Alyssa Burgart (Presenter)
Stanford University
Bio: Dr. Alyssa Burgart is a pediatric anesthesiologist at Stanford University and Lucile Packard Children's Hospital.
Authorship: Alyssa Burgart (1), Brian Rappold (2)
(1) Stanford University, (2) Essential Testing
| Short Abstract There are gaps in information during surgical procedures in which the promise of mass spectrometric analysis can provide surgeons and anesthesiologists with perhaps their most powerful tool: actionable information. This talk is an invitation to MS practitioners to think outside the laboratory to explore the potential applications of MS in the operating room, from simple sedation cases to organ transplantation. Promising research on these techniques is already in development and this talk will serve to address potential future, wide use application. |
Long Abstract
The use of mass spectrometry (MS) in clinical laboratories has grown significantly in recent years, and in some cases, is the certified reference methodology for clinical measurement. As the technology has become more prevalent, attempts at bringing the laboratory bench to the bedside have garnished interest. The use of intra-operative mass spectrometry is an example of direct measurement of biomarkers during surgery to assist physicians in making more informed decisions. However, mass spectrometry in the surgical theater should not be limited to the identification of cancerous versus non-cancerous tissue during resection. This presentation will introduce gaps in information during surgical procedures in which the promise of mass spectrometric analysis can provide surgeons and anesthesiologists with perhaps their most powerful tool: actionable information.
Millions of people undergo procedures requiring anesthesia every year. The real-time monitoring capabilities of general biomarkers, such as heart rate and rhythm, blood pressure, oxygen levels, etc., have provided mechanisms to evaluate patient status, decreasing adverse event occurrences. The introduction of continuous end-tidal carbon dioxide monitoring was one of the most important and indispensible improvements in standard patient monitoring. These measurements, however, are not enough. The practice of medicine is both science and art, but without reliable science, the art produced is poor. To a great degree, anesthesiologists make a number of educated guesses in the provision of patient care. The currently available biomarkers are combined to provide surrogates for the information surgeons truly want to confirm – analgesia, anesthesia, sufficient cerebral perfusion, liver and kidney function, etc. To what degree are these educated guesses impacting long-term patient outcomes? What can MS provide to the operating room to improve morbidity-free survival?
The real-time analysis of more difficult-to-measure compounds could provide improved confidence in medication levels provided to achieve appropriate anesthesia beyond the current “educated guess” model. In an ideal world, we would assess patient’s metabolic profiles pre-operatively to determine if our standard medications and standard doses are safe in the individual. Volatile agents, such as sevoflurane, have been measured in end-tidal concentrations for many decades and there is a known minimum alveolar concentration (MAC) necessary to reliably prevent patient awareness and movement. The use of total intravenous anesthesia (TIVA) has gained popularity, but there is currently no reliable way to determine that the plane of anesthesia is adequate in a prospective manner. Anesthesiologists use experience as a guide to determine which patients are likely to have pharmacokinetic profiles that deviate from the “norm”. Further complicating matters, metabolic inducing medications, such as the anti-epileptics carbamazepine or phenytoin, can drastically modify the metabolism of commonly utilized anesthetic agents such as fentanyl, propofol and rocuronium. Combining techniques such as processed EEGs with real-time pharmacokinetic profiles of these agents, or directly measured drug concentrations longitudinally during the provision of anesthesia has the potential to greatly enhance the margin of safety for patient’s undergoing TIVA (1). Such technologies can help to ensure that the necessary concentrations are provided to achieve both suitable anesthesia and analgesia, and avoid both under- and overdosing. Recent technological advances, such as paper-spray mass spectrometry and Membrane-Introduction Mass Spectrometry (MIMS), show the promise of real time analysis to provide such information.
Solid organ transplantation is another arena where MS could revolutionize care. A variety of biomarkers could be utilized to improve early decision making related to acute rejection or to determine the onset of other complications, such as hepatic artery thrombosis in liver transplantation. After the new organ is reperfused, it is often unclear to what degree organ function has returned (2). What biomarkers could predict acute cellular rejection, graft thrombosis, and other devastating complications? A similar need is found in kidney transplant procedures, where the sequential monitoring of urinary biomarkers peri- and post-reperfusion could provide direct evidence for graft function. In assessing patients for graft rejection in the post-operative period, the gold standard includes a biopsy of the organ. The development of non-invasive assays to quantify organ rejection could reduce significant risk to patients while still providing reliable clinical data (3).
This talk is an invitation to MS practitioners to think outside the laboratory to explore the potential day-to-day applications of MS in the operating room, from simple sedation cases to organ transplantation. An introduction to concepts related to surgical techniques currently utilized and how those techniques might be augmented by high-fidelity assays for utilization in the operating room to facilitate safe decision-making in clinically challenging settings. Promising research on these techniques is already in development and this talk will serve to address potential future, wide use application. A discussion of the mechanisms for sampling from appropriate matrices will included, as will the utilization of quantitation techniques (i.e. direct ratio via stable labeled isotopic internal standards).
References & Acknowledgements:
1. Cherebillo VY, Elizarov AY, Polegaev AV. Membrane-Introduction Mass Spectrometry Analysis of Desflurane, Propofol and Fentanyl in Plasma and Cerebrospinal Fluid for Estimation BBB Properties. Exp Neurobiol. 2015 Sep;24(3):206-210. http://dx.doi.org.laneproxy.stanford.edu/10.5607/en.2015.24.3.206
2. Fernández del Río R, O’Hara ME, Holt A, et al. Volatile Biomarkers in Breath Associated With Liver Cirrhosis — Comparisons of Pre- and Post-liver Transplant Breath Samples. EBioMedicine. 2015;2(9):1243-1250. doi:10.1016/j.ebiom.2015.07.027.
3. Berenguer, M. Non-invasive biomarkers of liver fibrosis in liver transplant patients with hepatitis C: Can we avoid liver biopsies?. Digestive and Liver Disease, Volume 41, Issue 3, 226 – 228.
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