Ryan Dreikorn BSN SRNA York College of Pennsylvania / WellSpan Health Nurse Anesthesia Program.

KETAMINE AND DEXMEDETOMIDINE IN “WIND-UP” PHENOMENON

Ryan Dreikorn BSN SRNAYork College of Pennsylvania / WellSpan Health Nurse Anesthesia Program

http://www.youtube.com/watch?v=90cj4NX87Yk&feature=related

http://www.youtube.com/watch?v=90cj4NX87Yk&feature=related

Objectives

Quick overview of the neuron and pain pathways

Go to “Receptorland”

Discuss traditional pain management techniques

Discuss the role of Ketamine in attenuating “wind-up”

Discuss the emerging research of Dexmedetomidine (Precedex) in attenuating “wind-up”

Wind-Up Phenomenon

Pain is pain and then its over.

Wind-Up phenomenon increases pain intensity

Wind-Up phenomenon increases pain duration

Wind-Up phenomenon is mediated and attenuated though the NMDA receptor

Wind-Up phenomenon can be attenuated by the Alpha 2 receptor

Wind-Up Phenomenon

Change in Neural Physiology Innocuous Stimuli Becomes

Noxious Mediated by AMPA, NMDA, and NK1

Receptors Involves the Neurotransmitters

Glutamate and Substance P (SP) Brain Perceives Pain Even in the

Absence of Painful Stimuli Occurs Within One Hour

The Neuron

The Synapse

First Order / Second Order

Axon

Dendrite

First Order Neuron

Second Order Neuron

Synapse

Pain

Soma / Cell Body

Dorsal Root Ganglion

First Order Neuron

Synapse

Free NerveEnding

Anterolater Spinothalamic Tract

A bit much

Spinothalamic Tract (Simplified)

Thalamus

Cerebral Cortex

1st Synapse

2nd Synapse

1st Order Neuron

2nd Order Neuron

3rd Order Neuron

Spatial Summation

Spatial SummationWhat was incision?

What time was

antibiotic given?

What's my blood

loss?

Patients awake!

How much Neo?

Now I understand why

they call this the

“Blood/Brain

Barrier.”

Temporal Summation

High Intensity Temporal Summation

TABLE UP!NO,

DOWN!NO, UP!WHAT ARE YOU

DOING TO ME!?!?

I’m going to show him an “Action

Potential.”

Lois, Lois, mom, mom, mummy, mummy, muma, muma, ma, ma, mum, mum, mummy, ma

WHAT!?!?!

Persistent Low Intensity

HI!

Wind-Up Phenomenon

Persistent Low Intensity Temporal Summation

Review Neuron Physiology and the Action Potential

Last Stop Before “Receptorland”

Ionic Movement (Quick Review)

Intra-Cellular Fluid Extra-Cellular Fluid

Increased K+

Decreased Na+

Decreased Ca++

Decreased K+

Increased Na+

Increased Ca++C

ellu

lar

Mem

bra

ne

All In The Search For Equilibrium

The Action Potential (Quick Review)

Action Potential

Increases Na+ Permeability

Fast Na+ Channels

Impulse / AP Sent

Ca++

THIS CAN CHANGE

Ah Finally, Receptorland

Speaking The Local Dialect Ligands

Neuroplasticity Up-Regulation Down-Regulation

Ionotropic Receptors

Metabotropic Receptors

Nociceptors / Free Nerve Endings

A Fiber & C Fibers (More Dialect)

C-Fiber

A-Fiber

C-Fiber Only

A-Fiber Only

XX

Wide Dynamic Range Neuron

alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA)

AMPA

Neurokinin 1 Receptor (NK1r)

N-methyl-D-aspartate (NMDA) Receptor

2nd Order Neuron

Intracellular

Extracellular

KETAMINE

AP

Alpha 2 Receptor

Precedex

Mu Opioid Receptor

Pres

ynap

tic

Post

syna

ptic

Pain Impulse

Put The Pieces Together

This Is Very Graphic Material

We Need to Build a Neuron

Where Are We

You Are Here

Our Neurons

NMDAr MUr

MUr

α2rAMPArNK1rMUr MUr

α2r

Postsynaptic / Second Order Neuorn

Presynaptic / First Order Neuorn

Threshold -45 Mv

RMP -65Mv

The Synapse

RMP -65Mv

Threshold -45 Mv

Under General Anesthesia

Masked Man With A Knife

Initial Pain Impulses

NMDAr MUr

MUr


α2r

Postsynaptic / Second Order Neuron

Presynaptic / First Order Neuron

Threshold -45 Mv

RMP -65Mv

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Na+

Na+

More Pain Impulses

NMDAr MUr

MUr


α2r



Threshold -45 Mv

RMP -65Mv

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Na+

Na+

Glutamate

Glutamate

Glutamate

Na+

Na+

Increased Pain Impulses

NMDAr MUr

MUr


α2r



Threshold -45 Mv

RMP -65Mv

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Na+

Na+

Glutamate

Glutamate

Glutamate

Na+

Na+

Glutamate

Glutamate

GlutamateGlutama

teGlutamate

Glutamate

NMDA Receptor

Beginnings of Wind-Up Phenomenon

NMDAr MUr

MUr


α2r



Threshold -45 Mv

RMP -65Mv

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Na+

Na+

Glutamate

Glutamate

Glutamate

Na+

Na+

Glutamate

Glutamate

GlutamateGlutama

teGlutamate

Glutamate

Na+

Na+

Na+

Na+ RMP -60Mv

Wind-Up Phenomenon

NMDAr MUr

MUr


α2r


Threshold -45 MvRMP -60Mv

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Na+

Glutamate

Na+

Glutamate

Glutamate

GlutamateGlutama

teGlutamate

Glutamate

Na+

Na+

SPSP

SP

SP

SPSP

SP

SPSP

SP

Phospholipase-C

DAG

PKCNa+

Na+ Na

+

Ca++RMP -50Mv

Wind-Up Phenomenon

NMDAr MUr

MUr


α2r



Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Na+

Glutamate

Na+

Glutamate

Glutamate

GlutamateGlutama

teGlutamate

Glutamate

Na+

Na+

SPSP

SP

SP

SPSP

SP

SPSP

SP

Ca++

CaMKII

Na+

Na+

Hyperalgesia / Allodynia

NMDAr MUr

MUr


α2r



Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Na+

Glutamate

Na+

Glutamate

Glutamate

GlutamateGlutama

teGlutamate

Glutamate

Na+

Na+

SPSP

SP

SP

SPSP

SP

SPSP

SP

Ca++Na+

Na+

Pain

Pain

Pain

Pain

Wind-Up on the WDR Neuron

Traditional Opioids

NMDAr MUr

MUr


α2r



Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Na+

Na+

FentanylFentanyl

Fentanyl

Fentanyl

Fentanyl

K+

K+ K

+

K+

K+

K+

K+

K+

RMP -75Mv

RMP -75MvRMP -65Mv

Opioid Problem

NMDAr MUr

MUr


α2r



Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Na+

Na+

FentanylFentanyl

Fentanyl

Fentanyl

FentanylK+ K

+K+

K+

Pain

Pain

Pain

RMP -75MvRMP -65Mv

Glutamate

Glutamate Glutama

teGlutamate

Glutamate

Na+

Na+ Na

+

Glutamate

Na+

RMP -65Mv

SP

SP

SP

SPSP

SP

NK1r

NK1r

SP

SPSP

SP

SP

SP

SP

SP

SP

Na+

Na+

RMP -60MvRMP -55MvRMP -50Mv

Opioid Problem

NMDAr MUr

MUr


α2r



Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

FentanylFentanyl

Fentanyl

FentanylK+

K+

K+

K+

SP

SP

SP

SP

SP

SP

I’m out of gas!

Help!

NK1r

NK1r

SP

SP

SPSP

SP

SP

SP

SP

SP

SP

SP

SP

Pain

Pain

Pain

Ketamine

NMDAr MUr

MUr


α2r



Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

GlutamateGlutama

teGlutamate

Glutamate

SPSP

SP

SP

SPSP

SP

SPSP

SP

Na+

Na+

Ketamine

Na+

Na+

Ca++

RMP -75Mv

RMP -50MvRMP -65Mv

FentanylK+

K+

RMP -65Mv

FentanylK+

K+

FentanylK+

K+

FentanylK+

K+

Ketamine Without Opioids

NMDAr MUr

MUr


α2r



Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

Glutamate

GlutamateGlutama

teGlutamate

Glutamate

SPSP

SP

SP

SPSP

SP

SPSP

SP

Na+

Na+

Ketamine

Na+

Na+

Ca++

RMP -75Mv

Ca++

CaMKII

Na+

Na+

RMP -55Mv

FentanylK+

K+

NK1r

NK1r

Fentanyl

FentanylK+

K+

FentanylK+

K+

FentanylK+

K+

RMP -65Mv

RMP -60MvRMP -55Mv

Practicality of Ketamine

How Much Ketamine?

Less Painful Procedures 0.25mg / Kg Prior to Incision 0.125mg / Kg every 30 minutes

Painful Procedures 0.5mg / Kg prior to Incision 0.25mg / Kg every 30 minutes

Myths of Sub-Anesthetic Ketamine

Ketamine and emergence phenomenon

Ketamine and PONV

Ketamine and ischemic heart disease

Using high dose narcotics do not need ketamine

What about Dexmedetomidine

Alpha 2 Receptor α2 agonist binds with the receptor

Gi α subunit is released from the β and γ subunits inhibits adenylate cyclase decreases cAMP decreased PKA decreased membrane permiability to ions K+ efflux hyperpolarization Inhibition of Ca++ entry No vesicles

out

Ryan Dreikorn BSN SRNA York College of Pennsylvania / WellSpan Health Nurse Anesthesia Program.

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Transcript of Ryan Dreikorn BSN SRNA York College of Pennsylvania / WellSpan Health Nurse Anesthesia Program.