Age	Decision-Making Capacity	Techniques
<6 year	None	Best interests standard
6-12 year	Developing	Informed permission Informed assent
13-18 year	Mostly developed	Informed assent Informed permission
Mature minor	Developed, as legally determined by a judge, for a specific decision. Although particulars vary by state, the mature minor doctrine in general requires adolescents to be at least 14 years old and tends to permit decisions of lesser risk.	Informed consent
Emancipated minor	Developed as determined by statutes defining eligible situations (e.g., being married, in the military, economically independent).	Informed consent

^*This broad outline should be viewed as a guide. Specific circumstances should be taken into consideration.

School-age children are developing decision-making capacity, so anesthesiologists should seek both informed permission from the parent and assent and participatory decision making from the child. School-age children are capable of using logic and reason and are able to define and relate multiple aspects of a situation. Such situations may include whether to sedate a 6-year-old before an inhalation induction, whether to use an inhalation or intravenous induction of anesthesia in an 8-year-old, and whether to place an epidural for postoperative analgesia in a 12-year-old.

Many adolescents older than 14 years of age have the ability to use abstract thought, apply complex reasoning, foresee outcomes, simultaneously evaluate multiple options, and understand concepts such as probability. Anesthesiologists should try to fulfill the ethical requirements of consent while obtaining assent. Although some adolescents have cognitive abilities similar to those of adults, adolescents may be hindered by insufficient emotional development. Situations involving these aspects may include obtaining consent from a 14-year-old for anesthesia for scoliosis surgery or from a 16-year-old for an awake thoracic epidural placement for a pectus repair.

Disclosure and Apology of Medical Errors

Hiding medical errors is indecent and breaches informed consent.¹⁴ Fear, inadequate support, and lack of education prevent physicians from disclosing and apologizing appropriately.¹⁴^–¹⁸ Forthrightly disclosing medical errors, although upsetting, often strengthens the patient−physician relationship. Learning about a hidden medical error destroys trust and rapidly (and often appropriately) triggers legal action.

Physician apologies or sympathetic comments often are prohibited as legal evidence of wrongdoing.¹⁹ Nonetheless, disclosing and apologizing may influence whether patients pursue legal action and whether such action is successful.^20,²¹ Sincere (not pro forma!) apologies and subsequent redress to prevent future occurrences improves the patient−physician relationship, minimizing the likelihood of legal action.¹¹

Physicians without expertise in disclosure and apology often botch the process. Disclosure is a process over time. Initial disclosure should take place as soon as possible after an event and should center on the medical implications.²²^–²⁴ Do not speculate about cause or fault. When disclosing, it is wise to bring along an appropriate colleague who can help with the disclosure by providing psychological support for the patient and family. Soon thereafter, a specific, permanent liaison to the family should be identified. The liaison should be available to arrange meetings, explain the results of the investigation into the cause of the event, and describe plans to prevent future events. The liaison should be trained and experienced in apology and disclosure (e.g., a colleague in risk management).

An apology expresses regret or sorrow. Sincere apologies followed by consistent actions are priceless; insincere apologies are costly. It is always appropriate to apologize for the adverse effects of an event. And although the standard teaching is that physicians should not assume responsibility for an event before an investigation is performed, it seems bizarre to dissemble about clear errors. As an example, after reassuring the parents that their child is unharmed, I would readily admit that because I had inadvertently given a muscle relaxant instead of an anticholinesterase, their child will require a brief stay in the intensive care unit until ready for tracheal extubation. To evade responsibility (e.g., “Somehow one drug was given when another was intended”) for a clear error mocks the apology.

Anesthesiologists should also acknowledge, apologize, and recommend remedies for future difficult situations such as multiple intravenous catheter insertions or a very stressful anesthetic induction.

Special Situations in Pediatric Informed Consent

Confidentially for Adolescents

The obligation to maintain confidentiality requires physicians to protect patient information from unauthorized and unnecessary disclosure. Confidentiality is necessary for an open flow of information.²⁵ The anesthesiologist enhances trust by interviewing the adolescent in private, acknowledging the adolescent’s concerns about confidentiality, and following through on promises. Emancipated and mature minors have a right to complete confidentiality. For other adolescents, if maintaining confidentiality entails minimal harm, physicians should encourage adolescents to be forthright with parents but respect their decision not to be. If maintaining confidentiality may result in serious harm to the adolescent, physicians may be ethically justified in notifying the parents.²⁵

The Pregnant Adolescent

Anesthesiologists face confidentially issues when an adolescent has a positive pregnancy test before anesthesia. Given the principles of confidentiality, it is ethically appropriate to inform only the adolescent of the positive pregnancy test.²⁶ Because many locales statutorily prohibit sharing pregnancy information with anyone other than the adolescent, anesthesiologists must share this information with the adolescent without letting the parents know. Anesthesiologists should involve pediatricians, gynecologists, and social workers with expertise in adolescent issues in this discussion.

Matters may become more complex if the surgeon, anesthesiologist, adolescent, and other advisors believe the case should be postponed and the adolescent chooses not to inform her parents about the pregnancy test. Anesthesiologists must be careful not to inadvertently inform the parents of the pregnancy test while postponing anesthesia and surgery. Nor should anesthesiologists betray the adolescent by saying, “The case is postponed. If you want to know why, ask your daughter.” Although such a statement is factually true and within the letter of the law of confidentially, terse obliqueness scorns the spirit of confidentially.

As a parent of an impregnable adolescent, I understand the desire of anesthesiologists to tell the parents. But I would suggest that anesthesiologists who feel that way are too narrowly applying their own experiences and expectations. Not all parents are wise and gentle, and not all homes are safe and healthy. Confidentially statutes specifically address concerns about child abuse in pregnant adolescents.

To what extent anesthesiologists should protect the adolescent’s confidentiality is debatable. Nonetheless, because the parents have no legal right to that information, I believe that more active deception, although less desirable, is appropriate if necessary. Successful deception avoids initiating diagnostic evaluations or treatment and does not unduly worry parents. For example, attributing the delay to “hearing a new murmur” or an abnormal laboratory value “just found” are poor reasons to give to parents. Vague, unremarkable reasons such as “an oncoming cold” are best.

It is rare to condone deception. Deception should not be undertaken without serious reservations. But under certain circumstances, the obligation to the patient may supersede prohibitions on deception. At times, the harms of not deceiving outweigh the harms of deceiving.

The Adolescent and Abortion

Even though pediatric patients who are pregnant may be considered emancipated, many states require some form of parental involvement, such as parental consent or notification, before an elective abortion.^27,²⁸ If a state requires parental involvement, the ability of the minor to circumvent this regulation by seeking relief from a judge, known as judicial bypass, must be available. Requirements and enforcement of statutes vary from state to state.²⁹ The need for parental involvement in a minor’s planned abortion is not always legally straightforward, and it may be best to consult with hospital counsel in determining these issues. Although this is clearly an area in which honorable people disagree, it is worth noting that both the AAP and the American Medical Association (AMA) have affirmed these rights.^25,^29,³⁰

Children of Jehovah’s Witnesses

Jehovah’s Witnesses interpret biblical scripture as prohibiting transfusion therapy because blood holds the “life force” and anyone who takes blood will be “cut off from his people” and not earn eternal salvation.^27,²⁸ Adults may refuse transfusion therapy because it is assumed they are making an informed decision about the risks and benefits of transfusion. However, based on the obligations of the state to protect the interests of incompetent patients, courts have uniformly intervened when parents desire to refuse transfusion therapy on behalf of their children.

Obtaining informed permission and assent for the care of a ward of a Jehovah’s Witness should address transfusion therapy. Anesthesiologists should clarify which therapy is acceptable. Synthetic colloid solutions, dextran, erythropoietin, desmopressin, and preoperative iron are usually acceptable. Note that erythropoietin is available in two forms: lyophilized, and dissolved in saline with trace concentrations of albumin. Jehovah’s Witnesses who accept albumin will accept either formulation, whereas those who refuse albumin should be offered the lyophilized formulation. Some Jehovah’s Witnesses will accept the removal and return of blood in a continuous loop (e.g., cell saver blood). The family should understand, however, that in a life-threatening situation, the anesthesiologist will seek a court order authorizing the administration of life-sustaining blood. In instances in which the likelihood of requiring blood is high or the local judiciary is not that familiar with case law for Jehovah’s Witnesses, the anesthesiologist may choose to obtain a court order in advance of the operation.

A common concern is the sudden need for an emergent transfusion in a healthy child undergoing a low-risk procedure. In emergencies, based on the obligation to protect children, anesthesiologists should take the legally correct and ethically appropriate action to protect the child by transfusing blood without a court order. A court order may then be sought if desired.

For procedures that may be safely delayed, decision makers may consider postponing the procedure until the child is of sufficient age and maturity to decide about transfusion therapy. The complexity is whether the delay may increase the risk or decrease the likelihood of a good outcome. This decision requires the same balancing act as for determining the best interests for a child. Relevant factors include the quantitative change in risk or benefit and the significance of the type of risk or benefit. For example, it may be easier to wait on a procedure that is purely cosmetic than on a procedure for which waiting entails a small chance of causing a permanent injury. If individual clinicians choose to honor the wishes of a mature minor, they must ensure the fidelity of the agreement by making certain that postoperative and on-call clinicians will honor the mature minor’s wishes.

Emergency Care

Anesthesiologists should provide necessary emergent care for minors who do not have a parent available to give legal consent.³¹ Emergencies include problems that could cause death, disability, and the increased risk of future complications.

The right of an adolescent to refuse emergency care treatment turns on the adolescent’s decision-making capacity and the resulting harm from refusal of care.¹ If the harm is significant and the adolescent’s rationale is decidedly short-term or filled with misunderstanding, it becomes necessary to consider whether the adolescent has sufficient decision-making capacity for this decision. In this situation, it may be appropriate to consider what is in the best interests of the adolescent. For example, a 15-year-old football player with a cervical fracture might refuse emergency stabilization, stating that he does not want to live life without football. Most would hold that his conclusion overly values short-term implications, especially in light of the suddenness of the injury, and that he should receive emergency treatment.

The Impaired Parent

Parents may be unable to fulfill surrogate responsibilities because of acutely impaired judgment, such as being intoxicated.³² Anesthesiologists will then have to weigh the benefits of waiting for appropriate legal consent against what is in the best interests of the child. It may be in the child’s best interests to proceed with a routine procedure in the situation of an impaired parent who is unable to give legal consent. Anesthesiologists may wish to consult legal and risk management colleagues for guidance.

End-of-Life Issues

Forgoing Potentially Life-Sustaining Treatment

Perioperative Limitations on Life-Sustaining Medical Therapy

The concept of limiting potentially life-sustaining medical therapy (LSMT) is the same for children as is for adults. Decision makers choose to limit LSMT because they do not consider the potential burdens worth the potential benefits.³³ The AAP, the American Society of Anesthesiologists (ASA), and the American College of Surgery mandate reevaluation of any limitations on LSMT before proceeding to the operating room.³⁴^–³⁶

Readers will note a shift from the term “Do Not Resuscitate” to terms similar to “Life-Sustaining Medical Therapy.” One purpose of this shift is to emphasize that desired limitations on medical treatment are continuous rather than dichotomous. The term “potentially” is often used to modify LSMT to emphasize the uncertainty about whether a therapy will be life sustaining.

Reevaluation of LSMT preferences for the perioperative period starts with clarifying the patient’s goals for the proposed surgery and end-of-life care (Table 5-2). Anesthesiologists should involve the patient, family, and other clinicians such as surgeons, intensivists, and pediatricians in determining what is in the best interests of the child.

TABLE 5-2 Components of a Pediatric Perioperative LSMT Discussion

LSMT, Life-sustaining medical therapy.

Adapted from Truog RD, Waisel DB, Burns JP. DNR in the OR: a goal-directed approach. Anesthesiology 1999;90:289-95; and Fallat ME, Deshpande JK. Do-not-resuscitate orders for pediatric patients who require anesthesia and surgery. Pediatrics 2004;114:1686-92.

Benefits of potentially LSMT include an improved quality of life and prolongation of life under certain circumstances. Burdens include intractable pain and suffering, disability, and events that cause a decrement in the quality of life, as viewed by the patient.³⁷ These guidelines help in considering short- and long-term goals and putting into appropriate context specific fears such as long-term ventilatory dependency, pain, and suffering.

Legitimate procedures for a child with limitations on LSMT include procedures that decrease pain, provide vascular access, enable the child to be at home, treat an urgent problem unrelated to the primary problem (e.g., appendicitis), or treat a problem that may be related but is not considered a terminal event (e.g., bowel obstruction). But seeking these interventions does not obviate the desire to avoid potential postresuscitation burdens such as need for extensive ventilator support, cognitive deficits, or physical limitations.

The goal-directed approach for perioperative limitations on LSMT permits decision makers to guide therapy by prioritizing outcomes rather than procedures.³³ After defining desirable outcomes, decision makers have anesthesiologists use their clinical judgment to determine how specific interventions will affect achieving the specific goals. Predictions about the success of interventions made at the time of the resuscitation are more accurate than predictions made preoperatively, when the quality and nature of the problems are unknown. Therapy may be guided by goals rather than specific procedures (as is done on the ward), because during the perioperative period children are cared for by dedicated anesthesiologists for brief, defined periods. It is helpful to define a goal-directed approach by discussing the acceptable burdens, the desirable benefits, and the likelihood of distinct outcomes. Most decision makers choose a goal-directed approach indicating that they would desire therapy if the interventions and burdens were temporary and reversible (i.e., if they could return to the present state without suffering too much).

Prior determination of acceptable postoperative LSMT is less critical in pediatrics, because usually parents are available in the postoperative period to make decisions regarding therapy. Nonetheless, when a sufficiently mature child participates in discussions about LSMT, anesthesiologists should ensure that the discussion incorporates the child’s preferences for postoperative trials of therapy. The willingness to undergo a trial of therapy indicates a belief that the burdens of the trial (e.g., a few days of ventilator support) may be worth the benefits (e.g., extubation of the trachea) initially, but at some point the increasing burdens may not be worth the decreasing likelihood of the benefits.

Barriers to Honoring Preferences for Resuscitation

Barriers to honoring limitations center on clinician attitudes, time pressures, and inadequate knowledge about policy, law, and ethics.³⁸^–⁴³ In short, whereas patients prioritize functional status in choosing to limit LSMT, clinicians tend to base their opinions on diagnosis and life expectancy.

Anesthesiologists may falsely believe that law or hospital policy requires full resuscitation during the perioperative period. Physicians who act in accordance with statutory requirements are often explicitly protected from liability when they honor a child’s or family’s refusal of resuscitation.⁴⁴ Given the well-established right of children and parents to refuse medical treatment and the paucity of cases finding physicians liable for honoring limitations on LSMT, the risk of liability for honoring an appropriately documented perioperative limitation on LSMT is not high and is likely to be lower than the risk of not honoring the limitations.⁴⁴

Iatrogenic problems such as cardiac arrest do not obviate decisions to limit LSMT.⁴⁵ To decision makers, the cause of the arrest is irrelevant. Decision makers care about the factors they considered in requesting limited resuscitation, including likelihood of successful resuscitation and physical and mental status after the arrest. The benefits of continued therapy after certain types of iatrogenic arrests should be addressed as part of the perioperative discussion.⁴⁵

Inadvisable Care

Treatments with low likelihoods of success may be considered inadvisable because of the burden to the child, cost, or uncertain benefit. Discussions about inadvisable treatment should bear in mind the goals of the treatment and the likelihood of achieving a defined result. When offering the likelihood of a result, physicians should be clear whether the information used to form the estimation is based on intuition, clinical experience, or rigorous scientific studies. Scoring systems that are useful for population predictions in determining potentially inadvisable care should be considered as contributory but not determinative for decision making for individuals.

Decision making for a child near the end of life should be based on the best interests of the child. A useful approach to resolving conflicts has been proposed by the Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (Table 5-3).³ In short, physicians may override parental preferences only if a therapy is clearly beneficial (e.g., blood transfusion for anemia). When physicians override parental preferences, the appropriateness of the treatment and the process of decision making should undergo an external review, which will often be medical, ethical, or legal in nature.

	*Parents Prefer to Accept* Treatment**	*Parents Prefer to Forgo* Treatment**
Physicians consider treatment clearly beneficial	Treat	Provide treatment during review process
Physicians consider treatment to be of ambiguous or uncertain benefit	Treat	Forgo
Physicians consider treatment to be inadvisable	Provide treatment during review process	Forgo

From President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Deciding to forgo life-sustaining treatment: ethical, medical and legal issues in treatment decisions. Washington, D.C.: U.S. Government Printing Office; 1983.

The improvement in long-term outcomes for the most preterm babies makes it very hard to predict the likelihood of successful treatment in very young children. The best information suggests that for those infants at the threshold of viability (22 to 25 weeks), survival increases with each week of gestation but the rate of moderate or worse disability does not improve and remains at 30% to 50%.^46,⁴⁷

Policies to help resolve differences of opinion about applying treatments with low likelihoods of success are important. Good policies are procedure based, are public, reflect the moral values of the community, and include processes for identifying stakeholders, initiating and conducting the policy, commencing appellate mechanisms, and determining relevant information.⁴⁸

Improving Communication in Pediatric Intensive Care Units

Pediatric intensivists should emphasize interdisciplinary communication, tailor the communication style to the parents, and maximize meaningful parental participation in the child’s care.⁴⁹ The goal is to be an empathic professional who establishes compassionate relationships with the child and family by managing emotional, informational, and care needs.⁵⁰ In almost all conversations, clinicians should explain the meaning of the conversation in terms of overall care.⁵¹ Table 5-4 lists characteristics of good communication in the intensive care unit.

TABLE 5-4 Parents’ Desires for Communication in the Intensive Care Units

1. Honest and complete information should be tailored to the parents’ needs and information-receiving preferences. Comprehension of the child’s potential trajectories permits better participation in care and a greater chance of appropriate end-of-life care.

2. Ready access to staff should include periodic scheduled informal visits to the bedside and the availability of e-mail interactions. The goal is to provide the parents with easy and frequent opportunities to have their questions answered, with sufficient repetition and clarification of the “big picture.”

3. To maximize successful communication, clinicians should actively assess the parents’ preferences for communication and decision making. This includes considering how to relate information to parents when clinicians have different management opinions. Parents frequently recognize that there are differences between options, and some prefer to hear the range of options whereas others prefer to hear only the recommended option.

4. Emotional expression and support by staff are critical to parents. To do this successfully, clinicians should adapt their style to parents’ preferences. Most clinicians should adopt practices that give parents more room to control the conversation, including talking less, listening more, and tolerating silence as parents gather themselves to continue communicating.

5. Parents respond and benefit from the relational aspects of compassion, mercy, authenticity, and integrity.⁵² More colloquially, the relational aspect is referred to as “being there,” interacting with the parents as a caring person with feelings and emotions.⁵³ For example, although some clinicians may believe it is inappropriate to show emotion, parents appreciate compassion and some level of distress at the sharing of bad news, rather than cold hard professionalism.⁵¹

6. Preservation of the integrity of the parent−child relationship means enabling parents to continue in their self-identified and prominent role as decision maker and protector. Loss of this role harms parents and may impair their ability to participate in decision making for the child.

7. Faith and spiritual matters are highly personal, and parents may feel uncomfortable expressing their faith in an institutional setting. Spiritual matters should be accepted and integrated into the intensive care unit practice to assist those who benefit from spiritual support.

8. Parents’ lifelong views of these events are profoundly colored by vivid memories and strong feelings about seminal discussions. How difficult discussions are handled and the quality of the communication among clinicians and families often become the bases for the family’s lifelong narrative of these events.

Modified from Meyer EC, Ritholz MD, Burns JP, Truog RD. Improving the quality of end-of-life care in the pediatric intensive care unit: parents’ priorities and recommendations. Pediatrics 2006;117:649-57.

Palliative Care

Anesthesiologists, in their role as pain management specialists, as intensive care unit doctors, or in the operating room, may participate in pediatric palliative care.^52,⁵³ Palliative care emphasizes relationship-centered care and should be available to children with a wide variety of diseases (Table 5-5).⁵⁴ Although pediatric palliative care has struggled for recognition, in 2011 there are signs of improvement.^55,⁵⁶

TABLE 5-5 Palliative Care

WHO

All children suffering from chronic, life-threatening, and terminal illnesses are eligible; this includes

• Diseases for which curative therapy may fail (e.g., malignancies with poor prognoses)

• Diseases that require long periods of hospitalization to prolong life (e.g., severe epidermolysis bullosa, immunodeficiencies)

• Progressive diseases for which treatment is palliative (e.g., severe osteogenesis imperfecta)

• Severe nonprogressive disabilities that place the child at risk for coexisting diseases

Do-not-resuscitate orders should not be required

Prognosis for short-term survival is not required

WHAT

Child-focused, family-oriented, and relationship-centered care that focuses on relief of suffering and enhancing quality of life

Prioritization of participation of the child and family in decision making

Caring for the child as a unique individual

Caring for the family as a functional unit

Care is not directed at shortening life

HOW

An interdisciplinary team is always available to families to provide continuity

Facilitation and documentation of communication are critical tasks of the team

Highly skilled, expert care is provided

WHY

Respite care and support are essential for families

WHERE & WHEN

Care is coordinated across all sites of care delivery

Care is incorporated into mainstream medical care

Bereavement care should be provided as long as it is needed

From U.S. Department of Human Services: 45 CFR 46 Subpart D. Additional protection for children involved as subjects in research. 2009.

Euthanasia

Although euthanasia has been permitted in the Netherlands for some time, only recently have there been reports of euthanasia for children. Sixteen-year-olds may now request euthanasia, and 12- to 15-year-olds may request euthanasia with their parent’s approval. On reflection, it is reasonable for teenagers to want to minimize suffering and pain at the end of life. Similar to euthanasia in the adult patient, the adolescent must have decision-making capacity; must clearly, voluntarily, and repeatedly request to die; must have an incurable condition associated with severe, unrelenting, and intolerable suffering; and should not be making the request due to inadequate comfort care.^56,⁵⁷ In the Netherlands, the deliberate ending of a neonate’s life is permitted under certain circumstances depending on the neonate’s life expectancy and intensive care dependency.^57,⁵⁸

Donation after Cardiac Death

In organ procurement after a declaration of death through neurologic criteria (i.e., brain death), the child is declared dead before being brought to the operating room. The organs are then retrieved while body homeostasis is maintained through mechanical ventilation, pharmacologic therapy, and other standard resuscitative techniques.⁵⁹

Concern about limited availability of organs for transplantation has resulted in the now widely accepted concept of donation after cardiac death (DCD).^60,⁶¹ In DCD, the child is not declared dead before being brought to the operating room for organ retrieval. Instead, after it is determined that therapy should be withdrawn based on a standard benefits and burdens assessment, the child is brought to the operating room and therapy is withdrawn. If the child dies after life-sustaining therapy is withdrawn, he or she is declared dead by cardiac criteria and the organs are retrieved. Ethical issues regarding DCD protocols center on whether the protocols seriously alter the dying process by shifting decision making away from the best interests of the dying child and by interfering with the family’s ability to be with their dying child (Table 5-6).

TABLE 5-6 Ethical Issues Surrounding Donation after Cardiac Death (DCD)

Should interventions be permitted prior to withdrawal of care?	The burdens from the interventions are not in the best interests of the child. On the other hand, the burdens of the interventions are mostly theoretical and may improve the quality of the transplanted organs.
Should withdrawal of therapy occur in the intensive care unit (ICU) or in the operating room?	Withdrawing therapy in the operating room may increase the quality of the organs transplanted. Withdrawing therapy in the ICU is likely to be less jarring to the family and more consistent with the premise of withdrawing therapy for the child’s benefit. In addition, it may remove some of the awkwardness that may occur if the child does not die within the defined interval.
Who should withdraw therapy?	To be consistent with the premises of withdrawal of therapy, it should be the same person who would normally withdraw therapy from the child. Even if the decision is made to withdraw therapy in the operating room, an anesthesiologist who has not been caring for the child should not be asked to withdraw therapy because of the physical location of the event.
How long should cessation of cardiac function exist for a child to be declared dead?	Proposed times may be based on the premises of how long it would take to autoresuscitate compared with how long it would take to be resuscitated through medical intervention.
What are the contents of a good DCD policy?	• Acceptable interventions before withdrawing therapy • Acceptable locations of withdrawing therapy • Amount of time to wait until death before forgoing procurement • Which individual should withdraw therapy • What to do if the family will not leave after death is declared

Clinical and Academic Practice Issues

Pediatric Research

The anesthesiologist Henry K. Beecher was one of the first to propose different requirements for pediatric research as compared to adult research.⁶² Pediatric research is closely examined because children are incapable of consenting to experiments, and because the developing child is at greater risk for long-term harm.⁶² Federal guidelines give four categories of pediatric research, with each ascending category requiring greater scrutiny of the risk-to-benefit ratio, especially in research without therapeutic benefit for the subject (Table 5-7).⁶³ Whereas obtaining the assent of the child whenever possible is important for therapeutic medical procedures, it is absolutely essential in the context of research, along with the informed permission of the parents.

TABLE 5-7 Federal Classification of Pediatric Research

1. Research not involving greater than minimal risk

a. IRB determines minimal risk

b. IRB finds and documents that adequate provisions are made for soliciting assent from children and permission from their parents or guardians

2. Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subject

a. IRB justifies the risk by the anticipated benefit to the subjects

b. The relationship of the anticipated benefit to the risk is at least as favorable as that presented by available alternative approaches

c. Adequate provisions are made for assent and permission

3. Research that involves greater than minimal risk and no prospect of direct benefit to the individual subject but is likely to yield generalizable knowledge about the subject’s disorder or condition

a. IRB determines that the risk represents a minor increase over minimal risk

b. The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations

c. The intervention or procedure is likely to yield generalizable knowledge … which is of vital importance for the understanding or amelioration of the subject’s disorder or condition

d. Adequate provisions are made for assent and permission

4. Research not otherwise approvable, which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children

IRB, Institutional review board.

From U.S. Department of Human Services: 45 CFR 46 Subpart D. Additional protection for children involved as subjects in research. 2009.

Minimal Risk

Minimal risks are defined as those risks that are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations. Most interpret this to mean the risks encountered in daily life by healthy children, such as running in the backyard, playing sports, or riding in a car.^64,⁶⁵ A less favored relative interpretation uses as a benchmark those risks encountered in the daily lives of children who will be enrolled in the research. In other words, if a child were living in a manner that exposed the child to risk (e.g., undergoing repeated general anesthesia), then it would be acceptable to expose the child up to that level of risk in a study.

Individuals are poor at estimating the risk levels of activities and often correlate risk to familiarity, control of the activity, and reversibility of the potential harms.⁶⁵ Institutional review boards (IRB) may reject low-risk studies because they involve unfamiliar matters while approving studies that have excessive risks.

Minor Increase over Minimal Risk

The pediatric research category that involves “greater than minimal risk and no prospect of direct benefit to the individual subject but is likely to yield generalizable knowledge about the subject’s disorder or condition … which is of vital importance” (see Table 5-8) is based on the idea that it is acceptable to expose a child to a “minor increase over minimal risk” under certain conditions.⁶⁶ Parsing the regulation may help clarify this somewhat unhelpful definition. One suggestion has been that minor increase means that the pain, discomfort, or stress must be transient, reversible, and not severe.⁶⁴ Condition of the subject should be used to mean a set of characteristics “that an established body of scientific or clinical evidence has shown to negatively affect children’s health and well-being or to increase the risk of developing a health problem in the future.”⁶⁴ Interpreting condition to include “having the potential to have the condition” permits otherwise healthy children to participate in research for diseases that they may develop (e.g., cellulitis). The term vital importance implies that the evidence supporting the relevance of the study should require a higher order of proof.

TABLE 5-8 Strategies Used by Drug Companies to Influence Physicians

1. Teach sales people subtle verbal and nonverbal techniques to influence physicians.

2. Instruct sales people to misdirect and to dissemble when questioned about possible complications.

3. Cherry-pick which data are distributed to physicians.

4. Prohibit distribution of studies that may criticize the product. (One strategy is to classify concerning studies as background studies and then prohibit distribution of background studies.)

5. Seek “opinion leaders” to speak in favor of the product.

6. Continue the well-established gift-giving strategy to subconsciously curry favor with the physician and to develop a positive association about the product and the company.

Socioeconomic Concerns and Distribution of Risk

Socioeconomically disadvantaged children living in urban areas may be overrepresented in research studies because urban academic centers in disadvantaged areas perform the majority of clinical research.⁶⁷ Children living in socioeconomically disadvantaged areas are often more affected by diseases associated with their environment, such as asthma or nutritional disorders complicated by limited access to stocked grocery stores. One could argue that this unequal burden of risk, primarily manifested by greater participation of socioeconomically disadvantaged children in research studies, is reasonable because these children are more likely to develop these diseases and therefore are more likely to benefit from the research.⁶⁸ Most reject that view and believe that in some sense, socioeconomically advantaged patients gratuitously gain the benefits of the research without sharing the risks. The disproportionate risk borne by one segment of society compared with another likely breeches the most accepted interpretation of the core ethical value of justice.

Socioeconomically disadvantaged families may be more likely to be influenced by the small gifts offered to research participants. Aside from compensating for costs (e.g., parking vouchers), gifts should not of themselves encourage participation. The problem is that gifts that represent a small expression of gratitude for some families may provide an incentive for participation for socioeconomically disadvantaged families.⁶⁹

Imperative for Pharmacologic Research

Through the mid-1990s, more than 70% of new molecular entities were without pediatric drug labeling. Inadequate information exposed children to age-specific adverse reactions, ineffective treatment due to inappropriate dosing, and lack of access to new drugs because physicians tended to prescribe less effective, known medications. Inadequate research into pediatric drugs forced physicians to prescribe drugs in nonstandard ways, such as sprinkled or crushed tablets. Even when there is some pediatric labeling, there is scant labeling for children younger than 2 years of age. In 2009, a survey of a Canadian pediatric tertiary hospitals found that even when comparing off-label use to contemporary pediatric references (an unofficial and very liberal interpretation), 16% of drug administrations during the perioperative period were considered off-label. Based on a more traditional standard of the Canadian Compendium of Pharmaceutical Specialties, 55% of drugs administered were used off-label.⁷⁰

The following selective history highlights the overall intent to ensure (1) that children get the same benefits of pharmacologic advances as adults and (2) that research is performed in the youngest children. Readers should also learn from this history that persistent advocacy is often required before regulatory change can be successfully obtained. In 1962, the Kefauver-Harris Amendments (passed after the thalidomide disaster) required that drug companies demonstrate safety and efficacy before marketing a drug. Because the vast majority of drugs did not undergo pediatric-specific investigation, this requirement actually led to less pediatric labeling, with the package insert (drug label) often reading, “Safety and efficacy have not been demonstrated for children <12 years,” because of the expense of getting this information (see also Chapter 6). In 1994, the U.S. Food and Drug Administration (FDA) began requiring sponsors to explain why pediatric labeling cannot occur but did not require sponsors to perform pediatric studies.

The 1997 FDA Modernization Act and the 1998 Final Rule were legislative initiatives designed to gain more data from drug companies through pediatric studies in exchange for the benefit of an additional 6 months of patent exclusivity. This effort was further codified with the passage of the Best Pharmaceutical Act for Children in 2002. With these requirements, the FDA mandated pediatric studies if a new drug might be used in a substantial number of children, if it might provide a meaningful therapeutic benefit, or if inadequate labeling could pose significant risks. The pharmaceutical industry responded with an explosion of pediatric studies. However, the exclusivity provision did not encourage study of generic drugs or drugs with insufficient sales. Further, once exclusivity was credited for older pediatric age groups, there was no incentive to conduct studies in younger groups.

In December 2003, the Pediatric Research Equity Act required pediatric studies for all drugs and biologic products that have a new indication, new dosage form, new route, new dosing regimen, or new active ingredient. Studies could be waived if they were impracticable, if the therapy would be ineffective or unsafe in pediatric patients, or if there would be no meaningful therapeutic benefit over existing therapies and the moiety would not used in a substantial number of children.

Other nations have adopted similar regulatory requirements and incentives to encourage drug research. The European Union offers scientific help for performance of studies and requires that drug applications contain pediatric information that covers “all paediatric age groups and all necessary age-appropriate formulations,” unless an exception is granted.⁷¹ Performing pediatric testing earns patent extensions even if the drug is not approved for pediatric use.

Managing Potential Conflicts of Interest

A conflict of interest is “a set of conditions in which professional judgment concerning a primary interest (such as a patient’s welfare or the validity of research) tends to be unduly influenced by a secondary interest.”⁷² Because these conditions in an individual are internal, they are best characterized by describing situations that may create the potential for conflicts of interest. Focusing on potential conflicts of interest moves the concept away from attacking an individual’s morals and toward more uniform definitions. Conflicts of interest may be induced by financial, personal, and professional benefits such as prestige, promotion, and personal gratification.⁷³ Anesthesiologists should be mindful of these potential conflicts, and attempt to identify them to better understand the likelihood of compromised judgment.

Conducting Research

Perhaps the most powerful conflict in conducting research is the loss of equipoise that can come from originating and developing an idea. Other sources of conflict related to research center on academic promotion and reputation. Physician disclosures do not help identify conflicts of interest. In one study, only 80% of physicians disclosed payments related to the research, and only 50% disclosed payments from the same company but unrelated to the product being discussed. Indirect payments were just as likely to influence behavior as direct payment.⁷⁴

In 2009, an anesthesiologist was accused of falsifying data that had encouraged multimodal pain therapy. A routine audit had found the irregularities that initiated the subsequent evaluation (supporting the benefits of oversight). Major journals retracted articles. Steven Shafer, editor of Anesthesia and Analgesia, was quoted as saying, “We are left with a large hole in our understanding of this [multimodal pain therapy].”⁷⁵ Shafer called the scandal “a tragedy” for the profession, for patients, and for the anesthesiologist involved personally. Given that the anesthesiologist’s studies were “robust” and influential, “the big chunk of what people have based their [multimodal] protocol on is gone.”^75,⁷⁶ It is important to emphasize that the anesthesologist’s coauthors were deceived by him and were not complicit. If fact, they assisted in assessing the legitimacy of articles that were not retracted.⁷⁷

Conflicts of interest also come from industry support of research. To be clear, the academic−anesthesia-industry research complex is necessary to continue the rapid advancement of science. Rigorous oversight minimizes these abuses. Researchers need to be involved in trial development, must have access to raw data, and must be able to publish without the company’s authorization. Cozy relationships between powerful members of the local academic community and industry should be examined and brought to light to minimize influence and potential conflicts of interest.

Interaction with Industry

Anesthesiologists need to be suspicious of industry attempts to “selflessly” educate clinicians.⁷⁸ Physicians should independently evaluate information supplied by industry. Industry representatives and materials routinely overrepresent the benefits and underrepresent the risks of drugs (Table 5-8).”⁷⁹ Wisely, there has been a strong movement in academic centers to stiffen rules about physician exposure to industry representatives.⁸⁰

Risks associated with industry misrepresentation will increase as increasing physician workload decreases time for study. For these reasons, it is instructive to look more closely at this problem. Evidence published in the 2000 VIGOR study indicated that the popular antiinflammatory drug rofecoxib (Vioxx) dramatically increased the rate of myocardial infarction in patients. In 2001, the FDA determined that physicians should be made aware of the cardiovascular effects of rofecoxib, and in 2004 it was withdrawn from the market. Congressman Henry Waxman later wrote the following ⁸¹:

Merck, the manufacturer of Vioxx, … has an excellent reputation within the drug industry and supports many products, such as vaccines, that are medically essential but not very profitable.… Yet as we learned, even a company like Merck can direct its sales force to provide clinicians with a distorted picture of the relevant scientific evidence.…

On February 7, 2001, the Arthritis Drugs Advisory Committee of the Food and Drug Administration (FDA) … voted unanimously that physicians should be made aware of VIGOR’s cardiovascular results.

The next day, Merck sent a bulletin to its rofecoxib sales force [which] ordered, “DO NOT INITIATE DISCUSSIONS ON THE FDA ARTHRITIS ADVISORY COMMITTEE … OR THE RESULTS OF THE … VIGOR STUDY.” It advised that if a physician inquired about VIGOR, the sales representative should indicate that the study showed a gastrointestinal benefit and then say, “I cannot discuss the study with you.”

Merck further instructed representatives to show those doctors who asked whether rofecoxib caused myocardial infarction a pamphlet called “The Cardiovascular Card.” This pamphlet, prepared by Merck’s marketing department, indicated that rofecoxib was associated with 1/8 the mortality from cardiovascular causes of that found with other antiinflammatory drugs.

The Cardiovascular Card … did not include any data from the VIGOR study. Instead, it presented a pooled analysis of preapproval studies, in most of which low doses of rofecoxib were used for a short period of time. None of these studies were designed to assess cardiovascular safety.… In fact, FDA experts had publicly expressed “serious concerns” … about using preapproval studies as evidence of the drug’s cardiovascular safety.…

[B]ut it would be a mistake to restrict the lessons learned to a single company. The testimony we heard indicated that Merck’s marketing practices may be less aggressive and more ethical than many of its competitors. It should be noted that Merck eventually paid $950 million USD to settle criminal charges and civil claims related to unlawful marketing of Vioxx and misleading statements about its safety.

Production Pressure

Anesthesiologists are prone to production pressure, which has been defined as “the internal or external pressure on the anesthetist to keep the operating room schedule moving along speedily.”^82,⁸³ Almost half of surveyed anesthesiologists reported seeing what they considered unsafe anesthetic practices in response to this production pressure.⁸⁴ As a consequence, anesthesiologists may not want to take the time to allow a child to ask questions about the anesthetic, to adequately premedicate an anxious child, or to engage the parents in a lengthy discussion about postponing the surgery because the child has a mild upper respiratory infection. Anesthesiologists should also be cognizant of their level of skill in providing anesthesia. For example, the “routine” tonsillectomy may be beyond some anesthesiologists’ ability in a child with multiple congenital deficits. Anesthesiologists have an obligation to the patient and themselves to only provide care that is within their skills and to recognize when economic and administrative pressures may induce them to do otherwise.

The Fetus

The positions of the AAP and the American College of Obstetricians and Gynecologists (ACOG) are helpful in considering care of the fetus (Table 5-9).⁸⁵^–⁸⁷ The statements indicate subtle differences when the interests of the mother and fetus diverge, such as when the mother wishes to refuse a treatment that would likely be beneficial for the fetus. Broadly, the AAP advocates more for the fetus, particularly when the intervention poses a small risk to the mother and can effectively treat a problem for the fetus that would otherwise cause irreversible harm. ACOG is more concerned about complex issues of overriding maternal autonomy, such as the criminalization of not complying with medical recommendations.

TABLE 5-9 Positions of the AAP and the ACOG Regarding Ethical Considerations and Maternal Choices in Fetal Therapy

American Academy of Pediatrics (AAP)	American College of Obstetricians and Gynecologists (ACOG)
Priority
Respect for principle of maternal autonomy Fetal concerns may trump maternal autonomy

Respect for principle of maternal autonomy

Fetal concerns may not trump maternal autonomy

Type of Medical Treatment Worthy of Judicial or Physical Intervention

If the intervention has been demonstrated to be effective

If nonintervention will lead to significant and irreversible harm

If there is minimal maternal risk from the intervention

If there is a high probability of serious harm to the fetus without intervention

If there is a high probability of significant benefit to the fetus from the intervention

If there is a relatively small risk to the pregnant woman from the intervention

If no comparably effective, less invasive options are available

Intervention only under extraordinary circumstances of conflict

Use of Physical Intervention

Physical intervention may be acceptable if judicial authorization has been obtained

Physical intervention is never acceptable

Psychosocial Aspects

Psychosocial aspects of overriding a woman’s autonomy are not addressed

Significant concern about overriding maternal autonomy, including

• criminalization of noncompliance with medical recommendations

• loss of trust in the health care system

• social costs of compromising liberty

Conflict Resolution

Does not ask physicians to consider subordinating their view

Does not suggest it is reasonable to transfer the patient’s care

Physicians should make reasonable attempts to explain recommended treatments and to persuade the woman to comply

Physicians should subordinate their values if necessary, because it is the woman’s decision

Suggests it may be reasonable to transfer care

Data from Brown SD, Truog RD, Johnson JA, Ecker JL. Do differences in the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists positions on the ethics of maternal-fetal interventions reflect subtly divergent professional sensitivities to pregnant women and fetuses? Pediatrics 2006;117:1382-7; American Academy of Pediatrics, Committee on Bioethics. Fetal therapy: ethical considerations. Pediatrics 1999;103:1061-3; American College of Obstetricians and Gynecologists. Committee Opinion 321: Maternal decision making, ethics, and the law. Obstet Gynecol 2005;106:1127-37.

Physician Obligations, Advocacy, and Good Citizenship

An implicit social contract obligates physicians to serve society beyond directly caring for patients. Society supports medical students, physicians in training, and physicians through providing opportunities to train, to perform research, and, perhaps most importantly, to learn from and with patients.⁸⁸ In return, society expects pediatric anesthesiologists to “manage all things pediatric anesthesia” (Table 5-10).⁸⁹^–⁹¹ Individual anesthesiologists are not expected to fulfill every obligation. “Units” of anesthesiologists, such as private practice groups, academic departments, and state societies, should fulfill these obligations collectively.

TABLE 5-10 Examples of Obligations of Anesthesiologists to Participate and Advocate

Obligations of Pediatric Anesthesiologists

Treat every child with the grace and consideration you would want for your child and family

Tailor the perioperative experience to the individual

Respond to problems that may harm children (e.g., impaired colleagues)

Practice mindfulness and critical self-reflection

Actively engage in continuing medical education

Support advancement of the science

Participate in quality improvement initiatives such as Wake Up Safe

Participate in professional organizations such as the Society for Pediatric Anesthesia and the American Academy of Pediatrics Section on Anesthesiology and Pain Medicine

Prepare future generations through teaching, mentoring, creating opportunities, and developing systems to enable anesthesiologists to fulfill these obligations

Community Advocacy and Participation

Participating in Patient Safety Efforts

Medical errors come from human mistakes and system flaws.⁹² Anesthesiologists have an obligation to work to reduce system flaws, including participating in quality improvement activities and data collection, following policies meant to improve care in high-risk situations (e.g., nosocomial infections), and actively engaging in policies designed to reduce medical errors, such as universal standards of patient identification.⁹³

Although physicians may not see the big picture and therefore resent doing “extra” steps, it is vital for physicians to accept on faith that participation is good patient care.⁹⁴ Surreptitiously circumventing policies may harm patients, does not permit remediation of the policy, and weakens the fidelity of the entire system, encouraging others to “make their own rules.”⁹⁵ When anesthesiologists believe that policies are harmful or unnecessary, they are obligated to raise these questions through appropriate channels.

Treating Suffering

Cassel described suffering as an intensely personal feeling that can be defined as “the state of severe distress associated with events that threaten the intactness of the person.”⁹⁶ Suffering should be considered when managing pain, and adequate steps should be taken to find and alleviate sources of suffering. Factors that contribute to a child’s suffering include not knowing the origin or meaning of the pain, believing that pain is a punishment, and fearing that the pain will never be relieved.⁹⁶ Anesthesiologists minimize suffering by clearly communicating about these issues with parents and children and affording children as much control of their care as possible.

Suspicion of Child Abuse

Child abuse includes acts of physical abuse, sexual abuse, emotional abuse, and neglect. Anesthesiologists should be particularly sensitive to bruises or burns in the shape of objects, injuries to soft tissue areas such as the upper arms, unexplained mouth and dental injuries, fractures in infants, height and weight less than the 5th percentile, and injures that are not explained by the history (see also Chapter 38).^97,⁹⁸ Children who have physical or mental handicaps are particularly prone to abuse.⁹⁹ Anesthesiologists, like all physicians, are legally required to report the suspicion of child abuse or neglect to appropriate authorities. Indeed, in most jurisdictions, a physician can be criminally prosecuted if found liable for failing to report suspected child abuse.

The Ethics Consultation Service

The ethical dilemmas that occur in the practice of anesthesiology may be difficult for the practitioner to resolve alone. Ethics committees and their consulting services act in an advisory role to help clinicians, patients, and families amicably resolve ethical dilemmas. Anesthesiologists may find ethics consultation helpful with questions about informed consent, decision-making capacity, and resuscitation decisions and in resolving disagreements among patients, families, and clinicians.

Although most ethics consultation services use a small group (typically three people) to perform consultations, some use the entire committee and some use a single individual.¹⁰⁰ Physicians, nurses, social workers, chaplains, administrators, and lay people serve on ethics committees and perform consultations. Common characteristics of ethics consultation services are that they permit anyone to request an ethics consultation; that they require notification (not permission) of the patient, parents, and attending physician prior to the consultation; and that choosing to follow the recommendations is wholly voluntary.

Following consultations, clinicians feel greater satisfaction in managing cases with ethical conflicts, not only because of their heightened awareness of the expert consulting services available but also because of their increased knowledge and comfort in dealing with these issues. Ethics committees are also available to consult on policy development and to organize continuing educational programs.

Annotated References

Cassel EJ. The nature of suffering and the goals of medicine. N Engl J Med. 1982;306:639–646.

Physicians relieve suffering. Cassel’s 30-year-old treatise is the unparralled explanation of suffering.

Committee on Bioethics, American Academy of Pediatrics. Informed consent, parental permission, and assent in pediatric practice. Pediatrics. 1995;95:314–317.

This article is the basis of informed consent for children. Pay particular attention to the introduction, in which Dr. William Bartholome (in abstentia) exhorts clinicians to respect “the experience, perspective and power of children.”

1997 Consensus statement of the Society of Critical Care Medicine’s Ethics Committee regarding futile and other possibly inadvisable treatments. Crit Care Med. 1997;25:887–891.

This article explicates the importance of recognizing the ethical and clinical differences between advisable and inadvisable treatments.

Fallat ME, Deshpande JK. Do-not-resuscitate orders for pediatric patients who require anesthesia and surgery. Pediatrics. 2004;114:1686–1692.

This article is a complete explanation of perioperative do-not-resuscitate orders for children.

Gruen RL, Pearson SD, Brennan TA. Physician-citizens: public roles and professional obligations. JAMA. 2004;291:94–98.

Gruen et al. provide a thoughtful perspective on the public and professional obligations of physicians. They provide a path on how to fulfill these obligations.