“Vitamin D deficiency and supplementation has been studied extensively in various critically ill populations,” explains David M. Hill, PharmD, BCPS, BCCCP, FCCM. “Outside of its benefits with calcium and phosphorus hemostasis, vitamin D is an essential component in immune modulation, and low vitamin D concentrations have been associated with greater risk for sepsis, lengths of stay (LOS), hospital costs, and mortality. Data are limited regarding outcomes in patients with burn injuries, but considering infectious complications and outcomes is paramount in this population.”

The destruction of the skin leads to physical compromise and metabolic dyscrasias, resulting in a profound state of immunocompromise, according to Dr. Hill. “Furthermore, patients with burns are in the hospital for longer periods than most populations, as it takes time to regrow skin or close large wounds. Longer hospital stays are associated with  higher risk for infection, antimicrobial exposure, and subsequent antimicrobial resistance and failure,” he says. “Measuring vitamin D concentrations and potentially supplementing is a simple intervention.”

For a study published in Burns, Dr. Hill and colleagues sought to examine the clinical impact of vitamin D deficiency on infectious complications in adult patients with burns. The study, which included seven centers, utilized generalized linear mixed modeling to control for center effect, percent total body surface area burn (%TBSA), age, and presence of inhalation injury. The analysis included 234 (56.8%) patients in the deficient group (vitamin D, <20 ng/mL) and 178 patients in the non-deficient group (25OHD ≥20 ng/mL).

Vitamin D Deficiency Worsens Multiple Outcomes

“The key takeaway is that patients with burns and vitamin D deficiency on admission have a 2.5 times higher risk of an infectious outcome,” notes Dr. Hill. “Not only was deficiency important, every day of delay in supplementation initiation further increased those odds by 14%. Both variables were significant in the multivariable regression after controlling for %TBSA burned, age, inhalation injury, and the possibility of a center effect.”

The most frequent infections were wounds, pneumonia, and bloodstream infections, which parallel clinical practice, according to Dr. Hill. Patients with vitamin D deficiency were more likely to have bloodstream infections, pneumonia, urinary tract infections, and graft loss.

Secondary outcomes included LOS, ICU LOS, renal replacement therapy in the context of acute kidney injury, ventilator-free days within 28 days of admission, number of days with vasopressor support, in-hospital mortality, type of 25OHD given, time to start of supplementation, and average daily dosage.

“With the patient’s life and functional status in mind, the severe outcome discrepancies are remarkable,” Dr. Hill says. “And financially, they are catastrophic. Deficient patients were more than four times more likely to acquire an acute kidney injury and need of renal replacement therapy, and nearly twice as likely to require use of a mechanical ventilator and have less ventilator-free days (Table). Patients with low vitamin D were more likely to exhibit shock and require the use of vasopressors. Lastly, deficient patients had a 50% higher LOS.”

Future Research Needed, But Unlikely

Dr. Hill notes that the findings from this retrospective analysis should be viewed “with a certain degree of caution” because of possible inherent bias, despite efforts made during the study design and analysis.

“With this understanding, however, I ask: ‘What if?’ Drawing vitamin D concentrations on admission is simple and subsequent supplementation is a fairly benign intervention,” Dr. Hill says. “The implications for the patient could be life-saving. The implications for the hospital system could lead to incredible savings that could then help attainment of resources for future patients.”

Based on the findings from this study and others, a large-scale, multicenter interventional study is warranted, Dr. Hill notes, but does not believe such an investigation will occur. “For such a trial to occur, funding must exist,” he says. “It is incredibly difficult to allocate resources to even request, not to mention be granted, funding for research for patients with burn injuries. If we are to continue advancing what we know about burns and the best way to care for the patients who live with these injuries, then more support is needed.”