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Ethical Issues in Neuroprognostication after Severe Pediatric Brain Injury
Ethical Issues in Neuroprognostication after Severe Pediatric Brain Injury Matthew P. Kirschen, MD, PhD,*,† and Jennifer K. Walter, MD, PhD, MS‡,§ Neurologic outcome prediction, or neuroprognostication, after severe brain injury in children is a challenging task and has many ethical dimensions. Neurologists and intensivists are frequently asked by families to predict functional recovery after brain injury to help guide medical decision making despite limited outcome data. Using two clinical cases of children with severe brain injury from different mechanisms: hypoxic-ischemic injury secondary to cardiac arrest and traumatic brain injury, this article first addresses the importance of making a correct diagnosis in a child with a disorder of consciousness and then discusses some of the clinical challenges with deducing an accurate and timely outcome prediction. We further explore the ethical obligations of physicians when supporting parental decision making. We highlight the need to focus on how to elicit family values for a brain injured child, how to manage prognostic uncertainty, and how to effectively communicate with families in these challenging situations. We offer guidance for physicians when they have diverging views from families on aggressiveness of care or feel pressured to prognosticate with in a "window of opportunity" for limiting or withdrawing life sustaining therapies. We conclude with a discussion of the potential influence of emerging technologies, specifically advanced functional neuroimaging, on neurologic outcome prediction after severe brain injury Semin Pediatr Neurol 22:187-195 C 2015 Elsevier Inc. All rights reserved.
Case 1—Hypoxic-Ischemic Brain Injury Secondary to Cardiac Arrest A 4-month-old girl with no significant medical history had a cardiac arrest at home. Her parents found her unresponsive, face down in her playpen, and not breathing. She was last seen 20 minutes prior. Her father performed
From the *Department of Anesthesia and Critical Care, Children’s Hospital of Philadelphia and Perelman School of Medicine, at the University of Pennsylvania, Philadelphia, PA. † Department of Neurology, Children’s Hospital of Philadelphia and Perelman School of Medicine, at the University of Pennsylvania, Philadelphia, PA. ‡ Pediatric Advanced Care Team, Children’s Hospital of Philadelphia, Philadelphia, PA. § Department of Medical Ethics, Children’s Hospital of Philadelphia and Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Address reprint requests to Matthew P. Kirschen, MD, PhD, Department of Anesthesia and Critical Care, The Children’s Hospital of Philadelphia, 3400 Civic Center Blvd, Suite 7C26, Philadelphia, PA 19104. E-mail: [email protected]
1071-9091/15/$-see front matter & 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spen.2015.05.004
cardiopulmonary resuscitation for 5 minutes and emergency medical personnel continued cardiopulmonary resuscitation (CPR) for an additional 2-3 minutes. Spontaneous circulation returned after a dose of epinephrine. She was intubated and taken to the emergency department, where she was noted to have seizure-like movements in her right arm and eye twitching. She received 2 doses of lorazepam and was started on treatment with dopamine before transfer to the pediatric intensive care unit, where she was placed on a therapeutic hypothermia protocol. The computed tomography (CT) scan of her head was unremarkable. On initial examination she was unarousable, pupils were 1-2 mm and sluggishly reactive, vestibular-ocular reflexes were absent, and she had weak cough and gag reflexes. She had no spontaneous movements, and no reaction to noxious stimuli. Over the next several days she developed seizures that were difficult to control, and required treatment with a combination of levetiracetam, phenytoin, and midazolam and ketamine infusions. Her electroencephalogram (EEG) consisted of highly attenuated and slow activity, and it showed that she was not clearly reactive to stimulation. Clinically observed myoclonic jerks were associated with epileptiform sharps. She became hemodynamically stable on 187
M.P. Kirschen and J.K. Walter
188 a dopamine infusion and was able to tolerate nasogastric feeds. A work up result for abusive head injury and metabolic diseases was unremarkable. The child’s magnetic resonance imaging (MRI) of the brain was compatible with hypoxic-ischemic injury, showing multifocal areas of restricted diffusion in the posterior limbs of the internal capsules and the cerebral peduncles bilaterally. Her examination 1 week after the cardiac arrest showed her to be awake, with occasional spontaneous eye opening. Her pupils were equal and reactive, but she did not fix on or follow objects, and she did not blink to threat. Her vestibularocular reflexes were intact. Her tone was increased throughout. She had cortical thumbs as well as palmar and plantar grasp reflexes. She moved all extremities spontaneously. Occasionally, she exhibited lip smacking and bicycling movements of the lower extremities as well as extensor posture of the extremities.
Case 2—Traumatic Brain Injury A 2-year-old boy with no significant medical history sustained a traumatic brain injury when a thick tree branch falling from several stories high struck him on the head. He had immediate loss of consciousness but did not have seizures or a cardiac arrest. He was intubated by emergency medical personnel and brought to the emergency department. On the initial examination he was unresponsive to voice and painful stimuli. His right pupil was reactive and his left pupil was dilated with minimal reactivity. Corneal reflexes were present, and he had a weak cough and gag. Head CT showed extensive calvarial and skull base fractures, left frontal subdural and subarachnoid hemorrhages, and small left lateral intraventricular hemorrhage. A CT angiogram of the brain was normal. Over the next several days his intracranial pressure was well controlled with sedation and hyperosmolar therapy; infrequent subclinical seizures were managed with levetiracetam. He required mechanical ventilation and had no major hemodynamic or respiratory complications. He was tolerating full nasogastric feeds. Brain MRI scan demonstrated multicompartmental intracranial hemorrhage with bilateral supratentorial and infratentorial small subdural collections, subarachnoid hemorrhage, intraventricular hemorrhage, and hemorrhagic contusions in the frontal and the temporal lobes. Widespread changes from diffuse axonal injury were apparent, including hemorrhage and restricted diffusion in the superolateral midbrain and cerebellar vermis, likely owing to Duret hemorrhages secondary to compression against the tentorial incisura at the time of injury. His examination approximately 10 days after injury demonstrated no spontaneous eye opening and no purposeful interaction with his environment. Cranial nerves were intact, except a persistent traumatic left dilated and nonreactive pupil. His extremities moved spontaneously and in response to painful stimuli, more vigorously on the left, with intermittent bilateral extensor posturing that had no EEG correlation.
Introduction Neurologic outcome prediction after severe brain injury is one of the most difficult tasks neurologists and intensivists face, and this process is filled with a unique set of clinical and ethical challenges. With the advancement of technology and clinical practices in critical care and neurology aimed at preserving and restoring neurologic function, prognostication has evolved from estimating the probability of survival to the more complicated task of predicting functional recovery. Despite limited outcome data and inevitable prognostic uncertainty, neurologists are often compelled to make management recommendations and counsel parents about the potential for neurologic recovery when a child remains critically ill. The cases presented in this article describe children with severe brain injury and resultant disorders of consciousness from 2 different mechanisms—hypoxic-ischemic injury secondary to cardiac arrest and traumatic brain injury. Although the etiologies of the brain insults are quite different, the clinical status of the children at the conclusion of these vignettes is comparable. However, the projected recovery may be quite divergent based solely on injury mechanism. Using these cases as a backdrop, we address the importance of making the correct diagnosis in a patient with a disorder of consciousness after severe brain injury and discuss some of the challenges in deducing an accurate prognosis in these situations. We then explore some of the clinical and ethical challenges relating to the obligations of physicians to inform families about the predicted trajectory of neurologic recovery after severe brain insult and discuss how the certainty of a prognosis may appropriately or inappropriately influence clinical management decisions. Finally, we examine the potential effect of new technologies, specifically advanced functional neuroimaging, on our current and future prognostic abilities.
Making the Correct Diagnosis The adage often quoted by medical ethicists—“good facts make good ethics”— aptly applies to children after severe brain injury and a disorder of consciousness. Consciousness comprises 2 clinical components—wakefulness and awareness of one’s self and the environment.1 A disordered state of consciousness, which can vary from acute and transient to irreversible and permanent, results when 1 or both of these components are compromised. Disordered states of consciousness are a spectrum of clinical syndromes that encompass a range of cognitive dysfunction, from confusional states such as delirium, to vegetative and minimally conscious states, coma, and locked-in syndrome.2 Although the diagnosis of these syndromes can be significantly more challenging in infants and children, it is essential to properly identify both the etiology of brain injury and the correct disorder of consciousness syndrome before attempting to prognosticate recovery. The etiology of the impaired consciousness is easily identified in the vignettes presented
Ethical issues in neuroprognostication earlier; however, it is not always as apparent and occasionally requires extensive diagnostic testing. Given the clinical and ethical implications for prognosis and management decisions, determining the extent of a child’s impaired consciousness should be completed meticulously. The assessment should be completed in a standardized manner, under conditions that maximize opportunities to observe responsiveness, and repeated over time. Careful considerations should be given to the published criteria that differentiate the subtleties of these disorders.2-5 As many as 40% of adult patients admitted to rehabilitation centers have been incorrectly diagnosed as a vegetative state, and patients in locked-in states have also erroneously been deemed unconscious.6-8 Although evaluating a brain-injured child for a disorder of consciousness is challenging, the Child Neurology Society and the American Academy of Neurology have published guidelines on the medical aspects of the persistent vegetative state.9 Additionally, a survey of child neurologists found that greater than 90% believe that a diagnosis of vegetative state could be made in children aged 2 years or older, 70% thought this diagnosis could be made in children aged 2 months to 2 years, and 16% believed that this applied to infants younger than 2 months.10 The children described in the vignettes presented here were both initially in a coma—an eye-closed pathologic state of unresponsiveness from which individuals cannot be aroused to wakefulness by stimuli. The comatose state after brain insult typically lasts for a few weeks and then individuals naturally progress into a state of eye-open wakefulness without awareness, called a vegetative state. The term persistent is typically applied when the vegetative state lasts more than a month. A persistent vegetative state is considered permanent 12 months after traumatic brain injury and 3 months after nontraumatic injury because of the high degree of certainty with which the irreversibility of the brain insult and resultant clinical manifestations can be determined at those points. The 4-month old with hypoxicischemic injury (case 1) was in a vegetative state 1 week after her injury, whereas the 2-year old (case 2) was still in a coma 10 days after his traumatic brain injury. Children can improve over time from a vegetative state to a minimally consciousness state—a chronic state of poor responsiveness to stimuli, but one in which patients demonstrate evidence of awareness of themselves and their environment.5
Deducing an Accurate and Timely Prognosis The first questions universally asked by family members after a child sustains brain injury are about the probability of survival and the chances for good neurologic recovery. For physicians, generating and communicating an accurate and timely prognosis is essential to establishing the goals of care and directing clinical care. An overly optimistic prediction may result in survival of a neurologically devastated child, whereas an overly pessimistic prediction may lead to
189 withdrawal of life-sustaining therapies in a child with a potentially good functional outcome. Although the answer to this inevitable prognosis question should be evidenced based whenever possible, prognostication is highly complex, and no single objective clinical, laboratory, imaging, or neurophysiological test or biomarker reliably predicts neurologic outcome, especially early after a severe brain insult.11,12 Outcome assessments are dependent on a multitude of patient-related factors such as age and preexisting medical conditions, injury-related factors including the etiology, location, and extent of the brain injury, and other associated organ system compromise. Assessments are also influenced by physician-related factors such as age, clinical experience, and medical specialty.13-15 Occasionally, it is reasonable to specify expected functional deficits based on the neuroanatomical pattern of injury (eg, motor and language impairments after a left middle cerebral artery stroke); however, it is often difficult, especially if the child has underlying neurodevelopmental delays, to predict performance in precise domains such as communication, feeding, and ambulation. Establishing preinjury neurologic baselines for patients is essential, as the same brain injury can have widely different implications for recovery depending on whether a child was previously healthy, has a chronic neurologic or developmental condition, or has a progressive neurodegenerative disease. Additionally, using existing outcome data can be challenging in clinical practice, as many of the predictive features are too coarse to guide individual patient management, specifically in pediatric patients, where the variability of injury is high, neurodevelopmental factors must be considered, and the data are more limited. A further complication preventing generalizability of existing data is that many of these studies use mortality as the outcome measure; however, the frequency of withdrawal of lifesustaining therapies is often not reported. Unlike other conditions, pediatric outcome data do exist for hypoxic-ischemic injury secondary to cardiac arrest (case 1) and traumatic brain injury (case 2), and this information can help guide recovery predictions. For children who had a cardiac arrest and achieved sustained return of spontaneous circulation, a favorable neurologic outcome is observed in approximately 5% of them after out-of-hospital cardiac arrest and 15%-45% after in-hospital cardiac arrest.16-20 Outcomes after severe TBI, although variable, are generally better than after cardiac arrest, and substantial recovery after TBI is often appreciated between hospital discharge and outcomes measured 6 months to several years after injury.2124 Some data indicate that at several years after the injury, and after extensive rehabilitation, 60% of survivors with TBI perform scholastically on par with their similar-aged peers and more than 80% are independent in activities such as feeding and mobilization.21 Factors such as a low postresuscitation Glasgow Coma Scale score and refractory increased intracranial pressure are still strongly associated with death and poor functional outcomes.22 Most of the prognosis literature is geared toward evaluating the effectiveness of particular metrics in predicting
190 outcome, whereas few studies have examined the accuracy of outcome prediction by clinicians and the ways in which physicians prognosticate. A recent study of outcome prediction in an adult neurointensive care unit found that neurointensivists correctly predicted 6-month functional outcome in 80% of patients with acute brain injury at approximately 4 days after the injury.14 Physicians had better accuracy for predicting poor outcomes over good outcomes, even after excluding patients who had lifesustaining therapies withdrawn. Our group recently evaluated the accuracy and timing of neurologic outcome predictions after pediatric cardiac arrest by both pediatric intensivists and neurologists.25 Prediction accuracy improved over the first week of care from 75% to 85% and was not significantly different between the 2 physician specialties. Interphysician prognosis agreement also improved over time for both physician groups from moderate to substantial levels. Similarly, outcome prediction confidence also improved over the first week of care for both physician groups and interestingly, increased regardless of whether prognoses were accurate or inaccurate. In the aforementioned study, we also examined which factors (ie, cardiac arrest characteristics, neurologic examination, MRI, and EEG) most strongly influenced physician outcome predictions for children after cardiac arrest. Both neurologists and intensivists reported that the most influential factor for prognostication was the patient’s physical examination. Other important factors were the brain MRI scan and EEG for neurologists and the cardiac arrest characteristics and brain MRI scan for the intensivists.25 Given the weight physicians place on the neurologic examination in prognosticating about recovery, neurology and critical care training programs should ensure that appropriate education is provided on conducting and interpreting the neurologic examination in critically ill brain-injured children.26-28 Further research is needed to determine how effective conventional neuroimaging29 and electrophysiological30,31 modalities are in assisting physicians to accurately predict neurologic outcome after cardiac arrest and other acute brain injuries.
Medical Decision Making After Severe Brain Injury Parents or guardians are usually the presumed authorized decision makers for their children who have sustained a severe brain insult. Unlike previously competent adults who may have expressed their wishes for what they would want if permanently unconscious, most children have not developed the decision-making capacity necessary to make such choices. Therefore, surrogates cannot use substituted judgment when making decisions for their children. Instead, they are expected to consider what is in their child’s best interest. This privilege is questioned only if parents are abusive or neglectful, which can occur if the brain injury is secondary to abusive head injury or nonaccidental trauma. Although the best interest standard appears straightforward
M.P. Kirschen and J.K. Walter and may be objectively determined, the fact that physicians and families often make different assessments of what is in a child’s best interest uncovers that there are many values imported into these assessments.32 Some individuals may value the physical presence of an individual, even if they are minimally interactive, whereas others prioritize a meaningful interaction with the hope of independence for their child. Although there may be consensus that it is in the interest of a child to not be in pain, there is no consensus about whether doing interventions to sustain a child in a vegetative or minimally conscious state is in the child’s best interest.
Physician Obligations to Support Parental Decision Making Physicians have several intertwined ethical obligations in supporting parental decision making while caring for children with acute brain injury. Their obligations are to first communicate, to the best of their ability, the nature of the brain insult, the potential and time frame for neurologic recovery, and their certainty in achieving the predicted functional state. Second and equally as important, physicians must elicit the families’ values and priorities for their child, concerns as caregivers, and what they would deem an acceptable quality of life for their child. The physician can then help design and implement a care plan that is mutually agreed upon that is most consistent with the family’s values for its child. This shared decision-making model encourages ongoing dialogue between the physician and a child’s family, and it has been endorsed by many professional organizations and the Institute of Medicine.33-35 Although this approach may seem straightforward, this process hinges on (1) being able to clearly elucidate parental values for their brain-injured child, (2) prognostic accuracy and certainty on the part of the physician, and (3) the ability of physicians to effectively communicate the prognostic information to the family. These components can have a profound influence on decisions regarding goals of care and clinical management, especially when prognostic information is fraught with a myriad of uncertainties.
Ascertaining Family Values for the Child Families of critically ill children are, understandably so, emotionally overwhelmed and struggling to navigate a highly complex system of care. The high rates of posttraumatic stress disorder experienced by parents of children who have been in the pediatric intensive care unit make apparent the strain they are under when being asked to make decisions for their children.36 Having these important conversations with families is therefore incredibly challenging and requires preparation and skill. Although some theories of decision making prioritize a purely rational approach to decisions, many more nuanced theories of decision making acknowledge the inherent emotional aspects of the process.37 Therefore, intensivists and neurologists should be prepared and equipped to acknowledge the
Ethical issues in neuroprognostication emotional experience of families and in many circumstances adjust the language they use while eliciting what is important to the family. Open-ended questions such as “what does it mean to be a good parent to your child now,” “what wishes or hopes do you have for your child,” or “what are you worried about” can initiate a conversation that offer invaluable information about which values families are prioritizing.
Managing Prognostic Uncertainty Families hope for prognostic certainty to guide medical decision making for their severely brain-injured child. Unfortunately, there is an unavoidable inherent uncertainty in any functional outcome prediction offered by physicians. It is often how physicians handle and communicate this uncertainty that drives clinical recommendations and decision making. It is the nature of some physicians to emphasize uncertainty, and this may correlate with a physician’s level of medical training or clinical experience.38,39 In one study, less-experienced physicians were more optimistic about a patient’s functional outcome, less certain of their outcome prediction, and felt that quality-oflife assessments were too subjective to comment on and best left to the prerogative of the patient’s family.13 This may be because physicians trained in recent decades frequently believe that being respectful of patients’ autonomy requires that they not offer a recommendation for treatment in order to avoid the appearance of paternalism.37 Physicians often recognize that the degree of prognostic certainty they express may influence the subsequent care decisions made by a child’s family. In some circumstances, this leads physicians to avoid any claim of certainty to avoid directing care, and in other instances, physicians may use this claim of certainty to influence the outcome that aligns with their perceived best interest for the patient. At least in 1 study, prognostic certainty improved over time after injury, independent of prognostic accuracy.25 Most physicians have instances in their career where their outcome prediction was worse than the patient’s actual outcome, sometimes even recommending withdrawal of lifesustaining therapies for a patient who recovered with reasonable neurologic function. It is not uncommon for these rare but memorable patients to influence the certainty or confidence with which prognoses are shared with families, even if contrary to the published evidence and guidelines. Some of these patients, like the case of Terry Wallis who began speaking after being in a minimally conscious state for nearly 20 years following a traumatic brain injury, are publicized in the popular press and reinforce the hope that families have for their braininjured children.40 The converse situations also exist where an overly optimistic recovery trajectory was outlined for a family and the patient’s residual neurologic function was minimal. These notable experiences for physicians, combined with other personal characteristics such as gender, ethnicity, and religious or cultural beliefs, form the implicit bias that physicians bring to any prognostic encounter.
191 A recommended approach to dealing with the uncertainty of prognosis is to normalize the uncertainty of prognosis, to address the family’s emotions about this uncertainty, and to encourage families to focus on the present and not primarily on wishing they knew what the future would bring.41 Physicians must respect the autonomy of parental decision making and ensure that when providing neuroprognostic information and potential treatment options, recommendations for these care plans are consistent with the families’ goals and values for their child. For example, if a child (as in case 1) is in a vegetative state after a cardiac arrest, and the physician with a high degree of certainty predicts that the child will not have further neurologic recovery, recommendations regarding treatment decisions must be consistent with the families’ stated values for that child. If on one hand the family believes that living in a vegetative state is not consistent with what they perceive is a good quality of life, it is appropriate to recommend goals of care that minimize pain and suffering, and consider limiting or withdrawing life-sustaining therapies. If on the contrary, the family is elated that their child is still alive after cardiac arrest and insists on pursuing all options to keep the child alive, discussing withdrawal of support may not be helpful and could strain an already fragile physician-family relationship. Instead, recommendations should focus on topics such as nutrition and control of seizures and spasticity. In these instances, where the family prefers to maximize therapy independent of neurologic prognosis, providing an outcome prediction may still be helpful in setting recovery expectations, rather than deciding on limitations of care. Although the complexity of these situations can grow exponentially, especially in situations where the certainty of an outcome prediction is low or neurologic improvements are expected but may not be apparent for several months (eg, TBI, case 2), the central tenant of focusing clinical care decisions so that they are aligned with the goals of values of a family for their child must be preserved.
Effective Communication With Families Information about neurologic recovery may be precise and definitive as in the case of brain death, or encompass a broad spectrum of functional possibilities. Likewise, it is also important to recognize that different parents may have variable information needs regarding their child’s condition and prognosis. Families should be queried about the nature of the information relating their child’s brain insult and recovery potential they wish to receive. Some may need precise outcome percentages or want to review the scientific data themselves, whereas others prefer summary statements or no information at all, and just the physician’s treatment recommendations. Physicians should be cautious of how they frame the decisions to be made for a child because how these conversations are conducted could bias many components of an encounter with a child’s family. It is important to recognize and plan for how to discuss questions relating to a child’s neurologic baseline, the presentation of outcome statistics, and discussions regarding parental values and treatment preferences.42,43 For example, in eliciting a family’s preferences regarding “do-not-resuscitate” status,
192 responses may vary depending on parental emotional and informational needs at the time and whether the information (and emotional support) provided is aligned with such needs. Even families who are clear about the goals they have for their child value hearing from the medical team that they are making a loving choice for their child. The language and communication strategies used by physicians when discussing outcome and prognostic information can have a profound influence on decisions regarding clinical management including withholding or withdrawing life-sustaining therapies. How physicians communicate prognoses to other health care providers and families is highly variable, and it is unclear how effectively the underlying messages are being received and interpreted.44 Additionally, the use of effective communication strategies (ie, being emotionally supportive or adopting an empathic manner) to communicate prognoses to families has been shown to help reduce anxiety and improve information recall, particularly for prognostic information.45 Research is needed to further characterize the most effective language and communication strategies used when discussing neuroprognostic information, so these can be distributed and taught to physicians engaged in this process.
Window of Opportunity for Treatment Withdrawal Many patient, family, and physician factors can influence the timing of clinical decisions after severe brain injury. For example, a critical period of physiological instability often exists, during which time withholding or withdrawal of lifesustaining therapies has a high likelihood of leading to death. This period is sometimes referred to as the “window of opportunity” and typically lasts several days, but it can extend longer.46,47 Unfortunately, both evidenced-based prognostic tests and clinical experience have lower prognostic certainty during this window.11,25 If treatment decisions are delayed past this window, greater prognostic certainty can be achieved, but the child may no longer require these life-sustaining interventions (eg, mechanical ventilation and inotropic support) and survive with profound neurologic injury even if the family opts to limit further intensive care. Complicating this situation are evolving therapies aimed at neuronal protection after brain insult (eg, therapeutic hypothermia), and prognosticating before the completion of these types of therapy may contribute to inappropriate decisions to limit care.15 This initial window of opportunity for treatment limitation is an important consideration for some physicians, particularly for children with hypoxic-ischemic injury, where outcome data are more robust. However, it can also apply to other types of brain injury such as severe traumatic brain injury, although prognostic uncertainty is usually greater in these instances, making management decisions during this period more complex. Although it is appropriate for physicians to consider the window of opportunity during post–brain injury goals of care conversations, families should not be pressured into making treatment decisions during this window, especially if the prognostic
M.P. Kirschen and J.K. Walter certainty is low. Understandably, many families are hopeful for a better-than-expected recovery or not emotionally ready to make such an irreversible decision in this crisis period. Strongly recommending a decision during this time frame can fracture the fragile physician-family relationship and lead to further challenges in providing optimal care for the child. Physicians should appreciate and be reassured that this stated “window of opportunity” of physiological instability is not the only opportunity families have to limit or withhold medical therapy to avoid care that is inconsistent with the family’s values or that causes the child pain and suffering. As part of the ongoing discussions between the medical care team and the family, the family’s values for the child can be used to establish overarching goals of care and treatment parameters for future illnesses, surgical procedures, and hospitalizations, to name a few. In many circumstances, what parents initially value (preserving their child’s life) may shift over time if they perceive their child to suffer from repeated hospitalizations or procedures and they start to prioritize other goals (protection from suffering). For children who are in a permanent vegetative state or other conditions that permanently lack conscious awareness and the ability to interact with the environment, options such as withdrawal of artificial hydration and nutrition are ethically permissible and consistent with American Academy of Pediatrics ethical guidance.48
When Physicians and Families Disagree It is not uncommon for physicians and families to have diverging views on the aggressiveness of care for children after severe brain injury. If a child’s prognosis is to survive in a neurologically devastated state, many physicians trying to protect their patient from perceived harm and persistent suffering would recommend withdrawal of life-sustaining therapies. Parents may maintain hope for recovery, holding tightly to the small degree of uncertainty in the prognosis or case reports of miraculous recoveries, and request continued aggressive care. The authors of several studies have documented differences in attitudes between medical professionals and parents regarding treatment plans for children with severe neurologic impairment. In one study, the authors found that health care professionals thought a childhood of profound neurologic impairment was worse than death.49 On the other end of the spectrum, rarer situations arise where a child has relatively minor brain injuries and a prognosis with mild neurocognitive sequelea; however, the parents feel that any degree of neurologic compromise is unacceptable and want to discontinue life-sustaining therapies (presuming intensive cardiorespiratory support is required for other concurrent systemic injuries). In these challenging situations, physicians have a responsibility to acknowledge that we have our own values and that they may be different from the values of any given family. Our obligation is to ensure that the values of the family are respected in clinical care decisions, particularly if the treatments being offered do not cause suffering to the patient. Consultation by an interdisciplinary ethics consultation service or palliative care team may be helpful if
Ethical issues in neuroprognostication physicians are uncomfortable providing care that, although consistent with the family’s values, may be perceived to be causing harm or contributing to suffering. These conversations should not be limited to discussions of end-of-life issues but should include strategies for improving the child’s quality of life, treating pain or other distressing symptoms (eg, seizures, spasticity, impaired secretion management, or constipation), and attending to other emotional or social needs of the child, caregivers, and family.
Effect of New Technologies Emerging technologies, specifically advanced functional neuroimaging modalities such as positron emission tomography and functional MRI are transitioning from the research setting into clinical care and are positioned to have a significant effect on neuroprognostication after severe brain injury.50-52 These techniques may contribute helpful information to aid in neurologic diagnosis and prognosis, particularly for patients with severe brain insult and a resultant disorder of consciousness. However, they may also contribute further to the uncertainty of the neuroprognostication process, which could affect discussions with families about goals of care and clinical management strategies. The authors of several functional neuroimaging studies have examined patients in vegetative and minimally conscious states and demonstrated functional activation patterns consistent with preserved awareness and in some cases, more complex language and cognitive functions.53-57 A subset of these patients subsequently showed evidence of clinical improvement by demonstrating awareness after several months. The authors of a single pediatric case report describe a 7-year-old girl who sustained traumatic and hypoxic brain injuries when she was 18 months old. She was noncommunicative and displayed minimal behavioral signs of awareness of self and others (probable diagnosis of minimally conscious state).58 Functional MRI demonstrated activation of language networks in response to personally relevant stimuli (patient’s own name and familiar voice), suggesting that some of her higher-level cortical cognitive processing could be intact. Being able to detect covert awareness using these neuroimaging techniques may alter the diagnostic criteria for disorders of consciousness, improve prognostic accuracy and confidence, and even facilitate communication with seemingly unresponsive patients. As the technology improves, these examinations may be able to provide assessments of levels of pain or discomfort and even express an individual’s wants and needs. Some have questioned whether it is ethical to withdraw or withhold life-sustaining therapies including artificial hydration and nutrition if a functional MRI scan provides evidence of consciousness or awareness.59,60 Although this evolving functional neuroimaging literature is promising and will hopefully help to reduce diagnostic and prognostic uncertainty in the future, it currently resides in the research domain. Physicians should be prepared that
193 some families may request these tests to be performed on their children as they struggle with care decisions resting on whether their child is conscious and the probability of recovering awareness, meaningful responsiveness, and other basic neurologic functions.61 It is noteworthy that the parents of the boy in case 2 requested a functional brain scan to help predict outcome potential. Physicians must proceed with caution before these technologies are fully vetted and validated through extensive research and experience and transitioned into mainstream clinical practice.52 As their use becomes more widespread, partnering with families and elucidating specific goals and values for their child will be even more important in guiding medical decisions and clinical care.
Conclusions At the time of the writing of this article, the 4-month old with hypoxic-ischemic brain injury from a cardiac arrest (case 1) is now 6 years old and continues to be followed up at our institution. She has a chronic static encephalopathy and is in a permanent vegetative state. She is severely microcephalic (o third percentile) and opens her eyes spontaneously and to stimulation, but she does not fix on or follow objects. She does not purposefully interact with her environment although she has occasional episodes of smiling or crying. She is nonverbal, nonambulatory, and unable to sit unassisted. She has severe global hypertonia and spasticity and is dependent on a gastrostomy tube for nutrition. She has refractory epilepsy and is on several antiepilepsy medications and requires medication to relieve spasticity. She is not currently in school and has home nursing support. This condition is congruent with the prognosis offered by her physicians after her cardiac arrest. The family continues to be appreciative of the life-saving medical care she received and values that she is alive and a part of their family. She has had several hospital admissions for respiratory illnesses, some requiring invasive mechanical ventilation, and the family has declined any limitations of care. The 2-year old who sustained a severe traumatic brain injury from a falling tree branch (case 2) is now approximately 1 month after the injury and continues with inpatient rehabilitation, demonstrating signs of improvement on a daily basis. He transitioned first from coma to a vegetative state and now resides in a minimally conscious state. He currently opens his eyes spontaneously and to commands and is intermittently able to track objects. He is able to hold his head up and intermittently follows simple commands. He is unable to sit unassisted and is nonverbal. He is being fed via a nasogastric tube. The medical team, including intensivists, neurologists, and rehabilitation specialists, had extensive discussions with the family about the uncertainty of his prognosis and the variability in TBI outcomes. The family is generally optimistic and hopeful, encouraged that he continues to make improvements, and understands that the recovery process may take numerous
194 months, will require intense therapy, and his eventual level of functioning is uncertain. Physicians have an ethical obligation to support parental decision making for their child after a severe brain injury. This obligation includes several different components. To the extent possible, physicians should confer a timely and accurate diagnosis and prognosis, acknowledging that it is common to have uncertainty in prognosis and that it may be upsetting. Equally importantly, physicians should elicit the values that parents have for their child, which can serve as the foundation for determining goals of care and treatment options. Physicians must remember the importance of respecting the autonomy of parental decision making and ensure that care plans are consistent with the families’ goals and values for their child. In some circumstances, physicians will find that families’ goals are not consistent with what they themselves would have chosen, but in most circumstances, the families’ values are given priority. These alreadydifficult discussions surrounding neuroprognostication after brain injury will become only more challenging with the introduction of functional neuroimaging technologies that may be able to help elucidate covert awareness or cognitive function in a seemingly comatose child. In these circumstances, such as those at present, clear and compassionate communication about what is known and unknown is central to supporting parental decision making.
References 1. Posner JB, Plum F: Plum and Posne’s Diagnosis of Stupor and Coma, ed 4 Oxford, NY, Oxford University Press, 2007 2. Bernat JL: Chronic disorders of consciousness. Lancet 367:1181-1192, 2006 3. The Multi-Society Task Force on PVS: Medical aspects of the persistent vegetative state (2). N Engl J Med 330:1572-1579, 1994 4. The Multi-Society Task Force on PVS: Medical aspects of the persistent vegetative state (1). N Engl J Med 330:1499-1508, 1994 5. Giacino JT, Ashwal S, Childs N, et al: The minimally conscious state: Definition and diagnostic criteria. Neurology 58:349-353, 2002 6. Childs NL, Mercer WN, Childs HW: Accuracy of diagnosis of persistent vegetative state. Neurology 43:1465-1467, 1993 7. Andrews K, Murphy L, Munday R, et al: Misdiagnosis of the vegetative state: Retrospective study in a rehabilitation unit. Br Med J 313:13-16, 1996 8. Smith E, Delargy M: Locked-in syndrome. Br Med J 330:406-409, 2005 9. The Quality Standards Subcommittee of the American Academy of Neurology: Practice parameters: Assessment and management of patients in the persistent vegetative state (summary statement). Neurology 45:1015-1018, 1995 10. Ashwal S, Bale JF Jr, Coulter DL, et al: The persistent vegetative state in children: Report of the Child Neurology Society Ethics Committee. Ann Neurol 32:570-576, 1992 11. Abend NS, Licht DJ: Predicting outcome in children with hypoxic ischemic encephalopathy. Pediatr Crit Care Med 9:32-39, 2008 12. Wijdicks EF, Hijdra A, Young GB, et al: Practice parameter: Prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 67:203-210, 2006 13. Racine E, Dion MJ, Wijman CA, et al: Profiles of Neurological Outcome Prediction Among Intensivists. Neurocrit Care 11:345-352, 2009
M.P. Kirschen and J.K. Walter 14. Finley Caulfield A, Gabler L, Lansberg MG, et al: Outcome prediction in mechanically ventilated neurologic patients by junior neurointensivists. Neurology 74:1096-1101, 2010 15. Perman SM, Kirkpatrick JN, Reitsma AM, et al: Timing of neuroprognostication in postcardiac arrest therapeutic hypothermia. Crit Care Med 40:719-724, 2012 16. Topjian AA, Berg RA, Nadkarni VM: Advances in recognition, resuscitation, and stabilization of the critically ill child. Pediatr Clin North Am 60:605-620, 2013 17. Topjian AA, Berg RA, Nadkarni VM: Pediatric cardiopulmonary resuscitation: Advances in science, techniques, and outcomes. Pediatrics 122:1086-1098, 2008 18. Donoghue AJ, Nadkarni V, Berg RA, et al: Out-of-hospital pediatric cardiac arrest: An epidemiologic review and assessment of current knowledge. Ann Emerg Med 46:512-522, 2005 19. Girotra S, Spertus JA, Li Y, et al: Survival trends in pediatric in-hospital cardiac arrests: An analysis from Get With the Guidelines-Resuscitation. Circ Cardiovasc Qual Outcomes 6:42-49, 2013 20. Kitamura T, Iwami T, Kawamura T, et al: Conventional and chestcompression-only cardiopulmonary resuscitation by bystanders for children who have out-of-hospital cardiac arrests: A prospective, nationwide, population-based cohort study. Lancet 375:1347-1354, 2010 21. Shaklai S, Peretz R, Spasser R, et al: Long-term functional outcome after moderate-to-severe paediatric traumatic brain injury. Brain Inj 28: 915-921, 2014 22. Jagannathan J, Okonkwo DO, Yeoh HK, et al: Long-term outcomes and prognostic factors in pediatric patients with severe traumatic brain injury and elevated intracranial pressure. J Neurosurg 2:240-249, 2008 23. Thakker JC, Splaingard M, Zhu J, et al: Survival and functional outcome of children requiring endotracheal intubation during therapy for severe traumatic brain injury. Crit Care Med 25:1396-1401, 1997 24. Vavilala MS, Kernic MA, Wang J, et al: Acute care clinical indicators associated with discharge outcomes in children with severe traumatic brain injury. Crit Care Med 42:2258-2266, 2014 25. Kirschen MP, Topjian AA, Hammond R, et al: Neuroprognostication after pediatric cardiac arrest. Pediatr Neurol 51:663-668, 2014 26. Mandel R, Martinot A, Delepoulle F, et al: Prediction of outcome after hypoxic-ischemic encephalopathy: A prospective clinical and electrophysiologic study. J Pediatr 141:45-50, 2002 27. Abend NS, Topjian AA, Kessler SK, et al: Outcome prediction by motor and pupillary responses in children treated with therapeutic hypothermia after cardiac arrest. Pediatr Crit Care Med 13:32-38, 2012 28. Bratton SL, Jardine DS, Morray JP: Serial neurologic examinations after near drowning and outcome. Arch Pediatr Adolesc Med 148:167-170, 1994 29. Christophe C, Fonteyne C, Ziereisen F, et al: Value of MR imaging of the brain in children with hypoxic coma. Am J Neuroradiol 23: 716-723, 2002 30. Abend NS, Topjian A, Ichord R, et al: Electroencephalographic monitoring during hypothermia after pediatric cardiac arrest. Neurology 72:1931-1940, 2009 31. Nishisaki A, Sullivan J 3rd, Steger B, et al: Retrospective analysis of the prognostic value of electroencephalography patterns obtained in pediatric in-hospital cardiac arrest survivors during three years. Pediatr Crit Care Med 8:10-17, 2007 32. Weisleder P: Dignified death for severely impaired infants: Beyond the best-interest standard. J Child Neurol 22:737-740, 2007 33. Institute of Medicine: Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC, National Academies Press, 2001 34. Davidson J, Powers K, Hedayat K, et al: Clinical practice guidelines for support of the family in the patient-centered intensive care unit: American College of Critical Care Medicine Task Force 2004-2005. Crit Care Med 35:605-622, 2007 35. American Academy of Pediatrics Committee on Hospital Care: Familycentered care and the pediatrician’s role. Pediatrics 112:691-697, 2003 36. Colville G, Pierce C: Patterns of post-traumatic stress symptoms in families after paediatric intensive care. Intensive Care Med 38: 1523-1531, 2012
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195 49. Saigal S, Stoskopf BL, Feeny D, et al: Differences in preferences for neonatal outcomes among health care professionals, parents, and adolescents. J Am Med Assoc 281:1991-1997, 1999 50. Bernat JL: Ethical issues in the treatment of severe brain injury: The impact of new technologies. Ann N Y Acad Sci 1157:117-130, 2009 51. Bernat JL: Can functional MRI detect awareness when a neurological examination does not? Nat Clin Pract Neurol 3:490-491, 2007 52. Fins JJ, Illes J, Bernat JL, et al: Neuroimaging and disorders of consciousness: Envisioning an ethical research agenda. Am J Bioeth 8:3-12, 2008 53. Owen AM, Coleman MR: Functional neuroimaging of the vegetative state. Nat Rev Neurosci 9:235-243, 2008 54. Owen AM, Coleman MR, Boly M, et al: Detecting awareness in the vegetative state. Science 313:1402, 2006 55. Schiff ND, Rodriguez-Moreno D, Kamal A, et al: fMRI reveals largescale network activation in minimally conscious patients. Neurology 64:514-523, 2005 56. Di HB, Yu SM, Weng XC, et al: Cerebral response to patient’s own name in the vegetative and minimally conscious states. Neurology 68:895-899, 2007 57. Monti MM, Vanhaudenhuyse A, Coleman MR, et al: Willful modulation of brain activity in disorders of consciousness. N Engl J Med 362:579-589, 2010 58. Nicholas CR, McLaren DG, Gawrysiak MJ, et al: Functional neuroimaging of personally-relevant stimuli in a paediatric case of impaired awareness. Brain Inj 28:1135-1138, 2014 59. Weijer C, Peterson A, Webster F, et al: Ethics of neuroimaging after serious brain injury. BMC Med Ethics 15:41, 2014 60. Wilkinson DJ, Kahane G, Horne M, et al: Functional neuroimaging and withdrawal of life-sustaining treatment from vegetative patients. J Med Ethics 35:508-511, 2009 61. Racine E, Bell E: Clinical and public translation of neuroimaging research in disorders of consciousness challenges current diagnostic and public understanding paradigms. Am J Bioeth 8:13-15, 2008
Case 1—Hypoxic-Ischemic Brain Injury Secondary to Cardiac Arrest A 4-month-old girl with no significant medical history had a cardiac arrest at home. Her parents found her unresponsive, face down in her playpen, and not breathing. She was last seen 20 minutes prior. Her father performed
From the *Department of Anesthesia and Critical Care, Children’s Hospital of Philadelphia and Perelman School of Medicine, at the University of Pennsylvania, Philadelphia, PA. † Department of Neurology, Children’s Hospital of Philadelphia and Perelman School of Medicine, at the University of Pennsylvania, Philadelphia, PA. ‡ Pediatric Advanced Care Team, Children’s Hospital of Philadelphia, Philadelphia, PA. § Department of Medical Ethics, Children’s Hospital of Philadelphia and Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Address reprint requests to Matthew P. Kirschen, MD, PhD, Department of Anesthesia and Critical Care, The Children’s Hospital of Philadelphia, 3400 Civic Center Blvd, Suite 7C26, Philadelphia, PA 19104. E-mail: [email protected]
1071-9091/15/$-see front matter & 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spen.2015.05.004
cardiopulmonary resuscitation for 5 minutes and emergency medical personnel continued cardiopulmonary resuscitation (CPR) for an additional 2-3 minutes. Spontaneous circulation returned after a dose of epinephrine. She was intubated and taken to the emergency department, where she was noted to have seizure-like movements in her right arm and eye twitching. She received 2 doses of lorazepam and was started on treatment with dopamine before transfer to the pediatric intensive care unit, where she was placed on a therapeutic hypothermia protocol. The computed tomography (CT) scan of her head was unremarkable. On initial examination she was unarousable, pupils were 1-2 mm and sluggishly reactive, vestibular-ocular reflexes were absent, and she had weak cough and gag reflexes. She had no spontaneous movements, and no reaction to noxious stimuli. Over the next several days she developed seizures that were difficult to control, and required treatment with a combination of levetiracetam, phenytoin, and midazolam and ketamine infusions. Her electroencephalogram (EEG) consisted of highly attenuated and slow activity, and it showed that she was not clearly reactive to stimulation. Clinically observed myoclonic jerks were associated with epileptiform sharps. She became hemodynamically stable on 187
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188 a dopamine infusion and was able to tolerate nasogastric feeds. A work up result for abusive head injury and metabolic diseases was unremarkable. The child’s magnetic resonance imaging (MRI) of the brain was compatible with hypoxic-ischemic injury, showing multifocal areas of restricted diffusion in the posterior limbs of the internal capsules and the cerebral peduncles bilaterally. Her examination 1 week after the cardiac arrest showed her to be awake, with occasional spontaneous eye opening. Her pupils were equal and reactive, but she did not fix on or follow objects, and she did not blink to threat. Her vestibularocular reflexes were intact. Her tone was increased throughout. She had cortical thumbs as well as palmar and plantar grasp reflexes. She moved all extremities spontaneously. Occasionally, she exhibited lip smacking and bicycling movements of the lower extremities as well as extensor posture of the extremities.
Case 2—Traumatic Brain Injury A 2-year-old boy with no significant medical history sustained a traumatic brain injury when a thick tree branch falling from several stories high struck him on the head. He had immediate loss of consciousness but did not have seizures or a cardiac arrest. He was intubated by emergency medical personnel and brought to the emergency department. On the initial examination he was unresponsive to voice and painful stimuli. His right pupil was reactive and his left pupil was dilated with minimal reactivity. Corneal reflexes were present, and he had a weak cough and gag. Head CT showed extensive calvarial and skull base fractures, left frontal subdural and subarachnoid hemorrhages, and small left lateral intraventricular hemorrhage. A CT angiogram of the brain was normal. Over the next several days his intracranial pressure was well controlled with sedation and hyperosmolar therapy; infrequent subclinical seizures were managed with levetiracetam. He required mechanical ventilation and had no major hemodynamic or respiratory complications. He was tolerating full nasogastric feeds. Brain MRI scan demonstrated multicompartmental intracranial hemorrhage with bilateral supratentorial and infratentorial small subdural collections, subarachnoid hemorrhage, intraventricular hemorrhage, and hemorrhagic contusions in the frontal and the temporal lobes. Widespread changes from diffuse axonal injury were apparent, including hemorrhage and restricted diffusion in the superolateral midbrain and cerebellar vermis, likely owing to Duret hemorrhages secondary to compression against the tentorial incisura at the time of injury. His examination approximately 10 days after injury demonstrated no spontaneous eye opening and no purposeful interaction with his environment. Cranial nerves were intact, except a persistent traumatic left dilated and nonreactive pupil. His extremities moved spontaneously and in response to painful stimuli, more vigorously on the left, with intermittent bilateral extensor posturing that had no EEG correlation.
Introduction Neurologic outcome prediction after severe brain injury is one of the most difficult tasks neurologists and intensivists face, and this process is filled with a unique set of clinical and ethical challenges. With the advancement of technology and clinical practices in critical care and neurology aimed at preserving and restoring neurologic function, prognostication has evolved from estimating the probability of survival to the more complicated task of predicting functional recovery. Despite limited outcome data and inevitable prognostic uncertainty, neurologists are often compelled to make management recommendations and counsel parents about the potential for neurologic recovery when a child remains critically ill. The cases presented in this article describe children with severe brain injury and resultant disorders of consciousness from 2 different mechanisms—hypoxic-ischemic injury secondary to cardiac arrest and traumatic brain injury. Although the etiologies of the brain insults are quite different, the clinical status of the children at the conclusion of these vignettes is comparable. However, the projected recovery may be quite divergent based solely on injury mechanism. Using these cases as a backdrop, we address the importance of making the correct diagnosis in a patient with a disorder of consciousness after severe brain injury and discuss some of the challenges in deducing an accurate prognosis in these situations. We then explore some of the clinical and ethical challenges relating to the obligations of physicians to inform families about the predicted trajectory of neurologic recovery after severe brain insult and discuss how the certainty of a prognosis may appropriately or inappropriately influence clinical management decisions. Finally, we examine the potential effect of new technologies, specifically advanced functional neuroimaging, on our current and future prognostic abilities.
Making the Correct Diagnosis The adage often quoted by medical ethicists—“good facts make good ethics”— aptly applies to children after severe brain injury and a disorder of consciousness. Consciousness comprises 2 clinical components—wakefulness and awareness of one’s self and the environment.1 A disordered state of consciousness, which can vary from acute and transient to irreversible and permanent, results when 1 or both of these components are compromised. Disordered states of consciousness are a spectrum of clinical syndromes that encompass a range of cognitive dysfunction, from confusional states such as delirium, to vegetative and minimally conscious states, coma, and locked-in syndrome.2 Although the diagnosis of these syndromes can be significantly more challenging in infants and children, it is essential to properly identify both the etiology of brain injury and the correct disorder of consciousness syndrome before attempting to prognosticate recovery. The etiology of the impaired consciousness is easily identified in the vignettes presented
Ethical issues in neuroprognostication earlier; however, it is not always as apparent and occasionally requires extensive diagnostic testing. Given the clinical and ethical implications for prognosis and management decisions, determining the extent of a child’s impaired consciousness should be completed meticulously. The assessment should be completed in a standardized manner, under conditions that maximize opportunities to observe responsiveness, and repeated over time. Careful considerations should be given to the published criteria that differentiate the subtleties of these disorders.2-5 As many as 40% of adult patients admitted to rehabilitation centers have been incorrectly diagnosed as a vegetative state, and patients in locked-in states have also erroneously been deemed unconscious.6-8 Although evaluating a brain-injured child for a disorder of consciousness is challenging, the Child Neurology Society and the American Academy of Neurology have published guidelines on the medical aspects of the persistent vegetative state.9 Additionally, a survey of child neurologists found that greater than 90% believe that a diagnosis of vegetative state could be made in children aged 2 years or older, 70% thought this diagnosis could be made in children aged 2 months to 2 years, and 16% believed that this applied to infants younger than 2 months.10 The children described in the vignettes presented here were both initially in a coma—an eye-closed pathologic state of unresponsiveness from which individuals cannot be aroused to wakefulness by stimuli. The comatose state after brain insult typically lasts for a few weeks and then individuals naturally progress into a state of eye-open wakefulness without awareness, called a vegetative state. The term persistent is typically applied when the vegetative state lasts more than a month. A persistent vegetative state is considered permanent 12 months after traumatic brain injury and 3 months after nontraumatic injury because of the high degree of certainty with which the irreversibility of the brain insult and resultant clinical manifestations can be determined at those points. The 4-month old with hypoxicischemic injury (case 1) was in a vegetative state 1 week after her injury, whereas the 2-year old (case 2) was still in a coma 10 days after his traumatic brain injury. Children can improve over time from a vegetative state to a minimally consciousness state—a chronic state of poor responsiveness to stimuli, but one in which patients demonstrate evidence of awareness of themselves and their environment.5
Deducing an Accurate and Timely Prognosis The first questions universally asked by family members after a child sustains brain injury are about the probability of survival and the chances for good neurologic recovery. For physicians, generating and communicating an accurate and timely prognosis is essential to establishing the goals of care and directing clinical care. An overly optimistic prediction may result in survival of a neurologically devastated child, whereas an overly pessimistic prediction may lead to
189 withdrawal of life-sustaining therapies in a child with a potentially good functional outcome. Although the answer to this inevitable prognosis question should be evidenced based whenever possible, prognostication is highly complex, and no single objective clinical, laboratory, imaging, or neurophysiological test or biomarker reliably predicts neurologic outcome, especially early after a severe brain insult.11,12 Outcome assessments are dependent on a multitude of patient-related factors such as age and preexisting medical conditions, injury-related factors including the etiology, location, and extent of the brain injury, and other associated organ system compromise. Assessments are also influenced by physician-related factors such as age, clinical experience, and medical specialty.13-15 Occasionally, it is reasonable to specify expected functional deficits based on the neuroanatomical pattern of injury (eg, motor and language impairments after a left middle cerebral artery stroke); however, it is often difficult, especially if the child has underlying neurodevelopmental delays, to predict performance in precise domains such as communication, feeding, and ambulation. Establishing preinjury neurologic baselines for patients is essential, as the same brain injury can have widely different implications for recovery depending on whether a child was previously healthy, has a chronic neurologic or developmental condition, or has a progressive neurodegenerative disease. Additionally, using existing outcome data can be challenging in clinical practice, as many of the predictive features are too coarse to guide individual patient management, specifically in pediatric patients, where the variability of injury is high, neurodevelopmental factors must be considered, and the data are more limited. A further complication preventing generalizability of existing data is that many of these studies use mortality as the outcome measure; however, the frequency of withdrawal of lifesustaining therapies is often not reported. Unlike other conditions, pediatric outcome data do exist for hypoxic-ischemic injury secondary to cardiac arrest (case 1) and traumatic brain injury (case 2), and this information can help guide recovery predictions. For children who had a cardiac arrest and achieved sustained return of spontaneous circulation, a favorable neurologic outcome is observed in approximately 5% of them after out-of-hospital cardiac arrest and 15%-45% after in-hospital cardiac arrest.16-20 Outcomes after severe TBI, although variable, are generally better than after cardiac arrest, and substantial recovery after TBI is often appreciated between hospital discharge and outcomes measured 6 months to several years after injury.2124 Some data indicate that at several years after the injury, and after extensive rehabilitation, 60% of survivors with TBI perform scholastically on par with their similar-aged peers and more than 80% are independent in activities such as feeding and mobilization.21 Factors such as a low postresuscitation Glasgow Coma Scale score and refractory increased intracranial pressure are still strongly associated with death and poor functional outcomes.22 Most of the prognosis literature is geared toward evaluating the effectiveness of particular metrics in predicting
190 outcome, whereas few studies have examined the accuracy of outcome prediction by clinicians and the ways in which physicians prognosticate. A recent study of outcome prediction in an adult neurointensive care unit found that neurointensivists correctly predicted 6-month functional outcome in 80% of patients with acute brain injury at approximately 4 days after the injury.14 Physicians had better accuracy for predicting poor outcomes over good outcomes, even after excluding patients who had lifesustaining therapies withdrawn. Our group recently evaluated the accuracy and timing of neurologic outcome predictions after pediatric cardiac arrest by both pediatric intensivists and neurologists.25 Prediction accuracy improved over the first week of care from 75% to 85% and was not significantly different between the 2 physician specialties. Interphysician prognosis agreement also improved over time for both physician groups from moderate to substantial levels. Similarly, outcome prediction confidence also improved over the first week of care for both physician groups and interestingly, increased regardless of whether prognoses were accurate or inaccurate. In the aforementioned study, we also examined which factors (ie, cardiac arrest characteristics, neurologic examination, MRI, and EEG) most strongly influenced physician outcome predictions for children after cardiac arrest. Both neurologists and intensivists reported that the most influential factor for prognostication was the patient’s physical examination. Other important factors were the brain MRI scan and EEG for neurologists and the cardiac arrest characteristics and brain MRI scan for the intensivists.25 Given the weight physicians place on the neurologic examination in prognosticating about recovery, neurology and critical care training programs should ensure that appropriate education is provided on conducting and interpreting the neurologic examination in critically ill brain-injured children.26-28 Further research is needed to determine how effective conventional neuroimaging29 and electrophysiological30,31 modalities are in assisting physicians to accurately predict neurologic outcome after cardiac arrest and other acute brain injuries.
Medical Decision Making After Severe Brain Injury Parents or guardians are usually the presumed authorized decision makers for their children who have sustained a severe brain insult. Unlike previously competent adults who may have expressed their wishes for what they would want if permanently unconscious, most children have not developed the decision-making capacity necessary to make such choices. Therefore, surrogates cannot use substituted judgment when making decisions for their children. Instead, they are expected to consider what is in their child’s best interest. This privilege is questioned only if parents are abusive or neglectful, which can occur if the brain injury is secondary to abusive head injury or nonaccidental trauma. Although the best interest standard appears straightforward
M.P. Kirschen and J.K. Walter and may be objectively determined, the fact that physicians and families often make different assessments of what is in a child’s best interest uncovers that there are many values imported into these assessments.32 Some individuals may value the physical presence of an individual, even if they are minimally interactive, whereas others prioritize a meaningful interaction with the hope of independence for their child. Although there may be consensus that it is in the interest of a child to not be in pain, there is no consensus about whether doing interventions to sustain a child in a vegetative or minimally conscious state is in the child’s best interest.
Physician Obligations to Support Parental Decision Making Physicians have several intertwined ethical obligations in supporting parental decision making while caring for children with acute brain injury. Their obligations are to first communicate, to the best of their ability, the nature of the brain insult, the potential and time frame for neurologic recovery, and their certainty in achieving the predicted functional state. Second and equally as important, physicians must elicit the families’ values and priorities for their child, concerns as caregivers, and what they would deem an acceptable quality of life for their child. The physician can then help design and implement a care plan that is mutually agreed upon that is most consistent with the family’s values for its child. This shared decision-making model encourages ongoing dialogue between the physician and a child’s family, and it has been endorsed by many professional organizations and the Institute of Medicine.33-35 Although this approach may seem straightforward, this process hinges on (1) being able to clearly elucidate parental values for their brain-injured child, (2) prognostic accuracy and certainty on the part of the physician, and (3) the ability of physicians to effectively communicate the prognostic information to the family. These components can have a profound influence on decisions regarding goals of care and clinical management, especially when prognostic information is fraught with a myriad of uncertainties.
Ascertaining Family Values for the Child Families of critically ill children are, understandably so, emotionally overwhelmed and struggling to navigate a highly complex system of care. The high rates of posttraumatic stress disorder experienced by parents of children who have been in the pediatric intensive care unit make apparent the strain they are under when being asked to make decisions for their children.36 Having these important conversations with families is therefore incredibly challenging and requires preparation and skill. Although some theories of decision making prioritize a purely rational approach to decisions, many more nuanced theories of decision making acknowledge the inherent emotional aspects of the process.37 Therefore, intensivists and neurologists should be prepared and equipped to acknowledge the
Ethical issues in neuroprognostication emotional experience of families and in many circumstances adjust the language they use while eliciting what is important to the family. Open-ended questions such as “what does it mean to be a good parent to your child now,” “what wishes or hopes do you have for your child,” or “what are you worried about” can initiate a conversation that offer invaluable information about which values families are prioritizing.
Managing Prognostic Uncertainty Families hope for prognostic certainty to guide medical decision making for their severely brain-injured child. Unfortunately, there is an unavoidable inherent uncertainty in any functional outcome prediction offered by physicians. It is often how physicians handle and communicate this uncertainty that drives clinical recommendations and decision making. It is the nature of some physicians to emphasize uncertainty, and this may correlate with a physician’s level of medical training or clinical experience.38,39 In one study, less-experienced physicians were more optimistic about a patient’s functional outcome, less certain of their outcome prediction, and felt that quality-oflife assessments were too subjective to comment on and best left to the prerogative of the patient’s family.13 This may be because physicians trained in recent decades frequently believe that being respectful of patients’ autonomy requires that they not offer a recommendation for treatment in order to avoid the appearance of paternalism.37 Physicians often recognize that the degree of prognostic certainty they express may influence the subsequent care decisions made by a child’s family. In some circumstances, this leads physicians to avoid any claim of certainty to avoid directing care, and in other instances, physicians may use this claim of certainty to influence the outcome that aligns with their perceived best interest for the patient. At least in 1 study, prognostic certainty improved over time after injury, independent of prognostic accuracy.25 Most physicians have instances in their career where their outcome prediction was worse than the patient’s actual outcome, sometimes even recommending withdrawal of lifesustaining therapies for a patient who recovered with reasonable neurologic function. It is not uncommon for these rare but memorable patients to influence the certainty or confidence with which prognoses are shared with families, even if contrary to the published evidence and guidelines. Some of these patients, like the case of Terry Wallis who began speaking after being in a minimally conscious state for nearly 20 years following a traumatic brain injury, are publicized in the popular press and reinforce the hope that families have for their braininjured children.40 The converse situations also exist where an overly optimistic recovery trajectory was outlined for a family and the patient’s residual neurologic function was minimal. These notable experiences for physicians, combined with other personal characteristics such as gender, ethnicity, and religious or cultural beliefs, form the implicit bias that physicians bring to any prognostic encounter.
191 A recommended approach to dealing with the uncertainty of prognosis is to normalize the uncertainty of prognosis, to address the family’s emotions about this uncertainty, and to encourage families to focus on the present and not primarily on wishing they knew what the future would bring.41 Physicians must respect the autonomy of parental decision making and ensure that when providing neuroprognostic information and potential treatment options, recommendations for these care plans are consistent with the families’ goals and values for their child. For example, if a child (as in case 1) is in a vegetative state after a cardiac arrest, and the physician with a high degree of certainty predicts that the child will not have further neurologic recovery, recommendations regarding treatment decisions must be consistent with the families’ stated values for that child. If on one hand the family believes that living in a vegetative state is not consistent with what they perceive is a good quality of life, it is appropriate to recommend goals of care that minimize pain and suffering, and consider limiting or withdrawing life-sustaining therapies. If on the contrary, the family is elated that their child is still alive after cardiac arrest and insists on pursuing all options to keep the child alive, discussing withdrawal of support may not be helpful and could strain an already fragile physician-family relationship. Instead, recommendations should focus on topics such as nutrition and control of seizures and spasticity. In these instances, where the family prefers to maximize therapy independent of neurologic prognosis, providing an outcome prediction may still be helpful in setting recovery expectations, rather than deciding on limitations of care. Although the complexity of these situations can grow exponentially, especially in situations where the certainty of an outcome prediction is low or neurologic improvements are expected but may not be apparent for several months (eg, TBI, case 2), the central tenant of focusing clinical care decisions so that they are aligned with the goals of values of a family for their child must be preserved.
Effective Communication With Families Information about neurologic recovery may be precise and definitive as in the case of brain death, or encompass a broad spectrum of functional possibilities. Likewise, it is also important to recognize that different parents may have variable information needs regarding their child’s condition and prognosis. Families should be queried about the nature of the information relating their child’s brain insult and recovery potential they wish to receive. Some may need precise outcome percentages or want to review the scientific data themselves, whereas others prefer summary statements or no information at all, and just the physician’s treatment recommendations. Physicians should be cautious of how they frame the decisions to be made for a child because how these conversations are conducted could bias many components of an encounter with a child’s family. It is important to recognize and plan for how to discuss questions relating to a child’s neurologic baseline, the presentation of outcome statistics, and discussions regarding parental values and treatment preferences.42,43 For example, in eliciting a family’s preferences regarding “do-not-resuscitate” status,
192 responses may vary depending on parental emotional and informational needs at the time and whether the information (and emotional support) provided is aligned with such needs. Even families who are clear about the goals they have for their child value hearing from the medical team that they are making a loving choice for their child. The language and communication strategies used by physicians when discussing outcome and prognostic information can have a profound influence on decisions regarding clinical management including withholding or withdrawing life-sustaining therapies. How physicians communicate prognoses to other health care providers and families is highly variable, and it is unclear how effectively the underlying messages are being received and interpreted.44 Additionally, the use of effective communication strategies (ie, being emotionally supportive or adopting an empathic manner) to communicate prognoses to families has been shown to help reduce anxiety and improve information recall, particularly for prognostic information.45 Research is needed to further characterize the most effective language and communication strategies used when discussing neuroprognostic information, so these can be distributed and taught to physicians engaged in this process.
Window of Opportunity for Treatment Withdrawal Many patient, family, and physician factors can influence the timing of clinical decisions after severe brain injury. For example, a critical period of physiological instability often exists, during which time withholding or withdrawal of lifesustaining therapies has a high likelihood of leading to death. This period is sometimes referred to as the “window of opportunity” and typically lasts several days, but it can extend longer.46,47 Unfortunately, both evidenced-based prognostic tests and clinical experience have lower prognostic certainty during this window.11,25 If treatment decisions are delayed past this window, greater prognostic certainty can be achieved, but the child may no longer require these life-sustaining interventions (eg, mechanical ventilation and inotropic support) and survive with profound neurologic injury even if the family opts to limit further intensive care. Complicating this situation are evolving therapies aimed at neuronal protection after brain insult (eg, therapeutic hypothermia), and prognosticating before the completion of these types of therapy may contribute to inappropriate decisions to limit care.15 This initial window of opportunity for treatment limitation is an important consideration for some physicians, particularly for children with hypoxic-ischemic injury, where outcome data are more robust. However, it can also apply to other types of brain injury such as severe traumatic brain injury, although prognostic uncertainty is usually greater in these instances, making management decisions during this period more complex. Although it is appropriate for physicians to consider the window of opportunity during post–brain injury goals of care conversations, families should not be pressured into making treatment decisions during this window, especially if the prognostic
M.P. Kirschen and J.K. Walter certainty is low. Understandably, many families are hopeful for a better-than-expected recovery or not emotionally ready to make such an irreversible decision in this crisis period. Strongly recommending a decision during this time frame can fracture the fragile physician-family relationship and lead to further challenges in providing optimal care for the child. Physicians should appreciate and be reassured that this stated “window of opportunity” of physiological instability is not the only opportunity families have to limit or withhold medical therapy to avoid care that is inconsistent with the family’s values or that causes the child pain and suffering. As part of the ongoing discussions between the medical care team and the family, the family’s values for the child can be used to establish overarching goals of care and treatment parameters for future illnesses, surgical procedures, and hospitalizations, to name a few. In many circumstances, what parents initially value (preserving their child’s life) may shift over time if they perceive their child to suffer from repeated hospitalizations or procedures and they start to prioritize other goals (protection from suffering). For children who are in a permanent vegetative state or other conditions that permanently lack conscious awareness and the ability to interact with the environment, options such as withdrawal of artificial hydration and nutrition are ethically permissible and consistent with American Academy of Pediatrics ethical guidance.48
When Physicians and Families Disagree It is not uncommon for physicians and families to have diverging views on the aggressiveness of care for children after severe brain injury. If a child’s prognosis is to survive in a neurologically devastated state, many physicians trying to protect their patient from perceived harm and persistent suffering would recommend withdrawal of life-sustaining therapies. Parents may maintain hope for recovery, holding tightly to the small degree of uncertainty in the prognosis or case reports of miraculous recoveries, and request continued aggressive care. The authors of several studies have documented differences in attitudes between medical professionals and parents regarding treatment plans for children with severe neurologic impairment. In one study, the authors found that health care professionals thought a childhood of profound neurologic impairment was worse than death.49 On the other end of the spectrum, rarer situations arise where a child has relatively minor brain injuries and a prognosis with mild neurocognitive sequelea; however, the parents feel that any degree of neurologic compromise is unacceptable and want to discontinue life-sustaining therapies (presuming intensive cardiorespiratory support is required for other concurrent systemic injuries). In these challenging situations, physicians have a responsibility to acknowledge that we have our own values and that they may be different from the values of any given family. Our obligation is to ensure that the values of the family are respected in clinical care decisions, particularly if the treatments being offered do not cause suffering to the patient. Consultation by an interdisciplinary ethics consultation service or palliative care team may be helpful if
Ethical issues in neuroprognostication physicians are uncomfortable providing care that, although consistent with the family’s values, may be perceived to be causing harm or contributing to suffering. These conversations should not be limited to discussions of end-of-life issues but should include strategies for improving the child’s quality of life, treating pain or other distressing symptoms (eg, seizures, spasticity, impaired secretion management, or constipation), and attending to other emotional or social needs of the child, caregivers, and family.
Effect of New Technologies Emerging technologies, specifically advanced functional neuroimaging modalities such as positron emission tomography and functional MRI are transitioning from the research setting into clinical care and are positioned to have a significant effect on neuroprognostication after severe brain injury.50-52 These techniques may contribute helpful information to aid in neurologic diagnosis and prognosis, particularly for patients with severe brain insult and a resultant disorder of consciousness. However, they may also contribute further to the uncertainty of the neuroprognostication process, which could affect discussions with families about goals of care and clinical management strategies. The authors of several functional neuroimaging studies have examined patients in vegetative and minimally conscious states and demonstrated functional activation patterns consistent with preserved awareness and in some cases, more complex language and cognitive functions.53-57 A subset of these patients subsequently showed evidence of clinical improvement by demonstrating awareness after several months. The authors of a single pediatric case report describe a 7-year-old girl who sustained traumatic and hypoxic brain injuries when she was 18 months old. She was noncommunicative and displayed minimal behavioral signs of awareness of self and others (probable diagnosis of minimally conscious state).58 Functional MRI demonstrated activation of language networks in response to personally relevant stimuli (patient’s own name and familiar voice), suggesting that some of her higher-level cortical cognitive processing could be intact. Being able to detect covert awareness using these neuroimaging techniques may alter the diagnostic criteria for disorders of consciousness, improve prognostic accuracy and confidence, and even facilitate communication with seemingly unresponsive patients. As the technology improves, these examinations may be able to provide assessments of levels of pain or discomfort and even express an individual’s wants and needs. Some have questioned whether it is ethical to withdraw or withhold life-sustaining therapies including artificial hydration and nutrition if a functional MRI scan provides evidence of consciousness or awareness.59,60 Although this evolving functional neuroimaging literature is promising and will hopefully help to reduce diagnostic and prognostic uncertainty in the future, it currently resides in the research domain. Physicians should be prepared that
193 some families may request these tests to be performed on their children as they struggle with care decisions resting on whether their child is conscious and the probability of recovering awareness, meaningful responsiveness, and other basic neurologic functions.61 It is noteworthy that the parents of the boy in case 2 requested a functional brain scan to help predict outcome potential. Physicians must proceed with caution before these technologies are fully vetted and validated through extensive research and experience and transitioned into mainstream clinical practice.52 As their use becomes more widespread, partnering with families and elucidating specific goals and values for their child will be even more important in guiding medical decisions and clinical care.
Conclusions At the time of the writing of this article, the 4-month old with hypoxic-ischemic brain injury from a cardiac arrest (case 1) is now 6 years old and continues to be followed up at our institution. She has a chronic static encephalopathy and is in a permanent vegetative state. She is severely microcephalic (o third percentile) and opens her eyes spontaneously and to stimulation, but she does not fix on or follow objects. She does not purposefully interact with her environment although she has occasional episodes of smiling or crying. She is nonverbal, nonambulatory, and unable to sit unassisted. She has severe global hypertonia and spasticity and is dependent on a gastrostomy tube for nutrition. She has refractory epilepsy and is on several antiepilepsy medications and requires medication to relieve spasticity. She is not currently in school and has home nursing support. This condition is congruent with the prognosis offered by her physicians after her cardiac arrest. The family continues to be appreciative of the life-saving medical care she received and values that she is alive and a part of their family. She has had several hospital admissions for respiratory illnesses, some requiring invasive mechanical ventilation, and the family has declined any limitations of care. The 2-year old who sustained a severe traumatic brain injury from a falling tree branch (case 2) is now approximately 1 month after the injury and continues with inpatient rehabilitation, demonstrating signs of improvement on a daily basis. He transitioned first from coma to a vegetative state and now resides in a minimally conscious state. He currently opens his eyes spontaneously and to commands and is intermittently able to track objects. He is able to hold his head up and intermittently follows simple commands. He is unable to sit unassisted and is nonverbal. He is being fed via a nasogastric tube. The medical team, including intensivists, neurologists, and rehabilitation specialists, had extensive discussions with the family about the uncertainty of his prognosis and the variability in TBI outcomes. The family is generally optimistic and hopeful, encouraged that he continues to make improvements, and understands that the recovery process may take numerous
194 months, will require intense therapy, and his eventual level of functioning is uncertain. Physicians have an ethical obligation to support parental decision making for their child after a severe brain injury. This obligation includes several different components. To the extent possible, physicians should confer a timely and accurate diagnosis and prognosis, acknowledging that it is common to have uncertainty in prognosis and that it may be upsetting. Equally importantly, physicians should elicit the values that parents have for their child, which can serve as the foundation for determining goals of care and treatment options. Physicians must remember the importance of respecting the autonomy of parental decision making and ensure that care plans are consistent with the families’ goals and values for their child. In some circumstances, physicians will find that families’ goals are not consistent with what they themselves would have chosen, but in most circumstances, the families’ values are given priority. These alreadydifficult discussions surrounding neuroprognostication after brain injury will become only more challenging with the introduction of functional neuroimaging technologies that may be able to help elucidate covert awareness or cognitive function in a seemingly comatose child. In these circumstances, such as those at present, clear and compassionate communication about what is known and unknown is central to supporting parental decision making.
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