Quantitative Pupillometry in Brain Injury Children : Variation After Osmotherapy

Overview

Intracranial hypertension (ICH) is a common and serious complication in children admitted to pediatric intensive care units. It is primarily caused by traumatic brain injury but can also result from brain malformations, brain tumors, or neuro-meningeal infections. Rapid identification of ICH in acute settings is crucial to ensure prompt management and mitigate potential consequences, such as severe neurological sequelae or death. The assessment of the pupillary light reflex is one of the key clinical parameters used to identify ICH in children with neurological injuries. This clinical sign is correlated with neurological prognosis. During an episode of ICH, regardless of the underlying cause, the oculomotor nerve becomes compressed between the midbrain and the temporal lobe, leading to anisocoria (unequal pupil sizes) and loss of pupillary reactivity. Other factors, such as episodes of ischemia or hypoperfusion in the midbrain, can also contribute to decreased pupillary reactivity.

Detailed description

Traditionally, the pupillary light reflex is assessed using a simple light source, with subjective evaluation by a healthcare professional. However, this method has significant inter- and intra-individual variability. Quantitative pupillometry offers a more objective and reproducible way to evaluate pupillary reactivity. In adults, some parameters are well-known indicators of ICH, such as a constriction velocity of less than 0.6 mm/sec and a constriction percentage below 10%. The constriction percentage can be simplified with the Neurological Pupil index (NPI), which ranges from 0 to 5. An NPI of 4 or 5 is considered to indicate good pupillary reactivity. The two quantitative pupillometers currently on the market (Neurolight, Neuroptics) appear to provide similar data for most variables assessed. However, there are few studies evaluating this tool in pediatric patients with neurological injuries.

One study on quantitative pupillometry found that children with neurological injuries and an intracranial pressure (ICP) above 20 mmHg had significantly lower pupillary reactivity, NPI, constriction percentage, and dilation and constriction velocities compared to children without ICH.

Osmotherapy is a commonly used pharmacological intervention in pediatrics to lower intracranial pressure and improve cerebral perfusion pressure. Based on the work of Freeman et al., we hypothesize that the pupillary constriction percentage improves after osmotherapy in children with neurological injuries.

Interventions

• Device pupillometer
  describe the feasibility of pupillometry measurements in sedated but non-cerebrosed children in intensive care and the operating room
• Device pupillometer
  Pupillometry measurements at 5 and 25 minutes for children treated with osmotherapy, followed by measurements twice a day during hospitalization in the intensive care unit

Primary outcome measures

• to describe and evaluate the variation in the percentage of pupillary constriction (CON) before, and after osmotherapy in neuro-injured children. [Time frame: at 10 days]
• Describe the feasibility of pupillometry in children for different age groups, and obtain baseline values for the sedated, non-neurosed child. [Time frame: at 1 minute and 25 minutes]
• Describe the feasibility of pupillometry in children for different age groups, and obtain baseline values for the sedated, non-neurosed child. [Time frame: at 1 minute and 25 minutes]
• Describe the feasibility of pupillometry in children for different age groups, and obtain baseline values for the sedated, non-neurosed child. [Time frame: at 1 minute and 25 minutes]
• Describe the feasibility of pupillometry in children for different age groups, and obtain baseline values for the sedated, non-neurosed child. [Time frame: at 1 minute and 25 minutes]

Secondary outcome measures (12)

• In the age subgroup of children with an intracranial pressure (ICP) sensor (pathological if ICP more than 20mmHg), evaluate the relationship between intracranial pressure and the various pupillometry values (LAT). [Time frame: per 12h during 10 days]
• In the age subgroup of children with an intracranial pressure (ICP) sensor (pathological if ICP more than 20mmHg), evaluate the relationship between intracranial pressure and the various pupillometry values (QPI). [Time frame: per 12h during 10 days]
• In the age subgroup of children with an intracranial pressure (ICP) sensor (pathological if ICP more than 20mmHg), evaluate the relationship between intracranial pressure and the various pupillometry values.(CON) [Time frame: per 12h during 10 days]
• In the age subgroup of children with an intracranial pressure (ICP) sensor (pathological if more than 20mmHg), evaluate the relationship between intracranial pressure and the various pupillometry values (Max; Min) [Time frame: per 12h during 10 days]
• In the age subgroup of children with an intracranial pressure (ICP) sensor (pathological if more than 20mmHg), evaluate the relationship between intracranial pressure and the various pupillometry values. (ACV and ADV) [Time frame: per 12h during 10 days]
• Comparison of pupillometry values between neuro-sedated and non-neuro-sedated children, adjusting for age [Time frame: at 1 and 25 minutes]
• Comparison of pupillometry values between neuro-sedated and non-neuro-sedated children, adjusting for age. [Time frame: at 1 and 25 minutes]
• Comparison of pupillometry values between neuro-sedated and non-neuro-sedated children, adjusting for age. [Time frame: at 1 and 25 minutes]
• Comparison of pupillometry values between neuro-sedated and non-neuro-sedated children, adjusting for age. [Time frame: at 1 and 25 min]
• Describe the evolution of different pupillometry measurements before and after osmotherapy [Time frame: at 15 , 25, 35, 45, 60, 120, 240 minutes]
• Describe the evolution of different pupillometry measurements before and after osmotherapy [Time frame: [Time Frame: at 15 , 25, 35, 45, 60, 120, 240 minutes]]
• Describe the evolution of different pupillometry measurements before and after osmotherapy [Time frame: [Time Frame: at 15 , 25, 35, 45, 60, 120, 240 minutes]]

Eligibility criteria

Inclusion criteria

• Hospitalized in a pediatric intensive care unit or neurosurgical intensive care unit
• Inclusion within 24 hours of ICU admission
• with clinically suspected HTIC (disorders of consciousness with transcranial Doppler abnormality, symptoms of involvement, poor cerebral perfusion pressure) for which osmotherapy is prescribed

Exclusion criteria

• Presence of eye damage (or antecedent)
• Refusal by parents and/or child Opposition by child or parental guardians.
• Persons not affiliated to the social security system.
• Protected persons (under guardianship, curatorship, pregnant or breast- feeding women, persons deprived of their liberty, persons not subject to a psychiatric measure

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 2 centers

• Chu Grenoble Alpes — Grenoble
• Grenoble Alpes University Hospital — La Tronche

Publications

• Winston M, Zhou A, Rand CM, Dunne EC, Warner JJ, Volpe LJ, Pigneri BA, Simon D, Bielawiec T, Gordon SC, Vitez SF, Charnay A, Joza S, Kelly K, Panicker C, Rizvydeen S, Niewijk G, Coleman C, Scher BJ, Reed DW, Hockney SM, Buniao G, Stewart T, Trojanowski L, Brogadir C, Price M, Kenny AS, Bradley A, Volpe NJ, Weese-Mayer DE. Pupillometry measures of autonomic nervous system regulation with advancing PMID 31555934
• Boev AN, Fountas KN, Karampelas I, Boev C, Machinis TG, Feltes C, Okosun I, Dimopoulos V, Troup C. Quantitative pupillometry: normative data in healthy pediatric volunteers. J Neurosurg. 2005 Dec;103(6 Suppl):496-500. doi: 10.3171/ped.2005.103.6.0496. PMID 16383247
• Rouche O, Wolak-Thierry A, Destoop Q, Milloncourt L, Floch T, Raclot P, Jolly D, Cousson J. Evaluation of the depth of sedation in an intensive care unit based on the photo motor reflex variations measured by video pupillometry. Ann Intensive Care. 2013 Feb 22;3(1):5. doi: 10.1186/2110-5820-3-5. PMID 23433043
• Freeman AD, McCracken CE, Stockwell JA. Automated Pupillary Measurements Inversely Correlate With Increased Intracranial Pressure in Pediatric Patients With Acute Brain Injury or Encephalopathy. Pediatr Crit Care Med. 2020 Aug;21(8):753-759. doi: 10.1097/PCC.0000000000002327. PMID 32195898
• Robba C, Moro Salihovic B, Pozzebon S, Creteur J, Oddo M, Vincent JL, Taccone FS. Comparison of 2 Automated Pupillometry Devices in Critically III Patients. J Neurosurg Anesthesiol. 2020 Oct;32(4):323-329. doi: 10.1097/ANA.0000000000000604. PMID 31033624
• Bower MM, Sweidan AJ, Xu JC, Stern-Neze S, Yu W, Groysman LI. Quantitative Pupillometry in the Intensive Care Unit. J Intensive Care Med. 2021 Apr;36(4):383-391. doi: 10.1177/0885066619881124. Epub 2019 Oct 10. PMID 31601157
• Ritter AM, Muizelaar JP, Barnes T, Choi S, Fatouros P, Ward J, Bullock MR. Brain stem blood flow, pupillary response, and outcome in patients with severe head injuries. Neurosurgery. 1999 May;44(5):941-8. doi: 10.1097/00006123-199905000-00005. PMID 10232526
• Manley GT, Larson MD. Infrared pupillometry during uncal herniation. J Neurosurg Anesthesiol. 2002 Jul;14(3):223-8. doi: 10.1097/00008506-200207000-00009. PMID 12172296

Identifiers

NCT: NCT06642896 · 38RC24.0212

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗