Clinician Distress with Treatments at the Frontier of Mortality

Over the past 50 years, advancements in pediatrics have transformed many infant and childhood disorders from lethal to treatable conditions.1Horbar J.D. Badger G.J. Carpenter J.H. Fanaroff A.A. Kilpatrick S. LaCorte M. et al.Trends in mortality and morbidity for very low birth weight infants, 1991-1999.Pediatrics. 2002; 110: 143-151https://doi.org/10.1542/peds.110.1.143Crossref PubMed Scopus (633) Google Scholar, 2Mahle W.T. Spray T.L. Wernovsky G. Gaynor J.W. Clark B.J. Survival after reconstructive surgery for hypoplastic left heart syndrome.Circulation. 2000; 102: 111-136https://doi.org/10.1161/circ.102.suppl_3.III-136Crossref Google Scholar, 3Rasmussen S.A. Wong L.-Y.C. Yang Q. May K.M. Friedman J.M. Population-based analyses of mortality in trisomy 13 and trisomy 18.Pediatrics. 2003; 111: 777-784https://doi.org/10.1542/peds.111.4.777Crossref PubMed Scopus (322) Google Scholar The medical and surgical interventions that enabled this progress have often, at the outset, generated considerable ambivalence and distress among clinical team members.4Muraskas J. Marshall P.A. Tomich P. Myers T.F. Gianopoulos J.G. Thomasma D.C. Neonatal viability in the 1990s: held hostage by technology.Camb Q Healthc Ethics. 1999; 8: 160Crossref PubMed Scopus (38) Google Scholar Current advances in therapeutics face these persistent challenges.5Boss R.D. Holmes K.W. Althaus J. Rushton C.H. McNee H. McNee T. Trisomy 18 and complex congenital heart disease: seeking the threshold benefit.Pediatrics. 2013; 132: 161-165https://doi.org/10.1542/peds.2012-3643Crossref PubMed Scopus (30) Google Scholar,6Munson D. Withdrawal of mechanical ventilation in pediatric and neonatal intensive care units.Pediatr Clin North Am. 2007; 54 (xii. https://doi.org/10.1016/j.pcl.2007.08.001): 773-785Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar Given the acceleration in the development of novel targeted therapies, deepening our understanding of the general situation that gives rise to this distress—emotional as well as moral—and how to better address the distress is warranted.7Nogrady B. Rapid progress transforms ideals of health.Nature. 2019; 569: S6-S7https://doi.org/10.1038/d41586-019-01438-6Crossref Google Scholar,8Gottlieb S. The quickening pace of medical progress and its discontents. Forbes n.d.https://www.forbes.com/sites/scottgottlieb/2015/06/17/the-quickening-pace-of-medical-progress-and-its-discontents/Date accessed: January 3, 2022Google Scholar We use the term frontier treatments to describe innovative treatments that have the potential to render a recently fatal disease treatable. At our institution, the treatment of patients with congenital or acquired lymphatic disorders is a current example of a frontier treatments that has generated distress among our staff. In this Commentary, we present a composite case of a patient with congenital lymphatic dysfunction, representing several key themes noted among similar cases from our institution. Our group of authors, comprising neonatologists, lymphatic experts, ethicists, and a neonatal nurse, examine reasons for providing frontier treatments, outline reasons for distress, and suggest ways to better support teams in caring for patients with diseases that until recently were considered fatal. A baby born at 36 weeks of gestation has bilateral pleural effusions and large volume ascites. He is stabilized on mechanical ventilation with bilateral chest tubes and a peritoneal drain. Drainage fluid is consistent with lymph. He undergoes a contrast-enhanced magnetic resonance lymphangiogram, which reveals no connection between his venous and lymphatic systems. His thoracic duct is obstructed, and lymph collects in his skin, causing diffuse anasarca that worsens daily until his facial features are hard to discern. He is diagnosed with congenital central lymphatic flow disorder. A surgeon incises his left flank and lymph begins to drain, and his anasarca quickly improves. He seems to be more comfortable, and his many caretakers are relieved. The incision matures into a lymphocutaneous fistula, but the outlet obstructs with fibrin every few hours and must be manipulated with forceps in a gentle opening motion to restore outflow. Although technically simple, each manipulation causes the patient pain, and clinicians avoid the procedure. Nurse practitioners and surgical fellows dispute who should do the manipulations. Eventually, the fistula closes irreversibly, and the patient's anasarca worsens. He is taken to the operating room and his thoracic duct is connected to a large vein, creating a lymphovenous anastomosis. Unfortunately, the procedure is ineffective, and the surgeons must create another incision in his skin for drainage, although they know this too will only temporize. The lymphatics team plans for a second procedure to create a more permanent, although novel, type of lymphovenous connection. His parents are distressed, but remain hopeful that this procedure will improve his condition. Rumors circulate that this procedure has not been done in humans and some clinicians describe the procedure as an experiment. Some members of the team question whether there is any chance of survival. A nurse at bedside says, “I feel like I am not upholding my duty to provide comfort and healing when I am required to provide hands-on care to a baby this uncomfortable.” Beneath the distress of the team described here lies a central question: should we continue to offer invasive care for this patient? When considering frontier treatments, like all clinical care, teams must balance anticipated benefits and harms and ensure that both clinicians and families make informed decisions.9Riskin A. Erez A. Foulk T.A. Kugelman A. Gover A. Shoris I. et al.The impact of rudeness on medical team performance: a randomized trial.Pediatrics. 2015; 136: 487-495https://doi.org/10.1542/peds.2015-1385Crossref PubMed Scopus (190) Google Scholar,10McCulloch P. Altman D.G. Campbell W.B. Flum D.R. Glasziou P. Marshall J.C. et al.No surgical innovation without evaluation: the IDEAL recommendations.Lancet Lond Engl. 2009; 374: 1105-1112https://doi.org/10.1016/S0140-6736(09)61116-8Abstract Full Text Full Text PDF PubMed Scopus (1277) Google Scholar For the patient described here, the team used a systematic process to maximize benefit and minimize risk throughout treatment and particularly as surgeons planned to create a novel lymphovenous connection that they believed better suited this patient's anatomy. The proposed surgery was similar to more proven techniques. The surgeons and lymphatics specialists thought it was likely to succeed. To minimize risk, the surgical team reviewed and excluded all more studied and routine courses of treatment. The lead surgeon prepared extensively and practiced the procedure on animal models. However, this situation leads to a question: when individual surgeons propose procedures, who should judge whether expected benefits sufficiently outweigh risks? Surgical innovation is unique in that it is not governed by a federal regulatory process, unlike pharmaceutical and medical innovation, which are regulated by the US Food and Drug Administration.11Reitsma A.M. Moreno J.D. Ethical regulations for innovative surgery: the last frontier?.J Am Coll Surg. 2002; 194: 792-801https://doi.org/10.1016/s1072-7515(02)01153-5Crossref PubMed Scopus (0) Google Scholar Interventional physicians must self-regulate their innovations, and several frameworks have been proposed to facilitate this process.10McCulloch P. Altman D.G. Campbell W.B. Flum D.R. Glasziou P. Marshall J.C. et al.No surgical innovation without evaluation: the IDEAL recommendations.Lancet Lond Engl. 2009; 374: 1105-1112https://doi.org/10.1016/S0140-6736(09)61116-8Abstract Full Text Full Text PDF PubMed Scopus (1277) Google Scholar,12Schwartz J.A.T. Innovation in pediatric surgery: the surgical innovation continuum and the ETHICAL model.J Pediatr Surg. 2014; 49: 639-645https://doi.org/10.1016/j.jpedsurg.2013.12.016Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Decisions about invasive interventions also must incorporate consideration of associated novel medical care, such as the complex fluid management required for a patient continuously losing lymphatic fluid. In this case, the lymphatic team called a meeting of a standing oversight committee. This oversight committee, established at the initiation of the lymphatic treatment program, is composed of senior scientists and clinicians at our institution who are not directly involved in the program. The committee was developed to oversee innovative treatments and ensure judicious clinical reasoning for activities that do not constitute human subjects research and are, therefore, outside the purview of the institutional review board. Similar committees have been effectively used to regulate other programs of innovative therapy that do not qualify as research at our institution, including the fetal therapy program. The committee meets regularly to review cases and additionally if needed for time-sensitive decisions. The committee then provides recommendations to the involved clinicians. Based on the available data and their collective expertise, the committee in this case determined that the proposed procedure was likely to be technically successful and, if so, had an approximately 50% chance of improving the patient's lymphatic flow, although the degree of improvement was uncertain. This assessment supported offering the treatment to the patient's family. Although the clinical team must determine whether a frontier intervention is sufficiently justifiable to be offered, ultimately the parents of pediatric patients should decide whether to proceed with the intervention. Frontier treatments, which by definition are innovative and uncertain, fall within the zone of parental discretion, where parents should be supported in choosing or declining the new intervention and palliative care is a valid, valuable alternative.13Gillam L. The zone of parental discretion: an ethical tool for dealing with disagreement between parents and doctors about medical treatment for a child.Clin Ethics. 2016; 11: 1-8https://doi.org/10.1177/1477750915622033Crossref Scopus (139) Google Scholar In this case, the medical team discussed the novel surgical procedure and the overall decision to continue invasive care extensively with the patient's parents. The parents reaffirmed through repeated conversations that they understood the unproven nature of the particular surgery and the overall care plan, as well as the uncertainty of their son's prognosis. They spent many hours at their son's bedside and acknowledged the physical pain he had intermittently experienced. When asked about the limits of acceptable suffering, the parents elected a time-limited trial, stating that they would redirect toward comfort care if their son's physical condition had not improved considerably in 2 months. The parents agreed to continue an open dialogue with the medical team about both improvement and suffering. Although we present a composite case in which the individual medical characteristics justified frontier treatments and parents elected them, the risks, benefits, and family values will balance differently in many other cases. Strategies for supporting clinicians and parents through palliative care are equally important, but beyond the scope of this article. One final consideration, societal benefit, warrants discussion. Frontier clinical care is distinct from research. The goal of frontier clinical care is to provide a benefit, which is deemed to be plausible for a specific individual, whereas the goal of clinical research is to generate new knowledge and thereby promote broader medical advancement.14Lantos J. Ethical issues. How can we distinguish clinical research from innovative therapy?.Am J Pediatr Hematol Oncol. 1994; 16: 72-75PubMed Google Scholar Although the 2 categories of treatment often have overlapping outcomes—therapeutic treatment has the potential to advance research and research has potential to benefit patients—the differing goals have important implications for oversight. The motivation of clinical innovators, who lead the development of new treatments, to drive medical progress creates a potential conflict of interest. In this situation, oversight mechanisms, such as the external oversight committee described here, are important in ensuring that frontier treatments have roots in the expected benefit to the individual patient. Nevertheless, frontier treatments can, and have, incrementally improved outcomes. Using the example of lymphatic disorders, 20 years ago, severe lymphatic disorders were almost always fatal and available treatments aimed to manage symptoms rather than change the disease processes.15Williams M.S. Josephson K.D. Unusual autosomal recessive lymphatic anomalies in two unrelated Amish families.Am J Med Genet. 1997; 73: 286-289https://doi.org/10.1002/(SICI)1096-8628(19971219)73:3<286::AID-AJMG11>3.0.CO;2-FCrossref PubMed Scopus (14) Google Scholar, 16Bengtsson B.-O.S. Neonatal lymphatic (chylous) disorders.NeoReviews. 2013; 14: e600-e612https://doi.org/10.1542/neo.14-12-e600Crossref Scopus (8) Google Scholar, 17Bouchard S. Di Lorenzo M. Youssef S. Simard P. Lapierre J.G. Pulmonary lymphangiectasia revisited.J Pediatr Surg. 2000; 35: 796-800https://doi.org/10.1053/jpsu.2000.6086Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar In contrast, a recent case series described the successful management of patients with central lymphatic flow disorder, the most generalized and severe group of lymphatic disorders.18Pinto E. Dori Y. Smith C. DeWitt A. Williams C. Griffis H. et al.Neonatal lymphatic flow disorders: impact of lymphatic imaging and interventions on outcomes.J Perinatol. 2021; 41: 494-501https://doi.org/10.1038/s41372-020-00771-3Crossref PubMed Scopus (11) Google Scholar Innovation has propelled many other diseases, such as hypoplastic left heart syndrome, down the bumpy road from lethal to treatable.2Mahle W.T. Spray T.L. Wernovsky G. Gaynor J.W. Clark B.J. Survival after reconstructive surgery for hypoplastic left heart syndrome.Circulation. 2000; 102: 111-136https://doi.org/10.1161/circ.102.suppl_3.III-136Crossref Google Scholar A pattern of gradual improvement over time may be built on the experience of individual patients. Medical progress is frequently and justifiably a secondary benefit of frontier treatments. Even when innovation is justifiable, application to individual patients may be difficult or distressing for clinicians, particularly those caring for the patient at the bedside. Caring for patients with lymphatic disorders, such as this one, often triggers ethics consults, leads clinicians of all disciplines to question medical plans, and may cause interpersonal conflict. In this case, several clinicians reported to charge nurses that they left in tears after a shift caring for the patient. Frontier treatments may create multidimensional distress, including anxiety about practical challenges in patient care, visceral unease with the appearance or perceived suffering of the patient, and moral distress and ambivalence. Caring for patients undergoing frontier treatments creates practical challenges in caring for patients, requiring both innovation and adaptation of regular nursing care. For example, lymphatic fluid is irritating to skin, and there are few protocols for collecting drainage from lymphocutaneous fistulas. In our unit, nurses have improvised by adhering gastrostomy bags and novel skin care products to limit skin breakdown. Similarly, clinicians have experimented with different techniques for manipulating lymphocutaneous fistulas to maintain their patency—using different types of forceps or stretching the surrounding skin in different directions. Additionally, common pain scales are not valid when anasarca conceals facial expressions and limits range of motion, so nurses have looked for other ways to evaluate and manage this patient's pain. Diaper changes and other movement can be painful for an edematous patient, so clinicians have tried different ways to lift and turn this patient, often with the assistance of many hands. Although learning new techniques and improvising are always challenging, doing so while caring for a patient with a very grave diagnosis may be particularly distressing. Although many of the examples described here are specific to lymphatic disorders, other frontier therapies present their own practical challenges. In the example of lymphatic disorders, the appearance of the patient and of the therapy itself may illicit visceral unease in clinicians. Deformity and swelling serve as visual evidence of the severity of illness and the reality that death is possible. As such, these conditions may elicit distaste and avoidance, an adaptive response to limit spread of infectious disease.19Curtis V. Why disgust matters.Philos Trans R Soc B Biol Sci. 2011; 366: 3478-3490https://doi.org/10.1098/rstb.2011.0165Crossref PubMed Scopus (109) Google Scholar The hallmark anasarca of lymphatic disorders, as well as the fistulas and external lymph associated with treatment, make clinicians uncomfortable. The appearance of the patient described here conveys and perhaps even amplifies the perception of his suffering. Swelling that limits facial expression and movement can also have a dehumanizing effect. Increasing recognition of newborn infants' ability to experience pain over the past decades and continued uncertainty about their ability to suffer may intensify clinicians' distress.20Anand K.J. Hickey P.R. Pain and its effects in the human neonate and fetus.N Engl J Med. 1987; 317: 1321-1329https://doi.org/10.1056/NEJM198711193172105Crossref PubMed Scopus (1295) Google Scholar, 21Wilkinson D. Zayegh A. Valuing life and evaluating suffering in infants with life-limiting illness.Theor Med Bioeth. 2020; 41: 179-196https://doi.org/10.1007/s11017-020-09532-xCrossref PubMed Scopus (8) Google Scholar, 22Taddio A. Goldbach M. Ipp M. Stevens B. Koren G. Effect of neonatal circumcision on pain responses during vaccination in boys.The Lancet. 1995; 345: 291-292https://doi.org/10.1016/S0140-6736(95)90278-3Abstract PubMed Scopus (391) Google Scholar Clinicians’ visceral unease is variable between different conditions and perhaps more intense for surgical frontier therapies that cause more dramatic visual effects on appearance than medical therapies. For instance, renal replacement therapy for infants with renal agenesis is another frontier treatment. Patients undergoing renal replacement therapy also have guarded prognoses, but may illicit less visceral unease because the condition and treatment are less visually disconcerting. Additionally, clinicians become acclimated to distressing images that they are familiar with; extracorporeal membrane oxygenation is visually unsettling, but more commonplace. The appearance of a patient undergoing treatment for a lymphatic disorder is both new and disconcerting, a difficult combination. Finally, when a therapeutic path is novel, clinicians often question both physicians' and parents’ rationale for persevering, which produces moral distress.23Dryden-Palmer K. Moore G. McNeil C. Larson C.P. Tomlinson G. Roumeliotis N. et al.Moral distress of clinicians in Canadian pediatric and Neonatal ICUs.Pediatr Crit Care Med. 2020; 21: 314-323https://doi.org/10.1097/PCC.0000000000002189Crossref PubMed Scopus (46) Google Scholar Disproportionate care, defined as “parents wanting too much,” is a leading source of moral distress among clinicians in the neonatal intensive care unit (NICU).24Prentice T.M. Janvier A. Gillam L. Donath S. Davis P.G. Moral distress in neonatology.Pediatrics. 2021; 148 (e2020031864. https://doi.org/10.1542/peds.2020-031864)Crossref PubMed Scopus (12) Google Scholar In our experience, frontier therapies are often seen as falling in this category, perhaps because they feel more like a choice compared with therapies with an equally low chance of success but a longer history. Clinicians often question the motives of the innovators who pioneer these treatments and offer them to families. Sometimes, innovators do not adequately explain the careful weighing of risks and benefits that justify treatments. Caring for such patients requires large teams, so information can easily be lost or misconstrued. Clinicians may be unable to imagine good outcomes. Many newly treatable conditions are rare, so even with the recent development of successful treatments, good outcomes will not accumulate quickly. Poor outcomes are likely to unduly influence clinician perceptions owing to negativity bias, a general phenomenon whereby bad events have greater psychological power.25Baumeister R.F. Bratslavsky E. Finkenauer C. Vohs K.D. Bad is stronger than good.Rev Gen Psychol. 2001; 5: 323-370https://doi.org/10.1037/1089-2680.5.4.323Crossref Scopus (4943) Google Scholar Clinicians often also worry that parents may feel unable to decline treatment, do not understand the uncertainty of the treatment, or prioritize their own needs over those of their child. Whatever the reason, parents may not act as clinicians imagine—rightly or wrongly—that they would act if facing the same predicament. NICU clinicians experience moral distress when forced to help execute frontier treatments they do not fully support. Nurses, who spend many hours at the bedside implementing innovative care plans, may feel less involved in decision-making and are particularly susceptible to moral distress.23Dryden-Palmer K. Moore G. McNeil C. Larson C.P. Tomlinson G. Roumeliotis N. et al.Moral distress of clinicians in Canadian pediatric and Neonatal ICUs.Pediatr Crit Care Med. 2020; 21: 314-323https://doi.org/10.1097/PCC.0000000000002189Crossref PubMed Scopus (46) Google Scholar A discrepancy between the care plan a clinician thinks is best and that which a parent elects can indicate prioritization of parental values and successful shared decision-making.26Janvier A. Nadeau S. Deschênes M. Couture E. Barrington K.J. Moral distress in the neonatal intensive care unit: caregiver’s experience.J Perinatol. 2007; 27: 203-208https://doi.org/10.1038/sj.jp.7211658Crossref PubMed Scopus (68) Google Scholar,27Prentice T.M. Gillam L. Davis P.G. Janvier A. The use and misuse of moral distress in neonatology.Semin Fetal Neonatal Med. 2018; 23: 39-43https://doi.org/10.1016/j.siny.2017.09.007Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Some degree of moral distress is an expected part of intensive care. Learning to manage distress in a supportive environment can lead to clinician growth and resilience.28Rushton C.H. Moral resilience: a capacity for navigating moral distress in critical care.AACN Adv Crit Care. 2016; 27: 111-119https://doi.org/10.4037/aacnacc2016275Crossref PubMed Scopus (105) Google Scholar However, moral distress that is excessive or experienced without support can take a psychological toll on clinicians and impair their ability to function.26Janvier A. Nadeau S. Deschênes M. Couture E. Barrington K.J. Moral distress in the neonatal intensive care unit: caregiver’s experience.J Perinatol. 2007; 27: 203-208https://doi.org/10.1038/sj.jp.7211658Crossref PubMed Scopus (68) Google Scholar These factors may interact to create situations that sometimes feel intolerable to clinicians who care for patients undergoing frontier treatments. When a patient seems to be ill and uncomfortable, clinicians may find it difficult to overcome practical challenges. When clinicians question the rationale for a care plan, they may be more upset by a patient who seems to be uncomfortable. Although the specific causes of distress vary between disease processes, the various dimensions of distress apply to many types of frontier treatments. Addressing distress occurring in the context of frontier treatments is not a simple task. However, we offer some suggestions for addressing distress and suggestions for how to move forward when distress persists. Hospital units that offer frontier treatments need to dedicate resources to resolving practical challenges, enhancing communication between team members and supporting staff caring directly for patients. The first step is creating opportunities for clinicians of all disciplines to share challenges and work together to create solutions. When leaders recognize and acknowledge that caring for patients who undergo frontier treatments is difficult, bedside clinicians feel comfortable asking for help. Additional resources are often required to resolve practical challenges. For example, some patients with lymphatic disease benefit from having 2 bedside nurses to manage care—measuring lymphatic output, dressing wounds, and manipulating patients as gingerly as possible. Units may also need to incorporate clinical experts from various disciplines who are invested in and skilled with a particular frontier therapy to support others in navigating clinical challenges. Finally, recognizing and appreciating the additional effort that bedside clinicians use in caring for such patients can alleviate distress. Coping with visceral unease and moral distress are more complicated and require communication within the clinical team and with parents. All members of an interdisciplinary team must feel comfortable expressing distress and describing their concerns, which in turn requires developing a safe, supportive culture in which power differentials are minimized.29Musto L.C. Rodney P.A. Vanderheide R. Toward interventions to address moral distress: Navigating structure and agency.Nurs Ethics. 2015; 22: 91-102https://doi.org/10.1177/0969733014534879Crossref PubMed Scopus (96) Google Scholar,30Zajac S. Woods A. Tannenbaum S. Salas E. Holladay C.L. Overcoming challenges to teamwork in healthcare: a team effectiveness framework and evidence-based guidance.Front Commun. 2021; 6Crossref PubMed Scopus (25) Google Scholar Clinical leaders play a fundamental role in this process and must invest resources and time into developing a culture of open communication. Clinical leaders should engage preexisting supports such as unit psychologists and chaplains to support clinicians throughout frontier treatments. Clinical innovators also play an important role in communication surrounding frontier treatments, particularly for surgical treatments where regulatory confines are less clear and a single clinician is more likely to lead an innovative therapy. Team communication should occur through regularly scheduled avenues and on an ad hoc basis whenever questions, doubts, or rumors start to emerge. In our NICU, we started an interdisciplinary ethics forum that has been particularly useful in addressing the distress of frontier treatments. The forum meets monthly for 1 hour on a virtual platform to discuss a case that creates an ethical conundrum or causes clinician distress. We have encouraged participation by clinicians of diverse disciplines by recruiting a multidisciplinary leadership panel for the forum and inviting guest presenters from varied disciplines. We also allow ample time for both discussion and silence to encourage participation by all attendees, not just those who speak most readily. Similar forums have been systematically shown to decrease moral distress in a broad NICU context.31Okah F.A. Wolff D.M. Boos V.D. Haney B.M. Oshodi A.A. Perceptions of a strategy to prevent and relieve care provider distress in the neonatal intensive care unit.Am J Perinatol. 2012; 29: 687-692https://doi.org/10.1055/s-0032-1314889Crossref PubMed Scopus (14) Google Scholar Weekly clinical conferences have been another productive venue for presenting the science behind frontier treatments. We are developing a program whereby any member of the medical team can request an interdisciplinary meeting if they are distressed or want to discuss the rationale for a particular care plan. Impromptu bedside conversations are additional avenues for targeted communication, so clinical leaders and innovators must remain open to these types of discussions. During conversations about frontier treatments, clinical innovators and medical leaders should be honest about the innovative and uncertain nature of treatments while also explaining the rationale and evidence in support of a frontier intervention. Although not every member of the clinical staff must be completely supportive of a care plan, all members should be completely informed about frontier treatments and understand the reasons for proceeding. Clinicians who disagree but feel respected experience less distress than those who feel disregarded.32Gordon E.J. Hamric A.B. The courage to stand up: the cultural politics of nurses’ access to ethics consultation.J Clin Ethics. 2006; 17: 231-254PubMed Google Scholar The innovators and medical leaders should state their degree of certainty for a good outcome for the patient explicitly, and support this statement with their reasons for optimism. The team will benefit from understanding what progress would look like for a particular disease process as well as uncertainty of prognosis. Again, clinicians may disagree about the likelihood of achieving a good outcome, but may feel distressed if they cannot even imagine such an outcome. Clinical leaders, particularly attending physicians, should communicate where they see the bounds of parental discretion. Leaders can also provide perspective by highlighting comparisons between frontier treatments and more established treatments for serious illness. Are the treatments for lymphatic disorders less successful than those for extreme prematurity? Is the discomfort from a lymphatic fistula greater than that of being cannulated on extracorporeal membrane oxygenation? Communication between the clinical team and the family must also be clear, committed, and interdisciplinary. This requirement begins when initially proposing an innovative intervention, and the standards escalate considerably when providing information and obtaining informed consent. Both clinicians and families will benefit from including members of varied disciplines in family meetings.33Walter J.K. Arnold R.M. Curley M.A.Q. Feudtner C. teamwork when conducting family meetings: concepts, terminology, and the importance of team-team practices.J Pain Symptom Manage. 2019; 58: 336-343https://doi.org/10.1016/j.jpainsymman.2019.04.030Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Documentation in the medical record of what was discussed, and in particular the innovative nature of treatments and both potential benefits and harms, serve the added purpose of enabling other members of the care team to understand parents’ decisions. From the outset of the therapeutic journey with the innovative intervention, the clinical team should provide parents with milestones of progress to look for that can be evaluated in the hours or days to come to gauge the success of the intervention. The family should be prepared for an ongoing dialogue with the clinical team about how the patient is responding to the intervention and about whether the intervention should be continued or, if not working, stopped. Discussing the limits of reasonable interventions with families will also build trust in the clinical team, who knows a line has been drawn beyond which care will not be escalated. Despite these measures, persistent distress is sometimes inevitable. One of the key recommendations for clinical leaders is to acknowledge that distress is occurring. Sometimes, circling back through the measures mentioned in this article will help to decrease distress. Redoubling efforts at identifying and easing practical challenges, enhancing medical understanding, and reviewing escalation limits are particularly effective. Other times, there is truly an impasse, and leadership needs to acknowledge this and turn its attention in new directions. This process may involve allowing clinicians time to process a situation that is difficult for them. For instance, in the composite case described here, nursing leadership ensured that bedside nurses who were distressed by the case did not care for the patient for multiple shifts in a row. Above all, it is the responsibility of clinical leaders and innovators to ensure that everyone feels their experience matters, their perspective is considered, and they are respected. This respect serves as a bulwark against differences of opinion and of desired plans of action. The case described in this article represents an amalgam of several real cases from our hospital. Some patients have lived and gone home; others have died. One stayed in an intensive care unit for nearly 2 years. Clinicians and innovators cannot always predict which patients have a reasonable chance of survival, and the threshold is slowly yet constantly shifting. As lymphatic disorders and other diseases transition away from being uniformly fatal, clinicians must support each other in the difficult realities of frontier treatments for sick patients. We hope that outlining reasons to proceed with innovative care, describing the inherent challenges, and discussing techniques for managing distress, will help others who care for patients with lymphatic disorders and other diseases that until recently were considered untreatable. The authors thank Steve Joffe, MD, and Pamela Nathanson, MBE, for their thoughtful reviews of this article. Dr Joffe received research funding from Pfizer through the University of Pennsylvania until May 2020.