The role of corticosteroids in attenuating stress response

In response to major stress (e.g., hemorrhage or sepsis) or if the stress is severe enough to cause a decrease in blood pressure (in the former, from a decrease in preload, stroke volume, and cardiac output; in the latter, from a decrease in systemic vascular resistance), the sympathetic nervous system is activated, and the parasympathetic system is inhibited. Efferent activity in the sympathetic nervous system increases. Postganglionic efferent nerves release norepinephrine in close proximity to smooth muscle cells in the peripheral vasculature. Norepinephrine binds to α-adrenergic receptors, thereby increasing cytoplasmic concentrations of Ca²⁺. (Think of a “wave” of Ca²⁺ sweeping across the cell—both the height [concentration] and periodicity [rate] have an effect.) The increased Ca²⁺ concentration stimulates binding of actin to myosin, causing the cell to contract. The lumens of the peripheral arterioles narrow, and systemic vascular resistance and blood pressure increase. The sympathetic efferent nerve cells simultaneously stimulate the adrenal medulla to release epinephrine into the adrenal vein, which empties into the renal vein or directly into the inferior vena cava. From the entry site into the inferior vena cava, it is but a short distance to the right atrium. Within the right atrium and subsequent cardiac chambers, epinephrine increases chronotropy (heart rate), inotropy (cardiac contractility), dromotropy (conduction velocity), and lusitropy (myocardial relaxation), all of which increase cardiac output. The α-adrenergic receptors are down-regulated within minutes of activation, certainly within 30 min. If nothing intervenes to restore the sensitivity of the α-receptors, blood pressure will fall progressively (especially if hemorrhage or sepsis continues unabated).

When the sympathetic nervous system is activated, a simultaneous activation occurs in the HPA axis. The pituitary gland releases ACTH, which, when it reaches the adrenal gland, stimulates the adrenal cortex to release corticosteroids. These corticosteroids bind to receptors on the smooth muscles in the peripheral vasculature, but they do not stimulate release of Ca²⁺ in the cytoplasm; instead, a complex interaction between the Ca²⁺ and the α-receptors restores the sensitivity to catecholamines.

Treatment of adrenal suppression

As described earlier, rather than performing the cosyntropin stimulation test, current practice is to administer hydrocortisone the day of surgery to all patients who are currently taking at least a 10-mg dose of hydrocortisone or its equivalent (enough to suppress the HPA axis) or who have taken that amount of corticosteroids for 14 days at any time in the preceding 3 months. (Previous recommendations were to administer perioperative steroids to any patients who had received this amount of corticosteroid in the previous year, but such recommendations have been found to be too liberal. Three months is sufficient for most patients to regain functionality of the HPA axis.)

Patients currently taking corticosteroids should take their regular dose of corticosteroids the morning of surgery and should then receive 100 mg of hydrocortisone or its equivalent over the next 24 h (Table 234-2). If dexamethasone is chosen, 10 mg before surgery may be adequate to protect the patient because of its potency and duration. These recommendations are the same if the patient is not currently taking corticosteroids but has taken an HPA axis–suppressive dose for 14 days in the previous 3 months.

The recommendation is to space the hydrocortisone dose over 24 h, but, obviously, a patient who was receiving a replacement dose of corticosteroids and develops hypotension intraoperatively that is refractory to treatment should be given a dose of corticosteroids intraoperatively. In fact, because some patients in the intensive care unit who are sufficiently stressed have been demonstrated to have suppression of the HPA axis, corticosteroids are used to treat hypotension in these patients. Similarly, some anesthesia providers who treat trauma patients routinely administer corticosteroids in the operating room to patients who have sustained traumatic injury.

Treatment of airway edema

Because of their antiinflammatory properties, corticosteroids have long been used to treat patients with or at risk of developing airway edema. Otorhinolaryngologists performing surgery often administer 4 to 10 mg of dexamethasone to reduce the risk of edema in the nose, pharynx, or larynx. Similarly, anesthesia providers will administer a comparable dose of dexamethasone when anesthetizing children with a small airway, in whom even a minimal amount of edema would compromise the airway, such as those who require a tracheal tube smaller than 4.5 mm or adults who require a wire spiral tracheal tube (usually used because the patient’s neck will be flexed or turned so much that a standard tracheal tube might collapse). A similar strategy is often used for patients who have been intubated for several days in the intensive care unit and who are anticipated to be imminently extubated. This is done because even a small amount of edema in a child’s airway will decrease the diameter of the airway, will significantly decrease the cross-sectional area of the airway, and will decrease the flow of air by an even greater amount. Similarly, if the anesthesia provider is apprehensive enough to intubate the trachea with a wire spiral tube because of concerns about positioning of the head, there is a high probability that venous drainage of the head will be compromised, which would increase the likelihood of edema developing in the airway or glottic opening. Finally, traction associated with a tracheal tube that has been in place for some time, especially in patients who are able to move their heads, will cause a small amount of repeated movement of the tube, which, in turn, will create friction between the tube and the tracheal mucosa, leading to inflammation. When the tube is in place, the tube stents the airway open, but once the tube is removed, edema will begin to form, narrowing the airway over time.

Timing of administration of the dose of corticosteroids

If time is sufficient in patients who have prolonged intubation, the patient should receive a dose of dexamethasone 6 to 8 h before extubation (onset of dexamethasone is 6-8 h), with a second dose administered when the patient is extubated. If only one dose of dexamethasone is planned, it should be given when the patient is extubated. For pediatric patients and for adults undergoing surgery on the head or neck, the dexamethasone, if it is to be given, should be administered at the beginning of the procedure—usually after induction and intubation of the airway. These guidelines are only suggestions, given that no large prospective, randomized, controlled study has shown a benefit with this use of dexamethasone. The results of smaller studies are mixed. Because of their belief that one to two doses of dexamethasone have minimal side effects, many anesthesia providers continue to administer dexamethasone to decrease the chance that patients will develop airway edema.

Treatment of postoperative nausea and vomiting

Postoperative nausea and vomiting (PONV) can occur in up to 33% of patients undergoing anesthesia and surgery (see Chapter 109), depending on the patient’s sex, age, and history (smoking, motion sickness, previous PONV) and type of operation the patient has undergone. As in many other situations, an ounce of prevention is worth a pound of cure. Typically, 5-HT₃-receptor blocking agents—because of onset and duration of action—are administered to patients at the end of a surgical procedure, with prochlorperazine and other related compounds used for rescue therapy. In years past, droperidol was administered prophylactically at the beginning of surgical procedures because of its efficacy and duration of action. However, when the U.S. Food and Drug Administration required a boxed warning on the label of droperidol in 2001 regarding the development of torsades de pointes in patients with long QT syndrome who received an intravenously administered bolus of more than 1.25 mg of droperidol, the use of droperidol fell out of favor. Some clinicians and departments of anesthesia continue to use droperidol, albeit in smaller doses (0.625-1.2 mg) for prophylaxis of PONV, but others have changed to the use of corticosteroids. Dexamethasone has been found to have the most efficacy—usually at a dose of 4 to 10 mg administered intravenously while the patient is still in the preoperative holding area prior to the patient’s transport to the operating room.

The use of corticosteroids for antiinflammatory properties

Because of their antiinflammatory properties, corticosteroids have been used in the past, and are still used by some, to treat systemic and localized inflammatory responses. In the past, some clinicians used corticosteroids to treat the generalized inflammatory response associated with cardiopulmonary bypass, transfusion reactions, allergic reactions, and anaphylaxis. As techniques for cardiopulmonary bypass have improved, there is less need for the administration of antiinflammatory drugs. With respect to allergic reactions, whether they are caused by transfusion of blood products or drugs, there are better medications that specifically block the degranulation of mast cells and that inhibit H₁ and H₂ receptors. Special note should be made of transfusion-related acute lung injury caused by a reaction between antibodies in transfused fresh frozen plasma (especially if the plasma is obtained from multiparous women) and antigens on the recipient’s white blood cells. Corticosteroids have no role in the treatment of transfusion-related acute lung injury, nor in the treatment of acute respiratory distress syndrome.

Anesthesia providers often administer corticosteroids during organ transplantation, but, in this circumstance, the corticosteroids are administered as part of the immunosuppression regimen and will be continued postoperatively, often indefinitely. Such use is beyond the scope of this chapter and will not be discussed further.

Adverse effects associated with the use of corticosteroids

Corticosteroids have multiple actions (Table 234-3) that highlight their role in maintaining homeostasis during a stress of sufficient magnitude to activate the fight-or-flight response (Figure 234-1). The sequelae of corticosteroid use are not so much adverse effects as they are the primary effects associated with the corticosteroids in general. However, for the purpose of this discussion, we consider these effects to be “adverse effects” when one or two doses of corticosteroids are administered for the treatment or prevention of PONV or edema.

The most recognized adverse effect of corticosteroids is hyperglycemia, which can be seen following one or two doses, usually in obese (but not in overweight) patients. Because of the emphasis on maintaining patients’ blood glucose levels at less than 180 to 200 mg/dL (depending upon which guidelines are used), obese patients (body mass index ≥ 30 kg/m²) who have received a corticosteroid intraoperatively should have a blood glucose level checked either intraoperatively or in the postanesthesia care unit.

Anesthesia providers should at least be aware of the potential negative effects of corticosteroid use on wound healing and surgical site infection, although no studies have confirmed these associations when only one or two doses of corticosteroids are administered perioperatively. However, these adverse effects should give anesthesia providers cause for concern if they plan to administer more than one or two doses of corticosteroids.