Pain Management in Pediatric Burn Patients: Review of Recent Literature and Future Directions.

Childhood burns are a profoundly traumatic and painful experience. Despite recognition of the prevalence of burn injuries in children and the severity of the associated pain, burn pain remains undertreated. At the same time, more evidence is emerging to suggest that undertreated pain has serious long-term medical and psychiatric consequences, many of which can be ameliorated with improved pain control. Pain in burn patients is, however, notoriously difficult to treat, perhaps because there is a chronic pain aspect underlying the acute pain that accompanies wound care and procedures. This difficulty is compounded by the fact that there are little data to guide decision making in these patients. This article aims to identify the best strategies to guide clinical practice through a review of the past 10 years' development in pediatric burn pain management. However, because clinical investigations remain limited in burned children, we also aim to draw attention to those areas where the data do not identify an optimal approach and further work is needed. Overall, in addition to just the traditional pharmacological approaches to pain, such as acetaminophen, benzodiazepines, and opioids, there is growing evidence to support more widespread use of regional anesthesia and novel technologies such as virtual reality. Starting with an improved understanding of the current state of the literature, we can identify areas of research and important questions whose answers will ultimately improve care and reduce suffering for this unfortunate population of children.

High vascular delivery of EGF, but low receptor binding rate is observed in AsPC-1 tumors as compared to normal pancreas.

PURPOSE: Cellular receptor targeted imaging agents present the potential to target extracellular molecular expression in cancerous lesions; however, the image contrast in vivo does not reflect the magnitude of overexpression expected from in vitro data. Here, the in vivo delivery and binding kinetics of epidermal growth factor receptor (EGFR) was determined for normal pancreas and AsPC-1 orthotopic pancreatic tumors known to overexpress EGFR. PROCEDURES: EGFR in orthotopic xenograft AsPC-1 tumors was targeted with epidermal growth factor (EGF) conjugated with IRDye800CW. The transfer rate constants (k(e), K12, k21, k23, and k32) associated with a three-compartment model describing the vascular delivery, leakage rate and binding of targeted agents were determined experimentally. The plasma excretion rate, k (e), was determined from extracted blood plasma samples. K12, k21, and k32 were determined from ex vivo tissue washing studies at time points ≥ 24 h. The measured in vivo uptake of IRDye800CW-EGF and a non-targeted tracer dye, IRDye700DX-carboxylate, injected simultaneously was used to determined k23. RESULTS: The vascular exchange of IRDye800CW-EGF in the orthotopic tumor (K12 and k21) was higher than in the AsPC-1 tumor as compared to normal pancreas, suggesting that more targeted agent can be taken up in tumor tissue. However, the cellular associated (binding) rate constant (k23) was slightly lower for AsPC-1 pancreatic tumor (4.1 × 10(-4) s(-1)) than the normal pancreas (5.5 × 10(-4) s(-1)), implying that less binding is occurring. CONCLUSIONS: Higher vascular delivery but low cellular association in the AsPC-1 tumor compared to the normal pancreas may be indicative of low receptor density due to low cellular content. This attribute of the AsPC-1 tumor may indicate one contributing cause of the difficulty in treating pancreatic tumors with cellular targeted agents.