9/25/2012
ANESTHESIA CASE STUDY
Vasospastic Myocardial Infarction
Objective
Objectives
 Overview of coronary vasospasm mechanisms
and risk factors
 Review of the perianesthesia events
surrounding this actual case study
 Pharmacology
gy review off medications
associated w/ risk of coronary vasospasm
 Rx of patients suspected of having coronary
vasospasm while under anesthesia, and while
recovering from anesthesia
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9/25/2012
“Just a TVH…”
 Relatively innocent
sounding case (?)
 “really fast surgeon”
 “no significant PMH”
 “… yada yada…”
 Your check is in the
mail…
Many times you don’t
suspect anything at all…
And then the demons
come out to play!
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9/25/2012
Just the Facts, Ma’am…
Heart Facts…
 The heart consumes the highest fraction of oxygen per
tissue mass of any organ in our bodies
 At rest, O2 consumption is 250 ml/min, or 5 % of normal
CO
 Blood flow to the myocardium occurs mainly during
diastole
 Arterial O2 extraction in the myocardium is around 60-
80%, vs. ~ 20% in the rest of the body
 Increased O2 demand must be met by an increase in
coronary flow vs. increase in O2 extraction
Flow depends on…
 Jean Louis Marie Poiseuille
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9/25/2012
Oh God, not Physics!
 … the volume of a
homogeneous fluid
passing per unit time
through a capillary tube
i directly
is
di
l proportional
i
l
to the pressure
difference between its
ends and to the fourth
power of its internal
radius, and inversely
proportional to its length
and to the viscosity of
the fluid …*
Coronary Vessel Diameter
 Intraluminal deposits
 Vasomotor tone

(alpha)
receptors
 (beta) receptors
 Muscarinic receptors
 AT (angiotensin)
receptors
 ET (endothelin)
receptors
Physiology Review
 Coronary arterial tone exists along a physiological
spectrum
 Pathophysiology alters the normal spectrum of vasomotor
homeostasis
 Multiple
p ffactors come into play…
p y
 Neurological (autonomic) control
 Presence of pathophysiology of coronaries
 Metabolic demands
 Endothelial factors
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9/25/2012
Let’s talk about those last
bullet points, shall we?
Autonomic Control
 Regular diurnal alterations in tone do exist, but are
generally regarded as weak
 Epicardial coronaries generally have receptors
(vasoconstriction)
 Intramuscular
I
l andd subendocardial
b d
di l coronaries
i
generally have receptors (vasodilation)
 Parasympathetic stimulation results in vasodilation
via acetylcholine
Metabolic Demands
 Local (cardiac) metabolic balance is the main regulatory
player in arterial vasomotor tone
 Tissue hypoxia, increased tissue CO2 and tissue acidosis
drive coronary vasodilation
 Adenosine is released and ATP-K+ channels are activated
 Pre-capillary sphincters are relaxed and more capillaries
are recruited
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9/25/2012
Endothelial Factors
 Vascular endothelium acts





as a barrier b/w flowing
blood and vascular wall
Regulates vascular growth,
platelet fxn, coagulation,
vascular tone
Responds to neural,
humoral and mechanical
(myogenic) stimuli
Injury/Repair cycle
Synthesizes/secretes
vasoactive substances
Responses d/o intact
vascular endothelium
Vascular Endothelium
 Single-cell lining of all blood vessels found in higher
organisms
 Proteins, lipids, and vasoactive substances secreted by the
endothelium
 Protects the vessels from environmental stress, oxidative
damage and thrombosis
 Ensures delivery of O2 and nutrients to tissues
 As such, it is the largest endocrine organ of the body
(surface area ~ 6 tennis courts!)
Vasodilatory Influences
 Nitric oxide
 Acetylcholine, via
release of nitric oxide
 Endothelium-derived
Endothelium derived
relaxing factor
(EDRF)
 Prostacyclin
 Bradykinin
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9/25/2012
Vasoconstrictor Influences
 Angiotensin II
 Enhances Ca2+ influx
 Causes release off
endothelin
 ACE inactivates
bradykinin
 Thromboxane A2
Balance
 The net effect on vasomotor tone is dependent upon
the balance between the two opposing systems
 Mechanisms are unreliable in the presence of
diseased vascular endothelium
 E.G. acetylcholine acts as a vasoconstrictor in
atherosclerotic arteries,, opposite
pp
off its normal action
 Genetic polymorphisms that diminish endothelial
nitric oxide production have been correlated with
coronary vasospasm
Vasospastic Imbalance…
 Heightened




vasoconstrictor response
to acetylcholine
Enhanced vasodilator
response to nitrates
Endogenous nitric oxide
deficiency
Autonomic imbalance
Sensitization towards
vasoconstriction
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9/25/2012
Predisposing Factors
 Genetic factors compromising endothelial NO production
 Markers of chronic low-level oxidative stress (monocyte
counts, C-reactive protein levels, thioredoxin levels, etc.)
 Type A personality
 Panic disorder
 Severe
S
anxiety
i t
 Incidence among Japanese elevated
 Gender preponderance unclear
 Presence of acknowledged ‘triggers’ in susceptible patients
Vasospastic Triggers
Hyperventilation
Illicit drugs, especially cocaine
Emotional stress
Exposure to cold
Tobacco use, especially
smokingg
 Alcohol use
 Intracoronary provocative
agents…Acetylcholine,
ergonovine, histamine,
serotonin





 OTC drugs, especially cold
meds
 Thyroxin preparations (rare)
 Chemotherapy agents
 Hypersensitivity rxns to
NSAIDs Abx and allopurinol
NSAIDs,
 Induction of anesthesia
 Prescription drugs
 Non-selective -blockers,
migraine medications
Let’s take a moment to have a
serious chat…
8
9/25/2012
A Word about Smoking…
 20 X the risk of coronary vasospasm (CV) vs. non-smokers
 Causes vasoconstriction through  adrenergic increase in vascular





tone, and via increases in platelet and plasma levels of vasopressin
and oxytocin
Imposes endothelial damage
Diminishes endogenous antioxidant activities (glutathione, etc.)
P i smokers
Passive
k have
h
a 25% iincrease iin the
h risk
i k off all
ll coronary
M&M
Passive smoking is the 3rd leading preventable cause of death after
active smoking and alcohol abuse
Case report relating that 1 cigarette during angiography provoked
an incident of CV
So, curious about the case?!
CASE REVIEW
 42 yo white female
 For TVH d/t fibroids,
extreme menorrhagia,
anemia
 Allergy: PCN
 Anesthesia
complications: PONV
 PIV #18g x 1
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9/25/2012
PMH
 Bilateral hip osteoarthritis
 (1999) Low grade astrocytoma of brainstem,
inoperable, treated w/ XRT (transmastoid rad
port), no major recent sequelae…
S
Sz diso
disorder,
de , none since early
ea ly in astrocytoma
ast ocytoma
XRT
 Migraines, none ‘recent’ per patient report
PMH (cont’d)
 She has chronic occipital pain as a
consequence of the astrocytoma and/or Rx
thereof, with exacerbations of this pain deemed
to be migraines;on a tiered pain regimen
 Maxalt used for breakthrough migraines
 She
Sh also
l has
h intermittent vertigo andd diplopia,
d l
speech hesitancy, and diminished hearing
 Hx bilateral TMJ syndrome
Patient Profile
 PSH
PSH: T & A, D & C, brainstem tumor bx 1999,
sinus sx 2001. No history of anesthetic
complications, except PONV
 MEDS
MEDS: Arthrotec,
Arthrotec FeSO4,
FeSO4 Ca2+,
Ca2+ MVI,
MVI Singulair,
Singulair
Prozac, Zonegran. PRNs are Maxalt, Alleve,
Toradol. By pt. report, no maxalt since 6-7 days
prior to DOS
 LAB
LAB: Hemoglobin approximately 3 weeks prior to
surgery = 12.4 **
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9/25/2012
Patient Profile (cont’d)
 Pleasant lady with noticeable speech hesitancy
 Pupils dilated wider than usual for light conditions
 Mild nystagmus when looking to the right.
 Heart S1S2 RRR, Lungs CTA bilaterally
 Normal A/W exam, except TMD just slightly > 3
FBs
 Baseline HR in PAPA approx. 55-60 bpm, and SBP
90-100s.
Preop EKG
Operative Course
 Uneventful induction, using propofol, fentanyl, lidocaine,




and divided dose of mivacron (total 12 mg)… easy
intubation
Maintenance with sevoflurane in Air and O2 (FiO2 ~
56=58%)
Post-induction, prolonged prep and drape* BP and HR
b
began
ddrifting
f
down
d
Inhalational agent turned down as low as 1.5% inspired,
IVF bolus
Upon sustained hypotension, ephedrine 5 mg x 2 doses,
approx. 3 minutes apart given.
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9/25/2012
Operative Course
 Hypotension (SBP 69) worsens plus significant brady (HR
30s) with ventricular escape beats develops
 Robinul 0.2mg given, MDA paged by circulator
 BP recheck not improved, brady continues
 Ephedrine 10mg given, FiO2 changed to 100%
 Surgeon
g
requested
q
to not begin
g pprocedure
 Sustained ventricular ectopy begins,and MDA arrives
 Total elapsed time from beginning of initial Rx for BP
approx. 10 minutes.
Intraoperative EKG Rhythms
Intraop/Postop Rhythms
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9/25/2012
There’s going to be, trouble…
Interventions
 Sustained pulsatile monomorphic VT x approx 1-2
minutes, then nodal rhythm with salvos of
polymorphic ventricular ectopy. Still hypotensive
 Extra lidocaine given, total of 100 mg
 Now,, ST 120s with hypertension,
yp
, initiallyy opposite
pp
electrical axis from baseline. Rx’d with esmolol
 2 inches NTG paste to chest wall
Postop Interventions
 Baseline axis in sinus resumed, with overt ST depression.




Patient allowed to wake up and extubated without need for
reversal agents. BP baseline briefly (100s/50s)
To PACU. Placed on hi flow O2, 12 lead EKG obtained,
showing 4-5mm ST depression in inferior,lateral, and v3-6
precordial leads
BP now consistently hypotensive; IVF running at moderate
pace, labs sent and dopamine gtt ordered
Magnesium 2 gm infusion run started
Cardiology consult placed; dopa gtt okayed with Cards
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9/25/2012
Initial EKG in PACU
Teamwork…
Postop Course
 Serial EKGs show progressive improvement in ST
depression
 Pt remains hypotensive, refractory to Rx including
eventually a dopamine gtt up to 5 mcg/kg/min
 Cards in to see pt.
pt and transferred to CCU
 Pt. denies discomfort of any kind, except for
occipital h/a, throughout PACU stay
14
9/25/2012
Initial EKG CCU
Course in CCU
 Ruled in for MI, peak CK 393, MB 47.9
 Cardiac cath shows clean coronaries, Ao 90/60, Lvedp
approx. 20
 Echo shows mildly decreased EF (50%), with posterior-
lateral dyskinesia/ hypokinesia, and inferior septal
akinesia
 Pt.
P remainedd markedly
k dl hypotensive
h
on dopa
d
gtt, as muchh
as 2 days postop
 She was eventually fluid challenged, and then transfused,
with hemodynamic improvement
Interesting Facts…
 Initial Hgb drawn in
PACU was 8.9
 Pt. recalled she did
indeed have a dose of
Maxalt 2 days
y prior
p
to
surgery
 Pt. admitted to having
CP and unusual fatigue
the day prior to surgery
 Told Cards that she does
occasionally smoke,
sometimes a great deal…
15
9/25/2012
Migraine Meds
 Cafergot, DHE 45, Midrin
 Triptans
 Axert, Almogran
 Relpax
 Frova, Migard,
Frovamig
 Amerge, Naramig
 Maxalt
 Imitrex
 Zomig
Triptans
 First introduced in the 1990s
 Used in the Rx of migraine/cluster headaches
 Acts by binding to serotonin subtype 5-HT1B and 5-HT1D
receptors and constricting cranial blood vessels
 Also binds on receptors in the peripheral terminals of the
trigeminal nerve that innervate the cranial blood vessels
 This leads to a subsequent decrease in release of nociceptive
mediators (CGRP, substance P)
 Mean plasma half-life after oral dosing is 2 hours
Triptans
 Contraindicated in IHD, variant angina, poorly controlled
HTN
 Contraindicated in those taking ergot preparations within
previous 24 hours
 Contraindicated in those taking MAOIs within prior 2 weeks
 Poses the risk of coronary vasospasm
 Poses the risk of serotonin syndrome if used in conjunction
with SSRIs, SNRIs
 Should be used with caution in those with epilepsy
16
9/25/2012
Better Living thro Chemistry?
So what the heck happened?
 Research re: CV continue to indicate many directions of
thought…
 Autonomic tone influences, specifically vagal withdrawal:
although -adrenergic input is not excluded as a factor
 Adrenergic agonist post-induction
 Local vasomotor hyperreactivity d/t receptor abnormality,
endothelial
d h li l dysfxn
d f or platelet
l l fxn
f alteration
l
i (smoking)
(
ki )
 Vitamin E deficiency, allowing oxidative modification of
LDL, which increases vasomotor reactivity (smoking)
 Central serotonin excess with prn 5HT agonist addition
Case Reports
 CV reported with GA, GA
+Epidural, SAB
 CV reported with triptans
alone, or with SSRIs
 CV reported with ephedrine
in pt. reporting ‘rare’
cocaine use
 CV reported with ephedrine
use for hypotension in SAB
cases in young smokers
 CV reported with induction
free of hypotension, other
agents
17
9/25/2012
CV Clinical Presentation
(Preoperative Clues)
 Patients without usual risk factors for IHD
 Young, normotensive, no lipid abnormalities
 No prior hx IHD
 Transient/sustained ST segment elevation or depression,
especially in a global pattern
 Global or focal transient/sustained T wave inversion
 Severe ventricular tachyarrhythmias and bradyarrhythmias up
to & including AV block
 If awake, typical symptoms of angina and associated signs
Important Principles
of Perioperative CV Rx
 Rx of life-threatening arrhythmias
 Immediate application of nitrates IV/topical/SL
 Avoidance of non-selective  blockers as blockade
may exacerbate CV
 Intravenous calcium channel blockers are potentially
of benefit
 Cards workup to rule out and/or treat atherosclerotic
heart disease
 Avoid hyperventilation
 Avoidance of histamine releasing meds
Ultimate Outcome
 LV fxn normalized after
2 weeks by echo
 Prozac dose reduced to
1/3 original dose
 Toradol
T d l discontinued
d
d
 Maxalt discontinued
 Midrin used for
migraines
 Surgery successfully
completed 6 weeks later
18
9/25/2012
So, in Hindsight…
 Pt. was a smoker
 On generous dose of
an SSRI (total
60mg/day prozac)
 On prn triptan that she
regularly takes
 ? Up-regulated
serotonergic receptors
 ? Altered autonomic
responses d/t CNS
lesion
 On anti-sz med that
acts as a carbonic
anhydrase inhibitor
 More volume-depleted
and anemic than it
appeared
What we don’t say enough..
Questions, Comments, etc.?
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9/25/2012
Thanks!
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