Clinical trial NCT03917342: Electroencephalographic Effects of Spinal Anaesthesia During Caesarean Delivery in Preeclampsia
Official title: Electroencephalographic Effects of Spinal Anaesthesia During Caesarean Delivery in Preeclampsia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pre-Eclampsia
Effects of; Anesthesia, Spinal and Epidural, in Pregnancy
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: National Council of Scientific and Technical Research, Argentina
name: University of Cape Town
First posted: 2019-04-17
Enrollment: 45
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three groups of subjects studied: A: Control group: 15 healthy women B: 15 Healthy parturients: elective cesarean delivery C: 15 preeclamptic parturients: cesarean delivery
Primary purpose: BASIC_SCIENCE

Brief summary: Neuraxial anesthesia has been associated with delayed brainstem conduction and decreasing afferent sensory transmission, thereby modifying reticulo-thalamo-cortical mechanisms regulating arousal. The state of entropy measured by EEG-monitors has detected sedative effects associated with neuraxial anaesthesia in healthy volunteers, as well as during caesarean delivery. Entropy is a measure of the irregularity or disorder of a brains activity - sedation leading to a decrease of irregularity or disorder in the EEG.The aim of this pilot study is to prospectively assess the effect of spinal anaesthesia in healthy and preeclamptic parturients on brain activity. Decreased epileptiform activity in patients with preeclampsia would suggest that early neuraxial analgesia in labouring preeclamptic patients is beneficial, and may protect against neurological complications.

Detailed description: Neuraxial anesthesia has been associated with delayed brainstem conduction and decreasing afferent sensory transmission, thereby modifying reticulo-thalamo-cortical mechanisms regulating arousal. The state of entropy measured by EEG-monitors has detected sedative effects associated with neuraxial anaesthesia in healthy volunteers, as well as during caesarean delivery. Entropy is a measure of the irregularity or disorder of a brains activity - sedation leading to a decrease of irregularity or disorder in the EEG.

The EEG activity in general can be separated into background activity, focal abnormalities, and intermittent and paroxysmal activity.8 Background electrical activity measured with the EEG by surface electrodes, are characterized by their corresponding frequency wave bands, ranging from slow waves (\< 1 Hz), Delta (1 - 4 Hz), Theta (4 - 8 Hz), Alpha (8 - 12 Hz), Beta (12 - 30 Hz) and Gamma (\> 30 Hz). In healthy volunteers, neuraxial anaesthesia was linked to increased activity - the so-called state of paradoxical excitation. This pattern is similar to the sedative low-dose GABAergic effects known to occur in response to the benzodiazepine midazolam. Epileptic potentials as paroxysmal EEG activity are typically seen with seizures, but they can be a sign of other changes of brain state as well (e.g. (pre)eclampsia or high doses of opioids).

Preeclampsia constitutes a heterogeneous multisystemic disorder defined by the new onset of hypertension and proteinuria after 20 weeks of gestation, affecting 2-8 % of all pregnancies world-wide. In this condition the nervous system is commonly affected, being the cause of significant morbidity and mortality, when seizures occur resembling an epileptic grand-mal convulsion. Significantly, cerebral white matter lesions are described several years after eclamptic episodes. Posterior reversible encephalopathy syndrome (PRES) is also suggested to be a core component of eclampsia. In this condition is associated extensive white matter changes have been detected, using advanced neuroimaging techniques. EEG changes can be detected before clinical signs of PRES are present, and before ischemia leads to irreversible brain damage.14 In preeclampsia EEG changes are also common, consisting of slow waves in the occipital lobe, as well as spike discharges. These EEG changes have been reported in eclampsia and in severe preeclampsia, with some differences between the two conditions. The prevention of eclampsia, which can occur pre-, intra-, or postpartum, is thus a critical management goal. Current literature only describes the use of EEG entropy - reflecting the state of arousal - during neuraxial anaesthesia in parturients. So far no study has assessed the quantitative (qEEG) or paroxysmal EEG changes induced by neuraxial anaesthesia in parturients undergoing caesarean delivery, and such monitoring has particular relevance in a high-risk patient population with preeclampsia.

Aims

The aim of this pilot study is to prospectively assess the effect of spinal anaesthesia in healthy and preeclamptic parturients on brain activity. Decreased epileptiform activity in patients with preeclampsia would suggest that early neuraxial analgesia in labouring preeclamptic patients is beneficial, and may protect against neurological complications.

Eligibility criteria: Inclusion Criteria:

* Group A: Healthy controls, American Society of Anesthesiology (ASA) I or II status, undergoing a hysteroscopic procedure under single shot spinal anaesthesia without intravenous or oral sedation.
* Group B:

  * Healthy ASA I or II status patients undergoing elective caesarean section at term (\>37 weeks of gestation) under spinal single shot anaesthesia without intravenous or oral sedation.
  * Singleton pregnancy.
* Group C:

  * ASA I, II or III status patients undergoing elective secondary caesarean section at term (\>37 weeks of gestation) under spinal single shot anaesthesia without intravenous or oral sedation
  * Singleton pregnancy
* Diagnosis of preeclampsia: Systolic blood pressure over140 mmHg or diastolic pressure over 90 mmHg and
* Proteinuria over 0.3 grams in a 24-hour urine or protein: creatinine ratio superior to 0.3 or signs of end-organ dysfunction (platelet count \< 100,000 µL, serum creatinine \>110 mg/L, or doubling of the serum creatinine, elevated serum transaminases to twice normal concentration)

Exclusion Criteria:

* Patient refusal.
* Active labour.
* Eclampsia.
* Hypertensive crisis as defined by systolic blood pressure over 210 mmHg or diastolic pressure over 120 mmHg.
* Known epilepsy.
* Anti-epileptic medication and magnesium sulphate.
* Reported or admitted medication or substance abuse (street drugs, opiates, benzodiazepines, alcohol).
* Known neurological condition with previously pathologic diagnostic imaging or EEG.
* Severe fetal malformations (gastroschisis and omphalocele, tracheo-oesophageal fistula, cerebral malformations in the category of cephalic disorders, pulmonary hypoplasia, congenital heart disease).
* Established rupture of membranes prior to spinal anaesthesia.
* Non-German and non-French speaking parturient.
* Lack of written consent

Primary outcomes:
measure: Spectral analysis through fast Fourier transformation
timeFrame: Baseline, one minute and 60 minutes, 5 minutes for each measure
measure: Spectral analysis of the detection of seizure activity by absolute slope analysis (composite endpoint)
timeFrame: Baseline, one minute and 60 minutes, 5 minutes for each measure
Secondary outcomes:
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Bern University Hospital
Study officials:
affiliation: Bern University Hospital
name: Heiko Kaiser, MD
role: STUDY_CHAIR
References: