TITLE: Anesthesiology
SOURCE: Grand Rounds Presentation, UTMB, Dept. of Otolaryngology
DATE: June 9, 2004
RESIDENT PHYSICIAN: Glen T. Porter, MD and Russell D. Briggs, MD
FACULTY PHYSICIAN: Francis B. Quinn, Jr., MD
SERIES EDITORS: Francis B. Quinn, Jr., MD and Matthew W. Ryan, MD
"This material was prepared by resident physicians
in partial fulfillment of educational requirements established for the
Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and
Neck Surgery and was not intended for clinical use in its present form. It was
prepared for the purpose of stimulating group discussion in a conference
setting. No warranties, either express or implied, are made with respect to its
accuracy, completeness, or timeliness. The material does not necessarily
reflect the current or past opinions of members of the UTMB faculty and should
not be used for purposes of diagnosis or treatment without consulting
appropriate literature sources and informed professional opinion."
History
Despite the
synthesis of ether in 1540 by the German scientist Valerius Cordus, the use of
anesthetic agents in a medical setting represents a totally American
contribution to medicine. Dr. Crawford
W. Long, a rural doctor in
Numerous other
developments paved the way for modern anesthesia to flourish. The endotracheal tube was discovered in 1878
which protected against the drug-induced respiratory failure. Nerve block anesthesia with cocaine was
popularized by Halsted in 1885 with epidural and spinal anesthesia emerging
shortly thereafter. Intravenous agents
became increasingly popularized after sodium thiopentone was first used in
1934. The current concept of “balanced
anesthesia” was first introduced after curare was used in anesthetic practice
in 1942. Over the next fifty years, many
additional anesthetic agents have been developed and refined with anesthesia
emerging as an important specialized field in medicine.
Basic Principles of General Anesthesia
Anesthesia is
defined as the absence or abolition of sensation. This term should be differentiated from
analgesia which is defined as the absence or abolition of pain. General anesthesia involves rendering a
patient unconscious whereas local anesthesia (or more correctly, local
analgesia) is aimed at blocking conduction of nerves to the operative
site. In order to provide safe,as well
as adequate general anesthesia, the
anesthesiologist must combine the need for unconsciousness, the need for
analgesia, and the need for muscle relaxation to provide the best operative
conditions for the surgeon. This
so-called ‘triad of anesthesia’ can be achieved with the use of only one drug,
however side effects have limited the successful application of single line
agents in modern anesthesia. Therefore,
utilizing various drugs for their particular muscle relaxing, sleep producing,
and analgesic properties, anesthesia can be safely and properly maintained.
Four main stages
of general anesthesia are recognized regardless of the method in which the
anesthesia is delivered. These stages
are based upon the patient’s body movements, respiratory rhythm, oculomotor
reflexes, and muscle tone. In general, a
patient in stage one is conscious and rational, however the perception of pain
is diminished. Stage one is commonly
termed the analgesia stage. Stage two,
the delirium stage, is marked by the patient becoming unconscious, however the
body responds reflexively and irrationally to stimuli. Breath holding may be present and can result
in hypoxia, however tone is maintained in pharyngeal muscles and a patient can
maintain and protect their own airway. Pupils
generally become dilated and gaze is discongugate. Stage three, the surgical anesthesia stage,
is characterized by increasing degrees of muscular relaxation. Protective pharyngotracheal reflexes are
absent and the patient is unable to protect the airway. Stage four is medullary depression. This stage is characterized by cardiovascular
and respiratory collapse due to depression of the cardiovascular and
respiratory centers in the brain stem.
Each anesthetic
agent has a varying effect on the pattern of surgical anesthesia. For example, certain agents are highly
analgesic (nitrous oxide) whereas others do not show stage I (thiopental). For a particular agent, the stage or depth of
anesthesia must be judged with reference to the known sequence of signs for
that agent. Various anesthetic agents
are used to achieve the aforementioned stages for general anesthesia. These include inhalational agents,
intravenous agents, analgesic agents, and muscle relaxants. Local anesthetics represent a category of
anesthesia outside the realm of general anesthesia and will be discussed
separately.
Inhalational Anesthetic Agents
Inhalational
anesthesia refers to the delivery of gases or vapors into the body via the
respiratory tract to produce anesthesia.
Through uptake and distribution, some portion of the anesthetic agent is
presented to the nervous system, resulting in the absence of sensation. Understanding the induction, maintenance, and
recovery from an inhalational anesthetic requires applications of the
pharmacokinetics of the particular drug.
In general, the aim in giving an inhalational anesthetic is to readily
achieve a partial pressure of that anesthetic in the brain sufficient to keep
the patient asleep and maintain that partial pressure until the operation is
complete. Certain factors such as the
solubility of the anesthetic agent, cardiac output of the patient, and alveolar
ventilation of the patient will influence the ability of the anesthetic to
achieve its result.
An important
concept in comparing inhalational anesthetics is knowing their measure of potency
called the minimum alveolar concentration (MAC). It is defined as the concentration of a
particular inhalational anesthetic at one atmosphere pressure in which 50
percent of patients do not move in response to a skin incision. Minimum alveolar concentration is analogous
to the ED50 value computed from a pharmacological dose-response curve. Therefore, the potencies (as well as side
effects at similar potencies) of different inhalational agents can be compared;
so can combinations of agents. In
general, a half MAC of each of two inhalational anesthetics is equivalent to
one MAC of either. This concept not only
has clinical applications but also suggests that the fundamental mechanisms by
which these inhalational agents induce anesthesia are similar. The use of MAC in comparing the potency of
different anesthetic gases has been criticized because it measures only a
single point, the abolition of muscular response to pain. The concept fails to recognize the importance
of the slope of the response curve.
Other comparisons have been advocated (e.g. MAC/AWAKE ratios) however
the MAC is the most widely used.
All the
inhalational agents impair respiratory and circulatory function as well as
influencing every organ system in one way or another. Some of these actions do not accompany the
anesthetic effect but are side effects that must be appreciated when these
agents are utilized. The potency,
systemic effects, and specific side effects of the most commonly used inhalational
agents will be discussed.
Nitrous Oxide
Nitrous oxide (N2O)
was first prepared by Priestly in 1776 (prior to the isolation of oxygen) and
its anesthetic properties described by Humphry Davy in 1799. Dr. Davy’s thought was that this inorganic
gas might “be used with advantage during surgical operations” went unheeded
until the mid 1800’s. Nitrous oxide is
characterized by its inert nature--it undergoes only minimal metabolism. It is colorless, tasteless, and odorless. It does not burn but will support combustion,
so it cannot be taken for granted in a high-risk environment (laser
surgery). It is stored as a liquid at 50
atmospheres in a cylinder.
Potency
The major
difference between nitrous oxide and the rest of the inhalational agents is its
low potency. The MAC of this agent is
105%, unreachable at normal atmospheric pressure in oxygen concentrations
compatible with survival. The value of
this agent is its ability to produce different effects over a wide range of
inspired concentrations. It is a weak
anesthetic but powerful analgesic.
Patients will have some degree of analgesia at 50% nitrous oxide and may
become amnestic at 66 2/3 %. Its
drawback is the need for some additional agent to achieve full surgical
anesthesia. It is poorly soluble in
blood, and thus the onset and recovery times for nitrous anesthesia are brief
(three to ten minutes).
Systemic Effects
Despite its
relatively low potency, nitrous oxide affects most of the major body
systems. It does cause direct mild
myocardial depression, and although its general effects on heart rate and blood
pressure are innocuous, it can cause major cardiovascular depression in
patients with underlying hemodynamic compromise (hypovolemia, myocardial
dysfunction, or septic shock). Nitrous
has little effect on respiration and does not affect the neuromuscular junction
to alter the requirement for a nondepolarizing neuromuscular blocking agent.
Side Effects
There are a number
of special concerns with nitrous oxide that are not present with the other
agents. Nitric oxide and nitrogen dioxide
are both highly toxic to the lung and fortunately have largely been eliminated
as impurities from the manufacturing process.
There is a very real danger of administering a hypoxic mixture of
nitrous oxide-oxygen mixture to a patient.
The large volume of gas administered poses another problem. Although nitrous oxide is the least soluble
anesthetic agent, it is still much more soluble than nitrogen. This means that the two agents take time to
equilibrate across the alveolo-capillary membrane. At the beginning of anesthesia, nitrous oxide
leaves the alveoli faster than nitrogen enters the lung, thereby raising the
concentrations of oxygen, carbon dioxide, and any other inhalational agent
used. Increasing the concentration of
other inhalational anesthetics can speed induction at the beginning of a case,
a phenomenon known as the second gas effect. At the end of anesthesia, the opposite is
true. The alveolus fills rapidly with
nitrous oxide and the nitrogen in the alveolus is unable to equilibrate as rapidly
with the blood. This dilutes the oxygen
present within the alveolus potentially creating hypoxemia especially if low
levels of supplemental oxygen are used and the patient has a depressed state of
consciousness at the end of a case. This
phenomenon is termed diffusion hypoxia and may be present for up to 30
minutes after administration of the gas.
The same principle applies when some portion of the body has trapped
air, such as in a pneumothorax, bowel obstruction, air embolism, or with middle ear surgery. The displacement of tympanic membrane grafts
is well described with the use of nitrous oxide anesthesia. Nitrous oxide also interferes with cell
division. High concentrations will stop
white cell formation after 36 hours of administration. It may also inhibit methionine synthetase
thereby resulting in a megaloblastic or aplastic anemia. Under a similar mechanism, it can also
inhibit vitamin B-12 metabolism producing its associated neurologic deficits.
Halothane
Fluorinated
anesthetic agents were discovered secondary to advances made by development of
the atomic bomb. They represented a
relatively safe and effective alternative to the flammable, often toxic agents
used until that time. Halothane was the
first of these gases and for many years has been the most commonly used
supplement to nitrous oxide anesthesia.
It was synthesized by Suckling in 1956 with the hopes of being an ideal
anesthetic agent. It exists as a
volatile liquid with a distinctive aroma and is added to the gas mixture delivered
to the patient by means of a vaporizer added to the anesthesia machine. It is a comparably stable compound,
nonflammable, and easy to vaporize.
Potency
Halothane has a
MAC of 0.75%, indicating that it is highly potent. It has poor direct analgesic properties which
makes it a perfect complement to nitrous oxide.
Halothane is very soluble in blood and fatty tissues and awaking from
halothane anesthesia may be prolonged if attention is not given at the time of
emergence.
Systemic Effects
Halothane has
profound effects on various body systems.
In addition to depressing consciousness, halothane reduces or eliminates
the sympathetic response to painful stimuli.
This depressant effect on the sympathetic nervous system also reduces
the protective baroreflex response to conditions such as hypovolemia. Depression of the respiratory drive is also
produced by halothane. Both the central
response to carbon dioxide and the peripheral response to tissue hypoxia are
depressed. The pattern of respiration
produced by halothane is rapid, shallow, and monotonous with no sighs. Such a pattern predisposes to
atelectasis. Halothane also depresses
protective airway reflexes thereby placing the patient at higher risk of
aspiration at induction. Halothane
directly decreases myocardial contractility and heart rate and slows conduction
through the AV and ventricular Purkinje system.
Although some vasodilation occurs with halothane, the hypotension
produced by this agent is primarily the result of myocardial depression and
decreased cardiac output. Exogenous
doses of catecholamines (e.g. during facial plastic surgery) may produce severe
ventricular dysarrhythmias due to the myocardial sensitization. Halothane also results in muscle relaxation
and can result in potentiation of paralytic agents.
Side Effects
One of the
well-known complications of halothane is “halothane hepatitis”. This syndrome appears following exposure to
halothane and may produce fever, jaundice, and possibly massive hepatic
necrosis and death. The mechanism is not
clear but allergic reactions to halothane byproducts are implicated. It is an extremely rare occurrence but is
seen in increased frequency in those patients who have suffered hepatic anoxia
thereby increasing the concentrations of hepatotoxic metabolites. Halothane is also a well-known trigger for
malignant hyperthermia. This anesthetic
reaction is usually detected in young fit individuals who have inherited a
susceptibility to this problem. It is
characterized by masseter spasm, sustained muscle rigidity, myoglobinuria, and
a rapidly rising core body temperature.
These symptoms and signs are manifestations of a hypermetabolic state
initiated by an inhibition of calcium reuptake into the sarcoplasmic reticulum
of skeletal muscle. It is universally
fatal unless total body cooling, vigorous hydration, and administration of Dantrolene
is delivered expeditiously.
Enflurane
Because of the
disadvantages of the available anesthetics at the time, enflurane was developed
in 1963 by Terrell and released for use in 1972. It is a stable, nonflammable liquid that is
somewhat less volatile than halothane.
It has a distinctive pungent odor that creates an unpleasant induction
in a non-premedicated patient.
Potency
Enflurane is
slightly less potent than halothane with a MAC of 1.68%. Onset and elimination is similar to that of
halothane.
Systemic Effects
The respiratory
drive is depressed to a greater extent with enflurane than halothane, and the
ventilatory response to hypoxemia is also decreased. Enflurane depresses cardiac contractility and
heart rate more than halothane and produces a similar baroreflex response
depression as halothane although sensitization to exogenous catecholamines is
much less with enflurane than halothane.
The metabolism of enflurane is one-tenth that of halothane thereby
reducing its potential as a hepatotoxic agent. Its metabolism does release one fluoride
ion which is potentially nephrotoxic but is rarely sufficient to produce clinical
concern except in hyperthyroid patients and in patients taking rifampin. Fluoride toxicity presents as nephrogenic
diabetes insipidus and, in extreme cases, high-output renal failure can occur.
Side Effects
There is one
unusual side effect that is not seen with the other agents. At deep levels of anesthesia and with a
lowered PaCO2, some patients show an epileptiform pattern on EEG. Even though no post-anesthetic neurologic
sequelae have been attributed to this pattern, this drug should be avoided in
patients with seizure disorders.
Isoflurane
Isoflurane was
synthesized in 1965 by Terrell but its development lagged behind that of its
isomer enflurane because of difficulties in its synthesis, purification, and
now refuted claims of carcinogenesis. It
is nonflammable, and has properties similar to that of halothane and enflurane
with a few striking exceptions.
Potency
Isoflurane is less
soluble in blood than halothane or enflurane which affords a more rapid
induction and recovery from anesthesia.
Its disadvantage is its pungent odor which is difficult to administer to
a conscious patient. With a MAC of 1.3%,
isoflurane is less potent than halothane but more potent than enflurane in
producing general anesthesia.
Systemic Effects
Isoflurane
depresses the respiratory drive and the ventilatory response to hypoxemia in a
similar degree to that of halothane, but much less than its isomer
enflurane. Although isoflurane is a
direct cardiac depressant, cardiac output decreases less than with either
halothane or enflurane. The baroreflex is
inhibited but again less than either halothane or enflurane. Isoflurane is much less likely than halothane
to produce arrythmias in the presence of circulating catacholamines. Isoflurane does however cause a significant
reduction in the systemic vascular resistance, with a marked increase in blood
flow to the muscle and skin. It is the
most potent vasodilator of the previous three inhalational agents and the
hypotension that results with its use is a result of it peripheral effects
rather than its direct effects on cardiac depression. Isoflurane results in more muscle relaxation
than the others in its class and can cause significant potentiation of
paralytic agents.
Side Effects
Isoflurane does
not create the elipetiform activity as seen with enflurane and may be used in
seizure prone individuals. A major
difference in this agent compared with the other is its extremely low level of
metabolism in the body, thereby nearly eliminating the possibility of
nephrogenic or hepatic toxicity.
Sevoflurane
Sevoflurane is a
new fluorinated ether compound that has similar properties to the other
fluorinated inhalational agents. It can
produce mild respiratory and cardiac depression. It is not bronchoirritative and is
characterized by a rapid degree of induction and recovery due to its low lipid
solubility. It has a similar
biotransformation profile as enflurane and may induce nephrogenic and hepatic
side effects.
Desflurane
Desflurane is
another new halogenated inhalational agent.
It is also characterized by a low blood and lipid solubility which
allows for rapid induction and emergence from anesthesia. It does produce bronchoirrative effects with
a high incidence of breath holding, coughing, and laryngeal spasm. This agent is not as widely used for
induction as the other inhalational agents.
It is not metabolized to any appreciable degree and its side effect
profile is advantageous.
Intravenous Anesthetic Agents
There are many
ways to design an anesthetic plan to meet the requirements for general
anesthesia: muscle relaxation appropriate for the procedure, unconsciousness,
and analgesia. Intravenous agents can be
used to meet each of these requirements.
These drugs are generally classified as nonopioids, opioids, and muscle
relaxants. The nonopioid intravenous anesthetic
drugs principally provide hypnosis and blunting of reflexes whereas the opioids
(narcotics) and neuromuscular blockers provide analgesia and muscle relaxation
respectively. In most surgical
procedures, the induction of anesthesia is carried out by the use of an
intravenous agent and is not an unpleasant experience. It has become customary to induce general
anesthesia with an intravenous agent regardless of the subsequent agents to be
used for maintenance.
Barbiturates and other Nonopioid Compounds
Barbiturates are
commonly separated into classes based on duration of action and onset. In general, anesthesiologists prefer to use
drugs that have a rapid onset of action but a short duration of action. Such drugs allow rapid titration to the
required effect and are usually used to induce anesthesia. Thiopental sodium is the prototype drug in
this class.
Thiopental
Thiopental is
water soluble and stable in aqueous solution for weeks. It is generally prepared as the sodium salt
and is quite alkaline in solution with a pH of 10.5. This alkalinity makes thiopental incompatible
with many other acidic agents such as opiates, catecholamines, and some
neuromuscular blockers. Because of this
alkalinity, thiopental must be injected into a freely flowing intravenous line
as extravasation can produce skin necrosis. Inadvertent intra-arterial
injection is a serious complication. A
chemical endarteritis occurs and thrombosis of the artery may follow. Tissue ischemia and gangrene are potential
complications. The use of less
concentrated suspensions of thiopental (2.5%) can decrease this risk and is now
the standard concentration used in practice today.
Thiopental is
generally delivered as a bolus dose of 3-5 mg/kg. The drug is rapidly diffused into vessel-rich
areas such as the brain and unconsciousness ensues within 10-20 seconds (one
circulation time). Unconsciousness from
thiopental results from dose-dependent suppression of neuronal activity within
the central nervous system. This
suppression is associated with a general decrease in cerebral metabolic
rate. Despite this depression in
metabolic rate, thiopental and other barbiturates are poor analgesics and, in
low doses, may even increase the perception of pain. The CNS effects of thiopental go beyond producing
unconsciousness. Adequate levels of
thiopental depress cortical brain activity measured on an EEG to the point of
electrical silence. The metabolism when
the EEG is flat presumably represents the basal metabolic requirements of cell
function. Thus, in patients with severe
brain injury and increased intracranial pressure, an induction dose can reduce
pressure in most cases.
The effect of
thiopental on the cardiovascular system is varied. It may have a profound effect in some
patients, whereas virtually no effect in others. Healthy patients may experience a transient
decrease in arterial blood pressure with a mild compensatory tachycardia and
return of blood pressure to normal. In
this situation, cardiac depression is limited.
In large doses, or in patients with limited ability to activate a
baroreceptor response (patients taking antihypertensives or hypovolemic
patients), myocardial depression is more pronounced. Adequate volume repletion and sympathomimetic
drugs all play a role in treating the hypotension in these patients.
Thiopental also
produces a dose-dependent depression of medullary and pontine respiratory
centers. Carbon dioxide responsiveness
is blunted as are ventilatory responses to hypoxia.
The short duration
of thiopental was originally thought to be a result of rapid metabolism. It is now clear that this is due to the rapid
redistribution of the drug into tissues.
Metabolism eventually occurs via the liver.
Etomidate
Several newer
drugs have been introduced to avoid the drowsiness associated with prolonged
metabolism of the barbiturates.
Etomidate is one of these newer agents and has a structural appearance
similar to ketoconazole. In terms of
onset, elimination, and reliability in producing unconsciousness, etomidate is
similar to thiopental. It produces
unconsciousness in less than 60 seconds at the usual induction dose of 0.2-0.4
mg/kg. As with thiopental, drug
redistribution from the brain to other tissue accounts for its short duration
of activity. Bolus doses cause less
change in blood pressure and heart rate than thiopental and this drug has less
depressant effect on cardiovascular function in patients with depressed
myocardial function. It also produces
less respiratory depression than thiopental.
It does have several disadvantages that limit its use. There is a high frequency of myoclonic
movements and pain with injection (due to propylene glycol). It has also been shown to produce cortisol
suppression and Addisonian crises when used in debilitated patients.
Ketamine
Ketamine is an
alkylamine structurally similar to phencyclidine (PCP) and produces a state of
“dissociative anesthesia”. An IV dose of
1-2 mg/kg may produce a cataleptic state characterized by intense analgesia,
amnesia, and commonly a slow nystagmus with the eyes open. Systemic effects are characteristic of
sympathetic nervous system stimulation.
The more commonly observed include increases in heart rate, blood
pressure, and cardiac output.
Respiratory function is not depressed in normal patients and laryngeal
reflexes are maintained. The onset of
action is rapid (within a few minutes) and consciousness returns within 10-15
minutes although retrograde amnesia may be prolonged. A major disadvantage associated with its use
occurs during emergence and consists of unpleasant dreams or even
hallucinations. Benzodiazapines greatly
reduce these side effects.
Propofol
Propofol is a
substituted phenol whose action is characterized by a rapid onset and short
duration of action. Therefore, propofol
is suitable for induction and can be used as a maintenance agent. The usual induction dose of 1.5-3 mg/kg
produces unconsciousness within a matter of minutes and is metabolized quickly
by the body. The major hemodynamic and
respiratory effects of propofol are similar to those of thiopental. Like, thiopental, propofol decreases systemic
blood pressure by dilating peripheral blood vessels. In patients with a blunted sympathetic
response, profound hypotension may occur.
Propofol mimics the action of thiopental by inducing a short period of
apnea after bolus. Side effects are
rare; the most common being the venous irritation upon administration (due to
the soybean solvent in its emulsion).
This can be diminished by the use of a large vein or injecting lidocaine
IV prior to its administration.
Benzodiazepines
Many
benzodiazepines are available in the United States and are used primarily for
the treatment of anxiety disorders.
These agents are excellent in producing amnestic and sedative responses. Three benzodiazepines are available for IV
injection and are commonly used in anesthesia practice: diazepam, lorazepam,
and midazolam. Benzodiazepines induce
amnesia and sedation secondary to potentiation of the inhibitory neurotransmitter
gamma amino-butyric acid (GABA).
Although sleep inducing doses of diazepam (0.3-0.6 mg/kg) or midazolam
(0.2-0.4 mg/kg) may produce unconsciousness in two to three minutes, these
drugs have a slower onset of action and a longer post anesthetic recovery
period than thiopental. Because of this,
benzodiazepines are less commonly used as induction agents, but are commonly
used for sedation and to ensure amnesia.
Diazepam is commonly used for premedication with a 5-10 mg IV dose. Induction with diazepam varies from 0.2-1.8
mg/kg dose and is marked by variability in onset and prolonged reactions. The effects of diazepam on the cardiovascular
system are minimal. Mild decreases in
blood pressure and heart rate are indicative of its sedative effect. There have been reports of respiratory depression
with diazepam, however this response is dose dependent and can be marked if
concomitant doses of narcotics are used.
It is known to produce venous irritation when injected. Lorazepam (0.04 mg/kg) is slow in onset of
action (10-20 minutes) and is not typically used as an induction agent. It is commonly utilized as an adjunct to
regional anesthesia because of its profound anxiolytic and sedative
effects. Pharmacological actions are
similar to diazepam but longer in duration.
Similar to diazepam, the parenteral form produces venous irritation and
pain when injected. Midazolam is
water-soluble and has a lower incidence of injection pain. As with the other benzodiazepines, induction
with midazolam is slow and recovery is prolonged. Midazolam is twice as potent as diazepam and
doses of 0.1 mg/kg are generally adequate.
Because of its potential for depressing respiration, especially if given
with narcotics, the respiratory response of these patients needs to be
monitored. Intravenous benzodiazepines
should be titrated to effect and the benzodiazepine antagonist flumazenil
should be immediately available.
Narcotic Agonists (Opioids) and Antagonists
Narcotics have
been used for centuries to control perioperative pain and anxiety. In the past twenty years, very large doses of
narcotics have been used not only for analgesia but also to produce
unconsciousness and suppress the usual hyperdynamic responses to surgery. The predominant effects of narcotics include analgesia,
a depressed sensorium, and respiratory depression. These effects are dose related. Narcotics have minimal effects on the
cardiovascular systems of healthy patients. Narcotics do not produce direct
cardiac suppression and are widely used for induction and maintenance of
anesthesia in patients with myocardial disease.
In hypovolemic patients, morphine may precipitate hypotension from its
vasodilatory effects. Bradycardia with
large doses of narcotics can occur due to direct stimulation of the vagal
nucleus, however in normal patients cardiac output is not compromised due to an
increase in stroke volume. Side effects
include nausea and vomiting, chest wall rigidity, seizure activity, and
decreased gastrointestinal motility.
The mechanism of
action of these agents is receptor mediated.
The sites of this receptor activity are opioid-specific and are most
commonly found in the amygdala and spinal cord.
Many opioid receptors have been identified and three appear related to
the analgesic and anesthetic effects of the narcotics. Stimulation of the mu receptor results in
analgesia, respiratory depression, euphoria, and physical dependence. Kappa receptors mediate spinal analgesia,
sedation, and meiosis. The omega
receptors mediate hallucinations, dysphoria, and tachycardia. Meperidine, morphine, fentanyl, sufentanil,
and remifentnil are commonly used increasingly potent narcotic agonists. Nalorphine is a concomitant narcotic agonist
and antagonist which has less analgesic effects as well as less respiratory
depression. Naloxone produces pure
antagonistic effects with no known agonistic properties. It reverses analgesia and respiratory
depression nonselectively. The duration
of action is approximately 30 minutes with a typical dose of 1-2 ug/kg and
additional doses may need to be delivered should the respiratory depression
recur as the naloxone is metabolized.
Hypertensive crises can occur in narcotic dependent patients in whom
naloxone is delivered producing acute withdrawal symptoms.
Muscle Relaxants
There is more to
anesthesia than simply rendering a patient unconscious and free of pain. In order to provide an optimal surgical
field, an anesthetist must also control muscle tone as the current use of
inhalational and intravenous anesthetic agents do not fully achieve this
goal. Paralytic agents were first
described in 1595 as explorers reported the use of “poisoned arrows” by south
American natives. It wasn’t until the
1930’s that physicians began using curare in an attempt to treat tetanus. In the 1940’s they were shown to decrease the
number of bone fractures resulting from electroconvulsive therapy. Finally, in 1942, Dr. Griffin introduced
these medications to the surgical community.
Thus, it wasn’t until the mid 1940’s that paralytic agents began to be
routinely used. Its inclusion in the
Muscle relaxants
produce their desired effect by action at the neuromuscular junction, but also
have nonspecific effects at other sites.
In order to understand the mechanism of action of neuromuscular relaxing
agents, it is necessary to understand the depolarization of nerves and
subsequent muscle contraction. In order
to achieve muscle contraction an action potential travels down an efferent
nerve to the terminal neuromuscular junction or motor end plate. Upon arrival, the action potential stimulates
the release of acetylcholine from the synaptic vesicles into the postsynaptic
cleft. The acetylcholine subsequently
attaches to nicotinic receptors located on the postjunctional membrane. Should two acetylcholine molecules attach to
the acetylcholine nicotinic receptor, the receptor will open allowing an influx
of sodium ions into the muscle cell and depolarizing the motor end plate. The acetylcholine rapidly diffuses away from
the motor end plate and is hydrolyzed by the enzyme acetylcholinesterase. The end-plate potential returns to resting
potentials due to an active Na-K pump and prepares for the next stimulus. Neuromuscular blockade occurs when the normal
events are disrupted at one or more sites.
The two classes of commonly used neuromuscular relaxing agents include
nondepolarizing and depolarizing agents.
Nondepolarizing Muscle Relaxants
All nondepolarizing
muscle relaxants bind to and competitively inhibit the end plate nicotinic
cholinergic receptor. With the
competitive blockade, an increase in the concentration of a nondepolarizing
relaxant at the multiple neuromuscular junctions of each myofibril will
increase the density of muscle paralysis.
Conversely, drugs that inhibit acetylcholinesterase increase the amount
of acetylcholine near the end-plate and competitively “reverse” the
neuromuscular blockade. Reversal is
often monitored by assessing muscular twitch response to electrical
stimuli.
Nondepolarizing
neuromuscular blocking agents can be classified into intermediate acting (15-60
minutes) and long-acting agents (over 60 minutes). This characteristic is arbitrary as the
duration of action is dose dependent.
Intermediate acting nondepolarizing agents include atracurium,
vecuronium, and mivacurium, whereas the long acting drugs include pancuronium,
metocurine, d-tubocurarine, and gallamine.
The intermediate acting drugs in comparison to the long acting muscle
relaxants have a similar rate of onset of neuromuscular blockade (3-5 minutes)
but are relatively independent of renal function for clearance and evoke less
circulatory effects. Most of these drugs
have hemodynamic effects. Tubocurarine
is known to block autonomic ganglia which can suppress sympathetic discharge
and can decrease systemic vascular resistance.
In addition, tubocurarine is known for its potential in mast cell
degranulation with subsequent histamine release and severe hypotension. Pancuronium is well known for its inhibition
of vagal and muscarinic receptors and commonly produces tachycardia with its
use.
When muscle
relaxation is no longer needed, any residual effects of the neuromuscular
blocking agent are “reversed” to ensure appropriate muscle function and to
sustain ventilation. Anticholinesterases
inhibit actylcholinesterase, thereby increasing the concentration of
acetylcholine. The three commonly used
drugs for this purpose are neostigmine, edrophonium, and pyridostigmine. The increased concentration of acetylcholine
may cause bradycardia and hypotension due to stimulation of the muscarinic
cholinergic receptors on the heart. These
unwanted side effects can be reduced by the preadministration of a muscarinic
blocker such as atropine or glycopyrrolate prior to its administration.
Depolarizing Muscle Relaxants
Depolarizing
muscle relaxants bind and depolarize the end-plate acetylcholine nicotinic
receptors. This depolarization continues
as long as the receptor is occupied.
Succinylcholine is the only depolarizing muscle relaxant used
clinically. Its duration of action with
the typical induction dose of 1 mg/kg is very short (five minutes) because of
rapid hydrolysis by plasma cholinesterases.
Patients with abnormal production of plasma cholinesterase due to
genetic abnormalities cannot hydrolyze succinylcholine resulting in prolonged
paralysis. A “phase II block” resulting from repeated dosing can result in repolarization
of the end plate that is only made more dense by administration of typical
reversal agents. This desensitization is
poorly understood, but may result in delay in recovery of muscle tone.
There are several
characteristics unique to succinylcholine that may cause undesired
effects. The sustained depolarization by
the administration of succinylcholine typically produces transient
fasiculations. Fasciculation of damaged
or weakened myocytes may cause myocyte rupture and intracellular extravasation
of potassium in patients at risk (burn patients, trauma patients, and patients
with neuromuscular disease).
Postoperative myalgias of the muscles of the neck, back, and abdomen are
occasionally seen with its use. It is speculated
that unsynchronized contractions of skeletal muscle fibers may lead to this
side effect. Prior administration of
low-dose nondepolarizing muscle relaxant (tubocurarine) can attenutate fasciculation,
although it requires an increase of the Succinylcholine dose by 50-75%. Sinus bradycardia, junctional rhythms, and
even sinus arrest may follow its administration. These responses likely reflect the action of
succinylcholine at cardiac postganglionic muscarinic receptors where this drug
mimics the normal response of acetylcholine.
These effects are more likely to occur with doses given close
together. Atropine, the muscarinic
receptor blocker, can attenuate these effects if given prior to its
administration. Increases in intraocular
pressure, intragastric pressure, and trismus have been associated with the use
of succinylcholine. Patients who develop
severe trismus with the use of this drug should be considered susceptible to
the triggering effect of succinylcholine on malignant hyperthermia.
Techniques in General Anesthesia
Prior to the
initiation of general anesthesia, a thorough history and physical examination
is warranted. Previous reactions to any
of the general anesthetics or a family history of reactions should be
noted. Any potential cardiac or
pulmonary risk factors should be elicited as these two organ systems are the
most commonly affected by general anesthesia.
An extensive cardiac and pulmonary evaluation should be made in those
patients at risk so that potential risk-reducing interventions can be performed
preoperatively.
With an adequate
understanding of the drugs used in achieving general anesthesia, it is useful
to understand the techniques used to induce and to maintain general anesthesia
throughout a surgical case. As discussed
earlier, induction of general anesthesia is most often accomplished by the
intravenous administration of thiopental.
Shortly thereafter, succinylcholine is also administered to produce
skeletal muscle relaxation so as to facilitate direct laryngoscopy for
intubation of the trachea. This
injection of drugs (barbiturates, benzodiazepines, opioids, etomidate,
ketamine, or propofol) to produce unconsciousness followed immediately by
succinylcholine is referred to as a “rapid sequence induction”. Preoxygenation prior to the administration of
the drugs minimizes the likelihood of arterial hypoxemia developing during the
period of apnea. A dose of tubocurarine
prior to the succinylcholine can reduce the fasciculations induced by the
depolarizing muscle relaxant. An
alternative to this rapid sequence induction is the inhalation of nitrous oxide
plus a volatile anesthetic. An
inhalational induction is commonly utilized for pediatrics patients,
particularly when insertion of an IV catheter is not practical.
After successful
induction and intubation of the patient, maintenance of anesthesia aims at the
aforementioned goals of analgesia, unconsciousness, skeletal muscle relaxation,
and control of sympathetic responses to the noxious stimuli. These objectives are most commonly met by the
use of a combination of drugs discussed earlier. Typically, nitrous oxide is the most
frequently used inhalational anesthetic.
It is commonly used in conjunction with an opioid or volatile
anesthetic. For muscle relaxation, a
nondepolarizing muscle relaxant is also commonly utilized to maintain a motionless
surgical field.
Local Anesthetics
The introduction
of local anesthesia followed that of general anesthesia by about 40 years. In 1884, Koller introduced cocaine as an
effective topical anesthetic for the eye.
Later that year, American surgeon Halsted employed cocaine to produce
the first nerve block by local injection.
Because of cocaine’s ability to produce psychologic dependence and its
irritant properties when used topically, a search was made for improved local
anesthetics. In 1905, Einhorn synthesized
the first synthetic local anesthetic, procaine, and by 1943, lidocaine was
successfully synthesized and employed for use.
Local anesthetic
drugs are used clinically to reversibly inhibit the generation and conduction
of impulses from an area of the body.
Local anesthetics produce conduction blockade of nerve impulses by
preventing increases in permeability of nerve membranes to sodium ions. Failure of this permeability to sodium ions
slows the rate of depolarization such that threshold potentials are not reached
and action potentials are not propagated.
This affect affects smaller nerves preferentially resulting in the loss
of pain sensation while preserving motor and proprioception ability. It is likely that the local anesthetic enters
the sodium channel from the axioplasmic (inner) side of the nerve membrane and
attaches to a receptor about halfway down the channel. While the local anesthetic molecule is within
the sodium ion channel, it prevents the sodium ion movements necessary for
depolarization. Although a local
anesthetic drug is injected to produce blockade of nerve impulses, the drug is
subsequently absorbed away from the nerve site and appears in the circulation. The concentration of the drug in the blood is
directly related to the systemic effects of the local anesthetic. Local injection into highly vascularized
areas such as the hypopharynx, nose, and trachea produces maximal levels that
approach that of intravenous injection.
Topical application, however, results in blood levels that are one-third
that of IV injection. Most of the local
anesthetics (with the notable exception of cocaine) are vasodilators, thus
necessitating the addition of epinephrine or phenylephrine to aid in vasoconstriction. This addition minimizes the risk of systemic
toxicity and allows for a bloodless field.
Of interest, the addition of 1:100,000 or 1:200,000 provides the same
vasoconstricting effects at the doses typically used for injection. The site of metabolism of a local anesthetic
drug is determined by the chemical structure of the drug. Local anesthetics can be divided into two
groups, depending on whether they have an ester linkage (cocaine, procaine,
benzocaine, and tetracaine) or an amide linkage (lidocaine, bupivacaine,
prilocaine, mepivacaine). The metabolism
of local anesthetics with an ester linkage are metabolized in plasma by plasma
cholinesterase (the same agent that metabolizes succinylcholine), whereas the
local anesthetics with an amide bond are broken down in the liver by hydrolysis
and dealkylation by the cytochrome p-450 enzyme system.
Local anesthetics
tend to be linear molecules consisting of a lipophilic end and a hydrophilic
end. The lipophilic end typically
contains a benzoic acid moiety while the hydrophilic end contains a hydrocarbon
chain that is ionizable. This is of use
clinically because the non-ionized form readily penetrates membrane barriers
(when the pH is high more is in the non-ionized state) whereas the cationic
form binds more readily to the sodium receptor (typically when the pH is
lower). Thus, tissue acidosis render
local anesthetics ineffective because the local anesthetic is relatively
cationic in this state and cannot cross the nerve membrane to bind to the
receptor. The addition of sodium
bicarbonate into the local anesthetic provides more anesthetic in the
non-ionized form which allows it to readily cross the nerve membrane and
produces local analgesia for extended periods of time (in addition to
decreasing the pain involved with injection of the parent weak acid compound).
The most commonly
used local anesthetic is Lidocaine.
Lidocaine injection, when coupled with a vasoconstrictor provides quick
onset of analgesia with relatively short duration of effect (60-120 minutes). Bupivicaine and Prilocaine are longer-acting
agents with special characteristics.
Each is slower in onset, but result in significantly longer periods of
anesthesia (240-480 minutes). Articaine
was introduced in 2000 and boasts a significant decrease in the risk of toxic
side effects due to increased metabolism (and decreased ½ life). It is rapidly absorbed with a quick onset of
action.
The major systemic
toxicity of local anesthetic agents involves the central nervous system and the
cardiovascular system. Because local
anesthetics cross the blood brain barrier, toxic levels can produce both CNS
excitability and depression. Initially,
toxicity is manifested by light-headedness, circumoral numbness, and dizziness,
followed by auditory (tinnitus) and visual disturbances. Drowsiness, disorientation, and a temporary
loss of consciousness may follow.
Slurred speech, shivering, muscle twitching, and tremors precede a
generalized convulsive state (CNS excitability). Further increases in the local anesthetic
dose results in cessation of convulsive activity, flattening of brain wave
patterns, and respiratory depression, consistent with generalized CNS
depression. Local anesthetics can
produce profound cardiovascular changes by direct cardiac and peripheral
vascular effects. It is manifested by
myocardial depression and peripheral vasodilation. Inadvertent, rapid intravenous injection of
an excessive dose can cause significant myocardial contractility and peripheral
vasodilation resulting in profound hypotension and circulatory collapse. Other systemic effects of local anesthetics
include methemoglobinemia and allergic reactions. Prilocaine, when administered in large doses
may result in accumulation of the metabolite, ortho-toludine, an oxidizing
compound capable of converting hemoglobin into methemoglobin. With sufficient methemoglobin, the patient
can appear cyanotic and the blood chocolate colored. This is easily revered by IV administration
of methyline blue. Allergic reactions to
local anesthetics are rare, despite their widespread use. Indeed, it is estimated that less than one
percent of all reaction to local anesthetics are related to allergic
etiology. Preservatives in the local
anesthetic (methylparabenor) or breakdown products particularly of the ester
groups (para-aminobenzoic acid) can produce typical allergic systems such as
rash, laryngeal edema, bronchospasm. It
is more likely that a systemic toxicity has occurred should any neurological or
cardiovascular symptoms present.
Treatment for a true allergic reaction is supportive. As there is no cross reactivity between
classes of local anesthetics, the use of an amide local anesthetic may be used
when an allergic reaction is documented for an ester group drug.
Preventing Toxicity
Local anesthetic
toxicity primarily results from accidental intravascular injection or injection
of an excessive dose. This must always
be anticipated. Resuscitative equipment
(oxygen, airways, bag and mask, suction), CNS-depressant drugs (diazepam,
midazolam, and thiopental), and cardiovascular drugs (ephedrine, phenylephrine,
epinephrine) should be on hand at all times.
An IV should be started prior before any major regional anesthetic is
started. Toxic reactions are best
avoided by frequent aspirations during injection and slow, intermittent
injection of the local anesthesia. When
large doses are injected slowly and intermittently, the patient should be asked
about symptoms related to CNS toxicity such as ringing in the ears, circumoral
numbness, feeling of light-headedness, etc.
Further, the slow injection rate allows dilution of the local anesthetic
in the blood, so that high concentrations are not reached quickly. If signs or symptoms of systemic toxicity
occur, the injection should be stopped immediately. In cases where large doses of anesthetic are
used, monitoring should be employed including the maintenance of verbal
contact, continuous ECG monitoring, noninvasive BP checks, and monitoring
oxygen saturations. If convulsions or
cardiac arrest occur due to local anesthetic usage, establishment of an airway,
adequate ventilation, and support of circulation is mandatory. If the patient cannot be adequately
ventilated, insertion of an oral airway after administration of succinylcholine
(20 mg) can be useful. Should mask
ventilation not be possible, tracheal intubation should be performed. CNS excitability (seizures) should be treated
with small amounts of benzodiazepines (diazepam 5-10 mg). Hypotension is treated with alpha and beta
agonists (ephedrine 5-10 mg or phenylephrine 40-80 micrograms). ACLS protocol should be instituted when life
threatening cardiac dysrhythmias occur.
Cocaine
The use of cocaine
dates back to the sixth century with South American Indians using the drug to
induce euphoria, to reduce hunger, and increase work tolerance. Sigmund Freud was the first to report its
clinical use. Dr. William Halstead
injected cocaine into a sensory nerve trunk and reported on its regional
anesthetic qualities. Today it most
commonly used as a topical application for accomplishment of anesthesia,
particularly in the head and neck region.
It has a rapid onset of action and a prolonged duration of
activity. In addition, its strong
vasoconstriction effects are unique among local anesthetics, providing
decongestion and decreased risk of hemorrhage, thereby obviating the need for
epinephrine. The mechanism of action of
cocaine is similar to other local anesthetics by blocking the sodium channel of
the nerve membrane. It also is the only
local anesthetic known to interfere with the reuptake of norepinephrine by the
adrenergic nerve terminal and, in addition, prevents the uptake of exogenously
administered epinephrine. This action
leads to increased levels of circulating catecholamines and sensitizes target
organs to the effects of sympathetic stimulation-- tachycardia leading to
ventricular and atrial ectopy, vasoconstriction leading to severe hypertension,
mydriasis, and an increase in body temperature.
While theoretically being a contraindication, the subcutaneous injection
of lidocaine with various doses of epinephrine in combination with topically
applied cocaine is safe. The use of such
dilute solutions of epinephrine and its slow release from subcutaneous tissues
result in such low concentrations of circulating epinephrine as to be
inconsequential if used with cocaine.
Many references state that the safe maximal limit for cocaine is 200 mg
(a 4% vial). Other authors mention
300-400 mg. Interestingly, the “safe”
level for topically applied cocaine has not been based on scientific evidence,
rather on early clinical experience when cocaine was injected for tonsillectomy
anesthesia.
Special Anesthetic Techniques in Otolaryngology
Ear Surgery
Ear surgery
provides numerous areas of concern for the surgeon as well as the anesthesiologist. A bloodless field for microsurgery is
important and various techniques are employed to maintain this state. Preoperatively, local injection with a
solution containing epinephrine can produce sufficient vasoconstriction. Maintaining low-normal blood pressure without
excessive elevations and keeping the neck veins free of compression can do much
to limit the bleeding associated with middle ear surgery. The middle ear is an anatomic air cavity that
is prone to diffusion of nitrous oxide.
If nitrous oxide is used during middle ear surgery and is not allowed to
diffuse out of the middle ear space, an increase in intracavitary pressure can
exist which can dislodge a tympanic membrane graft. Simply stopping nitrous oxide 15 minutes
prior to placement of the TM graft can prevent this occurrence. Facial nerve monitoring is also an important
concern in ear as well as parotid surgery.
Eliciting a facial grimace or the use of facial nerve monitors are
easily used methods of identifying and avoiding the facial nerve. The judicious use or elimination of muscle
relaxants allows the facial nerve to be identified by these methods. The use of potent inhalational anesthetics
during ear surgery cases can maintain a relaxed patient with preservation of
facial nerve conductance.
Tonsillectomy
The tonsillectomy
is a common procedure performed in children and adults, however, numerous
challenges are provided in anesthetic management. Patients commonly present with upper airway
obstruction from enlarged tonsils, peritonsillar abcess, or sleep apnea
syndrome. Careful attention to these
possibilities is needed in order to anticipate the possibility of a difficult
airway. Teeth should be inspected so
that these do not become dislodged during induction or placement of the mouth
gag. A patient that bleeds after a
tonsillectomy represents a high risk induction.
There is high rate of morbidity if not handled appropriately. The patient is at high risk for aspiration of
digested blood and for the development of severe hypotension during induction
due to hypovolemia. Adequate intravenous
infusion should be started immediately.
Blood should be immediately available for transfusion particularly if
evidence of hypovolemic shock occurs.
The patient who is
bleeding should be transported to the operating room in the semi-prone position
to facilitate the gravity drainage of blood from the oral cavity. Once in the operating room, the patient
should be placed in the same position with the right side down (for a
right-handed anesthesiologist).
Assistants should hold the patient in this position during induction of
anesthesia. A full size smaller tube
should be available to deal with potential edema from the previous
intubation. A high volume suction must
be available. The patient is pre-oxygenated
and an inhalation induction is employed.
When adequate depth is reached for laryngoscopy, the patient is turned
to the full lateral position with no support under the head. This allows the head and bleeding points to
be below the level of the larynx. The
laryngoscope is introduced and is lifted 45 degrees upward to give adequate
view for intubation. An older child or
adult may be intubated awake however effective use of topical anesthesia is
unlikely in the face of severe hemorrhage in addition to the higher risk of
inducing vomiting with laryngoscopy.
Facial Fractures
In severe facial
fractures, the anesthetic management is complicated by the presence of blood,
teeth, and bone fragments in the oral cavity and possibly the airway. Severe facial injury can be accompanied by
fractures of the larynx or cervical spine.
In addition, mandibular or maxillary fractures can present with
significant trismus or airway obstruction.
If one is called to evaluate a newly injured patient in acute
respiratory distress prior to cervical spine X-rays, the airway should be
established by cricothyrotomy or tracheotomy without manipulation of the
neck. If the patient is known to be free
of spinal fracture and is to be intubated for surgery, a decision must be made
for oral or nasal intubation versus a tracheotomy. In the patient with severe midface fractures
in the cribiform or nasoethmoid complex
area, nasal intubation should be avoided whenever possible, both to avoid
contributing to infection of the CSF and to avoid inadvertent insertion of the
tube into the cranium. In the patient
with a midface or mandible fracture, the tube may interfere with surgical
manipulation. A major hazard with an
endotracheal tube is the risk of carrying foreign bodies into the airway with
the tube. In these cases, awake
intubation with preparations for immediate tracheotomy should be performed.
Laryngeal Surgery
Surgery of the
larynx provides numerous anesthetic considerations for both the surgeon and
anesthesiologist. The anesthetic
objectives are to maintain oxygenation and ventilation while the surgeon must
have access to an unobstructed operating field.
Communication is critical so that both goals can be met safely for the
patient. For some cases with cooperative
patients, topical laryngeal anesthesia can be achieved. Cocaine or aerosolized lidocaine is effective
in achieving appropriate anesthesia of this area. Alternatively, a superior laryngeal nerve
block can be performed. In most
procedures, however, general anesthesia is usually required. The use of a small diameter cuffed
endotracheal tube can allow for most laryngeal work to be performed safely and
adequately. Should an endotracheal tube
be a hindrance to the surgery planned, the intermittent apneic technique,
jet-Venturi technique, or spontaneous respiration anesthesia technique can be
considered. The use of neuromuscular
relaxants and intravenous agents allow for appropriate oxygenation and
ventilation in those circumstances where these methods are used. At other times, a small catheter placed just
superior to the carina allows for adequate oxygenation and ventilation as
well. With any of these methods, pulse
oximetry and capnography is essential.
A carbon dioxide
laser is also commonly used during laryngeal surgery. The risk of fire is always of concern when
the laser is used. Certain measures
should be undertaken to help reduce the risk of a fire. It has been determined that polyvinyl
endotracheal tubes, even if wrapped in protective metallic tape, should not be
used. Instead, laser resistant endotracheal tubes such as the Xomed
Laser-Shield or Rusch red rubber tubes should be used and wrapped with metallic
tape as an added protective mechanism.
The safest anesthetic gas mixture has been found to be 30% oxygen in
helium and up to 2% halothane has not been found to add any further fire
risk. Additionally, the tube cuff should
be protected by inflation with saline colored with methylene blue, neurosurgical
cottonoids should be covered with saline, and the patient’s face should be
fully covered with saline impregnated gauze.
Finally, the use of pulse mode for laser use provides a significantly
decreased risk of laser induced fire than that used in the continuous mode.
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