medicine lecture 2 ga 20th novv 2012

7/28/2019 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


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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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.


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

medicine lecture 2 ga 20th novv 2012

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