Vitamin D insufficiency and sepsis severity in emergency department patients with suspected infection

Objectives: Vitamin D is increasingly recognized as an important mediator of immune function and may have a preventive role in the pathogenesis of sepsis. We sought to evaluate the association between vitamin D status and sepsis severity and hypothesized that vitamin D insufficiency would be associated with increased sepsis severity.

Methods: This was a pilot study of emergency department (ED) patients age ≥ 18 years evaluated for suspected infection at an urban, teaching hospital. The authors measured illness severity using the following assessments at baseline and 24 hours: 1) severe sepsis, defined as suspected infection plus two or more elements of systemic inflammatory response syndrome criteria and acute dysfunction of one or more organ systems; 2) Acute Physiology Age Chronic Health Evaluation (APACHE) II scores; and 3) Sepsis-related Organ Failure Assessment (SOFA) scores. Vitamin D insufficiency was defined as baseline serum 25-hydroxyvitamin D (25OHD) levels <75 nmol/L.

Results: Eighty-one patients were enrolled, with a median age of 62 years (interquartile range [IQR] = 48-76 years), 47% were female, and 77% were white. At baseline, 64 (79%) had 25OHD levels of <75 nmol/L, and 43 (53%) had severe sepsis. At 24 hours, 48 (59%) had severe sepsis. Patients with baseline 25OHD levels of <75 nmol/L, compared to patients with 25OHD levels of ≥ 75 nmol/L, were more likely to have severe sepsis (61% vs. 24%; p = 0.006) and SOFA scores ≥ 2 (44% vs. 18%; p = 0.049). Additionally, at 24 hours, those with 25OHD levels of <75 nmol/L were more likely to have severe sepsis (67% vs. 29%; p = 0.005), dysfunction of two or more organ systems (50% vs. 18%; p = 0.02), APACHE II score of ≥ 25 (19% vs. 0%; p = 0.06), and SOFA scores of ≥ 2 (63% vs. 29%; p = 0.02). Additionally, all four patients who died during the index hospitalization had 25OHD levels of <75 nmol/L.

Conclusions: Vitamin D insufficiency was associated with higher sepsis severity in ED patients hospitalized for suspected infection. Larger observational studies, mechanistic studies, and ultimately randomized controlled trials are needed to determine causation and to evaluate if vitamin D supplementation can reduce the risk of sepsis as a preventive or therapeutic strategy.