Hemodynamic Responses to Cardio-respiratory Events in Preterm Infants

January 27, 2020 updated by: Luigi Corvaglia, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Cardiovascular and Cerebrovascular Responses to Cardio-respiratory Events in Very Preterm Infants During the Transitional Period

Intermittent episodes of hypoxemia and/or bradycardia, also defined as cardio-respiratory events (CRE) are very frequent in preterm infants and may result in transient hypoxia and hypoperfusion of target organs, with possible clinical implications. The hemodynamic instability that characterizes the first 72 hours of life, also called as transitional period, place preterm infants at high risk of complications and may contribute to enhance fluctuations in end-organ perfusion and oxygenation induced by CRE. In this study we aimed to explore cardiovascular and cerebrovascular changes determined by different CRE types in preterm infants during the transitional period.

Study Overview

Detailed Description

Intermittent episodes of hypoxemia and/or bradycardia, also defined as cardio-respiratory events (CRE) are very frequent in preterm infants and may result in transient hypoxia and hypoperfusion of target organs, with possible clinical implications. The hemodynamic instability that characterizes the first 72 hours of life, also called as transitional period, place preterm infants at high risk of complications and may contribute to enhance fluctuations in end-organ perfusion and oxygenation induced by CRE. Moreover, during this period, several clinical variables (e.g., antenatal steroid administration, gestational age [GA], patent ductus arteriosus [PDA], respiratory support etc.) may contribute to modulate the hemodynamic fluctuations in response to CRE.

Hence, this study aims:

  • to explore changes in the main cardiovascular and cerebrovascular parameters elicited by different CRE types
  • to evaluate whether different antenatal, perinatal and postnatal factors may influence the observed cardiovascular and cerebrovascular responses to CRE.

Infants born at S. Orsola-Malpighi Hospital are consecutively enrolled in this observational, prospective study if fulfilling the following eligibility criteria: gestational age (GA) <32 weeks' gestation, birth weight <1500 g, 0-12 hours of life, written informed consent obtained from the parents/legal guardians of each infant.

As routinely performed in infants with the eligible characteristics, the enrolled infants undergo a simultaneous, continuous and non-invasive monitoring of

  • peripheral oxygen saturation (SpO2) and heart rate (HR) using a pulse oximeter
  • cerebral tissue oxygenation index (cTOI) and cerebral total hemoglobin index (cTHI), which represents a proxy of cerebral blood flow, using near infrared spectroscopy. Cerebral fraction of oxygen extraction (cFTOE) is also calculated as follows: (SpO2-cTOI)/SpO2.
  • cardiovascular parameters (cardiac output [CO], stroke volume [SV], cardiac contractility index [ICON], systemic vascular resistance [SVR]) using electrical cardiometry.

In the enrolled infants, each monitoring device is connected via a RS232 cable to a laptop running ICM+® (https://icmplus.neurosurg.cam.ac.uk/, Cambridge Enterprise, UK), a software tool that allows a real-time synchronized multi-parametric data collection, which recorded the above mentioned parameters continuously, from the time of enrollment up to 72 hours of life.

Cardiorespiratory event types are classified on the basis of SpO2 and HR values as follows:

  • isolated desaturation (ID): SpO2 <85% and classified into mild (SpO2 80-84%), moderate (SpO2 70-79%) and severe (SpO2 <70%).
  • isolated bradycardia (IB): any HR drop <100 bpm or >30% from baseline values, calculated daily over the first 72 hours of life
  • desaturation and bradycardia occurring within a 60-sec time window: combined events (DB).

The following antenatal and neonatal data are tracked down on a specific case report form: GA, antenatal steroids (complete course vs. incomplete course or not given) evidence of reversed end-diastolic flow at antenatal umbilical Doppler (uREDF) (present vs. absent); ventilatory status over the first 72 hours of life (continuous positive airway pressure [CPAP] vs. nasal cannulas or self-ventilating in air [SVIA]); surfactant administration; development of IVH over the first 72 hours of life.

A screening echocardiogram is routinely performed at the time of enrollment and repeated 6-12 hourly in the presence of a patent ductus arteriosus (PDA) or 12-24 hourly if there is no evidence of PDA. Based on echocardiographic features, the ductal status is classified as follows: no evidence of PDA (noPDA), restrictive PDA (rPDA; restrictive shunt pattern and left atrium to aortic root ratio [LA:Ao] ratio <1.5), hemodynamically significant PDA (hsPDA; pulsatile shunt pattern, LA:Ao ratio ≥1.5 or presence of reversed end-diastolic flow either in the descending aorta or in the anterior cerebral artery).

For statistical analysis, percentage changes of cardiovascular (CO, ICON, SVR) and cerebrovascular (cTOI, cTHI, cFTOE) parameters will be compared between different CRE types (ID, DB and IB) using Kruskal-Wallis test. Generalized estimating equation (GEE) models will be used to analyze the concomitant effect of clinical variables (e.g., GA, uREDF, antenatal steroids, ductal and ventilatory status etc.) on the percentage changes of the study parameters. IBM SPSS, version 25.0, will be used for statistical analysis. The significance level is set at p<0.05.

Study Type

Observational

Enrollment (Actual)

42

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
        • S. Orsola-Malpighi University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 3 days (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Preterm infants on spontaneous breathing during the transitional period (0-72 hours of life).

Description

Inclusion Criteria:

  • gestational age <32 weeks' gestation AND/OR birth weight <1500 g

Exclusion Criteria:

  • major congenital malformations
  • congenital heart disease
  • mechanical ventilation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase/reduction of cTOI during isolated desaturation, isolated bradycardia and desaturation-bradycardia
Time Frame: 0-72 hours of life
Comparison of percentage cTOI changes (cTOI at baseline/during the event) among isolated desaturation, isolated bradycardia and desaturation-bradycardia
0-72 hours of life
Increase/reduction of cFTOE during isolated desaturation, isolated bradycardia and desaturation-bradycardia
Time Frame: 0-72 hours of life
Comparison of percentage cFTOE changes (baseline/during the event) among isolated desaturation, isolated bradycardia and desaturation-bradycardia
0-72 hours of life
Increase/reduction of cTHI during isolated desaturation, isolated bradycardia and desaturation-bradycardia
Time Frame: 0-72 hours of life
Comparison of percentage cTHI changes (baseline/during the event) among isolated desaturation, isolated bradycardia and desaturation-bradycardia
0-72 hours of life
Increase/reduction of CO during isolated desaturation, isolated bradycardia and desaturation-bradycardia
Time Frame: 0-72 hours of life72 hours
Comparison of percentage CO changes (CO at baseline/during the event) among isolated desaturation, isolated bradycardia and desaturation-bradycardia
0-72 hours of life72 hours
Increase/reduction of SV during isolated desaturation, isolated bradycardia and desaturation-bradycardia
Time Frame: 0-72 hours of life
Comparison of percentage SV changes (baseline/during the event) among isolated desaturation, isolated bradycardia and desaturation-bradycardia
0-72 hours of life
Increase/reduction of ICON during isolated desaturation, isolated bradycardia and desaturation-bradycardia
Time Frame: 0-72 hours of life
Comparison of percentage ICON changes (baseline/during the event) among isolated desaturation, isolated bradycardia and desaturation-bradycardia
0-72 hours of life
Increase/reduction of SVR during isolated desaturation, isolated bradycardia and desaturation-bradycardia
Time Frame: 0-72 hours of life
Comparison of percentage SVR changes (baseline/during the event) among isolated desaturation, isolated bradycardia and desaturation-bradycardia
0-72 hours of life

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of neonatal characteristics on cerebrovascular parameters
Time Frame: 0-72 hours of life
Generalized estimating equation (GEE) analysis evaluating the effect of clinical variables (e.g., GA, uREDF, antenatal steroids, ductal and ventilatory status etc.) on percentage changes of cTOI, cFTOE, cTHI.
0-72 hours of life
Effect of neonatal characteristics on cardiovascular parameters
Time Frame: 0-72 hours of life
Generalized estimating equation (GEE) analysis evaluating the effect of clinical variables (e.g., GA, uREDF, antenatal steroids, ductal and ventilatory status etc.) on percentage changes of CO, SV, ICON, SVR
0-72 hours of life

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Luigi Corvaglia, MD, S. Orsola-Malpighi University Hospital, Bologna, Italy

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 22, 2018

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

January 3, 2020

Study Registration Dates

First Submitted

November 29, 2019

First Submitted That Met QC Criteria

December 2, 2019

First Posted (Actual)

December 3, 2019

Study Record Updates

Last Update Posted (Actual)

January 29, 2020

Last Update Submitted That Met QC Criteria

January 27, 2020

Last Verified

January 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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