Response

Abstract

We thank Lee et al for their interest in our study that suggests higher short-term mortality rates in previously healthy individuals hospitalized with community-onset sepsis compared with those with comorbidities and raises collider bias as a potential explanation.1Alrawashdeh M Klompas M Simpson SQ et al.Prevalence and outcomes of previously healthy adults among patients hospitalized with community-onset sepsis.Chest. 2022; 162: e63-e64Google Scholar We agree this is an important consideration and in fact pointed out the same issue through a clinical lens that Lee et al labeled using a statistical term. Specifically, we discussed that providers may be more concerned about possible sepsis in patients with comorbidities and thus may be more likely to order blood cultures and administer antibiotics (thereby triggering Center for Disease Control and Prevention Adult Sepsis Event [ASE] criteria) for less severe illnesses compared with healthy patients. This could lower the apparent sepsis mortality rate for patients with comorbidities partly because they are preferentially being flagged by ASE criteria for milder illnesses and partly because some noninfectious exacerbations of chronic illnesses may be more responsive to treatment than bona fide sepsis. These possibilities are supported by the lower rates of bloodstream infections and vasopressor use among patients with vs without comorbidities. Notably, any sepsis case-identification method risks selection bias, given the lack of a true diagnostic gold standard.2Rhee C. Kadri S.S. Danner R.L. et al.Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes.Crit Care. 2016; 20: 89Crossref PubMed Scopus (101) Google Scholar However, ASE at least uses consistent clinical criteria rather than relying on subjective diagnoses and has been shown in prior validation studies to have excellent sensitivity and specificity.3Rhee C. Dantes R. Epstein L. et al.Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014.JAMA. 2017; 318: 1241-1249Crossref PubMed Scopus (759) Google Scholar We are also careful to emphasize that our findings apply only to patients who were hospitalized with sepsis and not to the general healthy outpatient population. Indeed, healthy individuals are clearly less likely overall to develop and die of sepsis than patients with comorbidities, a fact underscored by our key finding that previously healthy individuals account for only a small fraction of sepsis cases treated in hospitals. Last, we highlight the plausibility of some of the other explanations that we considered. For example, the possibility that the resilience of previously healthy patients might make them present later to the hospital is supported by our observation that they had slightly higher requirements for vasopressors within the first 2 days of admission. Furthermore, the possibility that sepsis recognition and treatment are relatively delayed in previously healthy patients when they do seek care is supported by tragic stories about the untimely deaths of young and healthy people because of missed diagnoses.4Staunton O. Staunton C. The urgency of now: attacking the sepsis crisis.Crit Care Med. 2018; 46: 809-810Crossref PubMed Scopus (6) Google Scholar Ultimately, however, we consider our study to be hypothesis-generating and advocate for all potential explanations to be investigated more thoroughly with the use of rigorously designed studies. Financial/nonfinancial disclosures: See earlier cited article for author conflicts of interest. Collider Bias Rather Than a Healthy Condition Leads to the Unfavorable Outcome of SepsisCHESTVol. 162Issue 1PreviewWe applaud Alrawashdeh et al1 in this issue of CHEST for using three large administrative databases to investigate the impact of previously healthy conditions and comorbidities on sepsis outcomes. However, the unexpected finding that previously healthy patients were at greater risk of dying of sepsis than were patients with comorbidities caught our attention. The authors suggested that several characteristics associated with previously healthy patients could explain the counterintuitive finding, including delayed medical attention, more sepsis with unknown sources, late diagnosis of organ dysfunction, or genetic predisposition. Full-Text PDF Prevalence and Outcomes of Previously Healthy Adults Among Patients Hospitalized With Community-Onset SepsisCHESTVol. 162Issue 1PreviewThe vast majority of patients hospitalized with community-onset sepsis harbor pre-existing comorbidities. However, previously healthy patients may be more likely to die when they seek treatment at the hospital with sepsis compared with patients with comorbidities. These findings underscore the importance of early sepsis recognition and treatment for all patients. Full-Text PDF