Clinical trial NCT02423369: Cerebral Oxymetry and Neuronal Markers in Newborns and Infants Undergoing Surgery
Official title: Cerebral Oxymetry and Neuronal Biomarkers in Newborns and Infants During Perioperative Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peri-operative Injury
Newborn, Infant, Disease
Keywords: S-100B protein
Neuron-specific Enolase
Lead sponsor: Lithuanian University of Health Sciences
Sponsor class: OTHER
Collaborators: name: Research Council of Lithuania
First posted: 2015-04-22
Enrollment: 49
Sex: ALL
Maximum age (years): 93
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: The purpose of this study is to assess whether peri-operative period in neonates and infants is associated with an increase in blood biomarkers, specific for neuronal injury, and to correlate them with clinical variables and sedative/analgesic agents. Patients, who meet inclusion criteria and does not meet exclusion criteria, are enrolled. Blood samples for measurement serum concentrations of markers (S100-B and Neuron-Specific Enolase (NSE)) are drawn before surgery (baseline) and on the 1-st, 2-nd and 3-rd day after surgery. During surgery cerebral oxygenation (rSO2) monitoring is continuously applied; rSO2, hemodynamic and respiratory values are simultaneously recorded every 5 minutes. Anesthesia, pre and postoperative treatment, including analgesia and sedation, are given as per standard of care.

Detailed description: Retrospective studies have shown that surgery in infancy is associated with worse neurodevelopmental outcome, compared to general population. The reasons may be complex, and patients at risk are unknown. Brain growth and central nervous system formation are extremely active in neonates and infants. Metabolic or circulatory derangement may have negative influence on the developing brain. Disease and perioperative period, both may further put this population at risk for physiological abnormalities. Near infrared spectroscopy was shown to be a convenient method for monitoring of cerebral tissue oxygenation during surgery.

The great majority of anesthetics and sedative drugs, used in perioperative period, were shown to cause neuronal apoptosis in experimental animals. Some studies found that neurological marker S-100B increased in cerebrospinal fluid and blood immediately following anesthesia in animals. Several clinical studies supported this founding in children following cardiac and general surgery.

The aim of this study is to assess the dynamics of S-100B protein pre- and during 72 hours after surgery in neonates and infants aged 1-93 days, operated for abdominal/thoracic/urologic malformations/disease. As S-100B in blood may have extracranial sources, we simultaneously assess other neuronal marker Neuron-specific Enolase.

Eligibility criteria: Inclusion Criteria:

* patients, undergoing general, thoracic, urological surgery for congenital anomalies or disease
* signed written informed consent by parents/official caregivers

Exclusion Criteria:

* cardiac surgery
* any evidence of neurological disease
* sepsis
* limited ability to obtain blood samples
* clinically significant anemia
* physical status of the patients corresponding to American Society of Anesthesiologists (ASA) class 4 and 5.

Primary outcomes:
measure: change in S-100B and NSE concentrations in serum
timeFrame: within 24 hours and 3 days after surgery
Secondary outcomes:
measure: association of S-100B and NSE concentrations in serum with intraoperative cerebral near infrared spectroscopy values.
timeFrame: within 24 hours after surgery
Other outcomes:
measure: association of S-100B and NSE concentrations in serum with cumulative doses of sedative agents
timeFrame: within 24 hours pre surgery to 3 days after surgery
Locations:
city: Kaunas
country: Lithuania
facility: Lithuanian University of Health Sciences Kaunas Clinics
Study officials:
affiliation: Lithuanian University of Health Sciences
name: Danguole C Rugyte, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang S, Peretich K, Zhao Y, Liang G, Meng Q, Wei H. Anesthesia-induced neurodegeneration in fetal rat brains. Pediatr Res. 2009 Oct;66(4):435-40. doi: 10.1203/PDR.0b013e3181b3381b.
citation: Robertson DR, Justo RN, Burke CJ, Pohlner PG, Graham PL, Colditz PB. Perioperative predictors of developmental outcome following cardiac surgery in infancy. Cardiol Young. 2004 Aug;14(4):389-95. doi: 10.1017/S104795110400407X.
citation: Tina LG, Frigiola A, Abella R, Tagliabue P, Ventura L, Paterlini G, Li Volti G, Pinzauti S, Florio P, Bellissima V, Minetti C, Gazzolo D. S100B protein and near infrared spectroscopy in preterm and term newborns. Front Biosci (Elite Ed). 2010 Jan 1;2(1):159-64. doi: 10.2741/e78.
citation: Vicente E, Tramontina F, Leite MC, Nardin P, Silva M, Karkow AR, Adolf R, Lucion AB, Netto CA, Gottfried C, Goncalves CA. S100B levels in the cerebrospinal fluid of rats are sex and anaesthetic dependent. Clin Exp Pharmacol Physiol. 2007 Nov;34(11):1126-30. doi: 10.1111/j.1440-1681.2007.04687.x.
citation: Jensen E, Sandstrom K, Andreasson S, Nilsson K, Berggren H, Larsson LE. Increased levels of S-100 protein after cardiac surgery with cardiopulmonary bypass and general surgery in children. Paediatr Anaesth. 2000;10(3):297-302. doi: 10.1046/j.1460-9592.2000.00522.x.
citation: Razlevice I, Rugyte DC, Strumylaite L, Macas A. Assessment of risk factors for cerebral oxygen desaturation during neonatal and infant general anesthesia: an observational, prospective study. BMC Anesthesiol. 2016 Oct 28;16(1):107. doi: 10.1186/s12871-016-0274-2.