The subject of perioperative glucocorticoid replacement certainly needs no extensive preamble or introduction. Hospitalists are routinely required to exercise the art and science of estimating the steroid requirement for patients on steroids undergoing surgical procedures. What follows is a brief review of the literature for fellow internists.
History: Full Circle
It has been almost 60 years since corticosteroids were first recognized for their anti-inflammatory and immunosuppressive properties, initially in rheumatologic diseases. The beneficial effects of steroids in rheumatoid arthritis were described in 1949 by Philip S. Hench and colleagues, a discovery for which he received (together with Edward C. Kendall and Tadeus Reichstein) the Nobel Prize in medicine in 1950.1,2
Barely three years later, Fraser and coworkers reported the death of a 34-year-old man after routine orthopedic surgery due to shock, adrenal insufficiency, and circulatory collapse.3 The patient had been on corticosteroids for rheumatoid arthritis, but the treatment had been stopped prior to surgery. The potentially fatal consequences of steroid withdrawal prior to surgery were thrown into even greater prominence by a similar report, presented by Lewis and colleagues within a year of the first incident.4 This occurrence involved an even younger patient: a 24-year-old woman, who had been on steroids for rheumatoid arthritis and who died after her therapy was stopped a day prior to surgery.
The first recommendations for perioperative steroid replacement soon appeared.4 When loosely interpreted, routine steroid doses were often quadrupled prior to surgery—a practice that sometimes led to mammoth amounts of steroids administered during the surgical period.5 Not surprisingly, adverse clinical results were soon noted: decreased tissue repair and healing, infections, and hyperglycemia, to name a few.5 While mortality related to acute steroid withdrawal and circulatory collapse might have decreased, morbidity related to poor surgical wound healing and subsequent complications increased.
Finally, in 1994, the problem of perioperative glucocorticoid replacement was reassessed, and fresh guidelines were provided by Salem and colleagues.5 These guidelines recognized the need for steroid coverage but in more moderate doses than had previously been used, and this is where we stand today—replacement, but in moderation.
Why Perioperative Steroid Coverage?
Acute stress activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in increased plasma adrenocorticotropic hormone (ACTH) and cortisol levels.6 This increase is believed to be an adaptive mechanism meant to enhance the body’s ability to combat stress by increasing its sensitivity to catecholamines; its cardiac contractility and output; and its mobilization of energy sources with gluconeogenesis, proteolysis, and lipolysis.6 It follows that lack of increase in cortisol production during stress would cause the host to succumb to it. On the other hand, too much cortisol would be detrimental, causing increased tissue breakdown, poor wound healing, and immunosuppression.
Surgery is one of the most potent stressors that can cause activation of the HPA axis.6,7 The degree of activation depends on the type and duration of surgery and anesthesia, with many other variables adding to the picture, including analgesics, antihypertensive medications, infections, and age.5-9 The maximum stimulation of the HPA axis in uncomplicated surgery has been assessed to occur during reversal of anesthesia and in the immediate postoperative period.6,9,10 Normal daily cortisol production is about 15 to 20 mg/day.6 These levels can go up to as much as 75–100 mg/day with surgical stress.6,11,12
Given this background, it is clear that any patient who has inadequate cortisol production in response to surgical stress will fare poorly in such a situation. This patient will need to be recognized, and his acute steroid requirement will have to be estimated and supplemented; in addition, over- or under-dosing must be avoided in order to achieve a good post-surgical outcome.