Propofol
What are the properties of propofol?
What is an important advantage of propofol?
its an emulsion in soybean oil and egg lecithin therefore it is insoluble in aqueous solution
pain on injection
increases triglycerides (long infusion)
-Important advantage = rapid return to consciousness with minimal residual.
Possible MOA
- work on a- subunits of the GABA A receptor complex = enhance inhibitory postsynaptic channel activity
- inhibit excititory synaptic channel activity
- enhancement of the activity of K+ channels leading to hyperpolariziation of the plasma membrane, this influences the likelihood of neuronal action potential
What is the MOA of Etomidate?
- depresses the Reticular Activating system (RAS) and mimics the effects of GABA (enhances the affinity of GABA to the receptors)
What is MAC?
How does MAC correlate with potency
The alveolar concentration at which 50% of patients will not show a motor response to noxious stimuli.
The greater the potency = lower MAC
What receptor is affected?
Alpha2 adrenergic receptor agonist
What are the risk factors for the inhaled anesthetics that can be described as a good analgesic with weak anesthetic properties (low potency) and the least hepatotoxic.
Nitrous Oxide
- risk of bone marrow depression with prolonged administration.
can slow O2 uptake during recovery, thus 20% of O2 is always needed
Ketamine MOA
NMDA receptors (decrease glutamate activity/ increase the effects of inhibitory neurotransmitters)
opioid agonists (mu, delta, and Kappa)
Monoamines (antimuscarinic, 5-HT, DA, NE reuptake inhibition, D2 agonist)
Ion channels (inhibits Ca2+)
What are the effects that propofol can have?
induction
Iv sedation and maintenance
non-hypnotic therapeutic applications
antiemetic, antipruritic, anticonvulsant, antioxidant, reduces bronchoconstriction
Characteristics of ideal inhalation anesthetics:
nonflammable, easily vaporized, potent, low solubility, minimal metabolism, provides skeletal muscle relaxation, provides bronchodilation, absence of toxicity, minimal CV effects
Why is there pain upon injecting Etomidate and how can we prevent it?
it is dissolved in propylene glycol and to prevent pain you could either inject into larger veins or pretreat with lidocaine injection
How does cardiac output correlate with anesthetic uptake?
increased cardiac output = greater uptake of anesthetic from the lungs and rapid delivery to the tissues = less anesthetic in the lungs = slowing induction d/t lower alveolar concentration on anesthetic
conversely
lower CO = slower uptake= raises alveolar pressure and speeds induction
What is the desired result?
- the desired result is short term sedation of critically ill patients.
- produces both sedation and analgesia
______ has a sweet odor while _______ has a pungent odor.
- lack
- sevoflurane
- desflurane
Clinical effects
Dissociative effect
causes the pt to appear conscious
pt is unable to process or respond to sensory input
What precautions must we take with propofol to prevent bacterial growth
discard open ampule after six hours
change IV tubing every 12 hours
use aseptic technique
What is the difference between a non volatile gas and a volatile gas? What are examples of each?
Volatile = the tendancy of a substance to vaporize from a liquid at a relatively low temperature
- halogenated hydrocarbons
non volatile = a substance that does not readily evaporate into a gas under existing conditions
- nitrous oxide
How does etomidate effect the CNS and respiratory system?
CNS- decreases CMRO2, CBF, ICP
- caution in seizure patients and focal epilepsy
Respiratory - minimal depression, decrease tidal volume and increase rate (3-5 minutes)
- induction dose DOES NOT result in apnea unless an opioid has been administered
What is the difference between MAC awake, MAC Amnesia, MAC BAR, and MAC endotracheal intubation.
MAC awake- concentration required to prevent eye opening on verbal command (50% MAC)
MAC Amnesia- concentration that blocks anterograde memory in 50% of awake patients (25% MAC)
MAC BAR- concentrations required to prevent adrenergic response to skin incision (Blockade of autonomic response)(150%MAC)
MAC ET intubation- concentrations required to prevent movement and coughing in response to endotracheal intubation (130% MAC)
What are the most common side effects? are we concerned with respiratory depression?
hypotension and bradycardia (d/t decreased catecholamine release)
nausea, dry mouth
- minimal respiratory depression so no
This medication is similar to halothane but is less toxic. There is some risk for ________ because of CNS excitation and the induction and recovery is faster than halothane because of less accumulation in the _______. It is metabolized to fluoride ion and excreted in the kidney.
Enflurane
- seizures
- fat
What are the different Clinical uses of ketamine?
- depression
- analgesia
- Neuraxial analgesia
- sedation
-reversal of opioid tolerance
- dissociative sedation for acute agitation
What cardiovascular and CNS effects does propofol have
CV: negative inotropic effect, myocardial depressant, decrease vascular resistance (everything dilates), decrease in BP d/t changes in SVR and CO, blunts effect of tracheal intubation, attenuates desuflurane - mediated sympathetic activation response
CNS: decrease CMRO2, CBF, ICP, EEG burst suppression (neuroprotective)
True or False:
equilibrium is achieved when the partial pressure of anesthetic gas is equal in the two tissues.
true
What are the clinical uses for Etomidate?
What is the dose?
ideal for induction on unstable cardiovascular patient
- dose= 0.2 - 0.4mg/kg
How does obesity effect induction and emergence time? Which drugs have lower fat tissue solubility?
obesity causes a longer time to reach equilibrium and prolongs emergence time because the high absorption and slow release of anesthetic agent from fat tissues.
- sevoflurane and desflurane
True or False:
Precedex is highly protein bound and metabolized primarily in the liver (CYP2A6)
True
Which inhaled anesthetic is not widely used due to its metabolism to tissue toxic hydrocarbons and bromide ion? It's a potent anesthetic but is usually co administered with another medication.
What Adverse effects should we look out for?
Halothane
- arrhythmias
- reduced myocardial contractility and causes hypotension
How does ketamine effect the cardiovascular system and the respiratory system?
CV: sympathomimetic (inhibits the reuptake of NE), Central stimulation of the sympathetic nervous system, increase in arterial pressure, HR, cardiac output
R: minimally affects respiratory drive, potent bronchodilator, increases salivation, intact upper airway reflexes.
Propofols affect in the respiratory tract
- propofol has significant pulmonary uptake
dose dependent respiratory depression, decreased ventilatory response
maintenance infusion will decrease tidal volume increase RR, cause bronchodilation in pt. w/ COPD and Asthma
What does it mean that the inhaled anesthetics have a narrow therapeutic index?
- there is not a big difference between the lethal dose and the therapeutic dose
index range is from 2-4
Etomidate and the endocrine system?
inhibition of enzymes that are involved in cortisol and aldosterone synthesis.
adrenocortical suppression (associated with long term administration)
What factors increase MAC
fever
CNS stimulants
decreasing age
chronic Alcoholism
What is the loading dose and infusion rate for this medication?
Loading dose: 1ug/kg over 10 minutes
infusion rate: 0.2-1.5 ug/kg/hr
This is a stable molecule with a pungent odor. This medication does not induce cardiac arrhythmias and does not sensitize the heart to catecholamines. What progressive side effects do we need to look out for?
Isoflurane
- progressive respiratory depression and hypotension
What is emergence delirium and how can it be prevented?
how long does it last?
It is visual, auditory illusions that are frequently vidid and contains morbid content which may progress to delirium.
-Usually stops within a few hours
- prevented with midazolam (versed)
Adverse reactions of propofol.
Allergic reactions (hx of anaphylaxis w/ NMBAs)
Lactic Acidosis (infusion longer than 24hrs)
unexpected tachycardia (send labs)
abuse potential (intense dreaming activity, amorous behavior and hallucinations)
painful injection (pretreat with lidocaine)
incompatible in Y site w/ other anesthetic agents
How can other agents have an additional effect on anesthetic properties?
MAC can be decreased by giving medications that are:
- opioid receptor agonists
- agonist activity of GABA
- reduce central catecholamines
What are the properties of Etomidate?
Side effects?
it is a sedative - hypnotic that lacks analgesic properties
SE: post op N/V and could cause involuntary myoclonus which can be blunted if pretreated with an opioid
Factors that decrease MAC
hypothermia
CNS depressant, acute alcohol ingestion
increasing age
severe hypercapnia (PaCO2 >90)
severe hypoxemia (PaO2 <40)
severe anemia (Hct<10%)
Which of the IV anesthetics is closest to being a "complete" anesthetic and why?
Ketamine because it induces analgesia, amnesia and unconsciousness
This ether was one of the first inhaled anesthetics but has been replace with less flammable alternatives.
Diethyl Ether
Contraindications and drug interactions
C: CAD, uncontrolled HTN, CHF, arterial aneurysm, trauma causing depletion of catecholamines (end stage shock) and intracranial lesions
DI: Succinylcholine, Theophylline, Diazepam, Lithium