Electroencephalographic Effects of Spinal Anaesthesia During Caesarean Delivery in Preeclampsia

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.

Study Overview

• Status: Unknown
• Conditions: Pre-Eclampsia; Effects of; Anesthesia, Spinal and Epidural, in Pregnancy
• Intervention / Treatment: Device: EEG measure

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.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pascal H Vuilleumier, MD; Phone Number: +41 31 632 32 84; Email: pascal.vuilleumier@insel.ch
• Study Contact Backup: Name: Heiko Kaiser, MD; Phone Number: +41 31 632 21 11; Email: heiko.kaiser@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control Group; EEG measure in 15 healthy women undergoing elective hysteroscopy under single shot spinal anesthesia. Bupivacaine 10mg (+-2mg) spinal dose with 15 mcg Fentanyl spinal dose	Device: EEG measure; Frontal 3-derivation EEG measure under different conditions in pregnancy (healthy vs preeclampsia) and baseline non-pregnant women
ACTIVE_COMPARATOR: Healthy parturients; EEG measure in 15 healthy parturients undergoing elective cesarean delivery under single shot spinal anesthesia.Bupivacaine 10mg (+-2mg) spinal dose with 15 mcg Fentanyl spinal dose	Device: EEG measure; Frontal 3-derivation EEG measure under different conditions in pregnancy (healthy vs preeclampsia) and baseline non-pregnant women
ACTIVE_COMPARATOR: Preeclamptic parturients; EEG measure in 15 parturients with preeclampsia undergoing elective cesarean delivery under single shot spinal anesthesia.Bupivacaine 10mg (+-2mg) spinal dose with 15 mcg Fentanyl spinal dose	Device: EEG measure; Frontal 3-derivation EEG measure under different conditions in pregnancy (healthy vs preeclampsia) and baseline non-pregnant women

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spectral analysis through fast Fourier transformation	Change from baseline EEG, EEG after one and 60 minutes after neuraxial anaesthesia	Baseline, one minute and 60 minutes, 5 minutes for each measure
Spectral analysis of the detection of seizure activity by absolute slope analysis (composite endpoint)	Change from baseline EEG, EEG after one and 60 minutes after neuraxial anaesthesia	Baseline, one minute and 60 minutes, 5 minutes for each measure

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: University of Cape Town; National Council of Scientific and Technical Research, Argentina
• Investigators: Study Chair: Heiko Kaiser, MD, Bern University Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2019
• Primary Completion (ANTICIPATED): December 31, 2019
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: April 12, 2019
• First Posted (ACTUAL): April 17, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 17, 2019
• Last Update Submitted That Met QC Criteria: April 12, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia
• Other Study ID Numbers: 20190123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No