Sample
Research Protocol
Measuring the Impact of Neonatal Seizures
On Cerebral Hemodynamics and Oxygenation
1. Specific Aims / Objectives
The goal of the proposed research is to study the immediate effects of neonatal seizures
on cerebral hemodynamics and oxygenation and to identify factors that influence the
magnitude and timing of changes. Seizures are the most common clinical manifestation
of neurologic dysfunction in the newborn, and often result from serious brain injury.
Although the underlying cause of the seizures is a major determinant of long-term
outcome, there is ongoing concern among clinicians that seizures themselves may cause
or contribute to brain injury. Among the mechanisms implicated in seizure-induced brain
injury are disturbances in cerebral hemodynamics and oxygenation. To date, the ability to
study these potentially injurious mechanisms in the human newborn has been limited by
the lack of a reliable bedside technique for measuring the complex clinical,
electrographic, hemodynamic and oxygenation changes associated with seizures. This
study aims to bridge this impediment to progress by applying an innovative technique
which correlates continuously recorded seizure activity (by video-EEG) with
simultaneous and continuous measurements of systemic and cerebral hemodynamics and
oxygenation (by near infrared spectroscopy). Furthermore, this study will seek to identify
factors that influence the timing and severity of seizure-related changes in cerebral
hemodynamics and oxygenation. Ultimately, insights provided by this research will
translate directly into more informed, rational, and safe management of neonatal seizures.
Specific Aim 1: To determine whether neonatal seizures cause significant changes in
cerebral hemodynamics and oxygenation. Hypothesis: Seizures in the newborn will be
associated with impaired cellular oxygenation (decreased tissue oxygenation index and
oxidized Cytaa3), and impaired cerebral autoregulation.
Specific Aim 2: To identify factors that influence the magnitude and timing of changes in
cerebral hemodynamics and oxygenation during and after neonatal seizures. Hypothesis:
The magnitude and timing of changes in cerebral hemodynamics and oxygenation during
neonatal seizures will be influenced by seizure etiology, seizure type (electrical vs.
electroclinical), seizure duration, seizure recurrence rate, and anticonvulsant therapy.
2. Background and Significance
Seizures are the most common clinical expression of brain dysfunction in the
newborn.(1) The majority of neonatal seizures are symptomatic of a specific identifiable
etiology.(2) The long-term prognosis of neonatal seizures is variable and determined in
large part by the underlying seizure etiology.(1) However, there is persistent concern
Mock Research Protocol – Cecil Hahn, MD
among clinicians that neonatal seizures are not only a clinical manifestation of potentially
severe brain injury, but may also independently contribute to brain injury. Since neonatal
seizures are considered a neurological emergency, they are often treated aggressively
with anticonvulsant medications. However, many neonatal seizures are refractory to
conventional anticonvulsants, even at high doses of multiple agents.(3) The risk–benefit
ratio of such high-dose, multi-drug regimens in critically ill infants has been questioned.
Specifically, the potential for seizures to cause direct injury to the immature brain has to
be weighed against the potential toxic effects (e.g., systemic hypotension) of high-dose
anticonvulsants on the developing brain. These issues have triggered a vigorous but
unresolved debate about the management of neonatal seizures. The research proposed
here aims to address questions central to this controversy.
The ability of neonatal seizures to cause direct brain injury remains
controversial.(4-6) While some studies(4, 7) suggest that the immature brain is
remarkably resistant to seizure-induced injury, other lines of evidence support the notion
that seizures, particularly when prolonged or repeated, contribute independently to brain
injury. In a neonatal rat model,(7) prolonged seizures triggered by proconvulsant drugs
failed to cause neuropathological changes. However, when preceded by a hypoxicischemic insult, these drug-induced seizures were associated with significantly greater
neuronal injury than hypoxia-ischemia alone. Of note, cerebral hypoxia-ischemia is the
leading cause of seizures in the human newborn.(1)
A number of causal mechanisms have been proposed for seizure-induced brain
injury.(1) These include ‘excitotoxic’ injury due to massive accumulation of the
excitatory neurotransmitter, glutamate.(8) Currently, the direct study of excitotoxic
mechanisms at the infant’s bedside is not feasible. This research proposal focuses on
another potentially important mechanism, i.e., seizure-related disruption of normal
cerebral hemodynamics and energy supply. Evidence in support of this mechanism comes
from in vivo studies in neonatal dogs, piglets and humans, where seizures have been
shown to cause significant systemic and cerebral hemodynamic disturbances.(9, 10)
These studies show that the initial, probably adaptive, hemodynamic response to seizures
is a rapid increase in systemic arterial blood pressure and cerebral blood flow. However,
when prolonged or repeated, seizures are associated with sustained impairment of
cerebral autoregulation(11) and systemic hypotension due to impaired cardiac
function.(12) In addition, the repeated neuronal depolarization-repolarization associated
with seizures consumes massive amounts of cerebral energy. This combination of
reduced cardiac output, systemic hypotension, impaired cerebral autoregulation and
increased energy consumption constitutes a major risk for cerebral ischemic injury.(1)
To date, there have been few attempts to characterize the immediate cerebral
metabolic effects of seizures in the human newborn. In one study,(13) infants
experiencing seizures during 31P-labelled magnetic resonance spectroscopy (31P-MRS)
studies showed a marked decrease in cerebral high-energy phosphate concentration
during and shortly after seizures; in some cases cerebral high-energy phosphates
recovered rapidly after successful treatment with phenobarbital. Although 31P-MRS may
provide important insights into the cerebral metabolic consequences of neonatal seizures,
the need to transport infants to a scanner has limited its application to the prolonged study
of critically ill infants.
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Near infrared spectroscopy (NIRS) is an innovative technique for the continuous,
non-invasive bedside measurement of cerebral hemodynamics and oxygenation.(14, 15)
This technique is based on the principle that light in the near-infrared range passes readily
through skin, soft tissue and bone, allowing it to be transmitted into organs such as the
brain. Once in the brain, the absorption of near-infrared light is determined by the
concentration and oxygenation of two critical ‘chromophores’, i.e., hemoglobin and
cytochrome aa3 (Cytaa3), the terminal enzyme in the mitochondrial electron transport
chain. Changes in the absorption of near-infrared light at selected wavelengths therefore
reflect changes in cerebral intravascular (hemoglobin) oxygenation and intracellular
(Cytaa3) oxygenation. In this manner, NIRS makes quantitative measurements of changes
in the cerebral concentration of oxygenated hemoglobin (HbO2), deoxygenated
hemoglobin (Hb), and oxidized cytochrome aa3. Important information may be derived
from these primary measurements. Changes in total hemoglobin (THb) concentration,
and therefore in cerebral blood volume, are derived from the summation of changes in
HbO2 and Hb. Conversely, changes in the difference between HbO2 and Hb (i.e., HbD)
have shown a highly significant correlation with cerebral blood flow.(16, 17) In addition,
the tissue oxygenation index (TOI) may be calculated from the ratio of HbO2 to THb.
These unique features of NIRS have allowed continuous measurements of cerebral
hemodynamics and oxygenation at the bedside of critically infants.(18-26)
Although NIRS would appear to be an ideal technique for the study of the effects
of seizures on cerebral metabolism and hemodynamics, reports of this application are
few,(27-30) with no studies reported in the newborn. In one study using NIRS in older
epileptic children,(30) several different patterns of changes in THb, HbO2 and Hb were
associated with seizures, which was proposed to reflect the heterogeneity of seizure type
and etiology (see Figure 1). This earlier study suggested a potential role for NIRS in the
study of seizures. The current research proposal differs from the above study in important
ways. First, our study will focus on seizures in the newborn infant, which were not
included in the previous report. Second, we plan to study not only changes in cerebral
hemodynamics, but also the more important changes in tissue oxygenation (TOI) and
cellular oxygenation and energy status (Cytaa3).(31, 32)
3. Preliminary Studies / Progress Report
Over the past decade, we have applied the NIRS technique to the measurement of
cerebral hemodynamics and oxygenation in a number of animal(16, 17, 33-35) and
clinical studies.(36-41) Validation studies in a neonatal piglet model showed a robust and
highly significant association between changes in HbD and cerebral blood flow (CBF)
(measured by the gold standard radioactive microsphere technique) during large changes
in cerebral perfusion pressure induced by graded aortic ligature(16) or by changing
intracranial pressure (using mock cerebrospinal fluid infusions).(17) In a neonatal rodent
model of graded hypoxia, we demonstrated a highly significant correlation between
changes in Cytaa3 and changes in high-energy phosphate compounds (measured by 31PMRS);(31) in fact, the decrease in Cytaa3 actually preceded that in high-energy
phosphates. These findings were subsequently corroborated by others.(32)
Our clinical studies in over 400 infants have demonstrated the feasibility and
safety of using NIRS in critically ill infants in settings such as deep hypothermic infant
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cardiac surgery, extreme prematurity, infantile hydrocephalus, and perinatal
asphyxia.(36-43) In recent years, we have developed a technique for evaluating the
integrity of cerebral pressure autoregulation that uses rapid (2 Hz) simultaneous
measurements of changes in blood pressure and cerebral HbD changes. These
measurements are then subjected to coherence and transfer function analysis(40, 44-47)
in order to delineate the relationship between the blood pressure and HbD signals. This
approach will be used to study the effect of seizures on cerebral pressure autoregulation
in the current proposal.
In a recent review of all neonatal seizures occurring over a 3-year period at Children’s
Hospital, Brigham and Women’s Hospital and Beth Israel Deaconess Hospital
(manuscript submitted), we found an incidence of around 40 infants with neonatal
seizures per year. We also found a wide range of seizure etiologies, including global
hypoxia-ischemia (40%), arterial ischemic stroke (20%), intracranial hemorrhage (18%),
cerebral dysgenesis (5%), infection (3%) and unknown/other (15%). This frequent
occurrence and broad etiologic spectrum of neonatal seizures will be of major importance
for accomplishing the goals of the proposed research.
4. Experimental Protocol
Patient Selection and Inclusion/Exclusion Criteria
This research will be conducted in the neonatal intensive care unit. All infants diagnosed
with seizures by the attending neonatologist according to standardized criteria(48) during
the first 30 days of life will be eligible for enrollment in this study. Gestational age at
birth will not be a selection criterion, but extremely low birthweight infants may need to
be excluded due to technical limitations or medical instability. Because the goal of the
study is to measure the effects of seizures, treatment of seizures may be delayed until a
satisfactory NIRS recording is obtained. However, we will make every effort to begin the
study as soon as possible, in order to minimize any such treatment delay.
Research Design
This prospective observational cohort study aims to quantify the immediate effects of
neonatal seizures on cerebral hemodynamics and oxygenation. The current management
of most infants with seizures includes video-EEG monitoring. This study protocol will
supplement these video-EEG recordings with simultaneous measurement of cerebral
NIRS, and systemic parameters (heart rate, blood pressure, oxygen saturation) obtained
directly from the bedside monitor.
The study design for a hypothetical patient is outlined in Figure 2. One unique feature of
this design is that patients will serve as their own controls for time intervals prior, during
and after seizures (see below). The recording schedule for EEG and NIRS is illustrated in
Figure 3. Although video-EEG recordings are routinely performed for a continuous 72hour period, the duration of NIRS recordings is currently limited to 12 hours per day
because quality control necessitates the continuous presence of a technician at the
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bedside.
Measurement of Exposures: Neonatal Seizures
Neonatal seizures are the exposure of interest, and will be measured by continuous videoEEG monitoring (Ceegraph Biologic Systems) for a period of 72 hours. The video-EEG
recordings will be interpreted independently by two neurophysiologists, who will be
blinded to the patient’s identity, all clinical data, the NIRS data, and each other’s
interpretations. The diagnosis and timing of seizures will based on review of the EEG
tracing and the infant’s behavioral changes captured on video, according to standard
diagnostic criteria.(1, 2) Any disagreement between the two neurophysiologists will be
resolved by review of the data and formulation of a consensus opinion. Seizures will be
classified as electroclinical (EEG seizures accompanied by clinical signs), clinical
(clinical signs without EEG seizures) and electrical (EEG seizures without clinical signs).
Seizures will also be classified by cortical location, duration, recurrence rate, and
according to clinical signs according to the classification scheme of Volpe(1):
Classification of Neonatal Seizures
Subtle
Clonic
Focal
Multifocal
Tonic
Focal
Generalized
Myoclonic
Focal
Multifocal
Generalized
Definition of Pre-ictal, Ictal and Post-ictal Time Intervals
The period surrounding each seizure will be divided into time intervals based on the
video-EEG data, indicating pre-ictal, ictal and post-ictal periods according to the
definitions illustrated in Figure 4. The timing of these definitions is based on NIRS
measurements from previous studies conducted in non-neonates, and thus their
applicability to the neonatal study population has not been tested. Therefore, these
definitions will be evaluated and revised based on exploratory analyses of the data from
the first five subjects with usable NIRS data.
Measurement of Outcomes: NIRS Data and Systemic Parameters
The outcome of interest is an alteration in the NIRS signal during seizures, specifically
the change in Cytochrome aa3, tissue oxygenation index, and the integrity of cerebral
autoregulation. To measure these outcomes, continuous NIRS recordings (NIRO 300A
spectrophotometer, Hamamatsu Photonics) will be performed for 12 hours per day on
each of the three study days (which represents the maximum technically feasible
recording time). NIRS signals will be recorded simultaneously from both left and right
cerebral hemispheres. In addition, heart rate, mean arterial blood pressure and oxygen
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saturation will be recorded concurrently from the subject’s routine bedside monitor
(Marquette Solar 8000).
Measurement of Covariables
The following covariables will be recorded in order to permit adjustment for their
possible confounding or effect modification of the association between seizures and
NIRS signal changes. Covariables will be recorded in a structured manner at the time of
enrollment and on each subsequent study day.
 Demographic characteristics (i.e. gestational age, weight, family history of
epilepsy) will be obtained from patient records.
 Perinatal history will be obtained from labor and delivery records. Stringent
criteria will be used for the diagnosis of perinatal asphyxia.(49)
 Medications (i.e. antiepileptic drugs, inotropes): dosage will be obtained from
flow sheets; precise timing of medication administration will be obtained from
flow sheets and by observation of the patient video.
 Structural brain injury (infarction, epidural/subdural/intraparenchymal
hemorrhage, meningitis/encephalitis, hydrocephalus) or brain malformation will
be recorded from cranial ultrasound, CT, and MRI reports.
 Comorbidities, such as meningitis, sepsis, genetic syndromes, electrolyte
disturbances will be noted based on clinical records and laboratory data.
Routine Clinical Care of Subjects
Throughout the study, infants will continue to receive their usual clinical care once
sufficient baseline seizure recordings have been obtained. In particular, any seizures will
be managed according to a standardized protocol in a Manual of Neonatal Care(48) used
in the NICU.
5. Interpretation of Data
Characterization of NIRS Data
The NIRS data from each patient will consist of four paired series of signals for both left
and right cerebral hemispheres: oxygenated hemoglobin (HbO2), deoxygenated
hemoglobin (Hb), tissue oxygenation index (TOI) and oxidized cytochrome aa3 (Cytaa3).
Each of the NIRS signals will be recorded during three 12-hour intervals over a 72 hour
period (Figure 3). Two additional series will be derived from these signals: total
hemoglobin (THb=HbO2+Hb) and the difference between oxygenated and deoxygenated
hemoglobin (HbD=HbO2-Hb). Finally, a relative TOI will be derived by calculating the
ratio of TOI divided by systemic oxygen saturation.
Primary Outcomes: For each series of NIRS data, mean values will be calculated during
each of the pre-defined time intervals (see Figure 4): early pre-ictal, immediate pre-ictal,
ictal, immediate post-ictal and late post-ictal. The mean NIRS value for each interval
will be determined by the sum of all measured data points during that interval, divided by
number of measured data points during that interval.
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Secondary Outcome: In a subset of patients who have arterial lines in place, we will
examine the correlation between mean arterial blood pressure and HbD signals by
coherence and transfer function analysis in order to assess the integrity of cerebral
autoregulation.(40, 44-47) Each time interval will be classified as having intact or
impaired cerebral autoregulation according to whether the coherence score is <0.50 or
0.50, respectively.
Statistical Analysis Plan
Primary analyses will focus on changes from baseline (early pre-ictal mean) in the NIRS
signals for Cytochrome aa3 and tissue oxygenation index. For both of these measures, a
one-sample test of difference from the baseline value will be conducted for each of the
ictal and post-ictal time intervals. If the data appear normally distributed, or can be
transformed to achieve approximate normality, the one-sample t-test will be used.
Otherwise, the nonparametric Wilcoxon signed rank test will be used.
A secondary analysis will be performed when electrographic seizure activity may be
lateralized to one hemisphere. These lateralized seizures provide an opportunity to
control for the systemic hemodynamic effects of seizures (i.e. on blood pressure and heart
rate) by subtracting the NIRS signals from the unaffected hemisphere from the signals
from the affected hemisphere. We hypothesize that the resultant ‘adjusted’ NIRS signals
may more accurately represent the local effects of seizures on cerebral hemodynamics
and oxygenation.
Characteristics of the seizure and of seizure history, such as seizure etiology, duration of
seizure, type of seizure (electrographic only versus electroclinical), and number of known
prior seizures will be assessed for their associations with the NIRS measures using
correlation, ANOVA or nonparametric analogues as appropriate. For cases when
multiple seizures are captured in a single subject, generalized estimating equations (GEE)
will be used to account for correlated observations.
Statistical Power
The primary analyses will compare NIRS signals during and after seizures with the
baseline level prior to the seizure within the same patient. These are essentially
one-sample tests against a mean of zero. Therefore, the relevant power calculations are
for one-sample tests. Assuming a two-sided type I error of 0.05, the following table
illustrates how small an effect size can be detected with 85% power, for a range of
sample sizes, where effect size is the change from baseline measured in standard
deviation units. The table assumes one seizure recorded per subject.
Effect size:
Sample size:
.40
57
.50
36
.60
25
.70
19
.90
12
1.0
9
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Based on a recent review of all neonatal seizures at Children’s Hospital Boston, Brigham
and Women’s Hospital and Beth Israel Deaconess Hospital (see preliminary studies) we
estimate an incidence of approximately 30 neonatal seizures per year at the two study
sites. Assuming that 75% of families approached will choose to participate, we estimate
enrollment of approximately 40 patients over the two-year study period. Given that data
from five patients will be used for the initial exploratory analysis, and approximately 510 patients will yield no usable NIRS data (for example because no seizures were
captured by NIRS), we anticipate that approximately 25-30 patients will yield analyzable
data. The table above given this estimated sample size, effect sizes of between 0.5 and
0.6 standard deviations, or higher, will be detected with 85% power. Patients who
contribute more than one seizure will increase the power (or equivalently, decrease the
detectable effect size) but it is difficult to project the magnitude of improvement in
precision without knowing how highly correlated the within-subject responses will be
across seizures.
6. Risks
There are no reported risks or discomforts associated with video-EEG or neonatal NIRS.
We have studied over 300 critically ill infants with NIRS and to date have experienced no
significant adverse effects. There is potential risk for allergy to the tape applying the
optodes to the infant’s skin. Should this occur, an alternative fixation technique will be
applied.
7. Potential Benefits
Benefits to study participants: Study subjects are unlikely to receive direct potential
benefit from participation in this protocol, however the NIRS data generated during the
study period may be used for clinical decision-making.
Advancement of scientific knowledge: The ability to make precisely time-locked
quantitative measurements of cerebral hemodynamics, vasoregulation, and oxygenation
at the bedside of sick infants with seizures will present a major opportunity for advancing
our understanding of neonatal seizures and their consequences. Simultaneous
measurement of changes in the EEG, systemic parameters and cerebral perfusion and
oxygenation will provide new insights into the temporal relationships between these
changes. Comparing the hemodynamic responses to seizures of different etiologies will
increase our understanding of the relationship between etiology and long-term outcome.
Data generated by this research will also be critical for the design of future studies into
the long-term significance of these acute seizure-induced changes in cerebral perfusion
and oxygenation.
Benefits to society: This study is motivated by the current vigorous but unresolved
debate about the optimal management of neonatal seizures. Ultimately, insights provided
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by this research will translate directly into more informed, rational, and safe management
of neonatal seizures, with enormous potential benefit to society.
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Saul JP, Berger RD, Albrecht P, Stein SP, Chen MH, Cohen RJ. Transfer function analysis of the
circulation: unique insights into cardiovascular regulation. Am J Physiol 1991;261(4 Pt 2):H123145.
Saul JP, Berger RD, Chen MH, Cohen RJ. Transfer function analysis of autonomic regulation. II.
Respiratory sinus arrhythmia. Am J Physiol 1989;256(1 Pt 2):H153-61.
Zhang R, Zuckerman JH, Giller CA, Levine BD. Transfer function analysis of dynamic cerebral
autoregulation in humans. Am J Physiol 1998;274:H233-H241.
Giller CA. The frequency-dependent behavior of cerebral autoregulation. Neurosurgery
1990;27(3):362-368.
du Plessis AJ. Neonatal Seizures. In: Cloherty J, Stark A, editors. Manual of Neonatal Care. 5th
ed. Philadelphia: Lippincott-Raven; (In press).
du Plessis AJ. Perinatal asphyxia and hypoxic-ischemic encephalopathy in the term infant. In:
Spitzer AR, editor. Intensive Care of the Fetus and Newborn. St. Louis: Mosby-Year Book; In
press.
Figure 1: Example of the NIRS signal recorded during a secondarily generalized tonic-clonic
seizure in a 10-year old boy.
Haginoya K, et al. Brain 2002;125:1960-1971.
11
Mock Research Protocol – Cecil Hahn, MD
Figure 2: Overall Study Design for a Hypothetical Patient
Time Intervals of Interest
Begin
EEG/NIRS
Pre-Ictal
1st seizure
Ictal
Post-Ictal
Time
2nd seizure
+/- AED
Treatment
+/- AED
Treatment
Figure 3: Timing of EEG and NIRS Recordings
EEG Recording:
NIRS Recording:
Enrollment
12 hrs
24 hrs
36 hrs
48 hrs
60 hrs
Time
12
72 hrs
Mock Research Protocol – Cecil Hahn, MD
Figure 4: Definition of Pre-ictal, Ictal and Post-ictal Time Intervals
5 min
5 min
Seizure
5 min
5 min
Time
Early
pre-ictal
Early Pre-ictal:
Immediate Pre-ictal:
Ictal:
Immediate Post-ictal:
Late Post-ictal:
Immediate
pre-ictal
Immediate
post-ictal
Late
post-ictal
The 5 minute interval beginning 10 minutes before seizure onset
The 5 minute interval immediately preceding seizure onset
The interval from seizure onset to seizure termination
The 5 minute interval immediately following seizure termination
The 5 minute interval beginning 5 minutes following seizure termination
13
CONSENT FORM
Participant’s Name: ________________________________________
Date: _____
Date of Birth: _____________________________________________
Age: ______
Project Title: Measuring the Impact of Neonatal Seizures on Cerebral Hemodynamics
and Oxygenation
DESCRIPTION AND EXPLANATION OF RESEARCH:
We would like to ask you and your infant to participate in a research study being
performed by the Department of Neurology. We have identified your infant as a potential
participant in this study through a review of admissions to the Hospital. Your infant has
recently been diagnosed with seizures. Seizures are a common result of a number of
conditions in the newborn; however, there is a great deal we do not know about how
seizures affect the blood flow and oxygen levels in an infant’s brain.
The goal of this research study is to improve our understanding of the effects of seizures
on an infant’s brain and to help future doctors provide better care for babies with
seizures. We would like your permission to use an experimental technique called near
infrared spectroscopy (NIRS) to measure the blood flow and oxygen level in your baby’s
brain.
Near Infrared Spectroscopy (NIRS)
The NIRS technique involves attaching two pairs of tiny sensors to your baby’s skin, held
in place by a stretchy cloth. Through one disc a special type of light shines into the brain.
The second disc collects and measures the light that is reflected from the brain. All that
passes into the brain during this test is near infrared light, similar to the red light used to
measure oxygen at your baby’s fingertip or toe.
The NIRS measurements for this study will be made for 12-hour periods on each of the
next three days. At the same time that the NIRS measurements are being made, we will
also record changes in your baby’s blood pressure taken directly from the monitors
already in use by your baby’s doctor to monitor blood pressure and heart rate.
If you agree to enroll your baby in this study, we will collect a variety of information on
your baby. We will obtain some of the information we need from the tests that are
routinely used in the care of babies such as yours who are experiencing seizures. Some
of this routine information will come from your baby’s medical record, and some of it
will come directly from the video-EEG and bedside monitors routinely used by doctors to
manage babies such as yours. Although the near infrared spectroscopy (NIRS) is a
research technique, we may also use this information to help treat your baby’s seizures.
Throughout the study, your baby will continue to receive his/her routine clinical care.
However, because our aim is to capture seizures, we may slightly delay your baby’s
treatment until we have captured a minimum number of seizures to analyze using NIRS.
Study Duration
If you consent to your baby’s participation, then we will begin the study within the next
12 hours. The duration of the study will be 72 hours, during which we will collect EEG,
NIRS and clinical information on your baby as described above. Once the study has
begun, it will only be stopped in the case of severe medical risk, as defined by your
baby’s neonatologist. We will not discharge your child from hospital before completion
of the study.
EXPENSES/COMPENSATION/REIMBURSEMENT:
If you choose to participate, we will be pleased to offer you a gift or cash payment of
$100. There will be no extra cost to you or your insurance carrier for the near infrared
spectroscopy (NIRS) studies. Only those tests that are currently routinely performed for
babies experiencing seizures (such as the video-EEG) will be charged to you or your
insurance carrier.
RISKS AND DISCOMFORTS:
Because this is a monitoring study that does not make use of any drugs or invasive
procedures, there are few foreseeable risks and discomforts. In order to capture seizures,
it may be necessary to delay treatment of your baby’s seizures to perform optimal NIRS
recordings. There are no reported risks or discomforts associated with the NIRS
technique. We have studied over 300 critically ill infants with NIRS and to date have
experienced no adverse effects from this technique.
POTENTIAL BENEFITS:
Although the NIRS measurements made during the study are for research purposes, they
may also provide valuable information that can help us provide optimal care for your
baby. It is hoped that the information gathered during this study will advance scientific
understanding of any changes that occur in an infant’s brain because of seizures, and
might also help us learn how to better manage infants who experience seizures.
CONFIDENTIALITY:
All of the information gathered as part of this study will be kept confidential. Your baby
will be assigned a study number that will identify your baby with the data that is
collected. Only the investigators involved in this study will have access to the
information that links your baby’s study number to your baby’s name or medical record
number. Your baby will not be identified in any publication that may result from this
study.
ALTERNATIVES:
Your participation in this study is entirely voluntary. You have the alternative not to
participate in this study. Your refusal to participate in this study will in no way interfere
with any current or future care your child receives at the Hospital.
INVESTIGATOR’S AND/OR ASSOCIATE’S STATEMENT:
I have fully explained to ____________________________________________ the
participant/parent/guardian
nature and purpose of the above-described procedures and the risks involved in its
performance. I will inform the participant of any changes in the procedures or the risks
and benefits if any should occur during or after the course of the study. I have given a
copy of the consent/authorization form to the subject/family.
__________
Date
___________________________________
Investigator’s and/or Associate’s Signature
CONSENT/AUTHORIZATION:
I have been satisfactorily informed of the above-described procedure with its possible
risks and benefits, and I have been given a copy of this form.
________
Date
______________________________________
Signature of Parent/Guardian
_______________
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