Induction Agents

Question 1

Ideal Anesthetic Properties

Answer 1

Water-soluble
Minimal cardiovascular or respiratory depression
Lack toxicity or histamine release (hypersensitivity reactions)
Rapid & smooth onset
Rapid & smooth recovery
Quick return to baseline mental status
Rapid metabolism
Steep dose-response curve
Analgesia
Anti-emetic action
Bronchodilation
Advantageous PK & PD

Question 2

Propofol

Answer 2

Insoluble - requires lipid vehicle to emulsify
Supports bacterial growth
Not chiral
Pain on injection d/t phenol
No antagonist (married to the effects)
Rapid return to consciousness w/ minimal residual SE

Question 3

Diprivan

Answer 3

pH 7-8.5
pKa 11
0.05% EDTA (ethylenediaminetetraacetic acid)

Propofol pH 4.5-6.4
pKa 11
0.025% sodium metabisulfite or benzyl alcohol

Question 4

Propofol MOA

Answer 4

Selective GABA receptor modulator
GABA = inhibitory transmitter in CNS
Influx Cl¯ ions into cell resulting in cell hyperpolarization
Spinal motor neuron excitability not altered

Question 5

Propofol PK

Answer 5

Clearances exceeds hepatic blood flow
1st pass pulmonary uptake
Extensive hepatic metabolism CYP450
Active metabolite 4-hydroxypropofol
Context sensitive half-time infusion <40min
NOT influenced by hepatic or renal dysfunction
↓ plasma clearance rate in patients older than 60
Binds reversibly to erythrocytes & plasma proteins, plasma albumin, free
Increase free fraction seen in severe hepatic/renal disease & pregnancy

Question 6

Propofol PD

Answer 6

Rapid & pleasant loss & return to consciousness
Myoclonus induced secondary to disinhibition subcortical centers (less than etomidate)
Neuro protectant
Mild to moderate ↓ BP secondary to ↓ sympathetic tone & vasodilation & CNS, cardiac, & baroreceptor depression
Respiratory depression common in induction doses
Minimal bronchodilation

Question 7

Propofol Induction

Answer 7

1.5-2.5mg/kg
Effects exaggerated w/ CV disease
↓ dose in elderly
↑ dose in pediatrics

Question 8

Propofol Infusion

Answer 8

IV sedation 25-100mcg/kg/min
Prompt recovery w/out residual sedation (endoscopy)
Minimal/no analgesic properties
Used in conjunction w/ anxiolytic & opioid

Anesthesia maintenance
100-300mcg/kg/min
Associated w/ minimal post-op N/V
Used in conjunction w/ short-acting opioid

Question 9

Propofol Other Doses

Answer 9

Antiemetic 10-15mg followed by 10mcg/kg/min infusion
Antipruritic 10mg
Anticonvulsant 1mg/kg

Question 10

Propofol Contraindications

Answer 10

Hypersensitivity
Lipid metabolism disorder
Sulfate allergy (common in patients w/ asthma)
Caution in elderly, debilitated, & cardiac-compromised patients

Question 11

PRIS

Answer 11

Long-term, high dose infusions
Associated w/ significant morbidity & mortality
MOA unknown
Seen in acute inflammatory disease - infection, sepsis, acute neurologic disease
Propofol triggering agent (catechol/steroids) administered

Question 12

PRIS Risk Factors

Answer 12

> 4mg/kg/hr
> 48hrs
Critical illness
High fat-low carb intake
Concomitant catecholamine infusion
Steroid administration
Inborn mitochondrial fatty acid oxidation errors (creates oxygen supply-demand mismatch causing tissue necrosis)

Question 13

Propofol S/S

Answer 13

Hypotension, bradycardia, widening QRS, Vtach or Vfib, asystole, ischemic EKG, arrhythmia, heart failure
Hypoxia & pulmonary edema
Acute kidney injury & hyperkalemia
Rhabdomyolysis
Hyperthermia, high anion gap metabolic acidosis, urine discoloration
Hepatomegaly, abnormal LFTs, steatosis, lipidemia, hypertriglyceridemia

Question 14

Propofol Abuse

Answer 14

Addictive properties - develop tolerance & well-being on emergence
Incidence markedly increased over past 10yrs
Not controlled substance (facility dependent)

Question 15

Etomidate

Answer 15

pH 8.1 pKa 4.2
Weak base
Water soluble in acidic pH; lipid soluble in physiologic
Preferable induction agent in unstable cardiac patient
Chemically unrelated to any other induction drug

Question 16

Etomidate MOA

Answer 16

Administered as single isomer
R+ isomer 5x more potent
Selective GABA receptor modulator

Question 17

Etomidate PK

Answer 17

Large Vd
Significant tissue uptake
Moderate lipid solubility
75% bound to plasma albumin
↓ albumin ↑ active fraction
Prompt emergence 2nd to redistribution to tissues & rapid metabolism
Metabolized by hydrolysis - plasma esterases & microsomal enzymes in the liver

Question 18

Etomidate PD

Answer 18

Rapid onset w/in one arm-to-brain circulation
Return to consciousness in 5-15min
↓ CBF ↓ CMRO2
↓ ICP while maintain CPP
Involuntary myoclonic movements common - mistaken as seizures secondary to distribution to deep cerebral & brainstem
↓ amplitude ↑ latency
Maintain hemodynamic stability (acts on alpha 2 adrenergic receptors - mediated ↑ BP)
↓ minute volume
↑ RR

Question 19

Etomidate Clinical Uses

Answer 19

Cardiac depressive effects minimal
No longer used as infusion
Induction doses up to 0.3mg/kg result in minimal changes 
- HR, SV, CO
- MAP decrease secondary to SVR
- Doses > 0.45mg/kg result in ↓ BP & CO
- Apnea w/ rapid injection

Question 20

Etomidate Dose

Answer 20

Induction 0.2-0.4mg/kg

NO analgesic properties

Question 21

Etomidate SE

Answer 21

Spontaneous myoclonus (involuntary movements common)
Adrenocortical suppression
Increased post-op N/V incidence
Low allergic reaction incidence
Minimal pain on injection
Contraindicated in patients w/ porphyrias

Question 22

Ketamine

Answer 22

pH 3.5-5.5 pKa 7.5
Dissociative anesthesia
EEG dissociation b/w thalamocortical & limbic systems
Cataleptic state where eyes remain open w/ slow nystagmus gaze
Potent amnestic & analgesic
No significant respiratory depression
Racemic mixture

Question 23

Ketamine MOA

Answer 23

Binds non-competitively to phenylcyclindine site
N-methyl-D-apartate receptors
Glutamate antagonist
Direct cytokines inhibition
Limbic system activated
Weak action on GABA receptors

Question 24

Ketamine PK

Answer 24

Rapid distribution to tissues
Highly lipid soluble; rapid transfer blood-brain barrier
Not significantly bound to plasma proteins
Demethylation by CYP450 microenzymes
Metabolism dependent on hepatic flow
Active metabolite - Norketamine (broken down to form water-soluble and inactive metabolites)
Elimination half-life 2-3hrs

Question 25

Ketamine PD

Answer 25

Cataleptic dissociative state - eyes open, pupils reactive, corneal reflex intact, nystagmus present, lacrimation & blinking continue Airway reflexes intact Maintain spontaneous respirations Bronchodilator ↑ salivary secretions ↑ skeletal muscle tone ↑ CBF/CMRO2/ICP attenuated w/ opioid & benzodiazepine ↑ IOP (contraindicated in eye procedures) SNS activation ↑ HR/BP/SVR

Question 26

Ketamine Dose

Answer 26

IV 1-2.5mg/kg onset 2-3min IM 4-8mg/kg <10min PO 10mg/kg 10-20min Analgesic effects at sub-anesthetic doses 0.2-0.5mg/kg (somatic > visceral) Acts in thalamic & limbic systems NMDA receptors responsible for spinal cord sensitization

Question 27

Ketamine Clinical Uses

Answer 27

Hypovolemic patients (trauma) favorable CV effects Bronchodilation useful for patients w/ asthma Induction complicated in patients w/ CAD OB anesthesia w/out neonatal depression - does not compromise uterine tone, blood flow, or neonatal status Chronic pain syndromes Management in preventing hyperalgesia CRPS treatment & cancer pain Burn patients - extensive dressing changes & skin grafting procedures Ketamine "dart" pediatric patients + Propofol TIVA = more stable hemodynamic effects w/out unwanted emergence reactions

Question 28

Ketamine SE

Answer 28

Effects similar to SNS stimulation Potent cerebral dilator Intracranial pathology patients vulnerable to sustained increases in ICP ↑ pulmonary arterial BP, HR, CO, cardiac work, & myocardial O2 requirements Apnea after Succinylcholine prolonged Enhancement non-depolarizing neuromuscular blocking agents

Question 29

Emergence Delirium r/t Ketamine

Answer 29

5-30% incidence Partially dose dependent Visual, auditory, proprioceptive, & confusional illusions (up to 24hrs after admin) Morbid content & vivid color Floating sensation d/t loss skin & musculoskeletal sensation Transient cortical blindness Factors: >15yo female, personality problem history, frequent dreams Occurs less frequently w/ repeated doses Admin benzo 5min prior to surgery ↓ incidence (Midazolam > Diazepam) Atropine ↑ incidence

Question 30

Dextromethorphan

Answer 30

D-isomer opioid agonist Levomethorphan Low affinity NMDA antagonist Antitussive effects in cough medicines Psychoactive effects ↑ abuse potential Lack analgesic or physical dependence properties Excessive intake = hypertension, tachycardia, somnolence, agitation, slurred speech, ataxia, diaphoresis, skeletal muscle rigidity, seizures, coma Hepatic toxicity w/ acetaminophen ingestion

Question 31

Dexmedetomidine (Precedex)

Answer 31

``` Alpha 2 adrenergic agonist Locus coeruleus Vigilance, memory, analgesia, arousal Produces sedation by ↓ SNS activity Inhibits NE release Reversal agent - Atipamezole (specific & selective) ```

Question 32

Dexmedetomidine PK

Answer 32

Highly protein bound Extensive hepatic metabolism Inhibit CYP450 increasing plasma opioid concentrations Half-life 2-3hrs

Question 33

Dexmedetomidine Clinical Uses

Answer 33

Attenuates hemodynamic response to tracheal intubation ↓ MAC & opioid requirements ↑ hypotension Severe bradycardia/asystole Intranasal pre-op anxiolysis in pediatric patients

Question 34

Dexmedetomidine TIVA

Answer 34

IV anesthesia w/out ventilation depression 0.5-1mcg/kg bolus over 15min Infusion 0.2-0.7mcg/kg/hr (up to 24hrs)

Question 35

Scopolamine

Answer 35

Anticholinergic Only anticholinergic used for sedation ↓ reticular activating system activity Effects enhanced w/ concomitant opioid & benzo administration Strong antisialagogue effect (inhibits saliva) Less likely to produce cardiac effects Commonly admin transdermal for N/V

Question 36

Scopolamine SE

Answer 36

Mydriasis (Bella Donna) - block normal aqueous humor drainage Cycloplegia - inability to focus near vision Central anticholinergic symptom - restlessness & hallucinations to somnolence & unconsciousness Overdose (muscarinic cholinergic blockade characteristics) - dry mouth, difficulty swallowing, blurred vision, photophobia, tachycardia, skin dry & flushed, ↑ body temp (inability to sweat)

Question 37

Scopolamine Dose

Answer 37

Pre-op sedation | IV/IM 0.3-0.5mg

Question 38

Physostigmine

Answer 38

Anticholinesterase Scopolamine reversal IV 15-60mcg/kg Repeat doses as required