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Intravenous anesthetics
Toxicity of General Anesthesia
Hepatotoxicity:
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Hepatotoxicity is rarely seen after Anesthesia and
hepatic dysfunction mainly result from factors such as
blood transfusion, hypovolemic shock, and other
surgical stress.
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The mechanism underlying hepatoxicity from
Halothane remain unclear, but studies with animals
have implicated the formation of radioactive
metabolites that either cause direct hepatocellular
damage or initiate immune mediated responses.
Nephrotoxicity:
 The nephrotoxic potential of methoxyflurane has
limited its clinical use in anesthesia, renal dysfunction
following methoxyflurane is caused by inorganic
fluoride released during the extensive metabolism of
the anesthetic by hepatic and renal enzymes.
 Metabolism of enflurane and sevoflurane also leads to
the formation of fluride ions. Studies have showed
that enflurane causes Nephrotoxicity but not
sevoflurane.
Chronic toxicity:
 Mutagenicity:
Under normal conditions, most
modern and many older inhaled anesthetics are not
mutagens and probably not carcinogens. However,
older anesthetics that contain the vinyl moiety may be
mutagens. These agents are rarely used or never used.
 Carcinogenicity: Anesthetic agents may cause
Carcinogenicity to operating room personnel who have
been exposed to trace level of it. Such theory have not
been proved at 100%.
 Effects
of reproduction: The probability of
miscarriage amongst pregnant women increases more
than expected level.
 Hematotoxicity: Prolonged exposure to nitrous oxide
decreases methionine synthesis activity and may cause
megaloblastic anemia.
CLINICAL USE OF INHALED
ANESTHETICS
 Inhaled anesthetics are rarely used alone. They are usually
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combined with intravenous agents, the combination with
intravenous agents, the combination called “balanced
anesthesia”.
Nitrous oxide, Desflurane, Sevoflurane and isoflurane are
the most commonly used in the USA.
Halothane is still used in pediatric anesthesia, although
sevoflurane is replacing halothane.
Methoxyflurane is occassionaly used mainly in case of
obstetric anesthesia- but not for prolonged procedure for
Nephrotoxicity.
Chloroform is not used for its Hepatotoxicity.
Cyclopropane and diethyl ether are no longer used because
of their flammable and explosive characteristics.
Difference between Intravenous
anesthetics and Inhaled anesthetics
Intravenous Anesthetics
Inhaled Anesthetics
Specialized Equipments are not necessary for their
delivery or expensive facilities for the recovery and
disposal of exhaled gas.
Special Equipments are necessary for their delivery or
expensive facilities required for the recovery and
disposal of exhaled gas.
Onset of action for drugs such as Propofol, thiopental
is faster than newest inhaled drugs such as desflurane
and sevoflurane.
Rate of recovery is faster.
Most of the Inhaled Anesthetics has a onset of action
slower than the Intravenous anesthetics.
Extensive use in the outpatients.
Less use in outpatient.
Can be used solely to conduct anesthesia in short
surgical procedure. E.g., Thiopental, Propofol,
Ketamine.
Cannot be used solely.
Intravenous Opioids contribute cardiovascular
stability, sedation and marked analgesia to anesthesia
protocols and Opioid receptor antagonist can be used
to hasten their actions.
Have to be used in combination. Special procedures
required for their reversal.
Rate of recovery is slower.
ULTRA SHORT ACTION
BARBITURATES (THIOPENTAL)
 Thiopental is the most commonly used anesthetics for
the induction of anesthesia, often used in combination
with inhaled anesthetics.
 Following intravenous administration, thiopental
rapidly crosses blood brain barrier and if given
sufficient dosage, produces hypnosis in one circulation
time.
 Similar drugs such as thiamylal and methohexital,
causes plasma brain equilibrium occurs rapidly( within
1 min) because of high lipid solubility.
 Metabolism of thiopental is much slower than its
redistribution and takes place primarily in the liver.
Less than 1% of an administered dose of thiopental is
excreted unchanged by the kidney. Thiopental is
metabolized at a rate of 15-16% per hour in human
following a single dose.
 With large dosage thiopental causes dose dependent
decreases in arterial blood pressure, stroke volume and
cardiac output, this is due to its myocardial depressant
effect and increased venous capacitance.
 Cerebral metabolism and oxygen utilization are
decreased after thiopental administration in
proportion to the degree of cerebral depression.
 Thiopental may also reduce hepatic blood flow and
glomerular filtration rate. Thiopental has participated
porphyric crisis when used as a induction agent.
OPIOID ANALGESIS
 Intravenous Morphine 1-3 mg/kg, or high potency
Opioid fentanyl, 50-100µg/kg have been used.
 Intravenous may increase chest wall rigidity, which
may impair ventilation and post operative respiratory
depression may occur requiring assisted ventilation
and administration of Opioid antagonistic (e.g.,
Naloxane).
PROPOFOL
 Propofol or disprofol is an extremely important
intravenous anesthetic. It produces anesthesia at a rate
similar to that of intravenous barbiturates and
recovery is more rapid. In particular patients are able
to ambulate sooner after Propofol.
 Patient feel better, postoperative vomiting is
uncommon, Propofol is reported to have antiemetic
action.
 Propofol is used both in induction and maintenance of
anesthesia.
 The drug is also effective in producing prolonged
sedation in patients After intravenous administration,
distribution occur with half life of 2-8 min, the
elimination half life of Propofol is approximately 30-60
min. The drug is rapidly metabolize in liver by
conjugation to glucuronide and sulfate and excreted in
the urine. Less than 1% of the drug is excreted
unchanged.
 Propofol causes marked decrease in systemic blood
pressure during induction of anesthesia, primarily
through decreased peripheral resistance. In addition
Propofol has greater negative iontropic effects on the
heart than etomidate and thiopental. Apnea and pai at
the site of injection also occur.
 Propofol is very costly.