Preoperative Steroids for Laparoscopic Surgery

Laparoscopic surgery provides spectacular benefits to patients. Pain and disfigurement are much less, allowing for better cosmesis, shortened recovery time, and quicker return to preoperative well-being and normal activity. Despite the minimally invasive nature of laparoscopy, host physiologic responses to stress are still variably activated. The same gamut of metabolic, hormonal, inflammatory, and immune responses activated by open surgery are also induced by laparoscopy, but to a lesser degree and proportionate to the extent of surgical injury.¹ There are as many differences as there are similarities in the mechanisms and magnitudes of the relative stress responses. Intuitively, one might expect that any effort to modulate these responses would also depend on the extent of stress. What might work well for open or major surgery may not for laparoscopic or minor surgery and vice versa.

In this issue of Annals of Surgery, Bisgaard et al² from the University of Copenhagen test this concept in a randomized controlled trial evaluating preoperative steroids for laparoscopic surgery. On the basis of their findings, the authors recommend that patients undergoing laparoscopic cholecystectomy should routinely receive a single dose of glucocorticoid preoperatively. Although the risks seem minimal, what is to be gained?

Fifty years have passed since the realities of perioperative steroid administration were first highlighted. Frasier et al³ demonstrated that 2 young patients being treated with long-term glucocorticoid therapy died unexpectedly after routine orthopedic surgical procedures. Their deaths were attributed to adrenal insufficiency. In normal patients, the acute physiological stress induced by surgery and trauma activates the hypothalamic-pituitary-adrenal (HPA) axis, and a protective physiologic response ensues.⁴ Patients receiving long-term corticosteroid therapies have an iatrogenic HPA axis suppression that many presume leaves them unable to mount an optimal protective stress response. To avert potentially life-threatening secondary adrenal insufficiency, clinicians today provide such patients perioperative “stress steroid” boosts.⁵ This traditional and empiric standard of care, however, is being challenged more and more. Critics cite insufficient evidence-based evaluation of perioperative stress steroids and poor correlation between biochemical data of HPA axis function, chronic steroid use, and clinical outcome.⁶ Indeed, many of these patients have undergone major surgery uneventfully without stress steroids.

In the Bisgaard et al article,² all patients likely had an intact HPA axis as they underwent their elective, uncomplicated laparoscopic cholecystectomy. They did not receive stress steroid boosts, but instead a single dose of 8 mg of dexamethasone intravenously exactly 90 minutes preoperatively. This was purely an attempt to modulate the systemic physiologic response to the limited stress of a standardized laparoscopic procedure. Compared with placebo, this precise dosing of dexamethasone, as emphasized by the authors, reduced pain, fatigue, opioid use, nausea and vomiting, and duration of convalescence. Compared with historical controls for open cholecystectomy, these placebo-treated patients also did very well, as we now expect for laparoscopic cholecystectomy. Nonetheless, this simple, inexpensive, and apparently innocuous dose of preoperative steroid delivered just that much more benefit to patients. What is not clear is why it did.

To understand this, one can begin by considering the clinical efficacy of single-dose steroid therapy in elective major and minor surgery. There are several published trials available; however, variability in study populations, surgical procedures, protocols for steroid dosing, and endpoints of clinical outcome preclude any consensus. Holte and Kehlet,⁷ also from this unit in Denmark, provide a comprehensive review of these trials and endorse the use of single-dose preoperative steroids. As an immune modulation strategy, such therapy does appear to shift the balance of inflammation in favor of antiinflammatory mediators in a variety of surgical procedures. Some aspects of cardiac⁸ and pulmonary function⁹ have been shown to improve, but usually in small studies of insufficient statistical power to detect reliable clinical differences. Trials aimed at evaluating side effects of preoperative single-dose steroids have also been inconclusive because of size and design. When considered together, however, it appears that this therapy is safe; it particularly does not increase complications one might expect, such as infections and impaired wound healing. It also appears that the timing of steroid administration is key (1–2 hours preoperative) if excess inflammatory activation and related postoperative morbidity is to be attenuated.

The incidence and severity of postoperative nausea and vomiting have been significantly decreased by preoperative single-dose steroid administration in several studies.¹⁰ This can be explained by a central antiemetic mechanism involving endogenous prostaglandin and opioid production. Several studies suggest that pain is less as well; how this occurs is not known, though it may relate to reduced local tissue edema. These beneficial effects for nausea, vomiting, and pain are most reliably shown in studies of limited surgical trauma such as tonsillectomies, dental procedures, and now laparoscopic cholecystectomy. It has always been far more difficult to demonstrate any value from this therapy in major surgical procedures. For minor and minimally invasive procedures, one can expect that any positive impact on typical postoperative symptoms such as nausea, vomiting, and pain will directly translate to accelerated convalescence and return to normal activity.

Like any valuable study, the Bisgaard et al trial raises as many questions as it answers. Though generally well designed and executed, the trial still has certain peculiarities. When a statistical power analysis called for 39 patients/group to reveal effect of therapy, the authors evaluated 40/group. Will these results hold up with higher patient numbers? Also, some might question the exclusion criteria, especially those relating to infectious complications and even choledocholithiasis. Given any possibility that dexamethasone might promote infection or any unforeseen complication, larger numbers of patients may be better analyzed by intention-to-treat criteria. Certainly, the operative techniques and protocols for anesthesia and perioperative care as reported will differ from the nuances of others around the world. Only with substantially larger, multisite studies can these factors be tested and a recommendation for routine use be validated. If it is, issues of practicality, convenience, and logistics will arise next. We usually face issues of excess cost in dollars, equipment, and workforce, but not in this case. How will patients presenting for today’s typical outpatient laparoscopic cholecystectomy reliably receive an intravenous steroid dose 90 minutes before their operation? It is not as easy as it may seem. Are there any oral or other substitutes that can achieve the same desired clinical efficacy? Have they been evaluated?

In summary, we have an opportunity to enhance further the immediate benefits of minimally invasive surgery. This simple therapy warrants broader evaluation across many laparoscopic procedures. The capacity for single-dose steroid therapy to turn down the volume of a systemic stress and immune response¹¹ may only become clinically evident when the volume is not too high to begin with. This is an intuitive but key insight as to why these patients had measurably improved clinical outcomes after elective minimally invasive surgery.