General Anesthesia Flashcards
Anesthetics
- were introduces to American medicine 170 years ago; their importance is hard to over estimate
- are used very frequently (over 20 million times per year)
- are dangerous-very low therapeutic indices
General principles of surgical anesthesia
- minimize potentially deleterious direct and indirect effects of anesthetic agents and techniques
- sustain physiologic homeostasis during surgical procedures
- improves postoperative outcomes through dampening of the surgical stress response
Clinical definition of general anesthesia
- state of the patient in which no movement occurs in response to a painful stimuli; reversible
- patient is usually not conscious; unaware of sensory input
- what is conciousness
- studies of the effects of anesthetic could help answer this question
components of general anesthetic
-amnesia
-unconsciousness
analgesia
immobility
attenuation of autonomic responses
amnesia
absence of memory during anesthesia
unconsiousness
not always necessary
analgesia
inability to interpret, respond to and remember pain
immobility
in response to noxious (painful) stimuli
attenuation of autonomic responses
to noxious stimuli
Measurement of anesthetic property
- the dose of anesthetic that prevents movement in response to pain in 50% of patients
- the dose of gaseous anesthetic are directly related to concentrations at the alveolus
- gaseous anesthetic potency is quantified as the minimal alveolar concentration (MAC) that prevents movement in 50% of patients
advantages of MAC as a measure of anesthetic property
- can measure it (concentration of anesthetic in the end-tidal expired air)
- correlated well wth the concentration of drug at its site of action, the brain
- end-point ( lack of movement to pain) is easy to measure and define
- other “MAC” can be defined (MACawake)
Potency for intravenous anesthetics
-free plasma concentration that produces loss of response to a surgical incision in 50% of patients (EC50)
common effects shared by all general anesthetics
- hyperpolarize neurons
- particularly neurons that serve a pacemaker role
- reduced excitability results in reduced probabbility of action potential
- inhibit excitatory synaptic transmission and/or enhance inhibitory transmission
Targets of anesthetics
- GABA A receptors
- NMDA receptors
- other memebrane associated proteins are affected
GABA A receptors as a target for anesthetics
- GABA regulated Cl channel
- most anesthetics INCREASE GABA A opening via allosteric effects on the receptor protein
- increased Cl conductance results in hyperpolarization (membrane potential becomes more negative)
NMDA as a target for anesthetics
some anesthetics inhibit NMDA receptors
- results in reduced Na and Ca influx
- some hyperpolarization of membrane potential
Other membrane associated proteins are affected as targets of anesthetics
- anesthetics fill hydrophobi cavities in proteins
* can alter movement of proteins; alter transitions required for signaling and activation
3 stages of general anesthesia
- premedication
- induction
* want something that will not be frightening or painful
* parenterally (usually iv) anesthetic; only pain is establishing iv line
* only induce with inhalational anesthetic in emergency - maintenance
* gaseous anesthetics have short half lives; need to administer continually
tell me generally about parenterally administered anesthetics
- are all hydrophilic molecules
- administered as intravenous bolus (all at once)
- partition into the brain and spinal cord from the circulation during one pass; results in rapid induction of anesthesia
- redistribution back out of the brain as blood levels drop
describe the relationship with the duration and half life
-duration of action is shorter than half-life; multiple dosing is complex as storage depots come in and out of equilibrium with blood
Barbiturate drugs
-sodium thiopental
sodium thiopental
- barbituate
- activates GABA-A receptors
- used to induce anesthesia
- occurs 10-30 sec after intravenous injection
- duration of a single dose: 10 min at most
- half life in body: 12 hours (can produce hang over)
Traits about barbituates
- depressants are additive; reduce dose n combination with opiates, benzodiazepines, alpha 2 receptor agonists (all CNS depressants)
- intraarterial injection is contraindicated bc can lead to inflammation and necrosis
- can be given rectally to pediatric patients
Barbituates adverse effects
- CNS depression
- Cardiovascular
- respiratory depression
Barbituates and CNS depression
decreases oxygen demand, therefore, decreases blood flow and decreases intracranial pressure
barbituates and cardiovascular effects
- vasodilator-primarily venodilation
- can be a problem in patients with already reduced preload or cardiomyopathy; results in severe drop in BP
- since demand on the heart is reduced, barbituates are not contra indicated in patients with coronary artery disease; not arrythmogenic
Propofol
- most commonly used parenteral general anesthetic in US
- GABA A mechanism
- used to both induce and maintain anesthesia
- induction occurs 10-30 sec after intravenou sinjection
- duration of a single dose=10 min
- is antiemetic (an advantage since most patients are nauseated after surgery
- half-life in the body: 3.5 hours ( much less than barbiturates)
- this is an important advantage over thiopental; makes propofol very useful for out-patient surgery
unique adverse effects to Propofol
- elicits pain on injection; often given with lidocaine or into a large veins
- can cause initial excitation on induction
CNS effects of propofol
- about the same as thiopental
- has demonstrated abuse liability
Cardiovascular side effect propofol
- more severe reduction in BP than thiopental
- vasodilation
- AND depression of myocardial contractility
- blunts baroreflexes (therefore, these changes are not opposed by vasoconstriction, HR increase)
- therefore: used with caution in patients with intolerance to decreased blood ressure
- respiratory : more depression than thiopental at equianesthetic dose
Etomidate
- used to induce anesthesia in patients at risk for hypotension
- etomidate produces little or no effect on blood pressure; only a small increase in heart rate
- it is safer than propofol or thiopental in patients with hypotension or compromised baroreceptor function
adverse effects to etomidate
- high incidence of pain on injection, myoclonus (use lidocaine for pain and pretreat with benzodiazepines or opiates for the second)
- significant problems with nausea and vomiting
- suppression of the adrenocortical response to stress; can result in mortality
- worse during prolonged administration
- therefore, only used to induce anesthesia in patients with hemodynamic problems
CNS adverse events for etomidate
- same as thiopental
- decreases oxygen demand, therefore, decreases blood flow and decreases intracranial pressure
CV effects of etomidate
-MUCH less than thiopental
respiratory effect etomidate
less than thiopental
Ketamine
- produces “dissociative anesthesia”
- eyes open but patients are unresponsive to commands
- profound analgesia
- amnesia
- does not affect respiration, is a bronchodilator
- NMDA antagonist
- can be used via multiple routes: iv, im, oral, rectal
- these properties (primarly the analgesia; lack of effect on respiration and ability to use im) make it a useful agent
adverse efect for ketamine
- nystagmus, salivation, lacrimation, increased muscle tone and spontaneous movement
- increased intracranial pressure due to increase cerebellar blood flow
- emergence delirium (hallucinations, vivid dreams) not as bad in children as in adults
- PCP is ketamine like
- hypertension due to indirect sympathomimetic effect
usefulness of ketamine
- patients with bronchospasm (cannot be intubated)
- ketamine is a bronchodilator due to indirect sympathomimetic effects
- children undergoing short, painful procedures
Midazolam
- short acting benzodiazepine
- GABA A activator
- used for conscious sedation, anxiolysis, amnesia during short procedures
- can also be used as an induction agent
- adjunct during local anesthesia (eg during tooth extraction)
- useful as a pre-operative medication decreases anxiety
tell me about the induction time and duration for midazolam
- slower induction time and longer duration of action than thiopental
- metabolized by hydroxylation to an active metabolite
adverse effect midazolam
- can cause respiratory depression and respiratory arrest (especially when used intravenously)
- used with caution in patients with neuromuscular disease; Parkinson’s disease; bipolar disorder
- cardiovascular effects are similar to thiopental (depression in BP)
- adverse effects reversed by flumazenil
Flumazenil
can cause adverse effects
thiopental usefulness and problems
- U: induction for in patient surgery
- P: hypotension hang over
propofol u&p
U- induction/maintenance especially for out patient
P- hypotension and respiratory depression
Etomidate u&p
u-induction in patients at risk for hypotension
p-nausea/vomiting and adrenocortical suppression
Ketamine u&p
u- bronchospasm and peds short painful procedures
p- increased intracranial pressure, delirium
midazolam u&p
- u- conscous sedation; anti-anxiety
- p- slow induction and respiratory depression
commonalities among inhalation general anesthetics
- very low therapeutic indices; LD50/ED50 can be as low as 2-4
- pharmacokinetics are unique and important: gaseous or readily vaporized at room temperature
Pharmacokinetics of gaseous anesthetics
- for a gas, equilibrium between compartments is reached with the partial pressures (not concentrations) are the same
- what matters to us are the partition coefficients of the gas at each of these compartment barriers
partition coefficients
- determine the relative amounts of anesthetic in two compartments
- blood: gas
- brain: blood
- fat: blood
Blood: gas partition coefficient
-partition coefficient determines the ease of absorption at the alveoli
brain: blood
partition coefficient determines the anesthetic movement into the brain
fat: blood
partition coefficient determines the redistribution to fat
if the anesthetic had low blood: gas PC
- needs high amounts in inspired air (bc it doesn’t want to go into the blood but you need to make it)
- induction is quick ( bc equilibrium is reached quickly)
- recovery will be quick ( drug will move readily out of the blood into gas)
if anesthetic has a high Blood: gas partition coefficient
- need less in inspired air
- induction and recovery are slow (equilibria are reached slowly
if anesthetic has high fat: blood PC
-half life will be long (hang over) due to slow release into the blood, enough gets into the brain to make the patient feel sleep
anesthesia occurs in the brain
-anesthesia is achieved when the brain partial pressure is equal to MAC
-anesthetics are all lipophillic and brain is highly perfused, so the brain gets a large share of the anesthetics in the circultion
-thus amnesia is achieved shortly after MAC is reached in the
alveolae
define steady stae (equilibrium)
- no net movement of gas at this stage
- quick for gases with low blood: gas PC
- slow for gases with high fat: blood PC
- in clinical practice, instruments administering anesthetic measure the concentration of the anesthetic in expired air; end tidal concentration is an estimate of alveolar concentration
elimination of drugs
- reverse of induction; gas moves from the blood into the inspired air (which is now free of gas)
- rate of elimination is dependent upon the blood: gas partition coefficient
- lowest will be eliminated the fastest
- but the gas needs to get into the blood to be eliminated
- blood: fat PC of anesthetci determines half life
recovery of anesthesia
- agents that have a low solubility in blood and fat have rapid recovery
- agents with high solubility in blood and fat, have slower recovery and the duration of the recovery will depend upon the length of time that the anesthetic was administered
Malignant hypethermia
- serious adverse effect of gaseous anesthetic exposure; rare but potentially fatal
- heritable pockets of individuals in Wisconsin
- skeletal muscle disorder, triggered by anesthetic
- consists of muscle rigidity, hyperthermia, rapid onset of tachycardia and hyercapnia, hyperkalemia, metabolic acidosis
Isoflurane
- moderate blood: gas PC
- moderate rates of induction and recovery
- excreted unchanged in expired air
clinical uses of isoflurane
- commonly used inhalational anesthetic in US and (especially) worldwide
- can be used to induce and maintain anesthesia; but is mostly used for maintenance
- often used with nitrous oxide to reduce amount needed
adverse effects of isoflurane- respiratory
- respiratory
- airway irritant
- coughing
- decreases tidal volume and increases respiratory rate
- all anesthetics depress respiration (via effects in the CNS) and increase pCO2
adverse effects isoflurane-cardiovascular
- myocardial depression; results in decrease in BP
- arrythmias (sensitization of the heart to catecholamines)
- cerebral vessel vasodilation, can result in increase intracranial pressure
Desflurane-pharmacokinetics
- volatile liquid at room temperature
- very low solubility in blood * very low blood: gas partition coefficient) therefore induction an recovery are rapid
- excreted unchained in expired air
clinical uses of deflurane
- outpatient surgeries/maintenance
- not used to induce because of respiratory irritation
- skeletal relaxation is a good thing
side effects of desflurane relative to isoflurane
- cardiovascular-similar
- respiratory: worse irritant, can produce bronchospasm
sevflurane-pharmacokinetics
- very low blood: gas partition coefficient
- about 5% of the administered dose is metabolized to fluoride ion in the liver
- there is some concern that this can cause renal damage
- is degraded to “compound A” by absorbants in the anesthesia administration apparatus
- compound A is nephrotoxic in rats
Sevoflurane clinical use
- very popular
- inpatient and outpatient
- can but used to induce and maintain
- children and adults
- not a respiratory irritant
side effects of sevoflurane
-similar to isoflurane
however not as much respiratory depression
Nitrous oxide
- a gas at atmospheric, not a volatile liquid
- pharmacokinetics
- very insoluble in blood; therefore rapidly equilibrates
- uptake from air results in increased concentration of other anesthetics
- so it is useful as an agent to enhance induction with isoflurane for example
- during emergence can dilute oxygen so patients need to breath 100% oxgen
- 99%excretion unchaged via lungs
clinical uses nitrous oxide
- weak anesthetic, cannot get enough into the air to produce MAC
- good for sedation and analgesia at 50% concentration in inspired air
- used together with other inhaled anesthetics to reduce dose needed
nitrous oxide adverse effects
- contraindicated in pneumothorax
- negative inotrope but also sympathomimetic, cardiac output is preserved
- respiratory effects are minimal, except for oxygen dilution issue
- has abuse liability
- prolonged exposure reduces methionine synthase activity, could cause megaloblastic anemia
Isoflurane u&P
u- induction and maintenance inpatient
p- slowerl airway irritant
desflurane u&p
- u- outpatient maintenance only
- p- coughing bronchospasm
sevoflurane
-u-all types induction and maintenance
p- oxygen dilution, abuse
nitrous oxide
u-dentistry, adjunct
p-oxygen dilution, abuse
