Factors associated with hyperglycemia and low insulin levels in children undergoing cardiac surgery with cardiopulmonary bypass who received a single high dose of methylprednisolone

OBJECTIVES: Administering steroids before cardiopulmonary bypass in pediatric heart surgery modulates systemic inflammatory response syndrome and improves postoperative recovery. However, the use of steroids aggravates hyperglycemia, which is associated with a poor prognosis. Adult patients with systemic inflammatory response syndrome usually evolve with hyperglycemia and high insulin levels, whereas >90% of pediatric patients exhibit hyperglycemia and low insulin levels. This study aims to determine: A) the metabolic and inflammatory factors that are associated with hyperglycemia and low insulin levels in children who underwent cardiac surgery with cardiopulmonary bypass and who received a single high dose of methylprednisolone and B) the best predictors of insulin variation using a mathematical model. METHODS: This preliminary study recruited 20 children who underwent heart surgery with cardiopulmonary bypass and received methylprednisolone (30 mg/kg) immediately after anesthesia. Among the 20 patients initially recruited, one was excluded because of the absence of hyperglycemia and lower insulin levels after surgery. However, these abnormalities were confirmed in the remaining 19 children. The C-peptide, CRP, IL-6, and adrenomedullin levels were measured before surgery, immediately after cardiopulmonary bypass, and on the first, second, and third days after cardiac surgery. RESULTS: IL-6, CRP, and adrenomedullin increments were observed, whereas the C-peptide levels remained within reference intervals. CONCLUSION: The multiple regression model demonstrated that in addition to age and glycemia (two well-known factors that are directly involved in glucose metabolism), adrenomedullin and IL-6 levels were independent factors associated with lower insulin concentrations. These four parameters were responsible for 64.7% of the observed insulin variances. In addition, the fact that C-peptide levels did not fall together with insulin could have grounded the medical decision not to administer insulin to patients.

Prognostic value of plasma pro-adrenomedullin and antithrombin levels in neonatal sepsis

Neonatal sepsis is one of the major causes of morbidity and mortality in neonates. Proper diagnosis and management of neonatal septicemia can markedly affect prognosis of neonatal sepsis. In sepsis serum pro-Adrenomedullin level [pro-ADM] was known to be increased while Anti thrombin is rapidly depleted as a result of decreased synthesis, increased destruction, and enhanced clearance. The aim of this study was to clarify the prognostic value of serum Pro-ADM and Anti thrombin level in neonatal sepsis. 40 full term neonates with sepsis were enrolled in this study including 20 cases with mild sepsis and 20 cases with severe sepsis. They were admitted to the neonatal intensive care unit, they included 26 males and 14 females with a mean birth weight of 3.2 +/- 0.26 kg. Twenty healthy full term neonates of matched age and sex served as a control group. Serum levels of Pro ADM and Antithrombin were measured in all patients and control group. Serum Pro ADM level was significantly higher in neonates with sepsis than control group, was significantly higher in severe than mild sepsis and was significantly higher in the unsurvived cases. Antithrombin concentrations were significantly lower in neonates with sepsis than control group, significantly lower in severe than mild sepsis and significantly lower in neonates with sepsis who died than who survived. In conclusion, higher pro-ADM and lower initial AT levels in neonatal sepsis are associated with severe disease and increased risk of mortality

Plasma adrenomedullin level in systemic lupus erythematosus patients and its relation to disease activity and lupus nephritis

To study the plasma adrenomedullin [AM] level in systemic lupus erythematosus [SLE] patients and investigate its relation to disease activity and lap us nephritis. Taking, thorough clinical examination, laboratory investigations, disease activity assessment using SLE Disease Activity Index [SLEDAI] and plasma AM assay. Renal histopathology was done for the patients with overt renal involvement. Patients were divided into two subgroups: subgroup [1a] included patients with a history of renal involvement, and subgroup [1b] included patients without renal involvement. Ten age and sex-matched healthy subjects were included as a control group. SLE patients had highly significant higher plasma AM concentration than controls. In SLE patients, there was significant positive correlation between plasma AM concentration and each of SLEDAI and prednisolone dose. On the other hand, plasma AM concentration didn't show significant correlation with age, SLE disease duration, creatinine, proteinuria, C3 and C4. Subgroup [1a] had statistically significant higher plasma AM concentration and higher SLEDAI with increased proteinuria and creatinine than subgroup [1b]. SLE patients had higher plasma AM concentration than controls. SLE patients with a history of renal involvement had significant higher plasma AM concentration than those without renal involvement. These results suggest that AM has a role in the pathogenesis of SLE and lupus nephritis

Increased levels of nitric oxide, cortisol and adrenomedullin in patients with chronic schizophrenia

To investigate the levels of serum cortisol, dehydroepiandrosterone sulfate [DHEA-S], nitric oxide [NO] and adrenomedullin [AM] in schizophrenic patients. Sixty-six male patients with chronic schizophrenia and 28 normal male subjects participated in this study. The duration of disease was 145 +/- 120 [mean +/- SD] months. Serum levels of cortisol and DHEA-S were measured by electrochemiluminescence; plasma nitrite levels as an index of NO were measured with the Griess reaction, while plasma AM concentration was measured by using high-performance liquid chromatography. Patients [12.48 +/- 3.2 micro g/dl], as compared to controls [10.31 +/- 3.1 micro g/dl], had higher levels of baseline cortisol [p < 0.05]. DHEA-S levels were lower in patients though this did not reach statistical significance [302 +/- 156 micro g/dl compared to control, 322 +/- 96 micro g/dl, p > 0.05]. The mean levels of plasma AM and NO in the schizophrenic group [44.33 +/- 5.07 pmol/l and 36.27 +/- 17.6 micro mol/l] were significantly higher than the levels in the control group [14.56 +/- 4.03 pmol/l and 32.54 +/- 7.14 micro mol/l; p < 0.001, p < 0.03, respectively]. There was a positive association between duration of disease and cortisol/DHEA-S ratio and cortisol level. The data show that schizophrenia is associated with abnormal levels of cortisol, DHEA-S, NO and AM

Plasma levels of adrenomedullin and total nitrite in infants and children with heart failure

Localization of adrenomedullin [ADM] in peripheral tissues, including the heart, kidney, and vasculature, suggests an important role for the peptide as a regulator of cardiovascular function. ADM has hemodynamic effects including vasodilation, increases in cardiac contractility cardiac output, diuresis, and natriuresis. These effects may incorporate many of the therapeutic goals of heart failure management. The aim of our study was to find a relation between plasma level of ADM and Nitric Oxide [NO] in heat failure, with special interests to the type of heart disease, age, sex of patients, and severity of heart failure. We compared plasma levels of ADM and Nitric oxide [NO] in three groups of patients with heart failure: 14 patients diagnosed as rheumatic heart disease [RHD] [group I], 10 patients diagnosed as congenital heart disease [CHD] [group II], 6 patients diagnosed as dilated cardiomyopathy [DCM] [group III] and 20 apparently healthy children who were taken as controls [group IV]. Patients with heart failure had significantly higher levels of ADM and NO than controls [p=0.0001]. ADM and NO were highest among the patients with heart failure due to RHD then congenital heart disease and lastly dilated cardiomyopathy respectively [P=0.02 and 0.04 respectively]. We concluded that ADM is a biochemical marker for evaluating the severity of heart failure, and may be a new and promising approach for the treatment of patients with heart failure and pulmonary hypertension in children. In the future, insights into the role of NO in cardiac remodeling should allow the development of novel therapeutic strategies to treat cardiac remodeling and failure in infants and children

Effects of adrenomedullin on some vasoregulatory factors in hypertensive pregnant rats as an animal model of preeclampsia

The aim of this study was to investigate the effects of adrenomedullin [ADM] on plasma renin activity and the release of vasoregulatory peptides as endothelin-1 [ET-1], nitric oxide [NO] and norepinephrine in nitric oxide synthase [NOSG] deprived pregnant rats as an animal model of preeclampsia using N -nitro-L-arginine methyl ester [L-NAME], a NOS inhibitor. Also the aim was to elucidate the possible beneficial effects of ADM on regulation of renal function, blood pressure, blood supply to uteroplacental unit and consequently on fetal growth. The current study was carried out on 60 female Wistar rats. Their average weight was 250-300 g. They were 13-18 weeks old. Two or three cycling female rats were housed with a male for 24 hours. The presence of sperms in vaginal smears was considered as day 1 of pregnancy. Rats were divided into four groups [15 rats each] according to the following experimental design: group I included virgin non-pregnant rats, group II included pregnant rats that received saline solution starting from day 7 to day 20 of gestation, group III included pregnant rats that were treated with L-NAME daily starting from the same day of gestation and for the same duration as for group II, to make an animal model of preeclampsia, group IV included pregnant rats that were treated by both L-NAME [the same dose and for the same duration as for group III] and recombinant rat ADM, 3 times a day starting from day 14 to day 20 of gestation. The following parameters were measured in the control and all pregnant rats on day 13 of gestation and also on day 20 of gestation: - mean arterial blood pressure [MAP], some renal function tests [including urine volume, urinary Na[+] and K[+], creatinine clearance as a measure of glomerular filtration rate [GFR], 24 h urinary albumin excretion], pup weight, plasma levels of ADM, endothelin-1 [ET-I], norepinephrin, total nitric oxide [NO] products and plasma renin activity [PRA]. L-NAME treatment of pregnant rats [group III] starting from day 7 to day 20 of gestation produced significant reduction of urine volume, creatinine clearance and total plasma NO as compared to control and normal pregnant rats [group II]. Moreover, their pup weight on day 20 of gestation was significantly reduced as compared to that of normal pregnant rats [P< 0.0001]. On contrast L-NAME treated rats on days 13 and 20 of gestation had significant increase of MAP, 24 h urinary Na and albumin excretion, plasma levels of ADM, ET-1, norepinephrin and PRA as compared to controls and group II on corresponding days of gestation where P<0.0001. ADM treatment of pregnant rats for 7 days starting from day 14 to day 20 of gestation significantly increased urine volume, urinary Na[+] excretion, creatinine clearance, plasma levels of ADM and total plasma NO products as compared to the same group on day 13 of gestation and L-NAME treated rats on days 13 and 20 of gestation. Moreover, their pup weight was significantly increased as compared to that of L-NAME treated rats on day 20 of gestation. However, no significant changes were detected as regard urinary K[+] excretion and PRA when comparing them to the same group on day 13 of gestation and L-NAME treated rats on days 13 and 20 of gestation. Also no significant change in plasma norepinephrin was detected between ADM and L-NAME treated rats on day 20 of gestation. On the other hand, MAP, 24 h urinary albumin excretion and plasma ET-1 level were significantly decreased in ADM treated rats on day 20 of gestation as compared to the same group on day 13 and L-NAME treated rats on days 13 and 20 of gestation. Comparing ADM treated pregnant rats on day 20 of gestation with control and normal pregnant rats on days 13 and 20 of gestation, we observed significant increase of urine volume, 24 h urinary Na excretion, plasma levels of ADM, norepinephrin and PRA and significant decrease of total plasma NO [P<0.0001] and pup weight [P<0.05], while no significant changes were found as regard MAP, 24 h urinary albumin excretion, creatinine clearance and plasma ET-1 level. The current data suggest that the increased ADM concentration seen in L-NAME induced preeclampsia plays a compensatory role and may be necessary to maintain placental vascular resistance and/or fetal circulation, growth and response to a compromised intrauterine environment. ADM administration [which achieved plasma levels of this peptide in the pathophysiological range] to NOS deprived pregnant rats as an animal model of preeclampsia has powerful vasodilator/hypotensive actions and renoprotective effect. Moreover, this study confirms the interaction of ADM with other vasoactive factors that are involved in the pathogenesis of preeclampsia by producing difference in vasoconstrictors/vasodilators balance. Clarification of this possibility must await additional studies and, in particular, the development of specific blackers of ADM secretion or action. Therefore, ADM might be a new target of therapeutic approach to preeclampsia. Manipulations that augment production of this peptide or inhibit its breakdown might find a place in the management of pregnant women with preeclampsia

Correlation between plasma levels of adrenomedullin, severity of illness and outcome in critically ill patients

Adrenomedullin [AM] is a newly identified mutlifunctional endogenous peptide, widely distributed in human tissues. Recent studies demonstrate that AM has powerful and characteristically long lasting vasodepressor activity and it plays a role in the pathophysiology of inflammation and its levels Increase under stress conditions. The aim of this work was to evaluate plasma levels of adrenomedullin as a marker of severity of illness and outcome in critically ill patients. The plasma levels of AM were measured in 40 patients with various forms of systemic inflammatory response syndrome [SIRS] and 10 healthy volunteers serving as control. Plasma levels of AM in SIRS, severe trauma demonstrated 1826 +/- 10.64 Fmol/ml [Mean +/- SD], in traumatic shock, it was 76.20 +/- 45.04 Fmol/ml, in severe sepsis it was 70.10 +/- 40.8 Fmol/ml and in septic shock it was 273.0 +/- 232.84 FmoI/ml. These values were significantly higher than controls [5.81 +/- 1.15]. The patients with traumatic or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. In this study, as well, there was a significant difference of plasma AM levels between survivors and non survivors in septic shock. The plama AM level might seive as a useful marker for evaluating the severity of disease and as an early predictor of outcome in septic shock

Plasma adrenomedullin, a new predictor of prognosis and severity in patients with dilated cardiomyopathy and heart failure

Adrenomedullin, a potent endogenous vasodilating and natriuretic peptide, may play an important role in the pathophysiology of chronic heart failure associated with dilated cardiomyopathy. To determine the changes of plasma adrenomedullin [AM] in patients with heart failure due to dilated cardiomyopathy of ischemic and idiopathic etiology before and after treatment and the relations between plasma AM and some hormones involved in the pathophysiology of heart failure as plasma renin activity [PRA], atrial natriuretic peptide [ANP] and aldosterone as well as some echocardiographic parameters. Also, the predictive value of AM in assessment of severity of heart failure was evaluated. Design 44 patients with symptomatic dilated cardiomyopathy due to is chemic and idiopathic etiology [24 females and 20 males], aged 53.37 +/- 9.38 years and matched to 13 healthy volunteers [8 females and 5 males] aged 54.3 +/- 8.6 years. Cases were classified according to the New York Heart Association [NYHA] functional classification into: 12 cases class 1, 10 cases class 11, 13 cases class III and 9 cases class IV Cases were subjected to thorough history, clinical and laboratory investigations with special stress on plain x-ray chest, ECG, and echocardiography to exclude other etiologies of heart failure. Assay of plasma AM, PRA, ANP and aldosterone was done. Plasma AM, PRA, ANP and aldosterone were significantly higher in patients compared to controls [27.91 +/- 15.19 Vs 11.1 7 +/- 1.55 pmol/L 2.20 +/- 1.48 Vs 0.35 +/- 0.10 ng/L/s; 16.61 +/- 61 Vs 5.57 +/- 1.16fmol/ml, 686.81 +/- 442.78 Vs 176 +/- 18.5 pmol/L respectively] and plasma levels of these hormones increased with the severity of heart failure. There was significant correlation between AM and both PRA, ANP and aldosterone [r=0.650, P<0.001; r=0.612, P<0.001; r=0.677, P<0.001 respectively]. Also there was significant correlation between plasma AM and both ejection fraction [EF] and fractional shortening percentage [FS%] [r=-0.781, P<0.001; r=-863, P<0.001 respectively], Plasma AM decreased in response to treatment of heart failure. Class of heart failure could be predicted in 82.5% of cases by assessment of plasma AM. Plasma AM increases in patients with heart failure due to dilated cardiomyopathy in proportion to the severity of heart failure along with some hormones known to modulate the development of heart failure. AM has a high predictive value in the assessment of the severity of heart failure, Stratification of patients regarding severity of heart failure can be facilitated by plasma AM measurements which could reasonably included in the routine clinical workup of patients with CHF