Surgery is a necessity for managing a variety of health conditions including injuries, cardiovascular disease, Cesarean delivery, and cancer.¹ In 2012, almost 313 million operations took place across the world, an increase of over 38% from 2004. The pattern was similar in the United States, which accounted for almost 36.5 million of those surgeries in 2012. It is clear then that a significant number of people in the United States will undergo a surgical procedure in any given year, the expenditures associated with these procedures will continue to climb as surgical options increase, and patients are unable to work during the period of recovery.

Surgery, in general, is a disruption to the body and triggers a series of events that are very broadly referred to as the stress response. It is a normal reaction of great importance in both nature and medicine. The natural stress response in man is designed to first protect against threats and is highlighted by the surge of hormones needed to either “fight or run”.  This initial response is then followed by a response designed to promote survival, including activation of the immune system to promote wound healing and protect against infection. The surgical stress response has three key components: stimulation of the sympathetic nervous system, activation of endocrine system, and triggering of the immune system. The sympathetic nervous system can be equated to car’s gas pedal.² It provides the body with a burst of energy so that it can respond to danger or injury, primarily by releasing the hormone adrenaline into the bloodstream. As adrenaline circulates through the body, the heart beats faster allowing more blood to be delivered to muscles and vital organs. Other changes include dilation of the airways in the lungs so that more oxygen is taken in with every breath and release of glucose (sugar) and fats from storage sites in order to provide needed energy.

Activation of the endocrine system is primarily manifested as hormonal changes including increases in growth hormone, arginine vasopressin, cortisol, and aldosterone and decreases in insulin and thyroxine. The net effect of these hormonal changes can include a slowdown of gut motility; water and salt retention; increased energy expenditure; high glucose levels due to release from storage sites, new production from amino acids broken down from muscle protein, and insulin resistance; increased use of fats as an energy source; and increased tendency toward blood clotting.³

A final component of the surgical stress response is activation of the immune system, a necessary factor in recovery and wound healing. In the early postoperative period, innate immune mechanisms (immunity that is naturally present and is not due to prior exposure) are activated leading to an influx of white blood cells into the wound and the production of inflammatory mediators (cytokines and chemokines).⁴ If an infectious agent had been encountered by the patient prior to surgery itself, the acquired or adaptive immune system may also be activated. The inflammatory response associated with activation of the immune system is aimed at getting rid of the infectious agent, reducing tissue damage, removal of dead cells, and start of the healing process. A key part of that healing process is an increase in anti-inflammatory agents, which reduce the severity and duration of the inflammatory response. Although the stress response is highly protective by design, under certain conditions, such as surgery, instead of the sympathetic, endocrine, and immune activation being self-limiting and restorative, the response can lead to further injury. Factors affecting the likelihood of an injurious response include the magnitude of surgery, the presence of co-existing diseases particularly those affecting the lungs, heart, and kidney (e.g. diabetes), the occurrence of postoperative complications such as bleeding or infection, impaired exercise tolerance before surgery, and malnutrition.

1. Weiser TG, Haynes AB, Molina G, et al. Size and distribution of the global volume of surgery in 2012. Bull World Health Organ. 2016;94(3):201-209F.
2. Understanding the stress response. https://www.health.harvard.edu/staying-healthy/understanding-the-stress-response. Accessed April 4, 2020.
3. Barber MD, Fearon KCH. The physiological response to surgical trauma. In: Dunn GP, Johnson AG, eds. Surgical Palliative Care. Oxford, England: Oxford University Press; 2004.
4. Dabrowska AM, Slotwinski R. The immune response to surgery and infection. Cent Eur J Immunol. 2014;39(4):532-537.