1. Appropriate physiologic response to injury relies on the balance and timing of pro-inflammatory phase reactants and anti-inflammatory phase reactants.
2. Wound healing, in both children and adults, is divided into four temporally overlapping phases: (1) hemostasis, (2) inflammation, (3) proliferation, and (4) remodeling.
3. Neonates exhibit physiologic change in response to painful stimuli and procedures, such as increased heart rate, blood pressure, and breathing patterns.
4. Recently, there has been a large movement toward “enhanced recovery after surgery” (ERAS) protocols that use evidence-based interventions to create standardized perioperative care.
INTRODUCTION
The last few decades have witnessed tremendous advances in the technical aspects of pediatric surgery and in our ability to care for increasingly complex patients. These strides have been complemented by a parallel improvement in the understanding of the unique needs of the pediatric population with respect to the physiologic, functional, and psychological recovery following surgery. These needs include both the acute aspects of perioperative care (optimization of wound healing, pain management, and functional recovery from the acute operative insult) and the long-term needs of children with chronic, debilitating surgical illnesses. In the latter cohort of children, where operative treatment may lead to permanent disability and changes in body image, a thorough understanding of the developmental and psychological implications of these outcomes is imperative and often requires a multidisciplinary approach. The goal of this chapter is to review the unique needs of the pediatric surgical population in the context of both the medical and psychological recovery following operative procedures.
INITIAL RESPONSE TO INJURY
In children and adults, the initial physiologic and metabolic response to surgical injury is similar. Physiologic alterations after injury can be largely categorized into a proinflammatory phase and an anti-inflammatory phase, which are meant to maintain the appropriate balance. A prolonged period of time without counter regulation in either phase can create an uninhibited systemic inflammatory process or poor wound healing and risk of infection, depending on the relative imbalance of these processes.
GENERAL PRINCIPLES
Central Nervous System Effects
The initial sympathetic response after injury causes an increase in heart rate, respiratory rate, and blood pressure and decrease in gastrointestinal motility. Vasoconstriction occurs in most blood vessels supplying the skin and digestive tract; however, the sympathoadrenal response allows for shunting of blood preferentially to skeletal muscles, the heart, lungs, and brain. Proinflammatory factors and cytokines provide afferent stimulation to the vagus nerve, creating the counterbalance regulation to the initial sympathetic response. Acetylcholine release reduces proinflammatory mediator release, such as tumor necrosis factor-α (TNF-α) and interleukins.
Metabolic Effects
The initial wound healing process exerts increased catabolic demands on the body through the metabolism of proteins, carbohydrates, and lipids. The catabolic effects of surgery are associated with an increase in glucagon, catecholamine, and cortisol release, all of which cause protein breakdown, protein turnover, amino acid oxidation, and hyperglycemia (1,2).
Protein
Protein and glucose are used for making collagen fibers, allowing proliferation of cells, and synthesizing enzymes required for proper wound healing. Although the process of amino acid oxidation and protein turnover increases the amount of substrates required for protein synthesis, the net effect is a hypercatabolic state with a net negative nitrogen balance. Protein loss is evident by increases in urinary nitrogen excretion and decreases in transport proteins such as albumin and retinol-binding protein. The most severe consequences of a sustained negative nitrogen balance include muscle wasting and delayed wound healing. Increased mortality may even occur with prolonged negative nitrogen balance when muscle degradation begins to affect the diaphragm and cardiac muscles. Therefore, supplementation of dietary protein can facilitate wound healing and reduce morbidity in postsurgical patients. Although protein intake increases stores, it does nothing to reduce the catabolic breakdown. Research is now focused on introducing pharmacologic agents such as insulin growth factor-I (IGF-I), growth factor, and anabolic insulin to reduce protein breakdown and metabolic stress.
The most striking difference in pediatric and adult populations is the amount of protein reserves available at the time of injury. Adults have more than triple the protein reserves compared to a neonate (1) and a significantly greater amount than older children as well. Children also have an increased basal metabolic requirement, stemming from their growth needs and from their larger surface-area-to-volume ratio, which increases heat loss. This increased basal requirement coupled with decreased body stores makes children and neonates particularly vulnerable to the catabolic state imposed during wound healing. Children require 1.0 g/kg/day of protein, compared to 0.8 g/kg/day in adults (3). In acute illness, the rate of protein turnover can increase up to 80% greater than baseline (4).
Carbohydrates
Glucose is the primary energy source for the brain and red blood cells, which explains the initial increase in mobilization of glucose stores. The limited endogenous stores of glycogen in the liver result in increased gluconeogenesis further propagating the negative protein balance. This catabolic state and mobilization of glucose cause the initial hyperglycemia seen in postsurgical patients. Although several adult studies have advocated the use of tight glycemic control in postoperative and critically ill patients to reduce mortality (5,6), a recent randomized controlled trial in the pediatric population of postcardiac surgery patients showed no benefit in tight glycemic control (blood glucose 80 to 110 mg/dL) versus standard care (no target glucose range) (7).
Resting energy expenditure also differs between children and adults. Caloric requirement for a term infant is 100 kcal/kg/day, which is even higher in a preterm infant (130 to 140 kcal/kg/day), compared to a 10-year-old child which is around 60 kcal/kg/day. Unlike the response of adults to operative stress, infants reach a peak of oxygen consumption and energy expenditure requirements around 4 hours after surgery, and a relatively quick return to baseline within 24 hours (8). This increase in basal requirements, along with the hypermetabolic state induced by surgery and illness, must be taken into account when optimizing nutrition in children and neonates in the perioperative period.
In comparing term and preterm infants, the metabolic priorities are similar; however, the substrate stores and biochemical properties are strikingly different. The ability to rely on endogenous glucose stores is significantly lower in premature infants, making premature infants increased vulnerable to hypoglycemic crises in the perioperative period. Several factors contribute to this increase vulnerability. Most glycogen stores are created after 36 weeks gestation. Before 36 weeks, only 30% of glycogen stores are available. In addition, skeletal muscle and fat stores constitute a much lower percentage of total body weight in premature infants, decreasing the number of reserves for alternative energy substrates and metabolism.
Lipids
Lipid metabolism also increases during the perioperative period. Essential fatty acids, such as linoleic and linolenic acid, are involved in prostaglandin synthesis which plays a role in inflammation and platelet aggregation (9). This increase in lipid metabolism is reflected by a decrease in the respiratory quotient (RQ, the ratio of carbon dioxide produced to oxygen consumed). The RQ measures the ratio of carbon dioxide produced (VCO2) to oxygen consumed (VO2). The RQ value changes based on the primary energy source. When carbohydrates are the primary energy source, the RQ = 1.0. It decreases to 0.8 to 0.9 when proteins are the major energy source and decreases further to 0.7 when lipids are the primary energy source. Even when subjected to small abdominal surgeries, there is a small but significant decrease in RQ value, indicating the increased use of fatty acids for energy (10). Neonates are particularly vulnerable to essential fatty acid deficiency. It is recommended that 4.5% and 0.5% of total dietary calories are allotted to linoleic and linolenic acid, respectively (1).
Temperature Changes in the Postsurgical Patient
Without active warming, there is a tendency toward hypothermia in surgical patients. The immediate hypermetabolism causes heat loss which exceeds metabolic heat production. Heat loss through environmental factors such as cold operating rooms and postanesthesia care units also creates increased loss. Anesthetics reduce the threshold for triggering primary cold defenses, such as shivering and vasoconstriction.
Neonates are uniquely susceptible to changes in temperature, with multiple sources of heat loss. Increased surface-area-to-volume ratio and thinner skin create increased avenues for loss. Neonates have adapted nonshivering thermoregulatory mechanisms such as vasoconstriction and increased ratio of brown to white adipose tissue, which can be used for thermogenesis. However, these mechanisms have been shown to be inhibited by anesthetic agents, which makes neonates particularly susceptible to hypothermia during and after surgery and anesthesia. Mechanisms have been adapted to limit heat loss, such as increasing the temperature in operating rooms and using warming blankets, warming lights, forced warm air devices, warmed IV fluids, and warm humidified inspired gases.
WOUND HEALING
Wound healing, in both children and adults, is divided into four temporally overlapping phases: (1) hemostasis, (2) inflammation, (3) proliferation, and (4) remodeling.
HEMOSTASIS
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