1. Anesthesia Considerations
for Neurophysiologic Monitoring using the ProPep Nerve Monitoring System™ during
da Vinci® Prostatectomy
Because the ProPep Nerve Monitoring System is measuring stimulated electromyographic (EMG) signals emanating from the
muscles in which the nerves of interest terminate, it is important the muscles not be paralyzed during that portion of the surgery
when neurophysiologic monitoring is being performed. As a result, there are a number of anesthesia considerations that need to
be kept in mind to optimize the validity and quality of the neurophysiologic readings. Please note that all decisions regarding
anesthesia are the responsibility of the attending licensed medical practitioner administering anesthesia. It is important that the
surgeon discuss these issues preoperatively with the attending licensed medical practitioner administering the anesthesia.
Caution: The use of paralyzing anesthetic agents will significantly reduce, if not completely eliminate, EMG responses
to direct or passive nerve stimulation. Whenever nerve paralysis is suspected, consult the attending licensed medical
practitioner administering the anesthesia.
Before the Start of the Surgery:
- A conversation between the Surgeon and the attending medical practitioner administering the anesthesia should take
place to discuss:
o At what point during the surgery will the monitoring occur;
o How will the physician alert the medical practitioner administering the anesthesia that the portion of the case
requiring monitoring is approaching and how much lead time would the medical practitioner administering the
anesthesia like to be given.
This is important information that will allow the medical practitioner administering the anesthesia to
ensure the muscle relaxants have worn off adequately so that the surgeon can obtain the best
opportunity for recording useful and valid responses during the monitoring process.
During The Surgery:
- Only short acting muscle relaxants should be used.
- Muscle relaxants should be dosed incrementally.
o The goal is to keep the patient at 3-2 well defined twitches during the neurophysiologic monitoring.
- The surgeon will communicate with the medical practitioner administering the anesthesia when they are approximately
20 minutes (or the previously agreed upon time) away from performing the neurophysiologic monitoring.
o This will allow adequate time for the neuromuscular blockade to wear off sufficiently giving the surgeon the
best opportunity for optimal responses during the monitoring process.
Additional Considerations:
- The medical practitioner administering the anesthesia should be prepared to use pressure control ventilation as a
means to improve the ability to ventilate the patient when they are becoming “light” on muscle relaxants.
- During the period of reduced neuromuscular blockade, the stability of the surgical view for the operating surgeon can
be improved by reducing the drive to breath using:
o over-ventilation to reduce CO2
o narcotics.
ProPep Surgical wishes to thank Dr. Paul Playfair - Chief of Anesthesia at Westlake Medical Center – Austin, TX for his
contributions to this protocol.
References: Attached you will find references that address anesthesia considerations during neurophysiologic monitoring in
more depth. Please refer to the highlighted sections for considerations specific to the mode of neurophysiologic monitoring the
ProPep Nerve Monitoring System employs.
V2.1_12 April 2012
4. Contents
Preface ..................................................................................................................................... v
Acknowledgments ..................................................................................................................vii
1 Introduction ..................................................................................................................... 1
SECTION I: PRINCIPLES OF INTRAOPERATIVE NEUROPHYSIOLOGICAL MONITORING
2 Basis of Intraoperative Neurophysiological Monitoring .................................................. 9
3 Generation of Electrical Activity in the Nervous System and Muscles .......................... 21
4 Practical Aspects of Recording Evoked Activity From Nerves,
Fiber Tracts, and Nuclei ............................................................................................ 39
References to Section I .......................................................................................................... 49
SECTION II: SENSORY SYSTEMS
5 Anatomy and Physiology of Sensory Systems ................................................................ 55
6 Monitoring Auditory Evoked Potentials ......................................................................... 85
7 Monitoring of Somatosensory Evoked Potentials ......................................................... 125
8 Monitoring of Visual Evoked Potentials ....................................................................... 145
References to Section II ....................................................................................................... 147
SECTION III: MOTOR SYSTEMS
9 Anatomy and Physiology of Motor Systems ............................................................... 157
10 Practical Aspects of Monitoring Spinal Motor Systems ............................................... 179
11 Practical Aspects of Monitoring Cranial Motor Nerves ............................................... 197
References to Section III ...................................................................................................... 213
SECTION IV: PERIPHERAL NERVES
12 Anatomy and Physiology of Peripheral Nerves ........................................................... 221
13 Practical Aspects of Monitoring Peripheral Nerves ..................................................... 229
References to Section IV ..................................................................................................... 233
SECTION V: INTRAOPERATIVE RECORDINGS THAT CAN GUIDE THE SURGEON IN THE OPERATION
14 Identification of Specific Neural Tissue ....................................................................... 237
15 Intraoperative Diagnosis and Guide in Operations ..................................................... 251
References to Section V ...................................................................................................... 273
ix
5. x Contents
SECTION VI: PRACTICAL ASPECTS OF ELECTROPHYSIOLOGICAL RECORDING IN THE OPERATING ROOM
16 Anesthesia and Its Constraints in Monitoring Motor and Sensory Systems ................. 279
17 General Considerations About Intraoperative Neurophysiological Monitoring .......... 283
18 Equipment, Recording Techniques, Data Analysis, and Stimulation ........................... 299
19 Evaluating the Benefits of Intraoperative Neurophysiological Monitoring .................. 329
References to Section VI ..................................................................................................... 339
Appendix ............................................................................................................................. 343
Abbreviations ...................................................................................................................... 347
Index ................................................................................................................................... 349
7. 280 Intraoperative Neurophysiological Monitoring
and so forth will cause increased central conduc- interaction with the NMDA receptor) and it could
tion time (CCT) for somatosensory evoked provoke seizure activity in individuals with
potentials (SSEPs) and essentially make it epilepsy but not in normal individuals. Ketamine
impossible to elicit motor evoked potentials by has been reported to increase cortical somatosen-
single-impulse stimulation of the motor cortex sory evoked potential (SSEP) amplitude and to
(transcranial magnetic or electrical stimula- increase the amplitude of muscle and spinal
tion). This unfortunate effect is present even at recorded responses following spinal stimulation
low concentrations. and it could potentate the H reflex. Ketamine has
minimal effects on muscle responses evoked by
Intravenous Anesthesia transcranial cortical stimulation. Because of that,
Some intravenous agents have almost always ketamine combined with opioids has become a
been used together with inhalational agents, valuable adjunct during some TIVA techniques
but, recently, the TIVA regimen has become for recording muscle responses. The fact that ket-
increasingly prevalent. One reason for that is amine could cause severe hallucinations post-
that the inhalational agents, including nitrous operatively and increase intracranial pressure has
oxide, are obstacles when electromyographic reduced its use in anesthesia.
(EMG) responses are to be monitored in con- Opioids provide analgesia but do not pro-
nection with transcranial stimulation of the vide sufficient degrees of sedation, relief of
motor cortex. It is an advantage that the mech- anxiety, and loss of memory during operations
anism of action of intravenous agents appears (amnesia). Hence, TIVA usually includes some
to be different from that of inhalational agents sedative–hypnotic agents such as barbiturates
in such a way that benefits monitoring EMG (thiopental) and benzodiazepines such as mida-
and of MEPs (see Chap. 10). zolam. Propofol is an agent that is in increasing
use because it provides excellent anesthesia
Analgesia. Achieving analgesia (pain relief) and limited effect on MEPs.
is a primary component of anesthesia, and for Barbiturates that are often used for induction
many years, opioids have been used in the of general anesthesia have effects similar to
anesthesia regimen together with agents such that of inhalation agents on evoked potentials.
as inhalation agents for achieving unconscious- For example, muscle responses to transcranial
ness (3). One of the oldest synthetic opioids is stimulation are unusually sensitive to barbitu-
fentanyl, but now several different agents with rates and the effect lasts a long time, making
similar action are in use for that purpose, such barbiturates a poor choice in connection with
as alfentanil, sufentanil, and remifentanil. Mus- monitoring MEPs.
cle responses evoked by transcranial cortical Etomidate is another popular agent to be
stimulation (electrical and magnetic) are only used in intravenous anesthesia. It enhances
slightly affected by opioids. The effects of opi- synaptic activity at low doses; thus, opposite to
oids can be reversed by administering nalox- the action of barbiturates and benzodiazepines,
one, suggesting that the effect is related to it might produce seizures in patients with
µ-receptor activity. Intravenous sedative agents epilepsy when given in low doses (0.1 mg/kg)
are frequently used to induce or supplement and it might produce myoclonic activity at
general anesthesia, particularly with opioids induction of anesthesia. The ability to enhance
or ketamine, when inhalational agents are not neural activity or reduce the depressant effects
utilized. of other drugs has been used to enhance the
Ketamine is a valuable component of anes- amplitude of both sensory and motor evoked
thetic techniques allowing recording responses responses. The enhancing of evoked activity
that might be depressed by other anesthetics. occurs at doses similar to those that produce the
Ketamine could heighten synaptic function desired degree of sedation and loss of recall of
rather than depress it (probably through its memory when used in TIVA.
8. Chapter 16 Anesthesia 281
Benzodiazepines, notably midazolam, are of anesthetic agent; for instance, it is not possi-
often used in connection with TIVA in many ble to record EMG potentials if the patient is
kinds of operations because they provide excel- paralyzed, as is the case for many commonly
lent sedation and they suppress memories used anesthesia regimens. Recording of corti-
(recall). Benzodiazepines can also reduce the cal evoked potentials is affected by most of the
risk of hallucinations caused by ketamine. agents commonly used in surgical anesthesia.
Monitoring motor evoked responses elicited by
Muscle Relaxants transcranial magnetic or electrical stimulation
Muscle relaxants are usually not regarded as of the motor cortex requires special attention
anesthetics but often combined with agents on anesthesia and the use of a special anesthe-
(intravenous or inhalation) that produce uncon- sia regimen is necessary.
sciousness and freedom of pain. Muscle relax-
ants are part of a common anesthesia regimen–– Recording of Sensory Evoked Potentials
so-called “balanced anesthesia” (neurolept It is advantageous to reduce the use of
anesthesia)––that includes a strong narcotic for halogenated agents and nitrous oxide in anes-
analgesia plus a muscle relaxant to keep the thesia when cortical evoked potentials are
patient from moving, together with a relatively monitored. Monitoring of short-latency sen-
weak anesthetic such as nitrous oxide. sory evoked potentials is not noticeably
Muscle relaxants used in anesthesia are of two affected by any type of inhalation anesthesia;
different types, each affecting muscle responses therefore, short-latency sensory evoked poten-
differently: one blocks transmission in the neuro- tials should be used whenever possible for
muscular junction (muscle endplate) and the intraoperative monitoring instead of cortical
other type depolarizes the muscle endplate, evoked potentials. Auditory brainstem responses
thereby preventing it from activating the muscle. (ABRs), which are short-latency evoked poten-
The oldest neuromuscular blocking agent is tials, are practically unaffected by inhalation
curare, but that has been replaced by a long anesthetics and can be recorded regardless of
series of steroid-type endplate blockers with the anesthesia used. Short-latency components
different action durations. Pancuronium bro- of SSEPs are not affected by inhalation anes-
mide (Pavulon®) was one of the earliest of this thetics, but only upper limb SSEPs have
series and the effects of pancuronium bromide clearly recordable short-latency components.
last more than 1 h when a dose that causes total Short-latency SSEPs evoked by stimulation of
paralysis is administered. Other and newer drugs the median nerve are suitable for monitoring
of the same family have a shorter duration of the brachial plexus and the cervical portion of
action (about 0.5 h for vecuronium bromide, the spinal cord, but they are not useful for mon-
[Norcuron®] and atracurium [Tracurium®]). itoring the spinal cord below the C6 vertebra or
The most often used muscle-relaxing agent for monitoring central structures such as the
that paralyzes by depolarizing the muscle end- somatosensory cortex. Therefore, it is usually
plate is succinylcholine. The muscle-relaxing the long-latency components, which are gener-
effect of succinylcholine lasts only a very short ated in the cortex, that are used for intraopera-
time. tive monitoring of SSEP.
The general effect of anesthetics is a lower-
ing of the amplitude and a prolongation of the
EFFECTS OF ANESTHESIA latency of an individual component of the
ON RECORDING NEUROELECTRICAL recorded potentials (4) (see Chap. 7, Fig. 7.10).
POTENTIALS The effect is different for different components
of the evoked potentials, as the potentials are
Successful neurophysiological monitoring affected by inhalation anesthetics or barbitu-
often depends on the avoidance of certain types rates to varying degrees (5) and the effect varies
9. 282 Intraoperative Neurophysiological Monitoring
from patient to patient, with children being gen- the use of such “reversing” agents is that a fair
erally more sensitive than adults (6). amount of muscle response (10–20%) has
Because these components are affected by returned before reversing is attempted. It is also
inhalation anesthetics it is important to discuss important to note that such reversing does not
with the anesthesiologists in order to select a immediately return the muscle function to nor-
type of anesthesia that allow such monitoring. mal, as the effect of the muscle relaxant will last
for some time.
Recording of EMG Potentials When muscle relaxation is not used during
Response from muscles (electromyographic an operation, the patient could have noticeable
[EMG] potentials or mechanical response) can- spontaneous muscle activity, which increases
not be recorded in the presence of muscle the background noise level in recordings of dif-
relaxants. It is usually necessary to use a mus- ferent kinds of neuroelectrical potential. This is
cle-relaxing agent for intubation. When EMG important when monitoring of evoked poten-
recordings are to be done during an operation, tials of low amplitude, such as ABR, is to be
it is suitable to use succinylcholine together done. The resulting background noise will pro-
with 3 mg of d-tubocurarine (curare) or short- long the time over which responses must be
acting endplate blockers, such as atracurium averaged in order to obtain an interpretable
(Tracurium) or vecuronium bromide (Norcuron) recording. The muscle activity often increases
during intubation. This will allow monitoring of as the level of anesthesia lessens. If the muscle
muscle potentials 30–45 min after the adminis- activity becomes strong, it might be a sign that
tration of the drug, providing that only the min- the level of anesthesia is too low. Early infor-
imal amount of the drug is given and that it is mation about such increases in muscle activity
given only once for intubation. is naturally important to the anesthesiologist so
If a short-acting endplate-blocking agent is that he/she can adjust the level of anesthesia
used, it is important to be aware that the para- before the patient begins to move sponta-
lyzing action disappears gradually and at a rate neously. In this way, electrophysiological mon-
that differs from patient to patient. The rate at itoring can often provide valuable information
which muscle function is regained depends on to the anesthesiologist, because if anesthesia
the age, weight, and so forth of the patient, what becomes light, spontaneous muscle activity fre-
other diseases might be present, and what other quently manifests in the recording of evoked
medications might have been administered. potentials from scalp electrodes a long time
During the time that the muscle-relaxing before any movement of the patient is noticed.
effect is decreasing, stimulation of a motor To do that, the output of the physiological ampli-
nerve with a train of electrical shocks (such as fier must be watched continuously to detect any
the commonly used “train of four” test) will muscle activity.
give rise to a relatively normal muscle contrac- Intraoperative monitoring that involves
tion in response to the initial electrical stimu- recording EMG potentials from muscles is
lus, but the response to subsequent impulses becoming more and more common in the
decreases and will be less than normal. complex neurosurgical operations that can
The effect of muscle relaxants of the endplate- now be performed and demands on the
blocking type can be shortened (“reversed”) by selection of an appropriate anesthesia regimen
administering agents such as neostigmine, which have, therefore, increased. A close collaboration
inhibits the breakdown of acetylcholine and between the anesthesia team and the neuro-
thereby makes better use of the acetylcholine physiologist in charge of intraoperative
receptor sites that are not blocked by the muscle neurophysiological monitoring can often solve
relaxant that is used. However, a prerequisite for such problems.
10. Husain 00 1/17/08 11:51 AM Page iii
A Practical Approach to
Neurophysiologic
Intraoperative Monitoring
Edited by
Aatif M. Husain, MD
Department of Medicine (Neurology)
Duke University Medical Center
Durham, North Carolina
New York
14. Husain 04 1/17/08 11:55 AM Page 55
4 Anesthetic Considerations
Michael L. James
T he practice of anesthesia has histori-
cally relied on the induction of a
reversible state of amnesia, analgesia, and
consists of four basic stages: premedication,
induction, maintenance, and emergence. Prior
to entering the operating suite, “premedica-
motionlessness. With the improvement of med- tions” may be administered to prepare the
ical technology, advancement of knowledge, patient for the perioperative period. Usually
and practice of evidence-based medicine, mod- this takes the form of mild sedation for anxiol-
ern anesthesiology comprises a great deal more. ysis, analgesics for preprocedural pain, antihy-
It has become the role of the anesthesiologist pertensives, antiemetics for patients with a
during surgical, obstetrical, and diagnostic pro- high likelihood of postoperative nausea and
cedures to provide anesthesia, optimize proce- vomiting, antisialagogues to facilitate intuba-
dural conditions, maintain homeostasis, and, tion, etc. In the operating room the historic
should it be necessary, manage cardiopul- principles of anesthesia are still the foundation
monary resuscitation. Additionally, anesthesi- of practice, and analgesia (i.e., painlessness),
ology has found itself branching out into amnesia (i.e., memory loss), motionlessness,
chronic and acute pain treatment as well as the and hemodynamic stability can be obtained
intensive care unit. Obviously there has been an and maintained by a variety of means.
expansion of expectations for the practice of Commonly, general anesthesia is induced
anesthesia over the last few decades; however, through the administration of a large bolus
ultimately, anesthesiology is the practice of dose of an intravenous sedative-hypnotic (e.g.,
manipulating a patient’s neurologic system and propofol). A dose of intravenous opioid (e.g.,
physiology to effect some beneficial end. fentanyl) and a paralytic agent (e.g., vecuro-
nium) may be given at this time as well to facil-
itate endotracheal intubation. After induction,
anesthesia maintenance usually consists of
PRINCIPLES OF ANESTHESIA
some amount of inhaled volatile anesthetic
There are four basic types of “anesthesia”: agent (e.g., isoflurane) in a mix of oxygen and
general anesthesia, regional anesthesia, local either air or nitrous oxide and some dose of
anesthesia, and sedation. For the purposes of intravenous opioid. The amount of volatile
neurophysiologic intraoperative monitoring agent is quantified in terms of mean alveolar
(NIOM), general anesthesia (the creation of concentration (MAC). MAC is expressed as a
reversible coma) is nearly always required and percentage of inhaled gas and is defined as the
55
15. Husain 04 1/17/08 11:55 AM Page 56
56 • S E C T I O N I : B a s i c P r i n c iples
alveolar partial pressure of a gas at which 50% is arguably the most important factor, and a
of patients will not move with a 1-cm abdom- great deal of human physiology is influenced
inal surgical incision. However, in practice the by actions of the anesthesiologist. The manner
necessary amount of volatile agent is deter- in which these physiologic functions are
mined by effect. It is during anesthesia mainte- manipulated often directly determines meas-
nance that NIOM occurs (as does the surgical urable neurophysiologic function. Further, it
procedure). After the procedure is finished, the is reasonable to assume that physiologic func-
expectation is that the anesthetic coma will be tion determines, in large part, the survivability
completely reversible, and the patient must of nerves and their supporting structures.
emerge from anesthesia without experiencing
lasting effects from the agents. Emergence is
Temperature
usually accomplished by reversing any residual
neuromuscular blockade and allowing the It is well established that temperature
patient to eliminate volatile agent via breath- plays a significant role in nerve function, espe-
ing. Volatile anesthetic agents are minimally cially in the axon. Changes of a fraction of a
metabolized and largely removed from the degree can drastically alter latencies and
body in the same manner they were intro- amplitudes of neuronal potentials with corti-
duced: ventilation. cal structures being more affected than
In terms of NIOM, special considerations peripheral nerves (2). Relative hypothermia
for general anesthesia are discussed later; how- produces changes that invariably present as
ever, it is important for neurophysiologists and slowed latencies from slower nerve conduc-
technologists to have a clear expectation of the tion. In addition there are predictable, charac-
step-by-step nature whereby anesthetic and teristic effects of profound hypothermia that,
surgical procedures are undertaken, and it is at least initially, begin with slowing to a delta
important to remember that the operating frequency (3). The opposite is true with rela-
room is generally a highly active environment tive hyperthermia for both evoked potentials
with people, monitors, equipment, and electri- (EPs) and electroencephalograms (EEGs). It is
cal cords all moving about at once. Any change important to note that regional temperature
in the NIOM may be due to many factors, not changes are invariably difficult to predict, for
the least of which is the surgical procedure, and a variety of reasons. General anesthesia causes
every attempt should be made to regain fading an overall cooling effect in the body core due
or lost waveforms, as permanent loss may indi- to peripheral vasodilatation, which is usually
cate postoperative impairment (1). Therefore opposed by active surface warming and
the entire process becomes most efficient when warmed intravenous fluids. Additionally, cold
each individual in the room understands all the and/or warm irrigants are nearly always
steps, including those of every other individual, applied to the surgical field. As a result, the
required to prepare for, perform, and enable extremities, brain, and spinal cord are being
emergence from a procedure in an environment heated or cooled depending on where they lie
of open communication and respect for each in relation to warmed air blankets, intra-
other’s responsibilities. venous fluid lines, the surgical field, etc.
Therefore, unless it is individually measured,
the actual temperature of a given region is
impossible to know, but the potential effects
NONPHARMACOLOGIC FACTORS:
should be kept in mind during the course of
ANESTHETIC CONSIDERATIONS
monitoring. It is very common for patients to
Physiologic function of the human body experience a decrease in core body tempera-
plays a major role in neuronal functioning; it ture for the first 15 minutes after anesthetic
16. Husain 04 1/17/08 11:55 AM Page 57
CHAPTER 4: Anesthetic Considerations • 57
induction. With active warming during the tionally), patient positioning, tourniquets,
administration of most anesthetic agents— vasospasm, vascular ligation, etc. Anecdotally,
unless the surgical procedure requires an some have reported discovering incidental
alternative strategy—the patient’s temperature ulnar nerve ischemia secondary to compres-
will then be kept greater than 36°C by the sion during routine monitoring for spinal
anesthesiologist. fusion. When the compression was released,
the nerve potentials returned to normal.
Blood Flow
Ventilation
Logic dictates that ischemic nerves do not
function normally; therefore measurable neu- Optimal neural functioning depends on
ral potentials would become abnormal. In fact maintenance of a homeostatic extracellular
it has been demonstrated that somatosensory environment. Hypo- or hypercapnea can alter
evoked potentials (SEPs) can be lost when cellular metabolism by changing the acid-base
cerebral blood flow falls below 15 status of the individual. In general individuals
mL/min/100 g (2). This can be assumed to be tolerate relatively profound acid-base
true for the spinal cord and peripheral nerves derangements, especially upward trends in
as well. Unfortunately, it is difficult to actually pH. Unless the pH of a patient drops below
measure blood flow to any given structure, so 7.2, neuronal mechanisms are maintained.
systemic blood pressure is often used as a sur- Additionally, there is a suggestion that
rogate. Furthermore, systemic blood flow extremes in hypocarbia (< 20 mmHg partial
does not necessarily dictate regional blood pressure) can alter SEP monitoring (5).
flow, especially in the brain, which makes it Alternatively, profound hypoxia is poorly tol-
even more difficult to predict. Monitors are erated, especially in the surgical setting of
becoming available that purport to quantify ongoing blood loss and potential hypotension.
regional blood flow (e.g., cerebral oximetry,
microdialysis), but a discussion of these is
Hematology
beyond the scope of this chapter. Essentially
then, there are two main considerations for Like hypoxia, profound anemia can con-
the neurophysiologist: systemic hypotension tribute to neural dysfunction. Normally, ane-
and decreased regional blood flow. When pro- mia is well tolerated to levels of hemoglobin
found, systemic hypotension results in glob- less than 7 g/dL. However, in the surgical set-
ally reduced blood flow, which translates into ting of possible large volume blood loss,
tissue ischemia of varying degrees based hypotension, and hypoxia, it is generally
largely on autoregulation. For example, dur- accepted that hemoglobin levels should be
ing spinal surgery, controlled deliberate kept above 8 g/dL and may require optimizing
hypotension is often requested of the anesthe- at 10 g/dL. At approximately 10 g/dL of
siologist so as to assist in controlling blood hemoglobin, oxygen delivery appears to be
loss; however, surgical traction and hypoten- maximized and transfusion above this thresh-
sion can aggravate each other with deleterious old does not appear to improve augmenta-
effects to the patient, and NIOM can assist in tion. There are animal data that support this
determining the acceptable limit of systemic supposition in SEP monitoring (6).
hypotension (4). There are many examples of
causes of decreased regional blood flow, and
Intracranial Pressure
almost all are due to some interruption in
blood supply either due to compression from Increase in intracranial pressure is a rela-
surgical instruments (intentionally or uninten- tively well documented cause of shifts in cor-
17. Husain 04 1/17/08 11:55 AM Page 58
58 • S E C T I O N I : B a s i c P r i n c iples
tical responses of EPs and prolongation of EFFECTS OF SPECIFIC
motor evoked potentials (MEPs), presumably ANESTHETIC AGENTS
due to compression of cortical structures.
In general the anesthesiologist and neuro-
There is a pressure-related increase in latency
physiologist are constantly at odds in that
and decrease in amplitude of cortical SEPs
nearly all anesthetic agents, given in high
and as intracranial pressure becomes patho-
enough doses, cause depression of NIOM
logic, uncal herniation occurs with subsequent
potentials. However, with open communica-
loss of subcortical SEP responses and brain-
tion and mutual understanding of each other’s
stem auditory evoked potentials (BAEPs) (7).
activities, NIOM can be successful with nearly
Alleviation of this pressure can return EPs to
any anesthetic technique. The crucial concept
normal.
is that any change in either anesthetic or
NIOM must be communicated to the team, so
Other Factors that every person in the operating room is act-
ing under appropriate assumptions.
Neuronal function depends on mainte-
nance of a homeostatic intra- and extracellu-
lar environment determined by potassium, Inhalation Agents
calcium, and sodium concentrations. It is log-
Despite being the oldest form of anesthe-
ical to assume that alteration in these concen-
sia, the exact mechanism of action of inhala-
trations would result in dysfunction and
tion agents remains unclear. Inhalation
possible changes in measurable neuronal
anesthetics consist of two basic gases avail-
potentials. The concentration of these ions is
able in the United States: halogenated agents
largely in the control of the anesthesiologist,
(halothane, isoflurane, sevoflurane, desflu-
and maintenance within ranges of normal val-
rane) and nitrous oxide. Doses of gas are
ues is necessary. In addition, profound hyper-
given as percentage of inhaled mixture, and
or hypoglycemia should be avoided, as either
effective doses are expressed as some amount
extreme can result in cellular dysfunction;
of MAC. As discussed before, one MAC of an
although there is no evidence that they result
agent is sufficient to prevent 50% of patients
in intraoperative changes in NIOM, there are
from moving to the stimulation of surgical
data to suggest that both can lead to poor out-
incision (Tables 4.1 and 4.2).
comes (8).
TABLE 4.1 Effects of Inhaled Agents on Evoked Potentials
BAEP SEP MEP
Agents Latency Amplitude Latency Amplitude Latency Amplitude
Desflurane Inc 0 Inc Dec Inc Dec
Enflurane Inc 0 Inc Inc Inc Dec
Halothane Inc 0 Inc Dec Inc Dec
Isoflurane Inc 0 Inc Dec Inc Dec
Sevoflurane Inc 0 Inc Dec Inc Dec
Nitrous oxide 0 Dec 0 Dec Inc Dec
Inc = increased; Dec = decreased; 0 = no change.
18. Husain 04 1/17/08 11:55 AM Page 59
CHAPTER 4: Anesthetic Considerations • 59
TABLE 4.2 Effects of Anesthetics Agents on Electroencephalogram
INCREASED FREQUENCY SUPPRESSED
Barbiturate (low dose) Barbiturates (high dose)
Benzodiazepine Propofol (high dose)
Etomidate Benzodiazepine (high dose)
Propofol
Ketamine
Halogenated agents
(< 1 MAC)
INCREASED AMPLITUDE ELECTROCEREBRAL SILENCE
Barbiturate (moderate dose) Barbiturates
Etomidate Propofol
Opioid Etomidate
Halogenated agents Halogenated agents
(1–2 MAC) (> 2 MAC except halothane)
Inc = increased; Dec = decreased; 0 = no change.
Halogenated Agents ever, cord stimulation results in stimulation
The halogenated agents consist of the his- of the sensory and motor pathways, and
toric agent halothane, which is still used in halogenated gases preferentially block the
most countries outside the United States, and motor responses (10). Therefore it is impor-
the modern agents consisting of isoflurane, tant to remember that NIOM utilizing spinal
sevoflurane, and desflurane. Each has its own cord stimulation may not reliably monitor
MAC, onset and offset times, and metabolism motor function in the presence of halo-
based on the inherent properties of the gas. genated gases. For this and reasons men-
Their use results in a dose-related decrease in tioned above—namely, easy ablation when
amplitude and slowing of latency of SEPs, MEP monitoring is essential—halogenated
with the least effect seen in peripheral and gases should usually not be part of the anes-
subcortical responses (2). BAEPs are mini- thetic regimen when using this modality.
mally affected by halogenated anesthetics at The EEG is affected but usually without
usual doses but can be ablated at high doses. hindrance to monitoring. All halogenated
MEPs are enormously affected by the use anesthetics produce a frontal shift of the
of halogenated agents and can be entirely rhythm predominance when used at induction
ablated even with doses of 0.5 MAC. It doses (two to three times MAC doses). The
appears that this effect occurs proximal to the gases then produce a dose-dependent reduc-
anterior horn cell due to evidence that waves tion in frequency and amplitude. It is impor-
recorded distal to the anterior horn cell and tant to note that both isoflurane and
proximal to the neuromuscular junction desflurane can produce burst suppression and
remain recordable even at high doses of anes- electrocerebral silence at clinical doses. For
thetic (9). MEP monitoring may also occur practical purposes, however, all halogenated
through spinal or epidural stimulation with agents can be used for maintenance anesthesia
minimal effect on recorded responses; how- when NIOM requires EEG monitoring.
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60 • S E C T I O N I : B a s i c P r i n c iples
Nitrous Oxide tions vary rapidly with inhaled concentra-
Nitrous oxide is similar to halogenated tions, so that if NIOM is problematic and
anesthetic agents and causes a dose-related needs maximizing intraoperatively, discontin-
decrease in amplitude and prolongation of uance of nitrous oxide will quickly result in
latency of cortical SEPs and ablation of MEPs. the its elimination from the brain and body.
This effect seems somewhat limited in subcor-
tical and peripheral potentials of the SEPs. At
Intravenous Agents
equipotent doses to halogenated agents,
nitrous oxide may, in fact, cause greater EP Intravenous anesthetic agents are gener-
depression (2). Additionally, nitrous oxide has ally used to induce anesthesia and afterwards
somewhat indeterminate effects on the EEG to supplement inhalation maintenance anes-
that is highly dependent on other agents and thesia. Most modern anesthetic techniques
doses being used simultaneously. The effects consist of a variety of agents, intravenous and
on the EEG are not wholly predictable, but inhaled; nearly always an intravenous opioid
generally, there is frontally dominant high-fre- is administered to augment other agents for
quency activity and posterior slowing. Despite either tracheal intubation at induction or
this, a frequent anesthetic technique used dur- intense surgical stimulation exceeding a stable
ing NIOM is a “nitrous-narcotic” technique. maintenance anesthesia. If halogenated agents
The modern version of this technique consists are contraindicated or NIOM becomes prob-
of a high-dose remifentanil infusion (0.2 to lematic with their use, a complete anesthetic
0.5 µg/kg/min) with 60% to 70% inhaled can consist of intravenous drugs, or total
fraction of nitrous oxide. A high, but con- intravenous anesthesia (TIVA). TIVA exists in
stant, amount of nitrous oxide is delivered many forms. The most common regimen is
with varying amounts of remifentanil based based on continuous propofol infusion and
on surgical stimulation. As long as the per- supplementation with intravenous opioid.
centage of inhaled nitrous oxide is held con- However, all manner of TIVAs have been
stant, this practice generally allows recordable described, including the use of ketamine, bar-
responses for most NIOM except transcranial biturate, midazolam, dexmedetomidine, etc.,
MEPs, although even then 50% to 60% with drug selection depending on utilizing
nitrous oxide may be used. The benefit of specific attributes of an agent to effect a spe-
using nitrous oxide is that brain concentra- cific outcome (Tables 4.2 and 4.3).
TABLE 4.3 Effects of Intravenous Agents on Evoked Potentials
BAEP SEP MEP
Agents Latency Amplitude Latency Amplitude Latency Amplitude
Barbiturate
Low dose 0 0 0 0 Inc Dec
High dose Inc Dec Inc Dec Inc Dec
Benzodiazepine 0 0 Inc Dec Inc Dec
Opioid 0 0 Inc Dec 0 0
Etomidate 0 0 Inc Inc 0 0
Propofol Inc 0 Inc Dec Inc Dec
Ketamine Inc 0 Inc Inc 0 0
Inc = increased; Dec = decreased; 0 = no change.
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CHAPTER 4: Anesthetic Considerations • 61
Barbiturates drug can slow SEP latencies and decrease
Some of the oldest intravenous anesthet- amplitudes (12). Furthermore, as with most
ics include barbiturates (e.g., thiopental, pen- other anesthetics, even small doses of benzo-
tobarbital, phenobarbital, methohexital). diazepines (1 to 2 mg) can lead to a marked
These drugs exist in alkaline salt solution and reduction in MEP responses. However, owing
exert their mechanism of action at the GABAA to relatively rapid metabolism of single
receptor. Of these, thiopental remains in com- adminstration, if small doses of midazolam
mon use, in certain surgical cases, as an induc- are given preoperatively, their effects on
tion agent and as a means of achieving NIOM are usually minimal. Of note, benzodi-
neuroprotection through “burst suppression.” azepines are anticonvulsants and will all pro-
Additionally, methohexital is frequently used duce slowing of the EEG into the theta range;
to facilitate electroconvulsive therapy (ECT). however, at small doses they create beta-
However, much like halogenated agents, bar- rhythm predominance in frontal leads, which
biturates will produce EEG slowing and, at is also seen with chronic oral administration.
higher doses, burst suppression and electro-
cerebral silence. There appears to be little Propofol
class effect of barbiturates on SEPs, with each Propofol remains one of the most com-
agent producing somewhat different results. mon agents used for the induction of anesthe-
Thiopental produces transient decreases in sia and is the most common agent used for
amplitude and increases in latency with bolus maintenance anesthesia during TIVA. It is
dosing for induction, but phenobarbital pro- packaged in a lipid-soluble solution and its
duces little effect until doses causing cardio- site of action is also at the GABA receptor.
vascular collapse are reached (11). As with Owing to rapid redistribution after dosing,
inhaled agents, SEP cortical potentials seemed propofol is easily titratable to the desired
to be most affected, with relative sparing of effect, which makes it very useful for TIVA
subcortical and peripheral responses. In con- techniques. Induction doses of propofol (2 to
trast, whether with low-dose continuous infu- 5 mg/kg) cause amplitude depression of EEG,
sion or single-bolus dosing, MEP responses SEP, and MEP responses, as does high-dose
can be entirely abolished with the use of bar- continuous infusion (80 to 100 µg/kg/min).
biturates. Any anesthetic given for a surgical However, there is generally rapid recovery
procedure requiring MEP monitoring should after termination if long infusion times (>8
exclude the use of barbiturates in any form hours) are avoided (13). In recording SEPs or
unless their use (i.e., neuroprotection) super- MEPs from the epidural space, there seems to
sedes the benefit from MEP monitoring. be limited effect of the drug on the EPs; this
seems to hold true for recordings from the
Benzodiazepines scalp or peripheral muscle as well (14).
Midazolam is a common intravenous Propofol is also notable as an agent that can
benzodiazepine used in preoperative areas produce burst suppression and electrocerebral
prior to transfer to the operating suite. silence on the EEG. Despite profound EEG
Benzodiazepines also have their site of action suppression at high dose, propofol retains its
at the GABA receptor and have the desirable relatively quick termination, allowing for an
effects of amnesia, sedation, and anxiolysis. In awake, alert, and neurologically testable
general, single one-time doses of midazolam patient at the end of a surgical procedure.
given prior to induction have little effect on
NIOM during critical portions of the proce- Opioids
dure. However, induction doses of midazolam Intravenous opioids represent a critical
(0.2 mg/kg) or continuous infusions of the mainstay in the practice of modern “balanced”
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62 • S E C T I O N I : B a s i c P r i n c iples
anesthesia to control perioperative pain. ing NIOM. Additionally, the use of ketamine
Nearly all general anesthetics will have some can produce larger amplitudes, with mild
form and dose of intravenous opioid as a cen- slowing into the theta range on the EEG, and
tral component. Intravenous opioids in current there is anecdotal evidence that ketamine
use during the perioperative period include may be proconvulsant. The downside to ket-
morphine, hydromorphone, fentanyl, alfen- amine use (and the reason ketamine fell out
tanil, sufentanil, and remifentanil; they are of favor prior to the last 5 years) is the occur-
administered for various indications and at a rence of emergence delirium and dissociative
wide variation in dosing regimens. All intra- hallucinations. Additionally, increase in
venous opioids have almost no effect on intracranial pressure from enhanced cerebral
NIOM even at very high doses, making them blood flow due to ketamine makes it of lim-
of essential importance during anesthesia for ited use in neurosurgical patients with
procedures requiring NIOM. Even when given intracranial hypertension as well as in some
in the epidural or intrathecal space, they have other patient populations. Ketamine has been
minimal effect on EPs (2). It has been noted found particularly useful as a low-dose infu-
that generous application of opioids can result sion (10 to 20 µg/kg/min) to supplement a
in improved MEP monitoring owing to the propofol/opioid TIVA technique in proce-
reduction of spontaneous muscle contraction dures that require anesthetic-sensitive NIOM
and lowering of the MAC for other anesthetic (e.g., MEP). The addition of low-dose keta-
agents. With regards to the EEG, opioids pro- mine to a propofol-based TIVA allows for a
duce a mild slowing into the delta range with- substantial reduction in propofol infusion
out effect on amplitude. Opioids will not doses and enhancement of EP responses while
produce burst suppression or an isoelectric minimizing the undesirable side effects of ket-
EEG even at the highest doses. Of particular amine. For procedures requiring NIOM tech-
importance, the development of remifentanil niques that are highly sensitive to the effects
has revolutionized opioid use in TIVA. of anesthetics (e.g., transcranial MEP), the
Remifentanil is an ultra-short-acting opioid use of ketamine in the anesthetic armamen-
with a half-life on the order of 5 minutes tarium should be considered.
regardless of dose. This allows for very rapid
titration of analgesia with little or no effect on Etomidate
emergence times, thus permitting high-dose Etomidate represents another contradic-
opioid TIVA to minimize the dose of an asso- tion to the general rule that anesthetic agents
ciated sedative-hypnotic. cause EP depression. Induction doses and con-
tinuous intravenous infusion enhance both
Ketamine MEP and SEP recordings (16). Etomidate has
Ketamine is one of the older anesthetic been used in the past as a component of TIVA
agents and has undergone a recent resurgence during procedures that require anesthetic-sen-
of use owing to the finding that it helps to sitive NIOM (e.g., transcranial MEPs).
alleviate postoperative pain and chronic pain Etomidate is also somewhat contradictory in
states. Ketamine influences a variety of recep- its EEG effects; at low doses it may be some-
tors and has the unique characteristic among what proconvulsant, and it is occasionally
anesthetic agents of enhancing EP responses, used for ECT or epilepsy surgery; although at
especially in the cortex and spinal cord (15). higher doses it may produce burst suppres-
Whether given as single bolus at induction or sion. However, among its many unpleasant
as continuous infusion, ketamine can increase side effects, concerns have been raised regard-
EP amplitude in SEP, MEP, and BAEP record- ing etomidate-induced adrenal suppression,
ing, making it an attractive agent for use dur- which can occur with even single-bolus induc-
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CHAPTER 4: Anesthetic Considerations • 63
tion doses (0.2 to 0.5 mg/kg). Increased mor- nerve stimuli. MEP monitoring is acceptable
tality has been seen with prolonged infusion when neuromuscular blockade is maintained
of etomidate, mainly in the intensive care set- at a TOF of two responses. In using MEP
ting (17). Nevertheless, etomidate remains monitoring, it is important for the neuro-
valuable in cases where NIOM responses are physiologist and surgeon to know whether
difficult to obtain and otherwise may not be the patient is paralyzed. If the patient is not
recordable. paralyzed, MEP stimulation must be done at
times when patient movement is acceptable.
Dexmedetomidine If the patient is paralyzed, there are likely to
Dexmedetomidine is a relatively new be brief periods when MEP responses are not
agent used in human anesthesia. This selective recordable owing to intense paralysis; it is
alpha-2 agonist has seen widespread use in then imperative to communicate when a neu-
veterinary medicine and has found its way romuscular blocking agent is redosed.
into intensive care units and operating rooms However, either practice, paralysis or not, is
because of its desirable effects of sedation, acceptable; the main principle is, again, effec-
analgesia, and sympatholysis without respira- tive and open communication with all parties
tory depression. Though increasing ancedotal in the surgical suite.
reports are emerging, there are limited data on
the effects of dexmedetomidine on NIOM;
however, animal data suggest that there is lit-
ANESTHETIC TECHNIQUES
tle effect (18). It may be used as a low-dose
infusion (0.2 to 0.5 µg/kg/hr) to augment any A variety of anesthetic techniques are
anesthetic technique, and it allows for the use acceptable for use during NIOM; the type of
of considerably less volatile or intravenous anesthetic should be tailored to the type of
anesthesthesia or opioid. Its definitive role in NIOM and the requirements of the surgical
anesthetic techniques for highly sensitive procedure. There are, however, a few general
NIOM remains to be determined. principles. First, the least amount of anes-
thetic agent necessary should be utilized as
long as there is little possibility of awareness
Paralytics
or discomfort on the part of the patient. The
Neuromuscular blockers exert their effect liberal use of opioids can allow for a signifi-
by blocking acetylcholine at the nicotinic cant decrement in MAC. Second, the more
receptor in the neuromuscular junction. They stable an anesthetic dose can remain for the
have no effect on monitoring modalities that duration of the case, the less likely that the
are not derived from muscle activity (e.g., anesthetic agent might be contributing to
EEG, BAEPs, and SEPs). They will com- intraoperative changes in NIOM waveforms.
pletely negate MEP monitoring if intense neu- Supplementation of baseline anesthetic drugs
romuscular blockade is utilized. However, with opioids or less NIOM-offending agents
employing partial blockade will allow sub- can be made at times of more intense surgical
stantial reduction in patient movement with stimulation. Overall, there are essentially four
testing, improved surgical retraction, and classes of NIOM based on how easily the
favorable MEP monitoring. There are many monitoring technique is ablated by anesthetic
ways to monitor the amount of neuromuscu- agents. As the relative sensitivity of NIOM to
lar blockade; the most common is the “train anesthesia increases, the anesthetic technique
of four” (TOF) technique. It consists of meas- should be adjusted to maximize the least
uring muscle responses, or compound muscle offending agents. Each group and its anes-
action potentials, after four 2-Hz peripheral thetic implications are discussed below.
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64 • S E C T I O N I : B a s i c P r i n c iples
Relative Insensitivity Sensitivity to Anesthetics without
Sensitivity to Paralysis
NIOM that is relatively insensitive to
anesthetic agents in general includes BAEPs NIOM that is not negated by neuromuscu-
and SEPs recorded from the epidural space. lar blockade but is sensitive to anesthetic agents
With these monitoring methods, nearly all includes SEP monitoring. Care must be taken
anesthetic practices can be used with the to minimize offending anesthetic agents and
understanding that the general objective is to optimize non-anesthetic variables (i.e., temper-
maintain a constant level of anesthesia supple- ature). Generally, volatile or intravenous anes-
mented with intermittent opioid dosing to thesia is acceptable if relatively low doses are
control increased surgical stimulus. Of course maintained (0.5 MAC for anesthetic gases or
the least amount of anesthetic necessary to less than 80 µg/kg/min of propofol). The use of
ensure amnesia and analgesia should be used. neuromuscular blockade in this situation
Generally all patients have baseline EPs, so allows for a modest decrement in anesthetic
that once in the operating room, deviation dose, as patient movement and relaxation then
from that baseline can be assessed. If needed, become improbable. However, care must be
anesthetic level or technique can then be taken that anesthetic dose is not so low as to
adjusted to refine NIOM recordings. permit patient recall or discomfort.
Sensitivity to Paralytics Relative Sensitivity
Forms of NIOM that are sensitive to neu- The need for MEP monitoring can initiate
romuscular blockade include all monitoring some of the more challenging anesthetic issues.
that requires elicitation of muscle action Designing an anesthetic technique to optimize
potentials (i.e., electromyography, MEP, MEP monitoring adds to an already complex
spinal reflex testing, etc.). For these cases, if surgical procedure. A TIVA technique that lim-
very fine control of the amount of neuromus- its the amount of sedative-hypnotic agent (i.e.,
cular blockade can be maintained through propofol, barbiturate) is usually required.
vigilant monitoring and drug dosing, neuro- Limiting the dose of sedative-hypnotic to
muscular blocking agents can be employed. allow for optimal response recording of
Otherwise they should be entirely avoided NIOM requires the use of a second agent, usu-
once the patient has been intubated. In fact, ally opioid, to supplement and augment the
there are some practices that utilize intraoper- anesthetic properties. For instance, using a
ative neuromuscular blockade reversal when propofol-based anesthetic requires the addi-
critical monitoring periods approach. In gen- tion of opioid, ketamine, or dexmedetomidine
eral, with the exception of MEP recording, infusion to allow a much smaller dose of
which is exquisitely sensitive to anesthetic propofol to be administered. Additionally, if
technique, other forms of anesthetic agents neuromuscular blockade is used, it must be
are acceptable. For cases that rely on an tightly controlled so that profound paralysis
unparalyzed patient, relatively “deep” anes- does not preclude MEP responses from the
thesia (e.g., high doses of anesthetic agents) muscles. It is not uncommon for the patient to
can be used to offset lack of patient paralysis, be unparalyzed during critical monitoring por-
allowing optimal surgical conditions of immo- tions of the procedure. Therefore the anesthe-
bility and relaxation while maintaining the siologist is often faced with an unparalyzed
integrity of NIOM. However, the general patient, whose monitoring requires relatively
principle of stable, though relatively high, low doses of an anesthetic, and whose airway
anesthetic dose should be maintained. and accessibility is often remote. One current
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CHAPTER 4: Anesthetic Considerations • 65
practice is to utilize high-dose remifentanil in wave V significant? Neurology 2005;65:
infusion to supplement a low-dose propofol- 1551–1555.
ketamine based anesthetic. This allows very 2. Sloan TB. Evoked potentials In: Albin MS, ed.
low dose propofol (20 to 30 µg/kg/min), which A Textbook of Neuroanesthesia with
has minimal effects on MEP responses, to be Neurosurgical and Neuroscience Perspectives.
New York: McGraw-Hill, 1997:221–276.
offset by low-dose ketamine (10 to 20
3. Stekker MM, Escherich A, Patterson T, et al.
µg/kg/min), which enhances MEP responses,
Effects of acute hypoxemia/ischemia on EEG
and an amount of remifentanil that keeps the and evoked responses at normothermia and
patient motionless and relaxed. hypothermia in humans. Med Sci Monit
2002;8:CR223–CR228.
4. Dolan EJ, Transfeldt EE, Tator CH, et al. The
CONCLUSIONS effect of spinal distraction on regional spinal
cord blood flow in cats. J Neurosurg 1980;53:
In developing an anesthetic plan, the type 756–764.
of NIOM is often as important a consideration 5. Grundy BL, Heros RC, Tung AS, et al.
as the type of surgical procedure. The crucial Intraoperative hypoxia detected by evoked
factor for a successful procedure is open and potential monitoring. Anesth Analg 1981;60:
candid communication between the operating 437–439.
room staff, neurophysiologist, anesthesiologist, 6. Nagoa S, Roccaforte P, Moody RA. The
and surgeon. The majority of problems with effects of isovolemic hemodilution and reinfu-
sion of packed erythrocytes on somatosensory
intraoperative monitoring arise when operating
and visual evoked potentials. J Surg Res 1978;
room communication does not allow for each
25:530–537.
individual to have a clear understanding of the
7. Mackey JR, Hall JW III. Sensory evoked
actions of each of the other members. When responses in head injury. Central Nerv Syst
everyone involved in the procedure is knowl- Trauma 1985;2:187–206.
edgeable about reasonable expectations and 8. McGirt MJ, Woodworth GF, Brooke BS, et al.
aware of the current situation, the patient bene- Hyperglycemia independently increases the
fits from an operating team that is poised and risk of perioperative stroke, myocardial infarc-
fluid in its execution. With that understanding, tion, and death after carotid endarterectomy.
it is imperative for the neurophysiologist to Neurosurgery 2006;58:1066–1073.
understand the limitations produced by an 9. Gugino LD, Aglio LS, Segal NE, et al. Use of
anesthetic and for the anesthesiologist to under- transcranial magnetic stimulation for monitor-
stand the effects of certain medications on mon- ing spinal cord motor paths. Semin Spine Surg
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10. Deletis V. Intraoperative monitoring of the
there can be little coordinated activity between
functional integrity of the motor pathways.
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Adv Neurol 1993;63:201–214.
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11. Drummond JC, Todd MM, U HS. The effects
effect of a given anesthetic agent on monitoring of high dose sodium thiopental on brainstem
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