To determine if isoflurane anesthesia without surgery causes systemic inflammation in children. Inflammation is targeted as responsible for the development of many neurologic pathologies. The effect will be evaluated by measuring serum cytokine levels before and after isoflurane anesthesia. The possible neurotoxic effect of anesthetic agents is a concern in pediatric anesthesia. Questions remain as to the true effects of anesthesia alone on systemic inflammation. The current study assesses systemic inflammatory response to general anesthesia in children not exposed to surgical stress.
Twenty-five patients, aged 6 months to 11 years undergoing MRI scanning were recruited. Patients with ASA Physical Status Classification >II, known neurologic disease, prematurity, recent infection, or current treatment with anti-inflammatory medications were excluded. Each patient received a sevoflurane induction, peripheral intravenous catheterization, and laryngeal mask airway placement. Isoflurane was titrated to ensure adequate depth of anesthesia. Two peripheral blood samples were obtained: one immediately after placement of the PIV and one upon arrival to the post-anesthesia care unit. Serum cytokine levels were compared between pre- and post-isoflurane time points using paired t tests.
For all patients, interleukin-1β increased after isoflurane when compared to pre-isoflurane samples (pre = 25.97 ± 9.01, post = 38.53 ± 16.56, p = 0.0002). Serum levels of IL-6 (pre = 2.28 ± 2.27, post = 2.04 ± 2.15, p = 0.146) and tumor necrosis factor-α (pre = 94.26 ± 18.07, post = 85.84 ± 12.12, p = 0.057) were not significantly changed. Interleukin-10 and vascular endothelial growth factor were undetectable in pre- and post-isoflurane samples at a minimum detection threshold of 6.6 and 10 pg/ml, respectively.
A brief (approximately 60 min) exposure to isoflurane general anesthesia, without induced surgical stress, significantly increased serum IL-1β, a selective activation marker of systemic inflammation (IL-1β pathway).
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The authors wish to thank Dmitry Tumin for his invaluable contribution to biostatistical analysis. The authors are also grateful to the nurses and colleagues in the radiology department for their support and generosity.
This study was approved by the Nationwide Children’s Hospital IRB on 1/20/2015 (#IRB14-00625, NCT02512809).
This study was generously supported by departmental start-up funds (EW), a Nationwide Children’s Hospital Intramural Grant (EW), and the Ohio State University Center for Clinical and Translational Science Davis-Bremer Pre-K Award (EW). This work was also supported in part by the OSU College of Medicine Roessler research scholarship (BW, JX). EW is also supported by an NIH LRP Grant, funded by the NIH NICHD to investigate potential neurotoxicity mechanisms of anesthetics in a neonatal piglet model. FLC is supported by R01 DK093499.
Conflict of interest
The authors have no conflicts of interest to report.
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Whitaker, E.E., Christofi, F.L., Quinn, K.M. et al. Selective induction of IL-1β after a brief isoflurane anesthetic in children undergoing MRI examination. J Anesth 31, 219–224 (2017). https://doi.org/10.1007/s00540-016-2294-y
- Pediatric anesthesia
- Anesthesia-induced developmental neurotoxicity (AIDN)