Caring for the critically ill patient: challenges and opportunities.

FOR A QUARTER CENTURY, JAMA HAS SERVED AS A VENUE for articles relating to care of critically ill patients, beginning with the Concepts in Emergency and Critical Care section, in which these fields were initially described as “spanking new medical disciplines.” At the time, knowledge of the biology of critical illness was rudimentary, the focus was on initial patient care, such as airway management and resuscitation, and the few physicians trained in emergency or critical care medicine worked mainly in large teaching hospitals. During the following years, critical care and emergency medicine grew rapidly, training and accreditation became more standardized, and the focus changed to the definition, management, and outcome of postresuscitation syndromes, such as sepsis, shock, and organ dysfunction. Approximately 10 years ago, the section name was changed to Caring for the Critically Ill Patient, ushering in increased focus on high-quality multicenter randomized trials, organization and delivery of care, and attention to patient-centered outcomes. Today, the Caring for the Critically Ill Patient section of JAMA is devoted to publication of important articles in critical and emergency care at a time when the clinical and research landscape has shifted again. Advances in molecular biology now provide a wealth of information on the humoral and cellular responses to acute trauma, infection, and ischemia. This understanding has helped delineate the mechanisms of shock, sepsis, and organ dysfunction syndromes, such as acute respiratory distress syndrome (ARDS), acute renal failure, and traumatic brain injury, generating a plethora of therapeutic targets. The scale of critical care and emergency medicine services has also changed. Every acute care hospital in the United States boasts an intensive care unit (ICU), half of the nation’s ICU beds are located in small hospitals, and many teaching hospitals have built huge ICU services, often with 60 or more beds. Six million Americans, or 2% of the population, are admitted to the ICU each year, severe sepsis and ARDS affect hundreds of thousands of individuals annually, and 1 in 5 Americans receive ICU care at the end of life. All this care is provided by a workforce of hundreds of thousands of highly trained physicians, nurses, and allied health care personnel who function in integrated team systems, not just in the ICU and emergency department, but increasingly on hospital general units and in the community. With substantial investment of resources and advancement in knowledge, care of critically ill patients has no doubt improved. Mortality appears to have decreased for sepsis and ARDS, and headway has been made toward safer, quicker, more effective care. However, considerable challenges lie ahead on the path from basic science to improved public health, including a translational block between basic science and clinical trials; challenges in conducting clinical trials in critically ill patients; failure of clinical research to fully frame health issues facing critically ill patients; an inadequate evidence base for many aspects of care; and public health policy that is either lacking or uninformed by evidence. The first challenge, overcoming translation from basic science to clinical trials, is exemplified by the sepsis syndromes. Among the more than 30 large trials involving agents designed to modify the host response to infection, only 2 were positive (and neither of these are considered definitive). While trial design may be partly to blame, the problems run deeper. Severe sepsis, the subset of sepsis with acute organ dysfunction, is often difficult to define and encompasses a highly heterogeneous group of patients. Outcome and probably response to therapy are linked to multiple host, pathogen, and health care–related factors that neither in vitro nor in vivo models adequately address. Therapies enter clinical trials with little information on appropriate dosing or methods to monitor their biologic activity. A particular challenge for sepsis and other critical illnesses is that the pathways targeted for modification are as often helpful as harmful, and current clinical trial entry criteria provide no guarantee that the host response pathway of interest is either active in a particular patient or behaving in an injurious manner. Thus, clinical research needs better tools to select and monitor patients and their therapies, and basic science needs