Feasibility and Pilot Study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) Project

Abstract

Background Animal studies have documented that exposure of the developing brain to commonly used anesthetic agents induce neurotoxicity and late abnormal neurobehavioral functions as adults. Results from clinical studies have all been performed using existing datasets, and produced inconsistent results. To provide more definitive evidence to address the clinical relevance of anesthetic neurotoxicity in children, an interdisciplinary team of investigators designed and developed the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project. We present pilot study results in 28 sibling pairs recruited and tested at Columbia University Medical Center (CUMC) and Children’s Hospital of Boston (CHB) for the PANDA project. Methods The PANDA project uses an ambi-directional cohort design. We performed prospective neuropsychological assessment in 28 exposed-unexposed sibling pairs ages 6–11 years old. The exposed siblings were ASA 1 or 2 and had received a single episode of anesthesia for inguinal hernia repair prior to age 36 months and the unexposed siblings had no anesthesia before age 36 months. All sibling pairs were English speaking and were 36 weeks gestational age or greater. Each sibling pair underwent direct testing using WASI and NEPSY II, and the parents completed questionnaires related to behavior using CBCL and Conners’ rating. Data are presented as means ± SD. We conducted descriptive analyses of demographic data. We compared exposed and unexposed sibling groups on WASI and NEPSY II, and total and T-scores from CBCL and Conners’ as continuous data by paired t test between. A P< 0.05 was considered significant. Results Following IRB approval for the study at both CUMC and CHB, the full PANDA study protocol was implemented to perform a pilot feasibility study. Our success rate was 96.7% in obtaining detailed medical and anesthesia records in our historical cohort. Scores for verbal IQ (Exposed=106.1±16.3,Unexposed=109.2±17.9), performance IQ (Exposed=109.1±16.0, Unexposed=113.9±15.9) and full IQ (Exposed=108.2±14.0, Unexposed=112.8±16.8) were comparable between siblings. There were no differences between the two groups in T scores for any of the NEPSY II sub-domains, CBCL or Conners’. An abstraction protocol with web-based electronic data capture forms also was developed in conjunction with the International Center for Health Outcomes and Innovation Research (InCHOIR). Conclusions The pilot study provided useful information for feasibility to recruit the sample size and to obtain relevant clinical data. For the final study protocol, both the neuropsychological battery and the age range for testing were revised. Our results confirmed the feasibility of our study approach, and yielded pilot data from neuropsychological testing.

Anesthesia and Apoptosis in the Developing Brain: An Update

“…They will be matched with an unexposed sibling from a retrospective database. Participants will be evaluated prospectively with an extensive neuropsychological battery between age 8 and 15 years [49]. The scale of the study, the presence of detailed information about anesthesia, and the extensive test battery will allow detailed analyses of the relationship between timing of anesthesia and neurocognitive deviation.…”

Anesthetic Neurotoxicity in Pediatric Patients

“…The third meeting in 2012 was atended by diferent disciplines, parents, clinicians, FDA workers, and patient's rights advocates. In this meeting, atendees agreed to collaborate on advanced preclinical, clinical, and translational studies [75,76]. Additionally in 2012, pediatric anesthesiologists and pediatric surgeons met to discuss the neurotoxicity risk of some elective procedures and anesthesia applications performed in children and speciically to discuss questions and concerns of parents.…”

Pediatric glaucoma: current perspectives

“…However, the possible anesthetic neurotoxicity concerns should be considered within the context of the high risk of blindness from glaucoma in children not adequately assessed or surgically managed. [11][12][13][14] EUAs performed solely to make the diagnosis prior to referral for surgery should be avoided; it is best that the ophthalmologist undertaking the initial EUA be capable of performing the definitive surgery under the same anesthetic, to avoid unnecessary anesthesia and a delay in treatment.…”