Overview
A glioma is a primary brain tumor in adults that is characterized by a highly variable, but overall poor survival. The optimal timing of treatment is in part determined by the expected biological behavior of the tumor. At present the expected biological behavior, determined by the tumor genotype, can only be determined by tissue analysis, which requires brain surgery. Non-invasive and improved diagnostic methods are sought to obtain insight into the molecular profile of the tumor and the expected biological behavior to avoid surgery performed solely for diagnostic purposes. Vascularization is an important aspect of the biological behavior of a primary brain tumor. Tumor vascularization characteristics can be assessed by Magnetic Resonance Imaging (MRI), but with the currently available technology this can only be achieved with unacceptably long scan times. In this proposal, the investigators will develop and optimize a novel MRI protocol to gather a large set of quantitative vascularization parameters within an acceptable scan time. The hypothesis is that from such a 'vascular signature' the tumor genotype can be inferred by means of machine learning.
Description
Background and Rationale Spinal anesthesia-induced hypotension is the most common hemodynamic complication in obstetric anesthesia, with reported incidence rates ranging from 50% to 80% in parturients undergoing elective cesarean section. The underlying pathophysiology involves sympathetic blockade-mediated arteriolar and venous vasodilation, resulting in decreased systemic vascular resistance and reduced venous return, further compounded by aortocaval compression exerted by the gravid uterus.
Current prophylactic strategies including left uterine displacement, fluid co-loading, and vasopressor infusion remain the standard of care. However, these pharmacological approaches may be associated with tachycardia, hypertension, and inter-individual response variability, underscoring the need for complementary non-pharmacological interventions.
Preoperative anxiety exerts measurable effects on autonomic nervous system balance, potentially amplifying sympathetic tone and increasing hemodynamic instability following neuraxial blockade. Slow, controlled breathing exercises have been shown to enhance baroreflex sensitivity and augment parasympathetic vagal activity, suggesting that a brief mindfulness-based breathing intervention may attenuate sympathetic hyperactivity through an "autonomic preconditioning" mechanism.
Randomization and Allocation Concealment Participants will be randomized in a 1:1 ratio using a computer-generated random number sequence. Allocation concealment will be ensured through sequentially numbered, opaque, sealed envelopes (SNOSE), opened only after the patient has been transferred to the operating room and immediately before spinal anesthesia induction.
Intervention Protocol Participants in the intervention arm will receive a 5-minute guided mindfulness-based breathing exercise prior to spinal anesthesia, consisting of slow diaphragmatic breathing at approximately 6 breaths per minute (4-second nasal inhalation, 6-second oral exhalation). During each exhalation, participants silently repeat: "My body is relaxing as I exhale."
Anesthesia Management All participants will receive spinal anesthesia in the sitting position with intrathecal administration of 11.2 mg hyperbaric bupivacaine + 15 mcg fentanyl + 150 mcg morphine. Hypotension will be defined as a decrease in systolic arterial pressure (SAP) exceeding 20% from baseline and treated with norepinephrine or ephedrine. Bradycardia will be defined as heart rate ≤50 bpm and treated with intravenous atropine (1 mg).
Statistical Analysis All analyses will be performed using IBM SPSS Statistics (Statistical Package for the Social Sciences) version 20. Normality will be assessed using Shapiro-Wilk and Kolmogorov-Smirnov tests. Between-group comparisons will be performed using independent samples t-test or Mann-Whitney U test as appropriate. Categorical variables will be compared using chi-square test. Statistical significance will be set at p\<0.05.
Sample Size Sample size was calculated using G\*Power 3.1.9.7 software. A clinically meaningful difference of 4.5 mmHg in maximum SAP decrease (effect size = 0.48) was determined to require 70 participants per group at 80% power and 95% confidence level. Accounting for potential dropout, 150 participants (75 per group) will be enrolled.
Eligibility
Inclusion Criteria:
Pregnant women aged 18-45 years Singleton pregnancy Gestational age 37 weeks or greater American Society of Anesthesiologists (ASA) physical status classification II Scheduled for elective cesarean section under spinal anesthesia Body mass index (BMI) 35 kg/m2 or less Ability to comprehend verbal instructions and perform the breathing exercise Provision of written informed consent
Exclusion Criteria:
Emergency cesarean section Hypertensive disorders of pregnancy (gestational hypertension, preeclampsia, eclampsia, HELLP syndrome) Placenta previa, placental abruption, or active antepartum hemorrhage Multiple pregnancy Contraindications to spinal anesthesia Failed spinal anesthesia requiring conversion to general anesthesia Chronic hypertension or chronic hypotension Known cardiac disease (arrhythmia, valvular disease, cardiomyopathy) Diabetes mellitus with autonomic neuropathy Thyroid dysfunction Chronic pulmonary disease potentially affecting respiratory pattern Body mass index greater than 35 kg/m2 Regular use of beta-blockers, calcium channel blockers, alpha-agonists, or alpha-antagonists Regular use of anxiolytics, antidepressants, sedatives, or chronic opioids Diagnosed anxiety disorder, panic disorder, major depressive disorder, or other psychiatric illness Regular use of psychiatric medications Cognitive impairment or communication difficulties Attention or compliance problems precluding adequate performance of the breathing exercise Prior regular practice of meditation, yoga, or mindfulness-based training
