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ECMO in Adults
As the distribution and utilization of technology in critical care medicine expands, patients experiencing respiratory failure, heart failure, or cardiac arrest are increasingly being treated with extracorporeal membrane oxygenation (ECMO). Although not customarily responsible for managing ECMO, hospitalists need to understand the rudiments of this technology and its associated ethical issues to assure that ECMO use is consistent with patient preferences and goals of care. This review aims to help prepare hospitalists for these clinical responsibilities. Following a brief review of modern‐day ECMO, including both venoarterial extracorporeal membrane oxygenation (VA‐ECMO) and venovenous extracorporeal membrane oxygenation (VV‐ECMO), we highlight special ethical considerations that may arise with VA‐ECMO and present an ethically grounded approach to the initiation, continuation, and discontinuation of treatment.
Many of the questions regarding the use of ECMO will be familiar. Certainly, similar questions arise with other life‐sustaining therapies; however, the general hospitalist may be a bit unfamiliar with ECMO and its unique ethical challenges. For example, ECMO is only provided transiently and generally while patients are in an intensive care unit. Unlike mechanical ventilation, which may be provided long‐term via tracheostomy, there is no comparable, enduring form of ECMO. Next, patients requiring ECMO are utterly dependent on the machine for their survival. If they do not recover and are not candidates for a ventricular assist device (VAD) or transplantation, there are no other therapies to offer. In this scenario, terminal discontinuation is the only option.
Informed hospitalists, who bring to counseling sessions both an understanding of the patient and family, and technical knowledge and background information on ECMO, will be far better equipped to help patients and families facing these difficult choices. As the use of ECMO becomes more prevalent, hospitalists must be prepared to address questions related to this evolving technology.
TECHNICAL AND HISTORICAL BACKGROUND
Extracorporeal life support (ECLS) involves the use of mechanical devices when native organ function fails.[1] ECMO involves the application of ECLS to provide a replacement form of cardiac and/or pulmonary function. An illustrative figure of the ECMO circuit may be seen at The Extracorporeal Life Support Organization (ELSO) (
Encouraging outcomes of clinical trials have ushered in enthusiasm for adult ECMO in the United States.[9] For example, the Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial, a prospective study of adult VV‐ECMO for respiratory failure conducted in the United Kingdom from 2001 to 2006, demonstrated a measurable survival benefit. Patients with severe adult respiratory failure randomized to an ECMO center (75% received ECMO) had a 63% 6‐month survival without severe disability, versus 47% for patients managed conventionally at a tertiary care center.[10] Similarly, data from the 2009 H1N1 flu virus epidemic in Australia and New Zealand suggested a benefit when patients with acute respiratory distress syndrome, who had failed mechanical ventilation, were treated with ECMO; 76% survived, which was an improvement over previously reported mortality rates of 30% to 48%.[11]
With respect to VA‐ECMO, recent studies and case reports out of Taiwan, Germany, and France propose a survival benefit when ECMO is used in patients with cardiac failure.[12, 13, 14, 15] Patients with in‐hospital cardiac arrest refractory to cardiopulmonary resuscitation (CPR) in Taiwan had close to a 20% increase in survival to hospital discharge when treated with VA‐ECMO.[12] A retrospective study of 1764 patients who had cardiac surgery from 2002 to 2006 in Taiwan demonstrated that, of the nearly 3% who required ECMO for postoperative cardiogenic shock, 53% were successfully weaned from ECMO and had a 1‐year survival approaching 30%.[13] A 2003 to 2006 study of 5750 patients undergoing cardiac surgery in Germany found that of the 0.8% of patients requiring VA‐ECMO for refractory cardiogenic shock, 29% survived to discharge, and 22% were alive at 1 year.[14] In France, among 81 patients who received ECMO for refractory cardiogenic shock from 2002 to 2006, 42% survived to hospital discharge.[15]
The survival benefit associated with adult ECMO is thought to stem both from improvements in circuit design (advancements in the pump and oxygenator), as well as from better patient selection. Further, antithrombotic circuit tubing has allowed for lower levels of anticoagulation and less risk of fatal bleeding.[16] According to the ELSO, a group that maintains an active registry of data from medical centers providing ECMO, in 2013 there were approximately 223 ECMO centers, a significant increase from the 83 centers present in 1990; there were nearly 4400 ECMO cases (all ages) in 2013.[17]
Although the number of physicians, patients, and families who consider ECMO as a treatment option have all expanded considerably in recent years and continue to rise, the use of the technology is often discretionary, and decisions as to whether and when to initiate and discontinue ECMO are not always clear‐cut either clinically or ethically.
TREATMENT WITH ECMO
Typically ECMO is initiated not as a treatment itself, but rather as a means to support a patient with cardiopulmonary failure, in order to buy time. Time for an intervention that may serve to fix the underlying organ defect, or time to allow the organ to heal on its own. As such, ECMO is often considered either a bridge to recovery or a bridge to a definitive and longer‐term treatment option (ie, VAD, heart or lung transplantation).[16, 18] ECMO is especially valuable given that the mechanical oxygenation and perfusion provide time for additional workup and intervention, which would not otherwise be feasible for a patient suffering from acute cardiopulmonary collapse.
There are 3 possible clinical outcomes for patients treated with ECMO: (1) native cardiopulmonary recovery and successful weaning off ECMO; (2) failure to recover, with ECMO serving as a bridge to a longer‐term circulatory support device or heart or lung transplantation; or (3) death.
Presently, ECMO may only be provided in an intensive care setting and only temporarily. Patients on VV‐ECMO may be maintained on the machine for weeks to months in some cases, and may be awake, walking, and talking, potentially allowing for these individuals to directly participate in discussions about goals of care.[19, 20] In contrast, adult patients on VA‐ECMO historically have only been maintained for days to weeks on the machine, intubated and typically sedated, making their participation in goals of care discussions generally more difficult, if not impossible.[7] As collective expertise in adult VA‐ECMO grows, however, patients awaiting heart or heart/lung transplants are similarly finding support for longer periods of time, enabling wakefulness and the ability to participate in decision making. Generally speaking, if a patient on ECMO neither recovers nor is a candidate for a longer‐term support device or transplantation, the risks of thromboembolic and infectious complications from continuing the treatment will eventually outweigh any real benefit. Accordingly, ELSO recommends that ECMO should be discontinued promptly if there is no hope for healthy survival (severe brain damage, no hope of heart or lung recovery, and no hope of organ replacement by VAD or transplant).[21]
Given that approximately 32% of adults treated with ECMO for cardiac failure and 47% treated for respiratory failure will survive to hospital discharge, many patients and families will be forced to make difficult, end‐of‐life decisions with ECMO.[22] ECMO is different from other life‐sustaining therapy (LST), such as mechanical ventilation, in that it may only be provided in an intensive care setting. Furthermore, unlike patients who cannot wean from a ventilator and thus are transitioned to a tracheostomy, there is no long‐term treatment option with ECMO. Terminal discontinuation is the sole option for patients on VA‐ECMO who do not recover and are not candidates for VAD or transplantation.
The remainder of this article will examine the ethical issues that emerge with ECMO. We will focus more specifically on VA‐ECMO, although certainly issues described and the guidance offered are relevant to VV‐ECMO. VA‐ECMO presents some unique issues, however, as patients are generally (although not uniformly) intubated, sedated, and thus incapacitated and unable to participate in goals of care discussions once treatment is initiated. Thus, the hospitalist can help ensure, preemptively, that the provision of VA‐ECMO is consistent with patient preferences and goals of care. In addition, VA‐ECMO is also unique in that some patients suffering from cardiac arrest refractory to cardiopulmonary resuscitation and advanced cardiac life support may be successfully oxygenated and perfused with VA‐ECMO; thus, VA‐ECMO extends the boundaries of what we commonly consider to be the limits of cardiac resuscitation, perhaps suggesting a need to reframe do not resuscitate (DNR) discussions.
VA‐ECMO: ETHICAL CONSIDERATIONS
Ethical concerns and difficult decisions may arise at any time during treatment with VA‐ECMO. For teaching purposes, we have conceptualized the treatment trajectory as consisting of 3 phases: (1) initiation, (2) continuation, and (3) discontinuation, each with its own set of issues (Table 1). Clinically, however, each phase of treatment is intrinsically linked to the others, and in reality clinicians must look forward, anticipate upcoming decisions to the extent possible, and prepare families for what lies ahead. Before we attend to each phase, we will briefly review who makes these decisions.
| Treatment Phase | Ethical Issues | Suggested Ethical Theories |
|---|---|---|
| Initiation | Informed consent | Emergency presumption |
| Goals of Care | ||
| Proportionality | ||
| Religious or cultural objection to terminal discontinuation of life‐sustaining therapy | Preventive ethics | |
| Justice | ||
| Proportionality | ||
| Goals of care | ||
| Continuation | On‐going consent | Proportionality |
| Autonomy | ||
| Goals of care | ||
| Discontinuation | Informed consent | Goals of care |
| Autonomy | ||
| Futility disputes | Preventive Ethics | |
| Respect for persons | ||
| Mediation | ||
| Religious or cultural objection to terminal discontinuation of life‐sustaining therapy | Proportionality | |
| Goals of care |
Who Decides?
Central to contemporary Western medicine is the principle of autonomy, manifested in most medical encounters as allowing patients to decide for themselves what should be done to and for them.[23] When patients are incapacitated, however, others must decide for them. Physicians must be prepared to guide families, with limited knowledge and familiarity with VA‐ECMO, through this process, providing information so that they truly can make informed decisions.[24]
In the absence of a patient‐designated healthcare agent or proxy, we turn to the surrogate of highest priority to assist with decision making. Although this may vary by jurisdiction, the typical hierarchy for surrogate decision making is as follows from highest to lowest priority: a court‐ appointed guardian or committee, a spouse or domestic partner, an adult son or daughter (>18 years old), a parent, a sibling, and then other relatives or close friends.[25] It should be noted that all adult children, regardless of age or birth order, should have equal standing as surrogate decision makers. In addition, if the surrogate of highest priority is unavailable or unwilling to make decisions, he or she may not simply delegate decision making to another person; we instead turn to the next individual in the hierarchy presented above.
Initiation of VA‐ECMO
VA‐ECMO is often initiated in emergencies, leaving little time for customary informed consent prior to treatment. Given that the need for VA‐ECMO might be anticipated earlier in the course of illness, however, in patients with chronic heart failure, those undergoing heart surgery, or those at risk for myocardial infarction, there may be an opportunity to initiate the consent process earlier. When possible, for patients or for families/surrogates, the consent process should include a full discussion of the risks, benefits, and goals of the VA‐ECMO, to allow for consideration of both the benefits and burdens of this treatment. This process should occur in conjunction with an exploration of goals of care and current or prior expressed wishes about medical and/or end‐of‐life care. As such, the hospitalist, particularly a hospitalist who may have had a longitudinal relationship with the patient, is integral to this process.
The hospitalist can help patients to clarify goals of care and elucidate whether a trial of VA‐ECMO, should it be medically indicated, is consistent with goals and wishes. Anticipating the need for ECMO and discussing it in advance will be advantageous, regardless of the ultimate decision, for if the patient loses capacity at any point during the course of treatment, documentation from these prior discussions about goals of care and attitudes toward various treatment modalities may serve as an advance directive to guide treatment decisions. Looking forward, as the use of VA‐ECMO becomes increasingly more commonplace, discussions about advance directives may expand accordingly, routinely integrating discussions of VA‐ECMO as a vital topic for consideration and reflection.
Continuation of VA‐ECMO
Once a patient is stabilized on VA‐ECMO, an opportunity emerges to engage in more comprehensive discussions about prognosis, treatment benefit and burdens, and goals of care. If VA‐ECMO was started emergently, there may not have been an opportunity to obtain informed consent prior to treatment initiation, and this vital task must now be assumed. Regardless of the circumstances, once VA‐ECMO is underway, we recommend that physicians regularly engage in discussions of on‐going consent.
We find this term to be helpful as a reminder that, although the patient is already receiving treatment, frequent discussions regarding prognosis, burdens and benefits of treatment, and goals of care remain essential. Clinically, it is important to monitor cardiopulmonary recovery and also renal function and neurologic status. As previously discussed, VA‐ECMO will not serve to fix the underlying cardiopulmonary pathology, and in fact, complications related to VA‐ECMO may be expected to grow over time.[7] Proportionality, a careful analysis of the benefits of continuing treatment, balanced with the risks and burdens imposed, will allow for thoughtful consideration about whether continuation is in the patient's best interest and consistent with the goals of care.
Discontinuation of VA‐ECMO
Three primary clinical indications may prompt the recommendation to discontinue VA‐ECMO: (1) there may be sufficient recovery and cardiopulmonary support is no longer needed, (2) there may be insufficent recovery with plans to transition to a VAD or transplantation, (3) or there may be insufficient recovery and recommendation for terminal discontinuation.
The procedure for discontinuing VA‐ECMO may vary with the clinical circumstances and institution. To anticipate the likely outcome with VA‐ECMO removed, prior to decannulation (the removal of the ECMO cannulas), support might be weaned weaned down with echocardiography used to assess cardiac function. Should indications point to decannulation, this process may take place in the operating room or catheters may be removed at the bedside.[7] In cases of terminal discontinuation, the VA‐ECMO may be stopped (assuming the patient is adequately sedated), the patient will then be allowed to die, with the cannulas subsequently removed.
Analogous to discontinuation of other cardiac devices, such as a pacemaker or defibrillator, ceasing VA‐ECMO may result in: (1) no clinical consequences, as the patient has recovered sufficiently; (2) immediate declaration of death; or (3) the emergence of new symptoms, for example symptoms of heart failure, which may precede death.[26] So as to prospectively account for this variability, a full discussion of the rationale behind discontinuation, as well as the range of expected outcomes, should precede cessation. Similarly, clinicians should implement a plan for symptom management and palliation. In cases of expected recovery, a contingency plan should be developed in case the patient unexpectedly decompensates upon or shortly after cessation. In sum, it remains essential to understand the prospective course, as the lack of anticipatory planning may precipitate confusion, distress, and conflict for patients, family members, and the clinical team.
DNR on VA‐ECMO?
Hospitalists accustomed to writing DNR orders may be distressed to find that, in our opinion, DNR orders are not appropriate for patients who are maintained on VA‐ECMO.[9] (It should also be noted that patients on VV‐ECMO, a device that only provides pulmonary function, could suffer a cardiac arrest necessitating CPR; thus, DNR may be relevant in this clinical context.) VA‐ECMO provides more effective oxygenation and perfusion than traditional advanced cardiac life support with CPR. Thus patients on VA‐ECMO will generally not receive CPR and, consequently, there is effectively no clinical meaning to a DNR order for a patient on VA‐ECMO. That said, when discontinuing VA‐ECMO (and at times VV‐ECMO), depending on the goals of care, a DNR may be useful to prevent further aggressive treatment should the patient arrest following cessation of ECMO.
The clinician will be wise to recognize that if families request a DNR order for a patient on VA‐ECMO, they are asking for something. Although a request not to resuscitate may not make medical sense in this context, clinicians must take the time to explore what is intended by this request. For many families, DNR is a stepping stone toward de‐escalation of treatment and a first move toward withdrawal of life‐sustaining therapies.[27, 28] A nuanced understanding of what a family hopes to accomplish by the suggested order, and specifically whether and how goals of care may have changed, is vital toward the maintenance of an appropriate, timely, and evolving treatment plan.
Terminal Discontinuation of VA‐ECMO
Among clinical ethicists, some of the most distressing conversations and meetings we have had with families have emerged in the context of terminal discontinuation of VA‐ECMO. Unlike mechanical ventilation, which theoretically may be continued indefinitely via tracheostomy, VA‐ECMO is only a temporary measure and, according to ELSO, should be discontinued promptly if healthy survival is not anticipated with the possibility of stopping for futility explained to the family before ECLS is begun.[21] Given the time constraints for what may have been an emergency procedure, and given the frequent reluctance of families and surrogates to discontinue life‐sustaining therapies, how does a clinician or institution ethically enact these guidelines? With respect to practical guidance, we offer 3 suggestions for directing these conversations.
First, we suggest physicians discuss the possibility and potential rationales of terminal discontinuation early and often, ideally as part of the initial consent process. Second, informed consent conversations should address potential complications (stroke, hemorrhage, and thrombosis) and their sequelae alongside discussions with patients and surrogates about their wishes in the context of such an event. Finally, we also recommend frequently revisiting the goals of care with the surrogate throughout the course of treatment.[28] Thus, when goals of care can no longer be achieved by continuing VA‐ECMO, either: (1) because the patient has no chance for recovery; (2) because VA‐ECMO no longer serves its intended purpose; or (3) owing to harm from complications, families may be able to appreciate that continuation of the intervention has become ethically disproportionate, and ECMO is now more burdensome than beneficial. Continuous and open dialogue should build a strong foundation of trust and knowledge that allows the surrogate to understand and accept the rationale behind a recommendation to terminally discontinue treatment, should the clinical course necessitate such.[29]
CONCLUSION
With indications for and utilization of ECMO in adult patients expanding, hospitalists may be expected to encounter these technologies with greater frequency and guide patients and families with medical decision‐making. Although the ethical issues reviewed are certainly not exclusive to ECMO, specific facets of ECMO, as discussed, may precipitate unique challenges or exacerbate common ones. Hospitalists can help to uphold patient autonomy by providing information that enables patients and surrogates to actively participate in goal setting and decision‐making. As the utilization of this technology grows, further research will need to address decision‐making in the context of ECMO to ensure that the process remains optimally patient‐ and family‐centered.
Acknowledgment
Disclosures: All work was performed at Weill Cornell Medical College of Cornell University, New York Presbyterian Weill Cornell Medical Center, and University of Pennsylvania. The authors report no conflicts of interest.
- , . Current status of extracorporeal life support (ECMO) for cardiopulmonary failure. Minerva Anestesiol. 2010;76(7):534–540.
- . . The first 20 years of the heart‐lung machine. Tex Heart Inst J. 1997;24(1):1–8.
- , , , , . Venovenous extracorporeal membrane oxygenation in adults: practical aspects of circuits, cannulae, and procedures. J Cardiothorac Vasc Anesth. 2012;26(5):893–909.
- , , , et al. Extracorporeal life support for adult cardiorespiratory failure. Surgery. 1993;114(2):161–172; discussion 172–163.
- , . Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011;365(20):1905–1914.
- , , , , . Extracorporeal life support. BMJ. 2010;341:c5317.
- , , , , , . Extracorporeal membrane oxygenation for treating severe cardiac and respiratory failure in adults: part 2‐technical considerations. J Cardiothorac Vasc Anesth. 2010;24(1):164–172.
- , . Mechanical circulatory support for bridge to decision: which device and when to decide. J Card Surg. 2010;25(4):425–433.
- , , . DNR on ECMO: a paradox worth exploring. J Clin Ethics. 2013;25(1):13–19.
- , , , et al. Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR). Health Technol Assess. 2010;14(35):1–46.
- , , , et al. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome. JAMA. 2009;302(17):1888–1895.
- , , , et al. Cardiopulmonary resuscitation with assisted extracorporeal life‐support versus conventional cardiopulmonary resuscitation in adults with in‐hospital cardiac arrest: an observational study and propensity analysis. Lancet. 2008;372(9638):554–561.
- , , , et al. Extracorporeal membrane oxygenation for refractory cardiogenic shock after cardiac surgery: predictors of early mortality and outcome from 51 adult patients. Eur J Cardiothorac Surg. 2010;37(2):328–333.
- , , , et al. Venoarterial extracorporeal membrane oxygenation for treatment of cardiogenic shock: clinical experiences in 45 adult patients. J Thorac Cardiovasc Surg. 2008;135(2):382–388.
- , , , et al. Outcomes and long‐term quality‐of‐life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care Med. 2008;36(5):1404–1411.
- , . Extracorporeal life support as a bridge to lung transplantation. Clin Chest Med. 2011;32(2):245–251.
- Extracoporeal Life Support Organization. General Guidelines for all ECLS Cases. 2012; http://www.elsonet.org/. Accessed August 5, 2014.
- , , , et al. Impact of extracorporeal life support on outcome in patients with idiopathic pulmonary arterial hypertension awaiting lung transplantation. J Heart Lung Transplant. 2011;30(9):997–1002.
- , , , . Ambulatory extracorporeal membrane oxygenation: a new approach for bridge‐to‐lung transplantation. J Thorac Cardiovasc Surg. 2010;139(6):e137–e139.
- , , , et al. Ambulatory veno‐venous extracorporeal membrane oxygenation: innovation and pitfalls. J Thorac Cardiovasc Surg. 2011;142(4):755–761.
- Extracoporeal Life Support Organization. General Guidelines for all ECLS Cases. 2012; http://www.elsonet.org/. Accessed August 5, 2014.
- Extracorporeal Life Support Organization. ECLS Registry Report United States Summary. August 2014; http://www.elsonet.org/. Accessed August 5, 2014.
- , . Principles of Biomedical Ethics. 6th ed. New York, NY: Oxford University Press; 2009.
- , , , et al. Decision making in advanced heart failure: a scientific statement from the American Heart Association. Circulation. 2012;125(15):1928–1952.
- , , . Ethics in Clinical Practice. 2nd ed. Sudbury, MA: Jones and Bartlett; 2005.
- . Pacemaker and defibrillator deactivation in competent hospice patients: an ethical consideration. Am J Hosp Palliat Care. 2005;22(1):14–19.
- , , , . Limitation of medical care: an ethnographic analysis. J Clin Ethics. 1993;4(2):134–145.
- . A Palliative Ethic of Care: Clinical Wisdom at Life's End. Sudbury, MA: Jones and Bartlett; 2006.
- , , , , , . Extracorporeal membrane oxygenation as a bridge to chemotherapy in an orthodox Jewish patient. Oncologist. 2014;19(9):985–989.
As the distribution and utilization of technology in critical care medicine expands, patients experiencing respiratory failure, heart failure, or cardiac arrest are increasingly being treated with extracorporeal membrane oxygenation (ECMO). Although not customarily responsible for managing ECMO, hospitalists need to understand the rudiments of this technology and its associated ethical issues to assure that ECMO use is consistent with patient preferences and goals of care. This review aims to help prepare hospitalists for these clinical responsibilities. Following a brief review of modern‐day ECMO, including both venoarterial extracorporeal membrane oxygenation (VA‐ECMO) and venovenous extracorporeal membrane oxygenation (VV‐ECMO), we highlight special ethical considerations that may arise with VA‐ECMO and present an ethically grounded approach to the initiation, continuation, and discontinuation of treatment.
Many of the questions regarding the use of ECMO will be familiar. Certainly, similar questions arise with other life‐sustaining therapies; however, the general hospitalist may be a bit unfamiliar with ECMO and its unique ethical challenges. For example, ECMO is only provided transiently and generally while patients are in an intensive care unit. Unlike mechanical ventilation, which may be provided long‐term via tracheostomy, there is no comparable, enduring form of ECMO. Next, patients requiring ECMO are utterly dependent on the machine for their survival. If they do not recover and are not candidates for a ventricular assist device (VAD) or transplantation, there are no other therapies to offer. In this scenario, terminal discontinuation is the only option.
Informed hospitalists, who bring to counseling sessions both an understanding of the patient and family, and technical knowledge and background information on ECMO, will be far better equipped to help patients and families facing these difficult choices. As the use of ECMO becomes more prevalent, hospitalists must be prepared to address questions related to this evolving technology.
TECHNICAL AND HISTORICAL BACKGROUND
Extracorporeal life support (ECLS) involves the use of mechanical devices when native organ function fails.[1] ECMO involves the application of ECLS to provide a replacement form of cardiac and/or pulmonary function. An illustrative figure of the ECMO circuit may be seen at The Extracorporeal Life Support Organization (ELSO) (
Encouraging outcomes of clinical trials have ushered in enthusiasm for adult ECMO in the United States.[9] For example, the Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial, a prospective study of adult VV‐ECMO for respiratory failure conducted in the United Kingdom from 2001 to 2006, demonstrated a measurable survival benefit. Patients with severe adult respiratory failure randomized to an ECMO center (75% received ECMO) had a 63% 6‐month survival without severe disability, versus 47% for patients managed conventionally at a tertiary care center.[10] Similarly, data from the 2009 H1N1 flu virus epidemic in Australia and New Zealand suggested a benefit when patients with acute respiratory distress syndrome, who had failed mechanical ventilation, were treated with ECMO; 76% survived, which was an improvement over previously reported mortality rates of 30% to 48%.[11]
With respect to VA‐ECMO, recent studies and case reports out of Taiwan, Germany, and France propose a survival benefit when ECMO is used in patients with cardiac failure.[12, 13, 14, 15] Patients with in‐hospital cardiac arrest refractory to cardiopulmonary resuscitation (CPR) in Taiwan had close to a 20% increase in survival to hospital discharge when treated with VA‐ECMO.[12] A retrospective study of 1764 patients who had cardiac surgery from 2002 to 2006 in Taiwan demonstrated that, of the nearly 3% who required ECMO for postoperative cardiogenic shock, 53% were successfully weaned from ECMO and had a 1‐year survival approaching 30%.[13] A 2003 to 2006 study of 5750 patients undergoing cardiac surgery in Germany found that of the 0.8% of patients requiring VA‐ECMO for refractory cardiogenic shock, 29% survived to discharge, and 22% were alive at 1 year.[14] In France, among 81 patients who received ECMO for refractory cardiogenic shock from 2002 to 2006, 42% survived to hospital discharge.[15]
The survival benefit associated with adult ECMO is thought to stem both from improvements in circuit design (advancements in the pump and oxygenator), as well as from better patient selection. Further, antithrombotic circuit tubing has allowed for lower levels of anticoagulation and less risk of fatal bleeding.[16] According to the ELSO, a group that maintains an active registry of data from medical centers providing ECMO, in 2013 there were approximately 223 ECMO centers, a significant increase from the 83 centers present in 1990; there were nearly 4400 ECMO cases (all ages) in 2013.[17]
Although the number of physicians, patients, and families who consider ECMO as a treatment option have all expanded considerably in recent years and continue to rise, the use of the technology is often discretionary, and decisions as to whether and when to initiate and discontinue ECMO are not always clear‐cut either clinically or ethically.
TREATMENT WITH ECMO
Typically ECMO is initiated not as a treatment itself, but rather as a means to support a patient with cardiopulmonary failure, in order to buy time. Time for an intervention that may serve to fix the underlying organ defect, or time to allow the organ to heal on its own. As such, ECMO is often considered either a bridge to recovery or a bridge to a definitive and longer‐term treatment option (ie, VAD, heart or lung transplantation).[16, 18] ECMO is especially valuable given that the mechanical oxygenation and perfusion provide time for additional workup and intervention, which would not otherwise be feasible for a patient suffering from acute cardiopulmonary collapse.
There are 3 possible clinical outcomes for patients treated with ECMO: (1) native cardiopulmonary recovery and successful weaning off ECMO; (2) failure to recover, with ECMO serving as a bridge to a longer‐term circulatory support device or heart or lung transplantation; or (3) death.
Presently, ECMO may only be provided in an intensive care setting and only temporarily. Patients on VV‐ECMO may be maintained on the machine for weeks to months in some cases, and may be awake, walking, and talking, potentially allowing for these individuals to directly participate in discussions about goals of care.[19, 20] In contrast, adult patients on VA‐ECMO historically have only been maintained for days to weeks on the machine, intubated and typically sedated, making their participation in goals of care discussions generally more difficult, if not impossible.[7] As collective expertise in adult VA‐ECMO grows, however, patients awaiting heart or heart/lung transplants are similarly finding support for longer periods of time, enabling wakefulness and the ability to participate in decision making. Generally speaking, if a patient on ECMO neither recovers nor is a candidate for a longer‐term support device or transplantation, the risks of thromboembolic and infectious complications from continuing the treatment will eventually outweigh any real benefit. Accordingly, ELSO recommends that ECMO should be discontinued promptly if there is no hope for healthy survival (severe brain damage, no hope of heart or lung recovery, and no hope of organ replacement by VAD or transplant).[21]
Given that approximately 32% of adults treated with ECMO for cardiac failure and 47% treated for respiratory failure will survive to hospital discharge, many patients and families will be forced to make difficult, end‐of‐life decisions with ECMO.[22] ECMO is different from other life‐sustaining therapy (LST), such as mechanical ventilation, in that it may only be provided in an intensive care setting. Furthermore, unlike patients who cannot wean from a ventilator and thus are transitioned to a tracheostomy, there is no long‐term treatment option with ECMO. Terminal discontinuation is the sole option for patients on VA‐ECMO who do not recover and are not candidates for VAD or transplantation.
The remainder of this article will examine the ethical issues that emerge with ECMO. We will focus more specifically on VA‐ECMO, although certainly issues described and the guidance offered are relevant to VV‐ECMO. VA‐ECMO presents some unique issues, however, as patients are generally (although not uniformly) intubated, sedated, and thus incapacitated and unable to participate in goals of care discussions once treatment is initiated. Thus, the hospitalist can help ensure, preemptively, that the provision of VA‐ECMO is consistent with patient preferences and goals of care. In addition, VA‐ECMO is also unique in that some patients suffering from cardiac arrest refractory to cardiopulmonary resuscitation and advanced cardiac life support may be successfully oxygenated and perfused with VA‐ECMO; thus, VA‐ECMO extends the boundaries of what we commonly consider to be the limits of cardiac resuscitation, perhaps suggesting a need to reframe do not resuscitate (DNR) discussions.
VA‐ECMO: ETHICAL CONSIDERATIONS
Ethical concerns and difficult decisions may arise at any time during treatment with VA‐ECMO. For teaching purposes, we have conceptualized the treatment trajectory as consisting of 3 phases: (1) initiation, (2) continuation, and (3) discontinuation, each with its own set of issues (Table 1). Clinically, however, each phase of treatment is intrinsically linked to the others, and in reality clinicians must look forward, anticipate upcoming decisions to the extent possible, and prepare families for what lies ahead. Before we attend to each phase, we will briefly review who makes these decisions.
| Treatment Phase | Ethical Issues | Suggested Ethical Theories |
|---|---|---|
| Initiation | Informed consent | Emergency presumption |
| Goals of Care | ||
| Proportionality | ||
| Religious or cultural objection to terminal discontinuation of life‐sustaining therapy | Preventive ethics | |
| Justice | ||
| Proportionality | ||
| Goals of care | ||
| Continuation | On‐going consent | Proportionality |
| Autonomy | ||
| Goals of care | ||
| Discontinuation | Informed consent | Goals of care |
| Autonomy | ||
| Futility disputes | Preventive Ethics | |
| Respect for persons | ||
| Mediation | ||
| Religious or cultural objection to terminal discontinuation of life‐sustaining therapy | Proportionality | |
| Goals of care |
Who Decides?
Central to contemporary Western medicine is the principle of autonomy, manifested in most medical encounters as allowing patients to decide for themselves what should be done to and for them.[23] When patients are incapacitated, however, others must decide for them. Physicians must be prepared to guide families, with limited knowledge and familiarity with VA‐ECMO, through this process, providing information so that they truly can make informed decisions.[24]
In the absence of a patient‐designated healthcare agent or proxy, we turn to the surrogate of highest priority to assist with decision making. Although this may vary by jurisdiction, the typical hierarchy for surrogate decision making is as follows from highest to lowest priority: a court‐ appointed guardian or committee, a spouse or domestic partner, an adult son or daughter (>18 years old), a parent, a sibling, and then other relatives or close friends.[25] It should be noted that all adult children, regardless of age or birth order, should have equal standing as surrogate decision makers. In addition, if the surrogate of highest priority is unavailable or unwilling to make decisions, he or she may not simply delegate decision making to another person; we instead turn to the next individual in the hierarchy presented above.
Initiation of VA‐ECMO
VA‐ECMO is often initiated in emergencies, leaving little time for customary informed consent prior to treatment. Given that the need for VA‐ECMO might be anticipated earlier in the course of illness, however, in patients with chronic heart failure, those undergoing heart surgery, or those at risk for myocardial infarction, there may be an opportunity to initiate the consent process earlier. When possible, for patients or for families/surrogates, the consent process should include a full discussion of the risks, benefits, and goals of the VA‐ECMO, to allow for consideration of both the benefits and burdens of this treatment. This process should occur in conjunction with an exploration of goals of care and current or prior expressed wishes about medical and/or end‐of‐life care. As such, the hospitalist, particularly a hospitalist who may have had a longitudinal relationship with the patient, is integral to this process.
The hospitalist can help patients to clarify goals of care and elucidate whether a trial of VA‐ECMO, should it be medically indicated, is consistent with goals and wishes. Anticipating the need for ECMO and discussing it in advance will be advantageous, regardless of the ultimate decision, for if the patient loses capacity at any point during the course of treatment, documentation from these prior discussions about goals of care and attitudes toward various treatment modalities may serve as an advance directive to guide treatment decisions. Looking forward, as the use of VA‐ECMO becomes increasingly more commonplace, discussions about advance directives may expand accordingly, routinely integrating discussions of VA‐ECMO as a vital topic for consideration and reflection.
Continuation of VA‐ECMO
Once a patient is stabilized on VA‐ECMO, an opportunity emerges to engage in more comprehensive discussions about prognosis, treatment benefit and burdens, and goals of care. If VA‐ECMO was started emergently, there may not have been an opportunity to obtain informed consent prior to treatment initiation, and this vital task must now be assumed. Regardless of the circumstances, once VA‐ECMO is underway, we recommend that physicians regularly engage in discussions of on‐going consent.
We find this term to be helpful as a reminder that, although the patient is already receiving treatment, frequent discussions regarding prognosis, burdens and benefits of treatment, and goals of care remain essential. Clinically, it is important to monitor cardiopulmonary recovery and also renal function and neurologic status. As previously discussed, VA‐ECMO will not serve to fix the underlying cardiopulmonary pathology, and in fact, complications related to VA‐ECMO may be expected to grow over time.[7] Proportionality, a careful analysis of the benefits of continuing treatment, balanced with the risks and burdens imposed, will allow for thoughtful consideration about whether continuation is in the patient's best interest and consistent with the goals of care.
Discontinuation of VA‐ECMO
Three primary clinical indications may prompt the recommendation to discontinue VA‐ECMO: (1) there may be sufficient recovery and cardiopulmonary support is no longer needed, (2) there may be insufficent recovery with plans to transition to a VAD or transplantation, (3) or there may be insufficient recovery and recommendation for terminal discontinuation.
The procedure for discontinuing VA‐ECMO may vary with the clinical circumstances and institution. To anticipate the likely outcome with VA‐ECMO removed, prior to decannulation (the removal of the ECMO cannulas), support might be weaned weaned down with echocardiography used to assess cardiac function. Should indications point to decannulation, this process may take place in the operating room or catheters may be removed at the bedside.[7] In cases of terminal discontinuation, the VA‐ECMO may be stopped (assuming the patient is adequately sedated), the patient will then be allowed to die, with the cannulas subsequently removed.
Analogous to discontinuation of other cardiac devices, such as a pacemaker or defibrillator, ceasing VA‐ECMO may result in: (1) no clinical consequences, as the patient has recovered sufficiently; (2) immediate declaration of death; or (3) the emergence of new symptoms, for example symptoms of heart failure, which may precede death.[26] So as to prospectively account for this variability, a full discussion of the rationale behind discontinuation, as well as the range of expected outcomes, should precede cessation. Similarly, clinicians should implement a plan for symptom management and palliation. In cases of expected recovery, a contingency plan should be developed in case the patient unexpectedly decompensates upon or shortly after cessation. In sum, it remains essential to understand the prospective course, as the lack of anticipatory planning may precipitate confusion, distress, and conflict for patients, family members, and the clinical team.
DNR on VA‐ECMO?
Hospitalists accustomed to writing DNR orders may be distressed to find that, in our opinion, DNR orders are not appropriate for patients who are maintained on VA‐ECMO.[9] (It should also be noted that patients on VV‐ECMO, a device that only provides pulmonary function, could suffer a cardiac arrest necessitating CPR; thus, DNR may be relevant in this clinical context.) VA‐ECMO provides more effective oxygenation and perfusion than traditional advanced cardiac life support with CPR. Thus patients on VA‐ECMO will generally not receive CPR and, consequently, there is effectively no clinical meaning to a DNR order for a patient on VA‐ECMO. That said, when discontinuing VA‐ECMO (and at times VV‐ECMO), depending on the goals of care, a DNR may be useful to prevent further aggressive treatment should the patient arrest following cessation of ECMO.
The clinician will be wise to recognize that if families request a DNR order for a patient on VA‐ECMO, they are asking for something. Although a request not to resuscitate may not make medical sense in this context, clinicians must take the time to explore what is intended by this request. For many families, DNR is a stepping stone toward de‐escalation of treatment and a first move toward withdrawal of life‐sustaining therapies.[27, 28] A nuanced understanding of what a family hopes to accomplish by the suggested order, and specifically whether and how goals of care may have changed, is vital toward the maintenance of an appropriate, timely, and evolving treatment plan.
Terminal Discontinuation of VA‐ECMO
Among clinical ethicists, some of the most distressing conversations and meetings we have had with families have emerged in the context of terminal discontinuation of VA‐ECMO. Unlike mechanical ventilation, which theoretically may be continued indefinitely via tracheostomy, VA‐ECMO is only a temporary measure and, according to ELSO, should be discontinued promptly if healthy survival is not anticipated with the possibility of stopping for futility explained to the family before ECLS is begun.[21] Given the time constraints for what may have been an emergency procedure, and given the frequent reluctance of families and surrogates to discontinue life‐sustaining therapies, how does a clinician or institution ethically enact these guidelines? With respect to practical guidance, we offer 3 suggestions for directing these conversations.
First, we suggest physicians discuss the possibility and potential rationales of terminal discontinuation early and often, ideally as part of the initial consent process. Second, informed consent conversations should address potential complications (stroke, hemorrhage, and thrombosis) and their sequelae alongside discussions with patients and surrogates about their wishes in the context of such an event. Finally, we also recommend frequently revisiting the goals of care with the surrogate throughout the course of treatment.[28] Thus, when goals of care can no longer be achieved by continuing VA‐ECMO, either: (1) because the patient has no chance for recovery; (2) because VA‐ECMO no longer serves its intended purpose; or (3) owing to harm from complications, families may be able to appreciate that continuation of the intervention has become ethically disproportionate, and ECMO is now more burdensome than beneficial. Continuous and open dialogue should build a strong foundation of trust and knowledge that allows the surrogate to understand and accept the rationale behind a recommendation to terminally discontinue treatment, should the clinical course necessitate such.[29]
CONCLUSION
With indications for and utilization of ECMO in adult patients expanding, hospitalists may be expected to encounter these technologies with greater frequency and guide patients and families with medical decision‐making. Although the ethical issues reviewed are certainly not exclusive to ECMO, specific facets of ECMO, as discussed, may precipitate unique challenges or exacerbate common ones. Hospitalists can help to uphold patient autonomy by providing information that enables patients and surrogates to actively participate in goal setting and decision‐making. As the utilization of this technology grows, further research will need to address decision‐making in the context of ECMO to ensure that the process remains optimally patient‐ and family‐centered.
Acknowledgment
Disclosures: All work was performed at Weill Cornell Medical College of Cornell University, New York Presbyterian Weill Cornell Medical Center, and University of Pennsylvania. The authors report no conflicts of interest.
As the distribution and utilization of technology in critical care medicine expands, patients experiencing respiratory failure, heart failure, or cardiac arrest are increasingly being treated with extracorporeal membrane oxygenation (ECMO). Although not customarily responsible for managing ECMO, hospitalists need to understand the rudiments of this technology and its associated ethical issues to assure that ECMO use is consistent with patient preferences and goals of care. This review aims to help prepare hospitalists for these clinical responsibilities. Following a brief review of modern‐day ECMO, including both venoarterial extracorporeal membrane oxygenation (VA‐ECMO) and venovenous extracorporeal membrane oxygenation (VV‐ECMO), we highlight special ethical considerations that may arise with VA‐ECMO and present an ethically grounded approach to the initiation, continuation, and discontinuation of treatment.
Many of the questions regarding the use of ECMO will be familiar. Certainly, similar questions arise with other life‐sustaining therapies; however, the general hospitalist may be a bit unfamiliar with ECMO and its unique ethical challenges. For example, ECMO is only provided transiently and generally while patients are in an intensive care unit. Unlike mechanical ventilation, which may be provided long‐term via tracheostomy, there is no comparable, enduring form of ECMO. Next, patients requiring ECMO are utterly dependent on the machine for their survival. If they do not recover and are not candidates for a ventricular assist device (VAD) or transplantation, there are no other therapies to offer. In this scenario, terminal discontinuation is the only option.
Informed hospitalists, who bring to counseling sessions both an understanding of the patient and family, and technical knowledge and background information on ECMO, will be far better equipped to help patients and families facing these difficult choices. As the use of ECMO becomes more prevalent, hospitalists must be prepared to address questions related to this evolving technology.
TECHNICAL AND HISTORICAL BACKGROUND
Extracorporeal life support (ECLS) involves the use of mechanical devices when native organ function fails.[1] ECMO involves the application of ECLS to provide a replacement form of cardiac and/or pulmonary function. An illustrative figure of the ECMO circuit may be seen at The Extracorporeal Life Support Organization (ELSO) (
Encouraging outcomes of clinical trials have ushered in enthusiasm for adult ECMO in the United States.[9] For example, the Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial, a prospective study of adult VV‐ECMO for respiratory failure conducted in the United Kingdom from 2001 to 2006, demonstrated a measurable survival benefit. Patients with severe adult respiratory failure randomized to an ECMO center (75% received ECMO) had a 63% 6‐month survival without severe disability, versus 47% for patients managed conventionally at a tertiary care center.[10] Similarly, data from the 2009 H1N1 flu virus epidemic in Australia and New Zealand suggested a benefit when patients with acute respiratory distress syndrome, who had failed mechanical ventilation, were treated with ECMO; 76% survived, which was an improvement over previously reported mortality rates of 30% to 48%.[11]
With respect to VA‐ECMO, recent studies and case reports out of Taiwan, Germany, and France propose a survival benefit when ECMO is used in patients with cardiac failure.[12, 13, 14, 15] Patients with in‐hospital cardiac arrest refractory to cardiopulmonary resuscitation (CPR) in Taiwan had close to a 20% increase in survival to hospital discharge when treated with VA‐ECMO.[12] A retrospective study of 1764 patients who had cardiac surgery from 2002 to 2006 in Taiwan demonstrated that, of the nearly 3% who required ECMO for postoperative cardiogenic shock, 53% were successfully weaned from ECMO and had a 1‐year survival approaching 30%.[13] A 2003 to 2006 study of 5750 patients undergoing cardiac surgery in Germany found that of the 0.8% of patients requiring VA‐ECMO for refractory cardiogenic shock, 29% survived to discharge, and 22% were alive at 1 year.[14] In France, among 81 patients who received ECMO for refractory cardiogenic shock from 2002 to 2006, 42% survived to hospital discharge.[15]
The survival benefit associated with adult ECMO is thought to stem both from improvements in circuit design (advancements in the pump and oxygenator), as well as from better patient selection. Further, antithrombotic circuit tubing has allowed for lower levels of anticoagulation and less risk of fatal bleeding.[16] According to the ELSO, a group that maintains an active registry of data from medical centers providing ECMO, in 2013 there were approximately 223 ECMO centers, a significant increase from the 83 centers present in 1990; there were nearly 4400 ECMO cases (all ages) in 2013.[17]
Although the number of physicians, patients, and families who consider ECMO as a treatment option have all expanded considerably in recent years and continue to rise, the use of the technology is often discretionary, and decisions as to whether and when to initiate and discontinue ECMO are not always clear‐cut either clinically or ethically.
TREATMENT WITH ECMO
Typically ECMO is initiated not as a treatment itself, but rather as a means to support a patient with cardiopulmonary failure, in order to buy time. Time for an intervention that may serve to fix the underlying organ defect, or time to allow the organ to heal on its own. As such, ECMO is often considered either a bridge to recovery or a bridge to a definitive and longer‐term treatment option (ie, VAD, heart or lung transplantation).[16, 18] ECMO is especially valuable given that the mechanical oxygenation and perfusion provide time for additional workup and intervention, which would not otherwise be feasible for a patient suffering from acute cardiopulmonary collapse.
There are 3 possible clinical outcomes for patients treated with ECMO: (1) native cardiopulmonary recovery and successful weaning off ECMO; (2) failure to recover, with ECMO serving as a bridge to a longer‐term circulatory support device or heart or lung transplantation; or (3) death.
Presently, ECMO may only be provided in an intensive care setting and only temporarily. Patients on VV‐ECMO may be maintained on the machine for weeks to months in some cases, and may be awake, walking, and talking, potentially allowing for these individuals to directly participate in discussions about goals of care.[19, 20] In contrast, adult patients on VA‐ECMO historically have only been maintained for days to weeks on the machine, intubated and typically sedated, making their participation in goals of care discussions generally more difficult, if not impossible.[7] As collective expertise in adult VA‐ECMO grows, however, patients awaiting heart or heart/lung transplants are similarly finding support for longer periods of time, enabling wakefulness and the ability to participate in decision making. Generally speaking, if a patient on ECMO neither recovers nor is a candidate for a longer‐term support device or transplantation, the risks of thromboembolic and infectious complications from continuing the treatment will eventually outweigh any real benefit. Accordingly, ELSO recommends that ECMO should be discontinued promptly if there is no hope for healthy survival (severe brain damage, no hope of heart or lung recovery, and no hope of organ replacement by VAD or transplant).[21]
Given that approximately 32% of adults treated with ECMO for cardiac failure and 47% treated for respiratory failure will survive to hospital discharge, many patients and families will be forced to make difficult, end‐of‐life decisions with ECMO.[22] ECMO is different from other life‐sustaining therapy (LST), such as mechanical ventilation, in that it may only be provided in an intensive care setting. Furthermore, unlike patients who cannot wean from a ventilator and thus are transitioned to a tracheostomy, there is no long‐term treatment option with ECMO. Terminal discontinuation is the sole option for patients on VA‐ECMO who do not recover and are not candidates for VAD or transplantation.
The remainder of this article will examine the ethical issues that emerge with ECMO. We will focus more specifically on VA‐ECMO, although certainly issues described and the guidance offered are relevant to VV‐ECMO. VA‐ECMO presents some unique issues, however, as patients are generally (although not uniformly) intubated, sedated, and thus incapacitated and unable to participate in goals of care discussions once treatment is initiated. Thus, the hospitalist can help ensure, preemptively, that the provision of VA‐ECMO is consistent with patient preferences and goals of care. In addition, VA‐ECMO is also unique in that some patients suffering from cardiac arrest refractory to cardiopulmonary resuscitation and advanced cardiac life support may be successfully oxygenated and perfused with VA‐ECMO; thus, VA‐ECMO extends the boundaries of what we commonly consider to be the limits of cardiac resuscitation, perhaps suggesting a need to reframe do not resuscitate (DNR) discussions.
VA‐ECMO: ETHICAL CONSIDERATIONS
Ethical concerns and difficult decisions may arise at any time during treatment with VA‐ECMO. For teaching purposes, we have conceptualized the treatment trajectory as consisting of 3 phases: (1) initiation, (2) continuation, and (3) discontinuation, each with its own set of issues (Table 1). Clinically, however, each phase of treatment is intrinsically linked to the others, and in reality clinicians must look forward, anticipate upcoming decisions to the extent possible, and prepare families for what lies ahead. Before we attend to each phase, we will briefly review who makes these decisions.
| Treatment Phase | Ethical Issues | Suggested Ethical Theories |
|---|---|---|
| Initiation | Informed consent | Emergency presumption |
| Goals of Care | ||
| Proportionality | ||
| Religious or cultural objection to terminal discontinuation of life‐sustaining therapy | Preventive ethics | |
| Justice | ||
| Proportionality | ||
| Goals of care | ||
| Continuation | On‐going consent | Proportionality |
| Autonomy | ||
| Goals of care | ||
| Discontinuation | Informed consent | Goals of care |
| Autonomy | ||
| Futility disputes | Preventive Ethics | |
| Respect for persons | ||
| Mediation | ||
| Religious or cultural objection to terminal discontinuation of life‐sustaining therapy | Proportionality | |
| Goals of care |
Who Decides?
Central to contemporary Western medicine is the principle of autonomy, manifested in most medical encounters as allowing patients to decide for themselves what should be done to and for them.[23] When patients are incapacitated, however, others must decide for them. Physicians must be prepared to guide families, with limited knowledge and familiarity with VA‐ECMO, through this process, providing information so that they truly can make informed decisions.[24]
In the absence of a patient‐designated healthcare agent or proxy, we turn to the surrogate of highest priority to assist with decision making. Although this may vary by jurisdiction, the typical hierarchy for surrogate decision making is as follows from highest to lowest priority: a court‐ appointed guardian or committee, a spouse or domestic partner, an adult son or daughter (>18 years old), a parent, a sibling, and then other relatives or close friends.[25] It should be noted that all adult children, regardless of age or birth order, should have equal standing as surrogate decision makers. In addition, if the surrogate of highest priority is unavailable or unwilling to make decisions, he or she may not simply delegate decision making to another person; we instead turn to the next individual in the hierarchy presented above.
Initiation of VA‐ECMO
VA‐ECMO is often initiated in emergencies, leaving little time for customary informed consent prior to treatment. Given that the need for VA‐ECMO might be anticipated earlier in the course of illness, however, in patients with chronic heart failure, those undergoing heart surgery, or those at risk for myocardial infarction, there may be an opportunity to initiate the consent process earlier. When possible, for patients or for families/surrogates, the consent process should include a full discussion of the risks, benefits, and goals of the VA‐ECMO, to allow for consideration of both the benefits and burdens of this treatment. This process should occur in conjunction with an exploration of goals of care and current or prior expressed wishes about medical and/or end‐of‐life care. As such, the hospitalist, particularly a hospitalist who may have had a longitudinal relationship with the patient, is integral to this process.
The hospitalist can help patients to clarify goals of care and elucidate whether a trial of VA‐ECMO, should it be medically indicated, is consistent with goals and wishes. Anticipating the need for ECMO and discussing it in advance will be advantageous, regardless of the ultimate decision, for if the patient loses capacity at any point during the course of treatment, documentation from these prior discussions about goals of care and attitudes toward various treatment modalities may serve as an advance directive to guide treatment decisions. Looking forward, as the use of VA‐ECMO becomes increasingly more commonplace, discussions about advance directives may expand accordingly, routinely integrating discussions of VA‐ECMO as a vital topic for consideration and reflection.
Continuation of VA‐ECMO
Once a patient is stabilized on VA‐ECMO, an opportunity emerges to engage in more comprehensive discussions about prognosis, treatment benefit and burdens, and goals of care. If VA‐ECMO was started emergently, there may not have been an opportunity to obtain informed consent prior to treatment initiation, and this vital task must now be assumed. Regardless of the circumstances, once VA‐ECMO is underway, we recommend that physicians regularly engage in discussions of on‐going consent.
We find this term to be helpful as a reminder that, although the patient is already receiving treatment, frequent discussions regarding prognosis, burdens and benefits of treatment, and goals of care remain essential. Clinically, it is important to monitor cardiopulmonary recovery and also renal function and neurologic status. As previously discussed, VA‐ECMO will not serve to fix the underlying cardiopulmonary pathology, and in fact, complications related to VA‐ECMO may be expected to grow over time.[7] Proportionality, a careful analysis of the benefits of continuing treatment, balanced with the risks and burdens imposed, will allow for thoughtful consideration about whether continuation is in the patient's best interest and consistent with the goals of care.
Discontinuation of VA‐ECMO
Three primary clinical indications may prompt the recommendation to discontinue VA‐ECMO: (1) there may be sufficient recovery and cardiopulmonary support is no longer needed, (2) there may be insufficent recovery with plans to transition to a VAD or transplantation, (3) or there may be insufficient recovery and recommendation for terminal discontinuation.
The procedure for discontinuing VA‐ECMO may vary with the clinical circumstances and institution. To anticipate the likely outcome with VA‐ECMO removed, prior to decannulation (the removal of the ECMO cannulas), support might be weaned weaned down with echocardiography used to assess cardiac function. Should indications point to decannulation, this process may take place in the operating room or catheters may be removed at the bedside.[7] In cases of terminal discontinuation, the VA‐ECMO may be stopped (assuming the patient is adequately sedated), the patient will then be allowed to die, with the cannulas subsequently removed.
Analogous to discontinuation of other cardiac devices, such as a pacemaker or defibrillator, ceasing VA‐ECMO may result in: (1) no clinical consequences, as the patient has recovered sufficiently; (2) immediate declaration of death; or (3) the emergence of new symptoms, for example symptoms of heart failure, which may precede death.[26] So as to prospectively account for this variability, a full discussion of the rationale behind discontinuation, as well as the range of expected outcomes, should precede cessation. Similarly, clinicians should implement a plan for symptom management and palliation. In cases of expected recovery, a contingency plan should be developed in case the patient unexpectedly decompensates upon or shortly after cessation. In sum, it remains essential to understand the prospective course, as the lack of anticipatory planning may precipitate confusion, distress, and conflict for patients, family members, and the clinical team.
DNR on VA‐ECMO?
Hospitalists accustomed to writing DNR orders may be distressed to find that, in our opinion, DNR orders are not appropriate for patients who are maintained on VA‐ECMO.[9] (It should also be noted that patients on VV‐ECMO, a device that only provides pulmonary function, could suffer a cardiac arrest necessitating CPR; thus, DNR may be relevant in this clinical context.) VA‐ECMO provides more effective oxygenation and perfusion than traditional advanced cardiac life support with CPR. Thus patients on VA‐ECMO will generally not receive CPR and, consequently, there is effectively no clinical meaning to a DNR order for a patient on VA‐ECMO. That said, when discontinuing VA‐ECMO (and at times VV‐ECMO), depending on the goals of care, a DNR may be useful to prevent further aggressive treatment should the patient arrest following cessation of ECMO.
The clinician will be wise to recognize that if families request a DNR order for a patient on VA‐ECMO, they are asking for something. Although a request not to resuscitate may not make medical sense in this context, clinicians must take the time to explore what is intended by this request. For many families, DNR is a stepping stone toward de‐escalation of treatment and a first move toward withdrawal of life‐sustaining therapies.[27, 28] A nuanced understanding of what a family hopes to accomplish by the suggested order, and specifically whether and how goals of care may have changed, is vital toward the maintenance of an appropriate, timely, and evolving treatment plan.
Terminal Discontinuation of VA‐ECMO
Among clinical ethicists, some of the most distressing conversations and meetings we have had with families have emerged in the context of terminal discontinuation of VA‐ECMO. Unlike mechanical ventilation, which theoretically may be continued indefinitely via tracheostomy, VA‐ECMO is only a temporary measure and, according to ELSO, should be discontinued promptly if healthy survival is not anticipated with the possibility of stopping for futility explained to the family before ECLS is begun.[21] Given the time constraints for what may have been an emergency procedure, and given the frequent reluctance of families and surrogates to discontinue life‐sustaining therapies, how does a clinician or institution ethically enact these guidelines? With respect to practical guidance, we offer 3 suggestions for directing these conversations.
First, we suggest physicians discuss the possibility and potential rationales of terminal discontinuation early and often, ideally as part of the initial consent process. Second, informed consent conversations should address potential complications (stroke, hemorrhage, and thrombosis) and their sequelae alongside discussions with patients and surrogates about their wishes in the context of such an event. Finally, we also recommend frequently revisiting the goals of care with the surrogate throughout the course of treatment.[28] Thus, when goals of care can no longer be achieved by continuing VA‐ECMO, either: (1) because the patient has no chance for recovery; (2) because VA‐ECMO no longer serves its intended purpose; or (3) owing to harm from complications, families may be able to appreciate that continuation of the intervention has become ethically disproportionate, and ECMO is now more burdensome than beneficial. Continuous and open dialogue should build a strong foundation of trust and knowledge that allows the surrogate to understand and accept the rationale behind a recommendation to terminally discontinue treatment, should the clinical course necessitate such.[29]
CONCLUSION
With indications for and utilization of ECMO in adult patients expanding, hospitalists may be expected to encounter these technologies with greater frequency and guide patients and families with medical decision‐making. Although the ethical issues reviewed are certainly not exclusive to ECMO, specific facets of ECMO, as discussed, may precipitate unique challenges or exacerbate common ones. Hospitalists can help to uphold patient autonomy by providing information that enables patients and surrogates to actively participate in goal setting and decision‐making. As the utilization of this technology grows, further research will need to address decision‐making in the context of ECMO to ensure that the process remains optimally patient‐ and family‐centered.
Acknowledgment
Disclosures: All work was performed at Weill Cornell Medical College of Cornell University, New York Presbyterian Weill Cornell Medical Center, and University of Pennsylvania. The authors report no conflicts of interest.
- , . Current status of extracorporeal life support (ECMO) for cardiopulmonary failure. Minerva Anestesiol. 2010;76(7):534–540.
- . . The first 20 years of the heart‐lung machine. Tex Heart Inst J. 1997;24(1):1–8.
- , , , , . Venovenous extracorporeal membrane oxygenation in adults: practical aspects of circuits, cannulae, and procedures. J Cardiothorac Vasc Anesth. 2012;26(5):893–909.
- , , , et al. Extracorporeal life support for adult cardiorespiratory failure. Surgery. 1993;114(2):161–172; discussion 172–163.
- , . Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011;365(20):1905–1914.
- , , , , . Extracorporeal life support. BMJ. 2010;341:c5317.
- , , , , , . Extracorporeal membrane oxygenation for treating severe cardiac and respiratory failure in adults: part 2‐technical considerations. J Cardiothorac Vasc Anesth. 2010;24(1):164–172.
- , . Mechanical circulatory support for bridge to decision: which device and when to decide. J Card Surg. 2010;25(4):425–433.
- , , . DNR on ECMO: a paradox worth exploring. J Clin Ethics. 2013;25(1):13–19.
- , , , et al. Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR). Health Technol Assess. 2010;14(35):1–46.
- , , , et al. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome. JAMA. 2009;302(17):1888–1895.
- , , , et al. Cardiopulmonary resuscitation with assisted extracorporeal life‐support versus conventional cardiopulmonary resuscitation in adults with in‐hospital cardiac arrest: an observational study and propensity analysis. Lancet. 2008;372(9638):554–561.
- , , , et al. Extracorporeal membrane oxygenation for refractory cardiogenic shock after cardiac surgery: predictors of early mortality and outcome from 51 adult patients. Eur J Cardiothorac Surg. 2010;37(2):328–333.
- , , , et al. Venoarterial extracorporeal membrane oxygenation for treatment of cardiogenic shock: clinical experiences in 45 adult patients. J Thorac Cardiovasc Surg. 2008;135(2):382–388.
- , , , et al. Outcomes and long‐term quality‐of‐life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care Med. 2008;36(5):1404–1411.
- , . Extracorporeal life support as a bridge to lung transplantation. Clin Chest Med. 2011;32(2):245–251.
- Extracoporeal Life Support Organization. General Guidelines for all ECLS Cases. 2012; http://www.elsonet.org/. Accessed August 5, 2014.
- , , , et al. Impact of extracorporeal life support on outcome in patients with idiopathic pulmonary arterial hypertension awaiting lung transplantation. J Heart Lung Transplant. 2011;30(9):997–1002.
- , , , . Ambulatory extracorporeal membrane oxygenation: a new approach for bridge‐to‐lung transplantation. J Thorac Cardiovasc Surg. 2010;139(6):e137–e139.
- , , , et al. Ambulatory veno‐venous extracorporeal membrane oxygenation: innovation and pitfalls. J Thorac Cardiovasc Surg. 2011;142(4):755–761.
- Extracoporeal Life Support Organization. General Guidelines for all ECLS Cases. 2012; http://www.elsonet.org/. Accessed August 5, 2014.
- Extracorporeal Life Support Organization. ECLS Registry Report United States Summary. August 2014; http://www.elsonet.org/. Accessed August 5, 2014.
- , . Principles of Biomedical Ethics. 6th ed. New York, NY: Oxford University Press; 2009.
- , , , et al. Decision making in advanced heart failure: a scientific statement from the American Heart Association. Circulation. 2012;125(15):1928–1952.
- , , . Ethics in Clinical Practice. 2nd ed. Sudbury, MA: Jones and Bartlett; 2005.
- . Pacemaker and defibrillator deactivation in competent hospice patients: an ethical consideration. Am J Hosp Palliat Care. 2005;22(1):14–19.
- , , , . Limitation of medical care: an ethnographic analysis. J Clin Ethics. 1993;4(2):134–145.
- . A Palliative Ethic of Care: Clinical Wisdom at Life's End. Sudbury, MA: Jones and Bartlett; 2006.
- , , , , , . Extracorporeal membrane oxygenation as a bridge to chemotherapy in an orthodox Jewish patient. Oncologist. 2014;19(9):985–989.
- , . Current status of extracorporeal life support (ECMO) for cardiopulmonary failure. Minerva Anestesiol. 2010;76(7):534–540.
- . . The first 20 years of the heart‐lung machine. Tex Heart Inst J. 1997;24(1):1–8.
- , , , , . Venovenous extracorporeal membrane oxygenation in adults: practical aspects of circuits, cannulae, and procedures. J Cardiothorac Vasc Anesth. 2012;26(5):893–909.
- , , , et al. Extracorporeal life support for adult cardiorespiratory failure. Surgery. 1993;114(2):161–172; discussion 172–163.
- , . Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011;365(20):1905–1914.
- , , , , . Extracorporeal life support. BMJ. 2010;341:c5317.
- , , , , , . Extracorporeal membrane oxygenation for treating severe cardiac and respiratory failure in adults: part 2‐technical considerations. J Cardiothorac Vasc Anesth. 2010;24(1):164–172.
- , . Mechanical circulatory support for bridge to decision: which device and when to decide. J Card Surg. 2010;25(4):425–433.
- , , . DNR on ECMO: a paradox worth exploring. J Clin Ethics. 2013;25(1):13–19.
- , , , et al. Randomised controlled trial and parallel economic evaluation of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR). Health Technol Assess. 2010;14(35):1–46.
- , , , et al. Extracorporeal membrane oxygenation for 2009 influenza A (H1N1) acute respiratory distress syndrome. JAMA. 2009;302(17):1888–1895.
- , , , et al. Cardiopulmonary resuscitation with assisted extracorporeal life‐support versus conventional cardiopulmonary resuscitation in adults with in‐hospital cardiac arrest: an observational study and propensity analysis. Lancet. 2008;372(9638):554–561.
- , , , et al. Extracorporeal membrane oxygenation for refractory cardiogenic shock after cardiac surgery: predictors of early mortality and outcome from 51 adult patients. Eur J Cardiothorac Surg. 2010;37(2):328–333.
- , , , et al. Venoarterial extracorporeal membrane oxygenation for treatment of cardiogenic shock: clinical experiences in 45 adult patients. J Thorac Cardiovasc Surg. 2008;135(2):382–388.
- , , , et al. Outcomes and long‐term quality‐of‐life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care Med. 2008;36(5):1404–1411.
- , . Extracorporeal life support as a bridge to lung transplantation. Clin Chest Med. 2011;32(2):245–251.
- Extracoporeal Life Support Organization. General Guidelines for all ECLS Cases. 2012; http://www.elsonet.org/. Accessed August 5, 2014.
- , , , et al. Impact of extracorporeal life support on outcome in patients with idiopathic pulmonary arterial hypertension awaiting lung transplantation. J Heart Lung Transplant. 2011;30(9):997–1002.
- , , , . Ambulatory extracorporeal membrane oxygenation: a new approach for bridge‐to‐lung transplantation. J Thorac Cardiovasc Surg. 2010;139(6):e137–e139.
- , , , et al. Ambulatory veno‐venous extracorporeal membrane oxygenation: innovation and pitfalls. J Thorac Cardiovasc Surg. 2011;142(4):755–761.
- Extracoporeal Life Support Organization. General Guidelines for all ECLS Cases. 2012; http://www.elsonet.org/. Accessed August 5, 2014.
- Extracorporeal Life Support Organization. ECLS Registry Report United States Summary. August 2014; http://www.elsonet.org/. Accessed August 5, 2014.
- , . Principles of Biomedical Ethics. 6th ed. New York, NY: Oxford University Press; 2009.
- , , , et al. Decision making in advanced heart failure: a scientific statement from the American Heart Association. Circulation. 2012;125(15):1928–1952.
- , , . Ethics in Clinical Practice. 2nd ed. Sudbury, MA: Jones and Bartlett; 2005.
- . Pacemaker and defibrillator deactivation in competent hospice patients: an ethical consideration. Am J Hosp Palliat Care. 2005;22(1):14–19.
- , , , . Limitation of medical care: an ethnographic analysis. J Clin Ethics. 1993;4(2):134–145.
- . A Palliative Ethic of Care: Clinical Wisdom at Life's End. Sudbury, MA: Jones and Bartlett; 2006.
- , , , , , . Extracorporeal membrane oxygenation as a bridge to chemotherapy in an orthodox Jewish patient. Oncologist. 2014;19(9):985–989.
Surgical innovation and ethical dilemmas: Precautions and proximity
No! I am not Prince Hamlet, nor was meant to be;
Am an attendant lord, one that will do
To swell a progress, start a scene or two…
—T.S. Eliot, The Love Song of J. Alfred Prufrock
Let me start by thanking the organizers for their invitation to be here and to start this off. I am not sure if that invitation was an act of kindness or of throwing a fellow bioethicist to the lions, as we will be addressing a complicated set of issues upon which well-intentioned folks disagree and sometimes disagree with a passion.
What I would like to do is to lay out some of the inherent ethical problems related to surgical innovation. I will argue that some of these problems are unique to surgery and that others relate to how we have chosen to define categories like research and practice. Other problems involve how we view the proportionality of risks and benefits in surgical research. I will argue that we have falsely analogized surgical progress to progress made in other areas of biomedical research and misunderstood the highly personal, or proximate, nature of surgical inquiry. Without appreciating the import of what I will call “surgical proximity,” we will be unable to adequately address ethical issues in surgical innovation.
PROBLEMS OR DILEMMAS?
So let me begin with the title of our session, “Surgical Innovation and Ethical Dilemmas,” and why this juxta position is counterproductive. A colleague long ago taught me to distinguish problems from dilemmas—the former being resolvable, the latter intractable, often involving a choice between two equally unfavorable choices.
Although I may be making too much of the semantics, I do think the title betrays a presumption that surgical innovation invariably forces adversarial choices. It tends to dichotomize ethical reflection, pitting those who favor prudence against those who endorse progress, or it creates too stark a difference between ethical issues in surgical practice and those encountered in the conduct of surgical research.
Even therapeutic, validated surgery in many ways has the potential to become innovative, if not outright experimental. Patients may have anatomical differences that require surgical improvisation, or complications may arise during “routine” surgery, creating the need for an imaginative response.1 At what point do these departures from expected care become novel interventions, innovative or even experimental? A routine case with an unexpected turn can even become a case report opening up a new field of endeavor.
For instance, the field of stereotactic functional neurosurgery was born out of a “routine” case of ablative surgery for Parkinson’s disease in the 1980s, when the French neurosurgeon Alim Benabid was using electrodes to determine which areas of the brain should be destroyed. As he was mapping the thalamus, he noted that the tremor of his patient abated. This led him to wonder if one could treat drug-resistant Parkinson’s with electrical stimulation instead of destructive lesioning.2 Benabid’s translational insight during an ordinary case led to the development of the rather extraordinary field of stereotactic functional neurosurgery and neuromodulation.3,4
Another example from an earlier era comes from the life work of neurosurgeon Wilder Penfield, who did pioneering work in the surgical treatment of epilepsy. Here, the accumulation of experience from “routine care” led to generalizable knowledge, much like hypotheses are validated in experimental work. In Penfield’s case, his clinical use of electrical stimulation to plan resections of scar tissue causing epilepsy led him to map the human homunculus, a magnificent achievement of profound importance.5,6
So let us avoid simplistic and confounding demarcations. Instead of dichotomizing innovation and prudence—or surgical research and surgical practice—let us try to start our deliberations with an eye toward a more synthetic approach. Like most things in nature and in biology, ethics too is on a continuum with gradations that can fit into an Aristotelian taxonomy. Let us emulate what Aristotle called phronesis, or practical wisdom, these next 2 days so that we achieve constructive outcomes, or what the pragmatists would call instrumental goods.7
If we are successful in laying out the ethical issues in this clinically pragmatic fashion, we can turn intractable “dilemmas” into problems amenable to resolution through the particularistic invocation of ethical principles as they relate to the surgical context.8 If we follow this inductive method of moral problem solving, we will avoid sweeping ethical generalizations, or categoricals, that can misrepresent the complexity of innovative research and deprive society of its benefits.9
INNOVATION VS PRUDENCE: A FALSE DICHOTOMY
So let us start by understanding the presuppositions that led to the expectation that dilemmas will descend upon those who engage in surgical innovation. In my view, this expectation begins with what is called the precautionary principle, a concept with some currency in the realm of environmental ethics.10
The precautionary principle urges caution and prudence when facing unknowns and is an antecedent sort of utilitarianism. One makes judgments about the advisability of actions based on a prior assessment of foreseeable risks and benefits. If the risks are excessive or exceed benefits, the precautionary principle urges care, caution, and even avoidance of a given course of action.
When the precautionary principle is implicitly invoked in making judgments about research, the objective is to pursue a degree of safety that is comparable to that of established therapy. But interventions that have progressed to being deemed “therapeutic” have of course achieved a requisite degree of both safety and efficacy—that is what makes them therapeutic, as opposed to investigational, interventions. One cannot know before one has conducted a clinical trial, and completed statistical analysis, whether a new surgical advance or device meets these expectations. Because of this lack of knowledge, there is an inherent degree of risk in any novel intervention.
The challenge posed by innovation or novelty creates the possibility of untoward events. It leads to invocation of the precautionary principle, which, echoing the admonitions of the philosopher Hans Jonas, urges us to “give greater weight to the prognosis of doom than to that of bliss.”11,12
This is not a bad way to go through life, assuming one wants to emulate T.S. Eliot’s J. Alfred Prufrock, who lamentably “measured out my life with coffee spoons.”13 Unlike the surgeon, who must make decisions in real time, Eliot’s protagonist could not move forward. Despite his desire to avoid the indecision of Prince Hamlet, alluded to in this paper’s epigraph, Prufrock was paralyzed by doubts and fears, with “time yet for a hundred indecisions, and for a hundred visions and revisions.”13
Despite Eliot’s invocation of “a patient etherised upon a table,”13 the poem shares little with the surgical life. It has much more in common with the precautionary principle. Like Prufrock, the precautionary principle favors what is known— the status quo—as what is unknown is invariably more risky than the familiar. Needless to say, this is antithetical to innovation because discovery invariably requires scenarios that involve novelty and unknown risks. When faced with the certain security of stasis or the potential dangers of innovation, the precautionary principle will invariably choose stasis, leading us, as the legal scholar Cass Sunstein notes, “in no direction at all.”14
Seen through the prism of the precautionary principle, then, surgical innovation invariably presents a dilemma. Discovery and innovation are fundamentally at odds with the precautionary principle, because of their potential for risk.15
The challenge posed by the precautionary principle—which, to be fair, is seen in all areas of clinical research—becomes even more pronounced in surgical research because of the size and scope of clinical trials. As is well appreciated here, compared with drug trials, surgical trials are small. Sometimes they can involve a single subject, whereas drug trials may include thousands of participants. Because of drug trials’ large volume of subjects, therapeutic effects can be small to justify ongoing research. In a surgical trial or a device trial, the number of subjects is smaller, so the therapeutic impact has to be larger to warrant further development and ongoing study. This burden of scale increases the probability of reciprocally large adverse effects. This potential for disaster magnifies the impact of the precautionary principle and may lead to a distortion in ethical judgment along the lines of Hans Jonas’ admonition.12
By all of this I am not suggesting that we abandon precautions and prudence. Instead, my point is to explicate the additional challenges faced by surgical research and the sway of the precautionary principle over this area of inquiry and innovation. By being explicit about the impact of this principle, we can be cognizant of its potential to distort judgments about risks and benefits. Only then can we hope to balance the pursuit of progress with that of safety.
SURGICAL RESPONSIBILITY
These distortions also need to be recognized, and made explicit, because surgical research, more so than pharmacologic research, is much more personal and intimate. This point becomes clear if we consider a surgical trial that does not succeed.
In the surgical arena, such failures are taken to heart and personalized. Unlike trials that involve drugs, surgical research is more proximate. It is not just the failure of a drug or of pharmacology; it is also possibly the failure of the operator, the surgeon who did not achieve the desired goal because of poor execution of surgical technique.
This crucial difference in medical versus surgical cultures is captured by Charles Bosk in his magisterial sociological study of surgery, Forgive and Remember: Managing Medical Failure. In a discussion of morbidity and mortality rounds, Bosk writes:
The specific nature of surgical treatment links the action of the physician and the response of the patient more intimately than in other areas of medicine....When the patient of an internist dies, the natural question his colleagues ask is, “What happened?” When the patient of a surgeon dies, his colleagues ask, “What did you do?”16
As in clinical surgical practice, in surgical research, it is the personal and individualized mediation of the surgeon that is central to the intervention. Here the intermediary is neither a drug nor its bioavailability; rather, it is the operator’s technique plus or minus the operative design and the reliability of an instrument or a device. In either case, the contribution is more proximate and personal, stemming from the actions of individual surgeons and the work of their hands.
History is instructive on this theme of surgical causality and personal culpability if we consider the life of Harvey Cushing, a Cleveland native whose ashes are buried nearby in Lake View Cemetery.17 Cushing was a gifted and innovative surgeon whose technique handling tissues changed how the brain was approached operatively. He is acknowledged as the father of neurosurgery, having created a professional nexus to institutionalize and carry on his innovative work.18
Cushing’s greatest innovation was probably in his individual efforts as a working surgeon. Over the course of his lifetime, he made the resection of brain tumors a safe and sometimes effective treatment for an otherwise dread disease. Michael Bliss, Cushing’s most recent biographer, reports mortality data from more than 2,400 surgeries done by Cushing during his operative lifetime.17 Early in his career (from 1896 to 1911), while he was at Johns Hopkins, Cushing’s case mortality rate was 24.7%. During his later years at the Brigham Hospital, it was 16.2%. By 1930–1931 it was down to 8.8%.
These were extraordinary statistics: no one matched Cushing’s numbers, or his ability to do what he did. Bliss cites mortality data from his surgical contemporaries in the late 1920s as ranging from approximately 35% to 45%. By the numbers Bliss compares Cushing’s talent—his truly brilliant outlier performance—to that of his Jazz Age contemporary, Babe Ruth, who also had outsized talent compared with his peers.17
Cushing himself, a collegiate second baseman at Yale, linked sport and statistics in a most telling way. Documenting his ongoing surgical progress was a hedge against failure and lightened the emotional burdens of the surgical suite. Cushing observed: “A neurosurgeon’s responsibilities would be insufferable if he did not feel that his knowledge of an intricate subject was constantly growing—that his game was improving.”17
This quote and Cushing’s operative statistics point to his nascent effort to engage in evidence-based research and speaks to the spectacular difference that a surgical innovator can make. The extraordinary results achieved by Cushing in his day also suggest that surgeons are not fungible at the vanguard of discovery. History tells us, as contemporary assessments of current research cannot, that only Harvey Cushing could achieve Cushingoid results.
A second point that stems from Cushing’s comment about the burdens of operative work and surgical research is how personally taxing that responsibility can be. Without making progress, he said, the “responsibilities would be insufferable”17 (my italics).
Even the great Harvey Cushing perceived the weight of these burdens, suggesting that any effort to depersonalize the ethics of surgical innovation would be naïve. The singularity of Cushing’s surgical accomplishments (his operative excellence as compared with his peer group) and the felt weight of these achievements suggest that surgical innovation is highly personal and proximate to the surgical researcher in a way that is distinct for surgical innovation. This relationship of operative causality and personal culpability can be subsumed under what I will call surgical proximity.
SURGICAL PROXIMITY
Surgical proximity has several implications for the conduct of research. In this section I will address two issues: conflicts of interest and clinical equipoise.
Surgical proximity and conflicts of interest
As the Cushing example illustrates, at least at the outset of a clinical trial the surgeon himself is part of the actual design of the trial. The same surgical method in the hands of one of his contemporaries would have led to a dramatically different result. The surgeon who is at the forefront of innovation becomes an experimental variable until the methods can be generalized.
The importance of the operator as an essential ingredient in early surgical research points to a key difference with pharmaceutical trials, where the purity of the drug-based intervention can be maintained. This difference has implications for the “rebuttable presumption” stance promulgated by the Association of American Medical Colleges (AAMC), which looks askance at innovators conducting clinical trials if they have a conflict of interest, such as intellectual property rights for their discoveries.19,20
In many cases, the work that surgical innovators do, as in the case of device development, could not be done without collaborations with industry. Taking the surgical talent of the potentially conflicted—but highly talented—innovator out of the equation may be counterproductive.
Time does not allow me to fully address the conflict-of-interest issue in this forum; suffice it to say that the differential knowledge, skill, and talent of early surgical innovators may be the difference between a trial’s early success or failure. The role of such innovators should neither be truncated or precluded nor be viewed a priori in a prejudicial fashion. Instead, their talents and vision should be welcomed as instrumental to the potential success of the work, managed of course with the proper degree of transparency and disclosure.
As I have noted previously,4,21 if the rationale for a conflict of interest is to allow laudable work to continue that otherwise could not occur without the personal intervention, and talents, of a surgical innovator, it seems prejudicial to view the conflict of interest as disqualifying until proven otherwise. This view is consistent with the legal framework of the US Constitution, which explicitly authorizes Congress “to promote the Progress of Science and the useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries.”22 It is also embedded in the Patent Act of 1790,23 which balances the patent’s period of exclusivity against the inventor’s obligation to share and disseminate expertise. This role for the innovator is also consistent with the intent and incentives within the framework of the Bayh-Dole Act of 1980,24 which was passed with the expectation that industrial partnerships would move ideas from the bench to the bedside.
I hope that others at this conference will be able to return to the issue of conflicts of interest and how the question of surgical proximity may, or may not, alter our ethical judgments about the surgeon’s role in research where there may be a conflict of interest.
Surgical proximity and equipoise
Surgical proximity also has an impact on clinical equipoise, the ethical neutrality about outcomes felt necessary for the conduct of clinical trials.25 The surgeon’s sense of causality and proximity to the operative act makes surgical research different because the equipoise, which exists objectively about the research questions at hand, may not exist in the mind of the surgical researcher. Let me explain.
Taking a patient to surgery is highly consequential. As we have seen from Bosk’s work,16 surgeons feel a sense of responsibility for their operative acts and surgical work. This felt responsibility, inculcated in surgical training and surgical culture, obligates the surgeon to make a proportionality judgment about bringing a patient to the operating room, be it for research or for clinical practice. In this way, surgical investigators have determined, at least in their own minds, that net benefits outweigh net risks, thus breaching clinical equipoise.
It is hard for a surgeon to commit to an operative procedure—be it for clinical care or for research— with all its attendant risks if he or she does not believe that the intervention is safe and effective. We can appreciate the importance of the surgeon’s perspective on the utility of any proposed operation if we consider the opposing question of futility in clinical practice.26 Whereas internists or intensivists might be compelled by families to continue aggressive intensive care, surgeons cannot be compelled to take a patient to the operating room when they deem that the risks outweigh the benefits. Because the surgeon is such a proximate moral agent, he or she will be held culpable for the actions that occur in theater. This degree of responsibility is accompanied by a retained degree of discretion—an almost old-world paternalistic discretion27—to counter the demands for disproportionate care.
This same sense of culpability and responsibility informs the surgeon’s willingness to take any patient to the operating room. In the case of research, this willingness becomes an issue of concern because it means that in the surgeon’s mind, favorable operative proportionality has been achieved.
This process of self-regulation28 can have implications for the informed-consent process because surgeons believe in their work and can exert a strong dynamic transference on subjects who may be desperate for cure.29 Because of this potential bias, surgical research may become especially prone to a therapeutic misconception. That is, if the surgeon is willing to take the risks of doing an innovative procedure in the operating room, then it has crossed some sort of internal threshold of proportionality in which the risks, whatever they are, have become acceptable given the putative benefits. Given what Bosk has written about surgical failure,16 a high bar is crossed when a surgeon takes a patient to the operating room for a novel procedure, even though motivations at that bar may occasionally be mixed.* (*Lest I be misconstrued as too idealistic, this burdens-vs-benefits equation may be fueled by a complex mosaic of motivations and may not always be informed fully by patient-centered benefits. If the surgeon is the innovator and the inventor, these benefits may be for the pursuit of a hypothesis and associated with potential fame or fortune. But even in these cases, judgments about proportionality are informed by surgical proximity. [For more on the ethics of conflicts of interest, see references 4 and 21.])
FROM SURGICAL RESEARCH TO EDUCATION
This leads to my closing observations about transitions in surgical research, when the work of the pioneering surgeon is bequeathed to the broader surgical community to pick up the torch—or scalpel—and expand the work.
This takes me away from research and, fittingly here at a medical school dedicated to research training, brings me to medical education. To transcend the personal dimensions of surgical innovation—and the courage and vision of the founders—and sustain it more broadly, innovators also have to become educators of future surgeons, organizers of talent, and moral exemplars for the next generation. They have to appreciate that the work that they started, if it is important, will not be completed during their tenure but that future generations will carry it forward and expand upon it. They also have to prepare the next generation with the tools and orientation to appreciate their vision and to embrace what Thomas Kuhn might call new scientific paradigms.30
On several occasions Wilder Penfield, who founded the Montreal Neurological Institute, wrote with regret about Victor Horsley, the neurosurgeon at Queens Square in London. Penfield viewed Horsley as the founder of his field, but Horsley left no disciples. In his autobiography, fittingly entitled No Man Alone, Penfield noted that Horsley, “the most distinguished pioneer neurosurgeon, had died in 1916 without having established a school of neurosurgery.”5 This is in contrast to the discipline-building work of Cushing.
It is not an accident that Dr. Cushing founded a field full of trainees and protégés, of which my co-panelists are descendants. It was intentional and part of his ethos of being truly innovative. And it is not an accident that the distinguished surgical innovators at this symposium have also created institutional structures to continue their work for decades to come. Their achievements have transcended the individual innovator and have become systematic. It is said that Dr. Thomas Starzl launched a field.31 Dr. Denton Cooley founded the Texas Heart Institute.32 Dr. Thomas Fogarty started the Fogarty Institute for Innovation, whose mission statement explicitly notes that it is “an educational non-profit that mentors, trains and inspires the next generation of medical innovators.”33 Each of these pioneers, I believe, appreciates the need for continuity and dissemination.
But even here there is something that we nonsurgeons need to understand: although the work transcends the individual surgeon, the ties remain personal and linked to the impact and legacy of founders. Take, for example, highly prized membership in the Denton A. Cooley Cardiovascular Surgical Society.34 This too is about the importance of individuals and surgical proximity, but here it is transgenerational.
CONCLUSION
If we truly want to continue the dialogue begun here today, we need to understand these social and professional networks and the importance of surgical proximity in transmitting both methods and values. The proximate nature of surgical research—and the causality and responsibility that accrues to the surgeon—makes surgical research different than other areas of biomedical inquiry. This difference has implications for risk-benefit analysis, conflicts of interest, and clinical equipoise. I hope that my colleagues return to these themes in the coming days so that the regulation of this important area of research can be informed by a deeper understanding of the ethics of surgical discovery and innovation.35
Acknowledgments
Dr. Fins gratefully acknowledges the invitation to participate in this symposium, the helpful suggestions of Dr. Eric Kodish, and partial grant support of the Weill Cornell Medical College Research Ethics Core, NIH Clinical & Translational Science Center UL1-RR024966.
- Frader JE, Caniano DA. Research and innovation in surgery. In: McCullough LB, Jones JW, Brody BA, eds. Surgical Ethics. New York, NY: Oxford University Press; 1998:216–241.
- Speelman JD, Bosch DA. Resurgence of functional neurosurgery for Parkinson’s disease: a historical perspective. Mov Disord 1998; 13:582–588.
- Holstein WJ. Rewiring the brain: how a bright idea became an innovative medical device. US News & World Report. March 1, 1999:52–53.
- Fins JJ, Schachter M. Investigators, industry, and the heuristic device: ethics, patent law, and clinical innovation. Account Res 2001; 8:219–233.
- Penfield W. No Man Alone: A Neurosurgeon’s Life. Boston, MA: Little Brown; 1977.
- Feindel W. The contributions of Wilder Penfield to the functional anatomy of the human brain. Hum Neurobiol 1982; 1:231–234.
- Aristotle. The Nicomachean Ethics. Weldon JEC, trans. Amherst, NY: Prometheus Books; 1987.
- Fins JJ, Bacchetta MD, Miller FG. Clinical pragmatism: a method of moral problem solving. Kennedy Inst Ethics J 1997; 7:129–145.
- Miller FG, Fins JJ. Protecting human subjects in brain research: a pragmatic perspective. In: Illes J, ed. Neuroethics: Defining the Issues in Theory, Practice and Policy. New York, NY: Oxford University Press; 2005.
- Pollan M. The year in ideas: A to Z.; precautionary principle. New York Times. December 9, 2001.
- van den Belt H. Debating the precautionary principle: “guilty until proven innocent” or “innocent until proven guilty”? Plant Physiol 2003; 132:1122–1126.
- Jonas H. The Imperative of Responsibility: In Search of an Ethics for the Technological Age. Chicago, IL: University of Chicago Press; 1985:34.
- Eliot TS. The Love Song of J. Alfred Prufrock. In: Abrams MH, ed. The Norton Anthology of English Literature. Vol 2. 4th ed. New York, NY: W.W. Norton & Co; 1979:2259–2264.
- Sunstein CR. The paralyzing principle. Regulation. Winter 2002– 2003; 25(4):32–37.
- Holm S, Harris J. Precautionary principle stifles discovery. Nature 1999; 400:398.
- Bosk C. Forgive and Remember: Managing Medical Failure. Chicago, IL: University of Chicago Press; 1979:29–30.
- Bliss M. Harvey Cushing: A Life in Surgery. Oxford, UK: Oxford University Press; 2005.
- Pinkus RL. Mistakes as a social construct: an historical approach. Kennedy Inst Ethics J 2001; 11:117–133.
- AAMC Task Force on Financial Conflicts of Interest in Clinical Research. Protecting subjects, preserving trust, promoting progress I: policy and guidelines for the oversight of individual financial interests in human subjects research. Acad Med 2003; 78:225–236.
- AAMC Task Force on Financial Conflicts of Interest in Clinical Research. Protecting subjects, preserving trust, promoting progress II: principles and recommendations for oversight of an institution’s financial interests in human subjects research. Acad Med 2003; 78:237– 245.
- Fins JJ. Disclose and justify: intellectual property, conflicts of interest, and neurosurgery. Congress Quarterly (Official Newsmagazine of the Congress of Neurological Surgeons) 2007; 8(3):34–36.
- U.S. Constitution, art. I, §8, cl. 8; see also id. at art. I, §8, cl. 18.
- Patent Act of 1790, ch. 7, 1 Stat. 109–111 (1790).
- Patent and Trademark Act Amendments of 1980 (Bayh-Dole Act); Pub L No. 96-517. Codified as 35 USC §§200–212 (1994).
- Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987; 317:141–145.
- Callahan D. Necessity, futility, and the good society. J Am Geriatr Soc 1994; 42:866–867.
- Katz J. The Silent World of Doctor and Patient. New York, NY: Free Press; 1984.
- Jones RS, Fletcher JC. Self-regulation of surgical practice and research. In: McCullough LB, Jones JW, Brody BA, eds. Surgical Ethics. New York, NY: Oxford University Press; 1998:255–279.
- Kim SY. Assessing and communicating the risks and benefits of gene transfer clinical trials. Curr Opin Mol Ther 2006; 8:384– 389.
- Kuhn TS. The Structure of Scientific Revolutions. 2nd ed. Chicago, IL: University of Chicago Press; 1970.
- Starzl TE. The Puzzle People: Memoirs of a Transplant Surgeon. Pittsburgh, PA: University of Pittsburgh Press; 2003.
- Twenty Five Years of Excellence: A History of the Texas Heart Institute. Houston, TX: Texas Heart Institute Foundation; 1989.
- Fogarty Institute for Innovation Web site. Available at: http://01659a8. netsolhost.com/aboutus.html. Accessed June 6, 2008.
- Denton A. Cooley Cardiovascular Surgical Society Web site. Available at: http://www.cooleysociety.com/about.html. Accessed June 6, 2008.
- de Melo-Martín I, Palmer LI, Fins JJ. Viewpoint: developing a research ethics consultation service to foster responsive and responsible clinical research. Acad Med 2007; 82:900–904.
No! I am not Prince Hamlet, nor was meant to be;
Am an attendant lord, one that will do
To swell a progress, start a scene or two…
—T.S. Eliot, The Love Song of J. Alfred Prufrock
Let me start by thanking the organizers for their invitation to be here and to start this off. I am not sure if that invitation was an act of kindness or of throwing a fellow bioethicist to the lions, as we will be addressing a complicated set of issues upon which well-intentioned folks disagree and sometimes disagree with a passion.
What I would like to do is to lay out some of the inherent ethical problems related to surgical innovation. I will argue that some of these problems are unique to surgery and that others relate to how we have chosen to define categories like research and practice. Other problems involve how we view the proportionality of risks and benefits in surgical research. I will argue that we have falsely analogized surgical progress to progress made in other areas of biomedical research and misunderstood the highly personal, or proximate, nature of surgical inquiry. Without appreciating the import of what I will call “surgical proximity,” we will be unable to adequately address ethical issues in surgical innovation.
PROBLEMS OR DILEMMAS?
So let me begin with the title of our session, “Surgical Innovation and Ethical Dilemmas,” and why this juxta position is counterproductive. A colleague long ago taught me to distinguish problems from dilemmas—the former being resolvable, the latter intractable, often involving a choice between two equally unfavorable choices.
Although I may be making too much of the semantics, I do think the title betrays a presumption that surgical innovation invariably forces adversarial choices. It tends to dichotomize ethical reflection, pitting those who favor prudence against those who endorse progress, or it creates too stark a difference between ethical issues in surgical practice and those encountered in the conduct of surgical research.
Even therapeutic, validated surgery in many ways has the potential to become innovative, if not outright experimental. Patients may have anatomical differences that require surgical improvisation, or complications may arise during “routine” surgery, creating the need for an imaginative response.1 At what point do these departures from expected care become novel interventions, innovative or even experimental? A routine case with an unexpected turn can even become a case report opening up a new field of endeavor.
For instance, the field of stereotactic functional neurosurgery was born out of a “routine” case of ablative surgery for Parkinson’s disease in the 1980s, when the French neurosurgeon Alim Benabid was using electrodes to determine which areas of the brain should be destroyed. As he was mapping the thalamus, he noted that the tremor of his patient abated. This led him to wonder if one could treat drug-resistant Parkinson’s with electrical stimulation instead of destructive lesioning.2 Benabid’s translational insight during an ordinary case led to the development of the rather extraordinary field of stereotactic functional neurosurgery and neuromodulation.3,4
Another example from an earlier era comes from the life work of neurosurgeon Wilder Penfield, who did pioneering work in the surgical treatment of epilepsy. Here, the accumulation of experience from “routine care” led to generalizable knowledge, much like hypotheses are validated in experimental work. In Penfield’s case, his clinical use of electrical stimulation to plan resections of scar tissue causing epilepsy led him to map the human homunculus, a magnificent achievement of profound importance.5,6
So let us avoid simplistic and confounding demarcations. Instead of dichotomizing innovation and prudence—or surgical research and surgical practice—let us try to start our deliberations with an eye toward a more synthetic approach. Like most things in nature and in biology, ethics too is on a continuum with gradations that can fit into an Aristotelian taxonomy. Let us emulate what Aristotle called phronesis, or practical wisdom, these next 2 days so that we achieve constructive outcomes, or what the pragmatists would call instrumental goods.7
If we are successful in laying out the ethical issues in this clinically pragmatic fashion, we can turn intractable “dilemmas” into problems amenable to resolution through the particularistic invocation of ethical principles as they relate to the surgical context.8 If we follow this inductive method of moral problem solving, we will avoid sweeping ethical generalizations, or categoricals, that can misrepresent the complexity of innovative research and deprive society of its benefits.9
INNOVATION VS PRUDENCE: A FALSE DICHOTOMY
So let us start by understanding the presuppositions that led to the expectation that dilemmas will descend upon those who engage in surgical innovation. In my view, this expectation begins with what is called the precautionary principle, a concept with some currency in the realm of environmental ethics.10
The precautionary principle urges caution and prudence when facing unknowns and is an antecedent sort of utilitarianism. One makes judgments about the advisability of actions based on a prior assessment of foreseeable risks and benefits. If the risks are excessive or exceed benefits, the precautionary principle urges care, caution, and even avoidance of a given course of action.
When the precautionary principle is implicitly invoked in making judgments about research, the objective is to pursue a degree of safety that is comparable to that of established therapy. But interventions that have progressed to being deemed “therapeutic” have of course achieved a requisite degree of both safety and efficacy—that is what makes them therapeutic, as opposed to investigational, interventions. One cannot know before one has conducted a clinical trial, and completed statistical analysis, whether a new surgical advance or device meets these expectations. Because of this lack of knowledge, there is an inherent degree of risk in any novel intervention.
The challenge posed by innovation or novelty creates the possibility of untoward events. It leads to invocation of the precautionary principle, which, echoing the admonitions of the philosopher Hans Jonas, urges us to “give greater weight to the prognosis of doom than to that of bliss.”11,12
This is not a bad way to go through life, assuming one wants to emulate T.S. Eliot’s J. Alfred Prufrock, who lamentably “measured out my life with coffee spoons.”13 Unlike the surgeon, who must make decisions in real time, Eliot’s protagonist could not move forward. Despite his desire to avoid the indecision of Prince Hamlet, alluded to in this paper’s epigraph, Prufrock was paralyzed by doubts and fears, with “time yet for a hundred indecisions, and for a hundred visions and revisions.”13
Despite Eliot’s invocation of “a patient etherised upon a table,”13 the poem shares little with the surgical life. It has much more in common with the precautionary principle. Like Prufrock, the precautionary principle favors what is known— the status quo—as what is unknown is invariably more risky than the familiar. Needless to say, this is antithetical to innovation because discovery invariably requires scenarios that involve novelty and unknown risks. When faced with the certain security of stasis or the potential dangers of innovation, the precautionary principle will invariably choose stasis, leading us, as the legal scholar Cass Sunstein notes, “in no direction at all.”14
Seen through the prism of the precautionary principle, then, surgical innovation invariably presents a dilemma. Discovery and innovation are fundamentally at odds with the precautionary principle, because of their potential for risk.15
The challenge posed by the precautionary principle—which, to be fair, is seen in all areas of clinical research—becomes even more pronounced in surgical research because of the size and scope of clinical trials. As is well appreciated here, compared with drug trials, surgical trials are small. Sometimes they can involve a single subject, whereas drug trials may include thousands of participants. Because of drug trials’ large volume of subjects, therapeutic effects can be small to justify ongoing research. In a surgical trial or a device trial, the number of subjects is smaller, so the therapeutic impact has to be larger to warrant further development and ongoing study. This burden of scale increases the probability of reciprocally large adverse effects. This potential for disaster magnifies the impact of the precautionary principle and may lead to a distortion in ethical judgment along the lines of Hans Jonas’ admonition.12
By all of this I am not suggesting that we abandon precautions and prudence. Instead, my point is to explicate the additional challenges faced by surgical research and the sway of the precautionary principle over this area of inquiry and innovation. By being explicit about the impact of this principle, we can be cognizant of its potential to distort judgments about risks and benefits. Only then can we hope to balance the pursuit of progress with that of safety.
SURGICAL RESPONSIBILITY
These distortions also need to be recognized, and made explicit, because surgical research, more so than pharmacologic research, is much more personal and intimate. This point becomes clear if we consider a surgical trial that does not succeed.
In the surgical arena, such failures are taken to heart and personalized. Unlike trials that involve drugs, surgical research is more proximate. It is not just the failure of a drug or of pharmacology; it is also possibly the failure of the operator, the surgeon who did not achieve the desired goal because of poor execution of surgical technique.
This crucial difference in medical versus surgical cultures is captured by Charles Bosk in his magisterial sociological study of surgery, Forgive and Remember: Managing Medical Failure. In a discussion of morbidity and mortality rounds, Bosk writes:
The specific nature of surgical treatment links the action of the physician and the response of the patient more intimately than in other areas of medicine....When the patient of an internist dies, the natural question his colleagues ask is, “What happened?” When the patient of a surgeon dies, his colleagues ask, “What did you do?”16
As in clinical surgical practice, in surgical research, it is the personal and individualized mediation of the surgeon that is central to the intervention. Here the intermediary is neither a drug nor its bioavailability; rather, it is the operator’s technique plus or minus the operative design and the reliability of an instrument or a device. In either case, the contribution is more proximate and personal, stemming from the actions of individual surgeons and the work of their hands.
History is instructive on this theme of surgical causality and personal culpability if we consider the life of Harvey Cushing, a Cleveland native whose ashes are buried nearby in Lake View Cemetery.17 Cushing was a gifted and innovative surgeon whose technique handling tissues changed how the brain was approached operatively. He is acknowledged as the father of neurosurgery, having created a professional nexus to institutionalize and carry on his innovative work.18
Cushing’s greatest innovation was probably in his individual efforts as a working surgeon. Over the course of his lifetime, he made the resection of brain tumors a safe and sometimes effective treatment for an otherwise dread disease. Michael Bliss, Cushing’s most recent biographer, reports mortality data from more than 2,400 surgeries done by Cushing during his operative lifetime.17 Early in his career (from 1896 to 1911), while he was at Johns Hopkins, Cushing’s case mortality rate was 24.7%. During his later years at the Brigham Hospital, it was 16.2%. By 1930–1931 it was down to 8.8%.
These were extraordinary statistics: no one matched Cushing’s numbers, or his ability to do what he did. Bliss cites mortality data from his surgical contemporaries in the late 1920s as ranging from approximately 35% to 45%. By the numbers Bliss compares Cushing’s talent—his truly brilliant outlier performance—to that of his Jazz Age contemporary, Babe Ruth, who also had outsized talent compared with his peers.17
Cushing himself, a collegiate second baseman at Yale, linked sport and statistics in a most telling way. Documenting his ongoing surgical progress was a hedge against failure and lightened the emotional burdens of the surgical suite. Cushing observed: “A neurosurgeon’s responsibilities would be insufferable if he did not feel that his knowledge of an intricate subject was constantly growing—that his game was improving.”17
This quote and Cushing’s operative statistics point to his nascent effort to engage in evidence-based research and speaks to the spectacular difference that a surgical innovator can make. The extraordinary results achieved by Cushing in his day also suggest that surgeons are not fungible at the vanguard of discovery. History tells us, as contemporary assessments of current research cannot, that only Harvey Cushing could achieve Cushingoid results.
A second point that stems from Cushing’s comment about the burdens of operative work and surgical research is how personally taxing that responsibility can be. Without making progress, he said, the “responsibilities would be insufferable”17 (my italics).
Even the great Harvey Cushing perceived the weight of these burdens, suggesting that any effort to depersonalize the ethics of surgical innovation would be naïve. The singularity of Cushing’s surgical accomplishments (his operative excellence as compared with his peer group) and the felt weight of these achievements suggest that surgical innovation is highly personal and proximate to the surgical researcher in a way that is distinct for surgical innovation. This relationship of operative causality and personal culpability can be subsumed under what I will call surgical proximity.
SURGICAL PROXIMITY
Surgical proximity has several implications for the conduct of research. In this section I will address two issues: conflicts of interest and clinical equipoise.
Surgical proximity and conflicts of interest
As the Cushing example illustrates, at least at the outset of a clinical trial the surgeon himself is part of the actual design of the trial. The same surgical method in the hands of one of his contemporaries would have led to a dramatically different result. The surgeon who is at the forefront of innovation becomes an experimental variable until the methods can be generalized.
The importance of the operator as an essential ingredient in early surgical research points to a key difference with pharmaceutical trials, where the purity of the drug-based intervention can be maintained. This difference has implications for the “rebuttable presumption” stance promulgated by the Association of American Medical Colleges (AAMC), which looks askance at innovators conducting clinical trials if they have a conflict of interest, such as intellectual property rights for their discoveries.19,20
In many cases, the work that surgical innovators do, as in the case of device development, could not be done without collaborations with industry. Taking the surgical talent of the potentially conflicted—but highly talented—innovator out of the equation may be counterproductive.
Time does not allow me to fully address the conflict-of-interest issue in this forum; suffice it to say that the differential knowledge, skill, and talent of early surgical innovators may be the difference between a trial’s early success or failure. The role of such innovators should neither be truncated or precluded nor be viewed a priori in a prejudicial fashion. Instead, their talents and vision should be welcomed as instrumental to the potential success of the work, managed of course with the proper degree of transparency and disclosure.
As I have noted previously,4,21 if the rationale for a conflict of interest is to allow laudable work to continue that otherwise could not occur without the personal intervention, and talents, of a surgical innovator, it seems prejudicial to view the conflict of interest as disqualifying until proven otherwise. This view is consistent with the legal framework of the US Constitution, which explicitly authorizes Congress “to promote the Progress of Science and the useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries.”22 It is also embedded in the Patent Act of 1790,23 which balances the patent’s period of exclusivity against the inventor’s obligation to share and disseminate expertise. This role for the innovator is also consistent with the intent and incentives within the framework of the Bayh-Dole Act of 1980,24 which was passed with the expectation that industrial partnerships would move ideas from the bench to the bedside.
I hope that others at this conference will be able to return to the issue of conflicts of interest and how the question of surgical proximity may, or may not, alter our ethical judgments about the surgeon’s role in research where there may be a conflict of interest.
Surgical proximity and equipoise
Surgical proximity also has an impact on clinical equipoise, the ethical neutrality about outcomes felt necessary for the conduct of clinical trials.25 The surgeon’s sense of causality and proximity to the operative act makes surgical research different because the equipoise, which exists objectively about the research questions at hand, may not exist in the mind of the surgical researcher. Let me explain.
Taking a patient to surgery is highly consequential. As we have seen from Bosk’s work,16 surgeons feel a sense of responsibility for their operative acts and surgical work. This felt responsibility, inculcated in surgical training and surgical culture, obligates the surgeon to make a proportionality judgment about bringing a patient to the operating room, be it for research or for clinical practice. In this way, surgical investigators have determined, at least in their own minds, that net benefits outweigh net risks, thus breaching clinical equipoise.
It is hard for a surgeon to commit to an operative procedure—be it for clinical care or for research— with all its attendant risks if he or she does not believe that the intervention is safe and effective. We can appreciate the importance of the surgeon’s perspective on the utility of any proposed operation if we consider the opposing question of futility in clinical practice.26 Whereas internists or intensivists might be compelled by families to continue aggressive intensive care, surgeons cannot be compelled to take a patient to the operating room when they deem that the risks outweigh the benefits. Because the surgeon is such a proximate moral agent, he or she will be held culpable for the actions that occur in theater. This degree of responsibility is accompanied by a retained degree of discretion—an almost old-world paternalistic discretion27—to counter the demands for disproportionate care.
This same sense of culpability and responsibility informs the surgeon’s willingness to take any patient to the operating room. In the case of research, this willingness becomes an issue of concern because it means that in the surgeon’s mind, favorable operative proportionality has been achieved.
This process of self-regulation28 can have implications for the informed-consent process because surgeons believe in their work and can exert a strong dynamic transference on subjects who may be desperate for cure.29 Because of this potential bias, surgical research may become especially prone to a therapeutic misconception. That is, if the surgeon is willing to take the risks of doing an innovative procedure in the operating room, then it has crossed some sort of internal threshold of proportionality in which the risks, whatever they are, have become acceptable given the putative benefits. Given what Bosk has written about surgical failure,16 a high bar is crossed when a surgeon takes a patient to the operating room for a novel procedure, even though motivations at that bar may occasionally be mixed.* (*Lest I be misconstrued as too idealistic, this burdens-vs-benefits equation may be fueled by a complex mosaic of motivations and may not always be informed fully by patient-centered benefits. If the surgeon is the innovator and the inventor, these benefits may be for the pursuit of a hypothesis and associated with potential fame or fortune. But even in these cases, judgments about proportionality are informed by surgical proximity. [For more on the ethics of conflicts of interest, see references 4 and 21.])
FROM SURGICAL RESEARCH TO EDUCATION
This leads to my closing observations about transitions in surgical research, when the work of the pioneering surgeon is bequeathed to the broader surgical community to pick up the torch—or scalpel—and expand the work.
This takes me away from research and, fittingly here at a medical school dedicated to research training, brings me to medical education. To transcend the personal dimensions of surgical innovation—and the courage and vision of the founders—and sustain it more broadly, innovators also have to become educators of future surgeons, organizers of talent, and moral exemplars for the next generation. They have to appreciate that the work that they started, if it is important, will not be completed during their tenure but that future generations will carry it forward and expand upon it. They also have to prepare the next generation with the tools and orientation to appreciate their vision and to embrace what Thomas Kuhn might call new scientific paradigms.30
On several occasions Wilder Penfield, who founded the Montreal Neurological Institute, wrote with regret about Victor Horsley, the neurosurgeon at Queens Square in London. Penfield viewed Horsley as the founder of his field, but Horsley left no disciples. In his autobiography, fittingly entitled No Man Alone, Penfield noted that Horsley, “the most distinguished pioneer neurosurgeon, had died in 1916 without having established a school of neurosurgery.”5 This is in contrast to the discipline-building work of Cushing.
It is not an accident that Dr. Cushing founded a field full of trainees and protégés, of which my co-panelists are descendants. It was intentional and part of his ethos of being truly innovative. And it is not an accident that the distinguished surgical innovators at this symposium have also created institutional structures to continue their work for decades to come. Their achievements have transcended the individual innovator and have become systematic. It is said that Dr. Thomas Starzl launched a field.31 Dr. Denton Cooley founded the Texas Heart Institute.32 Dr. Thomas Fogarty started the Fogarty Institute for Innovation, whose mission statement explicitly notes that it is “an educational non-profit that mentors, trains and inspires the next generation of medical innovators.”33 Each of these pioneers, I believe, appreciates the need for continuity and dissemination.
But even here there is something that we nonsurgeons need to understand: although the work transcends the individual surgeon, the ties remain personal and linked to the impact and legacy of founders. Take, for example, highly prized membership in the Denton A. Cooley Cardiovascular Surgical Society.34 This too is about the importance of individuals and surgical proximity, but here it is transgenerational.
CONCLUSION
If we truly want to continue the dialogue begun here today, we need to understand these social and professional networks and the importance of surgical proximity in transmitting both methods and values. The proximate nature of surgical research—and the causality and responsibility that accrues to the surgeon—makes surgical research different than other areas of biomedical inquiry. This difference has implications for risk-benefit analysis, conflicts of interest, and clinical equipoise. I hope that my colleagues return to these themes in the coming days so that the regulation of this important area of research can be informed by a deeper understanding of the ethics of surgical discovery and innovation.35
Acknowledgments
Dr. Fins gratefully acknowledges the invitation to participate in this symposium, the helpful suggestions of Dr. Eric Kodish, and partial grant support of the Weill Cornell Medical College Research Ethics Core, NIH Clinical & Translational Science Center UL1-RR024966.
No! I am not Prince Hamlet, nor was meant to be;
Am an attendant lord, one that will do
To swell a progress, start a scene or two…
—T.S. Eliot, The Love Song of J. Alfred Prufrock
Let me start by thanking the organizers for their invitation to be here and to start this off. I am not sure if that invitation was an act of kindness or of throwing a fellow bioethicist to the lions, as we will be addressing a complicated set of issues upon which well-intentioned folks disagree and sometimes disagree with a passion.
What I would like to do is to lay out some of the inherent ethical problems related to surgical innovation. I will argue that some of these problems are unique to surgery and that others relate to how we have chosen to define categories like research and practice. Other problems involve how we view the proportionality of risks and benefits in surgical research. I will argue that we have falsely analogized surgical progress to progress made in other areas of biomedical research and misunderstood the highly personal, or proximate, nature of surgical inquiry. Without appreciating the import of what I will call “surgical proximity,” we will be unable to adequately address ethical issues in surgical innovation.
PROBLEMS OR DILEMMAS?
So let me begin with the title of our session, “Surgical Innovation and Ethical Dilemmas,” and why this juxta position is counterproductive. A colleague long ago taught me to distinguish problems from dilemmas—the former being resolvable, the latter intractable, often involving a choice between two equally unfavorable choices.
Although I may be making too much of the semantics, I do think the title betrays a presumption that surgical innovation invariably forces adversarial choices. It tends to dichotomize ethical reflection, pitting those who favor prudence against those who endorse progress, or it creates too stark a difference between ethical issues in surgical practice and those encountered in the conduct of surgical research.
Even therapeutic, validated surgery in many ways has the potential to become innovative, if not outright experimental. Patients may have anatomical differences that require surgical improvisation, or complications may arise during “routine” surgery, creating the need for an imaginative response.1 At what point do these departures from expected care become novel interventions, innovative or even experimental? A routine case with an unexpected turn can even become a case report opening up a new field of endeavor.
For instance, the field of stereotactic functional neurosurgery was born out of a “routine” case of ablative surgery for Parkinson’s disease in the 1980s, when the French neurosurgeon Alim Benabid was using electrodes to determine which areas of the brain should be destroyed. As he was mapping the thalamus, he noted that the tremor of his patient abated. This led him to wonder if one could treat drug-resistant Parkinson’s with electrical stimulation instead of destructive lesioning.2 Benabid’s translational insight during an ordinary case led to the development of the rather extraordinary field of stereotactic functional neurosurgery and neuromodulation.3,4
Another example from an earlier era comes from the life work of neurosurgeon Wilder Penfield, who did pioneering work in the surgical treatment of epilepsy. Here, the accumulation of experience from “routine care” led to generalizable knowledge, much like hypotheses are validated in experimental work. In Penfield’s case, his clinical use of electrical stimulation to plan resections of scar tissue causing epilepsy led him to map the human homunculus, a magnificent achievement of profound importance.5,6
So let us avoid simplistic and confounding demarcations. Instead of dichotomizing innovation and prudence—or surgical research and surgical practice—let us try to start our deliberations with an eye toward a more synthetic approach. Like most things in nature and in biology, ethics too is on a continuum with gradations that can fit into an Aristotelian taxonomy. Let us emulate what Aristotle called phronesis, or practical wisdom, these next 2 days so that we achieve constructive outcomes, or what the pragmatists would call instrumental goods.7
If we are successful in laying out the ethical issues in this clinically pragmatic fashion, we can turn intractable “dilemmas” into problems amenable to resolution through the particularistic invocation of ethical principles as they relate to the surgical context.8 If we follow this inductive method of moral problem solving, we will avoid sweeping ethical generalizations, or categoricals, that can misrepresent the complexity of innovative research and deprive society of its benefits.9
INNOVATION VS PRUDENCE: A FALSE DICHOTOMY
So let us start by understanding the presuppositions that led to the expectation that dilemmas will descend upon those who engage in surgical innovation. In my view, this expectation begins with what is called the precautionary principle, a concept with some currency in the realm of environmental ethics.10
The precautionary principle urges caution and prudence when facing unknowns and is an antecedent sort of utilitarianism. One makes judgments about the advisability of actions based on a prior assessment of foreseeable risks and benefits. If the risks are excessive or exceed benefits, the precautionary principle urges care, caution, and even avoidance of a given course of action.
When the precautionary principle is implicitly invoked in making judgments about research, the objective is to pursue a degree of safety that is comparable to that of established therapy. But interventions that have progressed to being deemed “therapeutic” have of course achieved a requisite degree of both safety and efficacy—that is what makes them therapeutic, as opposed to investigational, interventions. One cannot know before one has conducted a clinical trial, and completed statistical analysis, whether a new surgical advance or device meets these expectations. Because of this lack of knowledge, there is an inherent degree of risk in any novel intervention.
The challenge posed by innovation or novelty creates the possibility of untoward events. It leads to invocation of the precautionary principle, which, echoing the admonitions of the philosopher Hans Jonas, urges us to “give greater weight to the prognosis of doom than to that of bliss.”11,12
This is not a bad way to go through life, assuming one wants to emulate T.S. Eliot’s J. Alfred Prufrock, who lamentably “measured out my life with coffee spoons.”13 Unlike the surgeon, who must make decisions in real time, Eliot’s protagonist could not move forward. Despite his desire to avoid the indecision of Prince Hamlet, alluded to in this paper’s epigraph, Prufrock was paralyzed by doubts and fears, with “time yet for a hundred indecisions, and for a hundred visions and revisions.”13
Despite Eliot’s invocation of “a patient etherised upon a table,”13 the poem shares little with the surgical life. It has much more in common with the precautionary principle. Like Prufrock, the precautionary principle favors what is known— the status quo—as what is unknown is invariably more risky than the familiar. Needless to say, this is antithetical to innovation because discovery invariably requires scenarios that involve novelty and unknown risks. When faced with the certain security of stasis or the potential dangers of innovation, the precautionary principle will invariably choose stasis, leading us, as the legal scholar Cass Sunstein notes, “in no direction at all.”14
Seen through the prism of the precautionary principle, then, surgical innovation invariably presents a dilemma. Discovery and innovation are fundamentally at odds with the precautionary principle, because of their potential for risk.15
The challenge posed by the precautionary principle—which, to be fair, is seen in all areas of clinical research—becomes even more pronounced in surgical research because of the size and scope of clinical trials. As is well appreciated here, compared with drug trials, surgical trials are small. Sometimes they can involve a single subject, whereas drug trials may include thousands of participants. Because of drug trials’ large volume of subjects, therapeutic effects can be small to justify ongoing research. In a surgical trial or a device trial, the number of subjects is smaller, so the therapeutic impact has to be larger to warrant further development and ongoing study. This burden of scale increases the probability of reciprocally large adverse effects. This potential for disaster magnifies the impact of the precautionary principle and may lead to a distortion in ethical judgment along the lines of Hans Jonas’ admonition.12
By all of this I am not suggesting that we abandon precautions and prudence. Instead, my point is to explicate the additional challenges faced by surgical research and the sway of the precautionary principle over this area of inquiry and innovation. By being explicit about the impact of this principle, we can be cognizant of its potential to distort judgments about risks and benefits. Only then can we hope to balance the pursuit of progress with that of safety.
SURGICAL RESPONSIBILITY
These distortions also need to be recognized, and made explicit, because surgical research, more so than pharmacologic research, is much more personal and intimate. This point becomes clear if we consider a surgical trial that does not succeed.
In the surgical arena, such failures are taken to heart and personalized. Unlike trials that involve drugs, surgical research is more proximate. It is not just the failure of a drug or of pharmacology; it is also possibly the failure of the operator, the surgeon who did not achieve the desired goal because of poor execution of surgical technique.
This crucial difference in medical versus surgical cultures is captured by Charles Bosk in his magisterial sociological study of surgery, Forgive and Remember: Managing Medical Failure. In a discussion of morbidity and mortality rounds, Bosk writes:
The specific nature of surgical treatment links the action of the physician and the response of the patient more intimately than in other areas of medicine....When the patient of an internist dies, the natural question his colleagues ask is, “What happened?” When the patient of a surgeon dies, his colleagues ask, “What did you do?”16
As in clinical surgical practice, in surgical research, it is the personal and individualized mediation of the surgeon that is central to the intervention. Here the intermediary is neither a drug nor its bioavailability; rather, it is the operator’s technique plus or minus the operative design and the reliability of an instrument or a device. In either case, the contribution is more proximate and personal, stemming from the actions of individual surgeons and the work of their hands.
History is instructive on this theme of surgical causality and personal culpability if we consider the life of Harvey Cushing, a Cleveland native whose ashes are buried nearby in Lake View Cemetery.17 Cushing was a gifted and innovative surgeon whose technique handling tissues changed how the brain was approached operatively. He is acknowledged as the father of neurosurgery, having created a professional nexus to institutionalize and carry on his innovative work.18
Cushing’s greatest innovation was probably in his individual efforts as a working surgeon. Over the course of his lifetime, he made the resection of brain tumors a safe and sometimes effective treatment for an otherwise dread disease. Michael Bliss, Cushing’s most recent biographer, reports mortality data from more than 2,400 surgeries done by Cushing during his operative lifetime.17 Early in his career (from 1896 to 1911), while he was at Johns Hopkins, Cushing’s case mortality rate was 24.7%. During his later years at the Brigham Hospital, it was 16.2%. By 1930–1931 it was down to 8.8%.
These were extraordinary statistics: no one matched Cushing’s numbers, or his ability to do what he did. Bliss cites mortality data from his surgical contemporaries in the late 1920s as ranging from approximately 35% to 45%. By the numbers Bliss compares Cushing’s talent—his truly brilliant outlier performance—to that of his Jazz Age contemporary, Babe Ruth, who also had outsized talent compared with his peers.17
Cushing himself, a collegiate second baseman at Yale, linked sport and statistics in a most telling way. Documenting his ongoing surgical progress was a hedge against failure and lightened the emotional burdens of the surgical suite. Cushing observed: “A neurosurgeon’s responsibilities would be insufferable if he did not feel that his knowledge of an intricate subject was constantly growing—that his game was improving.”17
This quote and Cushing’s operative statistics point to his nascent effort to engage in evidence-based research and speaks to the spectacular difference that a surgical innovator can make. The extraordinary results achieved by Cushing in his day also suggest that surgeons are not fungible at the vanguard of discovery. History tells us, as contemporary assessments of current research cannot, that only Harvey Cushing could achieve Cushingoid results.
A second point that stems from Cushing’s comment about the burdens of operative work and surgical research is how personally taxing that responsibility can be. Without making progress, he said, the “responsibilities would be insufferable”17 (my italics).
Even the great Harvey Cushing perceived the weight of these burdens, suggesting that any effort to depersonalize the ethics of surgical innovation would be naïve. The singularity of Cushing’s surgical accomplishments (his operative excellence as compared with his peer group) and the felt weight of these achievements suggest that surgical innovation is highly personal and proximate to the surgical researcher in a way that is distinct for surgical innovation. This relationship of operative causality and personal culpability can be subsumed under what I will call surgical proximity.
SURGICAL PROXIMITY
Surgical proximity has several implications for the conduct of research. In this section I will address two issues: conflicts of interest and clinical equipoise.
Surgical proximity and conflicts of interest
As the Cushing example illustrates, at least at the outset of a clinical trial the surgeon himself is part of the actual design of the trial. The same surgical method in the hands of one of his contemporaries would have led to a dramatically different result. The surgeon who is at the forefront of innovation becomes an experimental variable until the methods can be generalized.
The importance of the operator as an essential ingredient in early surgical research points to a key difference with pharmaceutical trials, where the purity of the drug-based intervention can be maintained. This difference has implications for the “rebuttable presumption” stance promulgated by the Association of American Medical Colleges (AAMC), which looks askance at innovators conducting clinical trials if they have a conflict of interest, such as intellectual property rights for their discoveries.19,20
In many cases, the work that surgical innovators do, as in the case of device development, could not be done without collaborations with industry. Taking the surgical talent of the potentially conflicted—but highly talented—innovator out of the equation may be counterproductive.
Time does not allow me to fully address the conflict-of-interest issue in this forum; suffice it to say that the differential knowledge, skill, and talent of early surgical innovators may be the difference between a trial’s early success or failure. The role of such innovators should neither be truncated or precluded nor be viewed a priori in a prejudicial fashion. Instead, their talents and vision should be welcomed as instrumental to the potential success of the work, managed of course with the proper degree of transparency and disclosure.
As I have noted previously,4,21 if the rationale for a conflict of interest is to allow laudable work to continue that otherwise could not occur without the personal intervention, and talents, of a surgical innovator, it seems prejudicial to view the conflict of interest as disqualifying until proven otherwise. This view is consistent with the legal framework of the US Constitution, which explicitly authorizes Congress “to promote the Progress of Science and the useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries.”22 It is also embedded in the Patent Act of 1790,23 which balances the patent’s period of exclusivity against the inventor’s obligation to share and disseminate expertise. This role for the innovator is also consistent with the intent and incentives within the framework of the Bayh-Dole Act of 1980,24 which was passed with the expectation that industrial partnerships would move ideas from the bench to the bedside.
I hope that others at this conference will be able to return to the issue of conflicts of interest and how the question of surgical proximity may, or may not, alter our ethical judgments about the surgeon’s role in research where there may be a conflict of interest.
Surgical proximity and equipoise
Surgical proximity also has an impact on clinical equipoise, the ethical neutrality about outcomes felt necessary for the conduct of clinical trials.25 The surgeon’s sense of causality and proximity to the operative act makes surgical research different because the equipoise, which exists objectively about the research questions at hand, may not exist in the mind of the surgical researcher. Let me explain.
Taking a patient to surgery is highly consequential. As we have seen from Bosk’s work,16 surgeons feel a sense of responsibility for their operative acts and surgical work. This felt responsibility, inculcated in surgical training and surgical culture, obligates the surgeon to make a proportionality judgment about bringing a patient to the operating room, be it for research or for clinical practice. In this way, surgical investigators have determined, at least in their own minds, that net benefits outweigh net risks, thus breaching clinical equipoise.
It is hard for a surgeon to commit to an operative procedure—be it for clinical care or for research— with all its attendant risks if he or she does not believe that the intervention is safe and effective. We can appreciate the importance of the surgeon’s perspective on the utility of any proposed operation if we consider the opposing question of futility in clinical practice.26 Whereas internists or intensivists might be compelled by families to continue aggressive intensive care, surgeons cannot be compelled to take a patient to the operating room when they deem that the risks outweigh the benefits. Because the surgeon is such a proximate moral agent, he or she will be held culpable for the actions that occur in theater. This degree of responsibility is accompanied by a retained degree of discretion—an almost old-world paternalistic discretion27—to counter the demands for disproportionate care.
This same sense of culpability and responsibility informs the surgeon’s willingness to take any patient to the operating room. In the case of research, this willingness becomes an issue of concern because it means that in the surgeon’s mind, favorable operative proportionality has been achieved.
This process of self-regulation28 can have implications for the informed-consent process because surgeons believe in their work and can exert a strong dynamic transference on subjects who may be desperate for cure.29 Because of this potential bias, surgical research may become especially prone to a therapeutic misconception. That is, if the surgeon is willing to take the risks of doing an innovative procedure in the operating room, then it has crossed some sort of internal threshold of proportionality in which the risks, whatever they are, have become acceptable given the putative benefits. Given what Bosk has written about surgical failure,16 a high bar is crossed when a surgeon takes a patient to the operating room for a novel procedure, even though motivations at that bar may occasionally be mixed.* (*Lest I be misconstrued as too idealistic, this burdens-vs-benefits equation may be fueled by a complex mosaic of motivations and may not always be informed fully by patient-centered benefits. If the surgeon is the innovator and the inventor, these benefits may be for the pursuit of a hypothesis and associated with potential fame or fortune. But even in these cases, judgments about proportionality are informed by surgical proximity. [For more on the ethics of conflicts of interest, see references 4 and 21.])
FROM SURGICAL RESEARCH TO EDUCATION
This leads to my closing observations about transitions in surgical research, when the work of the pioneering surgeon is bequeathed to the broader surgical community to pick up the torch—or scalpel—and expand the work.
This takes me away from research and, fittingly here at a medical school dedicated to research training, brings me to medical education. To transcend the personal dimensions of surgical innovation—and the courage and vision of the founders—and sustain it more broadly, innovators also have to become educators of future surgeons, organizers of talent, and moral exemplars for the next generation. They have to appreciate that the work that they started, if it is important, will not be completed during their tenure but that future generations will carry it forward and expand upon it. They also have to prepare the next generation with the tools and orientation to appreciate their vision and to embrace what Thomas Kuhn might call new scientific paradigms.30
On several occasions Wilder Penfield, who founded the Montreal Neurological Institute, wrote with regret about Victor Horsley, the neurosurgeon at Queens Square in London. Penfield viewed Horsley as the founder of his field, but Horsley left no disciples. In his autobiography, fittingly entitled No Man Alone, Penfield noted that Horsley, “the most distinguished pioneer neurosurgeon, had died in 1916 without having established a school of neurosurgery.”5 This is in contrast to the discipline-building work of Cushing.
It is not an accident that Dr. Cushing founded a field full of trainees and protégés, of which my co-panelists are descendants. It was intentional and part of his ethos of being truly innovative. And it is not an accident that the distinguished surgical innovators at this symposium have also created institutional structures to continue their work for decades to come. Their achievements have transcended the individual innovator and have become systematic. It is said that Dr. Thomas Starzl launched a field.31 Dr. Denton Cooley founded the Texas Heart Institute.32 Dr. Thomas Fogarty started the Fogarty Institute for Innovation, whose mission statement explicitly notes that it is “an educational non-profit that mentors, trains and inspires the next generation of medical innovators.”33 Each of these pioneers, I believe, appreciates the need for continuity and dissemination.
But even here there is something that we nonsurgeons need to understand: although the work transcends the individual surgeon, the ties remain personal and linked to the impact and legacy of founders. Take, for example, highly prized membership in the Denton A. Cooley Cardiovascular Surgical Society.34 This too is about the importance of individuals and surgical proximity, but here it is transgenerational.
CONCLUSION
If we truly want to continue the dialogue begun here today, we need to understand these social and professional networks and the importance of surgical proximity in transmitting both methods and values. The proximate nature of surgical research—and the causality and responsibility that accrues to the surgeon—makes surgical research different than other areas of biomedical inquiry. This difference has implications for risk-benefit analysis, conflicts of interest, and clinical equipoise. I hope that my colleagues return to these themes in the coming days so that the regulation of this important area of research can be informed by a deeper understanding of the ethics of surgical discovery and innovation.35
Acknowledgments
Dr. Fins gratefully acknowledges the invitation to participate in this symposium, the helpful suggestions of Dr. Eric Kodish, and partial grant support of the Weill Cornell Medical College Research Ethics Core, NIH Clinical & Translational Science Center UL1-RR024966.
- Frader JE, Caniano DA. Research and innovation in surgery. In: McCullough LB, Jones JW, Brody BA, eds. Surgical Ethics. New York, NY: Oxford University Press; 1998:216–241.
- Speelman JD, Bosch DA. Resurgence of functional neurosurgery for Parkinson’s disease: a historical perspective. Mov Disord 1998; 13:582–588.
- Holstein WJ. Rewiring the brain: how a bright idea became an innovative medical device. US News & World Report. March 1, 1999:52–53.
- Fins JJ, Schachter M. Investigators, industry, and the heuristic device: ethics, patent law, and clinical innovation. Account Res 2001; 8:219–233.
- Penfield W. No Man Alone: A Neurosurgeon’s Life. Boston, MA: Little Brown; 1977.
- Feindel W. The contributions of Wilder Penfield to the functional anatomy of the human brain. Hum Neurobiol 1982; 1:231–234.
- Aristotle. The Nicomachean Ethics. Weldon JEC, trans. Amherst, NY: Prometheus Books; 1987.
- Fins JJ, Bacchetta MD, Miller FG. Clinical pragmatism: a method of moral problem solving. Kennedy Inst Ethics J 1997; 7:129–145.
- Miller FG, Fins JJ. Protecting human subjects in brain research: a pragmatic perspective. In: Illes J, ed. Neuroethics: Defining the Issues in Theory, Practice and Policy. New York, NY: Oxford University Press; 2005.
- Pollan M. The year in ideas: A to Z.; precautionary principle. New York Times. December 9, 2001.
- van den Belt H. Debating the precautionary principle: “guilty until proven innocent” or “innocent until proven guilty”? Plant Physiol 2003; 132:1122–1126.
- Jonas H. The Imperative of Responsibility: In Search of an Ethics for the Technological Age. Chicago, IL: University of Chicago Press; 1985:34.
- Eliot TS. The Love Song of J. Alfred Prufrock. In: Abrams MH, ed. The Norton Anthology of English Literature. Vol 2. 4th ed. New York, NY: W.W. Norton & Co; 1979:2259–2264.
- Sunstein CR. The paralyzing principle. Regulation. Winter 2002– 2003; 25(4):32–37.
- Holm S, Harris J. Precautionary principle stifles discovery. Nature 1999; 400:398.
- Bosk C. Forgive and Remember: Managing Medical Failure. Chicago, IL: University of Chicago Press; 1979:29–30.
- Bliss M. Harvey Cushing: A Life in Surgery. Oxford, UK: Oxford University Press; 2005.
- Pinkus RL. Mistakes as a social construct: an historical approach. Kennedy Inst Ethics J 2001; 11:117–133.
- AAMC Task Force on Financial Conflicts of Interest in Clinical Research. Protecting subjects, preserving trust, promoting progress I: policy and guidelines for the oversight of individual financial interests in human subjects research. Acad Med 2003; 78:225–236.
- AAMC Task Force on Financial Conflicts of Interest in Clinical Research. Protecting subjects, preserving trust, promoting progress II: principles and recommendations for oversight of an institution’s financial interests in human subjects research. Acad Med 2003; 78:237– 245.
- Fins JJ. Disclose and justify: intellectual property, conflicts of interest, and neurosurgery. Congress Quarterly (Official Newsmagazine of the Congress of Neurological Surgeons) 2007; 8(3):34–36.
- U.S. Constitution, art. I, §8, cl. 8; see also id. at art. I, §8, cl. 18.
- Patent Act of 1790, ch. 7, 1 Stat. 109–111 (1790).
- Patent and Trademark Act Amendments of 1980 (Bayh-Dole Act); Pub L No. 96-517. Codified as 35 USC §§200–212 (1994).
- Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987; 317:141–145.
- Callahan D. Necessity, futility, and the good society. J Am Geriatr Soc 1994; 42:866–867.
- Katz J. The Silent World of Doctor and Patient. New York, NY: Free Press; 1984.
- Jones RS, Fletcher JC. Self-regulation of surgical practice and research. In: McCullough LB, Jones JW, Brody BA, eds. Surgical Ethics. New York, NY: Oxford University Press; 1998:255–279.
- Kim SY. Assessing and communicating the risks and benefits of gene transfer clinical trials. Curr Opin Mol Ther 2006; 8:384– 389.
- Kuhn TS. The Structure of Scientific Revolutions. 2nd ed. Chicago, IL: University of Chicago Press; 1970.
- Starzl TE. The Puzzle People: Memoirs of a Transplant Surgeon. Pittsburgh, PA: University of Pittsburgh Press; 2003.
- Twenty Five Years of Excellence: A History of the Texas Heart Institute. Houston, TX: Texas Heart Institute Foundation; 1989.
- Fogarty Institute for Innovation Web site. Available at: http://01659a8. netsolhost.com/aboutus.html. Accessed June 6, 2008.
- Denton A. Cooley Cardiovascular Surgical Society Web site. Available at: http://www.cooleysociety.com/about.html. Accessed June 6, 2008.
- de Melo-Martín I, Palmer LI, Fins JJ. Viewpoint: developing a research ethics consultation service to foster responsive and responsible clinical research. Acad Med 2007; 82:900–904.
- Frader JE, Caniano DA. Research and innovation in surgery. In: McCullough LB, Jones JW, Brody BA, eds. Surgical Ethics. New York, NY: Oxford University Press; 1998:216–241.
- Speelman JD, Bosch DA. Resurgence of functional neurosurgery for Parkinson’s disease: a historical perspective. Mov Disord 1998; 13:582–588.
- Holstein WJ. Rewiring the brain: how a bright idea became an innovative medical device. US News & World Report. March 1, 1999:52–53.
- Fins JJ, Schachter M. Investigators, industry, and the heuristic device: ethics, patent law, and clinical innovation. Account Res 2001; 8:219–233.
- Penfield W. No Man Alone: A Neurosurgeon’s Life. Boston, MA: Little Brown; 1977.
- Feindel W. The contributions of Wilder Penfield to the functional anatomy of the human brain. Hum Neurobiol 1982; 1:231–234.
- Aristotle. The Nicomachean Ethics. Weldon JEC, trans. Amherst, NY: Prometheus Books; 1987.
- Fins JJ, Bacchetta MD, Miller FG. Clinical pragmatism: a method of moral problem solving. Kennedy Inst Ethics J 1997; 7:129–145.
- Miller FG, Fins JJ. Protecting human subjects in brain research: a pragmatic perspective. In: Illes J, ed. Neuroethics: Defining the Issues in Theory, Practice and Policy. New York, NY: Oxford University Press; 2005.
- Pollan M. The year in ideas: A to Z.; precautionary principle. New York Times. December 9, 2001.
- van den Belt H. Debating the precautionary principle: “guilty until proven innocent” or “innocent until proven guilty”? Plant Physiol 2003; 132:1122–1126.
- Jonas H. The Imperative of Responsibility: In Search of an Ethics for the Technological Age. Chicago, IL: University of Chicago Press; 1985:34.
- Eliot TS. The Love Song of J. Alfred Prufrock. In: Abrams MH, ed. The Norton Anthology of English Literature. Vol 2. 4th ed. New York, NY: W.W. Norton & Co; 1979:2259–2264.
- Sunstein CR. The paralyzing principle. Regulation. Winter 2002– 2003; 25(4):32–37.
- Holm S, Harris J. Precautionary principle stifles discovery. Nature 1999; 400:398.
- Bosk C. Forgive and Remember: Managing Medical Failure. Chicago, IL: University of Chicago Press; 1979:29–30.
- Bliss M. Harvey Cushing: A Life in Surgery. Oxford, UK: Oxford University Press; 2005.
- Pinkus RL. Mistakes as a social construct: an historical approach. Kennedy Inst Ethics J 2001; 11:117–133.
- AAMC Task Force on Financial Conflicts of Interest in Clinical Research. Protecting subjects, preserving trust, promoting progress I: policy and guidelines for the oversight of individual financial interests in human subjects research. Acad Med 2003; 78:225–236.
- AAMC Task Force on Financial Conflicts of Interest in Clinical Research. Protecting subjects, preserving trust, promoting progress II: principles and recommendations for oversight of an institution’s financial interests in human subjects research. Acad Med 2003; 78:237– 245.
- Fins JJ. Disclose and justify: intellectual property, conflicts of interest, and neurosurgery. Congress Quarterly (Official Newsmagazine of the Congress of Neurological Surgeons) 2007; 8(3):34–36.
- U.S. Constitution, art. I, §8, cl. 8; see also id. at art. I, §8, cl. 18.
- Patent Act of 1790, ch. 7, 1 Stat. 109–111 (1790).
- Patent and Trademark Act Amendments of 1980 (Bayh-Dole Act); Pub L No. 96-517. Codified as 35 USC §§200–212 (1994).
- Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987; 317:141–145.
- Callahan D. Necessity, futility, and the good society. J Am Geriatr Soc 1994; 42:866–867.
- Katz J. The Silent World of Doctor and Patient. New York, NY: Free Press; 1984.
- Jones RS, Fletcher JC. Self-regulation of surgical practice and research. In: McCullough LB, Jones JW, Brody BA, eds. Surgical Ethics. New York, NY: Oxford University Press; 1998:255–279.
- Kim SY. Assessing and communicating the risks and benefits of gene transfer clinical trials. Curr Opin Mol Ther 2006; 8:384– 389.
- Kuhn TS. The Structure of Scientific Revolutions. 2nd ed. Chicago, IL: University of Chicago Press; 1970.
- Starzl TE. The Puzzle People: Memoirs of a Transplant Surgeon. Pittsburgh, PA: University of Pittsburgh Press; 2003.
- Twenty Five Years of Excellence: A History of the Texas Heart Institute. Houston, TX: Texas Heart Institute Foundation; 1989.
- Fogarty Institute for Innovation Web site. Available at: http://01659a8. netsolhost.com/aboutus.html. Accessed June 6, 2008.
- Denton A. Cooley Cardiovascular Surgical Society Web site. Available at: http://www.cooleysociety.com/about.html. Accessed June 6, 2008.
- de Melo-Martín I, Palmer LI, Fins JJ. Viewpoint: developing a research ethics consultation service to foster responsive and responsible clinical research. Acad Med 2007; 82:900–904.