Anatomy and Physiology Past Paper Objectives Notes PDF

REGIONAL EXAM 1 OBJECTIVES ANATOMY AND PHYSIOLOGY Iden:fy the anatomical landmarks relevant to neuraxial anesthesia: spinal, epidural, and caudal anesthesia C7 ® Most prominent spinal process...

REGIONAL EXAM 1 OBJECTIVES ANATOMY AND PHYSIOLOGY Iden:fy the anatomical landmarks relevant to neuraxial anesthesia: spinal, epidural, and caudal anesthesia C7 ® Most prominent spinal process BE ABLE TO MATCH THESE! T7 ® Opposite the inferior angle of the scapula L4 - L5 ® Line connec+ng the iliac crests o Tuffier’s line SPINAL Opposite the inferior angle of the scapula Tuffier’s line Lumbar region (midline): skin to LF = 4-6 cm EPIDURAL LF = 5-6 mm (0.5 cm) thick Delivery of LA into epidural space in sacral region (i.e. caudal space is the sacral por0on of the epidural space) Needle inserted through sacrococcygeal ligament into sacral hiatus ◦ Sacral hiatus is notch above coccyx and between sacral cornua Landmarks easy to palpate in children, difficult or impossible in adults (due to calcificaIon of sacrococcygeal ligament) ◦ May use fluoroscopy for verificaIon of anatomy Anatomy ® Caudal epidural space is extension of lumbar epidural space Sacrum: 5 fused sacral vertebrae, triangular, dorsally convex, arIculates with L5 above and coccyx below coccyx Sacral hiatus should be 4-5 cm cephalad from coccyx Sacral cornua CAUDAL These are sacral cornua PSIS form equal triangle with sacral hiatus 1  Iden:fy meningeal layers and ligaments of the spinal cord and relevance to neuraxial anesthesia Posterior to Anterior (aka the direc=on your needle is moving): Skin Sub Q =ssue Supraspinous ligament Intraspinous ligament SPINAL ANATOMY: MIDLINE APPROACH Ligamentum flavum Know that for epidurals, stop aJer LF Dura mater before the Dura Mater in the epidural Subdural space space Arachnoid mater Subarachnoid space Posterior to Anterior (aka the direc=on your needle is moving): Skin Sub Q =ssue Ligamentum flavum Know that for epidurals, stop aJer LF SPINAL ANATOMY: PARAMEDIAN APPROACH Dura mater before the Dura Mater in the epidural Subdural space space Arachnoid mater Subarachnoid space Describe the curvature of the spinal column and relevance to neuraxial anesthesia Convex posteriorly Convex anteriorly Convex posteriorly Convex anteriorly In supine posi:on: Scoliosis = lateral curvature of High points/apex (lordosis) spine Convex posteriorly = C5 and L3-L5 (references vary) Kyphosis = excessive posterior concave anteriorly curve/hump Low points/trough (kyphosis) Lordosis = hollowing of back T4-T7 and S2 (references vary) (obesity/pregnancy) Discuss the most important factors affec:ng the spread of local anesthe:c with neuraxial anesthesia SPINAL ANESTHESIA PharmacokineIcs of subarachnoid local anestheIcs includes uptake and elimina-on of the drug Four factors play a role in the uptake of local anestheIcs from the subarachnoid space into neuronal Issue: (1) concentra:on of local anesthe:c in CSF The uptake of local anestheIc is greatest at the site of highest concentra-on in the CSF and is decreased above and below this site Uptake and spread of local anestheIcs aXer spinal injecIon are determined by mulIple factors Most important: Dose of LA injected Total dose (increase in mgs) causes higher spread and longer duraIons Baricity of local anesthe-c RelaIonship between density of LA and density of CSF Described as hypobaric, isobaric, hyperbaric in rela0on to CSF Hyperbaric solu0ons ® Denser than CSF Drug mixed with dextrose Flow to most dependent part of CSF column 2  Isobaric solu0ons ® As dense as CSF Remain at level injected (posi0on has no effect on block distribu0on) Drug mixed with CSF Predictable spread Hypobaric solu0ons ® Less dense than CSF Generally made by drug being mixed with disIlled sterile water Slowly rise to highest part of CSF column Pa-ent posi-oning during and just a?er injec-on (except with isobaric solu-ons) Si\ng: Easier to appreciate midline (obese, scolioIc) Chin down, shoulders relaxed, back flexed (angry cat/shrimp) Lateral: PaIent on his or her side, chin down, knees flexed (fetal posiIon) Note that males and females have different shoulder/hip width raIos, with the spine typically not horizontal CSF flow typically slower Prone: Spinal anesthesia for anorectal procedures with hypobaric anestheIc and jackknife posiIon or when fluoroscopic guidance used for neuraxial technique CSF may not flow freely and may need to be aspirated (2) surface area of nerve :ssue exposed to CSF Spinal nerve roots and spinal cord are involved in the uptake of local anestheIc injected into the subarachnoid space (3) lipid content of nerve :ssue Lipid content determines uptake of local anestheIcs Heavy myelin = high concentra0ons of local anesthe0c (4) blood flow to nerve :ssue ® also determines the rate of removal of LA from the spinal cord Issue Dependent on vascular absorp:on (blood flow): NO intrathecal metabolism Subarachnoid space Via vessels of pia mater and vessels on and within the SC Epidural space Free LAs move from subarachnoid to epidural space down a concentraIon gradient Absorbed by epidural vasculature EPIDURAL ANESTHESIA § DOSE (VOLUME X CONCENTRATION) § Larger dose = more intense analgesia and duraIon of block § Increased concentraIon = reduces onset Ime and increases intensity of motor block § Larger volume = greater verIcal spread § Pregnancy § Hormonal (increased sensiIvity to LA) and mechanical factors (venous plexus engorgement reduces size of epidural and subarachnoid space) § Standard pracIce: reduce dose by 1/3 § Other condiIons causing venous engorgement: ascites, obesity, vena cava ligaIon § Age (elderly pa:ents) ® Holly says > 50 yo § Areolar Issue becomes more dense and firm sealing the intervertebral foramina- this reduces lateral spread and increases cephalad § Areolar Issue changes also reduces vascular absorpIon increasing duraIon of block § Decrease in number of myelinated nerves and weak connecIve Issue allows for decreased dose § Dura more permeable to LA § May reduce LA dose by 50% in elderly § Addi:on of vasoconstrictors § Constricts vessels, prolongs duraIon, and increases intensity of agent’s effect 3 § Level and rate of injec:on § Ideal inserIon point is near surgical level ® Leads to more rapid onset and intense block § Lumbar: greater cranial than caudal spread § LA administered below L5 may have decreased effect due to increased fat in this area (which LA binds to and doesn’t exert its intended MOA) ® Also there is delay at L5-S1 due to large size of roots § Midthoracic: even spread from site of injecIon § Anatomy of the space § Cervical and thoracic epidural space narrower than lumbar- so greater distribuIon of the block § Lumbar area is widest- so larger volumes required to get same distribuIon § Lumbar injecIon- cephalad spread greater than caudad due to a narrowing at the lumbosacral juncIon § Rate of injec:on § Increased speed on injecIon has no effect on bulk flow in epidural space § Rapid injecIon may increase the CSF pressure leading to decreased spinal cord blood flow or increased ICP § RecommendaIon to inject LA slowly and incrementally (5 ml) § Pa:ent posi:on- only a slight effect § No clinically significant difference in cephalad spread in si\ng and lateral paIents § ExcepIon: obese paIents have lower block level when seated § Lateral posiIon the dependent side is favored Explain physiology of cerebrospinal fluid and its role in neuraxial anesthesia Clear colorless fluid that fills the subarachnoid space Ultra filtrate of plasma Total volume: 100-150 mL o Total volume in spinal subarachnoid space: 25-35 mL Daily secreIon o 500 mL o 0.3 - 0.4 mL/min Baricity of LA soluIon Baricity plays an important role in determining the spread of local anestheIc in the spinal space Density of substance compared to density of water is specific gravity Baricity is the resIng posiIon of 2 fluids with different specific graviIes when mixed in CSF (LA and CSF) Example: Density of bupivacaine 0.75% in 8% dextrose is 1.0247 and density of water is 0.9933 so the specific gravity is about 1.0300 (rounded down) Baricity = specific gravity 1.0300 divided by specific gravity of CSF 1.0069 (1.004-1.009) so about 1.023 This drug is hyperbaric because 1.023 is greater than CSF 1.004-1.009 Baricity described as hypobaric (disIlled water; rise against gravity), isobaric (CSF; remain where injected), hyperbaric (dextrose; follow gravity) in relaIon to CSF Discuss the dermatomal level and their clinical relevance in neuraxial block placement Dermatome = area of skin innervated by sensory fibers from a single spinal nerve o T 10 ® Umbilicus o T 6 ® Xiphoid process o T 4 ® Nipples PERINEAL AND ANAL S2-S5 (SADDLE) FOOT AND ANKLE L2 THIGH AND LOWER LEG L1 SPINAL ANESTHESIA LECTURE TURP, VAGINAL DELIVERY, HIP T10 LOWER EXTREMITY WITH TOURNIQUET T8 INTESTINAL, GYNECOLOGIC, UROLOGIC T6 UPPER ABDOMINAL T4 4  Mastectomy T1 Thoracotomy T4 Upper Abdominal T7-T8 EPIDURAL ANESTHESIA LECTURE Lower Abdominal T10 Catheter Inser+on Sites Lower Extremity (above knee) L1-L2 Lower Extremity (below knee) L3-L4 Perineal L4-L5 Explain differen:al sensi:vity of nerve fibers (know this well!) OVERVIEW DifferenIal blockade is a complex clinical phenomenon where nerve fibers have different sensiIviIes to local anesthesia blockade. Both anatomical and chemical factors determine the suscepIbility of a nerve fiber to LA. A combinaIon of the fiber blocked and LA selected determines the onset, duraIon, and differenIal blockade of different funcIons by LA. Large Myelinated 4 subgroups: alpha, beta, gamma, delta (categorized based on decreasing impulse conduc=on velocity and size) A Fibers Alpha (Largest): efferent neurons that innervated skeletal muscle - motor func=on, propriocep=on, reflex Beta: afferent sensory neurons from muscle, joints, skin - transmit sensa=ons of touch and pressure Gamma: smaller efferent neurons that control muscle spindle tone Delta (thinnest): afferent sensory neurons - pain and temperature Small Thinly myelinated B Fibers Preganglionic axons of autonomic system ® when these are blocked, you get a dila=on of the vascular smooth muscle = vasodila=on = sympathectomy Innervate vascular smooth muscle (important in spinal anesthesia!) Small Nonmyelinated (NEVER MYELINATED) C Fibers dC: afferent sensory - Pain and temperature (SLOW PAIN) sC: postganglionic autonomic funcXon Theories (or possible explana:ons) Nerve fiber size: Small fibers may be blocked faster related to spacing of nodes of Ranvier (myelinated fibers) Small fibers with closely spaced nodes of Ranvier may be blocked more rapidly because the local CriIcal length = 3 anestheIc can reach criIcal length of the nerve more rapidly (3 nodes) nodes Large fibers have larger distance between nodes of Ranvier and require a larger minimum concentraIon of LA to interrupt sodium conducIon in 3 nodes Nerve fiber size and func:on: Small fibers may be blocked faster then large because of Ime course of drug diffusion into the nerve Nerve fibers located on the outer layer of the nerve are anestheIzed prior to the deeper nerve fibers Small diameter nerve fibers are close to nerve root surface (shortening diffusion path) Larger nerve fibers are deep in nerve bundle (lengthening diffusion path) Smaller fibers that are located on the mantle are associated with autonomic funcIon (B fibers), pain and Local anesthe+c is administered temperature (A delta & C fibers) …so less of a path of diffusion and easier to block and less concentraIon needed around the spinal to block nerve roots and Larger fibers associated with propriocepIon and motor are closer to core…so longer path of diffusion and more then needs to local anestheIc needed to block diffuse. Spinal anestheIc: LA administered, highest concentraIon around injecIon, lower concentraIon as LA is mixed with CSF and spreads rostrally, so fibers that are easier to block (autonomic, pain, temperature) are blocked at higher levels when motor block ceases 5  “Core-mantle” concept (peripheral nerve blocks): Consider cross secIon of peripheral nerve LA is deposited near nerves, then it diffuses from the nerves outer surface (mantle) toward the center (core) Nerves see different concentraIons of LA depending on locaIon within the peripheral nerve Nerves innervaIng proximal structures are closer to surface of nerve so proximal structures blocked first Myelina:on: Myelinated nerves achieve blockade faster and at lower concentraIons compared to non-myelinated Myelin pools local anestheIcs molecules near the axon membrane Myelinated axons have increased conducIon velocity and are more sensiIve to local anestheIcs compared to unmyelinated nerves Myelinated axons have nodes of so that three consecuIve nodes of Ranvier will prevent acIon potenIal propagaIon, thereby increasing their sensiIvity to local anestheIcs. Unmyelinated nerves require larger amounts of local anestheIc to achieve effecIve blockade because the sodium-gated channels of these nerves must be blocked along an enIre sequenIal length of the nerve fiber Distribu:on of Na and K channels along axon or different membrane lipids Another important factor underlying differenIal block is a result of the state-dependent, or frequency-dependent, block by local anestheIcs. Voltage-gated sodium channels within the nerve membrane move between several different conformaIonal states. Local anestheIcs bind to the acIvated (open) and inacIvated (closed) states more readily than the reacIvaIon (resIng) state. Therefore, repeated depolarizaIon in rapidly firing axons produces more effecIve anestheIc binding, and hence progressive enhancement of conducIon blockade. Small-diameter nerve fibers are found close to the nerve Local anesthe:c path root surface, thereby shortening the A-delta diffusion path of C local anesthe:c injected A-gamma blocked last - A-beta large fibers in A-alpha the middle rder Onset: B, C/A delta, A gamma, A beta, A alpha o pp osite o LA in er from Recov What does this mean clinically??? Sequence of Neural blockade: 1. Loss of sympatheIc funcIon 2. Pain 3. SensaIons of cold, warmth, touch, deep pressure 4. PropriocepIon 5. Motor funcIon SPINAL LECTURE Neuraxial anesthesia: sympathe-c nerve fibers are blocked by the lowest concentra-on of local anesthe-c followed by nerve fibers responsible for pain, touch and finally motor func-on. This relaIve sensiIvity of certain nerve fibers is displayed by a spaIal separaIon (i.e. the sympatheIc block will be approximately 2-4 dermatomes beyond the motor block, the pain/touch will be 2-3 dermatomes beyond the motor block). 6  When the distance from the injected site increases, the amount of LA decreases and fewer molecules are available to produce a block of nerve transmission. This, together with the fact that different nerve fibers have different sensi-vi-es to LA, provides the ra-onale for zones of differen-al blockade. EPIDURAL LECTURE § Epidural: differen-al zones between autonomic and sensory (in comparison to spinal anesthesia) may be smaller or nonexistent § Related to liPle reduc-on in concentra-on of the LA by dilu-on or absorp-on in the epidural space Discuss zones of differen:al blockade Nerve fibers have different sensiIviIes to LA (more sensiIve or more resistant) Autonomic first, sensory second, motor third Recover opposite KEY POINTS: Larger nerves have more rapid conducIon of acIon potenIals ® the larger the fiber = the fastre it is Myelin forces current through nodes so increases conducIon velocity ® the more myelin = larger = fasteer Larger nerve fibers require more LA to block conducIon Small nerve fibers are blocked quicker than large nerve fibers (r/t distance btwn nodes, physical size, located on the mantle) The sensiIvity to local anestheIc blockade is inversely related to nerve fiber diameter Myelinated nerves, such as preganglionic B fibers, tend to be blocked before unmyelinated nerves of the same diameter, such as C fibers. B fibers of autonomic nervous system are blocked first…end of story The result of B fiber blockade is a sympatheIc blockade 7  Compare and contrast sensory and motor nerve fibers The impulse genera:ng and conduc:ng units of the nervous system! MOTOR May reach a meter in length SENORY Most incapable of dividing-unable to repair aher injury MOTOR NEURON Cell body (soma)- contains large nucleus, cytoplasm, Dendrites- branches of neuron that receive impulses protein synthesis from other cells via synapses or sImuli and transmit Maintains viability of the axon toward cell body Metabolic and repair funcIons Receive incoming messages from other neural structures or s:mulus Sites for iniIaIon of excitability Single axon- long projecIon of neuron, conducts acIon potenIal from soma to neurons or end organs Aka- “nerve fibers” Specialized for the conduc:on of ac:on poten:als Conduct outgoing messages Peripheral nerves contain 3 parts: Primary site of neural conducIon Afferent neurons (sensory) Vary in length Efferent neurons (motor) Long and slender in peripheral nerves Autonomic neurons* Yet thickness is related to conducIon velocity, Thicker = faster Only 1 per neuron Axon Terminal- distal terminaIon of axon, synapses with other nerves or end organs End of axon Makes synapIc contact with other nerves or end organs NTs released Neurotransmiper substances are release and iniIate depolarizaIon at the presynapIc side (dendriIc zone) of another nerve or motor end plate of motor fiber SENSORY NEURON MOTOR NEURON Motor nerves are mul=polar (many dendrites around cell body), cell Sensory nerves are unipolar (one process leaves cell body), cell body in body in ventral horn of spinal cord dorsal root ganglion (DRG), long branch to periphery, shorter branch to PNS func=ons as communica=on between CNS and body spinal cord Efferent division from CNS to peripheral structures PNS func=ons as communica=on between CNS and body (2 divisions) Afferent division from peripheral structure to CNS Motor fibers of somaXc nervous system- Afferent has soma=c and visceral sensory voluntary fibers Motor fibers of autonomic nervous Unipolar = one process from the cell body system (sympatheXc and One axon parasympatheXc)- involuntary Cell body in dorsal root ganglion SympatheXc: controls body One branch supplies receptors (dendrites) for incoming systems during acXvity signals and one for outgoing signals (axon terminal) ParasympatheXc: controls body systems during rest 8  MulXpolar= many dendrites surround cell body One axon that follows long course to periphery Cell bodies in ventral horn of spinal gray ma]er Impulses are produced at the “receptor” component (aka dendrites) Receptors are located in: Skin, Joints, Muscles, Connec+ve +ssue, and Viscera REMEMBER: *ONE AXON *CELL BODY IN DRG The nerve cell body, dendrites, and proximal part of the axon are in the CNS (ventral horn of spinal gray ma]er) *LONGER BRANCH TO PERIPHERY Axons exi=ng the CNS through intervertebral foramen *SHORTER BRANCH TO SPINAL CORD establish the main part of the PNS Dendrites and cell body are specially developed to receive and process Neural impulses are ac+vated by noxious (+ssue damaging), electrochemical signals and determine output ac=vity. thermal (hot or cold), or mechanical s=muli at the nerve endings. The axon conducts these impulses to its branched terminal Intense s=muli that cause pain may: enlargements, which contains neurotransmi_ers to ac=vate effector Directly opens ions channels (ini+a+ng AP) organs. Cause the release of sensi+zing chemicals (i.e. bradykinin, prostaglandins, and histamine) from the +ssues closely surrounding the end of nocicep+ve afferent neurons “effector organ” SENSORY AND MOTORNEURON NOTE: Sensory - Cell body in dorsal root ganglion NOTE: Motor - Cell bodies in ventral horn of spinal gray ma]er Describe anatomy of peripheral nerves Peripheral nerves are bundles of nerve fibers (aka axon) that lie outside the CNS and conduct impulses from one part of the body to another. All peripheral nerves are SIMILAR in structure. The basic unit of all nerves is the neuron. Peripheral nerves are: “Mixed nerves” containing 3 parts: afferent (sensory), efferent (motor), autonomic fibers that are myelinated or unmyelinated Peripheral nerves (mixed nerves) are classified as: cranial, spinal, or autonomic based on anatomic loca-on. And form the plexuses that innervate the periphery. Mixed peripheral nerves contain: Axons of sensory neurons (afferent fibers) Axons of motor neurons (efferent fibers) Myelinated or unmyelinated axons 9  at ed y elin u nm Peripheral nerves are made up of individual nerve fibers (or axons) and their Schwann cells that are bundled together by connec:ve :ssue THE ORGANIZATION OF PERIPHERAL NERVES (spinal nerve) Indiv id fibers ual nerve tha up a t make n are b erve undle tog d conn ether by ec:ve e is :ssue : ssu s ve indiv (like n n ec: ant. its idual w e co port ing to an el ectric ires in Th im cord rve cable ac ne ) med on in. N a i: re pos tructu s Endoneurium- a fine connecIve Issue that surrounds every individual nerve fiber (or axon) Perineurium- bundles of axons (fibers) form fascicles that are surrounded by perineurium Epineurium- surrounds enIre nerve, covering one or more perineurial bundles. Holds loosely to connecIve Issue through which it runs Perineurium: Mechanical strength Diffusion barrier (important for local anesthe0cs) Fascicles: Fascicular bundles are not conInuous Divide and anastomose frequently (a few millimeters) Clean cut may be surgically repaired Connec:ve :ssue of nerve tough yet allows stretch without damage Safety feature Local anesthe:c must diffuse across mul:ple structures before reaching their site of ac:on: Endoneurium- ALLOWS EASY DIFFUSION Perineurium- SEMIPERMEABLE BARRIER ® the diffusion barrier Epineurium- EASILY PERMEABLE CONNECTIVE TISSUE LAYER 10  Other factors influencing LA diffusion across axons: Thickness of perineurium Myelina:on Size of axon Anatomic posi:on of axon in peripheral nerve Nonmyelinated axons (nerve fibers) Perineurium- SEMIPERMEABLE BARRIER are encased by a Schwann cell that simultaneously Epineurium- EASY DIFFUSION Encloses 5-10 axons. Smaller in diameter. No nodes of Ranvier. Endoneurium- EASY DIFFUSION Myelinated fibers are segmentally enclosed by Schwann cells that wrap The heavier the myelina+on > the around 1 axon hundreds of dmes. thicker the axon > the faster the This accounts for most of the ac+on poten+al thickness of the axon. Non- myelinated nodes of Ranvier separate the myelinated regions of the axon. Axons are cylinders of axoplasm in the AXONS (aka- NERVE FIBERS) axonal membrane. 2 TYPES: Axons are always enveloped by a UNMYELINATED (NON-MYELINATED) Schwann cell. Schwann Cells are the main glial cells of Many unmyelinated axons (5-10) lie in a single Schwann Cell the PNS that surround nerve fibers. MYELINATED There are 2 types… myelinadng and One myelinated axon is encased by a single Schwann Cell nonmyelinadng What is Myelin?? A lipoprotein and synthe:c product of Schwann cell. Protec:ve func:ons around the axon Axonal membrane Nerve cell membrane review! Modern fluid mosaic membrane Main structural component are rows of phospholipid molecules: Hydrophilic and hydrophobic sides Hydrophobic facing center Proteins embedded in lipid bilayer: FuncIon as ion channels connecIng axoplasm and surface membrane Sodium channels and potassium channels Most ac:ve ions for excitable membranes: Sodium, Potassium, Calcium “Semipermeable membrane” Explain ac:on poten:al of axons including res:ng membrane poten:al, threshold level, depolariza:on and repolariza:on THE GENERATION AND PROPOGATION OF IMPULSES IN EXCITABLE NERVE CELLS ARE DEPENDENT ON THE FLOW OF SPECIFIC IONIC CURRENTS (Na+ and K+) THROUGH CHANNELS THAT SPAN THE PLASMA MEMBRANE. 11 CHANNELS OPEN AND CLOSE IN RESPONSE TO THE ELECTRICAL POTENTIAL OF THE CELL MEMBRANE AND ARE TARGETS FOR LOCAL ANESTHETICS AS THEY BLOCK PROPOGATION Membrane Poten:al: Voltage potenIal across the cell membrane of all living cells (measured from outside to inside) Membrane potenIal is maintained by ac-ve and passive diffusion of ions across the cell membrane via large proteins embedded in the membrane: Na+/K+ pump = ACTIVE Na+ & K+ ions channels (aka “leak channels”) = PASSIVE Na+/K+ pump: Na+/K+ pump ACTIVELY transports K+ into the cell and Na+ out of the cell…using APT as energy ein ia l prot c d Spe bedde rane em memb al xon in a Ac:vely pump s 3 Na out of the cell and 2 K into the cell! Creates a concentraIon gradient: K+ ion concentraIon higher inside the cell Na + ion concentraIon higher the cell Think about this…if the Na+/K+ protein pump just pumped Na+ and K+ without any other ac0vi0es at the cell membrane, there would be no more Na+ and K+ leT to pump…but there are Na+ and K+ ion channels (leak channels) that leak ions down their respec0ve concentra0on gradient Leak Channels Conduc=on within a nerve is transmission of an impulse created by sXmuli that starts at one end of the nerve and is propagated to the other Receptors serve as sensors and transducers following chemical, mechanical, or thermal sXmuli SXmuli is converted into small electric currents These electric currents make the nerve membrane less nega=ve If a threshold level achieved, an acXon potenXal results ACTION POTENTIALS An acXon potenXal increases the permeability of the nerve membrane to Na+ ions and a rapid influx of posi=vely (or NERVE IMPULSE): charged Na+ ions. This is depolariza+on This causes a transient reversal of charge The influx of Na ions causes a reversal of membrane poten=al to about +35mV However…very quickly (1 millisecond) there is a drop in Na+ ion permeability and increase in K+ outward movement…this returns the membrane to its res=ng state This is repolariza+on 12  Baseline maintained by the Na+-K+ pump THIS GENERATES AN ACTION POTENTIAL (or NERVE IMPUSE)! SUMMARY: Inward Na current and outward K current yield the net ionic movement across the membrane producing and acXon potenXal don Repolarizadon Depolariza a+on de p olariz rd f a rate o et inw a ximum ds with n ions. M spon Na + corre ement of n m o v iza+o f Re polar ard rate o h net outw mum t Maxi ponds wi f K+ ions. or re s nt o c me move Na Channels: Voltage-gated ion channels Part of nerve membrane MOST responsible for propagaXon of nerve signals Opening and closing of channel is controlled by conformaXonal changes in structural proteins driven by membrane electrical acXvity Potassium ion concentra=on greater intracelluarly Sodium ion concentra=on greater extracelluarly This concentra=on gradient (created by Na+-K+ pump) favors the extracellular diffusion of potassium and intracellular diffusion of sodium via “leak channels” The membrane is more permeable to K+ than Na+ resul=ng in a con=nuous leakage of K+ ions out of the interior of the cell This leakage of ca=ons creates a nega=ve res+ng membrane poten+al (or a nega=vely charged interior rela=ve to ResXng state: exterior) due to the excess of nega=vely charged ions (anions) intracellularly RESTING MEMBRANE POTENTIAL (RMP): APPROXIMATELY -70 to -90 millivolts SUMMARY: RMP is maintained by ac+ve and passive transport and that the Na+-K+ pump is key to this phenomenon Impulses are ini=ated when a net inward current occurs (of Na+ ions) This requires enough Na+ channels to be open to overcome the ac=ons of K+ channels Small depolariza+on (15-20mV) is usually sufficient to ini=ate an impulse in res=ng axon However, stronger s=mula=on is required during refractory period (just aJer repolariza=on) Do you remember what ini=ates depolariza=on?...chemical, mechanical or thermal s=muli! THRESHOLD LEVEL: Factors that elevate threshold level (i.e. make it harder to ini=ate and AP) Refractory period Demyelina=on of myelinated axons Presence of LA 13  Impulse current during depolariza+on flows within conduc=ng medium of axoplasm and spreads to adjacent inac=ve regions This is propaga+on of the ac+on poten+al When propaga=on of signal occurs then en=re length of the nerve it is called nerve conduc=on Difference in propaga=ng impulse between nonmyelinated and myelinated axons: Myelinated IMPULSE Myelin increases speed of PROPAGATION Unmyelinated conduc+on Poten+al changes in a Poten+al changes smooth con0nuous con+nuously however, shape because axon is a regions in which large cable with uniform inward currents flow into proper0es and the the axon (nodes of Ranvier) impulse propagates at a depolarize adjacent constant velocity internodes During an impulse, many nodes are simultaneously at some level of depolariza+on Describe the classifica:on of nerve fibers (myelina:on, diameter, velocity, func:on) UNMYELINATED AXON MYELINATED AXON MYELINATED NERVE FIBERS ARE SEGMENTALLY WRAPPED BY A SINGLE SCHWANN CELL. Interrupted by nodes of Ranvier: MANY (5-10) NONMYELINATED Contains structural elements for AXONS ARE EMBEDDED neuronal excita+on and allows IN FOLDS OF A SINGLE extracellular medium access to SCHWANN CELL axolemma (where LA gains ace to the axon and preforms its mechanism of NoXce how the ac=on) Schwann cell surrounds the axon loosely…allows for Nodes of Ranvier: uniform spread of depolarizaXon Density of sodium channels along the axon J is high in nodes, and sodium currents are adequate to ac=vate sodium channels at the next gap Saltatory conduc=on Conduc=on velocity is increased in myelinated cells Impulse conduc:on not uniform! MYELINATED VS. NON-MYELINATED AXON These characterisXcs (myelinaXon vs. non-myelinaXon) determine the electrophysiologic behavior of different nerve types (i.e. the speed of impulse and propagaXon of acXon potenXals). Nerve fibers (axons): These are classified by size, conduc:on velocity and func:on. Generally speaking ® Myelin = increased diameter = increased conduc:on velocity 14  Speed of conduc:on (conduc:on velocity) is measured as meters per second. Based on fiber diameter and conduc:on velocity nerve fibers are divided into 3 groups: A, B and C. Axon Efferent ® Larger diameter = faster conducIon velocity BIG IDEA: the bigger g the fiber = the more Smaller = slightly slower myelin = the faster the speed of d ® Fast Pain conducIon Small = slower = not myelinated ® Slow Pain PHARMACOLOGY Describe mechanism of ac:on of local anesthe:cs Local anestheIcs prevent transmission of nerve impulses by interfering with the funcIon of Na channels In the presence of local anesthesia, Na channels are less likely to open in response to a sImulated depolarizaIon Blocking impulses requires a defined length of the nerve become in-excitable Impulses can’t “jump” over blocked porIon anymore Difference in myelinated and non-myelinated neurons Myelinated: conducIon proceeds as impulse “jumps” from one node of Ranvier to the next Saltatory conducIon 3 nodes blocked Non-myelinated: slower r/t dispersal of Na channels** LA diffuses into the membrane in the nonionized, lipid soluble base form. It binds to the intracellular por@on of the alpha subunit on the sodium channels in the In axoplasm of nerve, the base form charged (ca@onic), water soluble form. accepts a hydrogen ion at equilibrates into the charged (ca@onic) form 15  Sodium ions aren’t able to pass through the channel. This process depresses the ini@a@on and propaga@on of ac@on poten@als. Resul@ng in no sensa@on transmiGed. Na channels exist in 3 conformaIonal states: Open Inac-vated Res-ng During an acIon potenIal, Na channels open briefly (extracellular Na travels into axoplasm during depolarizaIon) Quickly Na channels inac-ve (Na flow stops) Na channels rest with repolarizaIon Termed “ga-ng” Process of channels going from conducIng to non-conducIng states Describe mechanism of ac:on for local anesthe:cs administered in subarachnoid and epidural spaces SPINAL ANESTHESIA Primary sites of ac:on of LA aher injec:on into subarachnoid space: spinal nerve roots (when LA I injected into the subarachnoid space, it directly acts on the nerve roots) and spinal cord Spinal cord (2 mechanisms of uptake): SC takes up LA by diffusion through pia mater into the spinal cord (slow process affecIng superficial porIons of cord) LA penetrates deeper structures through extensions of the subarachnoid space (Virchow-Robin space) Virchow-Robin space = areas of pia mater that surround the blood vessels that penetrate the CNS. EPIDURAL ANESTHESIA § Spinal nerve roots in CSF, (primary site of ac:on for LA), mixed spinal nerves in epidural space, spinal cord. § Spinal nerve roots are away from the site of injecIon, therefore mulIple factors influence onset, quality and duraIon of acIon § DURA - acts as barrier § Absorp-on into circulatory system § Risk of toxicity! (also be aware that there is a large venous network in epidural space) § Reten-on in faPy -ssue § Fat acts as a reservoir, redistributed over -me § Remainder of LA reaches intended site of acIon: Spinal nerve roots in the CSF § Most important route of entry. In dural cuff region there are proliferaIons of arachnoid villi and granulaIons. GranulaIons effecIvely reduce the thickness of the dura mater, permi\ng rapid diffusion of anestheIcs from the epidural pace through the dura and into the CSF. 16  Compare and contrast the pharmacodynamics and pharmacokine:cs of local anesthe:cs used in regional anesthesia Pharmacodynamics: Study of the physiologic effects of drugs on the body and mechanism of drug ac-on Local anesthe-cs stop the propaga-on of ac-on poten-als in nerve axons by preven-ng the influx of Na through voltage-gated sodium channels at the level of the axonal membrane Pharmacokine:cs: Study of ac-on of drugs within the body Local anesthe-cs are typically injected near their target site instead of relying on systemic circula-on (primary excep-on IV lidocaine) Barriers to LA diffusion to target vary and are dependent on: site of injec-on, dose, speed of onset, dura-on of ac-on. Amino ester- Hydrolysis of ester bond by esterases in blood is primary biotransforma-on process Amino amide- Hepa-c extrac-on and biotransforma-on are primary elimina-on and biotransforma-on pathways } ESTER OR AN AMIDE????? – Look at the generic name. If there is an “i” before the “caine” it is an AMIDE AMIDES ESTERS Bupivicaine Benzocaine E=docaine Chloroprocaine Levobupivicaine Cocaine Lidocaine Procaine Mepivicaine Tetracaine Prilocaine Ropivicaine ESTER AMIDE Amide linkage is cleaved through iniXal N-dealkylaXon, than hydrolysis (in Ester linkage is cleaved by plasma cholinesterase liver) Half-life in circula=on is short (1 minute) Half-life is 2-3 hours Degrada=on product is p-aminobenzoic acid (PABA) Risk of allergic reac=on - RARE! Risk of allergic reac+on due to PABA Methyl-parabin preserva=ve may cause a poten=al reac=on Local anesthe:cs generally injected/applied near site of ac:on ◦ Mucus membranes (ocular conjunc=va, tracheal mucosa): provide MINIMAL barrier to LA penetra=on ◦ Intact skin: provide a GREAT barrier – EMLA = 1:1 mixture of 5% lidocaine and 5% prilocaine in oil-in-water emulsion ◦ Systemic absorp=on depends on BLOOD FLOW ◦ Determined by: – Site of injecXon AbsorpXon: – Presence of vasoconstrictors – Local anestheXc agent/dosage ◦ Site of injecXon: – Rate of systemic absorpXon related to vascularity of site: IV > tracheal > intercostal > paracervical > epidural > brachial plexus > scia=c > subcutaneous } Type of local anestheXc: ◦ More lipid-soluble LAs that are highly =ssue bound are more slowly absorbed Improve depth and dura=on of anesthesia ◦ Decrease rate of vascular absorp=on, allowing more anesthe=c molecules to reach nerve membrane Vasoconstrictors Decrease systemic toxicity (epinephrine ◦ Decreases rate of absorp=on of anesthe=c into circula=on, therefore minimizing peak blood levels of 1:200,000, LA 5mcg/ml) Local vasoconstric=on and decrease in surgical bleeding Assist in detec=on of intravascular injec=ons 17  Dependent on organ uptake Determined by: DistribuXon: ◦ Tissue perfusion ◦ Tissue/Blood parXXon Coefficient ◦ Tissue Mass Ester Amides: Metabolized by pseudocholinesterase Rapid Water-soluble metabolites excreted in urine BiotransformaXon Metabolize p-aminobenzoic acid (PABA) associated Metabolized by microsomal P-450 in the liver and ExcreXon: with allergic reac=on (slower than ester) Cerebral spinal fluid lacks esterase enzymes Decrease in hepa=c func=on (cirrhosis) or liver Determined by ◦ Termina=on of intrathecally administered blood flow (CHF, BB, H2-receptor agonist) chemical structure ester local anesthe=cs (tetracaine) is reduce metabolic rate and poten=al increase dependent on redistribu=on to blood risk of toxicity stream Pa1ents with abnormal pseudocholinesterase theore1cally have increase risk of toxicity First LA used clinically Only naturally occurring LA Current use primarily topical airway anesthesia ◦ Anesthe=ze nasal mucosa prior to nasotracheal intuba=on COCAINE Vasoconstrictor ◦ Vasoconstric=on related to direct ac=on of cocaine on inhibi=on of nitric oxide and to inhibi=on of reuptake of norepinephrine by =ssues. May cause cardiac arrhythmias Low potency, slow onset, short dura=on of ac=on- not oJen used for PNB or epidural 10% concentra=on used for short ac=ng spinal PROCAINE Good for local skin infiltra=on Allergic poten=al Rapid onset, short dura=on of ac=on Lowest systemic toxicity of all LA CHLOROPROCANIE Principal use- epidural for short procedures o 3% solu=on for epidural anesthesia produces a dura=on of ac=on between 30-60 minutes Principal use- spinal anesthe=c (hypobaric, hyperbaric, isobaric) o Rapid onset (3-5 minutes) and long dura=on 2-3 hours (4-6 hours with vasoconstrictor) when administered for spinal anesthesia § All LAs have a faster onset during spinal anesthesia because there is no nerve sheath barrier, and the drug is deposited into the CSF that bathes the spinal cord and spinal nerves TETRACAINE o Also used for topical anesthesia Intermediate to long dura=on Onset 3-5 minutes Dura=on up to 240 minutes 1% (10mg/ml) solu=on mixed with 10% glucose in equal parts to make hyperbaric spinal First clinically used amide Most widely used LA related to inherent potency, rapid onset, =ssue penetra=on, effec=veness during infiltra=on, PNB, spinal and epidural anesthesia Common concentra=ons: o PNB: 1-1.5% solu=on o Epidural: 2% Used for a lot of urologic o Spinal: 5% in Dextrose procedures LIDOCAINE Short to intermediate dura=on Onset 3-5 min Dura=on approximately 1-1.5 hr. Most common ampule 5% lido in 7.5% dextrose (50 mg/ml) Associated with transient neurologic symptoms (TNS) ® DOWNSIDE o Low back pain and lower extremity dysesthesias that radiate to the bu=ocks, thighs, and lower limbs (aJer the lidocaine has worn off) 18  Chemically related to lidocaine ETIDOCAINE Long-ac=ng amide Profound motor blockade Structurally related to lidocaine, slightly longer ac=ng MEPIVACAINE Used for infiltra=on, PNB, epidural in concentra=ons of 0.5-2.0% Not oJen used in OB as metabolism is markedly prolonged in fetus and newborn Long-ac=ng LA used for infiltra=on, PNB, epidural, spinal anesthesia Concentra=on from 0.125%-0.75% o Lower concentra=on= sensory blockade o Higher concentra=on = motor blockade Cardiotoxic during systemic toxic reac=ons BUPIVACAINE Intermediate to long dura=on Most widely used spinal anesthe+c Onset 5-8 minutes (a li_le bit longer) Dura=on up to 240 minutes Most common ampule is 0.75% in 8.25% dextrose (0.75%=7.5 mg/ml) o Manufactured as 2.5-7.5 mg/ml with and without glucose o Plain (without glucose) oHen referred to as “isobaric” Long ac=ng LA similar to bupivacaine o S-Isomer enan=omer of bupivacaine ROPIVACAINE Less cardiotoxic Concentra=on ranging from 0.25%-1% EXPAREL Aqueous chambers filled with bupivacaine FDA approved surgical site incision only Reliable plasma levels of bupivacaine for 72 hours Bupivacaine encapsulated with DepoFoam* Reduces use of indwelling catheters 20 ml vial at1.3% concentra=on Max dose 266 mg (1 vial) LIPOSOMAL BUPIVACAINE DepoFoam Microscopic, spherical, lipid-based par+cles o Par+cles: § Numerous aqueous chambers containing the drug Chamber: o Chambers separated from adjacent chamber by lipid membrane Recognize adjunct medica:on commonly used (opioids, epinephrine) and their effects Powerful vasoconstrictor with alpha and beta adrenergic receptors Typical concentra=on for regional: 1:200,000 (5 mcg/ml) Max adult dose: 200-250 mcg DO NOT USE EPINEPHRINE IN PERIPHERAL NERVE BLOCKS IN AREAS OF POOR COLLATERAL CIRCULATION (DIGITS) Systemic side effects: hypertension, tachycardia, arrhythmias (most likely aJer accidental intravascular injec=on) Local side effects: vasoconstric=on of terminal arteries leading to gangrene, avoid epi use in PNB in areas of poor collateral circula=on (digits) due to risk of digital gangrene Epinephrine (Adrenaline) Spinal Lecture Packaged as 1 mg/1 ml (1:1000) Dosage 0.1-0.5 mg or 0.1-0.5 mL of 1:1,000 Constricts blood vessels of spinal cord and dura, slowing absorp=on, increasing duraXon and intensity Epidural Lecture § Reduces vascular absorp=on and enhances efficacy § 1:200,000 of fresh epi enhances intensity of motor block, quality of sensory block, dura=on of block § More effec=ve for short/intermediate ac=ng LAs § Commercial prepara=ons of LA with epi very acidic resul=ng in greater latency to onset of block Phenylephrine 2-5 mg to spinal (Neosynephrine) Prolong anesthesia (similar to epi) 19  Raises the pH of local anesthe=c solu=on increasing concentra=on of non-ionized free base form Increasing rate of diffusion and speed of onset Sodium ◦ Research indicates greatest benefit when added to LA premixed with epinephrine by the bicarbonate manufacture. These solu=ons (compared to “plain LA”) have a reduced pH to increase shelf life. 1 cc of 8.4% sodium bicarbonate to 9 ml of LA; alkaliza=on speeds onset of ac=on Local anesthe=c proper=es in vitro Block Aa and C fibers Poten=al mechanisms of ac=on: (but the mechanism remains unclear in the literature) ◦ Acts synergis=cally with LA due to ac=on on K channels ◦ Pharmacodynamic prolonga=on of LA effects ◦ Direct ac=on of clonidine on nerves Clonidine ◦ Central ac=on of clonidine ◦ Combina=on of effects Alpha 2 adrenergic Prolongs sensory and motor blockade agonist ◦ Clonidine and intermediate ac=ng agents (lidocaine) significantly prolongs brachial plexus or femoral nerve blocks Side effects: ◦ Hypotension (due to direct inhibi=on of sympathe=c ouxlow of preganglionic neurons on spinal cord) ◦ Seda=on ◦ Bradycardia N-methyl-D-aspartate antagonist Blocks the open Ca channel on NMDA receptor thus inhibi=ng excitatory transmission by decreasing depolariza=on Ketamine (epidural Study results: lecture only) ◦ Reduc=on of onset – 25 mg of ketamine with bupivacaine ◦ Increased post op pain relief 1-4 mcg An=cholinesterase inhibitor thus inhibi=ng acetylcholinesterase enzyme from breaking down acetylcholine NeosXgmine Acetylcholine par=cipates in spinal cord’s modula=on of pain processing (epidural lecture Muscarinic receptors play a role in producing analgesia only) No respiratory depression Side effect: Nausea, vomi=ng, anxiety Opioid receptors: Brain stem Spinal cord (substan+a gela+nosa) ® Mu 1 ac+va+on provides analgesia Afferent neurons o Opioid agonists bind to receptor, hyperpolarizing the neuron, preven1ng response to s1muli Side effects that may be seen include pruritus, nausea and vomi=ng, and respiratory depression EPIDURAL ANESTHESIA § Combina=on of LA and opioids results in be_er anesthesia § Used alone: no sympathectomy, skeletal muscle relaxa=on, or loss of propriocep=on § Epidural opioids undergo uptake into epidural fat, systemic absorp=on or diffusion across dura to CSF § Penetra=on of dura: influenced by lipid solubility and molecular weight § Administra=on: § Single bolus, intermi_ent boluses, con=nuous infusion § Pa=ent controlled epidural anesthesia (PCEA) Opioids § Goal: establish basal rate with bolus component for breakthrough pain § Opioid crosses dura to receptors in brain stem and spinal cord (substan=a gela=nosa of lamina of dorsal horns) § Agonist binds to receptor and neurons hyperpolarized, preven=ng response to s=muli § Epidural dose 10x greater than spinal dose due to: § physical barrier of dura § epidural opioids may be deposited in epidural fat and connec=ve =ssues § uptake into systemic circulaIon SPINAL ANESTHESIA High lipid solubility ® Adheres quickly to lipoproteins of spinal cord Profound sensory analgesia Fentanyl Dose: 15-25 mcg mixed with LA Onset: 5-10 min Dura=on 2-4 hours 20  EPIDURAL ANESTHESIA Lipophilic: rapid onset (10-20 min), short dura=on (3-6 hr), low CSF solubility, minimal CSF spread Dose: 50-100 mg SPINAL ANESTHESIA Highly polarized (water soluble) Morphine moves freely in CSF May reach respiratory centers in brain aJer 6-8 hours causing delayed respiratory depression Dose: 0.1-0.5 mg Morphine Onset: 60-90 minutes EPIDURAL ANESTHESIA § Hydrophilic: slow onset (45-60 min), long dura=on (20 hr), high CSF solubility, extensive CSF spread § In 6-8 hr may reach respiratory centers in medulla causing delayed RD § Dose: 2-5 mg State maximum safe doses of local anesthe:cs Please remember: Max doses found in texts may vary and are not directly applicable to pracIce. ◦ Serum concentra-on is dependent on: – Injec-on technique – Site of injec-on – Addi-ves in LA AMIDES ESTERS Bupivacaine = 3 mg/kg Chloroprocaine =. 12 mg/kg Lidocaine = 4.5 mg/kg (7 mg/kg with epi) Procaine = 12 mg/kg Mepivacaine = 4.5 mg/kg (7 mg/kg with epi) Cocaine = 3 mg/kg Prilocaine = 8 mg/kg Tetracaine = 3 mg/kg Ropivacaine = 3 mg/kg Describe early and late signs of LAST and management Systemic toxicity: clinical symptoms associated with extreme plasma concentra-ons of LA Factors influencing plasma concentraIon: ◦ Dose of drug administered ◦ Rate of absorpIon of the drug ◦ Site injected, vasoacIvity of drug, use of vasoconstrictors ◦ BiotransformaIon and eliminaIon of drug Early signs: ◦ Lightheadedness, dizziness Late signs: ◦ Numbness of tongue ◦ Tonic clinic convulsions ◦ Difficulty focusing ◦ Coma ◦ Tinnitus ◦ Respiratory arrest ◦ Confusion ◦ Cardiac arrest ◦ Muscular twitching Cardiovascular effects: ◦ Local anestheIcs are myocardium depressants ◦ Arrhythmias can manifest as conducIon delays (prolonged PRI, complete heart block, sinus arrest, asystole) to ventricular dysrhythmias ◦ Dysrhythmias due to LA overdose may be recalcitrant to tradiIonal therapies Cardiovascular sequence of events: ◦ Low blood levels of LA: – Small increase in CO, BP and HR likely due to a boost in sympatheIc acIvity and direct vasoconstricIon ◦ High blood levels of LA: – Hypotension from reduced peripheral vascular resistance, reduced cardiac output and malignant arrhythmias – Cardiac arrest 21  TREATMENT: ◦ AIRWAY ® Clear airway, sucIon if needed ◦ BREATHING ® Oxygen with face mask, LMA or ETT ◦ CIRCULATION ® Elevate legs, increase IV fluids if hypotensive, CVS support with persistent hypotension ◦ DRUGS ® AnIconvulsant – Diazepam 0.15-3 mg/kg IV, midazolam 0.075-0.15 mg/kg IV – Propofol 1-20 mg/kg IV, Thiopental 1.4 mg/kg IV ◦ CVS SUPPORT ® Treat arrhythmias with standard life support protocols – Evidence suggests avoiding calcium channel blockers, sodium valproate, phenytoin ◦ Consider lipid infusion if unresponsive to standard resuscitaIon procedures: – Bolus Intralipid 20% 1.5 ml/kg over 1 minute – Infusion of Intralipid at 0.25 ml/kg/min – Chest compressions (circulate drug) – Repeat bolus q 3-5 minutes up to 3 ml/kg total dose unIl circulaIon is restored – May conInue Intralipid infusion unIl hemodynamically stable – Max recommended dose 8 ml/kg OXYGENATION AND VENTILATION IS EXTREMELY IMPORTANT AS HYPOXIA, HYPERCARBIA, AND ACIDOSIS POTENTIATE NEGATIVE INOTROPIC AND CHRONOTROPIC EFFECTS OF LA TOXICITY State safe dosing for spinal and epidural anesthesia (dose ranges for commonly administered local anesthe:cs via spinal and epidural routes for common procedures) SPINAL ANESTHESIA DuraXon (minutes) DuraXon (minutes) Dose (mg) to T10 Dose (mg) to T4 Onset (minutes) Plain with Epinephrine Commonly used Bupivacaine 0.75% 8–12 14–20 90–110 100–150 5–8 Less commonly used Lidocaine 5% 50–75 75–100 60–70 75–100 3–5 Tetracaine 0.5% 6–10 12–16 70–90 120–180 3–5 Mepivacaine 2% 30-60 60–80 140–160 N/A 2–4 Ropivacaine 0.75% 15–17 18–20 140–200 N/A 3–5 Levobupivacaine 0.5% 10–15 N/A 135–170 N/A 4–8 Chloroprocaine 3% 30 45 80–120 N/A 2–4 EPIDURAL ANESTHESIA Ini-al = 1-2 mL/segment to be blocked Top up dose = 33.3-75% of the ini-al dose (given at 2 segment dermatome regression) - sources vary Drug Concentra:on Onset Sensory block Motor block Chloroprocaine 2% Fast Analgesic Mild to moderate Chloroprocaine 3% Fast Dense Dense Lidocaine cerebral vessels dilate and brainstem sags into foramen magnum > stretches meninges and pulls on tentorium Fronto-occipital headache, N & V, photophobia, diplopia, =nnitus PDPH Supine posi=on, NSAIDS, caffeine (vasoconstric=on), epidural blood patch (10-20 ml sterile blood injected into epidural space > compresses spinal and epidural space and plugs to prevent further leaking), sphenopala=ne ganglion block Young, female, pregnancy increases risk Cauda equina syndrome (neurotoxicity due to high LA concentra=on; lidocaine indicated; S & S bowel and bladder dysfunc=on, sensory deficit, weakness, paralysis; treatment suppor=ve) Nerve Injury Transient neurologic symptoms (unlikely d/t neurotoxicity, likely d/t posi=oning, stretching of scia=c, myofascial strain, muscle spasm; lidocaine and lithotomy indicated; S & S severe back and bu_ pain that radiates to legs develops in first 36 hours may persist for 7 days; treatment NSAID, opioid, trigger injec=ons) Discuss cardiovascular response associated with sympathectomy including hypotension and bradycardia FACT MECHANISM CONSEQUENCE Preganglionic sympathe+c blockade ® B fiber blockade with B fibers being blocked first High block level = complete sympathe1c denerva1on Low block level = par1al sympathe1c denerva1on o Reflex increase in sympathe=cally intact areas compensates for Spinal anesthesia vasodila=on in sympathe=cally denervated areas via caro=d and causes hypotension aor=c response baroreceptors N&V Take home message: Effects preload, a`erload, contrac+lity and HR: Ischemia of cri+cal organs Sympathe+c Hypotension is caused by a reduc=on in cardiac output and reduc=on in CV collapse denerva+on is main systemic vascular resistance (SVR) Fetal compromise cause of CV changes Preload is decreased by sympathe=c block induced venodila=on (pooling (hypotension) of blood in the periphery reduces venous return to the heart) Venous system “maximally” dilated o Reliant on gravity for return to the heart o Posi=on and aortocaval compression (gravid uterus) have significant effect on venous return Arterial system dilated (thus reducing SVR) but not “maximally” Increase: Baroreceptor reflex o Nega=ve feedback loop to maintain BP o Hypotension (from spinal anesthesia) decreases baroreflex ac=va=on (stretch receptors in caro=d sinuses and aor=c arch) and causes heart rate to increase to restore BP Decrease: Sympathe+c block of cardiac accelerator fibers (T1-T4) Spinal anesthesia has o Slow onset complex effect on Reverse Bainbridge reflex ® Explains why low spinal levels (below cardiac accelerator fibers produces heart rate bradycardia o Bradycardia correlates with decreased arterial blood pressure § #1) bradycardia during spinal does not correlate with level of anesthesia but correlates with decrease in ABP Common factor linking heart rate and arterial blood pressure is venous return and right atrial pressure § #2) If a pa=ent is hypotensive with bradycardia and has a high spinal, Trendelenburg increases arterial pressure and heart rate If bradycardia was only due to blockade of cardiac sympathe=c fibers, posi=on changes would not increase heart rate 25  Bezold-Jarisch reflex (BJR) o Decreased stretch tension on mechanoreceptors located in the leJ ventricle o Empty LV triggers paradoxical reflex resul=ng in increased parasympathe=c ac=vity State level of surgical anesthesia required for common surgical procedures - SEE DERMATOMES SECTION ABOVE State test dose for epidural anesthesia and indica:ons for medica:ons used A test dose of 3-5 mL of 1.5% lidocaine with 1:200,000 epinephrine is given aher epidural catheter placement to help iden:fy accidental intrathecal or intravascular placement before administering the full dose of local anesthe:c. Detect Inadvertent Intrathecal Placement (Spinal Injec:on): - 1.5% Lidocaine acts as a fast-acIng local anestheIc. - If the catheter is mistakenly in the subarachnoid space, a rapid-onset spinal block will occur, leading to: - Sudden motor blockade (weakness or numbness in legs) - Hypotension due to sympathectomy - Profound sensory block below the level of injecIon - These effects typically appear within 3–5 minutes. Detect Inadvertent Intravascular Placement (IV Injec:on): - Epinephrine (15 mcg in 3 mL = 5 mcg/mL) acts as a marker for intravascular injecIon. - If the catheter is in a blood vessel, the epinephrine will cause: - Increased heart rate (HR) ≥ 20–30 bpm within 30–60 seconds - Possible hypertension, palpitaIons, or anxiety - A false-negaIve response may occur in beta-blocked paIents who cannot mount a tachycardic response. Discuss regional anesthesia in the an:coagulated pa:ent (focus on - ASA, UFH, LMWH, warfarin, Plavix) Aspirin or NSAID = no restric:ons Neuraxial blocks safe if coagula:on assessment normal and no other blood thinners used COX-2 inhibitors = neuraxial blocks safe Clopidogrel (Plavix) = discon:nue 5-7 days before; restart aher 24 hours Ticlopidine (Ticlid)= disconInue 10-14 days before; restart aXer 24 hours Dabigatran (Pradaxa) = disconInue 5 days before Apixaban (Eliquis)= disconInue 72 hours before; catheter removed 6 hours before 1st postop dose or hold 26-30 hours Tirofiban (Aggrastat)= hold 4-8 hours; contraindicated within 4 weeks of surgery> wait to restart Warfarin (coumadin) = discon:nue 4-6 (5) days & “normal” INR 4 days IV Heparin (low dose 5,000U up do TID) = hold 4-6 hours before block & “normal” coagula:on IV Heparin (intermediate dose < 20,000 U daily) = hold 12 hours IV Heparin (high dose > 20,000 daily) = hold 24 hours May restart heparin aher 1 hour of neuraxial or catheter Neuraxial catheter removal = wait 4-6 hours aher last SQ dose or infusion stopped Aher catheter removal= restart in 1 hour Low dose LMWH (Lovenox)/prophylac:c dose=wait 12 hours for placement/removal of catheter Higher dose LMWH (1 mg/kg q 12 hr or 1.5 mg/kg daily)/therapeu:c dose= wait 24 hours Aher block/catheter placement = delay 12 hours; neuraxial catheter removal= delay 1st dose 4 hours aher removal or remove 12 hours aher last dose and hold for 4 hours; blood in catheter when placed delay 24 hours Garlic (inhibiIon of platelet aggregaIon; increased fibrinolysis, anIhypertensive) = hold 7; gingko (increased platelet acIvaIng factor) = hold 36 hours; ginseng (lowers BS, increased PT) = hold 34 (some sources say safe to conInue if no other blood thinners and normal coagulaIon assessment) 26  EXTRA NOTES: Spinal Technical Procedure: PreoperaIve assessment and paIent preparaIon Iden-fy and document cogni-ve, sensory, motor, and coordina-on deficits Gather emergency equipment and drugs Gather equipment for spinal Select appropriate agent for procedure, sterile gloves, mask SedaIon PRN Monitors and oxygen on Posi:on* IdenIfy anatomy Performed below L2 L4-L5 =Tuffier’s line Use largest and most superficial space Assess spaces above and below chosen interspace Select interspace May mark with thumbnail impression or water-soluble marker Skin preparaIon Asep-c technique ® No current consensus regarding infec-on control. Full barrier technique recommended when placing an indwelling catheter Vigilance and follow-u