Severity of Hypoxic Ischemic Encephalopathy and Neurological Pupil Index in Neonates

Официальное название

A Study On Association Between Neurological Pupil Index and Clinical Severity of Hypoxic Ischemic Encephalopathy In Neonates Admitted To Neonatal Neurocritical Care Unit

Обзор

The goal of this observational study is to learn if the reactivity of a newborn's eye to light (measured as an index, using a new device -pupillometer) reflect the health of their brain recovering from disruption of blood/oxygen supply during birth (Hypoxic Ischemic Encephalopathy-HIE). The main questions it aims to answer are: * With a decreasing reactivity index, does the chance of an abnormal electrical function of brain (noted by electroencephalography (EEG)) increase? * With a decreasing reactivity index, do the odds of an indicator of severe impact on brain health (abnormal brain imaging, seizures, feeding difficulty) increase? Participants will undergo eye examination using the pupillometer instead of the regular penlight, as part of their routine neurological examination. This will not change the way in which the newborn is being treated and managed medically.

Подробное описание

BACKGROUND:

A newborn baby diagnosed with Hypoxic ischemic encephalopathy (HIE) needs frequent assessment of brain function which includes assessment of pupils in the eyes. However the traditional penlight does not provide a standard measurement and is not very accurate , as it varies based on interpretation of the observer. A new hand-held, non-contact device known as the automated "pupillometer", not only provides a safe, reliable, accurate measurement of the pupil size, but also provides additional information like Neurological Pupil Index (NPi). This value is used to assess the brain function in adults and older children, but the significance of the same has not been studied in a newborn population.

METHODOLOGY:

An Informed consent will be obtained prior to enrolment of the infant in the study. Neurological examination and pupillary assessment will be done at 5 different timepoints: - first at admission(baseline), followed by 24 hours, 48 hours and 72 hours of life, and once prior to discharge. Measurements will be done in both eyes and lesser score of the two will be considered for analysis. Outcome measures including EEG (which is continuous) and MRI (done on day 5 per unit protocol) will be documented and collated for analysis. This is an observational study and the measurement of NPi will not alter the treatment protocol.

The device has been approved by Health Canada for use across all patient population. This device poses no new risks and is safe to use, as it is a non-contact device and is relatively easy to use. Aseptic precautions will be followed when the device is used.

ANALYSIS:

SAMPLE SIZE CONSIDERATIONS:

This is a novel study, with no pre-existing literature. Hence, an initial small scale pilot study will be undertaken with a convenient sample size of all moderate to severe HIE within a year, with anticipation of 70% recruitment. An estimated sample size of 20-25 will help estimate the effect size, variability of NPi, explore relationship between NPi \& indicators of severity of HIE and further refine study design \& sample size calculation

STATISTICAL ANALYSIS:

Primary outcome:

The primary outcome (abnormal EEG pattern) will be a categorical variable (Yes/No type) The relationship between NPi and the primary outcome will be analysed using logistic regression model and expressed as Odds ratio with 95% confidence intervals.

Secondary outcome:

The secondary outcome (a composite measure of factors which indicate risk for severe HIE (including occurrence of seizure during admission, abnormal MRI finding or persistent feeding difficulty) will be assessed using logistic regression A Receiver-Operator Characteristic curve analysis will evaluate the diagnostic accuracy of NPi in predicting clinical severity of HIE indicating sensitivity \& specificity. Any novel threshold values which can predict the cut-off for abnormal EEG pattern, or risk of severe HIE using other indicators will be identified with AUC \>0.7

Вмешательства

• Устройство Automated Pupillometer
  An automated pupillometer will be used to measure pupil size and calculate NPi in newborns with HIE

Первичные конечные точки

• Abnormal EEG pattern [Срок оценки: From starting therapeutic hypothermia at admission (baseline) till completion of therapeutic hypothermia (72 hours from starting cooling therapy). EEG will be monitored CONTINUOUSLY during this period of 72 hours]

Вторичные конечные точки (3)

• Abnormal MRI findings [Срок оценки: MRI brain will be done and scored between day 4 and day 5 from admission]
• Presence of seizure [Срок оценки: baseline (day of admission) till day 5 after admission]
• persistent Feeding difficulty [Срок оценки: will be assessed at the time of discharge from NICU to home or transfer to ward (anytime between week 1 to week 4)]

Критерии участия

Критерии включения

• Neonates ≥35 weeks of GA, with Hypoxic ischemic encephalopathy admitted to neonatal neuro-intensive care unit at Alberta children's hospital, Calgary will be included in the study

Критерии исключения

• Infants with chromosomal abnormalities/ syndromic associations
• Infants with ocular / orbital injuries or structural anomalies of the eye obscuring the pupillometry measurement
• Infants with inadequate pupillometry data / EEG data

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Канада · 1 центр

• University of Calgary — Calgary

Публикации

• Oddo M, Sandroni C, Citerio G, Miroz JP, Horn J, Rundgren M, Cariou A, Payen JF, Storm C, Stammet P, Taccone FS. Quantitative versus standard pupillary light reflex for early prognostication in comatose cardiac arrest patients: an international prospective multicenter double-blinded study. Intensive Care Med. 2018 Dec;44(12):2102-2111. doi: 10.1007/s00134-018-5448-6. Epub 2018 Nov 26. PMID 30478620
• Riker RR, Sawyer ME, Fischman VG, May T, Lord C, Eldridge A, Seder DB. Neurological Pupil Index and Pupillary Light Reflex by Pupillometry Predict Outcome Early After Cardiac Arrest. Neurocrit Care. 2020 Feb;32(1):152-161. doi: 10.1007/s12028-019-00717-4. PMID 31069659
• Al-Obaidi SZ, Atem FD, Stutzman SE, Olson DM. Impact of Increased Intracranial Pressure on Pupillometry: A Replication Study. Crit Care Explor. 2019 Oct 30;1(10):e0054. doi: 10.1097/CCE.0000000000000054. eCollection 2019 Oct. PMID 32166235
• Kim TJ, Park SH, Jeong HB, Ha EJ, Cho WS, Kang HS, Kim JE, Ko SB. Neurological Pupil Index as an Indicator of Neurological Worsening in Large Hemispheric Strokes. Neurocrit Care. 2020 Oct;33(2):575-581. doi: 10.1007/s12028-020-00936-0. PMID 32096118
• Shah SS, Ranaivo HR, Mets-Halgrimson RB, Rychlik K, Kurup SP. Establishing a normative database for quantitative pupillometry in the pediatric population. BMC Ophthalmol. 2020 Mar 26;20(1):121. doi: 10.1186/s12886-020-01389-x. PMID 32216772
• Sandroni C, Citerio G, Taccone FS. Automated pupillometry in intensive care. Intensive Care Med. 2022 Oct;48(10):1467-1470. doi: 10.1007/s00134-022-06772-4. Epub 2022 Jun 30. No abstract available. PMID 35773500
• Jiang J, Sari H, Goldman R, Huff E, Hanna A, Samraj R, Gourabathini H, Bhalala U. Neurological Pupillary Index (NPi) Measurement Using Pupillometry and Outcomes in Critically Ill Children. Cureus. 2023 Oct 4;15(10):e46480. doi: 10.7759/cureus.46480. eCollection 2023 Oct. PMID 37927706
• Couret D, Boumaza D, Grisotto C, Triglia T, Pellegrini L, Ocquidant P, Bruder NJ, Velly LJ. Reliability of standard pupillometry practice in neurocritical care: an observational, double-blinded study. Crit Care. 2016 Mar 13;20:99. doi: 10.1186/s13054-016-1239-z. PMID 27072310

Идентификаторы

NCT: NCT07024771 · REB25-0010

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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