SAS: Sedation and Premedication

What complications am I expecting?

1. cat - laryngospasm

2. brachycephalic

3. heart disease

4. pain

5. hemorrhage

6. hypoventilation/hypoxemia

7. hypothermia

8. hypotension

9. bradycardia

10. regurgitation

What is premedication?

drugs given prior to anesthetic induction for stress reduction and facilitation of intravenous catheter placement

Why do we premedicate?

• sedation/anxiolysis

• analgesia

• muscle relaxation

• chemical restraint

• MAC reduction

What are at-home premedication options?

• Trazadone

• Gabapentin

• Melatonin

• Dexmedetomidine Gel?

• Acepromazine

MOA of Trazadone?

5HT-2A

• serotonin receptor antagonist

• serotonin reuptake inhibitor

When to give Trazadone?

night before and prior to exam

• 90 minutes before stressful event

MOA of Gabapentin?

Blocks Ca2+ channels?

When to give Gabapentin?

night before and prior to exam

• 90 minutes before stressful event

MOA of Melatonin?

neurohormone

• initiation and maintenance of sleep

When to give Melatonin?

90 minutes prior to stressful event

When to give Dexmedetomidine Gel?

30-60 minutes prior to exam

When to give Acepromazine?

30-60 minutes prior to exam

Opioid examples

• butorphanol

• buprenorphine

• morphine

• hydromorphone

• methadone

• fentanyl

Opioids sedation MOA

decrease sympathetic outflow from the CNS

About Opioids

• SIGNIFICANT MAC reduction (dogs » cats)

• Analgesia

  • Mu » kappa

How do opioids alter thermoregulation for dogs?

hypothermic, panting

How do opioids alter cat thermoregulation?

hyperthermic

Heart effects of Opioids

• bradycardia (increase vagal tone)

• no myocardial depression

• histamine release - drug specific, dose/route dependent

Lung effects of Opioids

• respiratory depression (increase PaCo2)

• anti-tussives

Stomach effects of Opioids

• gastroesophageal reflux

• emetic and anti-emetic

  • CRTZ vs. vomiting center

Intestine effects of Opioids

• ileus, constipation

  • increase non-propulsive contractions

  • decrease propulsive contractions

Bladder effects of Opioids

• full Mu agonists - decrease urine production

• Kappa agonists - increase urine production

Mu receptor: (Opioid) Drug Receptor Interactions

• sedation/analgesia

• urine retention

• decrease GI motility

• emesis/antiemesis (drugs)

• decrease uterine contractions

• respiratory depression

• antitussive

• dysphoria

Kappa Receptor: (Opioids) Drug Receptor Interactions

• sedation

• less analgesia than mu

• diuresis (inhibits ADH release)

• decrease GI motility (less than mu)

• respiratory depression

• antitussive

Mu agonists opioid examples

• Fentanyl

• Hydromorphone

• Methadone

• Morphine

• Buprenorphine - partial mu

Kappa Agonist, Mu Antagonist Opioid Example

Butorphanol

Buprenorphine

• partial mu agonist

  • binds to the receptor with high affinity

  • only exerts part of the effects of a full mu

• duration: 4-6 hours

Butorphanol

kappa agonist, mu antagonist

duration: 60-90 minutes

Morphine

• mu agonists

• histamine release

• high emesis potential

• cost-friendly

• duration: 4-6 hours

Hydromorphone

• less than morphine effects!!!

• mu agonist

• histamine release

• sedation

• high emesis potential

• cost-friendly

• duration: 1-3 hours

Methadone

• Mu agonist

• low emesis potential

• NMDA antagonism

  • increase upregulated in chronic pain

• NOT cost-friendly

• duration: 3-5 hours

Fentanyl

• mu agonist

• low emesis potential

• works well as CRI - titratable

• cost-friendly

• duration: 15-30 minutes

What is the opioid reversal?

Naloxone

What is the MoA of Naloxone?

• competitive antagonism

  • works at mu, kappa, and delta receptors

  • no intrinsic activity

What are the uses of Naloxone?

• CPR

• prolonged recoveries

• dysphoria

What is the duration of Naloxone?

30-45 minutes

What should you be worried about when giving Naloxone?

renarcotization

What does Naloxone reduce?

sedation and analgesia

What are examples of Anticholinergics?

• Atropine

• Glycopyrrolate

What is the MoA of anticholinergics?

• muscarinic antagonist

  • “sympathomimetic” drug

    • bronchodilation

    • antisialagogue

    • increased HR

What are anticholinergics used for?

treatment of hypotension induced by bradycardia

• high vagal tone

What is the example of an anti-emetic?

maropitant (cerenia)

What is the MoA for maropitant?

NK-1 antagonist

What are the emesis pros?

• ensures stomach is empty prior to anesthesia

• less $$ to client

What are the emesis cons?

• anthropomorphizing

• aspiration risk

• increase IOP and increase ICP

What drug is most commonly associated with hyperthermia in cats?

hydromorphone

What temperature is considered hyperthermia in cats?

>104 F in cats 5+ hours post-anesthesia

What are the 3 classes of sedatives?

1. alpha-2 agonists

2. phenothiazines

3. benzodiazepines

Effects of alpha-2 agonists on the brain?

• sedation MoA: alpah-2 agonist receptors in cerebral cortex/brainstem

  • decrease release and decrease binding NE

  • decreased sympathetic outflow

• mild → profound sedation

  • still touch/sound sensitive

• muscle relaxation'; analgesia

effects of alpha-2 agonists on the heart?

BIPHASIC RESPONSE

• bradyarrhythmias

• vasoconstriction → baroreceptor-reflex bradycardia

  • increase BR; decrease HR; decrease CO

• vessel tone returns to normal but bradycardia persists

  • decrease BP; decrease HR; decrease CO

Effects of alpha-2 agonists on the lungs?

• alone → minimal-to-no respiratory depression

  • respiratory depression when combined with other drugs

• activation of pulmonary interstitial macrophages in sheep!

  • hypoxemia - caution!

Effects of alpha-2 agonists on the stomach?

• emesis in both dogs and cats

• decreases GI motility (including rumen contraction

effects of alpha-2 agonists on the uterus?

• increase uterine tone

• decrease uterine blood flow

effects of alpha-2 agonists on the bladder?

increase urine production

examples of alpha-2 agonist examples?

• dexmedetomidine

• medetomidine

• zenalpha

• detomidine

• xylazine

Alph-2 Agonists: Clinical Use

• routes: IV, IM, SQ, PO

• short-acting

• avoid in pediatrics

  • reliant on HR for CO

• avoid in volume-overloaded heart disease or systolic dysfunction

  • degenerative valve disease

• avoid in bradyarrhythmias

• caution in pregnant animals, sheep

• avoid in sick animals that would not tolerate a decrease CO

The antagonists of alpha-2 agonists?

• competitive antagonists

• IM ADMIN

• Atipamezole

• Yohimbine, Tolazoline

Effects of Phenothiazines on the brain?

• sedation MoA: dopamine antagonism (D2)

  • alpha-1 antagonism

  • anti-muscarinic

  • anti-histaminergic (H1)

  • anti-sestotonergic (5HT-3)

• mild → moderate sedation

• muscle relaxation; NO analgesia

• significant MAC reduction (~30%)

• “decrease seizure threshold”

  • yes for Chlorpromazine, research does not support with Ace

Effects of Phenothiazines on the heart?

• decrease in systemic vascular resistance (decrease blood pressure; alpha-1)

• decrease stroke volume, decrease cardiac output (not at low doses)

• anti-arrhythmic

• bradyarrhythmias in Boxers → European breeds

effects of phenothiazines on the lungs?

little-to-no effect on pulmonary function

effects of phenothiazines on the spleen?

• splenic sequestration of RBC (alpha-1)

  • decrease PCV

  • decrease platelet aggregation

effects of Phenothiazines on the stomach?

anti-emetic

effects of Phenothiazines on bones?

penile-prolapse (priaprism) → stallions

What is an example of a phenothiazine?

acepromazine

clinical use of phenothiazines?

• routes: IV, IM, SQ, PO

• long lasting with no reversal

• no analgesia

• avoid in sick patients

  • hypovolemia → risk for hypotension

• avoid in pressure-overloaded heart disease

  • hypertrophic cardiomyopathy

the effects of benzodiazepines on the brain?

• sedation MoA: enhance GABAa receptor’s affinity for GABA

• mild sedation

• muscle relaxation; NO analgesia

• anti-convulsant

• MAC reduction

the effects of the benzodiazepines on the heart?

• generally cardiovascular friendly

  • decrease HR, decrease CO by 10-20%

  • blood pressure can decrease from central effects on vasomotor centers

effects of the benzodiazepines on the lungs?

little-to-no effect on pulmonary function

examples of benzodiazepines

1. Midazolam

2. Diazepam

clinical uses of benzodiazepines

• routes

  • midazolam: IV, IM, IN

  • diazepam: IV ONLY

• no analgesia

• patient selection critical!

  • pediatrics and geriatrics

  • sick

• paradoxical excitement when administered alone in young healthy patients

antagonist of benzodiazepines

antagonist: Flumazenil; competitive antagonist

• IV, IM

• rapid reversal → administered slowly

dissociative anesthetics examples

1. ketamine

2. tiletamine

clinical uses of dissociative anesthetics

• sedation MoA: NMDA antagonist

  • disrupts neuronal communication - “dissociates”

• routes: IV, IM, (PO)

• NEED A MUSCLE RELAXANT

• increases myocardial oxygen consumption

• analgesia

• inexpensive

• nonreversible

• low volume injection - stings

what is a neurosteroid

alfaxalone

the clinical uses of alfaxalone

• sedation MoA: GABAa hyperpolarization → agonism

• routes: IV, IM

• mild cardiovascular depression

• occasional mycoclonus

• nonreversible

• no analgesia

• expensive

• respiratory depression

• large volume required

What is the included in the triad of anesthesia?

1. unconsciousness

2. analgesia

3. immobilization

What are 4 induction agents?

1. Propofol

2. Alfaxalone

3. Ketamine (& tiletamine)

4. Etomidate

Propofol

• insoluble in water, highly lipid soluble

• supports bacterial growth!

Propofol MOA

agonist at GABAa receptors

Propofol Metabolism

hepatic and excreted by kidneys

What can happen with repeated use of propofol in cats

• heinz bodies

• facial edema

• malaise

• anorexia

• diarrhea

• slower recovery

Propofol CNS

• rapid depression

• decrease ICP

• anticonvulsant effects

Propofol

• decrease arterial BP

• decrease SVR

• decrease CO

• mycocardial depression

Propofol respiratory

apnea… dose dependent

Propofol muscle

muscle relaxation

Propofol pregnancy

crosses placenta but rapidly cleared by neonate - safe?

does propofol provide analgesia?

no

Propofol time to effect and duration

time to effect: 60s

duration of action: 2-10 minute

Alfaxalone characteristics

• insoluble in water

• no antimicrobial preservative

• dispose after 6 hour

Alfaxalone MOA

GABA receptors similar to propofol

Alfaxalone Metabolism

• hepatic

• excreted by hepatic/fecal and renal routes

Alfaxalone CNS

causes unconsciousness & dose dependent decrease EEG activity

Alfaxalone CV

• dose dependent cardio depression

• decrease arterial BP

• decrease CO

• myocardial depression

• can see increase HR in response to decrease MAP

Alfaxalone Respiratory

dose dependent respiratory depression (apnea)

Alfaxalone muscle

muscle relaxation

Does Alfaxalone provide analgesia?

none

Alfaxalone time of effect and duration of action

• time to effect: 30-60s

• duration of action: 2-8 minutes

Ketamine

• dissociative anesthetic

• phencyclidine derivative

• class III controlled substance

Ketamine MOA

• main action is at NMDA receptor

• glutamate opens the channel

• decreases receptive field, increases threshold potential

• HCN1 inhibition

Ketamine

• mild anticholinergic effects (anti-muscarinic)'

• mild effects at mu and kappa opioid receptors

• monoamine reuptake inhibition

• AMPA increases - antidepressant activity