Almas Iqbal, Huma Saleem, Romana Shaida Durrani.
Tolerance development in children undergoing repeated exposure to anesthesia drugs for radiation therapy.
Anesth Pain Intens Care Jan ;24(5):515-20.

Background & Objectives: Radiation therapy is one of the modalities used in cancer treatment to destroy rapidly growing tumor mass. The fractionated radiation session targets up to four fields of 90 sec each, over 10-15 min. Young children require deep sedation or general anesthesia to make them immobile, for the safe delivery of radiation fractions. Common drugs used for sedation are propofol, ketamine and midazolam. Repeated exposure to anesthetic drugs over a short period of time may lead to development of tolerance and increased dose requirements. We aimed to determine if drug tolerance phenomenon develops in children receiving frequent doses of anesthetic drugs over a short time period.  Methodology: This is a retrospective observational study of the pediatric population who underwent frequent radiotherapy sessions with deep sedation from January to May 2019. The data of the first and last day of drugs administered was analyzed to determine if the dose requirement for any of the three drugs increased over time. Results: We collected data of twenty-one patients and applied two tailed student’s t-test on the mean dose of drugs on the first day and the last day of the treatment. It remained unchanged with insignificant p value (propofol p = 0.15; midazolam p = 0.5; ketamine p = 0.32). To minimize the drug augmenting each other’s effect, multilinear regression analysis of the drugs over the time period showed that there was neither an increase nor a decrease in the doses used (αi- propofol coefficient 0.019 ± 0.053; βi- midazolam coefficient -0.002 ± 0.007; γi- ketamine coefficient 0.049 ± 0.218)). The overall duration of the recovery time was not different from the first to the last day of radiotherapy. Conclusion: Frequent and repeated doses of sedative drugs over a short period of time in children undergoing repeated deep sedation for radiation therapy, do not result in the development of tolerance. 

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