Since 1932, when Cuthbertson first described the systemic response to lower-limb injury, our understanding of surgical physiology has grown significantly, resulting in improved perioperative management, decreased complications, more efficacious analgesia, and faster recovery times. Better control of the sympathoadrenal pathway, endocrine response, and fluid management results in less patient fatigue, shorter functional recovery, and decreased hospital stays. In this chapter we will review the surgical stress response, fluid and electrolyte balance, and organ-specific responses to surgery.

Surgical stress response is the physiologic response to surgery and the name given to the hormonal and metabolic changes that follow surgery. This stress response has three key components: (1) sympathetic nervous system activation, (2) endocrine response with pituitary hormone secretion and insulin resistance, and (3) immunologic and hematologic changes including cytokine production, acute phase reaction, neutrophil leuokocytosis, and lymphocyte proliferation.

Sympathetic Nervous System

The sympathoadrenal response results from an increased secretion of catecholamines from the adrenal medulla. Circulating norepi-nephrine and epinephrine result in tachycardia and hypertension, and directly modify the function of numerous organs, including the liver, pancreas, and kidney. Gluconeogenesis is increased, glucagon production is stimulated, and water is retained to maintain fluid volume and cardiovascular homeostasis.

Endocrine Response

The endocrine response includes changes in pituitary secretion with secondary effects on hormone secretion from target organs. The overall metabolic effect is increased catabolism, which mobilizes substrate to provide energy, and retention of salt and water to maintain fluid volume and cardiovascular homeostasis. Specifically, corticotrophin stimulates cortisol secretion from the adrenal cortex resulting in increased blood glucose levels, arginine vasopressin stimulates the kidney to retain water, and insulin secretion by the pancreas is often diminished (Table 44-1).

Cortisol secretion increases rapidly following the start of surgery. It results in protein breakdown, gluconeogenesis in the liver, and in-creased lipolysis. Blood glucose concentrations increase and are related to the intensity of the surgical injury. Consequently, longer and more drastic elevations in blood glucose are seen in cardiac surgery than in minor surgical procedures such as herniorrhaphy. The usual mechanisms that maintain glucose homeostasis are ineffective in the postoperative period; cortisol promotes glucose production, there is a relative lack of insulin, and increased peripheral insulin resistance. Glycemic control is very important in surgical patients as the risks of perioperative hyperglycemia are well documented and include wound infection and impaired wound healing.

Protein catabolism is an important effect of increased perioperative cortisol concentrations. Both skeletal and visceral muscle are broken down to release amino acids for energy or to be used by the liver to form new protein including the acute phase reactants. This process results in weight loss, muscle wasting, and impaired healing. Studies have shown that surgical patients provided with nutritional supplements including glutamine and arginine, two essential amino acids, benefited from a faster recovery, fewer infections, and a shorter hospital stay.

Immunology

In addition to the endocrine response to surgery, other changes occur, most notably an increase in cytokine production and acute phase reactants. Cytokines are a group of low-molecular-weight proteins that include the interleukins and interferons, and they have a major role in the body’s response to surgery and trauma. They are responsible for local effects of mediating and maintaining the inflammatory response to tissue injury. The main cytokines released after surgery are interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and IL-6. The initial reaction of the body to surgery is to generate TNF-α and IL-1 from activated macrophages and monocytes in damaged tissues. This in turn stimulates the production of IL-6, the main cytokine responsible for the systemic changes known as the acute phase response. Cytokine production reflects the degree of tissue trauma; levels are lowest in laparoscopic and minimally-invasive procedures, and highest in major vascular procedures, joint replacements, and colorectal surgery. Cytokine levels peak 24-hours postoperatively and remain elevated for two to three days.

Acute Phase Response

The acute phase response is characterized by systemic changes including fever, granulocytosis, and the production of acute phase proteins in the liver. Acute phase proteins, including Creactive protein (CRP), fibrinogen, and α-2 macroglobulin, are inflammatory mediators, antiproteinases, and scavengers in tissue repair. D-dimer protein, a fibrin degradation product, will also be elevated in the postoperative period and may remain elevated for several weeks. Hematologic changes also occur along with the acute phase reaction, resulting in neutrophil leukocytosis and lymphocyte proliferation. Fever and leukocytosis can be expected in the first 48 hours after surgery, and should not prompt an infectious workup or antibiotic treatment in most cases.

Fluids

Patients often present for surgery after an overnight fast or inability to tolerate oral feeding, and will have a preexisting fluid deficit pro-portionate to the duration of the fast. This fluid deficit will be exacerbated by surgical wound losses and blood loss, although it may be partially replaced by careful intraoperative management by the anesthesia team. Obligatory fluid losses are proportional to the size of the surgical wound, and are due mainly to evaporative losses and internal redistribution of body fluids. This redistribution of fluids, also called “third-spacing,” can result in massive fluid shifts and intravascular depletion, and manifests as postoperative hypotension, tachycardia, and decreased urine output. Burn injuries, peritonitis, and extensive surgical dissections or bowel resection cases may result in extracellular fluid translocating across serosal surfaces as ascites or into the bowel lumen; this translocated fluid does not readily equilibrate with the intracellular compartment, further exacerbating postoperative hypovolemia. Postoperative intravenous fluid replacement may be guided targeting urine output to 0.5 mL/kg/hr.

In a healthy adult on a normal diet, water input may be 1600 mL/day. A minimum intake of 500 mL/day is based on concentrating urine to a maximum of 1200 mOsm/kg when 600 mOsm of solute is excreted. In addition, oxidation provides 300 mL and fruits and vegetables 800 mL. To maintain balance with water output of 1600 mL/day, daily water losses may be approximated as follows: 500 mL from urine, 500 mL from skin, 400 mL from the respiratory tract, and 200 mL from stool. The typical Western diet provides 100–250 mEq Na+ per day. Maintenance fluids replace physiologic ongoing losses of water and electrolytes from urine, sweat, respiration, and stool. Replacement fluids correct water and electrolyte deficits from GI, urinary, skin, bleeding, third spacing, and losses during surgery.

Crystalloids are fluids that pass through the intravascular to extravascular interstitial fluid compartment. The predominant effect of volume from crystalloids is the interstitial space that accounts for 70–80% of the extracellular space. Normal saline (0.95 NaCl) in the amount of 1.1 liter will result in 275 cc into plasma and 825 cc into the interstitium. Normal saline is somewhat hypertonic to cells so that there will be some shift of fluid out of cells. Colloids are high-molecular-weight solutions that include plasma, hetastarch, albumin, and dextran. Hetastarch, albumin, and dextran are rarely used in the postoperative period. There has been no evidence to demonstrate that colloids are more effective in volume resuscitation than crystalloids; they are nearly 100 times more expensive on a per-volume basis and have been associated with adverse effects including allergic reactions in certain patients.