Moderator: Dr G. Parameswara
By: Dr. Arati Mohan Badgandi
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Volatile Agents
Acute cardiac effects
Delayed effects
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IV Induction Agents
Acute Cardiac Effects
Vasculature
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Neuromuscular
blockers
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Individual Agents
Thiopental
Midazolam
Etomidate
Ketamine
Propofol
Opioids In Cardiac
Anesthesia
Opioid Receptors
Cardiac Effects of
Opioids
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Dose-dependent depression of contractile function.
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Halothane & enflurane equal & more potent
myocardial depression than isoflurane/ desflurane/
sevoflurane (reflex sympathetic activation with latter
agents).
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Preexisting myocardial depression - greater effect.
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Negative inotropic effects by modulating sarcolemmal
(SL) L-type Ca2+channels, SR, & contractile proteins.
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All volatile agents cause dose-dependent decreases in
SBP.
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Halothane & enflurane - predominantly due to
attenuation of myocardial contractile function.
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Isoflurane, desflurane, & sevoflurane - predominantly
due to decrease in SVR.
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Volatile agents obtund all components of baroreceptor
reflex arc. Effects on myocardial diastolic function not
well characterized.
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When confounding variables are controlled (e.g., SBP),
isoflurane does not cause “coronary steal” by direct
effect on coronary vasculature.
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Effects of volatile agents on systemic regional vascular
beds & on pulmonary vasculature are complex.
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Depend on specific anesthetic agent, vascular bed,
vessel size, whether endothelial-dependent or
endothelial-independent mechanisms are being
investigated.
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Volatile anesthetic agents lower arrhythmogenic
threshold for epinephrine.
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Order of sensitization being halothane > enflurane >
sevoflurane > isoflurane = desflurane. (mechanisms
underlying this effect not understood)
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Modulate several determinants of myocardial oxygen
supply & demand.
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Also directly modulate response of myocytes to
ischemia.
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Occurs when perfusion pressure for a vasodilated
vascular bed (where flow is pressure dependent) is
lowered by vasodilation in a parallel vascular bed, both
beds usually being distal to a stenosis.
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2 kinds of coronary steal: collateral and transmural
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Collateral steal - vascular bed (R3), distal to occluded vessel,
is dependent on collateral flow from (R2) supplied by
stenotic artery. Since collateral resistance is high, R3arterioles
dilated to maintain flow in resting condition
(autoregulation).
Dilation of R2arterioles increases flow across stenosis R1 &
decreases pressure P2.
If R3resistance cannot further decrease sufficiently, flow
decreases, producing/worsening ischemia.
Transmural steal - normally, vasodilator reserve less in
subendocardium. In presence of stenosis, flow may become
pressure dependent in subendocardium while
autoregulation maintained in subepicardium.
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Reports indicated direct coronary arteriolar
vasodilatation in vessels 100 μm or less could cause
“coronary steal” in patients with “steal-prone”
coronary anatomy (complete occlusion of coronary
artery with collateral flow from adjacent vessel with a
critical stenosis.)
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Studies in which potential confounding variables
controlled indicated that isoflurane did not cause
coronary steal.
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Studies of sevoflurane & desflurane consistent with
mild direct coronary vasodilator effect of these agents.
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Volatile anaesthetic agents
decrease SBP in dosedependent manner.
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Halothane & enflurane decrease in SBP due to
decreases in SV & CO.
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Isoflurane, sevoflurane &
desflurane decrease overall
SVR while maintaining CO.
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Baroreceptor Reflex
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Volatile agents attenuate baroreceptor reflex.
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Inhibition by halothane & enflurane >
isoflurane/desflurane/ sevoflurane, each of which
has a similar effect.
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Each component of the arc (afferent nerve activity,
central processing, efferent nerve activity) inhibited
by volatile agents.
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Delayed Effects
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Reversible effect on myocardial ischemia.
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Prolonged ischemia - irreversible myocardial damage
& necrosis.
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Nonacute manifestations of myocardial ischemia
include hibernating myocardium, stunning &
preconditioning.
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Volatile agents enhance systolic function recovery in
postischemic-reperfused (“stunned”) myocardium if
administered before brief periods of ischemia.
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Shorter durations of myocardial ischemia can lead to
preconditioning/myocardial stunning - reduction in
infarct size.
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Stunning, 1st described in 1975 - after brief ischemia,
characterized by myocardial dysfunction in setting of
normal restored BF & absence of myocardial necrosis.
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Ischemic preconditioning (IPC) 1st described by
Murray & colleagues in 1986.
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Important adaptive protective mechanism - provoked
by ischemia.
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Reduction/abolition in coronary BF usually
detrimental to myocardium, instances where brief
periods of coronary artery occlusion followed by
intermittent periods of reperfusion prior to more
prolonged coronary occlusion is beneficial to heart makes it resistant to stunning /infarction - ischemic
preconditioning
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Administration of halothane/isoflurane before
prolonged coronary artery occlusion & reperfusion
reduces myocardial infarct size in vivo.
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Beneficial effect persists despite discontinuation of
volatile anesthetic before coronary artery occlusion.
Schematic illustration of canine myocardium subjected to 60-min coronary artery
occlusion & reperfusion, then stained to identify region of MI (dark red area)
within myocardium at risk for infarction (light yellow area). Isoflurane decreased
extent of myocardial infarction.
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Effect independent of collateral flow.
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Requires different time intervals between exposure &
maintenance of a subsequent benefit –agent & dose
dependent.
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Volatile agents that exhibit APC activate mitochondrial
K+ATPchannels - effect blocked by specific mitochondrial
K+ATPchannel antagonists.
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Even though N2O directly depresses myocardial
contractility in vitro, ABP, CO & HR essentially
unchanged/slightly elevated in vivo due to stimulation
of catecholamines.
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Myocardial depression unmasked in patients with
CAD/severe hypovolemia, resulting drop in ABP may
occasionally lead to myocardial ischemia.
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Constriction of pulmonary vascular smooth muscle
increases pulmonary vascular resistance - results in
elevation of right ventricular end-diastolic pressure.
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Despite vasoconstriction of cutaneous vessels, SVR not
significantly altered.
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Increases endogenous catecholamine levels - associated
with higher incidence of epinephrine-induced
arrhythmias.
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Dose-dependent reduction of ABP due to direct
myocardial depression. 2.0 MAC of halothane - 50%
decrease in BP & CO.
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Cardiac depression— interference with Na-Ca exchange
& intracellular Ca utilization—causes increase in RAP.
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Coronary artery vasodilator, but coronary blood flow
decreases, due to drop in SBP.
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Adequate myocardial perfusion maintained as oxygen
demand also drops.
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Hypotension inhibits baroreceptors in aortic arch &
carotid bifurcation - decrease in vagal stimulation &
compensatory rise in HR. Halothane blunts this reflex.
Slowing of SAN conduction - junctional
rhythm/bradycardia.
In infants, decreases CO by combination of decreased HR
& depressed myocardial contractility.
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Sensitizes heart to arrhythmogenic effects of epinephrine
- doses of epinephrine above 1.5 microg/kg should be
avoided. (may be due to halothane interfering with slow
Ca conductance)
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Although organ blood flow is redistributed, SVR
unchanged.
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Minimal cardiac depression in vivo.
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CO maintained by rise in HR due to partial
preservation of carotid baroreflexes.
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Mild β-adrenergic stimulation increases skeletal muscle
BF, decreases SVR & lowers ABP.
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Rapid increase in isoflurane concentration leads to
transient increases in HR, ABP & plasma levels of
norepinephrine.
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Dilates coronary arteries - not as potent as
nitroglycerin/adenosine.
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Does not cause coronary steal phenomenon.
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CVS effects similar to isoflurane.
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Increasing dose associated with decline in SVR - fall in
ABP.
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CO relatively unchanged/slightly depressed at 1–2
MAC.
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Moderate rise in HR, CVP & PA pressure, often not
become apparent at low doses.
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Rapid increase in desflurane concentration - transient
elevations in HR, BP & catecholamine levels (more
pronounced than with isoflurane, esp in patients with
cardiovascular disease.)
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CVS responses to rapidly increasing desflurane
concentration - attenuated by fentanyl/
esmolol/clonidine.
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Unlike isoflurane, desflurane does not increase
coronary artery blood flow
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Mildly depresses
myocardial contractility.
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SVR & ABP decline
slightly less than with
isoflurane/desflurane.
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Little/no rise in HR - CO
not maintained as well as
with
isoflurane/desflurane.
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No coronary steal.
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Belong to different classes (barbiturates,
benzodiazepines, N-methyl-D-aspartate [NMDA]
receptor antagonists & α2-adrenergic receptor agonists).
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Effects on CVS are dependent on class to which they
belong.
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Cumulative effects on vasculature - summation of
effects on CNS, vascular smooth muscle & modulating
effects on endothelium.
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Prototype: Thiopental
Induction doses of IV barbiturates - fall in blood
pressure & elevation in heart rate.
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Depression of medullary vasomotor center vasodilates
peripheral capacitance vessels - increases peripheral
pooling of blood -decreases venous return to RA.
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Tachycardia due to central vagolytic effect. (10%-36%)
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CO maintained by rise in HR & increased myocardial
contractility from compensatory baroreceptor reflexes.
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Sympathetically induced vasoconstriction of resistance
vessels increase peripheral vascular resistance.
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In absence of adequate baroreceptor response (eg,
hypovolemia, CHF, adrenergic blockade), CO & BP
falls due to uncompensated peripheral pooling &
unmasked direct myocardial depression.
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Poorly controlled HTN prone to wide swings in BP
during induction.
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CVS effects of barbiturates vary, depending on volume,
baseline autonomic tone & preexisting CVS disease.
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Thiopental decreases cardiac output by:
A direct negative inotropic action
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Decreased ventricular filling, resulting from increased
venous capacitance
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Transiently decreasing sympathetic outflow from CNS.
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Hence, caution should be used when thiopental is
given to patients with LVF/RVF, cardiac tamponade,
or hypovolemia.
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Dose-related negative inotropic effects - due to
decrease in Ca influx into cells with resultant
diminished amount of Ca at sarcolemma sites.
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Minimal hemodynamic effects in normal patients &
heart disease when given slowly/infusion.
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Hypovolemic patients - significant reduction in CO
(69%) & large decrease in BP - patients without
adequate compensatory mechanisms may have serious
hemodynamic depression.
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Greater changes in BP & HR than midazolam in
induction of ASA Class III & IV patients.
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Used safely for induction in normal patients & those
with compensated cardiac disease.
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Due to negative inotropic effects, increase in venous
capacitance & dose-related decrease in CO, caution
should be used when given to patients with
LVH/RVH/cardiac tamponade/hypovolemia.
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Tachycardia is a potential problem in patients with
ischemic heart disease.
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Major CVS effect - decrease in ABP due to drop in SVR
(inhibition of sympathetic vasoconstrictor activity),
cardiac contractility, & preload.
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Hypotension > thiopental, usually reversed by
stimulation accompanying laryngoscopy & intubation.
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Factors exacerbating hypotension include large doses,
rapid injection, & old age.
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Markedly impairs normal arterial baroreflex response
to hypotension, particularly in conditions of
normocarbia or hypocarbia.
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Rarely, marked drop in preload may lead to a vagally
mediated reflex bradycardia.
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Changes in HR & CO - transient & insignificant in
healthy patients.
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May lead to asystole - extremes of age/ on negative
chronotropic medications/ undergoing surgical
procedures associated with oculocardiac reflex .
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Patients with impaired ventricular function - drop in
CO due to decrease in ventricular filling pressures &
contractility.
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Myocardial oxygen consumption & coronary BF
decrease to similar extent, coronary sinus lactate
production increases in some patients.
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Signifies regional mismatch between myocardial
oxygen supply & demand.
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Hemodynamic effects investigated in ASA Class I & II
patients, elderly, patients with CAD & good left
ventricular function, & impaired LVF.
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SBP falls 15%-40% after IV induction with 2 mg/kg &
maintenance infusion with 100 μg/kg/min. Similar
changes in DBP & MAP.
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Effect on HR variable. Majority of studies - significant
reduction in SVR (9%-30%), CI & SV after propofol points to dose-dependent decrease in myocardial
contractility.
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Acute Cardiac Effects
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Myocardial Contractility
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Propofol - studies controversial as to whether direct
effect on myocardial contractile function at clinically
relevant concentrations.
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Evidence suggests modest negative inotropic effect mediated by inhibition of L-type Ca2+
channels/modulation of Ca2+release from SR.
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Minimal CVS depressant effects even at induction
doses.
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ABP, CO & SVR usually decline slightly, while HR
sometimes rises.
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Tends to reduce BP & SVR more than diazepam.
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Changes in heart rate variability during midazolam
sedation suggest decreased vagal tone (ie, druginduced vagolysis).
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Small hemodynamic changes after IV midazolam (0.2
mg/kg) in premedicated patients with CAD.
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Changes of importance - decrease in MAP of 20% &
increase in HR of 15%. CI is maintained.
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Filling pressures unchanged/decreased in patients with
normal ventricular function, but decreased in patients
with elevated PCWP(18 mm Hg +).
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As in IHD, induction of anaesthesia in patients with
VHD associated with minimal changes in CI, HR & MAP
after midazolam.
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Intubation following induction with midazolam significant increase in HR & BP (as not an analgesic).
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Adjuvant analgesic required to block intubation
response.
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If given to patients who have received fentanyl,
significant hypotension may occur.
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Although routinely combined for induction &
maintenance of GA during cardiac surgery without
adverse hemodynamic sequelae.
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Midazolam (0.15 mg/kg) & ketamine (1.5 mg/kg) –
safe & useful combination for rapid-sequence
induction for emergency surgery.
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Combination superior to thiopental alone –
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less CVS depression
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more amnesia
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less postoperative somnolence.
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Minimal effects on CVS.
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Mild reduction in SVR - responsible for slight decline in
ABP.
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Myocardial contractility & CO usually unchanged.
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Does not release histamine.
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In comparison with other anesthetic drugs, etomidate
described as drug that changes hemodynamic variables
the least.
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Studies in noncardiac patients & with heart disease remarkable hemodynamic stability after
administration.
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Compared with other anaesthetics, least change in
balance of myocardial oxygen demand & supply.
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Etomidate (0.3 mg/kg IV), to induce GA in patients
with acute MI undergoing percutaneous coronary
angioplasty, did not alter HR, MAP & rate-pressure
product (RPP), demonstrating its remarkable
hemodynamic stability.
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Presence of VHD may influence hemodynamic responses
to etomidate.
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SBP may be decreased 10%-19% in patients with VHD.
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While most patients can maintain BP, patients with
aortic & mitral VHD - decrease of 17%-19% in SBP &
DBP, decreases of 11% -17% in PAP & PCWP.
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CI in patients who had VHD & received 0.3 mg/kg
remained unchanged/decreased 13%.
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No difference in response to etomidate between patients
with aortic valve disease & mitral valve disease.
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Uses
When advantages of etomidate outweigh disadvantages
(with the possible exception of ketamine).
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Uses include - when rapid induction is essential, patients
with hypovolemia, cardiac tamponade/low CO .
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Hypnotic effect is brief - additional analgesic &/or
hypnotic drugs must be administered.
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Etomidate - no real advantage over most other induction
drugs for patients undergoing elective surgical
procedures.
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Unique feature - stimulation of CVS - increase in HR,
CI, SVR, PAP & systemic arterial pressure.
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Appropriate increase in coronary blood flow &
myocardial work.
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Indirect CVS effects due to central stimulation of
sympathetic nervous system & inhibition of reuptake
of norepinephrine.
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For these reasons,should be avoided in CAD,
uncontrolled HTN, CHF & arterial aneurysms.
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Direct myocardial depressant effects of large doses due to inhibition of Ca transients, remain unmasked
by sympathetic blockade (eg, spinal cord transection)
or exhaustion of catecholamine stores (eg, severe endstage shock).
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Indirect stimulatory effects beneficial to patients with
acute hypovolemic shock - maintenance of BP & CO.
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Combination of diazepam & ketamine rivals high-dose
fentanyl technique with regard to hemodynamic
stability.
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Undesired tachycardia, HTN & emergence delirium
attenuated with BZDs.
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Similar hemodynamic changes in normal patients & in
those with IHD.
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In patients with elevated PAP (eg. MVD), causes more
pronounced increase in PVR than SVR.
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Marked tachycardia after ketamine & pancuronium
complicate induction in patients with CAD/VHD.
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Uses
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In adults, safest & most efficacious drug - decreased
BV or cardiac tamponade.
Studies demonstrated safety & efficacy of induction
with ketamine in hemodynamically unstable patients
requiring emergency operations.
In accumulation of pericardial fluid with/without
constrictive pericarditis, induction with ketamine (2
mg/kg) maintains CI & increases BP, SVR & RAP.
HR remains unchanged (cardiac tamponade already
produces compensatory tachycardia).
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Mild α-adrenergic blocking effects decrease ABP by
peripheral vasodilation.
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Hypovolemic patients can experience exaggerated
declines in BP.
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α-adrenergic blocking actions may be responsible for
antiarrhythmic effect.
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Associated with QT interval prolongation & torsades
de pointes.
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Prior to administering droperidol, a 12-lead ECG
should be recorded.
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If QT measures > 440 ms for men/> 450 ms for women,
should not be given.
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If QT interval is normal & droperidol is given, ECG
should be monitored for 2–3 h.
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Patients with pheochromocytoma should not receive
droperidol as it can induce catecholamine release from
adrenal medulla - severe hypertension.
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With exception of meperidine, opioids do not depress
cardiac contractility.

Meperidine increases HR (structurally similar to
atropine), while high doses of morphine, fentanyl,
sufentanil, remifentanil & alfentanil associated with a
vagus-mediated bradycardia.

ABP falls due to bradycardia, venodilation & decreased
sympathetic reflexes –due to histamine release,
reduced by slow administration (<10 mg/min).
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Meperidine & morphine - histamine release in some
individuals - profound drop in SVR & ABP.

Can be minimized slow opioid infusion/adequate
intravascular volume/ pretreatment with H1 & H2
histamine antagonists.

Combination of opioids with other anaesthetic drugs
(eg, nitrous oxide, BZDs, barbiturates, volatile agents)
can result in significant myocardial depression.

Major CVS effect of exogenous opioids - attenuate
central sympathetic outflow
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Endogenous opioids & opioid receptors, esp ∆ receptor
important in effecting early & delayed
preconditioning.

Plasma drug concentrations altered by CPB due to
hemodilution, altered plasma protein binding,
hypothermia, exclusion of lungs from circulation &
altered hemodynamics that modulate hepatic & renal
blood flow. (specific effects drug dependent)
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Opioid receptors regulating CVS –centrally at CVS &
RS centers of hypothalamus & brainstem, peripherally
at cardiac myocytes, BVs, nerve terminals & adrenal
medulla.
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Opioid receptors differentially distributed between
atria & ventricles.

Highest receptor density for binding of κ-agonists in
RA & least in LV. Similarly, distribution of δ-opioid
receptor favors atrial tissue Rt heart > lft.
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Mechanism of opioid-induced bradycardia is central
vagal stimulation.

Premedication with atropine can minimize
bradycardia, especially in patients taking βadrenoceptor antagonists.

Moderate slowing of HR beneficial in CAD-decreases
myocardial oxygen consumption.

Degree of myocardial impairment influences response.

Critically ill patients/with significant myocardial
dysfunction - lower doses of opioid –altered kinetics.

Decrease in liver BF due to decreased CO & CHF
reduces plasma clearance - patients with poor LVF
develop higher plasma & brain concentrations for
given loading dose/ infusion rate than patients with
good LVF.
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Infarct-reducing effect of morphine shown in hearts in
situ, isolated hearts & cardiomyocytes.
Morphine improves postischaemic contractility &
provides protection against ischemia-reperfusion
injury.
Fentanyl gp proved to be most reliable & effective for
producing anesthesia for patients with valvular
disorders & CABG.
Major advantage of fentanyl & analogs for patients
undergoing cardiac surgery is lack of cardiovascular
depression.

Succinylcholine stimulates nicotinic cholinergic
receptors at NMJ - & all ACh receptors.

CVS actions very complex.

Stimulation of nicotinic receptors in parasympathetic &
sympathetic ganglia & muscarinic receptors in SAN can
increase/decrease BP & HR.

Low doses can produce negative chronotropic &
inotropic effects, but higher doses usually increase HR &
contractility & elevate circulating catecholamine levels.

Children susceptible to profound bradycardia.

Bradycardia occurs in adults only if 2nd bolus of
succinylcholine is administered approximately 3–8 min
after 1st dose.

IV atropine (0.02 mg/kg in children, 0.4 mg in adults)
normally given prophylactically to children, prior to 1st
dose & always before 2nd dose.

Nodal bradycardia & ventricular ectopy reported.

Atracurium causes hypotension & tachycardia.

CVS side effects unusual unless doses > 0.5 mg/kg
administered.

Transient drop in SVR & increase in CI independent of
histamine release - slow rate of injection minimizes
these effects.

Cisatracurium, Doxacurium, Vecuronuim does not
affect HR or BP, nor does it produce autonomic effects.

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
Mivacurium releases histamine about same degree as
atracurium.
CVS side effects can be minimized by slow injection
over 1 min.
Patients with cardiac disease rarely experience drop in
ABP after doses > 0.15 mg/kg, despite slow injection
rate.
Pancuronium –HTN & tachycardia - vagal blockade &
sympathetic stimulation.
Latter - combination of ganglionic stimulation,
catecholamine release from adrenergic nerve endings &
decreased catecholamine reuptake.

Caution in patients where increased HR would be
detrimental (eg, CAD, idiopathic hypertrophic
subaortic stenosis).

Increased AV conduction & catecholamine release Ventricular dysrhythmias in predisposed individuals.

Principal advantage of pipecuronium over
pancuronium - lack of CVS side effects due to
decreased binding to cardiac muscarinic receptors.