“Our great struggle in medicine these days is not just with ignorance and uncertainty. It's also with complexity: how much you have to make sure you have in your head and think about. There are a thousand ways things can go wrong.”
Atul Gwande, M.D., American surgeon and writer
“A good doctor treats the disease; a great doctor treats the patient who has the disease.”
Sir William Osler, Canadian physician and founder of internal medicine
“Sepsis, defined as life-threatening acute organ dysfunction due to a dysregulated host response to infection, is a leading cause of illness and death worldwide.” (See Meyer, Nula and Prescott, Hallie, “Sepsis and Septic Shock,” The New England Journal of Medicine, 2024; 391:22, 2133- 2144.) Few areas of medicine are as serious and complex as the management of sepsis and septic shock. Fortunately, the mortality of sepsis and septic shock has fallen from 50% to about 30% over the past 50 years. Public health organizations like the Centers for Disease Control and Prevention, the World Health Organization, and international consortia of critical care specialists contributed to this reduction in mortality. In this Germ Gems post, I highlight key developments in managing sepsis/septic shock and lowering its mortality.
Sepsis and septic shock: a recap. Along with many areas of clinical and basic science research on sepsis and septic shock, the definitions of these entities as well as an understanding of their pathogenesis have evolved considerably over the past half century. The current definition of sepsis is “acute organ dysfunction due to a dysregulated host response to infection.” This definition points to the involvement of the host (the patient) in development of the disorder as well as to microbes that trigger a chain reaction by an activated immune system. (See, “Sepsis: What Everyone Needs to Know,” Germ Gems, November 3, 2019; “Sepsis in Children: Recent Developments,” Germ Gems, February 28, 2024.) When a certain pathogenic threshold is crossed “shock,” that is, a dangerously low blood pressure, develops.
A simple, yet complex concept of what an activated immune system does for and to us is this: we wouldn’t survive without it, but in the context of sepsis, an activated immune system is what makes us sick, and in some cases, kills us. In other words, the immune system can be a “double-edged sword.” (A dramatic example of this “double-edged sword” nature of the immune system was demonstrated in the early days of the COVID-19 pandemic when researchers focused on treating the “cytokine storm” generated by the immune response to the virus SARS-CoV-2. The use of high dose anti-inflammatory agents, like the glucocorticoid drug dexamethasone, was found beneficial in quelling the life-threatening cytokine storm provoked by SARS-CoV-2.)
Certain types of bacteria are the most notorious infectious agents that trigger sepsis/septic shock. We now know, however, that some viruses, fungi, and parasites can also be responsible. In addition, much has been learned about the organs that take the biggest “hit” by a reduced blood supply, namely, the lungs, kidneys, heart, and brain.
Managing a dysregulated immune system. The two advances that I believe contributed most to saving the lives of patients with sepsis are: (1) early recognition/diagnosis; and (2) understanding that this is a multiple organ system disorder thereby prompting a team approach with participation of multiple medical specialties to manage it.
Of the types of infections associated with sepsis/septic shock, those involving the lungs, i.e., pneumonia, are most fatal, followed by infections of the genitourinary tract (kidneys and bladder), intraabdominal, skin and soft tissue, and bloodstream. Over the past several years, corticosteroids were found in eight randomized controlled trials to decrease mortality of pneumonia by 28%, presumably by limiting the adverse effects of sepsis.
Most patients with sepsis and septic shock are managed in an intensive care unit (ICU). Once there, pulmonologists attend to failing lungs, nephrologists to failing kidneys, and cardiologists to failing hearts. Infectious diseases specialists are also on board advising about what antibiotics are best suited for the infectious agent that triggered the problem. In addition, modern technologies abound, such as, heart monitors, ventilators, infusion devices, and, in some cases, dialysis machines.
Advances in the science, but how about the “art?” When I began my medical school training at Columbia University College of Physicians and Surgeons (P&S) in New York City in 1966, ICUs were just being developed. At that time, technologies such as respirators and dialysis machines were capturing most of the attention, and caring for patients was becoming increasingly challenging.
I vividly remember an anecdote told about Dr. Robert Loeb, the legendary chairman of medicine at P&S and co-author of A Textbook of Medicine, who allegedly asked to have tattooed on his chest, “Never admit me to an ICU.” The basis of Dr. Loeb’s concern was that he was an “Old School” physician who, like Sir William Osler, the founder of internal medicine, believed that “medicine is an art informed by science.” And he worried that technology was getting in the way of patient care.
Since my graduation from P&S in 1970, the advances in scientific understanding and medical technology have been extraordinary, and, in my mind, get major credit for the decreased mortality of sepsis and septic shock. Yet, caring for patients and their anxious loved ones (the art of medicine) seems increasingly difficult when faced with the dilemma of when and how much technology to implement.
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