglycemia; a short-acting preparation administration of short-acting insulin and 5% to 10% glucose. should be substituted. Use of metformin should be stopped In some, glucose and insulin are administered together in a sin- because of the risk of lactic acidosis when renal function is gle infusion.The advantage of this approach is that if the glucose impaired, as it may be during any procedure requiring anesthe- infusion is accidentally disconnected or obstructed, the insulin sia. Chronically hyperglycemic patients are frequently dehydrat- infusion is disconnected or obstructed as well, so that the risk of ed, and this condition should be corrected before operation. hypoglycemia is eliminated. The disadvantage of this method is that it is impossible to change the delivery rate of one agent INTRAOPERATIVE MANAGEMENT without changing the delivery rate of the other. Administration of insulin and glucose in separate bags allows either infusion rate Metabolic Effects of Operation and Anesthesia to be adjusted without the other being affected.The insulin infu- During anesthesia and operation, endogenous insulin secre- sion rate is progressively increased and the glucose infusion rate tion is suppressed, but the plasma levels of counterregulatory progressively decreased in accordance with the capillary blood hormones (glucagon, epinephrine, cortisol, and growth hor- glucose levels, measured hourly [see Table 1]. With this protocol,
  3. 3. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 10 Endocrine Problems — 3 daily is recommended during the first 24 to 48 hours after cessa- Table 1—Representative Protocol for tion of the insulin and glucose infusions and before resumption of the patient’s usual insulin regimen. Insulin-Glucose Infusion during Total parenteral nutrition (TPN) [see 8:22 Nutritional the Perioperative Period Support], often required during the postoperative period, can cause serious metabolic derangements in diabetic patients. For a 1. Infuse 5% dextrose in water (D5W) I.V. via pump. diabetic patient receiving TPN, a variable insulin infusion sched- 2. Make insulin solution with 0.5 U/ml of short-acting insulin (i.e., ule [see Table 2] is recommended, with hourly determinations of 250 U of regular insulin in 500 ml of normal saline). Administer in piggyback fashion via infusion pump into D5W infusion or blood glucose; however, additional glucose is not needed, through a separate I.V. site. because it is included in the TPN solution. Initially, the insulin 3. After initiating glucose-insulin infusion, stop all subcutaneous should be given as a continuous infusion separate from the TPN insulin therapy. solution. Once a stable dose of insulin is reached (usually within 4. Measure capillary blood glucose levels every hour. 24 to 48 hours), the total amount of insulin required over a 24- hour period can be added to the TPN bag. This amount may be 5. On the basis of hourly blood glucose levels, adjust each infusion according to the following schedule: high—often more than 100 units. At this point, capillary blood glucose levels can be measured every 2 to 4 hours. Insulin Infusion Hypoglycemia can be difficult to detect in critically ill Blood Glucose D5W Infusion (mg/dl) (ml/hr) patients, in whom blood glucose levels are often elevated for any (ml/hr) (U/hr) of a number of reasons. Accordingly, it has been common prac- tice to accept blood glucose levels ranging from 150 to 200 < 70* 1.0 0.5 150 mg/dl in these patients. This practice, however, was called into 71–100 2.0 1.0 125 question by a 2001 randomized study of 1,548 ICU patients in 101–150 3.0 1.5 100 which liberal glucose control (blood glucose level, 180 to 200 151–200 4.0 2.0 100 mg/dl) was compared with tight control (blood glucose level, 80 201–250 6.0 3.0 100 to 110 mg/dl).5 ICU survival was significantly better in the tight 251–300 8.0 4.0 75 control group (95.4%) than in the liberal control group (92%). > 300 12.0 6.0 50 In addition, the tight control group had a lower incidence of sys- *Give 10 ml D5W I.V. and repeat blood glucose measurement 15 min later. temic infection, had less need of antibiotic therapy, required fewer transfusions, and were less subject to hypobilirubinemia. These findings support the view that tight regulation of glucose and insulin to maintain normal blood glucose levels is desirable a blood glucose level in the range of 125 to 200 mg/dl (6.9 to in critically ill patients. 11.1 mmol/L) can easily be maintained throughout the periop- erative period. Close observation of blood glucose levels and Cardiovascular and Renal Assessment prompt adjustment of insulin and glucose delivery are mandato- Serial postoperative electrocardiograms are recommended for ry for achieving a stable blood glucose level. Electrolyte supple- older diabetic patients, those with long-standing type 1 diabetes mentation is administered via a separate infusion. mellitus, and those with known heart disease. Postoperative myocardial infarction, which may be silent, is associated with a Minor procedures Diabetic patients who fast before minor high mortality. Careful monitoring of blood urea nitrogen and operations (e.g., endoscopic procedures and operations per- serum creatinine levels facilitates the detection of acute renal formed with the patient under local anesthesia) should omit the morning dose of insulin or oral hypoglycemic agent, and their capillary blood glucose level should be measured every 2 to 4 hours. Supplemental subcutaneous short-acting insulin can be Table 2—Management of Diabetes in Patients administered according to a variable insulin schedule, and the Undergoing Minor Surgical Procedures30 usual insulin or oral agent can be taken after the procedure [see Table 2].This method of administration, which is associated with If patient fasted unpredictable absorption and variable plasma insulin levels, is 1. Withhold morning dose of insulin or oral agent. restricted to surgical patients undergoing minor procedures and 2. Measure capillary blood glucose level before procedure should not be used in those undergoing major operations. and every 2–4 hr thereafter. POSTOPERATIVE MANAGEMENT 3. Give short-acting insulin every 2–4 hr, as follows: Insulin and Glucose Administration Blood Glucose (mg/dl) Short-Acting Insulin (U) After minor procedures, diabetic patients should receive I.V. < 150 0 glucose and insulin until their metabolic condition is stable and 151–200 2 oral feeding can be tolerated. To prevent ketosis, the insulin and glucose infusions should be continued for at least 1 hour after the 201–250 3 administration of subcutaneous short-acting insulin. After major 251–300 5 procedures, patients should receive I.V. glucose and in- > 300 6 sulin until they are able to take solid food without difficulty. A regimen consisting of multiple subcutaneous injections of short- 4. After procedure, give usual dose of insulin or oral agent. acting insulin before meals and intermediate-acting insulin twice
  4. 4. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 10 Endocrine Problems — 4 Adrenal Insufficiency failure [see 8:6 Renal Failure]. If a contrast agent is used, the patient should be well hydrated before and after the procedure. The anti-inflammatory properties of the glucocorticoid steroids [see Table 3] are commonly exploited to treat disease. Infection Patients are often treated for long periods with large pharmaco- SSI is common in diabetic patients with poor metabolic con- logic doses of steroids (commonly, prednisone by mouth) for trol. Impaired granulocyte function resulting from hyper- inflammatory or autoimmune diseases such as arthritis, systemic glycemia may predispose to bacterial infections. Autonomic neu- lupus erythematosus, inflammatory bowel disease, and bronchial ropathy, if present, may lead to difficulty in postoperative void- asthma. Primary failure of the hypothalamic-pituitary-adrenal ing, which increases the risk of urinary tract infection. Poor (HPA) axis (as in Addison disease, Sheehan syndrome, and pan- circulation as a result of macroangiopathy or microangiopathy hypopituitarism) is rare, but when it does occur, it must be treat- can also contribute to the likelihood of postoperative infection. ed with long-term administration of physiologic doses of corti- Tight metabolic control during the perioperative period can costeroids. It is not uncommon for patients who are receiving decrease the risk of postoperative infection.When SSIs do occur such corticosteroid therapy to require operations, and this surgi- in the diabetic population, they are usually caused by mixed cal population presents a unique perioperative management flora, including aerobic and anaerobic organisms such as challenge [see Figure 2]. It is axiomatic that any patient treated Escherichia coli, Enterobacteriaceae, various streptococci, with exogenous steroids may eventually manifest adrenal atro- Staphylococcus aureus, and Bacteroides fragilis. Necrotizing infec- phy as a result of suppressed endogenous production of adreno- tions (e.g., fasciitis, gangrene, and Fournier gangrene) are more corticotropic hormone (ACTH). Actual or relative adrenal common and spread more readily in diabetic patients. insufficiency may occur during or after a major operation, result- Surgical debridement and drainage, if needed, should be per- ing in a syndrome whose manifestations can range from nausea, formed early. Cultures should be obtained during drainage pro- vomiting, fever, abdominal pain, and electrolyte abnormalities to cedures. Ideally, antibiotic therapy awaits and is based on culture complete circulatory collapse. results; however, in practice, it is often preferable to initiate The adrenal cortex is central to the maintenance of homeo- empirical therapy for the most likely organisms before the results stasis both at rest and during stress.10 Cortisol, the predomi- are available. Swarming of Proteus organisms may obscure other nant glucocorticoid hormone, is produced by the fascicular and pathogens on culture plates. Unless the patient is clearly mani- reticular zones of the adrenal cortex. It is under the strict regula- festing a septic response, aminoglycosides should be avoided tory control of both the hypothalamus (via corticotropin-releasing because of their nephrotoxicity and the likelihood that diabetic hormone) and the anterior pituitary gland (via ACTH). Cortisol patients may have underlying renal disease. If severe infections itself participates in its own regulation, imparting a potent nega- do not respond to antibiotic therapy, the presence of Candida or tive feedback signal to both the hypothalamus and the ACTH- other fungal species should be suspected. producing basophilic cells within the adenohypophysis of the pitu- Many factors play a role in the increased susceptibility of dia- itary.Together, these components, which constitute the HPA axis, betics to infection, including macroangiopathy, microangiopa- form a finely regulated feedback loop for cortisol secretion. thy, neuropathy, impaired neutrophil and lymphocyte function, Under unstressed physiologic conditions, the adrenal cortex increased capillary permeability, and impaired granulation and constitutively produces approximately 20 to 25 mg of cortisol healing.6 An obvious example of this interaction of multiple con- daily.11 Cortisol secretion normally occurs in diurnal surges; tributing factors is a chronically infected nonhealing ulcer on a consequently, simple measurements of serum cortisol levels in neuropathic foot. A less obvious but more serious example is the isolation generally do not suffice for accurate evaluation of the failure of host defenses against peritonitis, soft tissue infection, status of the HPA axis. Much of the daily variability in cortisol and bacteremia that develops in diabetic patients. Chemotaxis, secretion can be tracked with 24-hour urinary measurements of adherence, phagocytosis,7 bacterial killing, and production of the hydroxysteroid metabolites; however, there can be significant cytokines and complement are all impaired in patients with type 1 diabetes mellitus. The greater prominence of such abnormali- ties in patients with type 1 diabetes mellitus suggests that the Table 3 Selected Corticosteroid Preparations most likely cause is related to chronic and irreversible glycosyla- tion of many proteins, which limits the function of intracellular Preparation Equivalent Glucocorticoid Mineralocorticoid and intercellular messengers. The implication of this theory is Doses (mg) Activity* Activity* that tight short- and long-term control of blood glucose should allow better control of infection.5 Short-acting (8–12 hr) The impaired wound healing seen in diabetic patients clearly is Hydrocortisone 20 1 1 related in part to increased susceptibility to infection; however, it Cortisone 25 0.80 0.80 is also observed with sterile wounds. Many animal studies have Intermediate-acting corroborated the clinical observation that skin, fascia, and bone (12–36 hr) all heal more slowly and with less strength in diabetic patients. Prednisone 5 4 0.80 Such studies have generally found that this impaired healing is Prednisolone 5 4 0.80 partially mitigated by insulin control, which suggests that glyco- Methylprednisolone 4 5 0 sylation of proteins is an important factor. A 1999 study indicat- Triamcinolone 4 5 0 ed that the impaired healing is significantly mediated by endoge- Long-acting (36–54 hr) nous corticosteroids.8 Local application of inflammatory sub- Betamethasone 0.60 25 0 stances or growth factors (e.g., platelet-derived growth factor, Dexamethasone 0.75 30 0 Mineralocorticoid tissue growth factor, bacterial by-products, growth hormone, Fludrocortisone — 10 125 and hyperosmotic sugar) has been shown to stimulate healing in diabetic animals.6,9 *Ranked on a scale rating hydrocortisone as 1.
  5. 5. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 10 Endocrine Problems — 5 Patient with history of steroid therapy is undergoing operation Perform history and physical examination, with particular attention to previous adrenal insufficiency or hypopituitarism. Determine extent of current or previous steroid use. Reduce steroid dose to lowest possible level before elective procedure. Patient is currently taking Patient previously received exogenous steroids steroid therapy Dosage < 10 mg/day Dosage ≥ 10 mg/day Steroid use < 3 mo ago Steroid use ≥ 3 mo ago Continue current dosage; Treat as if patient is currently Assume HPA axis function additional steroids are taking exogenous steroids is normal; additional unnecessary. (left). steroids are unnecessary. Procedure is minor Procedure is of moderate magnitude Procedure is major Give scheduled dose plus 25 mg of Give scheduled dose plus 25 mg of Give scheduled dose plus 25 mg of hydrocortisone before induction. hydrocortisone before induction, then hydrocortisone before induction, then 100 mg over next 24 hr. 100 mg/day for next 2–3 days. After operation Consider potential complications of long-term steroid use (immunosuppression, poor wound healing, hypoglycemia). Figure 2 Shown is an algorithm Consider administering vitamin A if risk of SSI is significant. outlining preoperative and postoper- Consider possibility of previously unidentified cause of adrenal ative care of the surgical patient at insufficiency in ICU (e.g., emergency operation, trauma). risk for adrenal insufficiency. overlap between normal patients and those with clinical adrenal ulated cortisol levels above which the HPA axis can be assumed insufficiency.12 Provocative testing of the HPA axis is based on to be intact, it has been suggested that a value higher than 600 the normal physiologic response of the adrenal gland to release mol/L at 30 minutes should be a sufficiently sensitive confirma- cortisol in a receptor-mediated G-protein–coupled response to tion of an intact HPA axis. circulating ACTH. Adrenal glucocorticoids are important modulators of the Although there is some controversy regarding which laborato- stress response: they play a complex role in the metabolic path- ry evaluation is the best predictor of adequate adrenal response ways for carbohydrates, fats, and proteins; modulate gluconeo- to a surgical stress, it is clear that ACTH stimulatory testing is genesis and lipolysis; mediate insulin resistance; and exert a host more sensitive and specific than unprovoked steroid measure- of well-documented effects on inflammation and wound healing. ment alone. Hypoglycemia-induced release of ACTH in It is clear that physiologic stresses (e.g., burns, trauma, and iatro- response to exogenous insulin infusion (the insulin tolerance genic tissue damage occurring during operations) result in an test, or ITT) has long been considered the gold standard for ACTH-induced surge in the adrenal steroid response.16,17 determination of relative adrenal insufficiency, but various com- Serum measurements reveal that this response can produce cor- plications, including discomfort, seizures, and even death, limit tisol elevations several times greater than those produced under its clinical usefulness as a routinely applied test.13 In several stud- basal conditions. It is becoming apparent that although this ies, strong correlations have been observed between the ITT and exaggerated adrenal stress response may have conferred a certain adrenal stimulation with a synthetic corticotropin construct.14,15 evolutionary benefit, prolonged exposure to high doses of In this test, the plasma cortisol response is measured 0, 30, and steroids may nonetheless have deleterious consequences. The 60 minutes after infusion of 250 µg of the ACTH analogue. potential complications of long-term or high-dose administra- Although there is no unanimously accepted cutoff value for stim- tion of glucocorticoids are well described: they include hyper-
  6. 6. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 10 Endocrine Problems — 6 tension, cataracts, myopathy (especially when glucocorticoids such as occur during surgery. Complete or even relative adrenal are used in conjunction with nondepolarizing paralytic drugs), insufficiency is preventable; when it does occur, it can have disas- osteonecrosis (particularly on the femoral head), impaired trous consequences if not recognized and appropriately treated. wound healing, and immunosuppression.18 Exogenous administration of steroids in sufficient doses is gener- It was the observed (and presumably physiologic) magnitude ally adequate to prevent the syndrome of adrenal insufficiency. of the cortisol response to stress that led to the long-held—albeit The decision to administer supplemental perioperative steroids never corroborated—assumption that supraphysiologic levels of should be based on the specific details of the history of steroid use steroids were required to maintain homeostasis in the stressed as well as on the magnitude of the proposed operation. environment. In the 1950s, two case reports were published that described perioperative deaths thought to result from untreated and unrecognized adrenal insufficiency.19,20 Thereafter, it Hormone Replacement became common practice to supply supraphysiologic doses of Many surgical patients are receiving thyroid or ovarian hor- exogenous steroids (i.e., doses two to three times that expected mone replacement therapy. In addition, the use of growth hor- under basal conditions) to patients believed to be at risk for mone, growth hormone precursors, and anabolic steroids has adrenal suppression and therefore unable to mount the expect- become more common in general practice. The effects of these ed cortisol surge during operation. Subsequently, this practice hormone medications must be taken into account in any patient came under scrutiny. Primary studies suggested that although undergoing an elective or emergency operation. Because all of HPA suppression could occur as a result of long-term steroid these substances have long half-lives, replacement is not neces- use, normal physiologic replacement doses were sufficient to sary for the first 2 weeks after operation; however, if the illness or maintain perioperative homeostasis; supraphysiologic doses were the operation itself prevents oral intake for more than 2 weeks, unnecessary.21 The concept that significantly lower doses of the possibility of hypothyroidism or estrogen depletion should be steroids are required to maintain homeostasis and normotension considered. Postoperative weakness, lack of energy, depression, in the perioperative period than was once believed has been sup- and sleeping disorders can all be caused by the lack of long-term ported by prospective clinical studies in humans.22 hormone supplements. It is clear that ACTH is not only stimulatory but also trophic Some patients exhibit decreased endogenous thyroid function for the adrenal cortex. There is evidence that if the adrenal cor- after operation, either because their thyroid-stimulating hor- tex is not exposed to ACTH, it is subject to hyposecretion and mone (TSH) levels are depressed as a consequence of long-term anatomic atrophy. It was once thought that exposure to even low thyroid medication or because they experience complications doses of steroids (< 10 mg of prednisone equivalent) was suffi- and become critically ill. Critical illness typically leads to cient to suppress the endogenous release of ACTH and thus to reduced blood levels of triiodothyronine (T3) and thyroxine result in a state of adrenal insufficiency. This belief led to the (T4). In addition, glucocorticoids, radiopaque dyes, propranolol, common practice of administering so-called stress-dose steroids and amiodarone all lower plasma T4 levels,27 and dopamine to surgical patients who had received exogenous steroids even in decreases TSH secretion directly.28 Most critically ill patients, small doses or as long ago as 1 year before operation. Provocative however, do not exhibit metabolic or hemodynamic changes studies on patients previously exposed to steroids demonstrated indicative of hypothyroidism. Measurement of TSH is helpful for that the HPA axis usually remains intact despite either ongoing determining the significance of thyroid function in critically ill exposure to small doses of exogenous steroids (< 10 mg of pred- patients. If the serum TSH level is lower than 5 µU/ml and the nisone equivalent daily) or earlier steroid use (if the time since patient is not on high-dose dopamine therapy, thyroid function discontinuance was longer than 2 to 3 months).23-26 is considered adequate regardless of other plasma markers. If the In summary, the glucocorticoids are essential components of TSH level is higher than 20 µU/ml, replacement with thyroxine human homeostasis both at rest and under stressful conditions is indicated.29 References 1. Root HF: Preoperative medical care of the dia- dence for a reaction between glucose and opso- assays: guidelines for the provision of clinical betic patient. Postgrad Med 40:439, 1966 nizing proteins. J Clin Pathol 37:783, 1984 biochemistry service. Ann Clin Biochem 22:435, 2. Galloway JA, Shuman CR: Diabetes and 8. Bitar MS, Farook T, Wahid S, et al: Gluco- 1985 surgery: a study of 667 cases. Am J Med 34:177, corticoid dependent impairment of wound heal- 13. Jacobs HS, Nabarro JDN: Tests of hypothalam- 1963 ing in experimental diabetes: amelioration by ic-pituitary-adrenal function in man. Q J Med 3. Walts LF, Miller J, Davidson MB, et al: Peri- adrenalectomy and RU486. J Surg Res 82:234, 38:475, 1969 operative management of diabetes mellitus. 1999 14. Kehlet H, Binder C: Value of an ACTH test in Anesthesiology 55:104, 1981 9. Qiu JG, Chang TH, Steinberg JJ, et al: Single assessing hypothalamic-pituitary-adrenocortical 4. Thompson J, Husband DJ, Thai AC, et al: Met- local installation of Staphylococcus aureus pepti- function in glucocorticoid-treated patients. BMJ abolic changes in the non-insulin-dependent doglycan prevents diabetes impaired wound 2:147, 1973 diabetic undergoing minor surgery: effect of glu- healing. Wound Repair Regen 6:449, 1998 15. Clayton RN: Short Synacthen test versus insulin cose-insulin-potassium infusion. Br J Surg 10. Orth DN, Kovacs WJ: The adrenal cortex. 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