Vitamin D deficiency in critically ill children with sepsis

Satheesh, Ponnarmeni; Angurana, Suresh Kumar; Singhi, Sunit; Bansal, Arun; Dayal, Devi; Kaur, Rajdeep; Patial, Ajay; Attri, Savita Verma

doi:10.1179/2046905515y.0000000042

Cited by 53 publications

(77 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Research on VitD and sepsis has increased in recent years [25]. The biological pleiotropy of VitD shows bright prospects for the treatment of sepsis [26,27,28].…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance and Prognostic Effect of Serum 25-hydroxyvitamin D Concentrations in Critical and Severe Hand, Foot and Mouth Disease

Dang

Liu

et al. 2017

Nutrients

View full text Add to dashboard Cite

Objective: To examine the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with critical and severe hand, foot and mouth disease (HFMD) and assess the clinical significance and prognostic effect of 25(OH)D concentrations in children with HFMD. Methods: This is a prospective observational study. The 138 children with HFMD were divided into common (49 cases), severe (52 cases), and critical (37 cases) HFMD groups. Another 59 healthy children undergoing outpatient medical examinations during the same period were chosen as the control group. Serum 25(OH)D concentrations were measured in all the subjects, and each group was subdivided by serum 25(OH)D concentration into 25(OH)D normal (≥30 ng/mL); insufficiency (20–29.9 ng/mL), and deficiency (<20 ng/mL) groups. The pediatric critical illness score (PCIS) was recorded for the critical and severe HFMD group upon admission to the pediatric intensive care unit (PICU). Children with critical and severe HFMD were also monitored for blood lactate (LAC), serum calcium ions (Ca++), D-dimer (DD), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) levels; the incidences of brainstem encephalitis, neurogenic pulmonary edema, and circulatory failure; and the 14-day mortality rate. Results: Serum 25(OH)D concentrations were generally low in all groups. The critical HFMD group showed a significantly lower serum 25(OH)D mean concentration (20.0 ± 8.4 ng/mL) and a higher proportion of deficiency (18%) compared with the control group (28.1 ± 6.6 ng/mL, 8%), common (29.5 ± 8.1 ng/mL, 10%) and severe (31.9 ± 9.7 ng/mL, 8%) HFMD groups (p < 0.05). In the critical and severe HFMD groups, the 25(OH)D deficiency group had lower PCISs than the 25(OH)D normal and insufficiency groups (p < 0.05); and had higher values than the latter two groups for LAC, LDH, CK-MB and DD; and the incidences of brainstem encephalitis, neurogenic pulmonary edema, circulatory failure, and mortality (p < 0.05). The death group showed significantly lower serum 25(OH)D concentrations and PCISs than the survival group (p < 0.05) and had higher LAC, LDH, CK-MB and DD levels and higher incidences of brainstem encephalitis, neurogenic pulmonary edema, and circulatory failure (p < 0.05). Logistic regression analysis revealed that the serum 25(OH)D concentration was an independent factor that influenced mortality in children with critical and severe HFMD. Conclusions: In this study, we find the serum 25(OH)D concentrations are substantially reduced in children with critical and severe HFMD and are associated with the severity of HFMD. The serum 25(OH)D concentrations may have clinical value for determining the progression of critical HFMD and predicting the risk of death. Further evidence is needed before it can be stated that 25(OH)D concentrations have clinical value in HMFD diagnosis.

show abstract

“…Research on VitD and sepsis has increased in recent years [25]. The biological pleiotropy of VitD shows bright prospects for the treatment of sepsis [26,27,28].…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance and Prognostic Effect of Serum 25-hydroxyvitamin D Concentrations in Critical and Severe Hand, Foot and Mouth Disease

Dang

Liu

et al. 2017

Nutrients

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

“…Studies demonstrated high prevalence of vitamin D deficiency in otherwise healthy children from high-income countries (9 to 24%) but also from middle and low-income countries in Indian subcontinent (36 to 90%). 8 We identified 48 studies representing a total of 5,520 children treated in ICU or emergency units for acute conditions who had blood vitamin D levels measured close to or upon admission. Our analysis shows that prevalence of vitamin D deficiency is high (range 5% 66 to 95% 54 ) across ICU and emergency units in the paediatric population, particularly in individuals with sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…We were unable to identify a sufficient number of studies assessing vitamin D and mortality for meta-analysis in individuals with sepsis. Three studies 8,58,60 measured vitamin D levels in paediatric patients with sepsis. One study 8 assessed mortality and did not find a significant association in children from 1 to 12 years with sepsis (n=124).…”

Section: Mortality In Patients With Sepsis and Respiratory Tract Infementioning

confidence: 99%

“…Vitamin D is critical in bone metabolism 5 and calcium homeostasis, 6 as well as acting as an important regulator in extra-skeletal metabolic processes, 7 cardiovascular and immune systems. 8 Many observational and laboratory studies have observed the anti-inflammatory properties of vitamin D, 9 including direct regulation of endogenous anti-microbial peptide production. 10 It is therefore crucial for humans to have sufficient vitamin D levels to maintain bone health and possibly improve response to infection.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Importance of vitamin D in critically ill children with subgroup analyses of sepsis and respiratory tract infections: a systematic review and meta-analysis

Cariolou

Cupp

Εvangelou

et al. 2018

Preprint

View full text Add to dashboard Cite

SummaryBackgroundCritical care and sepsis remain high priority concerns in children. Observational studies report high prevalence of vitamin D deficiency and present mixed results regarding the correlation between vitamin D status and adverse outcomes. Associations between deficiency and mortality, particularly in children with sepsis, remain unclear. We performed a systematic review and meta-analysis to address this uncertainty.MethodsPubMed, OVID and Google Scholar were searched for observational studies in critically ill children. We obtained pooled prevalence estimates for vitamin D deficiency and odds ratios for the association of mortality in critically ill children treated in intensive care units, with subgroup analysis for those with sepsis and those with respiratory tract infections. Meta-regression and sensitivity analyses were used to investigate heterogeneity.FindingsForty-eight studies were included. Total sample size was 7,199, with 1,679 (23%) children acting as controls in case-control studies. Of 5,520 critically ill children, 2,664 (48%) were vitamin D deficient (< 50 nmol/L). Results of the random effects model demonstrated a pooled prevalence of vitamin D deficiency of 54·9% (95% CI 48·0-61·6, I2=95·0%, 95% CI 94·0-95·8, p < 0·0001). In subgroup analysis of children with sepsis (16 studies, 788 total individuals) we observed higher prevalence of deficiency (63·8%, 95% CI 49·9-75·7, I2=90·5%, 95% CI 86·2-93·5%, p < 0·0001). In patients admitted for respiratory tract infections (24 studies, 1,683 total individuals), prevalence was 49·9% (95% CI 37·6-62·2; I2= 93·9%, 95% CI 92·1-95·3, p < 0·0001). Only one identified study assessed vitamin D levels in sepsis and mortality. A meta-regression model with all available variables (year of publication, total study sample size, quality score, study design, country group and clinical setting) explained 37·52% of I2(F = 5·1119, p = 0·0005) with clinical setting and country groups being significant predictors for prevalence.Meta-analysis of mortality (18 studies, 2,463 total individuals) showed an increased risk of death in vitamin D deficient critically ill children both with random (OR 1·81, 95% CI 1·24-2·64, p-value = 0·002) and fixed effects (OR 1·72, 95% CI 1·27-2·33, p= 0·0005) models with low heterogeneity (I2= 25·7%, 95% CI 0·0-58·0, p = 0·153) and low evidence of publication bias (p = 0·084, Egger’s test). There were insufficient studies to perform meta-analyses for sepsis and respiratory tract infection related mortality.InterpretationCirculating vitamin D deficiency is common amongst critically ill children, particularly in those with sepsis. Our results suggest that vitamin D deficiency in critically ill children is associated with increased mortality. Clinical trials, studies with larger sample sizes and standardized approaches are needed to further assess associations between circulating levels of vitamin D and mortality and other outcomes in the paediatric population.FundingMedical Research Council UKRegistrationPROSPERO (CRD42016050638)CopyrightOpen access article under terms of CC BYResearch in contextEvidence before this studyVitamin D deficiency is common worldwide and has been associated to numerous diseases in observational studies. The extent of deficiency and relevance to mortality in children receiving acute and intensive care is unclear and only recently has gained more attention. We searched PubMed, OVID, Google Scholar and the Cochrane Library from inception up until 5thNovember 2017 without language restrictions. Search terms used across these databases included: “critical care”, “acute care”, “vitamin D”, “pediatric”, “child”, “neonate”, “toddler”, “intensivecareunit”, “sepsis” and “septic shock” (full search terms are listed in the appendix). Most (81·3%) included studies were published between 2014 and 2017. We did not identify randomised clinical trials assessing the value of vitamin D supplementation in this population. We did not find sufficient studies to perform meta-analyses for mortality from sepsis or respiratory tract infection.Added value of this studyOur systematic review and meta-analysis provides an in-depth assessment of the magnitude and relevance of vitamin D circulating levels in paediatric acute and critically ill patients with pre-specified sub-group analyses. We found that studies were highly heterogeneous across a number of important study variables including clinical setting, patient age groups, sample size, geographic location, case definitions, study quality, study design, biomarker thresholds and assay measurements. Pooled estimates of prevalence of vitamin D deficiency were overall extremely high, showing that around half of patients in general and acute paediatric care are deficient. Estimates were similar for respiratory tract infections but higher in sepsis, with overlapping confidence intervals across all outcomes. Individual study estimates were highly variable however. We analysed this heterogeneity using meta-regression and identified clinical setting and country of study as important contributors, likely indicating that patient age and environmental exposure to vitamin D, amongst other likely important factors, are key determinants and should be adequately assessed and reported. Pooled estimates for mortality outcomes showed a clear increased risk with lower vitamin D levels, despite the variation in study characteristics. We were unable to assess the importance of vitamin D levels in sepsis and respiratory tract infections due to the small number of studies investigating these outcomes.Implications of the available evidenceVitamin D deficiency in acute and critical care settings is common and associated with increased mortality in paediatric patients. Our review highlights the heterogeneous nature of the study population however and emphasizes the need for adequate power and control of confounding factors in future work. Few studies have investigated specific diseases such as sepsis and respiratory tract infections in relation to vitamin D despite their high prevalence, social and economic costs. Understanding the causal nature and therapeutic value of vitamin D in paediatric critical care remain key areas for investigation.

show abstract

Vitamin D deficiency in critically ill children with sepsis

Abstract: A high prevalence of VDD in critically ill children with sepsis was found but it was not associated with greater severity of illness or other clinical outcomes.

Cited by 53 publications

References 44 publications

Clinical Significance and Prognostic Effect of Serum 25-hydroxyvitamin D Concentrations in Critical and Severe Hand, Foot and Mouth Disease

Clinical Significance and Prognostic Effect of Serum 25-hydroxyvitamin D Concentrations in Critical and Severe Hand, Foot and Mouth Disease

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

Importance of vitamin D in critically ill children with subgroup analyses of sepsis and respiratory tract infections: a systematic review and meta-analysis

Contact Info

Product

Resources

About