2010 MSARF Symposium Participants - Foundation for Anesthesia ...

anesthetics, the results of the present study suggest a novel strategy with which to minimize the potential for deleterious
consequences associated with the use of such anesthetics.
Student Name: Brian Ebert
Host Department: University of Utah
Primary Mentor Name: Harriet Hopf, MD
Additional Mentors: Sean Runnels, MD
Title of Research Project: Does the UU Butyrylcholinesterase genotype predict a normal clinical and biochemical
response to succinylcholine? A Model for Personalized Medicine in Anesthesia
Introduction: Personalized Medicine tailors treatment to genetic makeup, but has been little implemented in
anesthesiology. Butyrylcholinesterase (BChE), a plasma cholinesterase, metabolizes succinylcholine. The presence of
abnormal variants (A, S, K, etc.) results in prolonged neuromuscular blockade (NMB): moderate (20-40 min.) in ~1:300
individuals and profound (2-8 hrs.) in ~1:3000. Prediction of succinylcholine duration from an individual’s genome
would be a model for development of personalized medicine in anesthesiology. As a first step, we therefore examined
whether a UU (normal) BChE genotype predicts a normal clinical and biochemical response.
Methods: With IRB approval and informed consent, we enrolled 50 (of 200 planned) ASA 1-2 subjects undergoing GA
with intubation. Blood was collected prior to giving succinycholine (1mg/kg). Dibucaine Number (DN), activity (U/L)
and genotype were measured. NMB duration was measured using acceleromyography. DN, activity and genotype were
correlated with NMB duration.
Results: To date, 18/33 (55%) samples are UU. Median (range) NMB duration for UU was 8.0 (4 - 13.75) min. and for
UA (UAK) was 13.9 (6 - 14) min. DN was 85 for all UU samples, and lower for all other samples. BChE activity was
3763-6693 U/L and did not predict UU status.
Conclusions: NMB duration for the UU genotype is consistent. DN of 85 is highly predictive of UU genotype. Activity is
a poor predictor. Only 55% (18/33) of our samples were UU (82% were UU, UUK, or UK, despite a cited rated of 96%).
Future volunteer studies will evaluate rare genotypes.
Student Name: Steven Engel
Host Department: University of Miami Miller School of Medicine
Primary Mentor Name: Kenneth Proctor, MD
Additional Mentors: Chad Thorson, MD
Title of Research Project: BIS vs. RASS
In the inpatient critical care setting, both over and undersedation are common problems that lead to unfavorable outcomes.
Oversedated patients are at risk for increased days on the ventilator, prolonged hospital stays, and infections. Patients
who are inadequately sedated may require physical restraints due to attempts at self-extubation and/or removal of invasive
catheters. Numerous methods exist to measure the extent of sedation, and subjective sedation scales, including RASS
(Richmond Agitation and Sedation Scale), are the most commonly used. Subjective scales require frequent nursing
observations of patient’s reactivity to stimuli. Scores range from +4 in a combative patient to -5 in an unarousable state.
An objective tool for measuring sedation is the Bispectral Index (BIS), which is an objective number based on EEG and
EMG-derived parameters. A score of 100 corresponds to a fully functional awake patient, whereas 0 corresponds to a
brain dead patient. BIS has traditionally been used for tracking sedation in the operating room, but recent studies have
shown that BIS scores in the ICU correlate with subjective sedation scales. In this study, intubated trauma patients in the
ICU are randomly assigned to sedative monitoring with BIS or RASS. Sedative drugs are titrated to maintain a BIS score
of 60 to 80, or a RASS score of 0 to -2. The hypothesis is that a BIS-driven sedation will result in lower sedative drug
use, which may also lead to shorter ventilation time, less ICU associated infection, and decreased lengths of stay.
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