Anesthetic Considerations for Pediatric Surgical Conditions

Anesthetizing children is an increasingly safe undertaking. When discussing the risks and benefits of a child’s operation with his or her family, surgeons should feel confident that their anesthesiology colleagues can provide an anesthetic that facilitates the procedure while ensuring the child’s safety. Providing optimal perioperative care for children requires close collaboration between the surgeon and anesthesiologist on issues both large and small. The intent of this chapter is to inform pediatric surgeons about considerations important to anesthesiologists.

Risks of Anesthesia

Morbidity/Mortality

In an effort to reduce patient complications, anesthesiologists have carefully analyzed anesthetic morbidity and mortality over the past decades. Whereas anesthesia was historically considered a dangerous enterprise, serious anesthesia-related complications are now relatively rare, especially in healthy patients. Reasons for this improvement include advances in pharmacology, improved monitoring technology, increased rigor of subspecialty training, and the ability to target potential problems using an analysis strategy.

Quantifying the risk of pediatric anesthesia is difficult due to the difficulty in determining whether complications are attributable to the anesthetic and, if so, to what degree. The risk of cardiac arrest for children undergoing anesthesia was estimated in the 1990s to be 1:10,000. However, these studies did not take patient comorbidity or the surgical condition into consideration. A recent prospective, multicenter study of more than 31,000 anesthetics in children from birth to 15 years of age affirmed the significance of age, medical history, and physical status (PS) as risk factors for the occurrence of perioperative severe critical events requiring immediate intervention. The risk of a healthy child suffering cardiac arrest during myringotomy tube placement is significantly less than the likelihood of a child with complex cardiac disease arresting during a complex cardiac repair.

A review of cardiac arrests in anesthetized children compared 193 events from 1998–2004 to 150 events from 1994–1997. A reduction in medication-caused arrests from 37–18% was identified and was attributed to a decline in the use of halothane, which causes myocardial depression, and the advent of sevoflurane utilization, which is not associated with myocardial depression. A decrease was also noted in unrecognized esophageal intubation as a cause of arrest, due in large part to the advent of end-tidal carbon dioxide (ETCO ₂ ) monitoring, pulse oximetry, and an increased awareness of the problem.

Recent large single-center reports have yielded a current estimate of anesthesia-related mortality of 1:250,000 in healthy children. To put this into perspective for parents, the risk of a motor vehicle collision on the way to the hospital or surgery center is greater than the risk of death under anesthesia. However, risks of mortality and morbidity are increased in neonates and infants <1 year of age, those who are American Society of Anesthesiologists (ASA) PS 3 or greater, and those who require emergency operations.

Concern for Possible Anesthetic-Related Neurotoxicity

Since 1999, preclinical animal studies in species from mice to nonhuman primates have shown neurodegeneration and subsequent neurodevelopmental impairment after exposure of infant animals to virtually all available drugs used for general anesthesia. These findings have raised concern among the pediatric anesthesiology community as well as the United States Food and Drug Administration (FDA). One reassuring animal study showed that exposing rats to an enriched environment after exposure to anesthesia prevented the neurocognitive impairment seen in animals that were isolated during recovery. Multiple observational cohort studies of children exposed to anesthesia early in life have been inconclusive, with some demonstrating an association between multiple anesthetics and impaired neurodevelopment later in life, while others have shown no effect. These observational studies are confounded by many factors, including a lack of information regarding underlying medical conditions, the influence of the operation itself, wide age range at time of exposure to surgery and anesthesia, lack of control for socioeconomic circumstances and maternal education, small sample size, and inconsistent outcome measures determined at diverse age ranges (school testing to diagnosis of or medication prescribed for attention-deficit/hyperactivity disorder [ADHD]). Although some cohort studies suggest a dose–response relationship between anesthesia (multiple or prolonged exposure) and subsequent neurocognitive impairment, other studies have not confirmed this finding.

Because of the difficulty in translating animal studies to human infant experience (long exposure times, absence of surgery, isolation and absence of stimulation of animals in recovery, failure to control physiologic variables), and the inconsistent conditions and outcomes of exposed groups in cohort studies, further research has been pursued in the effort to clarify the potential impact of anesthesia neurotoxicity in human infants and its public health implications. The General Anesthesia compared to Spinal Anesthesia (GAS) trial, which compared neurodevelopmental outcomes in children who had general or awake regional anesthesia (spinal/caudal/ilioinguinal block with no supplemental sedative) for hernia repair in the first 6 months of life, showed no difference in cognitive testing (Bayley Scales of Infant and Toddler Development) at 2 years of age. These findings are similar to those seen in the Pediatric Anesthesia Neurodevelopment Assessment (PANDA), an ambidirectional sibling study of children up to 3 years of age who received anesthesia for hernia repair. Cognitive testing (IQ and cognitive sub-domains) of both exposed and unexposed siblings was performed between the ages 8–14 years and revealed no difference between groups. Mean duration of general anesthesia exposure in both of these studies was relatively brief (57 minutes in the GAS study and 84 minutes for PANDA), leading to continuing uncertainty about possible effects of longer or multiple exposures.

Concern regarding the human applicability of animal studies and the inconsistent results of the human cohort trials have led to several statements by the FDA voicing concern about this issue, advising caution but encouraging further inquiry, and the formation of a public–private partnership between the FDA and the International Anesthesia Research Society called SmartTots. This group has funded ongoing research and issued a consensus statement that includes advice for both health care providers and parents ( http://www.smarttots.org ). Parents should understand that no anesthetic drug or technique has been shown to be safer than any other in animal studies and that there are clear adverse neurodevelopmental and physiologic consequences of performing surgery with an inadequate level of anesthesia.

In 2016, the FDA issued a safety announcement expressing greater concern about the implications of the animal studies, especially for infants and young children undergoing anesthesia for >3 hours and including concern about prolonged fetal exposure to anesthetics. This announcement elicited responses from the pediatric and pediatric anesthesia and obstetric communities, raising concern for increasing anxiety among parents in light of the fact that the safety announcement does not appear to be based on new information.

In a joint statement, the American Academy of Pediatrics (AAP) and the ASA have said: “The potential risk of negative cognitive or behavioral effects of anesthetic agents remains uncertain and must be placed in the context of the known risks and benefits of both the anesthetic and the related surgical or diagnostic procedure for which the anesthetic is required. Clinicians and parents are cautioned against the possible risk of delaying needed surgical or diagnostic procedures. Until additional information is available from ongoing studies, parents and providers should carefully weigh the risk and benefit of each contemplated procedure before proceeding.”

After these subspecialty group responses, the FDA issued a supplemental statement in April 2017 emphasizing that “…surgeries or procedures in children younger than 3 years should not be delayed or avoided when medically necessary. Consideration should be given to delaying potentially elective surgery in young children where medically appropriate.” Interestingly, a panel at the 2016 PANDA symposium discussed implications of concerns regarding anesthesia neurotoxicity for surgeons and their decision-making with parents regarding timing of surgery in infants. Multiple surgical subspecialists (ophthalmology, general surgery, urology, plastic surgery) identified procedures that would result in morbidity if delayed beyond infancy and agreed that surgeons should partner with anesthesiologists to discuss the balance of concerns about the risk of proceeding or delaying surgery, particularly if concerns regarding potential neurotoxicity are raised by the parents.

Preoperative Anesthesia Evaluation

Patients undergoing anesthesia benefit from a thorough preanesthetic/preoperative assessment and targeted preparation to optimize any coexisting medical conditions. The ASA Physical Status (PS) score is a means of communicating the condition of the patient but is not intended to represent operative risk and serves primarily as a common means of communication among care providers ( Table 3.1 ). Any child with an ASA PS of 3 or greater should be seen by an anesthesiologist prior to the day of surgery. This may be modified in cases of hardship due to the distance from the surgical venue or when the patient is well known to the anesthesia service and the child’s health is unchanged. Finally, outstanding and unresolved medical issues may be significant enough to warrant cancellation of the procedure for optimization of anesthesia and/or further diagnostic workup.

Table 3.1

ASA Physical Status Classification

ASA Classification	Patient Status
1	A normal healthy patient
2	A patient with mild systemic disease
3	A patient with severe systemic disease
4	A patient with severe systemic disease that is a constant threat to life
5	A moribund patient who is not expected to survive without the operation
6	A declared brain-dead patient whose organs are being removed for donor purposes
E	An emergency modifier for any ASA classification when failure to immediately correct a medical condition poses risk to life or organ viability

Criteria for Ambulatory Surgery

Ambulatory surgery comprises 70% or more of the caseload in most pediatric centers. Multiple factors should be considered when evaluating whether a child is suitable for outpatient surgery, with some states regulating the minimum patient age allowed in an ambulatory surgical center. For example, the minimum age in Pennsylvania is 6 months. In most cases, the child should be free of severe systemic disease (ASA PS 1 or 2). Existing family and social dynamics are also important factors. Some institutions utilize a telephone screening evaluation process to determine whether a patient can have his or her full anesthesia history and physical on the day of surgery rather than being evaluated in a preoperative evaluation clinic prior to surgery.

Although well-controlled systemic illnesses do not necessarily preclude outpatient surgery, any concerns must be addressed in advance in a cooperative fashion between the surgical and anesthesia services. If a child has a moderate degree of impairment, but the disease is stable and the surgical procedure is of minimal insult, outpatient surgery may be acceptable.

General Principles

In addition to the physical examination, the essential elements of the preoperative assessment in all patients are listed in Box 3.1 . Patients and parents may be anxious about the occurrence or recurrence of adverse perianesthetic events such as those listed, and they should be reassured that efforts will be made to prevent these events from happening.

Box 3.1

Essential Elements of the Preoperative Assessment (in Addition to Physical Examination)

Vital signs
- Height/weight
- Heart rate
- Respiratory rate
- Blood pressure
- Pulse oximetry (both in room air and with supplemental O ₂ if applicable)
Allergies
Medications
Cardiac murmur history
Previous subspecialty encounters
Past anesthetic history including any adverse perianesthetic events
- Emergence delirium
- Postoperative nausea and vomiting
- Difficult intubation
- Difficult IV access
Past surgical history
Family history of pseudocholinesterase deficiency or malignant hyperthermia

Patient History

Documentation of allergy status is an essential part of the preoperative evaluation, particularly because prophylactic antibiotics may be administered prior to the incision. Allergies to certain antibiotics (especially penicillin, ampicillin, and cephalosporins) are the most common medication allergies in children presenting for an operation. Anaphylactic allergic reactions are rare, but can be life threatening if not diagnosed and treated promptly. Latex allergy is the most common etiology for an anaphylactic reaction, and children with spina bifida (myelomeningocele), bladder exstrophy, or those who have undergone multiple surgical procedures are at greatest risk for such reactions. In 1991, the FDA recommended that all patients should be questioned about symptoms of latex allergy prior to surgery. The general consensus among the pediatric anesthesia community is that children in the high-risk groups noted above should not be exposed to latex-containing products (e.g., gloves, adhesive tape, catheters) and latex-free alternatives should be used instead. Since 1997, the FDA has mandated that all latex-containing medical products should be labeled as such. Many pediatric hospitals have elected to remove all latex-containing products from their supply chain because of the high risk to these identified patient populations as well as the increasing prevalence of latex allergy in health care workers. It has been well documented that prophylactic medications (steroids, H ₁ and H ₂ blockers) are ineffective in preventing anaphylaxis in susceptible patients. If anaphylaxis occurs (hypotension, urticaria or flushing, bronchospasm), the mainstays of treatment are (1) stopping the latex exposure: stopping the operation, changing to nonlatex gloves, and removing any other sources of latex; and (2) resuscitation: fluids, intravenous (IV) epinephrine (bolus and infusion), steroids, diphenhydramine, and ranitidine. If anaphylaxis is suspected, blood should be drawn within 4 hours of the episode for tryptase determination, which can confirm the occurrence of an anaphylactic event but not the inciting agent. Patients should be referred to an allergist for definitive testing to identify the antigen. Such testing should occur at least 4–6 weeks after the episode of anaphylaxis to allow for reconstitution of the mediators, the depletion of which could cause a false-negative skin test.

In general, parents should be instructed to continue routine administration of anticonvulsant medications, cardiac medications, and pulmonary medications even while the child is fasting.

Family history should be reviewed for pseudocholinesterase deficiency (prolonged paralysis after succinylcholine) or any first-degree relative who experienced malignant hyperthermia (MH). A complete review of systems is important and should focus on those areas in which abnormalities may increase the risk of adverse events in the perioperative period.

Miscellaneous Conditions

Malignant Hyperthermia Susceptibility

The incidence of an MH crisis is 1:15,000 general anesthetics in children, and 50% of patients who have an MH episode have undergone a prior general anesthetic without complication. MH is an inherited disorder of skeletal muscle calcium channels, triggered in affected individuals by exposure to either inhalational anesthetic agents (e.g., isoflurane, desflurane, sevoflurane), succinylcholine, or both in combination, resulting in an elevation of intracellular calcium. The resulting MH crisis is characterized by hypermetabolism (fever, hypercarbia, acidosis), electrolyte derangement (hyperkalemia), arrhythmias, and skeletal muscle damage (elevated creatine phosphokinase [CPK]). This constellation of events may lead to death if unrecognized and/or untreated. Dantrolene, which reduces the release of calcium from muscle sarcoplasmic reticulum, when given early in the course of an MH crisis, has significantly improved patient outcomes. With early and appropriate treatment, the mortality is now less than 10%. Current suggested therapy can be remembered using the mnemonic “ S ome H ot D ude B etter GI ve I ced F luids F ast” and is summarized in Box 3.2 . Experts are available for consultation concerning suspected MH at the 24-hour MH hotline administered by the Malignant Hyperthermia Association of the United States (MHAUS). Recommendations for treatment of an acute MH episode are available at the MHAUS website. It should be noted that dantrolene must be prepared at the time of use by dissolving in sterile water. It is notoriously difficult to get into solution, and the surgeon may be asked to help with this process. Recently an alternative to dantrolene, dantrium, has become available. It is more soluble at higher concentration and therefore more quickly and easily prepared, allowing administration of a lower volume of drug for effective treatment.

Box 3.2

Treatment of Malignant Hyperthermia Crisis

“ S ome H ot D ude B etter Gi ve I ced F luids F ast”

S top all triggering agents, administer 100% oxygen
H yperventilate: treat H ypercarbia
D antrolene (2.5 mg/kg) immediately
B icarbonate (1 mEq/kg): treat acidosis
G lucose and I nsulin: treat hyperkalemia with 0.5 g/kg glucose, 0.15 units/kg insulin
I ced Intravenous fluids and cooling blanket
F luid output: ensure adequate urine output: Furosemide and/or mannitol as needed
F ast heart rate: be prepared to treat ventricular tachycardia

Patients traditionally thought to be MH susceptible include those with the spectrum of muscle diseases listed in Box 3.3 . However, many patients who develop MH have a normal history and physical examination. In the past, patients with mitochondrial disorders were thought to be at risk. Recent evidence suggests that the use of inhaled anesthetic agents appears safe in this population, but succinylcholine should still be avoided, as some patients may have rhabdomyolysis (elevated CPK, hyperkalemia, myoglobinuria) with hyperkalemia without having MH. Patients with myopathies of unknown origin, often presenting for diagnostic muscle biopsy, pose a unique dilemma, and anesthetics should be planned in consultation with genetic and metabolic teams if possible.

Box 3.3

Muscle Diseases Associated with Malignant Hyperthermia

Central core myopathy
Becker muscular dystrophy
Duchenne muscular dystrophy
Myotonic dystrophy
King–Denborough syndrome

Trisomy 21

Perioperative complications occur in 10% of patients with trisomy 21 who undergo noncardiac surgery and include severe bradycardia, airway obstruction, difficult intubation, post-intubation croup, and bronchospasm. Patients may experience airway obstruction due to a large tongue and mid-face hypoplasia. The incidence of obstructive sleep apnea (OSA) may exceed 50% in these patients and may worsen after anesthesia and operation. Airway obstruction may persist even after adenotonsillectomy. Many patients with trisomy 21 have a smaller caliber trachea than children of similar age and size; therefore, a smaller endotracheal tube (ETT) may be required. Some trisomy 21 patients may have a longer segment of tracheal stenosis due to complete tracheal rings below the level of the cricoid.

Congenital heart disease (CHD) is encountered in 40–50% of patients with trisomy 21. The most common defects are atrial and ventricular septal defects, tetralogy of Fallot, and atrioventricular (AV) canal defects. For children with a cardiac history, records from their most recent cardiology consultation and echocardiogram should be available for review at the time of preoperative evaluation. Recent clinical changes in their condition may warrant reassessment by their cardiologist prior to operation.

Patients with trisomy 21 have laxity of the ligament holding the odontoid process of C2 against the posterior arch of C1, leading to atlanto-axial instability in about 15% of these patients. Cervical spine instability can potentially lead to spinal cord injury in the perianesthetic period. The need for and utility of preoperative screening for this condition is controversial. Even if the radiographic exam is normal, care should be taken perioperatively to keep the neck in as neutral a position as possible, avoiding extreme flexion, extension, or rotation, especially during tracheal intubation and patient transfer. Any patient with trisomy 21 who has neurologic symptoms such as sensory or motor changes, or loss of bladder or bowel control should undergo preoperative neurosurgical consultation to exclude cervical cord compression.

Preoperative Fasting Guidelines

Fasting violations are one of the most common causes for cancellation or delay of operations. Preoperative fasting is required to minimize the risk of vomiting and aspiration of particulate matter and gastric acid during anesthesia induction. Although the risk of aspiration is generally small, it is a real risk that may be associated with severe morbidity or death.

Research performed at our institution has demonstrated that intake of clear liquids (i.e., liquids that print can be read through, such as clear apple juice or Pedialyte) up until 2 hours prior to the induction of anesthesia does not increase the volume or acidity of gastric contents. Our policy is to recommend clear liquids until 2 hours prior to the patient’s scheduled arrival time.

Breast milk is allowed up to 3 hours before arrival for infants up to 12 months of age. Infant formula is allowed until 4 hours before arrival in infants <6 months old, and until 6 hours before arrival in babies 6–12 months old. All other liquids (including milk), solid food, candy, and gum are not allowed <8 hours before induction of anesthesia. Although these are the guidelines for our institution, the surgeon should be aware that NPO (nil per os) guidelines are variable and institutionally dependent.

Mitigating circumstances for NPO rules are limited to emergency operations, in which steps are taken to protect the airway from aspiration through the use of rapid sequence intubation. Elective patients at particular risk for dehydration should be scheduled as the first case of the day when possible, and administration of clear liquids by mouth until 2 hours prior to arrival at the surgical facility should be encouraged. Insulin-dependent diabetics, infants, and patients with cyanotic or single ventricle (SV) cardiac disease are among those requiring careful planning to avoid prolonged fasting times.

Laboratory Testing

At the time of consultation, selected laboratory studies may be ordered, but routine laboratory work is usually not indicated. Policies vary among institutions regarding the need for preoperative hemoglobin testing. In general, for any patient undergoing a procedure with the potential for significant blood loss and need for transfusion a complete blood count (CBC) should be performed in the preoperative period. Certain medications, particularly anticonvulsants (tegretol, depakote), may be associated with abnormalities in blood components (white blood cells, red blood cells, platelets), making a preoperative CBC desirable.

Although serum electrolytes are not routinely screened, electrolytes may be helpful in patients on diuretics. Preoperative glucose should be monitored in neonates, insulin-dependent diabetic patients, and also in any patient who has been receiving parenteral nutrition or IV fluids with a dextrose concentration >5% prior to surgery.

Routine pregnancy screening in all females who have passed menarche is strongly recommended. An age-based guideline (at our institution, any female >11 years of age) may be preferable. Although it is easiest to perform a urine test for human chorionic gonadotropin (hCG), if a patient cannot provide a urine sample, blood can be drawn for serum hCG testing. Institutional policy may allow the attending anesthesiologist to waive pregnancy testing at their discretion.

Certain medications, particularly anticonvulsants, should be individually assessed regarding the need for preoperative blood levels. The nature of the planned operation may also require additional studies, such as coagulation screening (prothrombin time [PT], partial thromboplastin time [PTT], international normalized ratio [INR]) prior to craniotomy, tonsillectomy, or surgeries with anticipated large blood loss.

Clinical Scenarios and High-Risk Populations

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