5.6 General Anesthetics Flashcards
Anesthesia
partial or complete loss of all sensation w/ or w/o loss of consciousness
General anestesia
reversible loss of all sensation and consciousness
anestesia is a reversible condition of
comfort, quiescence and physiological stability in a patient before, during, and after performance of a procedure (usually surgical)
General anesthesia
for surgical procedure to render the pt unaware/unresponsive to the painful stimuli
GA is characterized by
loss of conciousness, analgesia, amnesia, skeletal muscle relaxation, inhibition of autonomic and sensory reflexes
analgesia
perception of pain eliminated
hypnosis
unconsciousness
essential components of GA
analgesia, hypnosis, depression of spinal motor refexes, muscle relaxation –> these terms together emphasize the role of insensibility and of immobility
Surgery before anesthesia
soprifics, Narcotics, marijuana, belladonna and jimson weed, induction of psychological state of anesthesia by mesmerism or hypnosis
Surgical stress
evokes HPA axis and sympathetic system
Tissue damage during surgery induces
coagulation factors and activates platelets leading to hypercoagulability of blood
Anesthesia decreases
the components of surgical stress response
hallmark of anesthesia
analgesia, amnesia, muscle relaxation
anestheisa is associated with
dec in systemic BP (due to myocardial depression and direct vasodialation), blunting of baroreceptor control and decreased central sympathetic tone, muscle relaxation (valuable during anesthesia –facilitates endotrachal intubation)
Pre-anesthetic medication
use of drugs prior to anesthesia to make it safer and more pleasant, aim is to relieve apprehension and facilitate smooth induction, to supplement analgesic, amnesic aciton of anesthetics, used of preanestetic can decrease requirment of general anesthetic
Preanestetics
benzos, antihitaminics, antiemetics, opiods, atropine
benzo
relive anxiety
antiheistameinics
prevent allergic reactiosn
antiemetics
prevent nausea and vomiting (antipeptic ulcer drugs can also be given)
opiods
provide analgesia
atropine/anticholinergics
prevent bradycardia and secretion
balanced anesthesia
no single drug achieves all of the desired goals of anesthesia, refers to a combination of drugs used to take advantage of individual drug properties while attempting to minimize their adverse effects, effects are additive, improves potency and provides rapid recovery
other drugs can be administered
pre, intra, or post operatively to achieve balanced anesthesia, to ensure smooth induction, analgesia, sedation, and smooth recovery. Cater to the individual drug need of the situation.
Stages of anesthesia
4
stage 1
analgesia
stage 2
excitement, combative behavir-dangerous state
stage 3
surgical anesthesia – further classified into 4 different substages
stage 4
medullary paralysis – respiratory and vasomotor control seases
General anesthetics unique drugs
not usually used for therapeutic or preventive, or diagnostic purposes
Molecular mechanisms of GA
Gaba-A rec Cl channes, glycine receptors
GabaA action of GA
facilitate Gaba mediated inhibition at Gaba-Arec sites
GabaA acting drugs
halothane, propofol, etomidate
glycine receptor action
activity increased, inhaled anesthetics
NMDA rec actions
inhibited by Ketamine, N2O
Mechanisms of Gas
depress synamptic transmission, potentiate, block cation channel, receoptor operated ion channels primary site of action
potentiation of gaba action
pzds, barbiturate, propofol
inhibit NMDA rec
Ketamine
induction
period of time from the onset of administration of the anesthetic to the development of effetive surgical anesthesia, induction of anesthetisa depends on how fast effective concentration of the anesthetic drugs reach the brain, maybe req for breif period then start maintanance drugs
maintainces
provides sustained surgical anesthesia, after pt is unconcious
recovery
time from discontinuation of administration of anesthesia until consciousness and protective physiologic reflexes are regained, recovery is the revers of induction and epends on how fast the anesthetic drug diffuses back from the brain, must restore muscle fn before removing endotrachal tube so ask pt to do things so you know pts voluntary muscls are functioning
two types of anesthetics
intravenous - for induction, inhalational - for mainenance
if procedure is short
induction drug can be used without a maintainance drug
intravenous inducing agents
thiopental, methohexital, propofol, etomidate, ketamine
ketamine
can be used for a brief surgical procedure
inhalational gas
nitrous oxide (N2O) – cant be used alone so use it with something – need to give O2 when you’re giving anesthesia!!
inhalational vaporized liquid
halothane, enflurane, isoflurane, desflurane, sevoflurane, ether
slower acting durgs as adjunct
benzos and opioids
benzo andjunct
diazepam, lorazepam, midazolam
opiods
fentanyl
IV anesthetics uased for
rapid induction of anesthesia, produce loss of conciousness in one arm-brain ciruculation time (10 to 20s), high lipophilicity, rapid onset of action, reduce the amount of inhalation anesthetic required for maintenance
recovery from IV anesthetics
maily by redistribution
Thiopental action
ultra short acting barb, having high libid solubility, also rapid recovery due to rapid redustribution
Thiopental time
produces unconsiousnes in approx 20 secons
Thiopental recovery
consciousness regained withing 10-20 min by redistribution to skeletal muslce/adipose
Thiopental effects
smooth, pleasant, rapid induction and minimal postoperative nausea and vomiting, eliminated slowly from the body and produce hangover (should not be left on his own –bc even after redistribution some amt of the drug enters the brain and dulls his mind)
thipental properties
not an analgesic and also a weak muscle relaxant, decreases cerebral blood flow, thus no increase in ICT–> can be used in head injury
thiopental adverse effects
laryngospasm can occur – atropine may be useful
Thipental and CVS
produces severe hypotension in hypovolemic pts, dose not sensitize the heart to catecholamines and hence arrhythmia is rare
Thiopental complication
can percipitate acute intermittent or veriegate porphyria insusceptible individuals –hence contraindicated
other uses of thipental
rapidly control the seizures since gaba facilitatory and also mimetic
Methoxital poency
3x more potent than thiopental, quicker and shorter action than thiopental, excitemtn and restlessness during indcution, pain on injection (like propofol)
most common IV anesthtic
Propofol
Propofol
most common IV anesthetic (milk of amnesia) , replaced thiopental as the first choice for anesthesia induction and sedation bc it procduces euphoric feeling (subjectivley “feel better”) in the pt and does not cause post anesthetic nausea and vomiting, dec intracranial pressure
propofol timeing
unconcsiousness in 45 s and lasts 15minutes
Propofol can cause
pain on injection, dose dependent dec in BP and resp depression, baradycardia, (frequent), excitatory effects (muscle twitiching, spontaneous movements, hiccups) noted in a few pts
Propofol benefits
is an antiemetic so no postoperative nasea and vomiting, used for sedation in intensive care untis, also suited for day care surgery bc residual imparmetn is less marked (not like thiopental with hangover effect)
Ethomidate
induction anesthetic, lacks analgesic effect, rapid onset and short duration of action (5-10 min) (briefer than thiopental
Ethomidate advantage
little CVS and resp depression, used for induction of anesthesia in pts with coronary artery disease or cardiovascular dysfn such as shock
what is more common with Ethomidate
restless rigidity
Why should repeated injections of Etomidate be avoided
it suppresses the production of steroids form th eadrenal gland
adverse effects of Etomidate
postoperative nasea and vomiting, also causes unpredictable and often sever myoclonus during induction
Ketamine
a short-acting, non barbituarate anesthetic
Ketamine induces
dissociative anesthsia by blocking NMDA receptors —an effect which pts feel dissociated form their surrouding; also produces analgesia and amnesia, with or without loss of consciousness
Inhalational anesthetics
are gases or vapors that diffuse rapidly across pulmonary alveoli and tissue barriers
advantages of Inhalational anesthetis
control the depth of anesthesia
Inhalational metabolism and excretion
metabolism is very minimal and is excreted by exhalation – what goes incomes out
Inhalation anesthetics
depth of anesthesia depends upon concnetration of anestehtics in the CNS
effectiv concentration of inhalation anesthetics
the rate at chich effective concentration achived in barin (induction) depends upon PK parameters of anesthetics, to achieve effective concentration in the CNS anesthetics requre to be transferred from alveoli to blood and from blood to brain
characteristics of inhalational anesthetics which goveren anesthesia are
solublility in the blood (blood;gaspartition) (soluble form does not produce anesthesia, gas from enters the brain, so lower the blood:gas, the more rapid is induction, sloubility in fat (oil:gas partition) (hihger solubility in fat high potency
solubiity in blood indicates
rapidity of onset
solubitiy in fate indicates
potency – MAC will be less –less amt of the drug will be responsible to mobility
blood gas coeff
measure of solubility in the blood, determins the rate of induction and reovery of ihalational anesthetics, lower the blood gas coeff, fater the induction and recovery–NO (.47—>but blood gas is low so faster but oil gas ratio is low so potency is very low, meaning lipid oil gas coeff is very low) –MAC is very high —only few molecules are required to raise its partial pressure in gth blood
higher blood gas coeff
higher the coeff, slower induction and recovery (Halothane) –more molecules soluble in blood, hence slowly raises its partial pressure tension and onset of action
NO produces
rapid action bic low blood gas coeff so rapid ly attains pp in gaseous form
halothane produces
slow action bc high blood gas coeff
rate of onset and recovery depend on
blood:gas ratio
the more soluble the anesthetic in the blood
the slower the anesthesia
high bood gas ratio
slow onset, slow recovery
low blood gas ratio
fast onset, fast recovery
higher oilgas coef
higer lipid solubility and potency will bi higher
higher the lipid solubility
higher the potnecy eg. Halothane
MAC
minium alveolar concentration (median alveolar concentration) –lowest conc of the anesthtic in pulmonary alveoli (% of the inspired air) needed to produce the immobility in response to painful stimuli (surgical) stimulus in 50% individuals –> ED50 for anesthetic agent
MAC is a valid measure of
potency of inhalational anesthetics
the more lipid soluble the anesthetic
the lower the MAC and greater the potency
MAC values are
additive (lower in the presence of opiods or sedative-hypnotics—so requirement of the inhalational anesthetic will be less) ; also are lower in elderly–so will also requrie less of the drug to produce anesthesia
concentration response curve
most inhalational anesthetics have a steep con-response curve.
increasing conc by 1/3 MAC
makes almost all individuals immobile and 2-4 MAC is often lethal, so its not good to go above the MAC value
relationship of oilgas and MAC
inverse
relationship of oilgas and potency
direct
relationship of MAC and potency
inverse
nonhalogenated gas
nitrous oxide
halogenated hydrocarbons
halothane, enflurane, isoflurane, desflurane, sevoflurane, methoxyflurane
what drug produces nephrotoxicity
methoxyflurane
what is the safest inhalational anesthetic
Nitrous oxide, no effect on respriation and heart, non toxic to liver, kidney and brain
Nitrous oxide metabolism
does not occur and quickly removed form the body by lungs. Used as a carrer and adjuvant to other anesthetics
NO mixture
70% N2O + 25-30% O2 + 0.2-2.0% another potent anesthetic _ employed for most surgical procedures
Nitrous oxide effeects
weak anesthetic (surgical anesthesia cannot be produced on its own), good analgesic, but poor muscle relaxant (often neuromuscular blockers are required)
NO and Second gas effect
N2O can concentrate the halogenated anesthetics in the alveoli when they are concoamitany adminstrered bc of its fast uptake from the alveolar gas, creating a vacuum space so the other drug is sucked in
NO and Diffusion hypoxia
when flow of N2O is turend off at the ned of anesthesia, then its concentration int eh alveoli will be lower than in the blood. Consequently N2O floods in from the blood and alveolar gas are diluted with N2o, making pt breathe hypoxic mixture. To overcome this 100% oxygen should be adminsitered to patent unto N2O is washed out.
NO can cause
pneumothroax and megaloblastic anemia
NO with O2
has been used for dental and obstetric analgesia
Halothane effects
potent anesthetic but weak analgesic, inductionis pleasant
Halothan is also
vagomimetic and can cause bradycardia, produces dose dependent hypotension (to counter excessive hypotension during halothane anesthesia, a direct acting vasoconstricor phenylephrine is given)
Halothane causes
direct depression of myocardial contractility by reducing intracellular Ca concentration, CO is reduced with deepening anesthesia, sensitizes heart to catecholamines
what drug is preferred in asthmatics
Halothane, dialates bronchus
halothane relaxes
skeltal and uterine musle and can be used in obstetrics when uterine relaxation is indicated
halothane adverse effects
Halothane Hepatitis, Malignant hyperthermia (with all halogenated hydrocarbon anesthetics and musle relaxants succinylcholine—withdraw anestheitc mixtuer and give dantrolene)
Halothane metabolism
metabolisme significantly (30%) to bromide, trifluoroacetate–responsible for rare heaptotoxicity
Enflurane difference from halothane
less potent than halothane, but produces rapid induction and recovery, does not sensitize the heart to catecholamines (less chance of arrhythmias), greater potentiation of muscle relaxant, due to a more potent “curare-like” effect
contraindications of enflurane
seizures (CNS excitation) occur at deeper levels so contraindicated in epileptics; caution in renal failure due to fluoride metabolite, pungent and may result in breath holding or couging and is less accepted by children
Isoflurane
produces more rapid induction and recovery than halothane, widely used, less likeley than halothane to sensitize the heart to catecholamines or cause arrhythmias, dialates coronary vasculature, increase coronary blood flow and increase oxygen supply to heart - hence beneficial in pts with IHD (ischemic heart disease) ( safe in myocardial ischemia)
Isoflurane effects
does not provoke seizures, hence preferred in neurosurgery, produces concentration dependent hypotension due to peripheral vasodialation, skeletal muscle relaxation is similar to enflurane, negligible metabolism hence less organ toxicity, postanesthetic nausea and vomiting is low
Desflurane
induction and recovery very very fast (faster than isoflurane) hence preferred for outpt surgical procedures, less potent than Isoflurane, delivered through special vaporizer (due to low volatility), short-lived postanesthetic cognitive and motor impairment, irritates the air passage (pungent) – coughing, laryngospasm, and excessive secretion
Desflurane similarites to isoflurane
degree of respiratory depression, musle relaxation, vasodialation and fall in BP, as well as maintained cardiac contractility and coronary circulation are like Isoflurane, lack of seizure provoking potential or arrhythmogenicity and absence of liver as well as kidney toxicity are similar to isoflurane
Sevoflurane
fast induction and recovery, absence of pungency and airway irritancy, makes it pleasant and acceptable in pediatric pts, causes bronchodialation, useful for pts with respiratory difficulties, metabolized by liver releaseing fluoride ions, thus like enflurane, raises concerns about nephrotoxicity, inaddition it is very unstable compound, degrades to a nephrotoxic compound
Neuroleptanalgesia/neuroleptanesthesia
characterized by analgesia, general quiexcnce, psychic indifference and intense analgesia without total unconsciousness, not commonly used, usually reserved where inhalational and or other parenteral anesthetics are relativley contraindicated
fentanyl (opiods)
short acting
droperidol
long acting neuroleptic
neuroleptanalgesia causes
drowsiness but respons to commands, respiratory depression and extra pyramidal s/s seen, used for endoscopies, angiographies and minor operations
Benzodizepiens as adjucnts
used for anxiolysis, amnesia, and sedation prior to induction of anesthesia, most frequenly used in perioperative period is midazolam (preferred), diazepam and lorazepam
Analgesics
analgesics are administered with general anesthetics to reduce anesthetic requirment and minimize hemodynamic chanes produced by painful stimulation, opiods are commonly used for these purposes,
major perenteral opiods given during perioperative period are
fentanyl (most common), sufentanil, alfentanil, remifentanil, meperidine and morphine
neuromuscular blocking agens
purpose is to relax muscles of the jaw, neck, and airway and thereby facilityate lanryngoscopy and endotrachal intubation, during the induction of anesthesia
exampls of neuromuscular blockers
pancuronium (non-depolarizing muslce relaxant), Succinylcholine (depolarizing muslce relaxant)
Properties of ideal gas for the pt
pleasant non irritating, non flammable, should not cause nasea/vomiting, induction and recovery should be fast with no after-effect
Properties of ideal gas for the surgeon
provide adequeate analgesia, immobility and muscle relaxation
Properties of ideal gas for the anesthetist
administration should be easy, controllable and veratile, should have wide margin of safety, should not affect ehart, liver, and other organs, rapid adjustment in depth should be possible, should be cheap, stable and easily stored, should not react with rubber tubing or soda lime
