CHAPTER 18 
– Anesthesiology Principles, Pain Management, (2) Halothane
and Conscious Sedation
INTRODUCTION
- history of anesthesiology began only a little more than 150 years ago
- risk of anesthesia-related mortality and morbidity was unacceptably high
▪ primitive equipment
▪ complication-prone drugs
▪ non-adequate monitors.
- In past 40 years, Anesthesiology has improved
▪ provided anesthesia safely for complex surgical procedures
▪ has addressed patients with severe underlying disease
- ADVANCES:
~ most notable advances in anesthesia equipment:
▪ development of anesthetic machines that reduce the possibility of
providing hypoxic gas mixtures
▪ vaporizers that provide more accurate doses of potent inhalational agents
▪ intraoperative anesthesia ventilators that provide more precise
physiologic support
~ pharmacologic advances:
▪ of shorter-acting drugs with fewer important side effects
~ monitoring devices (greatest advancement!!!)
in-circuit oxygen analyzers
capnometers
pulse oximeters
anesthetic vapor–specific analyzers
 markedly increased probability of success
PHARMACOLOGIC PRINCIPLES
- initial practice of anesthesiology used single drugs
▪ ether & chloroform
 provide the following:
~ abolish consciousness
~ prevent movement
~ ensure amnesia
~ analgesia
- In contrast, current anesthesia practice combines multiple agents
▪ inhalational agents remain the core of modern anesthetic combinations
▪ most anesthesiologists initiate anesthesia with intravenous (IV)
induction agents
▪ maintainance is supplemented by IV opioids and muscle relaxants
~ Benzodiazepines are often added to induce anxiolysis and amnesia
(anxiolysis = antianxiety)
Inhalational Agents
- the original inhalational anesthetics and limitations
 ether
▪ notoriously slow induction and equally delayed emergence
▪ but could produce unconsciousness, amnesia, analgesia, and
lack of movement by itself
 nitrous oxide
▪ both induction and emergence were rapid with nitrous oxide
▪ but the agent lacked sufficient potency to be used alone
▪ still used today in combination with other agents
 chloroform
▪ associated with hepatic toxicity and fatal cardiac arrhythmias
- drug development has emphasized rapid induction and emergence
and are nontoxic
▪ halothane, isoflurane, enflurane, sevoflurane, desflurane.
- most important characteristics of inhalational anesthetics
 blood/gas (B/G) solubility coefficient
~ measure of the uptake of an agent by blood
~ less soluble agents (lower B/G solubility coefficients) are
associated with more rapid induction and emergence
= such as nitrous oxide and desflurane
 minimum alveolar concentration (MAC)
~ concentration of agent required to prevent movement in response
to a skin incision in 50% of patients
~ way of describing the potency of a volatile anesthetic
~ higher MAC represents a less potent volatile anesthetic.
(1) Nitrous Oxide
- provides only partial anesthesia at atmospheric pressure
MAC is 104% of inspired gas at sea level
- minimally influences respiration and hemodynamics
has low solubility in blood
- often combined with one of the potent volatile agents to permit
a lower dose of the potent volatile agent
 side effects are limited, reducing cost, and facilitating rapid
induction and emergence
- problems with nitrous oxide:
 NO is that it is 30 times more soluble than nitrogen and diffuses
into closed gas spaces faster than nitrogen diffuses out
 NO increases the volume or pressure of these spaces
~ contraindicated in the presence of closed gas spaces
~ pneumothorax, small bowel obstruction, middle ear surgery, and in
retinal surgery (intraocular gas bubble is created)
~ NO gradually accumulates in the pneumoperitoneum
(contraindicated during laparoscopic procedures)
- However, periodic venting can prevent buildup, and some investigators have
suggested that NO might be preferable to CO2 as the insufflated gas
- introduced in the mid-1950s
- has a pleasant odor that facilitates mask induction
- has a variety of useful clinical characteristics (see Table 18-1 )
- most potent volatile anesthetic in modern practice,
with a MAC of 0.74 vol% in adults
- a potent bronchodilator
- previously the inhalational agent of choice in patients at risk for bronchospasm
 although other agents have subsequently been shown
to provide equivalent bronchodilation
- has numerous shortcomings that have contributed to its almost complete
replacement by newer agents
 powerful cardiac depressant
~ potentially precipitate acute decompensation in patients
with severe left ventricular dysfunction ( Table 18-2 ).
 sensitizes the myocardium to catecholamines
~ particular problem when epinephrine is added to local anesthetics
 associated with a rare form of fulminant hepatitis that is manifested
as postoperative fever and jaundice
~ microscopically indistinguishable from viral hepatitis
~ thought to be due to metabolites of halothane
▪ halothane is not a direct hepatotoxin
▪ incidence of hepatitis is increased 7x if halothane
anesthesia is repeated within 3 months
▪ best avoided in adults who have received the agent within 1 year
▪ hepatitis has not been reported in children younger than 8 years;
halothane can be used repeatedly in children
▪ avoided when there is a potential for postoperative liver injury
- trauma, history of viral hepatitis, liver surgery
- in pts.taking enzyme-inducing drugs [phenobarbital and isoniazid]
~ occurs in 1 in 35,000 pts.
- majority of halothane is eliminated through the lungs as are other
inhalational anesthetics
- approximately 20% is metabolized, primarily to nontoxic compounds
- Like all other potent inhalational agents, halothane can trigger
malignant hyperthermia
(3) Enflurane
- introduced in the 1970s as an alternative to halothane
- failed to achieve wide popularity
- less soluble than halothane and produces less cardiac sensitization
to catecholamines
- problems:
▪ the drug is metabolized to fluoride (F-)
 associated with mild renal dysfunction (chronic use and obesity)
▪ induces epileptiform electroencephalographic changes
 contraindicated in patients with seizure disorders
most pronounced at high concentrations and with hypocapnia
(4) Isoflurane
- approved by the FDA in 1979
- pungent odor virtually precludes use for inhalational induction
- rapidly replaced halothane as the most commonly used potent inhalational agent
- despite the recent release of sevoflurane and desflurane, isoflurane is commonly
used in modern operating rooms
 because the cost of the now-generic compound is well below
that of the newer agents
- several advantages over halothane
 less reduction in cardiac output
 less sensitization to the arrhythmogenic effects of catecholamines
 minimal metabolism
- problems with isoflurane:
▪ induces tachycardia, a variable response,
▪ can increase myocardial oxygen consumption
▪ can cause coronary artery disease [CAD]
~ observedcarefully the heart rate when it is
used in patients with CAD
▪ in concentrations of 1.0 MAC or less
~ isoflurane causes little increase in cerebral blood flow and
intracranial pressure (ICP) and depresses cerebral metabolic activity
~ more potent than halothane or enflurane does. Its pungent odor virtually
precludes use for inhalational induction.
(5) Sevoflurane
- relatively low solubility
- facilitates rapid induction and emergence
- associated with faster emergence than isoflurane is, especially in longer cases,
 BUT, faster emergence does not result in earlier discharge
after outpatient surgery
- associated with a lower incidence of postoperative somnolence and nausea
in the postanesthesia care unit (PACU) and in the first 24 hours after
discharge than isoflurane is
- pleasant to inhale  suitable for inhalational induction in children
(5) Sevoflurane continued…
- clinical differences between halothane and sevoflurane are subtle:
 anesthesiologists correctly identified the agent (to which they were blinded)
in only 56.6% of cases
- clinically suitable for outpatient surgery, mask induction of patients with
potentially difficult airways, and maintenance of patients with bronchospastic
disease
- sevoflurane, halothane, and isoflurane decreased respiratory resistance
in endotracheally intubated nonasthmatics; sevoflurane reduced
airway resistance more than halothane or isoflurane
- cardiovascular side effects are minimal [advantage of sevoflurane!!!]
- problem:
▪ metabolic transformation of  increases in the serum fluoride ion
concentration
▪ with soda lime or Baralyme sevoflurane produces compound A (toxic)
- However, the toxicity of compound A in humans appears to be theoretical
and not clinically important.
 β-lyase, the enzyme responsible for the formation of compound A,[4]
has 8 to 30 times greater activity in rat kidneys than in human kidney
(6) Desflurane
- rapidly taken up and eliminated
- associated with more rapid recovery than isoflurane (after >3 hours anesthesia)
- most volatile and least potent of the volatile anesthetics
 must be administered through electrically heated vaporizers
that release pure desflurane vapor
 then mixed with carrier gas to produce specific inspired concentrations
- pungent odor precludes inhalational induction
- associated with tachycardia and hypertension if the concentration is increased
too rapidly
- desflurane, isoflurane, and enflurane are partially converted to carbon monoxide
 CO produced greatly when:
▪ exposed to dry CO2 absorbent
~ prolonged use of ventilator will desiccate the CO2 absorbent
~ turn off machines when no longer necessary
▪ use of Baralyme instead of soda lime
▪ higher temperatures
▪ higher anesthetic concentrations
 desflurane, enflurane, and isoflurane produce more carbon monoxide than
halothane or sevoflurane does
~ prevented by automatic “turning off” of ventilating machines
Intravenous Agents
- started with the introduction of thiopental
- are indispensable components of modern anesthetic practice
- used primarily for induction of anesthesia and as part of a multidrug
combination to produce anesthesia
Induction Agents
- most adult patients and many older children prefer IV induction to
inhalational induction
- IV induction is rapid, pleasant, and safe for the vast majority of patients
- the five IV agents most commonly used in the United States for induction
(1) Sodium Thiopental
● oldest IV induction agent; rapid and pleasant
 redistribution of the agent from the brain to peripheral
tissues, particularly fat
 hepatic elimination only @ about 10% per hour
● well tolerated by a wide variety of patients BUT several clinical situations
necessitate caution (see Table 18-3)
● contraindicated in pts with congestive heart failure or are hypotensive
 thiopental-induced vasodilation and cardiac depression can lead
to severe hypotension unless doses are markedly reduced
 etomidate or ketamine is an alternative agent
● thiopental does not directly precipitate bronchospasm
 endotracheal intubation causes intense airway stimulation leading
to bronchospasm especially in pts with reactive airway disease
 propofol or ketamine is often chosen as an alternative for induction
in patients with reactive airway disease
(2) Ketamine
● pts with CHF & Hypotension
 15%-20% of the usual induction dose of ketamine is used
 appropriate choice for IV induction of severely hypovolemic patients
 causes the least fall in blood pressure of any of the induction agents
● pts with reactive airway disease
 appropriate agent for IV induction of asthmatic patients
 reduces the increase in bronchomotor tone with
endotracheal intubation
 causes the least amount of ventilatory depression and
loss of airway reflexes
● produces a dissociative state of anesthesia
 used as the sole anesthetic for brief, superficial procedures
because it produces profound amnesia and somatic analgesia
● ONLY agent that increases BP and HR and decreases bronchomotor tone
● increases sympathetic tone which causes direct cardiac depression
 evident if given to patients with high preanesthetic sympathetic tone
as in patients in hemorrhagic shock
● PROBLEMS:
▪ the induction of copious oropharyngeal secretions
 drying agent such as glycopyrrolate is generally administered
with ketamine
▪ produces no muscular relaxation, does not control visceral pain,
and may not completely control patient movement
 less useful in abdominal cases or delicate surgery
▪ increased BP and HR
 contraindicated in pts with CAD because tachycardia and increased BP
may cause myocardial ischemia
▪ ketamine may further increase ICP because it is the only IV agent
that increases cerebral blood flow
 caution in pts with traumatic brain injury
▪ clinically important side effect of ketamine is emergence delirium
 adults and older children, supplemental benzodiazepines or volatile
agents are generally effective in preventing this
● potent pain-relieving effects of ketamine have been exploited
for preemptive analgesia
 infused continuously before incision and continued through
wound closure
 postoperative morphine consumption was significantly lower than
pts not using ketamine
(3) Propofol
- commonly used as an induction agent for ambulatory surgery
- short-acting induction agent that is associated with smooth,
nausea-free emergence
- small doses useful for short-term sedation during brief procedures
such as retrobulbar or peribulbar eye blocks
- produces excellent bronchodilation
 useful in pts who smoke & asthmatic pts
~ 0% wheezing after 2-5 minutes intubation, 45% for thiobarbiturate
and 26% oxybarbiturate (in asthmatic pts)
~ airway resistance was less relative to those using thiopental
or etomidate (in smoking, non-asthmatic pts)
 bronchodilatory effects of propofol and ketamine are mediated through
blockade of vagus nerve–mediated cholinergic bronchoconstriction
- PROBLEMS:
▪ primary limitations of propofol are pain on injection and BP reduction
 NOT for pts with hypovolemia or those who may tolerate hypotension
poorly, such as those with severe CAD
(4) Etomidate
- pts with CHF & Hypotension
- an imidazole compound that produces minimal hemodynamic changes
- preserves blood pressure in most patients
 alternative for induction of patients with cardiovascular disease
- PROBLEMS:
▪ burning pain on injection
▪ abnormal muscular movements (myoclonus)
▪ adrenal suppression when given as prolonged infusion
for sedation of critically ill patients
(5) Midazolam
- sometimes used for induction
▪ causes minimal cardiovascular side effects
▪ much shorter duration of action than diazepam
- onset of action is acceptably rapid
- even in smaller doses
 profound amnesia for painful or anxiety-producing events
- frequently selected for induction of patients for cardiovascular surgery
- combines powerful anxiolytic and amnesic effects
- smaller doses used to premedicate anxious patients and as a component
of a multidrug anesthetic
Opioids
- are used in the majority of patients undergoing general anesthesia
- given systemically to many patients receiving regional or local anesthesia
- a component of a multifaceted anesthetic
 produce profound analgesia and minimal cardiac depression
- Problem:
▪ ventilatory depression and inconsistent hypnosis and amnesia
~ usually be provided by other agents
- Reasons of Opiod use:
▪ they reduce the MAC of potent inhalational agents
~ Fentanyl reduces MAC of sevoflurane by 59% & MACawake by 24%
** MACawake = alveolar concentration at which an emerging patient
responds to commands
▪ blunting hypertension and tachycardia associated with manipulations such as
endotracheal intubation and surgical incision
▪ provide analgesia
 extends through the early postemergence interval
 facilitates smoother awakening from anesthesia
▪ complete anesthetics in a high proportion of patients
 but in doses 10 to 20 times the analgesic dose
 providing not only analgesia but also hypnosis and amnesia
~ prompted their use in cardiac surgery patients sometimes as sole anesthetic
agents and more often as a major component of the anesthetic
 ▪ added to local anesthetic solutions in epidural and intrathecal blocks
 improve quality of analgesia
Intermediate-Acting Agents:
- Morphine, Hydromorphone, and Meperidine
- are inexpensive
- less commonly used for maintenance of anesthesia
- more common use in postoperative analgesia
▪ Fentanyl
- synthetic opioid that is 100 to 150 times more potent than morphine
- commonly used for maintenance of anesthesia
 shorter duration of action and rapid onset
Newer Synthetic, Short-Acting Opioids:
- sufentanil and alfentanil
- used during anesthesia because they are quickly metabolized and excreted
▪ Remifentanil
- metabolized by serum esterases
- is particularly short acting
- does not accumulate during prolonged infusions
 therefore often used as part of IV anesthetics.
Neuromuscular Blockers
- Anesthesiology 50 years ago
 use of only 1 agent  expected to produce all components of anesthesia
- Problem: amount of agent to produce deep muscle relaxation greatly
exceeded the amount to produce hypnosis & amnesia
 Solution: Combination of Agents
~ Muscle relaxants + IV Agents for Hypnosis, Amnesia, Analgesia
Two Categories of Neuromuscular Blockers
(1) Depolarizing (Noncompetitive)
- exert agonistic effects at the cholinergic receptors of the NM junction
- causing evident as fasciculations
- followed by an interval of profound relaxation
** Succinylcholine
- only depolarizing agent still in use (endotracheal intubation)
- rapid onset and short duration of action (only 5 minutes)
- can be administered in high doses
 rapidly metabolized by plasma pseudocholinesterase
 except in pts with atypical or absent pseudocholinesterase
- Problems:
• Life-Threatening Hyperkalemia
~ esp. in pts with Burns, Paraplegia, Quadriplegia, Massive Trauma
• Malignant Hyperthermia (MH)
~ when combined with a volatile agent
~ contraindicated in pts. With risk/history of MH &
Muscular Dystrophy
• Bradycardia (esp. in children)
• Masseter Spasm (in children)  a benign effect
• Implicated in causing postoperative muscle pain
 reduced by pretreatment of a Nondepolarizing agent
- due to many sporadic complications; use it only for
Rapid Sequence Induction
~aka; in situations in w/c airway must be rapidly secured
 usually, nondepolarizing agents are chosen (ex. Cisatracurium)
(2) Nondepolarizing (Competitive)
- compete for receptor sites with acetylcholine
- in situations not needing Rapid Sequence Induction; these are preferable
- magnitude of block dependent on the ff:
~ availability of acetylcholine
~ affinity of the agent for the receptor
- their use is chosen based on:
• mode of excretion
• duration of action
• side effects (usually Vagolysis & Histamine Release)
- used when Succinylcholine is contraindicated:
 in pts anticipated to have easy intubation
 also when intraoperative relaxation is required to facilitate
surgical exposure
- see Table 18-4 for specific dosages
- Dosing of Nondepolarizing Agents: Factors to Consider
• ensure anesthesia prior to chemical paralysis
 paralysis can mask the signs of inadequate anesthesia, sedation, and
analgesia in postoperative pts
 always prevent intraoperative awareness during general anesthesia
• intubation would require higher dosage of Neuromuscular blockers
than what is needed for surgical relaxation
 smaller dosage is required if neuromuscular blockers
are used after intubation
• other anesthetic drugs potentiate the actions of nondepolarizing agents
 check drug-drug interactions
 Ex. Desflurane potentiates Vecuronium ~20% more than Isoflurane
• individual responses to muscle relaxants vary widely
• subtle blockade can be difficult to detect and can be
associated with postoperative problems (most important factor)
 use of the TOF (Train-of-Four) Fade Ratio
~ technique used to asses adequacy of neuromuscular blockade
and the adequacy of pharmacologic reversal; is
semiquantitative
~ still controversial; some recommend TOFFR of >0.7, other >0.9 or 1.0
~ TOFFR of 0.7 means that the fourth of four muscle twitches in
response to supramaximal stimuli delivered at 0.5-second intervals to
the ulnar nerve is at least 70% of the magnitude of the first twitch
~ 1997 Study: (>0.7 TOFFR)
• >0.6 = able to sustain 5 seconds of head life
(commonly used clinical index of adequate reversal)
• >0.7 = pts able to maintain patent airways; O2 Saturation @ 96%
~ 2003 Study: (0.9 to 1.0 TOFFR)
• <0.9 = diplopia & difficulty tracking objects
= incapable of strong incisor opposition
** Cisatracurium
- largely metabolized in serum by Hoffman degradation
- for pts w/ reduced renal fnx.
 pts w/ reduced renal fnx. cannot use Pancuronium & Vecuronium
because these drugs are eliminated renally
** Atracurium, Vecuronium, Rocuronium (all intermediate-acting)
- found to produce TOFFR of 0.9 in 37% of pts after 2 Hours
after after receiving relaxants
Additional Notes on Neuromuscular Blockers:
-- complications associated with neuromuscular blockers relate to inadequate
reversal at the conclusion of cases or inadequate assessment of reversal
-- Nondepolarizing relaxants are reverse by anticholinesterase (neostigmine or
edrophonium), accompanied by atropine or glycopyrrolate to counteract the
muscarinic effects of the anticholinesterase
-- Study: Pancuronium was harder to reverse than Vecuronium or Atracurium
with the use of Neostigmine. Pancuronium was also associated
with higher incidence of atelectasis or pneumonia, others were not.
-- In renal disease, half-lives of ff. drugs were prolonged:
~ d-tubocurarine, rocuronium, vecuronium, and pancuronium
-- For such pts with renal ds., alternatives are: atracurium or cisatracurium
(which are metabolized by Hoffman degradation and thus
do not have prolonged half-lives)
ANESTHESIA EQUIPMENT
-- despite rapid development over the years, modern systems still require
monitoring for hazards of gas delivery
-- primary concern is inadvertent delivery of a hypoxic gas mixture.
-- adverse outcomes could be monitored using pulse oximetry or capnography
-- essential elements of an anesthesia machine:
▪ gas sources (oxygen, nitrous oxide, and air)
▪ flowmeters  allow independent administration of individual gases
▪ flow-proportioning device
 automatically reduce the flow of nitrous oxide if the flow of oxygen
is reduced below a safe concentration
** fail-safe valves
 minimize the chance of delivering a hypoxic gas mixture
** gas-scavenging systems
 permit the elimination of anesthetic gases and vapors that otherwise
would contaminate the operating room
-- H cylinders = deliver anesthetic gases
E cylinders = delivers oxygen
-- most commonly used anesthetic circuit is a circle system with one-way valves
that properly direct inspired and expired gas flow
-- circuits include CO2 absorbers:
▪ Soda Lime (sodium hydroxide, calcium hydroxide,
and potassium hydroxide)
▪ Baralyme (combination of barium hydroxide and calcium hydroxide)
PATIENT MONITORING DURING AND AFTER ANESTHESIA
-- essential components of monitoring:
▪ observation and vigilance
▪ instrumentation
▪ data analysis
▪ institution of corrective measures
-- goals: provide optimal anesthetic management and detect abnormalities
-- ASA Standards:
STANDARD 1:
▪ qualified anesthesia care provider must be continuously present in OR
▪ practitioner must continuously monitor the status of the patient
▪ practitioner must alter anesthesia care based on the patient's
response to anesthesia & surgery
STANDARD 2:
▪ continuous assessment of ventilation, oxygenation, circulation,
and temperature
▪ specifics:
~ O2 analyzer that alarms for low-O2 Concentration
~ Pulse Oximetry to quantitatively asseses Blood Oxygenation
~ Monitor CO2 content in expired gas & expired gas volume
~ Device capable of detecting disconnection of breathing
system components. Must be able to give audible alarm signal.
~ ECG continuously monitored during anesthesia.
 BP monitored every 5mins.
~ Temperature Evaluation

Blood Pressure Monitoring

-- use of noninvasive blood pressure monitoring
 automated oscillometric blood pressure analyzers
-- for other cases: invasive blood pressure monitoring used if:
▪ intraoperative use of deliberate hypotension
▪ continuous blood pressure assessment in patients
~ esp. if with significant end-organ damage or
high-risk surgical procedures
▪ anticipation of wide perioperative blood pressure swings
▪ need for multiple blood gas analyses
▪ noninvasive measures are insufficient (ex. morbidly obese pts)
-- sites for arterial cannulation
▪ Radial Artery
- most commonly cannulated
~ superficial; ease of cannulation; adequate collateral
flow from the ulnar artery
▪ Femoral, Brachial, Axillary, Ulnar, Dorsalis pedis, and Posterior Tibial
 Possible complications:
- hematoma, neurologic injury, arterial embolization,
limb ischemia, infection, and inadvertent intra-arterial injection of drugs
- intra-arterial catheters aren’t placed in extremities
~ potential vascular insufficiency

Electrocardiography
-- standard of care during the administration of anesthesia
-- informs if pt has dysrhythmias and cardiac ischemia
-- ECG tracings is the cornerstone of cardiopulmonary resuscitation
Ventilation Monitoring
-- ventilation is depressed or abolished with sedation, opiods, and anesthesia
-- means of assessment:
▪ chest expansion
▪ auscultation of breath sounds
▪ evaluation for evidence of upper airway obstruction
▪ stridor
End-Tidal Carbon Dioxide (ETco2)
-- enhanced monitoring of ventilation and detection of esophageal intubation
-- normally, difference between ETco2 and Paco2 is 2 to 5 mm Hg
-- gradient between end-tidal and arterial CO2 reflects dead space ventilation
 increased in cases of decreased pulmonary blood flow
 increased in pulmonary air embolism or thromboembolism
and decreased cardiac output
-- provide important information regarding systemic perfusion
Oxygenation Monitoring
-- monitoring of Fio2 and hemoglobin oxygen saturation is a standard of care
-- detect the delivered oxygen concentration (Fio2)
-- fail-safe devices, low–oxygen delivery alarms, and oxygen ratio monitors
 decreases the chance of delivering a hypoxic gas mixture