Research Article: Prognostic value of biomarkers after cardiopulmonary bypass in pediatrics: The prospective PANCAP study

Date Published: June 17, 2019

Publisher: Public Library of Science

Author(s): Sara Bobillo-Perez, Iolanda Jordan, Patricia Corniero, Monica Balaguer, Anna Sole-Ribalta, Maria Esther Esteban, Elisabeth Esteban, Francisco Jose Cambra, Claudio Passino.


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.

Partial Text

Procalcitonin (PCT), pro-adrenomedullin (pro-ADM) and brain natriuretic peptide have been proposed as useful biomarkers for therapeutic decision-making in patients that require cardiopulmonary bypass (CPB), at both pre-and post-surgical time [1–5]. Recent studies underlined the promising utility of them as prognostic predictors in patients with heart failure or low cardiac output syndrome also in children [6–9]. PCT is known to be more specific and earlier than classical biomarkers in the diagnosis of infectious complications [10,11]. Although PCT may increase slightly in the systemic inflammatory response syndrome, as it occurs after CPB, most studies point to better predictive values of PCT than other clinical or analytical markers to discriminate the presence or absence of infection [6,12–14]. Other biomarkers such as pro-ADM and pro-atrial natriuretic peptide (pro-ANP) would be more appropriate in the stratification of the severity of critically-ill patients. These biomarkers can be even better prognostic markers than the traditional severity scores such as the Pediatric Risk Score Mortality III (PRISM III) [15–17]. Adrenomedullin is a potent vasodilator that can act as a hormone or cytokine and plays a role in controlling pulmonary flow, migration of leukocytes and electrolyte balance. Pro-ADM is a peptide directly measuring the blood levels of adrenomedullin, but biochemically more stable and easier to determine. Several studies have shown the usefulness of pro-ADM as a marker of severity and prognosis in patients with respiratory infections, and sepsis [18–20]. Some studies have described increased levels of adrenomedullin after CPB, thus it could be useful in the post-operatory [21,22]. A more recent study has shown that pro-ADM could accurately detect pediatric heart failure [7]. The brain natriuretic peptide and the pro-ANP have been proposed as markers of heart dysfunction, and as prognostic markers for monitoring patients with heart failure, acute coronary syndromes and hypertension [7,8,23–25]. There are many publications about the usefulness of brain natriuretic peptide in children [26], but not about pro-ANP. An increase of pro-ANP has been described in septic patients, and its usefulness as a prognostic marker in the CPB has also been suggested [27,28].

A prospective and observational study (July 2012-October 2013) was conducted on patients attended in the Pediatric Intensive Care Unit (PICU) of a tertiary-care children’s hospital with 345 beds (18 PICU beds). Referral population: Catalonia, with ~7 million population and 1.2 million children under 18 years, this captured around 17% of all pediatric hospital admissions during the study period. The study was approved by the ethics committee of the hospital (CEIm Fundacion Sant Joan de Deu, Barcelona) and the institutional review board. Written informed consent was obtained from parents or the legal guardian of each child.

This study provides important information on the values of three biomarkers during the first 36 hours post-CPB. The results obtained underline for the first time the prognostic usefulness of pro-ADM and pro-ANP to predict need for prolonged MV and LOS after CPB on one hand, and confirm the value of the PCT to predict the infectious complication. The three biomarkers showed persistently high values in those patients that needed MV or inotropic support after surgery, but only the results of pro-ADM and pro-ANP were statistically significant at both times of the analysis. Pro-ADM and pro-ANP can be analysed with the same test in a few minutes (30–60 minutes), which provides valuable information for clinicians. In those patients with bacterial infection, pro-ADM and PCT showed statistically significant high values at post-CPB1 and post-CPB2. This finding could be due to the fact that pro-ADM and pro-ANP have a more important role in vasoregulation than PCT, which seems to be mainly activated by an infectious stimulus. During CPB there is a syndrome of systemic anti-inflammatory response with pathophysiological changes affecting homeostasis. There is an activation of the renin-aldosterone system increasing vascular resistances, diminishing urinary volume and presenting a third space due to fluid retention [34,35]. These changes may induce an increased production of ADM and pro-ANP to counteract the effects above mentioned and protect the heart muscle.

The persistently high values of pro-ADM and pro-ANP after CPB in those patients that needed MV or inotropic support underline their prognostic usefulness. Pro-ADM and pro-ANP are good predictors of need for MV and LOS after CPB. A high value of these biomarkers at admission in PICU after CPB should alert the intensivist not to proceed to an early extubation. Further investigations are needed to enhance our knowledge about these biomarkers.