Navigating Biases in Sepsis Diagnosis

Reference: Agnello et al. Monocyte distribution width (MDW) as a screening tool for early detecting sepsis: a systematic review and meta-analysis. Clinical Chemistry and Laboratory Medicine 2022; 60(5):786-792 Clin Chem Lab Med. 2022 Date: February 21, 2025 Guest Skeptic: Dr. Aaron Skolnik is an Assistant Professor of Emergency Medicine at the Mayo Clinic Alix School of Medicine and Vice Chair of Critical Care Medicine at Mayo Clinic Arizona.  He is board-certified in Emergency Medicine, Medical Toxicology, Addiction Medicine, Internal Medicine-Critical Care, and Neurocritical Care.  Aaron is a full-time multidisciplinary intensivist.  He is the Medical Director of Respiratory Care for Mayo Clinic Arizona and enjoys serving as medical student clerkship director for critical care. Case: A 62-year-old male presents to the Emergency Department (ED) with fever, confusion, and shortness of breath. His symptoms began two days ago, starting with generalized malaise and chills, followed by progressive dyspnea and mental status changes. The patient also reports decreased urine output over the past day. He has a history of Type 2 diabetes mellitus, hypertension, and chronic kidney disease (stage 3). His home medications include metformin, lisinopril, and amlodipine, though he hasn’t taken his antihypertensives for the last two days. He is tachycardic, tachypneic, and febrile with a BP of 92/58, and an oxygen saturation of 91% on room air. Physical examination reveals diffuse crackles bilaterally and chest x-ray shows bilateral infiltrates consistent with pneumonia. His WBC is elevated at 23,000 with a left shift. Lactate is 3.8 mmol/L and blood cultures are pending. Background: Rapid and accurate diagnosis of sepsis is critical, as early intervention can significantly reduce patient mortality. However, diagnosing sepsis early remains challenging because it presents with nonspecific symptoms. New biomarkers, such as procalcitonin and lactate, offer some utility but are not sufficiently reliable on their own​​. Recently, monocyte distribution width (MDW) has emerged as a promising biomarker in this diagnostic challenge. MDW, an indicator of variability in monocyte size, can be rapidly assessed as part of an automated complete blood count differential and may flag potential sepsis early in patients. This parameter has the advantage of being available very quickly without additional blood draws, which could be helpful in the fast-paced ED setting. Current evidence suggests MDW could be used alongside existing clinical criteria to help screen for sepsis risk and guide further assessment and treatment, even in patients where sepsis is not immediately suspected​​. Clinical Question: What is the diagnostic accuracy of monocyte distribution width for early detection of sepsis? Reference: Agnello et al. Monocyte distribution width (MDW) as a screening tool for early detecting sepsis: a systematic review and meta-analysis. Clinical Chemistry and Laboratory Medicine 2022; 60(5):786-792 Clin Chem Lab Med. 2022 Population: Adults admitted to various clinical settings, particularly the ED, intensive care unit (ICU), and one infectious diseases unit (I don’t have one of those Ken – do you?). Excluded: Pediatric patients, COVID-19 patients, non-diagnostic studies (ie studies evaluating only the prognostic role of MDW), non-English studies and case reports and reviews. Intervention: Monocyte distribution width (MDW) Comparison: Sepsis-2 and Sepsis-3 diagnostic criteria. Sepsis-2 is based on systemic inflammatory response syndrome (SIRS) markers, while Sepsis-3 relies on organ dysfunction as assessed by the sequential organ failure assessment (SOFA) score​. Outcome: Diagnostic accuracy of MDW for early sepsis detection, measured by pooled sensitivity, specificity, and likelihood ratios​. Type of Study: Systematic review and meta-analysis for diagnostic accuracy