Exam 2 Flashcards
Sedative-Hypnotics
A drug that reversibly depress the activity of the CNS.
Procedural Sedation/Conscious Sedation/ Monitored Anesthesia Care (MAC)
The administration of a combination
of sedative(s) and analgesic(s) to induce a depressed level
of consciousness, allowing patients to tolerate unpleasant procedures and enabling clinicians to perform procedures effectively.
Vessel rich group CO and locations
75%
brain
heart
kidney
liver
muscle group CO and locations
18%
skm
skin (highly vascular)
(lean tissue)
Fat CO
5%
Vessel poor group CO and locations
2%
bone
tendon
cartilage
Components of General Anesthesia (Stage 3)
- Hypnosis- sleep state
- Analgesia- pain free
- Muscle Relaxation- safe
- Sympatholysis- HD stability
- Amnesia- don’t remember
Stages of General Anesthesia
Stage 1: Analgesia
Stage 2: Delirium
Stage 3: Surgical Anesthesia
Stage 4: Medullary Paralysis
Protective reflexes lower airway
cough, gag, swallow
sneeze = upper ariway
Stage 2 characteristics of excitement
undesired CV instability excitation, dysconjugate ocular movements, laryngospasm, and emesis.
Response to stimulation is exagerrated and violent.
Medullary paralysis
Stage 4 of GA.
May lead to death.
Marked hypotension with weak, irregular pulse
Flaccid paralysis
All reflexes are absent
Associated with cessation of spontaneous respiration and medullary cardiac reflexes.
Gold standard for drugs to compare to
Barituates
Thiopental
Derived from barbituric acid
Barbiturates Mechanism of Action (MOA) and cns effects
Potentiate GABAAchannel activity; directly mimics GABA
Acts on glutamate, adenosine, and neuronal nicotinic acetylcholine receptors.
Cerebral vasoconstrictor (help w/ sz)
-> decreases CBF and decreases CMRO2 55%
***No analgesia (but has hypnosis and muscle relaxation)
Barbiturates Prolonged infusion
lengthy context-sensitive half-time
Thiopental onset
30 seconds
rapid awakening d/t rapid uptake/ redistribution from brain to other tissues
Site of initial redistribution for thiophental
skm
equilibrium at 15 min to plasma
Dose thiophental based on
Lean body wt
IBW
Barbiturates Pediatric consideration
Elimination half time is shorter from inc drug clearance/ higher drug metabolism
Thiopental protein binding
Albumin 70% to 85% (inactive)— if stays in the blood
Thiopental Dose
4 mg/kg IV
Thiopental Elimination ½ time
Longer than methohexital
30 minutes only 10% in brain from rapid redistribution to skm
Partition coefficient definition
Describes the distribution of a given agents at equilibrium between two substances at the same temp, pressure, and volume
Blood-gas coefficient
describes the distribution of a anesthetic between blood and gas at the same partial pressure
Methohexital (Brevital) dose
1.5 mg/kg IV
what does a decreased sensitivity to CO2 mean
need more co2 to breath/ trigger medullary / poontine section (need ETCO2 50-55)
if more senstive= start breathing at 30.
Methohexital (Brevital) Per Rectum (PR) dose
20-30 mg/kg
Barbiturates enzyme induction of what meds
anticoagulants, phenytoin, TCAs, digoxin, corticosteroids, bile salts, and vit. K.
increase metab = dec drug effect
Barbiturates Intra-arterial Injection
Results in immediate, intense vasoconstriction and excruciating pain that radiates along the distribution of the artery
obscure distal arterial pulses
blanching of the extremity followed by cyanosis
gangrene and permanent nerve damage
tx; lidocaine or papaverine
Prop induction dose
1.5 to 2.5 mg/kg IV
children; 3-3.5 mg/kg
elderly; 1mg/kg
prop conscious sedation dose
25 to 100 µg/kg/min
Prop maintenance dose
100 to 300 µg/kg/min
Prop Rapid injection (<15 seconds)
Produces unconsciousness within 30 seconds
Prop soybean oil
10%
1mg/ml
Prop glycerol
2.25%
Prop purified egg phosphatide (lecithin)
1.2%
egg yolk has the lecithin
Prop E1/2
0.5 to 1.5 hours
Prop Context-sensitive half-time
40 minutes (8-hour infusions)
Prop VOD
3.5-4.5 (L/kg)
Prop Clearance
30-60 (ml/kg/min)
Through the lungs > hepatic bf
Tissue uptake > Cyp450
Prop metabolism
Cyp450 to Water-soluble sulfate and glucuronic acid metabolites
excreted in the kidneys
Prop on systemic bp
decreased
Inhibition of SNS…vascular smooth muscle relaxation… ↓ SVR
Decreases intracellular calcium
Modulated by laryngoscopy stimulus
Exaggerated in hypovolemia, elderly, LV compromise
avoid in cardiovascular pts.
Prop on heart rate
decreased
Decreases SNS response
May depress baroreceptor reflexes
Profound bradycardia and asystole with healthy adult patients
Etomidate half time
2-5 hr
Etomidate VOD
2.2-4.5 L/kg
Etomidate clearance
10-20 ml/kg/min
Large Vd; clearance is 5x faster than Thiopental
Prompt awakening
Etomidate systemic bp
no change to decrease
Etomidate on heart rate
no change
Ketamine elimination half life
2-5h
2-3 hr
Ketamine VOD
2.5-3.5 L/kg
(3 L/kg)
Ketamine clearance
16-18 ml/kg/min
Ketamine on systemic bp
increased
Ketamine on hr
increased
Barbiturates half life
5 min = 1/2 total dose
30 min = 10% total dose
prolonged infusions = contest sensitive half time
Bariburates ionized/ non ionized components
Non-ionized drug ( wants to stay in fat/skm)
More lipid soluble
Acidosis favors
Ionized drug
Less lipid soluble
Alkalosis favors
Thiopental fat/ blood partition coefficeint
11
dose calcualted on IBW
Methohexital (Brevital) Ionized/ non ionized component
Lower lipid solubility than Pentothal
At normal pH, 76% non-ionized (pentothal 61% non-ionized)
Faster metabolism
More rapid recovery
Prop MOA
GABA A agonist -> inc chloride conductance -> hyperpolarized
Prop SE
support bacterial growth
increased plasma trig concentrations (prolonged infusion)
Pain on injection- based on vein size
Prop effects on N/V
more effective than zofran
moa; depresses subcortical pathways and has direct depressant effect on the vomiting center
Prop Sub- hypnotic dose
10-15 mg IV followed by 10 mcg/kg/min
Prop dose for truncal puritis
10mg IV
usually from neuraxial opioids (morphine) or cholestasis
Prop CNS effects
Decreases CMRO2 , CBF, ICP
Large doses may decrease Cerebral Perfusion Pressure (support map)
Excitatory movements on induction/emergency; myoclonus
less effect on EEG compared to other drugs
Prop airway effects
Bronchodilator effects; good for asthma, copd, restrictive lung disease
Prop anticonvulsant dose
1 mg/kg
SSEP
Sensory evoked potentials studies measure electrical activity in the brain in response to stimulation of sight, sound, or touch
Prop on Pulmonary
Dose-dependent depression of ventilation-> Apnea
With opioids (synergistic)
Intact hypoxic pulmonary vasoconstriction response
Prop on urine
pheonls cause green urine
uric acid cystalization cause cloudy urine
but no alteration on renal function
Propofol Infusion Syndrome
-High dose infusions of >75 µg/kg/ minute longer than 24H
-Severe, refractory, and fatal bradycardia in children
-S/sx: Lactic acidosis, Brady-dysrhythmias, Rhabdomyolysis
-Dx: ABG and serum lactate concentrations
-Reversible in the early stage
Cardiogenic Shock: Extracorporeal membrane oxygenation (ECMO).
Etomidate MOA
Selective modulator of GABAA receptors
Etomidate onset
within 1-minute s/p IV injection
Etomidate protein bound
76% albumin bound
Etomidate elimination location
85% in urine & 10% - 13% in bile
Etomidate dose
0.3 mg/kg IV
0.2-0.4mg/kg
Medication with the highest incidence of myoclonus
50% to 80% Etomidate
An alteration in balance of inhibitory and excitatory influences on the thalamocortical tract.
Can be attenuated by prior administration of opioids or benzos. Fent 1-2 mcg/kg IV
Etomidate and adrenocortical suppression
Dose dependent inhibition of the conversion of cholesterol to cortisol . overtime = decreased stress response.
result; Severe hypotension, longer
Enzyme inhibition lasts 4 to 8 hours after initial dose.
Etomidate on CNS
Decreases CBF and CMRO2 35% to 45%
Potent, direct cerebral vasoconstrictor
Dec ICP
Similar to thiopental
Caution: patients with history of seizure activity
Etomidate on respiratory
VT decreases are offset by compensatory increases in frequency of breathing.
Transient: 3 to 5 minutes
Stimulates CO2 medullary centers
MIV forumula
MIV = Tv x RR
Dissociative anesthesia
Resembles a cataleptic state in which the eyes remain open with a slow nystagmic gaze
s/s; noncommunicative, but wakefulness is present; hypertonus and purposeful skeletal muscle movements
most abundant excitatory neurotransmitter in CNS
Glutamate
Gylcine (co agonist)
Ketamine MOA
Binds noncompetitively to N-methyl-D-aspartate (NMDA) receptors.
Inhibits activation of NMDA receptors by glutamate and decreases the presynaptic release of glutamate.
Other receptor sites: opioid (µ, δ, and κ; weak σ), monoaminergic, muscarinic, and voltage-sensitive sodium and L-type calcium channels & neuronal nicotinic acetylcholine receptors.
Weak actions at GABAAreceptors.
Ketamine advantages over prop and etomidate
Lipid emulsion vehicle is not required = no pain @ injection.
Profound analgesia at subanesthetic doses
use for w/d but can cause abuse
Ketamine preservatives
Benzethonium Chloride
nachR inhibit effects -> sns stimulation
Ketamine onset
Peak plasma concentrations @ 1 minute after IV & 5 mins (IM)
Ketamine duration of action
10 – 20 mins
Ketamine lipid solublility
High lipid solubility (5x to 10x than Thiopental)
Brain -> not plasma bound -> distributed to tissues
Ketamine induction dose IV and IM
0.5 - 1.5 mg/kg IV
4 - 8 mg/kg IM
Ketamine metabolism
Hepatic, cytochrome P450 enzymes
Norketamine: active metabolite (1/3 potency); prolonged analgesia)
Ketamine maintenance dose IV and IM
0.2 - 0.5 mg/kg IV analgesia
4 - 8 mg/kg IM
Ketamine Subanesthetic (analgesic dose)
0.2 - 0.5 mg/kg IV
Ketamine Post Op Sedation and Analgesia dose
1 - 2 mg/kg/hour (pediatric cardiac surgery)
Ketamine Neuraxial Analgesia dose
30 mgs Epidural
5 - 50 mg in mL of saline Intrathecal/Spinal/Subarachnoid
ERAS
enhanced recovery after surgery
Barbiturates Pediatric consideration
Elimination half time is shorter from inc drug clearance/ higher drug metabolism
what does a decreased sensitivity to CO2 mean
need more co2 to breath/ trigger medullary / poontine section (need ETCO2 50-55)
if more senstive= start breathing at 30.
Ketamine induction considerations
Ketamine-induced salivary secretions
Use antisialagogue as preoperative medication
Glycopyrrolate > Atropine/Scopolamine (emergence delirium)
Ketamine Induction LOC effect
30 secs – 1 min (IV); 2 to 5 mins (IM)
Ketamine Return of consciousness (ROC)
10-20 min
Ketamine Full consciousness
60 to 90 minutes.
Ketamine Amnesia persists after ROC
60-90 min
Ketamine Clinical Uses
Acutely hypovolemic patients (no hyptotension)
Asthmatic & MH patients (bronchdilate)
Reversal of opioid tolerance
Improvement of psychiatric disorders
Restless Leg Syndrome (PO dose)
Ketamine Avoid or caution
Pulmonary: Systemic/pulmonary HTN
Neuro: Increased ICP
Ketamine on the CNS
Potent cerebral vasodilator
↑ CBF by 60%
0.5 to 2 mg/kg IV: no further ↑ ICP
Excitatory activity in EEG does not alter seizure threshold.
Increased amplitude with SSEP -> reduced by N20
Ketamine CV side effects
Resemble SNS stimulation: Increases sBP, PAP, HR, CO, MRO2
Increases plasma Epi & Norepinephrine levels
Blunted by pre-med with benzos or inhaled anesthetics & N20
Unexpected drops in sBP and CO…depleted catecholamine stores (cant give ephederine)
Ketamine on : Ventilation & Airway
↑ salivary and tracheobronchial mucous gland secretions
Bronchodilator activity
Ketamine Emergence Delirium and Mia of delirium
AKA Psychedelic Effects in 5% to 30% of patients
S/Sx: visual, auditory, proprioceptive, and confusional illusions -> delirium.
Morbid & vivid dreams (in color) and hallucinations up to 24H
MOA: depression of the inferior colliculus and medial geniculate nucleus (separate reality and fantasy)
Prevention: Benzodiazepine IV (5 minutes prior)
Ketamine Drug Interactions
Volatile anesthetic -> hypotension
NDNMB drugs ->enhanced
Succinylcholine -> prolonged
What induction agent has the highest analgesic properties
Ketamine
