Serial circulating vasopressin levels in children with septic shock.

BACKGROUND: Septic shock is an important cause of death in pediatric intensive care units. Initial evaluations have shown that vasopressin may have a role in catecholamine refractory shock in adults. It is important to determine whether children with septic shock have deficiency of vasopressin. This will help in defining the role of vasopressin in septic shock. DESIGN: Prospective cohort study. SETTING: Pediatric intensive care unit of a tertiary care hospital in north India. PATIENTS: Patients were children with septic shock, and controls were children with sepsis but no shock. STUDY DESIGN: Vasopressin levels in plasma were determined by enzyme-linked immunosorbent assay for children with septic shock at diagnosis (baseline) and thereafter at 24, 48, and 96 hrs to determine the time trends. The baseline vasopressin values for children with septic shock were compared with those for children without shock. RESULTS: The median (95% confidence interval) vasopressin level at baseline in children with septic shock was 116 (63.3-130.7) pg/mL, and in children with sepsis but no shock it was 106 (61.7-131.77) pg/mL. The median value for survivors was 76 (44.6-130.9) pg/mL, and for nonsurvivors, 118 (81.7-259) pg/mL (p = .16). The serial values also did not show any significant changes; the values at 24 hrs (n = 17), 48 hrs (n = 16), and 96 hrs (n = 15) were 105 (76.1-125.9), 105 (41.4-155.5), and 109.5 (54.9-154.8) pg/mL, respectively. CONCLUSIONS: The results of our study suggest that vasopressin levels are elevated in children with septic shock and that serial values up to 96 hrs do not show any decline.     

Adrenal status in children with septic shock using low-dose stimulation test.

OBJECTIVES: There is paucity of data on the magnitude of absolute or relative adrenal insufficiency in septic shock, especially in children. We conducted a prospective study to determine the prevalence of adrenal insufficiency in children with septic shock using a low-dose Synacthen (1 microg) stimulation test. DESIGN: Cross-sectional study. SETTING: Pediatric intensive care unit in a tertiary care hospital in northern India. PATIENTS: Children with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed cortisol estimation at baseline and after low-dose Synacthen (1 microg) stimulation at 30 and 60 mins in children with fluid refractory septic shock admitted to our pediatric intensive care unit. Basal cortisol levels <7 microg/dL and peak cortisol level <18 microg/dL were used to define adrenal insufficiency. An increment of <9 microg/dL after stimulation was used to diagnose relative adrenal insufficiency. As there is lack of consensus on the cutoffs for defining relative adrenal insufficiency using the low-dose adrenocorticotropic hormone test, we evaluated different cutoff values (increment at 30 mins, increment at 60 mins, greater of the two increments) and evaluated their association with the incidence of catecholamine refractory shock and outcomes. Children with sepsis but without septic shock were sampled for baseline cortisol levels as a comparison. Thirty children (15 girls) with septic shock were included; median age (95% confidence interval) was 36.5 (9.39- 58.45) months. Median Pediatric Risk of Mortality score was 22.5 (14.13-24.87). Fifteen (50%) children survived. The median (95% confidence interval) cortisol values at baseline and 30 mins and 60 mins after stimulation were 71 (48.74-120.23) microg/dL, 78.1 (56.9-138.15) microg/dL, and 91 (56.17-166.44) microg/dL, respectively. The median baseline cortisol value in age- and gender-matched children with sepsis was 11.5 microg/dL. None of the children with septic shock fulfilled the criteria for absolute adrenal insufficiency. However, nine (30%) patients had relative adrenal insufficiency (increment in cortisol <9 microg/dL). Of these nine patients, five (56%) died; of the 21 patients with a greater increment in cortisol after stimulation, ten died (p = .69). Compared with patients in septic shock with normal adrenal reserve, those with relative adrenal insufficiency had a higher incidence of catecholamine refractory shock (p = .019) but no difference in mortality rate (p = .69). On the sensitivity and specificity analysis using various cutoffs of increment, the best discrimination for catecholamine refractory shock was obtained with a peak increment <6 microg/dL. CONCLUSIONS: Relative adrenal insufficiency is common in children with septic shock and is associated with catecholamine refractory shock.     

Association between lymphotoxin alpha (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke in North Indian population: a hospital-based case-control study

Purpose: Lymphotoxin alpha (LTA), a proinflammatory cytokine, plays an important role in promoting atherosclerosis which is an independent risk factor for stroke. Recent genetic studies have suggested that polymorphisms in the LTA gene, which affect its expression and biological function, may contribute to the development of stroke. The aim of this case-control study was to determine the association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. Methods: Genotyping was determined by using SNaPshot method for 250 ischemic stroke (IS) patients, 250 age and sex matched IS free controls, 100 intracerebral hemorrhage (ICH) patients and 100 age and sex matched ICH free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. The linkage disequilibrium (LD) was analyzed by using HaploView 4.2 software. Results: The distribution of LTA (-252 A/G and -804 C/A) genotypes was consistent with Hardy–Weinberg equilibrium. Adjusted conditional logistic regression analysis showed no significant association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of both IS and ICH. Based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, a significant association between LTA -252 A/G gene polymorphism and small vessel disease subtype of IS under dominant model (OR, 2.06; 95% CI, 1.03–4.12; p value 0.04) with the risk of IS was observed. No LD was observed for both single nucleotide polymorphisms (SNPs) in north Indian population. Conclusion: Neither -252 G/A nor -804 C/A polymorphism of the LTA gene was found to be associated with overall stroke as well as any subtype of IS excluding SVD in North Indian population.     

Thyroid function in children with sepsis and septic shock

AIM: A prospective study was conducted to determine thyroid hormone levels and their relationship to survival in children with septic shock and sepsis. METHODS: We estimated thyroid hormone levels (T3, T4, TSH, fT3 and fT4) in children with septic shock and compared with those in children with sepsis. RESULTS: Twenty-four children (13 boys) with septic shock and 25 children (14 boys) with sepsis were enrolled. The median T3, T4, fT3, fT4 and TSH (95% confidence interval) were 40 (40-40.23) ng/dL, 4.45 (1.9-6.03) microg/dL, 1.85 (1.2-2.37) pg/mL, 0.77 (0.57-0.95) ng/dL, 0.51 (0.26-1.15) microIU/mL, respectively in children with septic shock group compared with 130 (98.28-163.48) ng/dL, 9.3 (7.66-10.63) microg/dL, 3.2 (3-4.27) pg/mL, 1.3 (1.1-1.4) ng/dL, 2.85 (1.07-3.61) microIU/mL, respectively, in children with sepsis. Children with septic shock who died (n = 12) had higher TSH levels compared to those who survived (p = 0.04). There was no difference in hormone levels between children with catecholamine responsive and catecholamine resistant septic shock. CONCLUSION: Children with septic shock had lower levels of T3, T4, fT3, fT4 and TSH compared to those with sepsis. Findings of our study suggest that derangement of thyroid functions in children is not an important factor contributing to the severity of septic shock.     

Association of transforming growth factor-β1 gene C509T,G800A and T869C polymorphisms with intracerebral hemorrhage in North Indian Population: a case–control study

Transforming growth factor-β1 (TGF-β1) is a multifunctional pro-inflammatory cytokine involved in inflammation and pathogenesis of cerebrovascular disease. As per our knowledge, there is no published study investigating the association between variations within the TGF-β1 gene polymorphisms and risk of intracerebral hemorrhage (ICH). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A and T869C) polymorphisms, and their haplotypes with the risk of ICH in North Indian population. 100 ICH patients and 100 age- and sex-matched controls were studied. Genotyping was performed using SNaPshot method. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of ICH. Hypertension, diabetes, dyslipidemia, low socioeconomic status, smoking, physical activity were found to be associated with the risk of ICH. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy–Weinberg Equilibrium (HWE) in the ICH and control group. Adjusted conditional logistic regression analysis showed an independent association of TGF-β1 G800A (OR 9.07; 95 % CI 2.3–35.6; P = 0.002) and T869C (OR 5.1; 95 % CI 1.9–13.2; P = 0.001) with the risk of ICH under dominant model. Haplotype analysis showed that C509-G800-C869 and C509-A800-C869 haplotypes were significantly associated with the increased risk of ICH. C509T and T869C were in strong linkage disequilibrium (D’ = 0.53, r ² = 0.23). Our results suggest that TGF-β1 (G800A, T869C) gene polymorphisms and their haplotypes are significantly associated with the risk of ICH in North Indian population. Further prospective studies with large sample size are required for independent validation. Our findings could be helpful in identifying individuals at increased risk for developing ICH.     

Decreased prevalence of lymphatic filariasis among subjects with type-1 diabetes

Several animal studies have shown a protective effect of helminth infections against type-1 diabetes mellitus (T1DM). However, epidemiologic studies demonstrating this protective relationship with T1DM are largely lacking, although an inverse correlation between the prevalence of lymphatic filariasis (LF) and prevalence of allergies and autoimmunity has been shown. A cross-sectional study was undertaken in southern India to assess the baseline prevalence of seropositivity of LF among persons with T1DM (n = 200) and normal glucose tolerant (NGT) persons (n = 562). The prevalence of LF was 0% among persons with T1DM and 2.6% among NGT persons (P = 0.026). The percentage of persons who were positive for filarial antigen-specific IgG4 (but not antigen-specific IgG) was also significantly lower in persons with T1DM (2%) compared with NGT persons (28%) (P < 0.001). Thus, there appears to be a striking inverse relationship between the prevalence of LF and T1DM in southern India.     

Intravenous fluid regimen and hyponatraemia among children: a randomized controlled trial

The aim of this study was to compare the effect of three different intravenous (i.v.) fluid regimes on the incidence of hyponatraemia in hospitalized children ranging in age from 3 months to 12 years. Children who required the administration of i.v. maintenance fluid for at least 24 h following hospitalization were eligible for inclusion. The children were randomized to three i.v. fluid groups: Group A, 0.9% saline in 5% dextrose at the standard maintenance rate; Group B, 0.18% saline in 5% dextrose at the standard maintenance rate; Group C, 0.18% saline in 5% dextrose at two-thirds of the standard maintenance rate. The primary outcome measure was incidence of hyponatraemia (plasma sodium < 130 mEq/L). Of the 167 patients enrolled, 58, 56 and 53 patients were randomized to Group A, B and C, respectively. We observed that 14.3% (8/56) of the children administered 0.18% saline in 5% dextrose at the standard maintenance rate (Group B) developed hyponatraemia compared with 1.72% of the children in Group A and 3.8% of those in Group C. Based on these results, we conclude that the administration of 0.9% saline in 5% dextrose as i.v. maintenance fluid helps in reducing the incidence of hospital-acquired hyponatraemia among children.