Análise de biomarcadores séricos de hipóxia pré e pós-operatórios em pacientes com cardiopatia congênita

Abstract

Introduction: in patients with congenital heart disease, only preoperative and postoperative analysis of the patient through neurological examination has shown a low predictive value for neuropsychomotor outcome, suggesting the need to incorporate other neurological status assessment methods. Objectives: To verify the dosage of biomarkers, substances that can be used in clinical practice for the diagnosis or to identify risks of occurrence of a disease, in peripheral blood of patients with congenital heart disease, in the pre- and postoperative periods, as indicators of prognosis neurological, and to correlate previous clinical aspects with follow-up. Methods: Cross-sectional observational, descriptive study. Patients were selected at the Inpatient Unit and at the Pediatric Intensive Care Unit of the Santo Antônio Children's Hospital, at the Santa Casa de Misericórdia Hospital Complex, Porto Alegre / RS. The sample consisted of 22 patients with ages ranging from zero to 17 years and 11 months of age, with congenital heart disease who underwent cardiac surgery. Preoperative neurological examination and collection of pre and postoperative blood samples were performed. The biomarkers studied were interleukin-10, brain derived neurotrophic factor or BDNF, endothelial growth factor receptor 1 or VGEFR-1 and tumor necrosis factor alpha or TNF-alpha). Samples were analyzed by a multiplex and assay kit using the Luminex technique in the IPB. Patients whose parents did not allow blood collection, whose parents did not sign the consent form, were either under the age of eighteen years or those who showed signs and symptoms of clinical instability and / or complex genetic syndromes that could alter biomarkers for reasons unrelated to heart disease. In addition, those patients who have suffered intercurrences of collection such as fear, refusal, vaso-vagal reaction, arterial puncture, pain and nerve damage, persistent bleeding, hematoma, allergy and infection in which it is not possible to collect blood during the first attempt and the family does not wish to submit the patient to a new collection, at another time. Results: Postoperative IL-10 and VEGFR1 showed higher values than preoperative measurements, but this variation did not show statistical significance (p = 0.34 and p = 0.09, respectively). Variations in pre and postoperative BDNF and TNF-alpha dosages were statistically significant (p = 0.05 and p = 0.03, respectively). Comparing the biomarkers with two ECC (Extracorporeal Circulation) time slices, more or less than 95 min, no statistically significant variations were found, but the TNF-alpha dosages in the postoperative period were those patients with longer CPB, had a more significant fall, obtaining a value of p = 0.06, which may not have presented statistical significance, as a function of the small sample size. Comparing the clinical data regarding neurological complications, it was found that the longer the total time of hospitalization and surgery, the greater the probability that the patient presented postoperative neurological complications (p = 0.012 and 0.025, respectively). In addition, if there was a previous history of seizures, it is more likely to present seizures in the postoperative period (p = 0.05). Comparing clinical data regarding postoperative sepsis, it was shown that the higher the postoperative IL-10, the greater the probability of occurrence of sepsis (p = 0.029). Regarding the traditional physical neurological examination, it was pointed out that if modified, the likelihood is also greater that the individual presented delay of neuropsychomotor development (p = 0.001). Conclusion: Preoperative levels of IL-10, VGEFR-1, BDNF and TNF-alpha are not directly related to any of the variables investigated. There is a decrease in the levels of TNF alpha and BDNF in the postoperative period that demonstrates the greater immunological and neurological vulnerability of the patients in this period, evidencing that the inflammatory cascade triggered by the surgical procedure is involved in sepsis and neurological complications. In addition, most of the patients studied had neurological examination and neuropsychomotor development alterations before they were submitted to any procedure, especially those with lower peripheral oxygen saturations, making it clear that the congenital heart disease itself should involve cerebral changes and the damage is proportional to the degree of cyanosis. Finally, the increase in IL-10 levels in the postoperative period is specifically related to a higher occurrence of sepsis.