1/3/2018

CREDIBILITY FACTOR?

WHAT’S NEW IN

Anesthesiology ANESTHESIA/ ANALGESIA? BS Biochemistry 8 yrs DVM Residency

LYSA PAM POSNER, DVM, DACVAA DACVAA Faculty Faculty 2005 PROFESSOR OF ANESTHESIOLOGY 1-2018

PLAN?

• Introduce new products • Introduce new ways to use established products ANALGESICS

CLASSIC 3-NEURON CHAIN MODEL OF NOCICEPTIVE PROCESSING (SOMATIC)

REVIEW OF PAIN PATHWAY

1 1/3/2018

PERIPHERAL SENSITIZATION

Ganong; physiology

CENTRAL SENSITIZATION / WIND-UP PERCEPTION

• Dorsal horn of the spinal cord • Must reach cortex to be perceived as pain • Extreme or repeated activation • Mediated by glutamate • If patient is unconscious/ anesthetized, they won’t “feel” pain but the entire • Results in pathway may be activated – Decreased threshold – Expansion of receptive field – Increased spontaneous firing • When consciousness returns, pain – Hyperalgesia/allodynia pathway will be in full activation – Spontaneous pain – With less descending modulation

LOCAL ANESTHETICS

– Mechanism of action • Sodium channels propagate action potential • Local anesthetics block sodium channel

– Routes of administration • Perineural • IV LOCAL ANESTHETICS • Dermal – Species Differences • Sensitivity to toxicity

2 1/3/2018

LOCAL ANESTHETIC UPDATES: LOCAL ANESTHETIC UPDATES: LIDOCAINE PATCHES LIDOCAINE CRI IN DOGS

• IV lidocaine in DOGS • Lidocaine Patches • Systemic analgesia • Antiinflammatory – Little to no systemic absorption (dogs/cats) • GI Prokinetic – CAN be cut to size/area wanted – Should be replaced daily • Dose of IV lidocaine in dogs: – Potential uses – Loading: 1.0 mg/kg • IVDD, bone pain, inflammatory – CRI: 25 mcg/kg/min

LOCAL ANESTHETIC UPDATE: NOCITA LOCAL ANESTHETIC UPDATE: NOCITA

• Long acting local anesthetic • Off label use – Extended-release bupivacaine technology – Amputations – Multivesicular liposomes • 72 hr duration – Orthopedics (besided CCL) • Labeled for dogs following CCL surgery – Soft tissue procedures • Dosage –Cats – 5.3 mg/kg (0.4 mL/kg) – Infiltration injection into the tissue layers • No data on perineural administration • Caution? – At the time of incisional closure – Infected wounds • Very effective – Patients with immune disturbances • Expensive • Short shelf life once opened – Labeled for 4 hr once opened

DISSOCIATIVE ANESTHETICS KETAMINE/TILETAMINE/PHENCYCLIDINE AMANTADINE

•NMDA (N-methyl-D-aspartate) antagonists –NMDA receptors are excitatory receptors

•Dissociative anesthetic –Thalamo-cortical and limbic systems NMDA –Altered consciousness (at anesthetic doses) –Catalepsy (at anesthetic doses) –Amnesia (at anesthetic doses) ANTAGONISTS –Analgesia –at subanesthetic doses •Ketamine –Approved for use in cats and primates •Tiletamine (part of the combination Telazol) –Telazol approved for cats and dogs

3 1/3/2018

NMDA RECEPTOR ANTAGONISTS PAIN PATHWAY DORSAL HORN OF SPINAL CORD

• Dorsal horn of spinal cord – Opioid receptors – Alpha-2 receptors – NMDA receptors

• Central sensitization – Wind-up pain

NMDA ANTAGONISTS DISSOCIATIVES: WHAT’S NEW?

•At least 24 hr CRI needed to “break” windup cycle (in humans) • Mechanism of action – Unclear how long dogs/cats – Antagonize activation of NMDA receptor – Induction dose unlikely enough with glutamate at dorsal horn of spinal cord – With extended inactivation can interrupt central sensitization •Injectable ketamine CRI • >24 hr (days? weeks?) – At least 24 hr is recommended to alter/ prevent windup •Oral amantadine – Ketamine, amantadine – At least 2-3 week trial – Can use with NSAIDs, gabapentin, opioids, etc – Chronic pain/ wounds/ burns – Amputations

NMDA ANTAGONISTS

• Ketamine: side effects – Anesthetic doses CALCIUM • 5mg/kg induction dose • Increased CV work • Hallucinations/ behavioral effects CHANNEL – Analgesic doses—few side effects • 5-10 mcg/kg/min (ketamine) BLOCKERS • Amantadine: side effects –Not reported • 3-5mg/kg PO SID

4 1/3/2018

CALCIUM CHANNEL BLOCKERS CALCIUM CHANNEL BLOCKERS GABAPENTIN (GABAPENTIN) • Mechanism of action • Side effects –Binds α2δ subunit-voltage gated – Somnolence calcium channels • Decreases with time • Upregulated in pain states –Humans • Rapid withdrawal associated with seizure risk – May (?) interacts with NMDA receptors, protein kinase C, • Species Differences inflammatory cytokines – Administered in many species – Little adverse effects – Unknown dosing ideals

TRPVI RECEPTOR AGONISTS

• Mechanism of Action TRVP1 – Calcium channels – Activated by • Heat • H+ RECEPTOR • Capsaicin • Resiniferatoxin (RTX) AGONISTS – More on c-fibers (?) • “burning, itching, stinging” sensation

– Activate then desensitize nerve

TRPVI RECEPTOR AGONISTS

• Side effects – First must “activate” then desensitize receptor – Tingling up to pain – Some treatments require anesthesia ANESTHETICS

5 1/3/2018

NEUROSTEROIDS: ALFAXALONE

•GABA is the primary inhibitory neurotransmitter

•Binds to specific site on GABA receptor NEUROSTEROIDS – GABA enhancer/ agonist

ALFAXALONE •Structurally similar to steroids –Does not bind to sex hormone, glucocorticoid or mineralocorticoid receptors

ALFAXALONE NEUROSTEROIDS & VETERINARY MEDICINE NEUROSTEROID STRUCTURE

• Saffan PROGESTERONE ALFAXALONE – Alfaxalone and alfadolone (3:1) – Clinical trials and marketed in UK – Hard to dissolve in water-based solutions • Solubilized in Cremophor – Reports from 1974 & 1980 • Allergic reactions (69% of cats!) – Ear swelling to anaphylaxis • Many dogs died from anaphylaxis

ALFAXAN® ALFAXALONE: DOSE AND SAFETY ALFAXALONE

•Alfaxalone only DOGS CATS –Difficult to dissolve in water based solution •~2mg/kg IV •4-5 mg/kg IV •Cyclodextrin ring –Water soluble delivery •> 10 weeks age •> 4 weeks age •Approved in USA –Schedule IV controlled drug (USA) •C-sections –Labeled for dogs and cats, IV use •C-sections

•Clear solution •Safety with 5x dose –< 6 hr once opened •Safety at 10 x dose

6 1/3/2018

ALFAXALONE: PHYSIOLOGIC EFFECTS ALFAXALONE: MISCELLANEOUS

•CV • Induction and recovery not as smooth as propofol – CV depression similar or better than propofol – Particularly as a solo agent • Head bob, uncoordinated gait •Respiratory – Depression to apnea • Does not cause tissue reaction if administered outside of vein or SQ – Product literature and Heit 2004 •Analgesia – No analgesia • Can us as a CRI (constant rate infusion)

•Metabolism • More expensive that propofol in USA – Liver metabolism

ALFAXALONE: WHAT'S NEW? ALFAXALONE: WHAT'S NEW?

• Off Label Use • Off label, published, use in other species – IM administration for sedation – Not labeled for in USA, but is in Australia –Ferrets – Volume is the limiting factor – Rabbits –Turtles –Dose – Dogs: ~ 1 mg/kg (with opioid or midazolam) – Reptiles – Cats: ~ 1-2 mg/kg (with opioid or midazolam) – Fish by immersion

• Indication – e.g. Fractious animal with CV disease – e.g. Echo without dexmedetomidine/ketamine

QUESTIONS ON ALFAXALONE?

ETOMIDATE

7 1/3/2018

ETOMIDATE ETOMIDATE

•Ultrashort non-barbiturate (imidazole compound) • CV – Introduced in human anesthesia 1972 – NO CV EFFECTS • Not approved for use in veterinary species • HR, BP, SVR, CO

•Not scheduled in USA • CNS Effects – GABA enhancer • Respiratory •Propylene glycol vehicle (35%) – Moderate depression – Long shelf life • Metabolism – Pain on injection – Liver metabolism (+ propylene glycol) – Can cause hemolysis with CRI • Decreases adrenal gland hormones

ETOMIDATE: ENDOCRINE EFFECTS ETOMIDATE: MISCELLANEOUS

• Decreased adrenocortical activity • Poor muscle relaxation – lasts, 2 - 6 hr – Muscle rigidity, myoclonus, vocalization, opisthotonus

•Inhibits 11-B hydroxylase – Administer with muscle relaxant (e.g. benzodiazepine) – cholesterol to cortisol • Emesis • Decreased adrenal stress response

•Multiple doses / CRI • Expensive (2015) (~ $5/ml) – hypoadrenocorticism – 4kg cat ~ $12.00 – +/- death (dogs and humans) – 40kg dog ~ $100.00

WHAT’S NEW: ETOMIDATE?

• Available

• Non scheduled • Fills particular patient needs QUESTIONS?

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