Cardiovascular Anesthesia: Choice of Agents and
Related Issues
Overview:
Probably no single "ideal" anesthetic for patients
with coronary vascular disease
Anesthetic choice, as assessed by large, randomized clinical
trials, does not appear to influence outcome, i.e. perioperative
myocardial infarction incidence {MI incidence = about 4%;
mortality = approximately 2%-3%}
Rationale
for anesthetic choice:
Nature and extent of pre-existing cardiac
disease/dysfunction
Pharmacology of the individual drug(s)
Examples:
Case I -- patient has severe congestive heart failure +
evidence of significant loss of myocardial muscle mass due
to previous infarction
Anesthetic choice should favor agents
which have relatively less myocardial depressants
characteristics
Case II -- patient has angina which occurs only on
significant exertion; otherwise the patient appears healthy
Anesthetic choice would favor a
volatile agent which would tend to reduce myocardial
oxygen demand (myocardial depressant)
Most
patients would benefit most likely from some degree of
myocardial depression induced by the anesthetic agent (with
attendant reduction in myocardial oxygen demand); however,
patients with very limited myocardial reserve are at risk for
congestive heart failure caused by the anesthetic.
Good patient tolerance to the presence of an endotracheal
tube, nasogastric tube, and/or airway suctioning
Disadvantages:
Hypertension/tachycardia during surgical stimulation {for
cardiac surgery, these effects could be expected during
sternotomy & aortic manipulation}
Bradycardia/Hypotension when opioids are combined with
benzodiazepines/other sedatives, during induction
Muscular rigidity during induction {may occur also during
emergence}
Awareness may not be noted by intraoperative personnel, if
patient is totally paralyzed
Recall of intraoperative activity may occur unless an amnestic
agent is also administered
Extended recovery time possible {noting here particularly
spontaneous ventilation} -- Less likely with careful dosage
selection of opioid and other CNS depressants agents--
[exception remifentanil (Ultiva) common extremely short-acting
fentanyl (Sublimaze) derivative which is rapidly hydrolyzed by
tissue esterases]
Limited ability to titrate with high-dose procedures
Use
of a "primary opioid" technique: in a patient with
significant/severe myocardial dysfunction
With
normal ventricular function, opioids would likely be combined with
other anesthetics or vasoactive drugs
Planned
extubation time: major factor in selection of opioid dosage &
specific opioid to be used.
Opioid actions that indirectly
affect cardiac status
Bradycardia-- vagus nerve activation
Arterial & venous dilatation due to
sympathetic reflex selective suppression (manifestation --
orthostatic hypotension)
Histamine release {particularly for morphine,
meperidine (Demerol) and other chemically similar agents)
Indirect actions: readily managed; do not
prevent large opioid dosages for anesthesia application
Management of Opioid Effects
"Cholinomimetic" effects --
antagonized by anticholinergic agents, e.g.
glycopyrrolate (Robinul), atropine -- use of these
agents avoided or limit opioid-induced bradycardia
Hemodynamic (hypotensive) effects:
Normovolemic patient, supine, with
slow opioid IV infusion for example with morphine 5
mg/minute: minimal hypotension would be seen
Histamine effects can be prevented
by histamine1 &
histamine2
receptor blocking drugs
Hypotensive effects also respond
to:
legs-up position
IV infusion of fluids
vasoactive drugs such as
phenylephrine (Neo-Synephrine) (alpha-adrenergic
agonist)
ephedrine is indicated in
the management of hypotension secondary to
bradycardia and vasodilation
Characteristics
of a commonly used opioid, fentanyl (Sublimaze)
Dosage, when used as a single agent: 20-50 ug/kg
[starting] + 2-3 micrograms/minute subsequently
Consequence:
very significant analgesia
sleep
on consciousness
Similar large dosages of morphine, meperidine
(Demerol) and similar agents are avoided due to side effects
associated with these large dosages
More
about disadvantages associated with high-dosage opioid use:
Typically
opioid elimination is SLOW [Exception: remifentanil (Ultiva)
{rapidly hydrolyzed by tissue esterases}]
Consequences of slow opioid elimination:
Prolonged times for consciousness recovery
Prolongation of time to spontaneous ventilation
Note that prolonged recovery, in this context, may be
advantageous since mechanical ventilation support will
be continued into the postoperative time-frame, which
may last several hours or overnight -- in patients with
cardiovascular disorder, the use of narcotic
antagonists, e.g. naloxone (Narcan); naltrexone (ReVia)
is relatively contraindicated
Positive-pressure
ventilation is impeded by opioids, which induced apnea &
skeletal muscle rigidity
In
patients breathing pure oxygen prior to anesthesia
induction, rigidity which prevents positive-pressure
ventilation is not an immediate emergency
Rationale:
if lungs are filled with
oxygen, oxyhemoglobin desaturation will be prolonged
{due apneic oxygenation} -- typically ample time for
rigidity to subside
CO2
tension rises slowly during this period
When rigidity subsides, it is important
to correct hypercarbia probably, thus relieving elevated
PA pressures and possible systemic hypotension.
Forcing positive-pressure ventilation during opioid-induced
rigidity tends to impede cardiac function by reducing venous
return, secondary to increased intrathoracic pressure
To relieve opioid-induced rigidity: a fully paralyzing
muscle relaxant dose, given IV, will reverse the rigidity
within 1-2 minutes
Opioid-related rigidity can occur both during induction and
emergence
Reduction in rigidity intensity: small dose of muscle
relaxants {reversal by fully, paralyzing doses}
Rigidity, varied in presentations, may resemble seizures;
however, in humans seizure is probably not produced even
with the very highest doses of fentanyl (Sublimaze)
Intraoperative Awakening
Occurring in response to painful stimuli
Associated with reduced drug concentration
Significant problem because:
Paralyzed patient will not be able to
indicate somatic signs of awakening
Autonomic nervous system and/or
hemodynamic changes are not reliable indicators of
patients' awakening
Approaches
which reduce likelihood of patient intraoperative awareness
Adequate administration of preanesthetic agents or
intraoperative anesthetic supplementation (for
example addition of a benzodiazepine)
Opioid Dose titration [titrating to effect, than
maintenance by IV infusion of drug]
Using muscle relaxants only if needed and only at the
minimum dosage required
Anesthetist awareness of inadequate anesthesia signs
Signs of inadequate anesthesia include:
Somatic signs, which may be difficult to result in
the presence of muscle relaxants
increased electromyographic
activity
coughing, bucking on
endotracheal tube
movement {particularly when
correlated with noxious/painful stimulation which
may include manipulation of endotracheal tube, skin
incision, sternotomy, electrocautery of skin or
periosteum}
Sympathetic nervous system signs:
tearing
sweating
mydriasis -- may be confounding in
the presence of some autonomic nervous system drugs
Hemodynamic effects-observation of hemodynamic
changes may be made more difficult by drug therapy or by
cardiovascular disease itself
increased blood-pressure associated
with painful stimulation
increased heart rate associated
with painful stimulation [increased heart rate is
observed less frequently than an increase in BP}
EEG -- index of CNS electrical activity
presence of "arousal"
patterns in the electroencephalogram
evoked potential recovery (e.g.
auditory)
Intraoperative
awareness-solution to the problem:
Primary
anesthetist responsibility: maintain patient's
unconsciousness for the duration of the procedure
The use of an amnestic drug such as midazolam
(Versed) or scopolamine is not a substitute for
insuring patient unconsciousness
It is possible that intraoperative awakening leads
later to sleep disturbances, anxiety attacks, and
other unpleasant effects during the postoperative
time frame
A
reduced opioid approach involves adjuvants, typically a
short-acting sedative administered by IV infusion, e.g.
midazolam (Versed) or propofol (Diprivan)
Favorable
characteristics:
administration can be continued
postoperatively in the ICU setting
"fairly rapid" awakening
Analysis of two protocols: (1) propofol (Diprivan)
infusion in combination with low-dose fentanyl (Sublimaze) with
(2) high-dose fentanyl (Sublimaze) in a subset of
cardiac surgical patients with low myocardial output
Conclusion: (a) propofol (Diprivan)/reduced-dose
fentanyl (Sublimaze) patients awakened earlier with earlier
extubation possible. (b) no adverse effect on myocardial
contractility
Midazolam
(Versed) is often used to supplement opioid anesthesia -- and heart
because of relatively minimal, non-dose-dependent cardiovascular
effects
Etomidate (Amidate):
maintenance of reflex responsiveness
maintenance of sympathetic nervous tone
relatively limited use due to concerns about
steroid synthesis inhibition
Propofol (Diprivan):
vasodilation effect
slight negative chronotropic effect
Advantages: rapid control of patient responds
to noxious stimulation; short recovery time
Thiopental (Pentothal) -- similar overall to propofol (Diprivan) with a longer
recovery time
Interaction
of Sedative-Hypnotics & Opioids:
Hypnotics
reduce opioid dosage requirements
recovery time length may not be shortened
Without concommittant reduction of sedative-hypnotic and
opioid dosages, prolonged recovery times may be observed
{greater than that associated with either drug alone}
Opioid-mediated Ventilatory/respiratory depression & sleep: Important
synergistic interaction
Significant concern (dangerous) in the immediate
post-operative time {reduction in noxious stimulation
associated with surgery; stimulation which promotes
respiration}
Patient may be monitored with less vigilance and early signs
of respiratory depression may be missed
Combination
of opioids at anesthetic dosages with sedative-hypnotics can
precipitate a hypotensive response during induction
Low-dose (< 75 ug fentanyl (Sublimaze); 20 ug sufentanil
(Sufenta))administration of an opioid following induction
with a hypnotic can produce significant systemic
hypertension, which responds to sympathomimetic vasopressor
drugs
Advantage of combining a hypnotic and an opioid, insuring
unconsciousness, during intraoperative periods of total
paralysis, is that resulting hypotension may be really
controlled
for very critically ill patients who
may not tolerate even mild hypotension, the combination
of opioid-sedative-hypnotics should be avoided
Effective
management of sudden, arousal in response to noxious simulation
may involve a drug that produces a rapid CNS response. CNS
agents are preferable to vasodilators/sympatholytics because the
somatic and/or sympathetic responses may be associated with pain
awareness.
Supplemental for both intravenous anesthetics & potent
inhaled agents
May be the primary anesthetic used with muscle relaxants
Cardiac
surgical application concerns:
Mild, but potentially detrimental effects in patients with
compromised cardiac function
NO:
decreases
cardiac output
increases
systemic vascular resistance (afterload)-this effect on
vascular resistance occurs when nitrous oxide is given alone
or in combination with opioids
Occasionally, NO-induced hypertension and reduced myocardial
contractility are sufficient to mandate discontinuation of the
agent -- cardiac function typically recovers within minutes
{this rapid recovery allows ready testing of patients tolerance
to NO}
A particular concern has been the observation that in patients
with coronary vascular disease, NO may induce ischemia in the
region supplied by a "critically" stenotic artery and,
as a result, induce regional myocardial dysfunction-- this
ischemic NO effect has not been observed in coronary bypass
surgery when NO is used to supplement fentanyl (Sublimaze)
anesthesia
Other detrimental effects:
NO
expands air-filled spaces {including air emboli}-spaces
which may occur in cardiac chambers or in saphenous vein
grafts. -this characteristic has led some to suggest that
nitrous oxide should not be used in operations involving
extracorporeal circulation
if, during a procedure, arterial air
embolism is suspected, NO use should be discontinued
NO
should not be used with pneumothorax, unless a functioning
thoracotomy tube has been inserted
Some
NO advantages {e.g. rapid onset/recovery} are also observed
with more current inhaled agents such as desflurane (Suprane)
and sevoflurane (Sevorane, Ultane). These agents do
not exhibits expansion in air-filled volumes
NO
may potentiates truncal rigidity caused by opioids
The use inhalational agents in cardiac surgery
involves a balancing between desirable features and
disadvantages
Advantages
of inhalation anesthetics
Fulfill objectives of anesthesia:
causes unconsciousness
muscle relaxation
rapid ventilatory function recovery {allowing early tracheal
extubation postoperatively}
Dose-related reduction in ventricular work/oxygen
consumption
Easily reversible
Amnesia
Titratable myocardial depression
Attenuation of autonomic {sympathetic} response to surgical
stimulation and cardiopulmonary bypass
Disadvantages of inhalation anesthetics
Myocardial depression-excessive under some conditions
Hypotension, secondary to either vasodilation or reduced by
myocardial contractility
Incomplete suppression of sympathetic responses to
noxious/painful stimulation
Absence of postoperative analgesia {i.e., sub-anesthetic
concentrations do not provide analgesia}
Post-operative shivering, secondary to peripheral vasodilation
-- would be accompanied by increased oxygen demand because of
excessive heat loss
In
cardiovascular surgery, the combination of volatile anesthetics and
narcotics optimizes advantages of both, while reducing the
likelihood of untoward systemic responses
Tailoring
of inhalational agents to the patient's needs-- examples:
Patient
has a high systemic vascular resistance [high afterload, which
necessarily increases myocardial oxygen requirements by
increasing ventricular wall tension]: Appropriate inhalational
agent = possibly isoflurane (Forane) which produces vasodilation
Hypertrophic cardiomyopathy is usually asymmetrical
(affecting only one side) --
Myocardial dysfunction occurs because
of:
reduced
(narrowed) ventricular outflow
reduced
ventricular chamber size
valvular
dysfunction
Factors that worsen hypertrophic cardiomyopathy --
factors which increased myocardial contractility, e.g.
sympathetic
nervous system simulation (stress)
medications,
for example digoxin (Lanoxin, Lanoxicaps)
reduced
blood return which may occur in dehydration or
following excessive diuretic use
Forms of the disease:
idiopathic
hypertrophic subaortic stenosis: inherited,
autosomal dominant; incidence = about 1 out of
10,000 individuals
acquired
hypertrophic cardiomyopathy secondary to high blood
pressure (hypertensive hypertrophic cardiomyopathy)
Hypertrophic Cardiomyopathy*
"In this case the muscle thickening
use of equal severity throughout the whole left
ventricle"
"In some cases of asymmetric
septal hypertrophy obstruction to the outflow blood from the
heart may occur as shown here. Note that the mitral
valve now touches the septum, blocking the outflow tract
(Systolic Anterior Motion of the Mitral Valve or SAM). Some
blood is leaking back through the mitral valve (Mitral
Regurgitation)."
"In this form of hypertrophic
cardiomyopathy the muscle thickening occurs predominately at
the tip (apex of the left ventricle). Only a small
slit-like cavity remains"
Isoflurane (Forane): significant coronary vasodilator {other
volatile anesthetics also, but to a reduced extent}--
dose-dependent effect; clinically significant at 1 MAC or
greater
Coronary steal: with specific, regional
coronary stenosis, isoflurane (Forane)-mediated dilation of
other coronary vessels tend to cause blood shunting away
from stenotic arteries
Because of coronary steal, isoflurane (Forane)
should be used in limited dosages, noting that it is rarely
used alone at high concentrations for general anesthesia,
but rather in combination with other agents.
Faster recovery may not be advantageous in the context
of postcardiac patients, since more sedation may be
required in the ICU before attainment of hemodynamic
stability and before extubation which occurs, in the case of
early extubation, about 4-6 hours post surgery
More about Inhalational Agents
Volatile agents in patients with good cardiac
performance:
Isoflurane (Forane) (& halothane (Fluothane),
infrequently used in adult patients): effective as primary
anesthetics
Desflurane (Suprane) & sevoflurane (Sevorane,
Ultane): similar properties {hemodynamic} to
isoflurane (Forane)
very rapid onset
rapid recovery
Particularly useful in patients with
coronary vascular disease but with normal ventricular
function
Low cardiac index (< 2.0 liters/min/m2 with
normal/elevated preload)
Mechanical abnormalities such as valvular heart disease
Other factors to consider include:
Response to stress, hypertension
Ventricular wall motion abnormalities-may not be sufficient
to be reflected in abnormal cardiac performance indices;
however, may be indicative of underlying problems which will
be evident intraoperatively
Anesthetics
Use in myocardial dysfunction: Note the importance of dose-related
dependencies
Example: a drug may be contraindicated, because of excessive
myocardial depression, if used as the primary anesthetic agent;
however, when used in combination with another drug, it may be
useful
Full anesthetic isoflurane (Forane) dose:
possibly unacceptable attenuation of cardiac performance
Reduced anesthetic isoflurane (Forane)
dose: acceptable and allows better management of systemic
responses to noxious/painful stimulation
reduce pain which may be associated with vascular cannulation
(without producing cardiac/ventilatory depression)
amnesia
anxiolytic effects
These objectives are similar to those for other
surgeries; however, doses may be affected in accord with the
specifics of the cardiovascular disease, the presence of other
co-existing diseases as well as the presence of other chronic
drug treatments
Premedication
Examples:
Patient condition: coronary vascular disease,
but with normal or least adequate left ventricular resting
function; no pulmonary insufficiency
Medications
-- generally heavily premedicated before surgery using:
an opioid
a sedative-hypnotic agent
Example
#1:
Diazepam (Valium) [0.1-0.2 mg/kg, orally {sip of
water}] -- timing = 1-2 hours before transfer to the
operating room
Morphine: 0.1 mg/kg intramuscular injection --
timing = 30 minutes before transfer to the operating
room
Example
#2:
Lorazepam (Ativan) 25-50 ug/kg orally -- timing =
1-2 hours before transferred to the operating room
IV fentanyl (Sublimaze) 0.5-1 ug/kg administered as
needed following the first IV cannulation
These sequences provide amnesia
(diazepam (Valium); lorazepam (Ativan))
Larger doses of longer-acting agents
provide an advantage for long-duration surgery;
note the absence of cardiac depression with these agents
[respiratory depression: minimal; however the patient
may be encouraged to take the occasional deep breath to
avoid atelectasis and hypercarbia]
During anesthesia/surgery
preparation-- it may be useful for the patient to
breathe oxygen-enriched air
For patients on calcium channel blockers,
continued use of the agents may be preferable:
Rationale:
The calcium channel blocker was
probably given to manage angina, hypertension, or
arrhythmias. If the drug was efficacious in these
applications, it would be an advantage to continue the
use of the blocker during the surgery when surgical
conditions might provoke these cardiac abnormalities
The anesthetist would be prepared to
manage a side effect of calcium channel blockade word to
occur during the procedure {these side effects could be
reasonably expected to include systemic hypotension and
atrioventricular conduction blockade [recall that the
main depolarizing ion at the AV node is calcium, hence
calcium channel blockade could slow AV conduction})
Appropriate
to take first-daily dose of the following classes of agents
(particularly if the surgery scheduled for late morning)
long-acting nitrates
adrenergic receptor antagonists
calcium channel antagonists
possibly antiarrhythmic agents, including digoxin (Lanoxin,
Lanoxicaps), especially for patients predisposed to atrial
arrhythmias with high ventricular following rates [note that
digitalis glycosides decrease AV conduction, secondary to
increased vagal tone; reduced may be conduction protects the
ventricles in the presence of atrial tachyarrhythmias]
Clonidine
(Catapres): controversial in this setting:
Possible reduction in intraoperative opioid requirement with
shortening of post-operative ventilation requirements
Possible problems with low systemic blood pressures (reduce
systemic vascular resistance) -- this problem may be
sufficiently serious to require intraoperative vasopressor
support for patients chronically receiving clonidine (Catapres)
During cardiopulmonary bypass, low BP/refractory response to
vasopressors may be caused by ACE inhibitors
Drug discontinuation on the surgical day is reasonable; however
hypertension may still require inner operative management using
vasopressors, e.g. phenylephrine (Neo-Synephrine) (0.5-1 mg); or
norepinephrine (Levophed)
Combination of oral antacids & antisecretory drugs
such as glycopyrrolate (Robinul) cimetidine (Tagamet) --
rationale = reduction of mucosal damage/symptoms
perioperatively
Glaucoma
medication:
Continued use of pilocarpine (Pilocar) eyedrops for narrow angle
glaucoma
Normal dosage regimen should be continued during the
perioperative.
Systemic anticholinergic agents may be used providing topical
miotic treatment is maintained
Intraoperative
management of insulin-dependent diabetes
Primary
objective: monitor perioperatively serum glucose [maintain
between 100-250 mg/dL]
Cardiopulmonary bypass may pose significant challenges for
appropriate blood glucose maintenance
Factors contributing to insulin resistance (leading to
significant hyperglycemia)
Sympathetic nervous system/endocrine stress response to
cardiopulmonary bypass
Administration of sympathomimetic agents
Resolution:
may require bolus insulin
administration at high concentration to avoid
physiological consequences of severe hyperglycemia,
including hyperosmolar coma, CNS ischemic damage,
excessive diuresis
Intraoperative management-one approach2
regular insulin infusion 2-5 U/hr for
diabetic patients (with or without insulin dependencies)
throughout the operation
hourly glucose level determination
(administration note 10-20 g glucose is serum glucose
decreases to below 100 mg/dL
adjust insulin infusion rate up using
intravenous bolus administration of 10-20 units of
regular insulin, if needed, after cardiopulmonary bypass
to provide a serum glucose range of 100-200 mg/dL.
Overview: Multiple methods are available for
managing intraoperative ischemia; interventions are often
implemented at the same time
Hemodynamic
abnormalities:
reduce
tachycardia if present
correct
for hypotensive or hypertensive states
ß-adrenergic
receptor blockade
Rationale: reduction in myocardial oxygen requirement
secondary to negative chronotropic (reduced rate) &
negative inotropic (reduced contractility)
In patients with unstable (vasospastic or Prinzmetal's)
angina: reduction in ischemia & myocardial infarction
Cautious use in patients with impaired pulmonary function
(e.g. beta-adrenergic blockers are typically contraindicated
in asthma because sympathetic,ß-adrenergic
receptor-mediated tone causes bronchodilation, which is
obviously desirable); also cautious use in patients with
significant left ventricular function deficits, even though
ß-adrenergic
receptor blockers may be helpful in patients with
mild/moderate congestive heart failure
Nitroglycerin
(intravenous)
Mainstay
of medical treatment for the ischemic myocardium
Nitroglycerin reduces preload (particularly important with
high filling pressures & arterial pressure)
Hypotensive states & sympathetic nervous system
reflex-mediated tachycardia may occur
Heparin
Pathologic
thrombosis -- important etiology in myocardial ischemia
Heparin:
reverses ischemia
may prevent myocardial muscle damage
(infarction)
Note that in cardiopulmonary bypass (CPB): patients are
usually heparinized in advance; however, immediate
anticoagulation before CPB would be indicated for pre-bypass
myocardial ischemia
Use specific antagonist,
e.g. protamine sulfate (note!- excess protamine also has
an anticoagulant effect)
Calcium
Channel Blockers (management of intraoperative ischemia
cont'd)
Especially effective in management of intraoperative ischemia
secondary to vasospastic (Prinzmetal's) angina
Effective for angina induced by hypertension (recall that
hypertension can induce ischemia by increasing myocardial oxygen
requirements secondary to the increased wall tension [afterload])
Effectiveness of calcium channel antagonists in managing
myocardial ischemia interoperability depends on concurrent use
of other interventions, including the use of ß-adrenergic
receptor antagonists & anticoagulation
Cardiopulmonary bypass (CPB)
Hemodynamically
unstable patients with myocardial ischemia should be placed on
CPB assumed as possible
Rationale-
on CPB the heart is
allowed to "rest", significantly reducing
oxygen demand with maintenance of coronary vascular
perfusion pressure
while on the bypass the
patient may be given other drugs such as ß-adrenergic
receptor antagonists without the risk of cardiovascular
instability
Intra-aortic
balloon pump
Appropriate for ischemia which is not manageable by drugs
Rationale:
reduces myocardial oxygen
demand (wall tension) by decreasing resistance to left
ventricular ejection
improves coronary vascular
perfusion by increasing diastolic pressures
Circumstances for use:
Preoperatively-these patients
have persistent symptoms (should not delay CPB for the
hemodynamically unstable patient)
Use during the
procedure:-for patients with ischemia refractory even after
CPB
Patient myocardial performance
evaluation following revascularization (coronary artery bypass
grafting)
Adequacy
of grafting may be assessed following CPB through the use
transesophageal ultrasound [TEE ultrasound], which may detect
abnormal ventricular wall motion [hypokinetic regions]
A "problem" graft may be due to a surgical technical
problem or even vasospasm (internal mammary artery) -- which may
respond to calcium channel antagonist treatment or to the
use of vasodilators
Other
post-bypass grafting ischemia episodes may occur because of air
embolization (especially in the right coronary artery)-rate
country can or failure secondary to this event may require
returning to CPB with high coronary perfusion pressure and
administration of nitroglycerin (vasodilator)
1Primary Reference: Ross,
AF, Gomez, MN. and Tinker, JH Anesthesia for Adult Cardiac
Procedures in Principles and
Practice of Anesthesiology (Longnecker, D.E., Tinker, J.H. Morgan,
Jr., G. E., eds) Mosby, St. Louis, Mo., pp. 1659-1698, 1998.
2Primary Reference:
Shanewise, JS and Hug, Jr., CC, Anesthesia for Adult Cardiac
Surgery, in Anesthesia, 5th edition,vol 2, (Miller, R.D, editor;
consulting editors, Cucchiara, RF, Miller, Jr.,ED, Reves, JG,
Roizen, MF and Savarese, JJ) Churchill Livingston, a Division of
Harcourt Brace & Company, Philadelphia, pp. 1753-1799, 2000.
3Primary Reference:
Wray Roth, DL, Rothstein, P and Thomas, SJ Anesthesia for Cardiac
Surgery, in Clinical Anesthesia, third edition (Barash, PG,
Cullen, BF, Stoelting, R.K, eds), Lippincott-Raven Publishers,
Philadelphia, pp. 835-865, 1997
