Phosphopyruvate Hydratase Clinical Trial
Official title:
Neural Damage and Anesthetic Treatment in the Preeclamptic Parturient; a Prospective Observational Cohort Study.
Objectives: Our primary objective is to evaluate the effect of anesthetic method (general
versus regional anesthesia) on neural outcomes in the preeclamptic population undergoing
cesarean delivery. Secondary outcome is to examine the fetal cerebral outcomes associated
with the anesthetic method.
Methodology: This prospective, observational study, will include 50 preeclamptic parturients
undergoing cesarean section under general and regional anesthesia.
Neuron specific enolase and S100B Protein are neuronal injury biomarkers. Increased levels of
these biomarkers in serum indicate neuron damage. Following enrollment venous blood will be
drawn from the participants and assessed for NSE and S100B serum levels at the following
points; Upon hospital admission and one day postpartum. Furthermore in order to evaluate
fetal outcomes upon fetal delivery, umbilical cord blood will be examined for NSE and S100B.
Study significance: While spinal anesthesia is the preferred anesthetic method for the
preeclamptic parturient undergoing cesarean delivery, it remains uncertain which anesthetic
method is neuroprotective.
This study will be the first study, to our knowledge, to examine the effect of anesthetic
method on neuronal outcomes for a parturient with preeclampsia undergoing cesarean delivery,
by the use of noninvasive cerebral biomarkers.
Scientific background:
Preeclampsia is an idiopathic maternal, multi organ, specific pregnancy disorder, associated
with significant maternal and perinatal morbidity and mortality. Preeclampsia complicates
approximately 2-8% of all pregnancies. The disorder is characterized by new-onset of
hypertension and proteinuria developing after gestational week 20. While the pathogenesis of
the disease remains not completely understood, a possible explanation is endothelial cell
dysfunction in which placenta-derived mediators causes multisystem organ dysfunction .
Preeclampsia increases the risk for acute cerebrovascular complications such as intracerebral
hemorrhage, cerebral edema and eclampsia. Treatment with magnesium sulfate reduces the risk
for seizures and treatment with antihypertensive therapy reduces the risk for a stroke ,
however the only effective treatment for the syndrome is prompt delivery of the fetus .
When considering the optimal anesthetic method for a preeclamptic parturient undergoing
cesarean delivery, neuraxial anesthetic techniques, when feasible, are strongly preferred to
general anesthesia (GA) . Spinal anesthesia (SA) is favored over general anesthesia since it
is associated with increased benefits and reduced risks compared with general anesthesia.
Increased benefits of SA include higher patient satisfaction, decreased pain and favorable
neonatal outcomes. GA has been associated with increased risk for aspiration, unstable
hemodynamics and difficult airway management . In addition GA has been shown to increase the
risk for a stroke in women with preeclampsia . Nevertheless GA is sometime used in the
preeclamptic parturient due to maternal or fetal indications with an incidence as high as 44%
in some European countries .
Accumulative evidence from animal studies indicate that general anesthetic agents are
neurotoxic and can induce subsequent behavioral abnormalities in the developmental mind .
However the fetal and pediatric implications remain inconclusive. In a population-based birth
cohort study fetal exposure to general anesthesia during cesarean delivery was not associated
with increased risk for learning disabilities compared to delivering vaginally . In contrast
in a population-based birth cohort study conducted in Taiwan the incidence of autism was
increased in neonates who were delivered by cesarean delivery under general anesthesia
compared with regional anesthesia .
Despite experts favoring neuraxial anesthesia for the preeclamptic population, to date
research remains inconclusive regarding which anesthetic method is neuroprotective.
In recent years numerous biochemical tests have become usual clinical cerebral damage
biomarkers, amongst them is the Neuron specific enolase (NSE). The NSE is an intracytoplasmic
glycolytic enzyme enolase . The enzyme is expressed in neurons and neuroendocrine tissue .
Increased levels of NSE are released into the blood circulation according to the death rate
of those cells . Elevated levels of NSE have been observed after severe head trauma and in
association to postoperative cognitive dysfunction .
S100B Protein, an additional neuronal injury biomarker, is an acidic calcium-binding protein,
and physiological serum levels of S100B protein are low . The protein is found primarily in
astrocytes and Schwann cells and has both intracellular and extracellular targets.
Elevated serum and CSF levels of S100B indicate neural damage . Research evaluating cerebral
damage biomarkers in parturients with preeclampsia has found increased levels of neuronal
injury biomarkers compared with healthy parturients . Furthermore increased plasma levels of
S100B have been correlated with neurological symptoms in the form of visual disturbances .
Lisa et al demonstrated persistent increased levels of NSE up to one year postpartum .
Additionally, various studies have examined the correlation between cerebral biomarkers
levels in umbilical cord blood, amniotic fluid and fetal pathological conditions: intra
uterine fetal death, preterm delivery, cerebral palsy and preeclampsia . Tskitishvili, et al
showed increased levels of cerebral injury damage in amniotic fluid of parturients with
preeclampsia .
In this study we aim to evaluate the effect of anesthetic method on neural outcomes in the
preeclamptic population undergoing cesarean delivery.
Specific Aims:
Our primary objective is to examine which anesthetic method (GA versus RA) is associated with
reduced neural damage as measured by NSE and S100B serum levels in preeclamptic parturients
undergoing cesarean delivery.
Our secondary objective is to examine the effect of anesthetic method on fetal cerebral
outcomes as measured by NSE and S100B umbilical cord blood levels in parturients with
preeclampsia.
Study Design:
This is a prospective, single center, observational trial to assess the effect of anesthetic
method on cerebral outcomes. The study will be conducted at the Rabin Medical Center
(Beilinson Campus), Petach Tikva, Israel, a tertiary university hospital.
Fifty preeclamptic parturients aged 18 and above, undergoing cesarean delivery under SA or
GA, will be included in the study.
This study is a purely observational study, it will not have any clinical intervention nor
will it interfere with standard cesarean delivery protocols in any way. Inclusion criteria
Fifty preeclamptic parturients age 18 and above presenting for cesarean delivery under SA or
GA, with ability to comply with study requirements will be enrolled in the study.
Exclusion criteria
The following parturients will be excluded:
1. Parturients under age 18
2. Parturients undergoing a vaginal delivery.
3. Parturients unable to sign an informed consent forum.
Study enrollment:
All preeclamptic parturients will be recruited upon admission to the women's emergency room.
All participating patients will undergo an informed consent process, which will include a
through explanation of the study design and patient requirements, by the study investigator.
Following which patients will be requested to sign the informed consent document.
Index procedure:
Following obtaining approval from parturients 5 cc of venous blood will be drawn from each of
the participants and will be examined for NSE and S100B serum levels at the following time
points:
1. Upon hospital admission following obtaining informed consent approval.
2. Upon fetal delivery, umbilical cord blood will be examined for NSE and S100B.
3. 1 day postpartum. The blood samples will be collected in heparin containing tubes, the
samples will be kept in room temperature for no longer than an hour before being sent to
the laboratory for centrifugation. Following centrifugation the samples will be frozen
at −70 °C until levels of NSE and S100B can be analyzed. Plasma levels will be tested to
detect NSE and S100B levels using commercially available kits (Liasion Sangtec 100)
according to the manufacturer's recommendations.
Intraoperative anesthetic technique will be administered at anesthesiologists' discretion.
The study cohort will be divided into two groups: women undergoing cesarean delivery under
general anesthesia, and women undergoing cesarean delivery under regional-spinal anesthesia.
NSE and S100B levels will be compared for both groups in order to evaluate which anesthetic
method is associated with reduced neuronal injury Additionally, umbilical cord blood NSE and
S100B levels will be compared for both groups, in order to assess the fetal outcomes of each
anesthetic method.
Data collection:
For each participant the following additional data will be collected and documented:
1. Demographic data obstetric age, weight, height,
2. Obstetric data; gravidity and parity, obstetric history comorbidities, regular
medication and preeclampsia management protocols and more.
3. Anesthetic and analgesic data: type of anesthesia / analgesia, anesthetic drug solution,
anesthetic drug doses, vasopressor treatment, hemodynamic data, and other anesthetic
data.
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