adrenomedullin and Postoperative-Complications

Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients.. Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery.. We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups.. TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.

Topics: Adrenomedullin; Aged; C-Reactive Protein; Defecation; Eating; Esophageal Neoplasms; Esophagectomy; Female; Gastrointestinal Tract; Humans; Length of Stay; Male; Middle Aged; Nutritional Status; Panax; Phytotherapy; Plant Extracts; Postoperative Complications; Prospective Studies; Recovery of Function; Serum Albumin; Weight Loss; Zanthoxylum; Zingiberaceae

Mid-Regional-Pro-Adrenomedullin (MR-Pro-ADM) is a marker of severity in a wide spectrum of pathological conditions such as sepsis, and cardiovascular dysfunction. Its usefulness as a predictor of morbidity and mortality in surgical patients has yet to be elucidated. We examined the ability of preoperative MR-Pro-ADM in predicting Postoperative Requirement of Organ Support (PROS).. One centre, pilot, prospective observational cohort study, enrolling adult patients scheduled for major abdominal surgery. The accuracy of the MR-Pro-ADM to predict PROS was determined by area under the receiver operating characteristic curve (AUROC) analysis. An univariate analysis was performed to identify the association of PROS and the MR-Pro-ADM value with the best combination of sensitivity and specificity. A multivariate analysis was performed to identify preoperative MR-Pro-ADM as independent risk factor for PROS.. A total of 59 patients scheduled for major abdominal surgery were enrolled. The incidence of PROS was 13.6%. The association of MR-Pro-ADM levels with the incidence of PROS, was determined by an area under the ROC curve of 0.85 (95% CI: 0.74-0.96, p=0.002). The preoperative value of MR-Pro-ADM with the best combination of sensitivity and specificity to predict PROS was 0.87 nmol/l. Patients with preoperative serum levels of MR-Pro-ADM≥0.87 nmol/l had a significantly higher incidence of PROS (33.3% vs 4.9%, p=0.007). MR-Pro-ADM≥0.87 nmol/l was shown to be an independent risk factor for PROS (p=0.001; OR 9.758; IC 1.73-54.78) in the multivariate analysis.. The preoperative serum level of MR-Pro-ADM may be a useful biomarker of perioperative risk and to predict postoperative requirement of organic support (PROS) in adult patients scheduled for major abdominal surgery.

Topics: Abdomen; Adrenomedullin; Aged; Biomarkers; Female; Hospital Mortality; Humans; Incidence; Logistic Models; Male; Pilot Projects; Postoperative Complications; Preoperative Period; Prospective Studies; ROC Curve; Sensitivity and Specificity

To assess the usefulness of procalcitonin, pro-adrenomedullin and pro-atrial natriuretic peptide as predictors of need for mechanical ventilation and postoperative complications (need for inotropic support and bacterial infection) in critically ill pediatric patients after cardiopulmonary bypass.. A prospective, observational study.. Pediatric intensive care unit.. Patients under 18 years old admitted after cardiopulmonary bypass.. Serum levels of procalcitonin, pro-adrenomedullin and pro-atrial natriuretic peptide were determined immediately after bypass and at 24-36 hours. Their values were correlated with the need for mechanical ventilation, inotropic support and bacterial infection. One hundred eleven patients were recruited. Septal defects (30.6%) and cardiac valve disease (17.1%) were the most frequent pathologies. 40.7% required mechanical ventilation, 94.6% inotropic support and 15.3% presented invasive bacterial infections. Pro-adrenomedullin and pro-atrial natriuretic peptide showed significant high values in patients needing mechanical ventilation. Cut-off values higher than 1.22 nmol/L and 215.3 pmol/L, respectively for each biomarker, may indicate need for mechanical ventilation with an AUC of 0.721 and 0.746 at admission and 0.738 and 0.753 at 24-36 hours, respectively but without statistical differences. Pro-adrenomedullin and procalcitonin showed statistically significant high values in patients with bacterial infections.. After bypass, pro-adrenomedullin and pro-atrial natriuretic peptide are suitable biomarkers to predict the need for mechanical ventilation. Physicians should be alert if the values of these markers are high so as not to progress to early extubation. Procalcitonin is useful for predicting bacterial infection. This is a preliminary study and more clinical studies should be done to confirm the value of pro-adrenomedullin and pro-atrial natriuretic peptide as biomarkers after cardiopulmonary bypass.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Bacterial Infections; Biomarkers; Cardiopulmonary Bypass; Child; Child, Preschool; Humans; Infant; Myocardial Contraction; Pediatrics; Postoperative Care; Postoperative Complications; Procalcitonin; Prognosis; Prospective Studies; Protein Precursors

Adrenomedullin is released by different tissues in hypoxia, oxidative stress, and inflammation and is found in general and medical patients and, recently, in sepsis patients in emergency departments. The aim of this study was to evaluate biologically active adrenomedullin that mirrors directly the active peptide levels in plasma of surgical intensive care unit (ICU) patients with sepsis.. In this single-center observational pilot trial, 42 ICU patients with sepsis and 14 patients after major surgery were included after sepsis diagnosis or ICU admission.. This is the first study investigating adrenomedullin in patients with sepsis following major surgery. Higher adrenomedullin on admission is associated with increased vasopressor need and mortality after 90 days. Thus, adrenomedullin may be a useful additional parameter in surgical patients with sepsis.

Topics: Adrenomedullin; Adult; Aged; Biomarkers; Case-Control Studies; Critical Care; Emergency Service, Hospital; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Pilot Projects; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Shock, Septic

To assess the predictive value of atrial natriuretic peptide, β-type natriuretic peptide, copeptin, mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I) as indicators of low cardiac output syndrome in children with congenital heart disease undergoing cardiopulmonary bypass (CPB).. After corrective surgery for congenital heart disease under CPB, 117 children (aged 10 days to 180 months) were enrolled in a prospective observational pilot study during a 2-year period. The patients were classified according to whether they developed low cardiac output syndrome. Biomarker levels were measured at 2, 12, 24, and 48 hours post-CPB. The clinical data and outcome variables were analyzed by a multiple logistic regression model.. Thirty-three (29%) patients developed low cardiac output syndrome (group 1) and the remaining 84 (71%) patients were included in group 2. cTn-I levels >14 ng/mL at 2hours after CPB (OR, 4.05; 95%CI, 1.29-12.64; P=.016) and MR-proADM levels>1.5 nmol/L at 24hours following CPB (OR, 15.54; 95%CI, 4.41-54.71; P<.001) were independent predictors of low cardiac output syndrome.. Our results suggest that cTn-I at 2hours post-CPB is, by itself, an evident independent early predictor of low cardiac output syndrome. This predictive capacity is, moreover, reinforced when cTn-I is combined with MR-proADM levels at 24hours following CPB. These 2 cardiac biomarkers would aid in therapeutic decision-making in clinical practice and would also enable clinicians to modify the type of support to be used in the pediatric intensive care unit.

Topics: Adrenomedullin; Analysis of Variance; Biomarkers; Cardiac Output, Low; Cardiopulmonary Bypass; Child; Child, Preschool; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Operative Time; Peptide Fragments; Pilot Projects; Postoperative Complications; Protein Precursors; Troponin

Primary graft dysfunction (PGD) after lung transplantation (LT) is a heterogeneous syndrome that comprises clinical presentations with diverse grades of severity. Proadrenomedullin (proADM) levels may be associated with PGD and may enhance its relationship with outcomes. We prospectively included 100 LT recipients. Plasma levels of proADM were measured at 24, 48 and 72 h after admission to the intensive care unit (ICU). We assessed their relationship with PGD grade and ICU mortality. Fifty patients (50%) presented grade 3 PGD at ICU admission. Twenty-two patients (22%) developed grade 3 PGD at 72 h, the only grade associated with higher mortality (odds ratio 6.84, 95% confidence interval [CI] 1.47-38.44). ProADM levels measured at 24 h (3.25 vs. 1.61 nmol/L; p = 0.016) and 72 h (2.17 vs. 1.35 nmol/L; p = 0.011) were higher in these patients than the rest of the population. When we added the individual predictive utility of grade 3 PGD at 72 h for ICU mortality (area under the curve [AUC] 0.72, 95% CI 0.53-0.90) to that of ProADM at 72 h, the predictive value of the model improved (AUC 0.81, 95% CI 0.65-0.97). Higher levels of proADM measured following LT are associated with grade 3 PGD at 72 h. ProADM enhances the association of this entity with mortality.

Topics: Adrenomedullin; Adult; Biomarkers; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Intensive Care Units; Lung Diseases; Lung Transplantation; Male; Middle Aged; Postoperative Complications; Primary Graft Dysfunction; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; Risk Factors; Severity of Illness Index

Recently, increased plasma mid-regional pro-adrenomedullin (MR-proADM) concentrations have been demonstrated in patients with chronic renal failure. In this study, we attempted to identify significant clinical factors associated with MR-proADM concentration in stable kidney transplant recipients.. Forty-seven Japanese kidney transplant recipients who underwent transplantation >180days prior to the study were analyzed. To facilitate comparability of anti-hypertensive regimens across recipients taking different drugs, we calculated the treatment intensity score of anti-hypertensive drugs in each recipient. Morning blood samples were collected and plasma MR-proADM concentrations were measured using an enzyme immunoassay.. Multiple regression analysis identified treatment intensity score for anti-hypertensive drugs, serum albumin, creatinine clearance and use of lipid-lowering agents as significant independent factors associated with plasma MR-proADM concentration. Adjusted coefficient of determination for this model was 0.46.. Apart from indicating lowered renal function, plasma MR-proADM concentration may be a useful biomarker for metabolic disorders, especially hypertension and hyperlipidemia, in stable kidney transplant patients.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Female; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Protein Precursors; Young Adult

In patients after the Fontan procedure, assessment of a failing Fontan circuit is difficult. Natriuretic peptides failed to be reliable markers of functional status or systemic ventricular function in this patient cohort. The aim of the study was to assess the clinical utility of mid-regional pro-adrenomedullin (MR-proADM) in patients after the Fontan procedure.. Plasma MR-proADM levels were measured in 53 patients after the Fontan procedure and compared with clinical status, echocardiographic, and laboratory parameters including NT-proBNP. Median MR-proADM levels were 0.668 nmol/L in patients with a failing Fontan circuit as compared with 0.357 nmol/L in those without Fontan failure (P = 0.001). Levels of MR-proADM were significantly related to the presence of Fontan failure (r = 0.444, P = 0.001), NYHA class (r = 0.434, P < 0.001), and γ-glutamyltransferase levels (r = 0.554, P < 0.001). According to receiver operating characteristic (ROC) curve analysis, Fontan failure was best predicted by MR-proADM [area under the curve (AUC) 0.985, P = 0.001], NT-proBNP (AUC 0.947, P = 0.003), NYHA class (AUC 0.962, P = 0.002), and the inspiratory/expiratory ratio of the inferior vena cava diameter (AUC 0.973, P = 0.007). The optimal cut-off of MR-proADM for the prediction of Fontan failure was 0.520 nmol/L with a sensitivity of 100%, specificity of 93.9%, positive predictive value of 57.1%, negative predictive value of 100%, and overall accuracy of 94.3%. However, the data should also be validated in a larger cohort of patients.. Serial measurements of MR-proADM levels may help identify patients at risk for a failing Fontan circulation especially when exceeding 0.520 nmol/L. In these patients, intensified medical care should be considered to prevent further clinical deterioration.

Topics: Adolescent; Adrenomedullin; Area Under Curve; Biomarkers; Child; Female; Fontan Procedure; Heart Failure; Heart Ventricles; Humans; Male; Peptide Fragments; Postoperative Complications; Predictive Value of Tests; Prognosis; Protein Precursors; Risk Assessment; Ventricular Function

Low cardiac output syndrome (LCOS) remains a major perioperative complications in infants subjected to open-heart surgery with cardiopulmonary bypass (CPB). The present study investigated whether perioperative blood assessment of a potent vasoactive peptide namely adrenomedullin (AM) can predict the risk of LCOS.. We measured AM levels in 48 patients (LCOS: n = 9; controls: n = 39) undergone to open-heart surgery with CPB at five predetermined time points before, during and after the surgery. Clinical, laboratory and perioperative data were analyzed by a multiple logistic regression model.. AM significantly decreased (p < 0.01) during and after the surgical procedure exhibiting a dip at the end of the CPB. Multivariable analysis demonstrated significant correlations among LCOS, AM measured at the end of CPB (p < 0.001), and cooling duration (p < 0.05). AM at 27 pg/L cutoff achieved a sensitivity of 100% and a specificity of 64.1%, while cooling at 11-min cutoff combined a sensitivity of 55.6% and a specificity of 92.3% for LCOS prediction.. This study suggests that AM can constitute, alone or combined with standard parameters, a promising predictor of LCOS in infants subjected to open-heart surgery with CPB.

Topics: Adrenomedullin; Age Factors; Cardiac Output, Low; Cardiopulmonary Bypass; Case-Control Studies; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Postoperative Complications; Prognosis; Sensitivity and Specificity

Leakage from colonic anastomosis is a major complication causing increased mortality and morbidity. Ischemia is a well-known cause of this event. This study was designed to investigate the effects of adrenomedullin on the healing of ischemic colon anastomosis in a rat model.. Standardized left colon resection 3 cm above the peritoneal reflection and colonic anastomosis were performed in 40 Wistar rats that were divided into four groups. To mimic ischemia, the mesocolon was ligated 2 cm from either side of the anastomosis in all of the groups. The control groups (1 and 2) received no further treatment. The experimental groups (3 and 4) received adrenomedullin treatment. Adrenomedullin therapy was started in the perioperative period in group 3 and 4 rats (the therapeutic groups). Group 1 and group 3 rats were sacrificed on postoperative day 3. Group 2 and group 4 rats were sacrificed on postoperative day 7. After careful relaparotomy, bursting pressure, hydroxyproline, malondialdehyde, interleukin 6, nitric oxide, vascular endothelial growth factor, and tumor necrosis factor alpha levels were measured. Histopathological characteristics of the anastomosis were analyzed.. The group 3 animals had a significantly higher bursting pressure than group 1 (p<0.05). Hydroxyproline levels in group 1 were significantly lower than in group 3 (p<0.05). The mean bursting pressure was significantly different between group 2 and group 4 (p<0.05). Hydroxyproline levels in groups 3 and 4 were significantly increased by adrenomedullin therapy relative to the control groups (p<0.05). When all groups were compared, malondialdehyde and nitric oxide were significantly lower in the control groups (p<0.05). When vascular endothelial growth factor levels were compared, no statistically significant difference between groups was observed. Interleukin 6 and tumor necrosis factor alpha were significantly decreased by adrenomedullin therapy (p<0.05). The healing parameters and inflammatory changes (e.g., granulocytic cell infiltration, necrosis, and exudate) were significantly different among all groups (p<0.05).. Adrenomedullin had positive effects on histopathologic anastomotic healing in this experimental model of ischemic colon anastomosis.

Topics: Adrenomedullin; Anastomosis, Surgical; Anastomotic Leak; Animals; Colon; Disease Models, Animal; Female; Ischemia; Postoperative Complications; Postoperative Period; Rats; Rats, Wistar; Time Factors; Vasodilator Agents; Wound Healing

To assess the clinical value of pro-adrenomedullin (pro-ADM) in the prognosis and risk stratification in sepsis.. Fifty-one critically ill patients admitted to the intensive care unit (ICU) were prospectively stratified into four groups according to internationally recognized criteria: systemic inflammatory response syndrome (SIRS, 25 cases), sepsis (12 cases), severe sepsis (9 cases) and septic shock (5 cases). The levels of plasma pro-ADM was determined in every patient using a new sandwich immunoassay, and compared with procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and the acute physiology and chronic health evaluation II (APACHE II) score.. (1) Median pro-ADM concentration was 0.34 microg/L for SIRS, 2.23 microg/L for sepsis, 4.57 microg/L for severe sepsis and 8.21 microg/L for septic shock. The plasma concentration of pro-ADM exhibited a gradual increase, and the median pro-ADM value was highest in the septic shock group (all P<0.05). (2) Compared with the other biomarkers, in the sepsis, severe sepsis and septic shock groups, the plasma concentration of pro-ADM and APACHE II score in the non-survivors was significantly higher than in the survivors (pro-ADM: 2.01 microg/L vs. 9.75 microg/L, APACHE II score: 23.44 scores vs. 38.21 scores, both P<0.05). (3) By the receiver operating characteristic (ROC) curve plot analysis of pro-ADM in sepsis, the area under the ROC curve for pro-ADM (0.87) in survivors was similar to the area under the ROC curve for PCT (0.81) and APACHE II score (0.81), and was significantly higher than the area under the ROC curve for CRP (0.53) and IL-6 (0.71).. The measurement of pro-ADM is a new and useful marker in sepsis prognosis and risk stratification.

Topics: Adrenomedullin; Adult; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Protein Precursors; Risk Assessment; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Topics: Adrenomedullin; Humans; Liver Transplantation; Peptides; Postoperative Complications; Radioimmunoassay; Reproducibility of Results; Vascular Diseases; Vasodilator Agents

Adrenomedullin (AM) is a potent vasodilating peptide that increases rat platelet cyclic adenosine monophosphate levels and acts on endothelial cells to stimulate nitric oxide release. Both mechanisms inhibit platelet function. Considering these effects, AM may have a role in cardiovascular regulation after orthotopic liver transplantation (OLT) and could have an antithrombotic effect. The aim of the present study is to investigate plasma AM levels in the early postoperative period after OLT and their relationship with vascular complications in OLT. We measured plasma AM levels in 35 patients with cirrhosis who underwent OLT at baseline and 1, 7, and 15 days postoperatively. We found that AM levels were significantly greater in patients with cirrhosis compared with healthy subjects. Of the 35 patients, 10 had vascular complications. In these 10 patients, AM concentrations were significantly greater than those observed in the nonthrombotic group in the early postoperative period. In addition, we also noticed in the nonthrombotic group a significant increase in AM levels from baseline to day 1, then a decrease to baseline levels in the early postoperative period. Our study shows that AM might act as a new humoral factor involved in the response to surgery in OLT and is significantly associated with vascular thrombosis in OLT.

Topics: Adrenomedullin; Calcitonin Gene-Related Peptide; Female; Humans; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Peptides; Postoperative Complications; Thrombosis; Vasodilator Agents

Adrenomedullin is an intrinsic vasodilator which is metabolized mainly in the pulmonary circulation. We measured plasma levels of adrenomedullin in children with congenital cyanotic heart disease (CY group, n = 6), children with high pulmonary blood flow due to congenital heart disease (PH group, n = 8), and in adults with mitral valve disease (MV group, n = 7) before and 3 h after cardiopulmonary bypass (CPB). Before CPB, the adrenomedullin level was the highest in the MV group, possibly due to chronic heart failure. Three hours after CPB, the plasma adrenomedullin level (pg/ml) increased to 1712.7 +/- 498.4 in the CY group, 167.6 +/- 26.4 in the PH group, and 1404.3 +/- 313.7 in the MV group, the level in the PH group being significantly lower than the rest. In the PH group, there was statistically significant negative correlation between the mean pulmonary arterial pressure at the preoperative catheter study, and the adrenomedullin level 3 h after CPB. These results illustrate that the adrenomedullin level increased after CPB, but that the increase was less marked in the PH group, implying that where the pulmonary vasculature was damaged most, this results in increased vasoconstriction.

Topics: Adrenomedullin; Adult; Aged; Cardiopulmonary Bypass; Child, Preschool; Female; Heart Failure; Humans; Infant; Male; Middle Aged; Mitral Valve Insufficiency; Peptides; Postoperative Complications; Vasoconstriction