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CARIN HAGBERG, MD
AUTONOMIC NERVOUS SYSTEMCLINICAL ANESTHESIA, CHP 15
AUTONOMIC NERVOUS SYSTEM
SARA SLABISAK, MS4
Autonomic Nervous SystemThe wizard of regulation and balance
Autonomic Nervous System
…involuntary regulation of visceral reflexes that occur below the level of consciousness
‣ Cardio-Pulmonary ‣ Thermoregulation ‣ GI motility ‣ GU function ‣ Metabolic ‣ Endocrine ‣ Adaptive Stress Response
… Essentially, anesthesiology is the practice of autonomic medicine
CENTRAL INTEGRATION
CENTRAL AUTONOMIC ORGANIZATION“BE KIND, FOR EVERYONE YOU MEET IS FIGHTING A GREAT BATTLE.” IAN MACLAREN
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
!
“IT’S NOT WHAT HAPPENS, IT’S HOW YOU REACT TO IT THAT MATTERS.” EPICTETUSPERIPHERAL ANS ORGANIZATION
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.
“BE HAPPY - IT’S ONE WAY OF BEING WISE.” COLETTEPERIPHERAL ANS ORGANIZATION
SYMPATHETICSThoracolumbar 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 AUTONOMIC NERVOUS SYSTEM
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
SYMPATHETICS
“DON’T CRY BECAUSE IT’S OVER, SMILE BECAUSE IT HAPPENED.” DR. SEUSS
Cervical Ganglia T1-T5 spinal segments generate preganglionic fibers !➺ Superior Cervical ➺ Middle Cervical ➺ Stellate
PERIPHERAL ANS ORGANIZATION
PARASYMPATHETICS
“UPON THE CONDUCT OF EACH, DEPENDS THE FATE OF ALL.” ALEXANDER THE GREAT
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 pre-ganglionic neurons (1-3:1)
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
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
“NEVER PRACTICE TWO VICES AT ONCE.” TALLULAH BANKHEADCHOLINERGIC TRANSMISSION
CARDIOVASCULAR“HEARTS WILL NEVER BE PRACTICAL UNTIL THEY ARE UNBREAKABLE.” WIZARD OF OZ (1939)
CARDIO AUTONOMICSCHRONOTROPIC 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
CARDIOVASCULARAUTOMATICITY
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
CARDIOVASCULARCONTRACTILITY
Contractility Sympathetic Stellate InnervationNormal 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 cross-bridges 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
CARDIOVASCULARHIGH-PRESSURE ARTERIAL BARORECEPTORS
Carotid Sinus Reflex [carotid sinus + aortic arch]!Acute rise in arterial pressure activates baroreceptors through stretch-sensitive Na+-channels. ↑afferent activity ultimately ↓HR via post-synaptic, 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.
CARDIOVASCULARHIGH-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.
CARDIOVASCULARLOW-PRESSURE VENOUS 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.
PERIPHERAL CIRCULATION“A PINT OF SWEAT SAVES A GALLON OF BLOOD.” GENERAL GEORGE PATTON (1944)
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
HEMODYNAMICSMEAN ARTERIAL PRESSURE
Primary neural control of CV function exerted by sympathetic
neurons to: !
1) SA node to control HR2) Ventricular myocardium to control
ventricular contractility3) Veins to control venomotor tone4) Arterioles to control vascular
resistance
PULMONARY“REMEMBER TO BREATHE. IT IS AFTER ALL, THE SECRET OF LIFE.” GREGORY MAGUIRE
BRONCHOMOTOR CONTROL
Non-Ventilatory Function ✤ Metabolizes local mediators {ie, NE} ✤ Converts Angiotensin I
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
PULMONARYVENTILATION REGULATION
Dorsal Respiratory Group Primarily inspiratory neurons
Medulla Central Pattern Generator Network of neurons that generates regular, repeating pattern of neural activity, called the ventilation cycle.
Pons Inspiratory + Expiratory Facilitate transition between each breath
Ventral Respiratory Group 2 expiratory and 1 inspiratory regions
PULMONARYPERIPHERAL CHEMORECEPTORS
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
PULMONARYCENTRAL 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.
AUTONOMIC TRANSMISSION“GOD MAY FORGIVE YOUR SINS, BUT YOUR NERVOUS SYSTEM WON’T.” ALFRED KORZYBSKI
CHEMICAL CODING
Pre Ganglionic ✤ PNS ACh ✤ SNS ACh
Post Ganglionic ✤ PNS ACh ✤ SNS NE
(exception sweat glands)
PARASYMPATHETIC TRANSMISSION
!
!
✦ 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 pre-
and post-synaptic membranes.
“DON’T LONG FOR THE UNRIPE GRAPE.” HORACE
ACETYLCHOLINE
AUTONOMIC TRANSMISSION“BE HAPPY, IT’S ONE WAY OF BEING WISE.” COLETTE
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.
SYMPATHETIC TRANSMISSION“PRESSURE IS CALMING TO THE NERVOUS SYSTEM.” TEMPLE GRANDIN
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
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
“DON’T HAVE GOOD IDEAS IF YOU AREN’T WILLING TO BE RESPONSIBLE FOR THEM.” ALAN PERLIS
CATECHOLAMINES
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
“IF YOU JUDGE PEOPLE, YOU HAVE NO TIME TO LOVE THEM” MOTHER THERESASYMPATHETIC TRANSMISSION
SYMPATHOMIMETICS
A ADRENERGIC
a1 VasoConstriction �Do not rely on Ca2+ ↑Preload
↑Afterload
‣ Phenylephrine
a2 VasoConstriction ↑ myocardial ischemia Highly dependent on Ca2+
Inhibit NE release‣ Clonidine
CORONARY ARTERIES
“NOTHING GREAT IN THIS WORLD WAS EVER ACCOMPLISHED WITHOUT PASSION.” HEBBEL
“A MERRY HEART DOETH GOOD LIKE MEDICINE” KING SOLOMONA ADRENERGIC
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
“THE BEST WAY IS ALWAYS THROUGH.” ROBERT FROSTA ADRENERGIC
a2 CENTRAL NEURAXIS Inhibit Insulin and ADH release Inhibit bowel activity Increase GH release
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.
“MEDICINE IS A SCIENCE OF UNCERTAINTY, AN ART OF PROBABILITY.” WILLIAM OSLERB ADRENERGIC
!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)
Located in the myocardium, SA node, and ventribular conduction system; functionally coupled to adenylate cyclase
“MEDICINE IS A SCIENCE OF UNCERTAINTY, AN ART OF PROBABILITY.” WILLIAM OSLERB ADRENERGIC
b2 VASODILATION Improved renal flow
b1 RENIN RELEASE Predominant
JuxtaGlomerular Apparatus
“HAPPINESS ISN’T GOOD ENOUGH FOR ME - I DEMAND EUPHORIA!” BILL WATTERSONDOPAMINERGIC
!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“SPEND THE AFTERNOON. YOU CAN’T TAKE IT WITH YOU.” ANNIE DILLARD
!Da1 RENAL TUBULES
Inhibit Na+ reabsorption Natriuresis, Diuresis !
JUXTA GLOMERULAR APPARATUS ↑ Renin release !
GASTRO-INTESTINAL ↑�secretions: esophagus, stomach, small intestine Hypomotility
“A PATH WITH NO OBSTACLES DOES NOT LEAD ANYWHERE.” FRANK CLARKGANGLIONIC DRUGS
Agonists Nicotine prototype !!!!Antagonists Nicotine prototype !High Dose ganglionic/NMJ blockade !Compete, mimic and interfere with Ach metabolism Hexamethonium, trimethaphan, d-tubocure
Low Dose autonomic ganglia + NMJ
MUSCARINIC AGONISTS
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.
DIRECT CHOLINOMIMETICS
MUSCARINIC AGONISTSINDIRECT 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)
“EVERYTHING IN EXCESS IS OPPOSED TO NATURE.” HIPPOCRATESCHOLINERGIC ANTAGONISTS
P.347
Figure 15-14. Structural formulas of clinically useful reversible anticholinesterase drugs. Physostigmine is a tertiary amine and crosses the blood–brain barrier. It is useful in treatingthe central anticholinergic syndrome.
The irreversible cholinesterase inhibitors are mostly organophosphate compounds. The organophosphate compounds are highly lipid-soluble, readily pass into the CNS, and are rapidlyabsorbed through the skin. They are used as the active ingredient in potent insecticides and chemical warfare agents known as nerve gases (see Chapter 60). The only therapeutic drug ofthis group is echothiophate, which is available in the form of topical drops for the treatment of glaucoma. Its primary advantage is its prolonged duration of action. Topical absorption isvariable but considerable. Echothiophate can remain effective for 2 or 3 weeks following cessation of therapy. A history of use of echothiophate is important in avoiding prolonged action ofsuccinylcholine, which requires pseudocholinesterase for its hydrolysis. Organophosphate poisoning manifests all the signs and symptoms of excess ACh. The antidote cartridges dispensed totroops to counter the effects of anticholinesterase nerve gases contain only atropine, which would effectively counter the muscarinic effects of the gas; however, atropine does little tocounter the high-dose nicotinic muscle paralysis or the central ventilation depression that contributes to death from nerve gases. Treatment requires high doses of atropine, 35 to 70 mg/kgintravenously (IV) every 3 to 10 minutes until muscarinic symptoms abate. Lower doses at less frequent intervals may be required for several days. Central ventilatory depression andweakness require respiratory support and specific therapy of the cholinesterase lesion. Pralidoxime has been reported to reactivate cholinesterase activity by hydrolysis of the phosphate
enzyme complex. It is particularly effective with parathion poisoning and is the only cholinesterase reactivator available in the United States.26
Muscarinic Antagonists
Muscarinic antagonist refers to a specific drug action for which the term anticholinergic is widely used. Any drug that interferes with the action of ACh as a transmitter can be considered ananticholinergic agent. The term anticholinergic refers to a broader classification that also includes the nicotinic antagonists.
Atropine-Like Drugs
Atropine, scopolamine, and glycopyrrolate are the most commonly used muscarinic antagonists used in anesthesia (Fig. 15-15). The actions of these drugs include inhibition of salivary,bronchial, pancreatic, and gastrointestinal secretions and antagonism the muscarinic side effects of anticholinesterases during reversal of muscle relaxants. Historically, atropine was
introduced to anesthesia practice to prevent excessive secretions during ether anesthesia and to prevent vagal bradycardia during the administration of chloroform.26 Antimuscarinic agentsdo not inhibit transmission equally, and there are marked variations in sensitivity at different muscarinic sites owing to differences in penetration and affinities of the various receptors.Differences in relative potency between the different antimuscarinics are outlined in Table 15-6. Atropine and scopolamine are tertiary amines (Fig. 15-15) and easily penetrate the blood–brain barrier and placenta. Glycopyrrolate is a quaternary amine that, like the reversible anticholinesterase drugs, does not easily penetrate these barriers. Glycopyrrolate, a syntheticantimuscarinic, has gained popularity because it avoids the central effects of the other two drugs. Atropine and scopolamine have notable CNS effects that are dissimilar. Scopolaminediffers from atropine mainly in its central depressant effects, which produce
sedation, amnesia, and euphoria. Such properties are widely used for premedication for cardiac patients in combination with morphine and a major tranquilizer. It also has been used toinduce amnesia in patients who have a high risk for intraoperative awareness, such as trauma victims who are hemodynamically unstable and cannot receive adequate anesthesia. Atropine,as a premedicant, has slight effects on the CNS, including mild stimulation. Higher doses such as those given for reversal of muscle relaxants (1 to 2 mg) may produce restlessness,disorientation, hallucinations, and delirium (see “Central Anticholinergic Syndrome”).
Figure 15-15. Structural formulas of the clinically useful antimuscarinic drugs.
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
!Side Effects heat stroke, fever, delirium, xerostomia, urinary retention, diarrhea
CASE INEOSTIGMINE
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 INEOSTIGMINE
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 INEOSTIGMINE
Administered ‣ 10x neostigmine intended ‣ 10x glycopyrrolate inteneded !!
Patient is otherwise non-symptomatic Where to discharge him to?
CASE INEOSTIGMINE
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 INEOSTIGMINE
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 REPORTNEUROMUSCULAR BLOCKADE
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 REPORTNEUROMUSCULAR 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
LESSONS LEARNED
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”
SYMPATHOMIMETICS“CARRY ON AND PRESERVE YOURSELVES FOR BETTER TIMES.” VIRGIL
!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 !
“IF YOU NEVER ASSUME IMPORTANCE, YOU NEVER LOSE IT.” LAO-TZUSYMPATHOMIMETICS
NOREPINEPHRINE!MOA A > B DELIVERY IV !!!!!!! INDICATIONS Cardiogenic shock Initiate adreneregic response Cardiopulmonary bypass separation Steady hemodynamic maintenance !
SIDE EFFECTS ��Renal arteriolar constriction ���Reflex bradycardia ��Oliguria ��Tissue necrosis !
EFFECTS VasoConstriction
‣ Low dose ↑ CO, ↑ BP ‣ High dose arteriolar constriction
“DON’T LET YOUR HEARTS GROW NUMB. STAY ALERT.” ALBERT SCHWEITZERSYMPATHOMIMETICS
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 !!!
“NEVER DO ANYTHING AGAINST CONSCIENCE, EVEN IF THE STATE DEMANDS IT.” ALBERT EINSTEINSYMPATHOMIMETICS
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 !!!
“PRAY FOR THE DEAD AND FIGHT LIKE HELL FOR THE LIVING.” MARY HARRIS JONESSYMPATHOMIMETICS
ISOPROTERENOLMOA 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
“READ EVERYTHING.” JIM ROGERSSYMPATHOMIMETICS
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 !!
“IT’S DIFFICULT TO THINK NOBLY WHEN ONE THINKS ONLY OF INCOME.” JEAN-JAQUES ROUSSEAUSYMPATHOMIMETICS
DOPAMINEMOA D > B > A DELIVERY IV 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 !
“THERE IS A WAY TO DO IT BETTER. FIND IT.” THOMAS EDISONSYMPATHOLYTICS
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
“YOU WERE BORN WITH WINGS. WHY PREFER TO CRAWL THROUGH LIFE?” RUMISYMPATHOLYTICS
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
“IN WHATEVER YOU DO, FAILURE IS AN OPTION. FEAR IS NOT.” JAMES CAMERONDRUG CLASS: OTHER ANTIHYPERTENSIVES
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 !
“LOVE WHAT YOU DO AND GET GOOD AT IT. COMPETENCE IS A RARE COMMODITY.” JON STEWART
CLONIDINE
A AGONIST
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
“ALL IS WELL, PRACTICE KINDNESS, HEAVEN IS NIGH.” JACK KEROUAC
DEXMEDETOMIDINE
A AGONIST
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
“START WHERE YOU ARE, USE WHAT YOU HAVE, DO WHAT YOU CAN.” ARTHUR ASHENON-ADRENERGIC SYMPATHOMIMETICS
VASOPRESSINMOA 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
“ALWAYS BE ON THE LOOKOUT FOR THE PRESENCE OF WONDER.” E.B. WHITENON-ADRENERGIC SYMPATHOMIMETICS
ADENOSINEDELIVERY 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
“UNLESS YOU HAVE UNANSWERED QUESTIONS, YOU HAVEN’T READ ENOUGH.” DANIEL BERNSTEINNON-ADRENERGIC SYMPATHOMIMETICS
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 !
“YOU CAN’T BUILD A REPUTATION ON WHAT YOU INTEND TO DO.” LIZ SMITHNON-ADRENERGIC SYMPATHOMIMETICS
GLUCAGONMOA 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 !
“TAKE IT EASY, BUT TAKE IT.” WOODY GUTHRIENON-ADRENERGIC SYMPATHOMIMETICS
DIGITALIS GLYCOSIDESMOA ⊝ Na+/K+ ATPase � Ca2+ DELIVERY IV 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 !
“NEVER LET YOUR SENSE OF MORALS GET IN THE WAY OF DOING WHAT’S RIGHT.” ISAAC ASIMOVNON-ADRENERGIC SYMPATHOMIMETICS
CALCIUM SALTSDELIVERY 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 !
“THERE’S ALWAYS A REASON TO SMILE. FIND IT.” BOB PARSONSANTIDEPRESSANTS
MONOAMINE OXIDASE INHIBITORS MOA Non-selective inhibition EFFECTS ✤ Accumulate: NE, EPI, DA, 5HT ✤ Potentiate sympathomimetic amines
‣ Hypertensive crisis ‣ Convulsions ‣ Coma ‣ Hepatotoxicity
TRICYCLIC ANTIDEPRESSANTS MOA Inhibit neuronal NE uptake EFFECTS
✤ Atropine ‣ Exaggerated effect 2º anticholinergic property
✤ Neuroleptics ‣ Potentiate TCA; hepatic metabolic competition
✤ Barbituates ‣ Microsomal enzyme induction ↑metabolism
✤ Thiopental ‣ Prolonged sedation
✤ Ketamine ‣ Acute HTN, cardiac dysrhythmia
SELECTIVE SEROTONIN REUPTAKE INHIBITORS MOA Selectively inhibit neuronal 5HT uptake EFFECTS
✤ Potentiates behavioral changes ✤ Discontinuation not indicated prior to
surgery
HERZOG’S RULES
1. Be on time. 2. Bust your butt. 3. Play smart. 4. Have some laughs while
you’re at it.
SARA SLABISAK - MICHAEL EVANS - SETH HAYES - MONICA CHEN
“THE FUTURE OF OUR PRACTICE” HAGBERG
THANKS FOR YOUR ATTENTION!
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