medicine lecture 2 ga 20th novv 2012
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LECTURE 2,
GENERAL ANAESTHETICS
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Intravenous agents
Ketamine
Propofol
Thiopental Etomidate
midazolam
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Intravenous anaesthetics
Intravenous anaesthetics may be used either
to induce anaesthesia or for maintenance of
anaesthesia throughout surgery.
Intravenous anaesthetics nearly all produce
their effect in one arm-brain circulation time
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They are contraindicated if the anaesthetist is
not confident of being able to maintain the
airway (e.g. in the presence of a tumor in the
pharynx or larynx)
Extreme care is required in surgery of the
mouth, pharynx, or larynx and in patients with
acute circulatory failure (shock) or fixedcardiac output.
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To facilitate tracheal intubation, induction is
usually followed by a neuromuscular blocking
drug or short-acting opioid.
The dose of all intravenous anesthetic drugs
should be titrated to effect
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The dose and rate of administration should be
reduced in the
Elderly
Those with hypovolaemia
In cardiovascular disease
Premedicated patients
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PHARMACOLOGICAL EFFECTS
3 main neurophysiologic process takes place
Unconsciousness
Loss of response to pain stimuli
Loss of reflexes(both motor and autonomic)
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At supra anaesthetic doses all can cause death
by loss of cardiovascular reflexes and
respiratory paralysis
At cellular level these agents affect synaptic
transmission and neuronal excitability
Main targets of action of these agents are the
cortex,thalamus,hippocampus,midbrain and
spinal cord
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All agents have similar neurophysiologic
profiles but differ in pharmacokinetics and
toxicology
Most cause cardiovascular depression by
effects on myocardium and blood vessels
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Total intravenous anesthesia
This is a technique in which major surgery is
carried out with all drugs given intravenously.
Respiration can be spontaneous, or controlled
with oxygen-enriched air.
Neuromuscular blocking drugs can be used to
provide relaxation and prevent reflex muscle
movements
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The main problem to be overcome is the
assessment of depth of anesthesia.
Target Control Infusion (TCI) systems can be
used to titrate intravenous anaesthetic
infusions to predicted plasma-drug
concentrations in ventilated adult patients.
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Drugs used
for
intravenous
anesthesia
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Propofol
Is a 2,6 diisopropylphenol
Most popular GA
It the agent of choice in ambulatory surgery Rate of onset is similar to barbiturates but
recovery is rapid
Postoperatively patients feel better because ofreduction of nausea and vomiting
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Propofol
the most widely used intravenous anesthetic
It was introduced in 1983
can be used for induction or maintenance ofanesthesia in adults and children, but it is not
recommended in neonates.
Propofol is associated with rapid recovery and
less hangover effect than other intravenous
anaesthetics
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Propofol has a rapid onset(30 seconds)
Metabolism in the liver Excretion in the urine as glucoronide and
sulfate conjugates
Rapid metabolism, with a half life of 2-4mins
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Cardiovascular effects may cause bradycardia
and hypotension
Is good for day care surgery, has quick
recovery
Has less nausea and vomitting as compared to
inhaled agents
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It causes pain on intravenous injection, which
can be reduced by intravenous lidocaine.
Significant extraneous muscle movements
may occur.
Rarely, convulsions, anaphylaxis, and delayed
recovery from anesthesia can occur after
Propofol administration
the onset of convulsions can be delayed
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Propofol is associated with bradycardia
Intravenous administration of an
antimuscarinic drug is used to treat this.
In adults, Propofol can be used for sedation
during diagnostic procedures or in intensive
care.
It can induce Propofol infusion syndrome
when administered at high doses for
prolonged periods of time
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It is contraindicated in children under 17 years
receiving intensive care because of the risk of
potentially fatal effects including
metabolic acidosis
cardiac failure
rhabdomyolysis,
hyperlipidaemia,
hepatomegaly
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Breast-feeding: present in milk but amount
probably too small to be harmful
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Side-effects
hypotension
tachycardia,
flushing; transient apnea,
hyperventilation
coughing,
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SIDE EFFECTS..
hiccup during induction
headache
less commonly thrombosis phlebitis
rarely arrhythmia
headache vertigo, shivering
euphoria;
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very rarely pancreatitis,
pulmonary edema
sexual disinhibition, discoloration of urine
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serious and sometimes fatal side-
effects
reported with prolonged infusion of doses
exceeding 5 mg/kg/hour
metabolic acidosis,
rhabdomyolysis
hyperkalaemia,
cardiac failure dystonia
dyskinesia
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DOSE
Dose
Induction of anaesthesia using 0.5% or 1%
injection, by intravenous injection or infusion,
ADULT under 55 years, 1.5-2.5 mg/kg at rate
of 20-40 mg every 10 seconds until response;
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Thiopental sodium (thiopentone
sodium
is a barbiturate that is used for induction of
anesthesia
Has high lipid solubility and this accounts for
high speed of onset
Has short duration,(5mins) due to
redistribution
Reduces intracranial pressure
Narrow margin between anaesthetic dose and
cardiovascular depression
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has no analgesic properties.
Induction is generally smooth and rapid, but
dose-related cardiovascular and respiratory
depression can occur.
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Awakening from a moderate dose of
thiopental is rapid because the drug
redistributes into other tissues, particularly
fat.
However, metabolism is slow and sedative
effects can persist for 24 hours
Repeated doses have a cumulative effect and
recovery is much slower.
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Thiopental is not used for maintenance but
only for induction
accidental injection into the area around the
vein or artery causes pain, local tissue necrosis
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INDICATIONS
induction of general anesthesia
anesthesia of short duration;
reduction of raised intracranial pressure ifventilation controlled
status epilepticus
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Dose
Induction of general anaesthesia,
by slow intravenous injection usually as a
2.5% (25 mg/mL) solution,
ADULT over 18 years, fit and premedicated,
initially 100 150 mg (reduced in elderly or
debilitated) over 10 15 seconds (longer in
elderly or debilitated), followed by further
quantity if necessary according to response
after 30 60 seconds; or up to 4 mg/kg (max
500 mg
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CHILD 1 month 18 years
initially up to 4 mg/kg, then 1 mg/kg
repeated as necessary (max total dose 7
mg/kg)
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Raised intracranial pressure, by slow
intravenous injection, 1.5-3 mg/kg repeated
as required.
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Status epilepticus (only if other measures
fail), by slow intravenous injection as a 2.5%
(25 mg/mL) solution,
ADULT over 18 years, 75 125 mg as a single
dose
CHILD 1 month 18 years, initially up to 4
mg/kg by slow intravenous injection, then up
to 8 mg/kg/hour by continuous intravenous
infusion, adjusted according to response.
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Etomidate
is an intravenous agent associated with rapidrecovery without hangover effect.
It causes less hypotension than thiopental and
Propofol during induction. Etomidate produces a high incidence of
extraneous muscle movement, which can beminimized by an opioid analgesic or a short-
acting benzodiazepine given just before induction A wide margin of safety between anesthetic dose
and dose that can cause cvs depression
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Pain on injection can be reduced by injecting
into a larger vein or by giving an opioid
analgesic just before induction.
Etomidate suppresses adrenocortical
function, particularly during continuous
administration, and it should not be used for
maintenance of anesthesia.
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More rapidly metabolized than thiopental
Causes less hypotension than Propofol and
thiopental
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Indications: induction of anaesthesia
Cautions: avoid in acute porphyria
Hepatic impairment: reduce dose in liver
cirrhosis Pregnancy: depresses neonatal respiration if
used during delivery
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Breastfeeding: avoid for 24 hours after
administration
Side-effects: coughing, hiccups, shivering,
allergic reaction (including Bronchospasm and
anaphylaxis); respiratory depression,
arrhythmia, and convulsions .
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Ketamine
Is an analogue of phencyclidine
Action is mainly through inhibition of NMDA-
type glutamate receptors
Onset is slower (1-2 mins)
Is a powerful analgesic
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Ketamine
It has good analgesic properties and sub-
anaesthetic dosage and is used under
specialist supervision in palliative care for pain
that is unresponsive to standard treatment
i.v dosing gives effect in 1-2mins
Produces dissociative anaesthesia-which
means marked sensory loss,amnesia,analgesia without loss of
consciousness
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Ketamine increases both blood pressure and
heart rate
Respiratory effects are not manifest at
therapeutic doses
Makes it safe
However it causes raise in intracranial
pressure so should be avoided in patient at
risk
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Ketamine causes less hypotension than
thiopental and Propofol during induction.
It is used mainly for paediatric anaesthesia,
particularly when repeated administration is
required (such as for serial burns dressings)
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recovery is relatively slow and there is a high
incidence of extraneous muscle movements
The main disadvantage of Ketamine is the
high incidence of hallucinations, nightmares,
and other transient psychotic effects
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Are reduced by a benzodiazepine such as
diazepam or midazolam.
Ketamine also has abuse potential and can
itself cause dependence.
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midazolam
Is a benzodiazepine
Is slower in onset as compared to others
Causes less respiratory and CVS depression
Used as a preoperative sedative
Used in procedures like endoscopy where full
anesthesia is not required Overdose can be reversed by flumazenil
P ti f i t
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Properties of intravenous
anesthetic agentsDrug Speed of induction and
recovery
Main unwanted effect(s) Notes
Propofol Fast onset, very fast recovery Cardiovascular and
respiratory depression
Rapidly metabolised
Possible to use as continous
infusion
Causes pain at injection site
Thiopental Fast (accumulation occurs,giving slow recovery)
Hangover
Cardiovascular andrespiratory depression
Largely replaced by propofolCauses pain at injection site
Risk of precipitating porphyria in
susceptible patients
Etomidate Fast onset, fairly last recovery Excitatory effects during
induction and recovery
Adrenocortical suppression
Less cardiovascular and
respiratory depression than with
thiopental
Causes pain at injection site
Ketamine Slow onset, after effects
common during recovery
Psychotomimetic effects
following recovery
Postoperative nausea,
vomiting and salivation
Raised intracranial pressure
Produces good analgesia and
amnesia
Midazolam Slower than other agents Little respiratory or
cardiovascular depression
I h l i l h i
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Inhalational anaesthetics
Inhalational anaesthetics may be gases or
volatile liquids
Gaseous anaesthetics require suitable
equipment for storage and administration.
They may be supplied via hospital pipelines or
from metal cylinders.
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Volatile liquid anaesthetics are administeredusing calibrated vasoprisers, using air, oxygen, ornitrous oxide oxygen mixtures as the carriergas.
To prevent hypoxia, the inspired gas mixtureshould contain a minimum of 25% oxygen at alltimes
Higher concentrations of oxygen (greater than
30%) are usually required during inhalationalanesthesia when nitrous oxide is beingadministered.
V l il li id h i
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Volatile liquid anaesthetics
Volatile liquid anaesthetics can be used for
induction and maintenance of anaesthesia,
and following an induction with an
intravenous anaesthetic.
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Volatile liquid anaesthetics can trigger
malignant hyperthermia and are
contraindicated in those susceptible to
malignant hyperthermia.
They can increase cerebrospinal pressure and
should be used with caution in those with
raised intracranial pressure
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They may also cause hepatotoxicity in those
sensitized to halogenated anaesthetics
halothane has been associated with severe
hepatotoxicity
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Isoflurane
is a volatile liquid anesthetic.
Heart rhythm is generally stable during
isoflurane anesthesia, but heart-rate can rise,
particularly in younger patients
May cause hypotension and is a coronary
vasodilator
May exacerbate cardiac ischemia in patient
with coronary disease
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systemic arterial pressure can fall and cardiac
output can decrease owing to a decrease in
vascular resistance.
Muscle relaxation occurs and the effects of
muscle relaxant drugs are potentiated.
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Isoflurane can irritate mucus membranes
causing cough, breath-holding, and
larynospasm.
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ISOFLURANE
Dose: Induction of anaesthesia, using specifically
calibrated vaporizer, in oxygen or nitrous oxide-
oxygen, increased gradually from 0.5 3% Maintenance of anaesthesia, using specifically
calibrated vaporizer, 1 2.5% in nitrous oxide
oxygen; an additional 0.5 1 % may be requiredwhen given with oxygen alone; caesarean
section, 0.5 0.75% in nitrous oxide-oxygen.
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ISOFLURANE
Pregnancy: depresses neonatal respiration if
used during delivery
Breastfeeding: manufacturer advises avoid
withhold for at least 12 hours after
termination of anaesthesia.
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ISOFLURANE
Pregnancy: depresses neonatal respiration if
used during delivery.
Side-effects
urinary retention, leucopenia, agitation in
children; dystonia, rash and seizures also
reported.
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Desflurane
is a rapid acting volatile liquid anesthetic
Is similar to isoflurane but faster onset and
recovery
Has about one-fifth the potency of
isoflurane.
Emergence and recovery from anaesthesia
are particularly rapid because of its low
solubility.
Useful in day care surgery
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Desflurane is not recommended for induction
of anaesthesia as it is irritant to the upper
respiratory tract; cough, breath-holding,
apnoea, laryngospasm, and increasedsecretions can occur.
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Sevoflurane
is a rapid acting volatile liquid anesthetic and
is more potent than desflurane.
Emergence and recovery are particularly
rapid, but slower than desflurane.
Sevoflurane is non-irritant and is therefore
often used for inhalational induction of
anesthesia
it has little effect on heart rhythm compared
with other volatile liquid anaesthetics
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Sevoflurane can interact with carbondioxde
absorbents to form compound A, a potentially
nephrotoxic vinyl ether.
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Halothane
is a volatile liquid anesthetic that has largelybeen superseded by newer agents
it is occasionally used for inhalation
induction of anaesthesia with carefulmonitoring for cardio respiratory depressionand arrhythmias.
It is potent, induction is smooth, and thevapor is non-irritant and seldom inducescoughing or breath holding.
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Halothane hepatotoxicity
Severe hepatotoxicity can follow halothane
anesthesia.
It occurs more frequently after repeated
exposure to halothane and has a high
mortality.
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The risk of severe hepatotoxicity appears to be
increased by repeated exposures within a
short time interval, but even after a long
interval (sometimes of several years),susceptible patients have been reported to
develop jaundice.
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Since there is no reliable way of identifying
susceptible patients, the following precautions
are recommended before the use of
halothane A careful anaesthetic history should be taken
to determine previous exposure and previous
reactions to halothane
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Repeated exposure to halothane within a
period of at least 3 months should be avoided
unless there are overriding clinical
circumstances A history of unexplained jaundice or pyrexia in
a patient following exposure to halothane is
an absolute contraindication to its future usein that patient.
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Pregnancy: depresses neonatal respiration if
used during delivery.
Breastfeeding: present in milk withhold for
24 hours after termination of anaethesia
Halothane relaxes the uterus and may give
rise to postpartum bleeding limiting use in
obstetrics
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Dose: Induction of anesthesia, using specificallycalibrated vaporizer, in oxygen or nitrous oxide-oxygen,
ADULT and CHILD over 1 month, initially 0.5%then increased gradually according to response to2-4%
Maintenance of anesthesia, using specifically
calibrated vaporizer, in oxygen, oxygen-air, ornitrous oxide-oxygen, ADULT and CHILD over 1month, 0.5 2%
Nitrous Oxide
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Nitrous Oxide
Nitrous oxide is used for maintenance of
anesthesia and, in sub-anaesthetic
concentrations, for analgesia.
For anesthesia, nitrous oxide is commonlyused in a concentration of 50 to 66% of
oxygen as part of a balanced technique in
association with other inhalational orintravenous agents
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Nitrous oxide is unsatisfactory as a sole
anaesthetic owing to lack of potency, but is
useful as part of a combination of drugs since
it allows a significant reduction in dosage. Has rapid onset of action and an effective
analgesic
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Nitrous oxide may have deleterious effect if
used in patients with an air-containing closed
space since nitrous oxide diffuses into such a
space with a resulting increase in pressure. This effect may be dangerous in the presence
of a pneumothorax, which may enlarge to
compromise respiration, or in the presence ofintracranial air after head injury.
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Hypoxia can occur immediately following the
administration of nitrous oxide;
additional oxygen should always be given for
several minutes after stopping the flow ofnitrous oxide.
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Exposure of patients to nitrous oxide for
prolonged periods, either by continuous or by
intermittent administration, may result in
megaloblastic anemia It interferences with the action of vitamin B12
neurological toxic effects can occur without
preceding overt hematological changes.
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Exposure of theatre staff to nitrous oxide
should be minimized.
Depression of white cell formation may also
occur
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Assessment of plasma-vitamin B12
concentration should be considered in those
at risk of deficiency,
Nitrous oxide should not be givencontinuously for longer than 24 hours or more
frequently than every 4 days without close
supervision and hematological monitoring.
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For analgesia (without loss of consciousness),
a mixture of nitrous oxide and oxygen
containing 50% of each gas is used.
Self-administration using a demand valve ispopular in obstetric practice, for changing
painful dressings, as an aid to postoperative
physiotherapy, and in emergency ambulances.
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Contraindications: susceptibility to malignanthyperthermia.
Pregnancy: depresses neonatal respiration if
used during delivery. Dose: Maintenance of light anesthesia (using
suitable anesthetic apparatus), up to 66% inoxygen.
Analgesia, up to 50% in oxygen, according tothe patients needs.
fl
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enflurane
Is halogenated anesthetic like halothane
Has moderate speed of action
Is less metabolized ,less risk of toxicity
Has faster recovery than halothane
Can cause seizures
Is not used nowadays
h
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ether
Obsolete
Is easy to administer and control
Has slow onset and recovery
Causes vomiting and nausea
Highly explosive and irritant
Characteristics of inhalation anesthetics
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Drug Blood:
Gas
Oil: Gas Minimum
alveolar
concentration
Induction/
recovery
Main adverse effects and
disadvantages
Notes
Nitrous oxide 0.5 1.4 Fast Few adverse effects, risk of anaemia(with prolonged or repeated use),
accumulation in gaseous activities
Good analgesic effect,low potency precludes
use as sole anesthetic
agent normally
combined with other
inhalation agents
Isoflurane 1.4 91 1.2 Medium Few adverse effects, possible risk of
coronary ischemia in susceptible
patients
Widely used, has
replaced halothane
Desflurane 0.4 23 6.1 Fast Respiratory tract irritation, cough,
bronchospasm
Used for day-case
surgery because of fast
onset and recovery
(comparable with
nitrous oxide)
Sevoflurane 0.6 53 2.1 Fast Few reported, theoretical risk of
toxicity owing to flouride
Similar to desflurane
Halothane 2.4 220 0.8 Medium Hypotension, cardiac arrhythmias,
hepatotoxicity (with repeated use),
malignant hyperthermia (rare)
Little used nowadays,
significant metabolism
to trifluoracetate
Enflurane 1.9 98 0.7 Medium Risk and convulsions (slight),
malignant hyperthermia (rare)
Has declined in use,
May induce seizures
top related