Download Anesthesia

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Anesthesia
Source: Institute of Medicine Study Home:
http://iomstudy.com/dabnm/anesthesia.htm
Intracranial pressure
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Normal Intracranial Pressure (ICP) is defined the
pressure inside the lateral ventricles/lumbar
subarachnoid space in supine position.
The normal of ICP is 10-15 mm Hg in adults. It is
around 2-4 in neonates and infants.
About two thirds of patients with severe head injury
have intracranial hypertension (ICP>20 mmHg).
Elevated ICP is associated with reduced amplitudes
and increased latencies of cortical SSEPS
Transcranial doppler
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Transcranial Doppler sonography is used to
measure the blood flow velocity in the major
cerebral blood vessels.
Normal skull offers barrier for ultrasonic beam. An
examination carried out through the temporal
window, orbital foramen or foramen magnum by
using a 2 MHz probe has been found to provide
clinically useful information that has a good
correlation with the cerebral blood flow (CBF)
changes.
Middle cerebral artery is commonly chosen for
examination as it can be easily insolated and 75
80% of ipsilateral carotid blood flow, flows through
MCA.
The amplitude of the normal EEG is 10-100 mV.
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Clinically, the EEG activity can be divided into four
frequency bands:
Beta - 13-20 Hz
Alpha - 8-13 Hz
Theta - 4-8 Hz
Delta - 2-4 Hz.
An isoelectric EEG represents total abolition of cortical
electrical activity.
Manual interpretation of EEG consists of eliminating the
artifacts followed by appreciation of the
predominant frequencies and the amplitudes of the sine
waves in the recording. The record is also examined for
abnormal patterns such as spikes. Since this form of
analysis is cumbersome during the course of continuous
monitoring, the signal is normally subjected to computer
processing and the interpretation is carried out based on
some of the measures obtained from the processed EEG.
In time domain analysis, the raw EEG is split into small
epochs of a given duration, usually about 1-4 sec. The
frequency and/or amplitude information contained in each
epoch is depicted graphically. A change in the value of the
variables derived form this display is expected to
represent a change in the raw EEG.
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Compressed Spectral Array: Note shift of EEG power from high to low frequencies over time
Compressed Spectral Array (CSA) and Density Modulated Spectral Array (DSA).
CSA displays frequency Vs power plots of successive epochs as lines one
over the other.
In DSA, power in various frequency bands of each epoch is represented by
dots, the density of which is proportional to the power; successive epochs are
plotted one above the other.
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Some of the measures derived from the power spectrum that are clinically
used are:
Peak Power -Frequency, the frequency with maximum power in an epoch
Mean Power Frequency-the frequency that divides the power spectrum of the
epoch into equal halves
Spectral Edge Frequency-the frequency below which 95% of the power in the
epoch is contained.
Burst Suppression Ratio: This parameter represents the percentage of time the
EEG is suppressed (isoelectric) in a given epoch.
Anesthesia Affects on EEG:
Though anaesthetic agents have been documented to have variable effects on
the EEG, there exists a general pattern which is characterised by an initial
excitation resulting in a high frequency low amplitude activity followed by a
progressive decrease in the frequency and increase in the amplitude, and
finally, a decrease in both frequency and amplitude until an isoelectric trace
occurs at high doses.
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Inhalational Anaesthetics:
During induction, halothane, enflurane, isoflurane, sevoflurane and desflurane
cause loss of occipital ? activity and genesis of frontal synchronised _ to b
activity. In surgical planes of anaesthesia, the anaesthetics differ in their
effects on EEG.
Isoflurane and desflurane, at1.2 MAC concentration, cause burst suppression
without any further slowing in the frequency of the EEG activity in the bursts.
Enflurane causes spike and wave complexes/seizure-like activity at 1.5 MAC.
Halothane causes linear slowing of frequency without burst suppression in
clinical
concentrations.
When used alone, nitrous oxide, in subanaesthetic concentrations, causes fast
rhythmic activity in frontal region with a peak frequency of 34 Hz. When
combined with volatile agents, it has been shown to antagonise or potentiate
the EEG effects of volatile agents. In some studies, nitrous oxide decreased
the amplitude and increased the frequency of the volatile agent-induced fast
activity and decreased the duration of burst suppression suggesting
antagonism between nitrous oxide and volatile agents.
In other studies, nitrous oxide increased the delta activity and decreased the
alpha to beta activity at non-burst suppressing doses of volatile agents
suggesting a potentiation of the two agents.24
Intravenous Anaesthetics:
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Barbiturates, in small doses cause drug-induced fast activity. In
higher doses
they cause EEG suppression. Very high doses cause burst
suppression.
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Methohexital enhances interictal epileptiform activity in patients with
seizure disorders.
Etomidate and propofol cause myoclonic activity at induction. Etomidate
increases interictal epileptiform activity when used in small doses and causes
burst suppression at high doses.
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Propofol in anaesthetic doses may increase or decrease interictal
epileptiform activity. High doses of propofol cause burst suppression.
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Ketamine causes high amplitude theta activity and a significant
increase in beta activity. Seizures may be caused in epileptic patients.
EEG changes during cerebral ischemia
Under stable anesthetic conditions, any change in EEG may represent
cerebral ischemia and hypoxia.
Slowing and flattening of EEG progressing to isoelectricity are the
characteristic changes seen during ischemia. Loss of slow activity may be one
of the earliest signs of ischemia. Seizure activity could be another
manifestation of cerebral ischaemia.
Intraoperatively, the CBF threshold for signs of cerebral ischemia depends on
the background anaesthetic;
ischemic changes occur at a CBF of:
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10mL 100gm–1.min–1 under isoflurane anaesthesia
15-20 mL 100gm–1.min–1 under halothane anaesthesia.
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Clinical applications of EEG
1. EEG is a gold-standard for monitoring cerebral ischaemia. A 16-channel
EEG has been shown to be as sensitive as direct CBF measurement
intraoperatively during carotid endarterectomy.
2. Intraoperative EEG monitoring could be helpful to identify cerebral
ischaemia during procedures associated with temporary vessel occlusion and
during cardioplumonary bypass procedures
3. In the intensive care unit, EEG monitoring may be helpful to monitor seizure
activity in patients with status epilepticus under the effect of muscle relaxants.
Subclinical seizures causing neurological deterioration may also be diagnosed
by EEG.
4. EEG has also been used to prognosticate the outcome of coma. It is also an
ancillary tool for confirmation of brain death.
5. Various mathematical measures derived from EEG have been investigated
for their potential to quantify the depth of anaesthesia. These include median
frequency, spectral edge frequency, bispectral index and approximate entropy.
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Anesthetic agents work as the result of direct inhibition of synaptic pathways or
the result of indirect action on pathways by changing the balance of inhibitory or
excitatory influences
Narcotics
depress electroexitability by increasing inward K+ current and depressing
outward Na+ current via a G-protein mechanism linking the receptors to the
ion channel
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Non-synthetic opiate
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Morphine
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Synthetic opiates
 Fentanyl
 Sufentanyl
 Afentanyl
The effects of opiods can be reversed by giving nalaxone- suggesting
that the effects are related to µ-receptor activity.
Sedation
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Inhalents
 Usually effective at low concentration (<10%)
 potency varies with lipohilicity- suggesting the mechanism
depends on changes in the membranes of tissues such as
alteration of synaptic function-may alter conformational
shape of the receptor ion channel at the protein-lipid
interface
Hallogenated Agents
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Produce a dose related increase in latency and reduction in
amplitude of cortical SSEPs
 Isoflurane -most potent
 Enflurane -intermediate potency
 Halothane -least potent
 Sevoflurane and Desflurane -similar potency to isoflurane
but has a more rapid onset and offset (more insoluble than
ISO) so they may be more potent than ISO when
concentrations are increasing.
 MEPs are easily abolished by halogenated agents
 When recordable, MEPs may occur only at low
concentrations (i.e. >.2 to .5% ISO)
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Affects are likely the result of depression of synaptic
transmission either in the anterior horn cell synapses on
alpha motor neurons or in the cortex on the internuncial
synapses with a loss of I waves
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Nitrous Oxide (requires higher concentration than
halogentatied to be effective anesthetic (~50%)
Common MAC values
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Nitrous oxide - 104[5]
Desflurane - 6[5]
Sevoflurane - 2[5]
Enflurane - 1.7
Isoflurane - 1.2[5]
Halothane - 0.75[5]
Methoxyflurane - 0.16
Injectables - IV sedatives
Barbituates, etomidate, althesin, propofol and benzodiazapines
work primarily by enhancing the inhibitory effects of GABA
(gamma-aminobutyric acid). They are known to bind to the GABA
receptor where activiation increases chloride conductionhyperpolarizing the membrane and producing synaptic inhibition
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Propofol (non-barbituate sedative)
Thiopental – barbiturate sedative
Pentathal – barbiturate sedative
Barbituates - sedative-hypnotics
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often used for induction (i.e. Thiopental)- will cause transient
decreases in amplitude and increased latencies of cortical
response
have effects similar to that of inhalational agents on evoked
potentials
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MEPs are sensitive to barbituates- effects last a long time - poor
choice for MEP monitoring
effects caused by up regulation of the NMDA receptors
Phenobarbital is a barbituate
Benzodiazapines:
Midazolam- has desirable properties of amnesia and has been used for
monitoring cortical SSEPs.
Doses consistent with induction (.2mg/kg) in the absence of other agents,
produces mild depression of cortical SSEPS but may produce marked
depression of MEPs suggesting that it may be a poor induction choice for MEP
monitoring.
Ketamine
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Can heighten synaptic function - higher amplitude
cortical SSEP responses
Inhibits NMDA receptor- thereby reducing sodium
influx and intracellular calcium levels
Can provoke seizure activity in patients with epilepsybut not in normal individuals
Can cause severe hallucinations postoperatively
Can cause increased intracranial pressure
Etomidate
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Can heighten synaptic function at low doses
can produce seizures in low doses (.1 mg/kg) in patients with
epilepsy
can produce myoclonic activity at induction-suggesting
heightened cortical activity
Been used for induction and a component of TIVA combined with
opiods
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Propofol
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Propofol produces amplitude depression in cortical SSEPs with
rapird recovery after termination of infusion.
Studies show MEPS are depressed with an effect on response
amplitude consistent with a cortical effect.
Rapid metabolism allows rapid adjustment of depth of anesthesia
and effects on evoked responses.
Component in TIVA combined with opiods is thought to produce
acceptable conditions for monitoring SSEPs/MEPs
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Paralytics
2 catagories based on function:
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Depolarizing agents:
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Succinylcholine
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Non-Depolarizing agents: End Plate Blockers
o Vecruronium Bromide (Norcuron)
o Rocurinmium
o Atracuronium (Traccurium)
The effects of short acting end plate blocking muscle relaxants can be
shortened ("reversed") by administering agents such as neostigmine
which inhibits the breakdown of acetylcholine and thereby makes better
use of the
ACH receptor sites that are not blocked by the relaxant.
They are also compared by length of action including short vs long acting.
Shortest acting agent is Succinylcholine.
TOF-train of four
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Involves examining muscle response where 4 peripheral motor
nerve stimuli are delivered at a rate of 2 Hz. In this technique, the
amount of ACH released decreases with each stimulation such that
its effectiveness to compare with the neuromuscular blocking agent
is reduced with each stimulation.
Quantitatively the TOF can be measured by comparing the
amplitude of the M wave of the fourth twitch (T4) with that of the
first (T1) in the T4:T1 ration.
Practically, the number of visible twitches produced is usually
recorded with declining numbers of twitches as the blockade
increases.
Accepatble CMAP monitoring has been conducted with 2/4
twitches.
The mechanism of muscle activation differs for the M response
from peripheral nerve stimulation (TO4) and TceMEP, and the
relationship between the 2 and neuromuscular blockade is nonlinear. The MEP response is much larger because centrally applied
pulses lead to repetitive activiation of spinal motor neurons, with
attendant spatial and temporal summation. For this reason, MEPs
are more robust during the blockade and may not be abolished as
markedly as the M response (T1).
Goals of neuromuscular blockade with MEP testing is to prevent
sufficient patient movement so that stimulation is not distracting or
hazardous during the surgery (particularly when the scope is used).
Furthermore, some relaxation may be required to allow surgical
manipulation of structures adherent to or over peripheral nerves, or
to reduce muscle artifacts that may be interpreted as neural
responses (i.e. paraspinous muscle responses seen in epidural
recordingss of MEP. A T1 blockade of 10-20% of baseline appears
to accomplish this goal adequately (this corresponds to 2/4
twitches).
Because of varying muscle sensitivity to muscle relaxants, the
neuromuscular blockade should be evaluated in specific muscle
groups for monitoring.
Blood Flow
Numerous studies have demonstrated a threshold relationship between regional
blood flow and cortical evoked responses.
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Cortical SSEP remains normal until blood flow is reduced to approzimately 20
mL/min/100 g.
At more restriced blood flow between 15 and 18 mL/min/100g of tissue, the
SSEP is altered and lost.
As with anesthetic effects, subcortical responses appear less sensitive than
cortical responses in blood flow.
Because MEPS and SSEP tracts are removed topigraphically from one another,
they may have different sensitivities to ischemic events.
Blood Rheology
Changes in hematocrit can alter both O2 carrying capacity and blood viscosity,
the maximum O2 delivery is often thought to occur in a midrange hematocrit (3032%).
Ventilation
Temp
Drug Administration and Models
Application & Measurement of Inhalents
MAC: Minimum Alveolar Concentration
1.0 MAC is the concentration of inhalational anesthetic required to blunt the
muscular response to surgical skin incision of 50% of a population of
unparalyzed patients.
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Intubation Tube & Respirator
N20 is mixed with 02 and administered through a respirator. 02 or N20/02 mix
are blown across volatile inhalants like isoflorine.
Specifics of Inhalant Measurements
ET: End Tidal is the amount of anesthetic agent exhaled; thus present in the
patient’s circulation.
IT: Inhaled Tidal is the % of gas going into the lungs
Factors that Decrease MAC:
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Hypotension
Anemia (PCV < 13%)*******
Hypothermia
Metabolic Acidosis
Extreme Hypoxia (Pa O2<38 mm/Hg)
Age- older animal requires less anesthetic
Pre-medication (opiods, sedatives, tranquilizers)
Local Anesthetics
Pregnancy
Hypothyroidism
Factors that Increase MAC:
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Increasing body temp – increases cerebral metabolic rate of
brain
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Hyperthyroidism
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Hypernatrimia
Factors NOT affecting MAC:
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Duration of anesthesia
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Speciea (MAC varies by only 10-20% from species to species
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Gender
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PaCO2 between 14-95 mm/Hg
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Metabolic Alkalosis
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PaCO2 between range of 38-500 mm/Hg
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Hypertension
Anesthetics act at the neuronal cellular membrane and synapse at both
cortical and spinal neurons. In general, synapses are more sensitive to
anesthetics than are axons. Specifically, ligand gated channels are
more sensitive than are voltage-gated channels. Channels are the most
widely studied protein target for anesthetics but that doesn’t mean that
other proteins are not involved.
Stages of Anesthesia
Stage 1
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The cerebral cortex is inhibited
The onset of analgesia & loss of conciousness
Stage 2
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This is the excitement phase
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There is an overall increase in sympathetic tone including;
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Increase in BP, HR, respiration and muscle tone
Side effects include possible cardiac arrhythmias that
anesthesiology will be monitoring for
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Stage 3
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This is the surgical anesthesia stage at which surgery is most
efficiently performed
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Four panes of surgical anesthesia reflect progressive CNS
depression
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The cardiovascular and respiratory functions return to normal
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No skeletal muscle contractions
Stage 4
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This is the overdose of anesthesia leading to medullary paralysis
The cardiovascular and respiratory centers are inhibited leading to
death
A “Complete” anesthetic produces all stages.
Routes of Administration
Inhalation
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Halogenated volatile drugs administered through the lungs mixed
with respiratory air or oxygen and NO2 mixture.
Intravenous
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Drugs administered `via venous vascular supply either by infusion
(continuous over time) or bolus (single dose or doses)
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Intramuscular
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Drug administration through syringe injection into the muscle
General Anesthesia Pharmacologic Effects
CNS specific effects of general anesthesia include:
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Voluntary motor function is inhibited
Involuntary (autonomic) motor function is inhibited
Respiratory function is depressed centrally
Cardiovascular specific effects of general anesthesia include:
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Heart muscle contractility and BP are depressed
Salivary and bronchial secretions effects of general anesthesia include:
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Secretions of mucous increases
/The breathing tube and some inhalational agents stimulate
coughing but coughing but coughing is surpressed during general
anaesthesia
Skeletal muscle specific effects of general anesthesia include:
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Spinal reflexes are depressed
Also some agents block acetylcholine leading to neuromuscular
inhibition
Gastrointestinal tract effects
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Nausea and vomiting effects depend on specific agents and
usually occur during recovery f at all.
Also decreased intenstinal motility causing constipation are side
effects of specific agents
Liver specific effects of general anesthesia include:
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Hepatotoxic effects
o Altered enzyme production
o Jaundice and hepatic necrosis
Administered Types of Standard Anesthesia
Inhalation Agents (volatile anesthetics)
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Administered in % concentration value
Typically, when administered alone, inhalation concentration of
less than 1 MAC has little effect on neurophysiological testing
Examples: isoflurane, desflurane, sevoflurane, N20 (non-volatile)
There is a relationship between soluability of inhalent – the less
soluable the higher the MAC (<1% isoflurane, < 2% sevoflurane
and < 6% desflurane).
Cardopulmonary Aspects:
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Overall all inhalant anesthetics depress cardiopulmonary
function in a dose dependent manner as shown by deceases
in cardiac output, BP, respiratory rate and increase partial
pressure in CO2 concentrations.
Myocardial Depression’:
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Halothan
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Injectable Agents
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Administered either bolus or drip infusion methods
MEPs are susceptible to aneshtetic agents at 3 sites:
1. The motor cortex: stimulation of neurons associated with
movement such as pyramidal cells is either by direct stimulation to
these cells (D-waves) or indirect stimulation via internuncial
neurons (I waves). The D Waves are relatively unaffected by
anesthetics because no synapses are involved in their production.
I waves are markedly affected.
2. Anterior Horn Cells - where D and I waves summate. Partial
synaptic blockade at the anterior horn cell can make it more
difficult to reach threshold. The combination of the cortical
blocking of I wave generation and reduced transmission at the
anterior horn may inhibit synaptic transmission regardless of the
composition of the descending spinal cord volley of activity.
3. The NMJ- fortunately with the exception of NMJ blocking agents,
anesthetics have little effect at the NMJ