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!