IOD is always difficult. It is particularly difficult in patient populations such as obstetrics and pediatrics, where death is very rarely a probable outcome. Many pediatric anesthesiologists are involved in the care of patients when they are in their most clinically tenuous state. As Soto argues, an anesthesiologist’s brief and seemingly superficial encounter with a patient prior to surgery “leads to situations in which we potentially internalize the impact of death…[and] we find ourselves ill-equipped to deal with the grieving process” (J Clin Anesth 2003;15:275-7). Many anesthesiologists thus experience overwhelming feelings of guilt and anxiety, often attributable to “disenfranchised grief,” or overlooked pain, while other physicians involved in these tragic events are permitted to and trained to grieve among their colleagues (Anesthesiology 2017;126:1200-1). However, resources from the pediatric critical care field, where these outcomes are infrequent but not uncommon, do exist. Pediatric anesthesiologists can look to emotional training and grief counseling techniques employed by pediatric and neonatal intensivists (J Clin Anesth 2003;15:275-7).

By contrast, in the obstetric population, anesthesiologists may find limited resources for support. A study found that, following a maternal death, there is a professional culture of silence, likely driven by fear of individual accountability (Acta Obstet Gynecol Scand 2015;94:1346-53). However, this study – one of the first and only to provide direct insight into how the multidisciplinary teams are affected by maternal death – fails to include a survey of anesthesiologists involved in the IOD. These feelings can be further exacerbated in resource-limited settings, often where maternal mortality remains elevated (BMC Pregnancy Childbirth 2022;22:206).

While anesthesiologists are rarely the sole players in the management of a patient on the verge of IOD, they may be questioned or blamed for ineffective resuscitation, which amplifies feelings of guilt and responsibility in the death of a patient. Specialties with higher burdens of unexpected and sometimes catastrophic patient events – emergency medicine, surgery, and anesthesiology – have higher rates of provider “second victim syndrome.” Described by Dr. Albert Wu, the “second victim syndrome” is a framework expanded to include any emotional burden experienced by a health care worker after a traumatic event. Symptoms include troubling memories, fear of repeating errors in the future, embarrassment, and guilt (Second Victim Syndrome. 2024). A survey study found that in anesthesiologists who had experienced IOD, over 70% exhibited these symptoms and 19% of respondents never fully recovered. Over 12% of anesthesiologists considered a career change. More worrisome is that two-thirds of respondents felt most compromised in their ability to provide care for the immediate four hours, but only 7% were permitted time off (Anesth Analg 2012;114:596-03).

Because of the rarity of an IOD, anesthesiologists may not know how to cope nor where to look for guidance. Surveys have shown that anesthesiologists faced difficulty with disclosing an IOD, and many felt they had inadequate support (Can J Anaesth 2010;57:361-7). Anesthesiologists, like other physicians, may feel they are a part of a culture of infallibility; however, it is crucial that anesthesiologists have support from their institution regarding reporting of an IOD as well as support of their emotional needs (Acta Anaesthesiol Scand 2005;49:728-34). Having a system in place for debriefing and analysis of the events leading up to the IOD is critical in managing emotional outcomes in physicians and for quality improvement. Particularly with maternal death, team members point to the lack of organized support in navigating the aftermath (Second Victim Syndrome. 2024).

Organized support is even more crucial when considering that medical trainees are often involved in the care of patients prior to IOD. Trainees frequently witness poor outcomes for the first time in the observer role and do not always have resources to debrief and process the event. For instance, a cross-sectional study of 188 doctors managing care across a population that experienced a high rate of patient death found that junior residents reported needing significantly more emotional support than attending physicians after the death of their patients (BMJ 2003;327:185). Debriefing and creating spaces for trainees to reflect on their emotional experiences have proven to be beneficial in helping them recover (Cureus 2023;15:e39715).

The growing role of simulation of patient death among trainees offers a potential for enhancing existing curricula that prepare trainees to navigate these outcomes. While few studies point to greater levels of stress and anxiety in medical students in simulated patient death, this research is primarily focused on small cohort studies that do not follow long-term educational outcomes (Cureus 2023;15:e39715). We argue for further research in this growing field as high-fidelity simulation becomes a more standard practice in anesthesiology training.

The assumption that most anesthesiologists may remain insulated from intraoperative death is a fallacy and may further lead to poor support systems for navigating the aftermath. We strongly advocate for the incorporation of routine discussions of intraoperative death at the anesthesiology trainee level through lectures and simulations. Additionally, we call for systemic changes to ensure that all anesthesiology trainees have immediate access to robust emotional and psychological support resources in the event of an intraoperative patient death. Our training should prepare us to handle every outcome, especially the most unimaginable.

At a minimum, these unexpected outcomes force us to shine a light inward to answer the questions: What makes a good anesthesiologist? What makes a good career? It is hard to say. But perhaps “being good” comes from knowing that taking care of a patient can mean both comforting a patient as they fall asleep, and rapidly resuscitating them in the face of a crisis. It comes from also knowing that our patients can be both extremely resilient and exquisitely tenuous at the same time – that our cases can be simple and complex, routine and emergent. And finally, it comes from knowing that we, as anesthesiologists, can be both strong and vulnerable, sensitive and brave, as we handle the good outcomes and the bad.

After reading Dr. Olga L. Quintero’s article, “A Lesson in Loss: A Novice Anesthesiologist’s Journey,” I was deeply moved by the profound challenges she encountered early in her career.  For any newly graduated anesthesiologist, such an experience is an emotional and psychological blow. First and foremost, I want to express my deepest sympathy to the author and encourage her to maintain her resilience as she continues her long and challenging journey in this profession. This poignant narrative has prompted me to reflect on five key aspects that I believe warrant further discussion.

Dr. Quintero’s detailed account of handling a critically ill patient highlights the ethical and clinical decision-making challenges that anesthesiologists face. In dealing with a patient with severe comorbidities, she had to make rapid decisions about whether to proceed with a high-risk intervention. This ethical dilemma, particularly when it involves principles like “do no harm” and informed consent, can be deeply troubling for any physician. Although the outcome was unfortunate, her internal struggle showcases the complexity of weighing the benefits of treatment against the potential risks. This decision-making process requires not only extensive medical knowledge but also a deep understanding and respect for the ethical principles guiding patient care.

In the context of managing critically ill patients, even experienced anesthesiologists may find their individual capacity limited. As the Chinese proverb goes, “A fence needs three posts,” and “Three humble tailors make a great strategist.” Teamwork is crucial in anesthesiology. While surgeons often have assistants in the operating room, placing a single anesthesiologist in a specialized medical unit poses significant risks. Although this may be due to a shortage of anesthesiologists from a patient safety perspective, it is essential to have at least two anesthesiologists present. This incident should serve as a wake-up call for department managers to reassess staffing policies to ensure that anesthesiologists receive the support they need during critical moments.

Dr. Quintero’s experience also sheds light on the significant psychological pressures that novice anesthesiologists face, which can lead to burnout. The work environment for anesthesiologists is often filled with uncertainty and tension, particularly in emergency situations. Her narrative vividly portrays how this pressure can impact the mental well-being of a novice physician. With increasing awareness of mental health issues within the medical profession, Dr. Quintero’s story serves as a reminder that medical training should not only focus on technical skills but also on psychological resilience. Building effective psychological support systems is crucial to helping physicians manage the inevitable stresses and challenges of their careers.

The article also addresses the critical issue of doctor-patient communication, especially in the aftermath of an adverse outcome. Dr. Quintero describes her feelings of confusion and helplessness when faced with the task of communicating a patient’s death to their family. This highlights the challenges that healthcare professionals often face in conveying difficult news and engaging with families during critical moments. Effective communication requires empathy and skill, especially when dealing with life-and-death situations. Enhancing training in crisis communication and emotional support is an essential aspect of modern medical education.

Novice anesthesiologists may feel overwhelmed when faced with complex cases due to their limited experience. Ongoing professional education not only helps them improve their technical skills but also boosts their confidence in handling complex and emergency situations. Medical institutions should encourage participation in continuing education and professional training, including simulations and case studies, to help physicians continually advance their skills and approach future challenges with greater confidence.

In closing, I would like to express my respect and support for Dr. Quintero once again. I hope she continues to walk the path of anesthesiology with determination, growing stronger with each challenge she faces, and ultimately becoming an even more exceptional physician.

First, we would like to thank Strauss et al. for their insight regarding the problem of primary graft dysfunction in response to our recent clinical review article. 

This article correctly points out that primary graft dysfunction, or perioperative allograft injury due to ischemia or reperfusion injury, is a significant problem after lung transplantation and is multifactorial. In 2017, the International Society for Heart and Lung Transplantation (Chicago, Illinois) published the clinical definition of primary graft dysfunction, which created a consensus for diagnosis, that can be consistently measured across centers at specific time points, and quantified severity.  We appreciate Strauss et al. highlighting the other contributing factors to primary graft dysfunction, which include the disruption of the endothelial-epithelial alveolar membrane of the new allograft and the direct result of ischemia-reperfusion injury. Primary graft dysfunction is a diagnosis that well characterizes the clinical injury to the new allograft, with ischemia and reperfusion being the most obvious inflammatory insult in the setting of many other potentially injurious risk factors in the perioperative period.

Although there is overlap in the molecular markers of primary graft dysfunction and transfusion-related injury the intent of our review was not to suggest that transfusion is the sole variable influencing primary graft dysfunction. In fact, many studies in this space prove only a retrospective association of transfusion with primary graft dysfunction, which should not presume causation. We intend to encourage the reader to understand who is at high risk for perioperative transfusion and the myriad clinical implications in this niche patient population, investigate recipient optimization processes when possible, and examine transfusion decision-making. The goal of our review was to point out variability in the literature in how we quantify bleeding and define significant transfusion, and the influences on our decisions to transfuse in clinical practice. We present concepts central to pragmatic, judicious blood product use in a unique patient population that has a significant incidence of perioperative complications. However, we understand that reducing unnecessary transfusion is only one potentially modifiable variable of many that contribute to primary graft dysfunction. Unlike ischemia and reperfusion injury, the judicious use of goal-directed transfusion is easily within our capacity as intensivists and anesthesiologists.

The final comment in the letter to the editor suggests that ischemia and reperfusion injury should be best prevented through more investigation of immunosuppression, immunomodulation, and new therapies and technologies (e.g., therapies provided through ex vivo lung perfusion). Developing therapies for the lung donor and recipient to prevent primary graft dysfunction specifically would undoubtedly be an incredible step forward. However, the goal of our review was not to identify all of the treatable risk factors or potential future therapies to prevent the outcome of primary graft dysfunction. A review centered on reducing primary graft dysfunction would require an extensive review of existing literature on molecular targets and developing therapies, and an examination of many perioperative processes, starting in the preclinical period, that influence both the donor and recipient.

Because anesthesiologists and intensivists are key perioperative providers who both make decisions and provide therapies in the perioperative space, we are uniquely qualified to examine processes and optimize outcomes alongside the multidisciplinary team. We encourage the reader to consider their daily clinical practices to identify and reduce risk factors not limited to improving the outcome of primary graft dysfunction, but that might reduce all types of perioperative injury. Topics for additional study should include management and preservation of the donor organ, ventilator management of both the donor and the recipient, anesthetic and pain management, volume management, selection and management of hemodynamics on mechanical circulatory support mode, recipient and donor selection, management of perioperative immunosuppression, infection prevention, and other experimental therapies.

Thank you again for your interest in our clinically focused review and your response to the editor. We agree that primary graft dysfunction and ischemia or reperfusion may be significantly reduced through a more comprehensive examination of perioperative risk factors and the use of specific therapies under development. We hope that our review prompts a careful evaluation of not only transfusion practice, but an in-depth look at each modifiable risk factor for perioperative injury.

The review by Bottiger et al.  highlights several recent studies related to allogenic transfusions for lung transplantation. The authors discuss perioperative factors that increase the risk of bleeding, report the evidence that connects transfusion to worse outcome, and suggest strategies to decrease transfusion. Many studies suggest an association between higher perioperative transfusion totals and primary graft dysfunction which as the authors report is a problem encountered in 15 to 20% of lung transplants, but this association is complicated by multiple variables. Anesthesiologists should appreciate the evidence showing a connection between perioperative transfusion and lung transplantation outcome but also need to be aware of the additional factors involved in this issue.

The severity of primary graft dysfunction (grades 1 to 3) is based on the presence of infiltrates on chest x-ray, decreased ratio of arterial oxygen partial pressure (Pao₂) to the fraction of inspired oxygen (Fio₂), and the need for extracorporeal life support.  The data from some transplant centers show an increased incidence of chronic lung allograft dysfunction in patients who developed grade 3 primary graft dysfunction within 72 h after transplantation.  The stronger inflammatory cascade seen in worsened primary graft dysfunction may allow more recipient immune cells access to the microvascular areas typically protected by the endothelial-epithelial alveolar membrane causing higher levels of allorecognition and promoting a greater long-term immune response to the allograft.  Likewise, a stronger inflammatory response may cause increased systemic vasodilation and decreased organ perfusion, leading to hypotension and acidosis, which compels perioperative physicians to respond by administering intravenous fluids and lowering the threshold for transfusion.

Ischemia or reperfusion injury is the major cause of primary graft dysfunction and, as mentioned in the review, lung injury in the categories of transfusion-associated lung injury and transfusion-associated circulatory overload are difficult to differentiate from primary graft dysfunction at the cellular level.  In fact, the differences boil down to the precipitating event that causes the disruption of endothelial-epithelial alveolar membrane.  The immunologic or inflammatory cascade that occurs in transfusion-associated lung injury versus the increased pulmonary hydrostatic edema of transfusion-associated circulatory overload. Any factors that can worsen transfusion-associated circulatory overload and transfusion-associated lung injury will worsen primary graft dysfunction. Poor diastolic function is known to worsen transfusion-associated circulatory overload and is one important example of such a factor. For recipients, the severity of the injury or the degree of primary graft dysfunction can be worsened not only by increased transfusion but also by diastolic dysfunction of the recipient’s heart.  Transesophageal echocardiography can measure the degree of diastolic dysfunction and monitor the left ventricular filling pressures in the perioperative period to provide a more nuanced approach to fluid management and guide the administration of inotropes. It is hoped that increased awareness and vigilance regarding this factor will help perioperative physicians make decisions that decrease the incidence or severity of primary graft dysfunction.

Ultimately, the issue may be improved by the development of new techniques that are focused on mitigating ischemia or reperfusion injury. Several studies have examined the use of normothermic ex vivo lung perfusion systems with varying perfusates and show some improvement in primary graft dysfunction at 72 h after transplantation.  Additional preclinical research continues that focuses on new immunosuppression and immunomodulating medications and therapies targeting the complement and cytokine signaling pathways and include gene knockdown therapy via RNA interference to silence the expression of genes involved in ischemia or reperfusion injury.  Improving judgment with regard to perioperative transfusion and blood management techniques is a worthy objective, but decreasing ischemia or reperfusion injury should be our primary goal.