This Mentored Patient-Oriented Research Career Development Award (K23) is a resubmission by a new investigator. It will provide the candidate (a pediatric anesthesiologist, with previous research experience focusing on the perioperative complications of obesity), the training needed to establish a program of research related to understanding how key clinical and biological factors (i.e. high body mass index and perioperative systemic inflammatory markers) impact post-tonsillectomy pain outcomes in children. The comprehensive career development plan has three primary components: 1) structured coursework and seminars in the applicant's area of interest as well as biostatistics and research design; 2) mentorship utilizing in-house internationally known experts in clinical pain, obesity and inflammation research; and 3) a specific prospective clinical study that will serve as a vehicle for training in the conduct of randomized controlled study as well as an opportunity to gain comprehensive experience in the pathobiology of inflammation and obesity. The candidate will take advantage of particularly strong institutional resources in obesity and pain research. Tonsillectomy adenoidectomy (T&A) remains one of the most common surgical procedures in children. Unfortunately, despite advances in anesthetic and surgical techniques, post-tonsillectomy pain (PTP) remains a significant problem affecting up to 62% of children. The mainstay of treatment of PTP is opioids. Systemic corticosteroids are routinely given to reduce postoperative nausea and vomiting (PONV) and they are also showing promise in reducing PTP severity. However, the role of corticosteroids in reducing early PTP has not been fully characterized. Reducing early PTP can improve the entire perioperative experience. In addition to treatment of PTP, risk factors for pediatric PTP have not been fully delineated. Recent data suggests that obesity in adults is associated with poor postoperative pain experience and we, through a retrospective study, recently showed that childhood obesity is indeed a risk factor for moderate/severe early PTP. We therefore propose to, through a randomized controlled study, assess the effect of a single preoperative dose of oral dexamethasone (0.25mg/kg up to a maximum of 10mg) given the night before surgery on early PTP (pain occurring within the first postoperative hour) in children. We further seek to systematically explore the association of body mass index (BMI) with postoperative pain experience in children undergoing elective T&A. Additionally, as a potential mechanistic link between obesity and PTP, we will determine whether overweight/obese children undergoing T&A have higher levels of systemic inflammatory markers than their lean peers and whether increased systemic pro-inflammatory burden correlates with PTP. If we find that use of preoperative modulation of inflammation with corticosteroids decreases PTP, this could decrease the need for rescue opioid administration in the early postoperative period, which could in turn reduce the risk of opioid-induced respiratory depression.
Public Health significance: Post-tonsillectomy pain (PTP) remains an important challenge and it causes unnecessary suffering in children. Early PTP (occurring upon emergence from anesthesia) can be quite distressing and blemish the entire perioperative experience for children and their parents. Establishing whether a single preoperative dose of oral dexamethasone could significantly reduce the severity of early PTP could lead to a paradigm shift in the management of pain associated with T&A. Furthermore, determining both whether PTP is worsened by obesity, as well as why this occurs, will facilitate the development of 'personalized analgesic' regimens for different children undergoing tonsillectomy, and this information would be expected to be transferable to other pediatric surgical procedures.
