AUTONOMIC NERVOUS SYSTEM
CLINICAL ANESTHESIA, CHP 15
CARIN HAGBERG, MD
SARA SLABISAK, MS4
Autonomic Nervous System
The wizard of regulation and balance
…involuntary regulation of visceral reflexes
that occur below the level of consciousness
‣
‣
‣
‣
‣
‣
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Cardio-Pulmonary
Thermoregulation
GI motility
GU function
Metabolic
Endocrine
Adaptive Stress Response
… Essentially, anesthesiology is the practice of autonomic medicine
CENTRAL INTEGRATION
Central Control
Integration of ANS activity occurs at all levels of the
cerebrospinal axis. Can be initiated locally and by centers
in the spinal cord, brainstem, and hypothalamus.
!
!
Hypothalamus
Principle Site various hypothalamic nuclei control both
branches of the ANS
Long-term BP control, reactions to physical and
emotional stress, sleep, and sexual reflexes
!
‣
Medulla Oblongata, Pons
Acute Site physiologic responses that must be immediately
enacted
Integrate momentary hemodynamic adjustments and
maintain the sequence/automation of ventilation
!
‣
CENTRAL AUTONOMIC ORGANIZATION
“BE KIND, FOR EVERYONE YOU MEET IS FIGHTING A GREAT BATTLE.” IAN MACLAREN
PERIPHERAL INTEGRATION
Peripheral Efferent (Motor)
Dual Innervation of all effector organs except
skeletal muscles
!
‣ Pre-Ganglionic originates within the CNS and
relays impulses to ANS ganglia
! ‣ Post-Ganglionic cell bodies originate within the
ganglia and axons contact effector organs
Sympathetic
Thoracolumbar most active during times of
excitement and physical activity.
!
Parasympathetic
Craniosacral most active during rest and
stimulates digestive activities.
PERIPHERAL ANS ORGANIZATION
“IT’S NOT WHAT HAPPENS, IT’S HOW YOU REACT TO IT THAT MATTERS.” EPICTETUS
SYMPATHETICS
Thoracolumbar
Originate in the interomediolateral gray column of T1-T12 & L1-L3
!!
‣
Post-Ganglionic
synapse w/ post-ganglionic fibers at exit level
course up/down to synapse at paired, lateral ganglia
track variable distances and synapse at unpaired, collateral
ganglia
Adrenal
Exception pre-ganglionic fibers pass directly into the
adrenal medulla w/out synapsing in a ganglion
!
Mass Reflex
Diffuse, Physiologic Response SNS post-ganglionic neurons
outnumber the pre-ganglionic neurons (20-30:1)
PERIPHERAL ANS ORGANIZATION
“BE HAPPY - IT’S ONE WAY OF BEING WISE.” COLETTE
SYMPATHETICS
Cervical Ganglia
T1-T5 spinal segments generate preganglionic fibers !
➺ Superior Cervical
➺ Middle Cervical
➺ Stellate
Stellate Ganglion
SNS innervation coronary vasculature,
lung, & cerebral circulation. PNS cardiac
vagal fibers approach the stellate and
join efferent cardiac SNS fibers.
!
Left Stellate distribution to posterior
and lateral surfaces of both ventricles
!
‣ Right Stellate distribution to anterior
epicardial surface and the
interventricular septum
‣
Afferent Pain Fibers travel w/
fibers accounting for chest,
neck, & upper extremity pain
during myocardial infarctions
PERIPHERAL AUTONOMIC NERVOUS SYSTEM
“DON’T CRY BECAUSE IT’S OVER, SMILE BECAUSE IT HAPPENED.” DR. SEUSS
PARASYMPATHETICS
Craniosacral
Brainstem, CN 3, 7, 9, 10 Sacral segments, S2-S4
!
! ‣ Vagus N. (75% PNS activity)
heart, lungs, esophagus, stomach, small intestine, proximal
colon, liver, gallbladder, pancreas, upper ureters
‣ Sacral nerves
distal colon, rectum, uterus, bladder, lower ureters
!
Discrete Response
Viscera-specific PNS post-ganglionic neurons to preganglionic neurons (1-3:1)
PERIPHERAL ANS ORGANIZATION
“UPON THE CONDUCT OF EACH, DEPENDS THE FATE OF ALL.” ALEXANDER THE GREAT
Nicotinic: Ionotropic
Open channels for small cations (NA+, K+)
Located in PNS in certain autonomic neurons,
skeletal muscles, and some regions of the CNS.
!
SNS & PNS
Low-Dose Stimulation
Hypertension, Tachycardia
High-Dose Depression
Hypotension
Neuromuscular weakness
Muscarinic: Metabotropic
Operate via G-proteins; open or close ion channel
or activate an enzyme depending upon the
postsynaptic neuron. Dominant cholinergic
receptor in the CNS.
!
Post Ganglionic PNS
Bradycardia
Decreased inotropism
Bronchoconstriction
Miosis, salivation
Increase GI motility & secretions
CHOLINERGIC TRANSMISSION
“NEVER PRACTICE TWO VICES AT ONCE.” TALLULAH BANKHEAD
CARDIO AUTONOMICS
CHRONOTROPIC
Rate ! ‣
SNS ↑HR: ↓systolic duration
! ‣
PNS ↓HR: ↓SA node discharge rate
↓AV junctional fiber excitability
INOTROPIC
Force + Energy ↓Contractile Force
! ‣ Primary Mediator SNS
! ‣ Minor Mediator intrinsic myocardial mechanisms
HEMODYNAMICS
Coronary Blood Flow
! ‣ Primary Mediator Auto-regulation
! ‣ Minor Mediator ANS
CARDIOVASCULAR
“HEARTS WILL NEVER BE PRACTICAL UNTIL THEY ARE UNBREAKABLE.” WIZARD OF OZ (1939)
Heart Rate
Vagal Nodal Innervation [sinoatrial + atrioventricular]
! ‣↓
rate of SA node discharge
‣↓
conduction velocity
Automaticity
Spontaneous depolarization magnitude & slope of nodal
automaticity are important in the regulation of HR and
depend on the activity of the ANS.
!
Slowing the rate of depolarization increases time
required to reach threshold potential (TP); ↓HR. !
Observed w/ vagal stimulation & ACh agonists
CARDIOVASCULAR
AUTOMATICITY
Contractility
Sympathetic Stellate Innervation
Normal SNS tone maintains baseline contractility level
!
Vagal stimulation can ↓LV maximum rate of tension
development and ↓contractile force by as much as
10-20%.
Inotropic Force
Myocardial contraction is dependent on
the number of contractile element crossbridges and the relative sensitivity to Ca2+
!
Positive inotropic effect is reflected by an
increase in pressure-volume work at each
end-diastolic volume. !
Observed w/ sympathetic stimulation &
beta-adrenergic drugs
CARDIOVASCULAR
CONTRACTILITY
Carotid Sinus Reflex
[carotid sinus + aortic arch]
!Acute rise in arterial pressure activates
baroreceptors through stretch-sensitive Na+channels. ↑afferent activity ultimately ↓HR via postsynaptic, medullary control and depresses SNS
tone. ‣
↓ CO + SVR
‣↑
vascular capacitance
Volatile & IV anesthetics inhibit regulation of
heart rate through this reflex. Concomitant
use of calcium-channel blockers, ACE
inhibitors, or PDE inhibitors will decrease the
cardiovascular response.
!
Patients with chronic HTN often exhibit
perioperative circulatory instability as a result
of a decrease in their baroreceptor reflex
response.
CARDIOVASCULAR
HIGH-PRESSURE ARTERIAL BARORECEPTORS
Valsalva Maneuver
Sustained intrathoracic pressure diminishes venous
return, CO, BP Reflex vasoconstriction + tachycardia !
!
!
Valsalva has been used to identify patients at risk for
anesthesia because of ANS instability.
!
!
!
!
Dysfunction can be assumed if the HR does not
respond appropriately to BP changes. Normal (A) HR
moves in a reciprocal direction. Abnormal (B) Valsalva
response shown in a patient w/ C5 quadriplegia.
CARDIOVASCULAR
HIGH-PRESSURE ARTERIAL BARORECEPTORS
Venous Baroreceptors
[right atrium + pulmonary v.]
↑HR when stretched by ↑right atrial pressure;
similarly, ↓ venous pressure ↓ HR !
!
!
Unlike arterial baroreceptors, venous sensors are not
thought to alter vascular tone. Venous baroreceptors
sample preload via atrial stretch and arterial baroreceptors
survey resistance (afterload) as reflected in MAP.
Bainbridge Reflex Characteristic, paradoxical, slowing of HR seen w/ spinal anesthesia. Blockade of SNS levels T1-T4: ablates efferent cardiac accelerator nerves and
allows unopposed vagal (afferent) stimulation.
CARDIOVASCULAR
LOW-PRESSURE VENOUS BARORECEPTORS
HEMODYNAMICS
Sympathetic Control
SNS most important regulator of peripheral circulation with
vasoconstriction > vasodilation
Basal Vasomotor Tone
Medulla Oblongata continual SNS transmission maintains
partial arteriolar & venular constriction. Circulating adrenal
Epi has additive effects.
!
Venular Tone
SNS reduce or increase capacity - by functioning as a reservoir
for app 80% total blood volume, small changes in venous
capacitance produce large changes in venous return = cardiac
preload
PERIPHERAL CIRCULATION
“A PINT OF SWEAT SAVES A GALLON OF BLOOD.” GENERAL GEORGE PATTON (1944)
Primary neural control of CV
function exerted by sympathetic
neurons to:
!
1) SA node to control HR
2) Ventricular myocardium to control
ventricular contractility
3) Veins to control venomotor tone
4) Arterioles to control vascular
resistance
HEMODYNAMICS
MEAN ARTERIAL PRESSURE
BRONCHOMOTOR CONTROL
SNS
Bronchi + Pulmonary Vasculature
↳ BronchoDilation + VasoConstriction
✤
✤
Critical to physiologic stability during stress & exercise
Vasculomotor tone adjustment accomodates RV output
PNS
Ventilation Cycle Reflex
Alveolar Duct {Vagal} Receptors
↳ BronchoConstriction + Gland Secretion
Hypoxic Pulmonary Constriction
✤
Local phenomenon regulating immediate adjustments
Non-Ventilatory Function
Metabolizes local mediators {ie, NE}
✤ Converts Angiotensin I
✤
PULMONARY
“REMEMBER TO BREATHE. IT IS AFTER ALL, THE SECRET OF LIFE.” GREGORY MAGUIRE
Medulla Central Pattern Generator
Network of neurons that generates
regular, repeating pattern of neural
activity, called the ventilation cycle.
Dorsal Respiratory Group
Primarily inspiratory neurons
Ventral Respiratory Group
2 expiratory and 1 inspiratory regions
Pons
Inspiratory + Expiratory
Facilitate transition between each
breath
PULMONARY
VENTILATION REGULATION
Chemoreceptors respond to change in arterial
P02, PCO2, pH. The primary stimulus being pH, a
direct reflection of [PCO2]
!
Chemoreceptors only responsd to changes in
arterial PO2 when it drops below 60 mmHg
Chemoreceptors are specialized cells in direct
contact with arterial blood that communicate with
afferent neurons projecting to respiratory control
regions
!
Peripheral chemoreceptors are located in the carotid
bodies near the carotid sinus
PULMONARY
PERIPHERAL CHEMORECEPTORS
Central Medullary Centers
chemosensitive areas of the brainstem
respond primarily to changes in [H+] !
!
Acute increase in PaCO2 is a more
potent ventilatory stimulus than an
acute increase in arterial [proton] from a
metabolic source.
!
!
CO2 crosses BBB readily but is not
neutralized as quickly - thus, central
values are ~10 mm Hg higher than in
arterial blood.
PULMONARY
CENTRAL CHEMORECEPTORS
CHEMICAL CODING
Pre Ganglionic
✤
✤
PNS ACh
SNS ACh
Post Ganglionic
✤
✤
PNS ACh
SNS NE
(exception sweat glands)
AUTONOMIC TRANSMISSION
“GOD MAY FORGIVE YOUR SINS, BUT YOUR NERVOUS SYSTEM WON’T.” ALFRED KORZYBSKI
ACETYLCHOLINE
Most abundant NT in PNS
✦ Synthesized in cytoplasm of axon
terminal from acetylCoA+choline
catalyzed by choline acetyl
transferase.
✦
!
✦
✦
✦
Stored in synaptic vesicles until
action potential causes its release
via exocytosis.
Binds to cholinergic
! receptors. Degraded by AChE at both preand post-synaptic membranes.
PARASYMPATHETIC TRANSMISSION
“DON’T LONG FOR THE UNRIPE GRAPE.” HORACE
Terminal filaments end in presynaptic
enlargements, variscosities, in which NTs are
stored.
!
The rate of synthesis depends on the level of
ANS activity and is regulated by local feedback.
!
!
Depolarization releases vesicular contents into
synaptic cleft.
!
Time for diffusion is directly proportional to
the width of the synaptic cleft.
AUTONOMIC TRANSMISSION
“BE HAPPY, IT’S ONE WAY OF BEING WISE.” COLETTE
CATECHOLAMINES
NE is released from localized presynaptic
vesicles of nearly all postganglionic
sympathetic nerves
Additionally, vascular SNS terminals also
release ATP as a synergistic cotransmitter
!
!
!
ACh stimulates adrenal chromaffin cells to
release a surge of EPI and NE, taking the place
of postganglionic neurons
Sympathetic fibers in the adrenal medulla
are preganglionic, thus ACh is the NT
SYMPATHETIC TRANSMISSION
“PRESSURE IS CALMING TO THE NERVOUS SYSTEM.” TEMPLE GRANDIN
CATECHOLAMINES
Presynaptic Reuptake
!
Major stereospecific; structurally similar compounds may enter
vesicles and displace NE
TCAs, cocaine inhibit reuptake = accentuated receptor response
Extraneuronal Uptake
Minor extraneuronal tissues endocytose & metabolize
!
Kidney + Liver Diffusion
Minor endogenous catecholamines
Major synthetic catecholamines
!
!
Vanillylmandelic Acid
Major metabolite (80-90%) excreted metabolic products provide a
gross estimate of SNS activity and can facilitate the clinical
diagnosis of pheochromocytoma and other autonomic disorders
SYMPATHETIC TRANSMISSION
“DON’T HAVE GOOD IDEAS IF YOU AREN’T WILLING TO BE RESPONSIBLE FOR THEM.” ALAN PERLIS
SYMPATHOMIMETICS
Structurally similar to catecholamines, thus
also exhibit effect via adrenergic receptors
All clinically useful catecholamines are
sympathomimetics, but not all
sympathomimetics are catecholamines.
!
!
Indirect stimulate release of stored NE
Efficacy dependent on neuronal storage of
endogenous NE.
!
!
Direct independent of endogenous NE stores
SYMPATHETIC TRANSMISSION
“IF YOU JUDGE PEOPLE, YOU HAVE NO TIME TO LOVE THEM” MOTHER THERESA
C ORONARY A RTERIES
a1 VasoConstriction
Do not rely on Ca2+
↑Preload
↑Afterload
‣
Phenylephrine
a2 VasoConstriction
↑ myocardial ischemia
Highly dependent on Ca2+
Inhibit NE release
‣
A ADRENERGIC
Clonidine
“NOTHING GREAT IN THIS WORLD WAS EVER ACCOMPLISHED WITHOUT PASSION.” HEBBEL
Tubular a1
Predominant in renal vasculature
Renal vasoconstriction
Modulates renal blood flow
Enhance Na+/H2O reabsorption
Anti-natriuresis, Anti-diuresis
!
Tubular a2
Dominant a receptor
Promote Na+/H2O excretion
A ADRENERGIC
“A MERRY HEART DOETH GOOD LIKE MEDICINE” KING SOLOMON
Sympathetic influence is most important during stress. When the body is
challenged the sympathetic activity increases levels of plasma glucose and fatty
acids. The extra availability of fuel enables the body to more readily respond to a
stressful situation.
a2 CENTRAL NEURAXIS
A ADRENERGIC
“THE BEST WAY IS ALWAYS THROUGH.” ROBERT FROST
Inhibit Insulin and ADH release
Inhibit bowel activity
Increase GH release
Located in the myocardium, SA node, and ventribular conduction system;
functionally coupled to adenylate cyclase
!
b1 INOTROPIC, CHRONOTROPIC
Post-Synaptic
Innervated; respond to NE
!
!
b2 INOTROPIC, CHRONOTROPIC
Pre-Synaptic/Post-Synaptic (EPI)
Noninnervated; accelerate NE release
40% atrium, 20-30% ventricle
Effects oppose a2 receptors
(b2 antagonists = a2 agonists)
B ADRENERGIC
“MEDICINE IS A SCIENCE OF UNCERTAINTY, AN ART OF PROBABILITY.” WILLIAM OSLER
b1 RENIN RELEASE
Predominant
JuxtaGlomerular Apparatus
B ADRENERGIC
b2 VASODILATION
Improved renal flow
“MEDICINE IS A SCIENCE OF UNCERTAINTY, AN ART OF PROBABILITY.” WILLIAM OSLER
!
Ða1
HYPOTHALAMUS
Prolactin release
BASAL GANGLIA
Motor function coordination
MEDULLA
ChemoReceptor Zone (N/V)
Da1 VASODILATION
Postsynaptic; Vascular smooth muscle cells of kidney and mesentery
Coronary, cerebral, cutaneous arteries
Da2 VASOCONSTRICTION/VASODILATION
Postsynaptic (similar to postsynaptic a2); renal vasculature
Presynaptic inhibit NE release (presynaptic a2); postganglionic SNS
DOPAMINERGIC
“HAPPINESS ISN’T GOOD ENOUGH FOR ME - I DEMAND EUPHORIA!” BILL WATTERSON
!
Da1
RENAL TUBULES
Inhibit Na+ reabsorption
Natriuresis, Diuresis
!
JUXTA GLOMERULAR APPARATUS
↑ Renin release
!
GASTRO-INTESTINAL
↑ secretions: esophagus, stomach, small intestine
Hypomotility
DOPAMINERGIC
“SPEND THE AFTERNOON. YOU CAN’T TAKE IT WITH YOU.” ANNIE DILLARD
Agonists
Nicotine prototype
!
Low Dose autonomic ganglia + NMJ
!
!
!
Antagonists
Nicotine prototype
!
High Dose ganglionic/NMJ blockade
!
Compete, mimic and interfere with Ach
metabolism
Hexamethonium, trimethaphan, dtubocure
GANGLIONIC DRUGS
“A PATH WITH NO OBSTACLES DOES NOT LEAD ANYWHERE.” FRANK CLARK
ACh Derivatives
More selective muscarinic activity than ACh
More resistant to inactivation by cholinesterase and thus
prolonged action.
!
Choline Esters
Methacholine Slows HR, dilates vessels, increases
intestinal tone. Treat over-dose w/ atropine.
‣
PSVT
!
Bethanechol GI + Urinary tracts.
Post-Op abdominal distension
‣
Gastric atony
‣
Neurogenic bladder
‣
!
Alkaloids
Pilocarpine No anesthestic use. Topical miotic in the
treatment of glaucoma to reduce IOP.
MUSCARINIC AGONISTS
DIRECT CHOLINOMIMETICS
Cholinesterase Inhibitors
Produce cholinomimetic effecs via inhibition or inactivation of
acetylcholinesterase and/or pseudocholinesterase
!
Reversible
Anion Competition Ammonium compounds; delay hydrolysis from 1 to 8
hrs. Most do not cross the BBB. [Exception: physostigmine]
‣
Neuromuscular blockade reversal
‣
Atropine poisoning, Myasthenia Gravis
!
Non-Reversible
Esteratic Competition Organophosphates; may last from days to weeks. Highly
lipid-soluble, readily pass into CNS.
‣
Glaucoma
‣
Chemical warfare, potent insecticides
!
Side Effects
‣
Bradycardia
‣
Hypotension
‣
Bronchospasm
‣
Intestinal spasm
‣
Muscle paralysis (excessive dose)
MUSCARINIC AGONISTS
INDIRECT CHOLINOMIMETICS
disorientation, hallucinations, and delirium (see “Central Anticholinergic Syndrome”).
Atropine readily crosses BBB/placenta
!
Reverse muscle relaxant
‣ ↑
CO during sinus bradycardia
‣
Organophosphate antidote
‣
Pre-medication (cardiac patients)
‣
Amnesia induction (trauma patients)
‣
!
Side Effects Central Anticholinergic Syndrome (physostigmine)
Scopolamine readily crosses BBB/placenta
‣
!
Amnesia, sedation, euphoria
Side Effects Paradoxical bradycardia, mydriasis, cycloplegia
Glycopyrrolate does not cross BBB/placenta
‣
‣
!
salivary,bronchial, pharyngeal secretions
↑ gastric acid pH
Figure 15-15. Structural formulas of the clinically useful antimuscarinic drugs.
Side Effects heat stroke, fever, delirium, xerostomia, urinary retention, diarrhea
CHOLINERGIC ANTAGONISTS
“EVERYTHING IN EXCESS IS OPPOSED TO NATURE.” HIPPOCRATES
Lap G-Tube Placement
9 m/o (4.3 kg) male w/ failure-to-thrive
!
✤
✤
✤
Former 36 wk twin A
SVD w/o complication
At 3 mos of age:
RSV ➺ cardiac/pulmonary failure
➺ CPR (43 mins)
➺ ECMO (11 days)
➺ shock, liver/kidney failure
✤
Past Medical History
‣ Post fossa SDH w/ non-communicating
hydrocephalus
‣ Seizures
!
CASE I
NEOSTIGMINE
Pt came w/ 24 g PIV R hand
Administered
10 mg Propofol
2 mg Rocuronium
5 mcg Fentanyl
✤
✤
✤
3.0 microcuff ETT placed atraumatically
(x1 attempt)
‣ Procedure proceeded without
complication
‣ Reversal calculated with student and
given
‣ Patient breathing well after procedure
and extubated without complications
‣
CASE I
NEOSTIGMINE
Administered
‣ 10x neostigmine intended
‣ 10x glycopyrrolate inteneded
! !
Patient is otherwise non-symptomatic
Where to discharge him to?
CASE I
NEOSTIGMINE
SIDE EFFECTS
‣
‣
‣
‣
‣
Cardiac bradycardia, hypotension
Pulmonary bronchospasm, hypoxia, secretions
GI hypermotility, PONV
Opthalmic miosis, decrease intraocular pressure
Musculoskeletal potential for recurization ➺ respiratory failure
HALF-LIFE
‣
‣
T1/2 60-90 minutes
Intended to give 0.3 mg, patient received 3 mg 1hr
2hr
3hr
3 mg ➺ 1.5 mg ➺ 0.75 mg ➺ 0.375 mg
1.5 hr
3 hr
4.5 hr
!
Decision made to admit patient to IMU overnight for closer monitoring and
potential for delayed neostigmine toxicity
CASE I
NEOSTIGMINE
PATIENT COURSE
No acute events in IMU
Patient discharged to floor next morning
Standard monitoring on floor for 48 hrs w/ no complications
Patient discharged from hospital on 12/21/12
‣
‣
‣
‣
WHAT HAPPENED?
Calculated dose w/ student (70 mcg/kg) x (4.3 kg) = 300 mcg
‣
‣
‣
‣
Student states “okay” so 3 was administered
Student grabs 5 ml syringe of neostigmine
Student was asked to put it in a smaller syringe
Student begins to switch syringes, but then asks if he can just give it
from the current syringe
CASE I
NEOSTIGMINE
Epigastric Hernia Repair
28 yo (50 kg) ASA I
!
‣
‣
5 mg Vec, TOF kept at 0 throughout case; 90 min surgery time
1 mg atropine + 2.5 mg neostigmine
given twice due to miscommunication between resident & attending
-
‣
‣
TOF became 0 and patient was once again paralyzed
Increased secretions noted but VS remained stable
‣
Ventilated for 35 mins before TOF reappeared
‣
Patient extubated after TOF ratio of 95%
‣
Patient monitored in ICU for 6 hr w/ unremarkable discharge
CASE REPORT
NEUROMUSCULAR BLOCKADE
Neuromuscular Blocked by Neostigmine in Anesthetized Man
‣
Studied effects of neostigmine in 26 patients
- Found repeated doses of 2.5 mg, 2-5 mins apart produced depressed
peak tetanic contraction and re-established tetanic fade
-
-
A single dose of 5 mg rapidly produced a slight depression in tetanus
and brief reappearance of fade, but not as prominent as repeated doses
In patient not given neuromuscular blocking agents, peak tetanic
contraction and severe tetanic fade persisted for about 20 minutes
CASE REPORT
NEUROMUSCULAR BLOCKADE
Attendings - Residents - AA/CRNA
~
Clear communication w/ confirmation
Don’t assume preceptee understands
Be careful calculating mcg and administering mg
Set preceptees for up success, not failure
Repitition, repitition, repitition!!
LESSONS LEARNED
Students - Residents - AA/CRNA
~
If you aren’t positive about something...ASK.
If something doesn’t sound right...confirm.
Positive communication feedback, repitition
Realize what you know & admit what you don’t know
Avoid statements like “that’s what I meant” or “I knew
that”
LESSONS LEARNED
!HENYLEPHRINE
MOA A
DELIVERY Bolus, Peripheral IV
EFFECTS
Venous & Arterial Constriction
↑ Preload
↑ Stroke Volume
Reflex Bradycardia (thus no change in CO)⟷⟷⬄⟷
INDICATIONS
Tetralogy of Fallot shunt reversal
Increase BP during cardiopulmonary bypass
Reverse vasodilatory states
Reverse anesthetic hypotension
!
SIDE EFFECTS
!
Cardiac dysrhythmias
SYMPATHOMIMETICS
“CARRY ON AND PRESERVE YOURSELVES FOR BETTER TIMES.” VIRGIL
NOREPINEPHRINE
!
MOA A > B
DELIVERY IV
!
!EFFECTS
!
! VasoConstriction
! ‣ Low dose ↑ CO, ↑ BP
! ‣
! High dose arteriolar constriction
INDICATIONS
Cardiogenic shock
Initiate adreneregic response
Cardiopulmonary bypass separation
Steady hemodynamic maintenance
!
SIDE EFFECTS
!
Renal arteriolar constriction
Reflex bradycardia
Oliguria
Tissue necrosis
SYMPATHOMIMETICS
“IF YOU NEVER ASSUME IMPORTANCE, YOU NEVER LOSE IT.” LAO-TZU
EPINEPHRINE
MOA A, B
DELIVERY Central IV
EFFECTS
VasoConstriction
a skin, mucosa, renal
b striated/skeletal m.
INDICATIONS
Cardiac arrest
Asthma
Anaphylaxis
Peri-Operative period
Produce bloodless field
Prolong regional anesthesia
!
SIDE EFFECTS
!
!
!
Cardiac dysrhythmias
SYMPATHOMIMETICS
“DON’T LET YOUR HEARTS GROW NUMB. STAY ALERT.” ALBERT SCHWEITZER
EPHEDRINE
MOA A, B
DELIVERY IM, IV
EFFECTS
NE Release (predominant indirect)
Restore HR, ↑Preload, ↑CO, ↑BP
VasoConstriction: Venous > Arterial
Central Redistribution of Blood
Restores Uterine Perfusion (hydrated)
INDICATIONS
Epidural anesthesia hypotension
OB/GYN pressor of choice
Prolong regional anesthesia
!
SIDE EFFECTS
!
!
!
Tachyphylaxis
SYMPATHOMIMETICS
“NEVER DO ANYTHING AGAINST CONSCIENCE, EVEN IF THE STATE DEMANDS IT.” ALBERT EINSTEIN
ISOPROTERENOL
MOA B
DELIVERY IM, SL, Inhalant
EFFECTS
↑ HR
↑ contractility
↓ SVR
INDICATIONS
Potent dysrhythmogenic
Cardiac failure
Chemical pacemaker (3rd degree AV block)
Regurgitant aortic valvular disease
Pulmonary hypertension
!
SIDE EFFECTS
Cardiac dysrhythmias
Decrease diastolic perfusion pressure
Increase myocardial O2 demand
Redistributes BF nonessential organs,
don’t use in shock
SYMPATHOMIMETICS
“PRAY FOR THE DEAD AND FIGHT LIKE HELL FOR THE LIVING.” MARY HARRIS JONES
DOBUTAMINE
MOA B1 > B2
DELIVERY IM, SL, Inhalant
EFFECTS
↑ HR
Coronary Artery VasoDilation
Diastolic Coronary Filling Pressure
Pulmonary Vasculature VasoDilation
INDICATIONS
Cor Pulmonale
Cardiac Units: DBT > DA
SIDE EFFECTS
b blockade unmasks a1 agonism
!
!
Dramatic ↑ HR
SYMPATHOMIMETICS
“READ EVERYTHING.” JIM ROGERS
DOPAMINE
MOA D > B
DELIVERY IV
>
A
EFFECTS
d Low “Renal” Dose [0.5-2 mg/kg/min]
VasoDilation
Tubular Cell Natriuresis
Diastolic BP
↑ HR
b Intermediate Dose [2-10 mg/kg/min]
Chronotropic
VenoConstriction: Preload
Systemic VasoDilation: Afterload
a High Dose [ >10 mg/kg/min]
↑ BP
↑ SVR
INDICATIONS
Low-Output Syndrome
Congestive Heart Failure
Pulmonary Failure
Cardiogenic Shock
Third-Space Edema
!
SYMPATHOMIMETICS
“IT’S DIFFICULT TO THINK NOBLY WHEN ONE THINKS ONLY OF INCOME.” JEAN-JAQUES ROUSSEAU
A-ANTAGONISTS
MOA B1 > B2
EFFECTS
Smooth m. relaxation
Hypotension, Orthostatic hypotension
Tachycardia
Miosis
Diarrhea
Ejaculatory inhibition
Nasal stuffiness
!
CLASSIFICATION
Phenoxybenzamine
Phentolamine
Prazosin
!
ANESTHETIC MANAGEMENT
Anti-hypertensive, often administered w/ diuretics
Preload IV fluids to ensure adequate central volume
SYMPATHOLYTICS
“THERE IS A WAY TO DO IT BETTER. FIND IT.” THOMAS EDISON
B-ANTAGONISTS
PROPRANOLOL
MOA Non-selective (B1, B2) EFFECTS
✤ ↓HR, ↓Contractility
✤ ↑SVR
✤ ↓Renin activity
SIDE EFFECTS
✤ Bradycardia, heart block, CHF exacerbation
✤ Bronchospasm
✤ Sedation
✤ Suppression of insulin secretion
✤ Blunting of catecholamine response to hyoglycemia
✤ Rebound ↑HR, NOT orthostatic hypotension A1
LABETALOL
MOA Mixed antagonist (A1, B1, B2)
✤ ↓SVR, ↓HR
‣
Very beneficial in coronary artery disease
↓Renin activity
SIDE EFFECTS
✤ CHF exacerbation
✤ Bronchospasm
✤
SYMPATHOLYTICS
“YOU WERE BORN WITH WINGS. WHY PREFER TO CRAWL THROUGH LIFE?” RUMI
FENOLDOPAM
MOA D1
DELIVERY Continuous IV
EFFECTS
Potent, Direct Renal Vasodilator
Natriuresis, Diuresis
Increase Creatinine Clearance
INDICATIONS
Acute Resolution of Severe HTN
Vascular Anesthesia Renal Protector
!
SIDE EFFECTS
!
Tachycardia
Vasodilation, Hypotension
Flushing, Dizziness, Headache
Hypokalemia
DRUG CLASS: OTHER ANTIHYPERTENSIVES
“IN WHATEVER YOU DO, FAILURE IS AN OPTION. FEAR IS NOT.” JAMES CAMERON
CLONIDINE
MOA A2
DELIVERY IV, IM, ED
EFFECTS
Central Anti-HTN
Peripheral Decrease Renin, NE, EPI
Dose-Dependent Analgesia (ED/SAB)
INDICATIONS
Severe/Renin-Dependent HTN
Enhance Post-Op Analgesia
Blunt Reflex Tachycardia {Intubation}
Reduce Vasomotor Liability
Decrease [Catecholamines]
SIDE EFFECTS
Sedation
Xerostomia
Hypotension, Bradycardia, Withrawal syndrome
A AGONIST
“LOVE WHAT YOU DO AND GET GOOD AT IT. COMPETENCE IS A RARE COMMODITY.” JON STEWART
DEXMEDETOMIDINE
MOA A2
DELIVERY Continuous IV
EFFECTS
Sedation
Decrease HR, BP
Decrease [Catecholamines]
INDICATIONS
Peri-Operative Hypothermia
Anti-Shivering
PreMedication: Awake, Fiberoptic Intubation
Anxiolytic, Sedative
Decrease MAC: Volatile Anesthetics
SIDE EFFECTS
Rebound hypertension
HyperExcitability
Arrythmias
A AGONIST
“ALL IS WELL, PRACTICE KINDNESS, HEAVEN IS NIGH.” JACK KEROUAC
VASOPRESSIN
MOA V1
DELIVERY SC, IM, IV, INJ
EFFECTS
Passive H2O Reabsorption Increase Extra-Cellular Fluid
Vascular Smooth m. Intense VasoConstriction
Cardiac Myocytes Inotropic
INDICATIONS
Diabetes Insipidus
Abdominal Distension
Adjunt Therapy: GI Hemorrhage, Esophageal Varices
Septic Shock Pressor
Cardiac Arrest 2º Ventricular Arrythmias
Pulseless Electrical Activity, Asystole
SIDE EFFECTS
Sedation
Xerostomia
Hypotension, Bradycardia
NON-ADRENERGIC SYMPATHOMIMETICS
“START WHERE YOU ARE, USE WHAT YOU HAVE, DO WHAT YOU CAN.” ARTHUR ASHE
ADENOSINE
DELIVERY IV
EFFECTS
Cardio-Protection
Myocardial O2 Regulation
Atrial Myocyte HyperPolarization
Decreased AP duration
Anti-Dysrhythmic
Interrupts Re-Entrant AV Nodal Tachycardias
Antagonizes Inward Ca2+ Current
Vasomotor Tone Regulation
INDICATIONS
PSVT Conversion
ACLS: Narrow-Complex Tachycardia
ACLS: Wide-Complex Tachycardia
SIDE EFFECTS
Hypotension, Bradycardia
Headache, Dyspnea, Bronchospasm
NON-ADRENERGIC SYMPATHOMIMETICS
“ALWAYS BE ON THE LOOKOUT FOR THE PRESENCE OF WONDER.” E.B. WHITE
PHOSPHODIESTERASE INHIBITORS
MOA Selective ⊝ PDE III
DELIVERY IV
EFFECTS
Impedes cAMP metabolism
Inotropic + VasoDilation
Diastolic Relaxation
Dose-Dependent HemoDynamic Effects
INDICATIONS
Short-term IV therapy for CHF
Decompensated heart failure
!
SIDE EFFECTS
!
Hypotension, Bradycardia
Headache, Dyspnea, Bronchospasm
NON-ADRENERGIC SYMPATHOMIMETICS
“UNLESS YOU HAVE UNANSWERED QUESTIONS, YOU HAVEN’T READ ENOUGH.” DANIEL BERNSTEIN
GLUCAGON
MOA GPCR (G protein coupled receptors)
DELIVERY IM, IV
EFFECTS
Inhibit GI Motility
Inorganic Electrolyte Urinary Excretion
Increased Insulin Secretion
Hepatic Glycogenolysis, Gluconeogenesis
Inotropic, Chronotropic
Anorexia
INDICATIONS
Insulin-Induced Hypoglycemia
Excessive B-blockade
SIDE EFFECTS
!
Nausea, Vomiting
Hypoglycemia
HypoKalemia
NON-ADRENERGIC SYMPATHOMIMETICS
“YOU CAN’T BUILD A REPUTATION ON WHAT YOU INTEND TO DO.” LIZ SMITH
DIGITALIS GLYCOSIDES
MOA ⊝ Na+/K+ ATPase
DELIVERY IV
Ca2+
EFFECTS
Inotropic
Enhance Myocardial Automaticity
Slows Conductive Tissue Impulse Propagation
INDICATIONS
Congestive Heart Failure
Supra-Ventricular Cardiac Dysrhythmias
PSVT Conversion
SIDE EFFECTS
!
Digitalis Toxicity
HypoKalemia
Dysrhythmias
GI Disturbance
NON-ADRENERGIC SYMPATHOMIMETICS
“TAKE IT EASY, BUT TAKE IT.” WOODY GUTHRIE
CALCIUM SALTS
DELIVERY IM, IV
EFFECTS
Key Cardiac AP Component
IntraCellular Energy Storage & Utilization
Smooth m: Vascular, Uterine
INDICATIONS
Massive Blood Transfusion
HypoCalcemia
HyperMagnesemia
Ca2+ Channel Blocker Toxicity
Osteoporosis
SIDE EFFECTS
!
Dysrhythmias
GI Disturbance
NON-ADRENERGIC SYMPATHOMIMETICS
“NEVER LET YOUR SENSE OF MORALS GET IN THE WAY OF DOING WHAT’S RIGHT.” ISAAC ASIMOV
MONOAMINE OXIDASE INHIBITORS
MOA Non-selective inhibition
EFFECTS
✤ Accumulate: NE, EPI, DA, 5HT
✤ Potentiate sympathomimetic amines
‣
‣
‣
‣
TRICYCLIC ANTIDEPRESSANTS
MOA Inhibit neuronal NE uptake
EFFECTS
✤ Atropine
✤
✤
✤
✤
‣
Exaggerated effect 2º anticholinergic property
‣
Potentiate TCA; hepatic metabolic competition
‣
Microsomal enzyme induction ↑metabolism
‣
Prolonged sedation
‣
Acute HTN, cardiac dysrhythmia
Neuroleptics
Hypertensive crisis
Convulsions
Coma
Hepatotoxicity
SELECTIVE SEROTONIN REUPTAKE INHIBITORS
MOA Selectively inhibit neuronal 5HT uptake
EFFECTS
✤ Potentiates behavioral changes
✤ Discontinuation not indicated prior to
surgery
Barbituates
Thiopental
Ketamine
ANTIDEPRESSANTS
“THERE’S ALWAYS A REASON TO SMILE. FIND IT.” BOB PARSONS
THANKS FOR YOUR ATTENTION!
HERZOG’S RULES
1. Be on time.
2. Bust your butt.
3. Play smart.
4. Have some laughs while
you’re at it.
“THE FUTURE OF OUR PRACTICE” HAGBERG
SARA SLABISAK - MICHAEL EVANS - SETH HAYES - MONICA CHEN