Inadequate vitamin D levels are associated with culture positive sepsis and poor outcomes in paediatric intensive care

Onwuneme, Chike; Carroll, Aoife; Doherty, Dermot; Bruell, Heike; Segurado, Ricardo; Kilbane, Mark; Murphy, Nuala; McKenna, Malachi J.; Molloy, Eleanor J.

doi:10.1111/apa.13090

Cited by 37 publications

(36 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional studies of vitamin D deficiency in the pediatric intensive care unit (ICU) (PICU) population have reported a prevalence of between 30 and 86% (18)(19)(20)(21). We found lower 25(OH)D levels to be associated with greater illness severity (22); other pediatric critical care studies have confirmed this finding (19,21,23,24), although equal numbers have reported no correlation with illness severity or ICU outcomes (18-20, 25, 26). Despite the rapidly increasing volume of evidence linking 25(OH)D deficiency with ICU morbidity and mortality over the past 10 years (1-4, 6-8, 10, 11, 27, 28), the question of whether vitamin D repletion will improve clinical outcomes in critical illness remains unclear.…”

Section: Low Serum Concentrations Of Total 25-hydroxyvitamin D (25[oh]d)mentioning

confidence: 40%

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Madden¹,

Feldman²,

Chun³

et al. 2015

Annals ATS

View full text Add to dashboard Cite

Rationale: Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25[OH]D) ,20 ng/ml, is common in critically ill patients, with associations with increased mortality and morbidity in the intensive care unit. Correction of vitamin D deficiency in critical illness has been recommended, and ongoing clinical trials are investigating the effect of repletion on patient outcome. The biologically active amount of 25(OH)D depends on the concentration and protein isoform of vitamin D-binding protein (VDBP), which is also an acutephase reactant affected by inflammation and injury.Objectives: We performed a secondary analysis of a cohort of critically ill children in which we reported a high rate of vitamin D deficiency, to examine how VDBP level and genotype would impact vitamin D status. Methods:We prospectively enrolled 511 children admitted to the pediatric intensive care unit over a 12-month period. Measurements and Main Results:We measured serum VDBP in 479 children. We genotyped single nucleotide polymorphisms rs7041 and rs4588 in the VDBP gene (GC) to determine haplotypes GC1F, GC1S, and GC2 in 178 subjects who consented, then calculated bioavailable 25(OH)D from serum 25(OH)D, VDBP, albumin, and GC haplotype. The median serum VDBP level was 159 mg/ml (interquartile range, 108-221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age ,1 year, nonwhite race, being previously healthy, 25(OH)D ,20 ng/ml and greater illness severity. In the subgroup that was genotyped, GC haplotype had the strongest association with VDBP level; carriage of one additional copy of GC1S was associated with a 37.5% higher level (95% confidence interval, 31.9-44.8; P , 0.001). Bioavailable 25(OH)D was also inversely associated with illness severity (r = 20.24, P , 0.001), and ratio to measured total 25(OH)D was variable and related to haplotype.Conclusions: Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower VDBP levels increase bioavailability. Treatment studies conducted on the basis of total 25(OH)D level, without consideration of VDBP concentration and genotype, may increase the risk of falsely negative results.

show abstract

Section: Low Serum Concentrations Of Total 25-hydroxyvitamin D (25[oh]d)mentioning

confidence: 40%

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Madden¹,

Feldman²,

Chun³

et al. 2015

Annals ATS

View full text Add to dashboard Cite

show abstract

“…Further, VDD was associated with higher illness severity, multiple organ dysfunction, and mortality across these studies. Six of these studies focused on or separately analyzed children with sepsis [433][434][435][436][437]. Three studies reported a greater need for vasoactive agents in VDD children [433][434][435], although mortality across these six studies was not associated with VDD [433][434][435][436][437] (Supplemental Table 26, Supplemental Digital Content 1, http://links .lww.com/PCC/B139).…”

Section: We Suggest Against the Acute Repletion Of Vitamin D Deficienmentioning

confidence: 99%

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

et al. 2020

View full text Add to dashboard Cite

Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those The Society of Critical Care Medicine guidelines are intended for general information only, are not medical advice, and do not replace professional advice, which should be sought for any medical condition. The full disclaimer for guidelines can be accessed at https ://www.sccm.org/Resea rch/Guide lines /Guide lines . panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. Conclusions:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research. S14 the group heads, panel members, and methodologists. Searches utilized ...

show abstract

“…Several studies investigated the prevalence of VitD deficiency in intensive care unit (ICU) patients and found that most critically ill patients had very low levels of VitD [18][19][20] . Furthermore, VitD deficiency was associated with increased mortality in septic adult [21][22][23] and paediatric 24 patients.…”

Section: Introductionmentioning

confidence: 99%

Altered Blood Levels of Vitamin D, Cathelicidin and Parathyroid Hormone in Patients with Sepsis—a Pilot Study

Greulich

Regner

Branscheidt

et al. 2017

Anaesth Intensive Care

View full text Add to dashboard Cite

It has been recognised that vitamin D (VitD) has a potential role in the regulation of inflammation and protection from infection. In a prospective clinical observational pilot study, we investigated the serum levels of 25-hydroxyvitamin-D3 (25(OH D3), 1,25-hydroxyvitamin-D3 (1,25(OH)2D3), parathyroid hormone (PTH), and cathelicidin in intensive care unit (ICU) patients with or without systemic inflammatory response syndrome (SIRS). We included 32 patients with SIRS (septic patients), 16 ICU patients without SIRS, and 16 healthy controls. To substantiate the findings of the clinical study, we stimulated monocyte-derived macrophages with microbial patterns and analysed the impact of VitD on release of cytokines and antimicrobial activity. We found that patients with or without SIRS had relatively low levels of 25(OH)D3 and 1,25(OH)2D3. Patients with sepsis had significantly lower levels of 25(OH)D3 as compared to ICU control patients and healthy controls (10.53 ± 11.3 µg/l versus 16.46 ± 12.58 µg/l versus 24.04 ± 12.07 µg/l); the same was true for 1,25(OH)2D3. Serum levels of PTH and cathelicidin were significantly increased in sepsis patients, as compared to the other groups. In vitro, VitD significantly decreased the release of pro-inflammatory cytokines from macrophages and increased the antimicrobial activity of the cells. We concluded that patients with sepsis have significantly lower VitD levels. In vitro, VitD modulates inflammation and increases the antibacterial activity of innate immune cells. These findings suggest that VitD insufficiency is mechanistically related to increased susceptibility to SIRS and sepsis.

show abstract

Inadequate vitamin D levels are associated with culture positive sepsis and poor outcomes in paediatric intensive care

Abstract: Children admitted to the PICU with suspected sepsis had lower 25OHD than controls and inadequate 25OHD status was associated with confirmed sepsis and poor outcomes.

Cited by 37 publications

References 31 publications

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

Altered Blood Levels of Vitamin D, Cathelicidin and Parathyroid Hormone in Patients with Sepsis—a Pilot Study

Contact Info

Product

Resources

About