INTRAVENEOUS ANESTHETICS

INTRAVENOUS INDUCTING AGENTS

An intravenous injected drugs use to induce unconsciousness at the onset of general
anesthesia but allows rapid recovery after termination of its effects.
QUAUT1ES OF AN IDEAL INTRAVENOUS ANESTHETICS
I. Rapid nearly instantaneous onset without causing pain on injection.
2. Smooth induction without any signs of muscular twltchlngs and excitement.
3. Safe and cause minimal perturbation of cardiovascular and respiratory function.
4. Short acting allowing the patient to awaken rapidly to full normal CNS function.
5 . Metabolism to Inert substances and excretion would be rapid and complete so
that ac~cumulatlon would not occur thereby allowing the drug to be used as a
constant Infusion over long periods of time.
6 . Amnesia for Intraoperatlve event should be complete.
No ideal intravenous inducting drugs exist but many agents possess most of the desired
physical and pharmacologic properties.
With increasing age the total volume of distribution increases and elimination clearance
decreases so that longer lasting drugs effects.
Older patients are more sensitive to Intravenous anesthetics thus dose reduction are
required.

Appropriate dosing of intravenous anesthetics requires consideration :

1. Intravascularvolume status
2. Comorbldities
3. Age
4. Chronic medications
I. BARBITURATES
Derived (Tom barblturic acid only the shorter acting barbiturates have clinical use
in anesthesia
Thiobarbiturates (3-5mg/kg)
1. Thlopental "L_ similar potency and pharmacologic profile
2. Thlam.ylal _J-
Oxybarblturates (1.5mg/k8)
1. Methohexital
Has a greater potency than the thlobarbiturates and is associatecl with a high
Incidence of myoclonic like muscle tremors and other signs of excitatory activity.

THIOPENTAL
Highly alkaline a 2.S% solution has a pH of 11
Will precipitate when added to an acidic solution (LR)
Accidental Intraarterlal Injection of,barbiturates mat result in the formation of crystals in
arterioles and capillaries causing intense vasoconstriction, thrombosis and even tissue
necrosis causing chemical endarterltls.

Management :
Treat with tntraarterlal administration of ltdocalne, heparaine.
)~ Geriatric patients require a 30% to 40% reduction in the usual adult dose
because of a decrease of the volume of the central compartment and a slowed
redistribution of the drug from the vessel rich tissue to lean muscle.
Contralndtcatlon: Absolute
1, Porphyrla
Increase in amino levullnic acid synthetase activity Increases porphyrin synthesis
(abdominal pain, neurotoxlclty, autonomic dysfunction, peripheral nerve
denlage, as well as intercostal and phrenlc nerve damage.)
 2. ~Jlerly
} * There is an Increased risk of histamine release with thiopental when compared
with other barbiturates secondary to the sulfur molecule in its chemical
structure.
Relative contraindication:
1. Hypovolemla
) * Due to cardiovascular depression, thlopental may result in slRnlflcant
hypotension.
~" If slowly titrated to loss of consciousness, thiopental maybe used successfully.
2. Hepatic failure
)" Metabolism maybe delayed resultln8 in a prolonlled ffect,

CENTRAL NERVOUS SYSTEM EFFECT

Reduces the brain's oxyRen consumption and may reduce ischemla-inducad
brain damage.
)* Used for the treatmeot of increased Intracranlal pressure.
CARDIOVASCULAR EFFECTS
Direct myocardial depression.
Decreases MAP secondary to peripheral vasodllatation.
Maintained cardiac output secondary to reflex tachycardla and vaRolytic effects.
RESPIRATORY EFFECTS
All intravenous anesthetics produces respiratory depression, decreases tidal
volume and minute ventilation as well as right shift in carbon dioxide responsive
curve.

TERMINATION OF EFFECTS
) * AS plasma concentration falls, some drug leaves the highly perfused organs
(brain) to ma!ntain equilibrium.
}~ This redistribution is responsible for termination of effects of many anesthetic
druEs.
This explains the awakenin8 from the effects of thiopental not due to
metabolism or excretion but rather to redistribution of the drug from the brain
to the muscle.

I1. ETOMIDATE
), A carboxyleted Imtdazole.
Unlike the barbiturates it may have dlsinhtbitory effect on the part of the
nervous system that controls extra pyramidal motor activity.
- this Inhibition is responsible for a 30-60% incidence of myodonus.
Dissolve In propylene Rlycol thus this solution often causes pain on injection that
can be lessened by a prior injection of lidocaine.
CARDIOVASCULAR EFFECTS
> This drui~ Is dlsttnl[uished from the other intravenous agents by its minimal
effects on the cardiovascular system,
a. Myocardial contractility and cardiac output are maintained
b. Mild decrease in MAP
} , Thb lru8 is the agent of choice whenever cardiovascular stability is potentially
an Imue.
) , Kncmm to cause edrenocortical suppression resulting to increased morbidity in
cdecany iii patients.
) . Thedo,~ for induction is 0.2-0.4 mE/k8 IV

po~-l~e dde effects

1. klrenocort~l suppression
 2. Myocionus
3. Actlvetion of seizure

III. KETAMIN E
> A phencydldlne derivative
Produces dose dependent CNS depression to a so called DISSOCIATIVE ANESTHETIC
STATE characterized by profound analgesia and amnesia and nystasmus
Induction dose :
1-2 mR/k8 IV -'I,_ producing an effect lasting for 10-20 minutes
4-8 mR/l~ IM-J '
AJthough recovery to full orientation may require an additional 60-90 minutes.

CARDIOVASCULAR EFFECTS
1. Stimulation of the sympathetic nervous system ---) Increase In MAP
2. Increasi~s heart rate aff~rdlac output
~> This Is an excellent Inductinll alent for hypovolemlc patient
) " However If catecholamlne stores are exhausted (end-stage shock ) Induction may result
In decrease MAP and a decrease In cardiac output.
METABOUSM
)~ Extensively metabolized In the liver to NORKETAMINE which is 1/3 to 1/5 as potent as the
parent compound.

THE GOOD ABOUT KETAMINE

1. Significant analgesic effect
2 . No suppression of the cardiovascular system and respiratory system
3 . Dose related unconsdousness and dlssocllltlve state of analResla
4 , Fast onset
5 . Bronchial smooth muscle relaxation (asthmatic induction)

THE BAD ABOUT KETAMINE

1. Related to phencyclldlne (LSD) - may cause hallucinations and disturbing dreams especially in
adults (PHSYCOMIMETIC REACTION)
Less likely in patients treated with benzodlazeplne, barbiturates, or propofol
2 . Not as amnestlc as benzodiasepioe
3. Dilates the pupil and trlsers nystaEmus,
4 . Increase cerebral metabolic rate for oxygen, cerebral blood flow and Intracranial pressure
(minimized by hyperventllatlon of the lungs and pretreatment with benzodlazeplne)
S. Increa~ salivation M-) laryngos spasm
6 . Can activate epilel~J:~enlc fosl In patients with known seizure disorder
7 . It~crelsed mu~ke toni with purposeless movements of the extremities

Co~trelndlcation :
> ContrMndlcated In pltients with Intracranlal pathology, as it Increases Intracrankd pressure and
tumbrel bbod flow.
IV.PROPOFOL

) Most ~ ~ Intravenous drub for Induction of anesthesia.

M ECHANI.Td¥1 OF ACTION
> The ~ by ,dnlch It Induces a state of general anesthesia may involve f~cllltatlon of
Inhibita(y neum~wwmKter mediated by GABA.
It MS ~ ~ because it is associated with :
1. I~1 k~ of ~U~lousness

|, Snml~ly fewer residual effects on patient's brain

CARDIOVASCULAR EFFECTS
1. MyocardLal depressant effect greater than thiopental
2 . Markedly decreases MAP up to 40~ secondary to peripheral vasodllatation
3 . Blockade of erterLal baroreceptor response to hypertension
4 . Minimal effecton heart rate
5. Decreased cardiac output
6. No reflex tachvcardla
AvaiLable as :
1~ aqueous solution (10mg/ml) available for Intravenous administration containing soy bean oil,
gtvcero! and ~ lecithin.

ADVERSE EFFECTS
1 . Allergies- patients with a history of previous allergic reaction to pmpofot or allerl~ to soy
beans and eggs.
A history of egg allergy does not necessarily contraindicate the use of propofol because most
egg allergy involve the reaction to egg white (albumin)
The above formulation can cause pain during injection
2 , Pregnancy-shouldbeusedcautiouslyforlnductionsecondarytoltsabllitytodecreaseMAP
it crosses the placenta rapidly and can lead to neonatal depression
3 . HypercholesterolemLa - it can result in a further increase in serum trlglycaddes.
4 . Muscle relaxants- use a non-histamine muscle relaxants to prevent bronchospasm
5. Cardiovascular challenged patients - patients who are hypovolemic or who have cardiovascular
disease may not tolerate the decrease In MAP and myocardial depression associated with
pmpofol.

Metabellsm
It is rapidly cleared from the central compartment by hepatic metabolism,

Dose;
It is used as a holus for the induction of anesthesia io adults (1-S-2 mg/kg W)
IV infusion rate for hypnosis 100200 mcgJkg/min
For sedation 25-7S mcg~min
The administration of propofoi can cause slliniflcant pain upon injection which can be
attenuated by using intravenous needle placadln a Large vain and or administerinR lidocaine at
.5-1 mgJiF~ IV Just prior to injecting propofor
Propofol has never been associated with a case of malignant hyperthermia, so it is the agent of
choice for general anesthesia In this setting.

APPROPRIATE INDUCTING AGENTS FOR ACTIVE WHEEZING /TRAUMA PATIENTS

When a patient Is actively wheezing and scheduled for elective surgew the case should be
postponed un~ the patient has been adequately optimized for surgery (broncho dilators,
Improvement of cold symptoms)
In any patient with a history of asthma or prone to histamine release Propofol or ketemtne is the
best optJon.
Propofol has shown to decrease airway resistance after incubation
Ketamlne Is a Oroncho lllaT~r and may be the Inducting agent of choice in apatient with active
wheezlrql requiring emergency surgery,
TRAUMA PATIENTS
Generally Intnlvascu~rly volume depleted
Kemmb~ ts ~e drug of choice secondary to its maintenance of MAP by stimulating the
sym e~ nervous system
> In all hylPevolemic patient administer the smallest dose possible titreting to loss of

PATIENT WITH A SCREW DRIVER IN HIS EYE, NEEDS EMERGENCY SURGERY, JUST EATEN A FULL MEAL
> The gilman/concern is the risk of aspiration
> In are/trauma patient it is considered to have a full stomach secondary to delayed
 > The Induction agent should have a fast onset and decrease intraocular pressure
Take In to consideration:
Ketamlne can increase Intraocular pressure
Etomldate can cause myoclonus and therefore can Increase lntraocular pressure
Propofol and Thiopental - best option
A patients should be assessed before laryngoscopy with the goal ---) total paralysis as
coughing on the tube remarkably increase intraocular pressure
)* REMEM8ER : basic bllnkin¢ stress, and Intubatlon can all increase Intraocular pressure

CLINICAL PEARL:
Benzodiazeplne and oplods have synerEIstic effect with Intravenous induction requiring
idju~tmcnt in doslnll,
Ketimlne Is the best induction for hypovotemlc trauma patients as long as there is no risk for
increase in Intracranlal pressure.
increase cerebral blood flow, Intracranial pressure and cerebral metabolism Is due to its
stimulation of the sympathetic nervous system.
it is also a Rood inducting agents Inactive bronchospastlc disease.

A~~ ~ther ~nduct~n~ a~ents cause a decrease ~ntracrania~ pressure by decreasin~ cerebra~ b~~~d
flow and cerebral metabolic rate.