Induction Agents Flashcards
Ideal Anesthetic Properties
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
Propofol
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
Diprivan
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
Propofol MOA
Selective GABA receptor modulator
GABA = inhibitory transmitter in CNS
Influx Cl¯ ions into cell resulting in cell hyperpolarization
Spinal motor neuron excitability not altered
Propofol PK
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
Propofol PD
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
Propofol Induction
1.5-2.5mg/kg
Effects exaggerated w/ CV disease
↓ dose in elderly
↑ dose in pediatrics
Propofol Infusion
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
Propofol Other Doses
Antiemetic 10-15mg followed by 10mcg/kg/min infusion
Antipruritic 10mg
Anticonvulsant 1mg/kg
Propofol Contraindications
Hypersensitivity
Lipid metabolism disorder
Sulfate allergy (common in patients w/ asthma)
Caution in elderly, debilitated, & cardiac-compromised patients
PRIS
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
PRIS Risk Factors
> 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)
Propofol S/S
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
Propofol Abuse
Addictive properties - develop tolerance & well-being on emergence
Incidence markedly increased over past 10yrs
Not controlled substance (facility dependent)
Etomidate
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
Etomidate MOA
Administered as single isomer
R+ isomer 5x more potent
Selective GABA receptor modulator
Etomidate PK
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
Etomidate PD
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
Etomidate Clinical Uses
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
Etomidate Dose
Induction 0.2-0.4mg/kg
NO analgesic properties
Etomidate SE
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
Ketamine
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
Ketamine MOA
Binds non-competitively to phenylcyclindine site N-methyl-D-apartate receptors Glutamate antagonist Direct cytokines inhibition Limbic system activated Weak action on GABA receptors
Ketamine PK
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
Ketamine PD
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
Ketamine Dose
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
Ketamine Clinical Uses
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
Ketamine SE
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
Emergence Delirium r/t Ketamine
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
Dextromethorphan
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
Dexmedetomidine (Precedex)
Alpha 2 adrenergic agonist Locus coeruleus Vigilance, memory, analgesia, arousal Produces sedation by ↓ SNS activity Inhibits NE release Reversal agent - Atipamezole (specific & selective)
Dexmedetomidine PK
Highly protein bound
Extensive hepatic metabolism
Inhibit CYP450 increasing plasma opioid concentrations
Half-life 2-3hrs
Dexmedetomidine Clinical Uses
Attenuates hemodynamic response to tracheal intubation
↓ MAC & opioid requirements
↑ hypotension
Severe bradycardia/asystole
Intranasal pre-op anxiolysis in pediatric patients
Dexmedetomidine TIVA
IV anesthesia w/out ventilation depression
0.5-1mcg/kg bolus over 15min
Infusion 0.2-0.7mcg/kg/hr (up to 24hrs)
Scopolamine
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
Scopolamine SE
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)
Scopolamine Dose
Pre-op sedation
IV/IM 0.3-0.5mg
Physostigmine
Anticholinesterase
Scopolamine reversal
IV 15-60mcg/kg
Repeat doses as required
