Analgesic-Behavioral and Neurophysiological Correlates of Opioid-Sparing Spinal Anesthesia Compared to General Anesthesia in Human Infants

PROJECT SUMMARY/ABSTRACT Each year, approximately 6 million children receive anesthesia in the United States alone. The ongoing opioid epidemic has forced the medical community to examine how it uses opioids for pain management. There is now evidence that early life exposure to opioids is associated with greater sensitivity to pain, adverse long-term ef- fects on physiology, cognition, motors skills and behavior, higher opioid requirements for pain control, and higher risk of persistent opioid use. Accordingly, opioid-sparing anesthetic and analgesic regimens are being investi- gated intensely. For infants in particular, spinal anesthetics are able to provide analgesia without opioids while further inducing a sedated brain state, unlike adults who require co-administration of traditional sedative-hypnotic agents to blunt awareness. The neurological basis underlying this clinical observation is not fully understood and we have begun to collect pilot data to help further clarify these properties. My mentorship team and I are now well-positioned in this K23 Mentored Patient-Oriented Research Career Development Award application to rig- orously and reproducibly investigate the acute effects of early opioid exposure in the brain and its potential long- term impact on development, with comparison to opioid-sparing spinal anesthesia. I began assembling an an- esthesia electroencephalogram (EEG) dataset beginning in 2016 - with a sample size to date now consisting of 143 subjects with a median age of 7 months that continues to grow. Our preliminary data demonstrate that a hallmark of spinal anesthesia appears to be the sleep spindle complex, which resembles normal physiologic sleep that is distinct from general anesthetic (GA) effects that employ opioids. I have a unique opportunity to address critical gaps in knowledge of the effects of early anesthesia on the brain with additional K23-support to continue the subject recruitment and mentored research training activities necessary to analyze the entire EEG dataset. This work, which we have already demonstrated is feasible, will further contribute to fundamental dis- covery of the analgesic-behavioral and neurophysiological correlates of opioids vs. opioid-sparing alternatives, with the following aims: (1) prospective quantification of analgesic-behavioral and neurophysiological correlates of infant spinal anesthesia in 100 subjects, (2) comparison of neurophysiological properties of infants receiving spinal anesthesia compared to 100 infants of similar age in normal physiologic sleep and 200 infants undergoing similar surgeries receiving general anesthesia, and (3) comparison of clinical and behavioral outcomes between infants undergoing similar surgeries under spinal (n=100) versus general anesthesia (n=200). The research en- vironment at Montefiore-Einstein is exceptional and my team of mentors has the expertise to guide me in rigorous assessments of early anesthetic effects on the brain. My training plan is specifically designed to develop my skills in clinical study design, data science, developmental neuroscience, and neural data analysis. By the com- pletion of the career development award, I will have successfully applied for R01-level funding and will be ready to transition to a fully independent clinician-investigator dedicated to improving anesthesia care in children.
Public Health Relevance Statement