3. • Ketamine comes as a clear colourless liquid in an ampoule.
10mg/ml
50mg/ml
100mg/ml
Actions:
• Unconsiousness
• Analgesia
• Amnesia
4. • Intravenous (IV)- ind:1-2mg/kg main:0.5
mg/kg
• Intramuscular (IM)-ind:5-10mg/kg, main:3-
5mg/kg
• Oral (sedation)- children:15mg/kg max 500mg
It has a slower onset after an i.v. bolus (1-5 minutes).
The duration of action depends on the route of
administration (20-30 minutes for i.m. and 10-15
minutes for iv).
Route of administration
5. Using IV ketamine
• Premedicate with an antisialogogue (e.g.
atropine 10- 20mcg/kg)
• Anaesthesia: give 1-2mg/kg in small increments
initially to avoid episodes of apnoea. For
example 30mg boluses every 60 secs to a total of
100mg in a 70kg man. Onset is rapid (1-2 mins)
with a duration of 10 minutes. Anaesthesia can
be maintained by repeated boluses 0.5mg/kg
every 15-20 minutes or by continuous infusion
2-4 mg/kg/hr.
• (Add 500mg of ketamine to 500ml of a
crystalloid solution. Spontaneous ventilation = 1
drop/kg/min (4mg/kg/hr); Controlled ventilation
= 0.5 drop/kg min (2mg/kg/hr). The infusion is
stopped roughly 30 minutes prior to the end of
surgery.7
• Diazepam 0.1-0.2mg/kg helps to reduce
intraoperative movement and also limits
postoperative delirium.
• Analgesia - 0.5mg/kg produces rapid and
profound analgesia
Using IM ketamine
• Ideal for children and for
painful repeated procedures.
Atropine can be mixed with
ketamine for a single injection.
• Anaesthesia: 6-8mg/kg. Onset
is gradual over 5-10 minutes
and is preceded by intense
analgesia. IM titration of
maintenance doses is difficult
but 5 mg/kg every 30min is
usually adequate. An easier
technique is to prolong
anaesthesia using IV
supplements.
• Analgesia - 2-4mg/kg. Onset is
again 5-10 minutes
6. Pharmacokinetics of ketamine
Absorption Absorption Well absorbed orally, nasally, rectally and
intramuscularly Oral bioavailability 20%
Distribution Distribution 20-50% protein bound in plasma Volume
of distribution 3L/Kg Distribution half life is 11 mins
Recovery primarily due to redistribution from brain to
periphery
Metabolism Metabolism N-demethylation & hydroxylation of the
cyclohexylamine ring in the liver Some metabolites are
pharmacologically active
Excretion Excretion Urinary excretion of conjugated metabolites
Clearance 17ml/kg/min Elimination half life 2.5 hours
7. System Effect positive Effect negative
RS • preserves the laryngeal and
pharyngeal reflexes to some
degree
• ketamine is given slowly
respiration is usually well
maintained(Always have a self-
inflating bag and mask available)
• no oxygen or only limited
oxygen available
• Ketamine is an effective
bronchodilator.
• RR
• Saturation decreases when
airway obstruction
• after rapid i.v. injection the
breathing may stop for a short
while but usually restarts
within a minute.
CVS • increase in both blood
pressure and heart rate
• This is very useful in the
shocked patient but in patients
with a history of heart attack
or angina this can make their
heart disease worse.
• occasionally there can be a
large rise in blood pressure.
• patients with ischaemic heart
disease, Patients with diabetes
should have an ECG, if
available, to rule out “silent”
ischaemia (ischaemia without
chest pain)- avoided
Effect of Organ system
8. System Effect positive Effect negative
CNS • Ketamine provides very good
analgesia
• Co-administration of opiates or
tramadol intraoperatively can
reduce the amount of ketamine
required for maintenance of
anaesthesia and therefore reduce
the incidence and duration of
postoperative hallucinations.
• hallucinations can be reduced by
premedication with
benzodiazepines (usually
diazepam 0.15mg/kg orally 1
hour preoperatively or 0.1mg/kg)
• dissociative anaesthesia ( patient
may have their eyes open and
make reflex movements during
the operation)
• Patients can become tolerant of
ketamine. With frequent repeat
anaesthetics bigger doses are
needed, this tolerance usually
wears off over 3 days
• Co-administration (however increase the
risk of the breathing stopping during the
operation.)
• Ketamine increases the intracranial pressure
and for this reason should be avoided
wherever possible in those patients with
recent head injuries.
GIS /-/ • Ketamine increases salivation.
This can lead to airway problems
due to laryngeal spasm or
obstruction.
• It may also make the taping of
endotracheal tubes more difficult.
To reduce this salivation atropine
is usually given either as a premed
(20mcg/kg i.m.) 30 minutes
preoperatively, or at the time of
induction iv (10- 20mcg/kg).
9. System Effect positive Effect negative
Eyes /-/ Ketamine increases intraocular
pressure. The eyes also commonly
move continually during ketamine
anaesthesia (nystagmus). This
makes it an unsuitable anaesthetic
for eye surgery.
Skeletal Muscle /-/ Ketamine increases skeletal muscle
tone. This is most prominent after
the initial iv bolus and gradually
decreases. It is improved by
administration of benzodiazepines.
It is rarely a problem
intraoperatively.
Pain on injection No No
10. Patients suitable for ketamine
• Children - nausea, vomiting
and hallucinations are less
common in children
• Burns (repeated painful
procedures), trauma,
radiotherapy
• Shocked patients
• Status asthmaticus
Patients unsuitable for ketamine
• Avoid ketamine with:
Hypertension
• Ischaemic heart disease
• Pre-eclampsia
• Raised intracranial pressure
• Open eye procedures
• Acute porphyrias
11. Case 1 A 22 year old man has been admitted with a gunshot wound to the
abdomen. He is shocked from major internal bleeding and requires a
laparotomy. You have a very small supply of inotropes and want to try and not
use them. What will you do for induction and maintenance of anaesthesia?
• This gunshot victim is shocked and requires a laparotomy, you have limited inotropes.
• Ketamine would be an ideal anaesthetic agent in this case due to its cardiovascular effects of
raising the blood pressure and heart rate, all other anaesthetic agents tend to have a cardiac
depressant effect.
• Inductioan can be performed with iv ketamine (1-2mg/kg), atropine (10-20mcg/kg) and
diazepam (0.1mg/kg). It is still possible to perform a modified rapid sequence intubation with
ketamine, despite its slower onset time.
• There are several options for maintenance:
• 1) intermittent boluses of iv ketamine (0.5mg/kg) given according to patient’s response - pupil
size, heart rate, blood pressure, movement etc
• 2) ketamine infusion. Put 500mg of ketamine in a 500ml bag of saline or dextrose. Run this
at 1-2mls/min (1-2mg/min). Some patients may require more and others less depending on
what other drugs have been given and the type of surgery. Generally the ketamine will need to
be discontinued 20-30 minutes before the end of the operation to avoid a long wait for the
patient to wake up. This technique for laparotomy is best used with non-depolarising muscle
relaxants (avoid pancuronium as combined with ketamine may have very high blood pressure
increases). It is however possible, although more difficult, to perform the laparotomy under
ketamine alone.
12. Case 2 Your laparotomy patient (case 1) is back on the ward. He has severe
postoperative pain but you have been unable to get any morphine this month.
How can you manage his postoperative pain?
• ketamine for postoperative analgesia
• Ketamine is a very good analgesic and can be a solution for severe pain
when morphine is not available. Its use postoperatively is limited by the
occurrence of hallucinations, however these are less of a problem when
relatively low doses are used.
• For adult patients in severe pain a loading dose of 0.5-1 mg/kg i.m. may be
given. This can then be followed by an infusion of 60-180mcg/kg/hr (4-12
mg/hr for a 70kg adult).
.
13. Case 3 A 37 year old woman is recovering from 45% burns, she needs dressing changes
every two days which are very painful. She has very few sites left for i.v. access and
you don’t want to use them as she has further surgery to come. She is also very scared
of needles. How will you manage the sedation she requires for her dressing changes?
• This woman requires recurrent sedation for painful burns dressings.
IV ketamine is possible but in burns patients there are often limited
sites for cannulation and these are best saved for trips to theatre.
• IM ketamine is also an option but requires relatively large painful
i.m. injections. Instead the intravenous preparation of ketamine can
be given orally. For an adult give 500mg of ketamine + diazepam
5mg. For a child use 15mg/kg ketamine + 0.2mg/kg diazepam (you
can use the i.v. preparation but it tastes very bad and may have to be
hidden in juice). The dressing change can usually start after 20-30
minutes. Responses can sometimes be unpredictable and onset time
may be slower.
• There should always be equipment for suction and face mask
ventilation available and if possible, oxygen and a pulse oximeter.
14. Case 6 An 18 year old girl has been admitted with severe asthma. You have
been asked to see her as she has not improved with subcutaneous injections of
salbutamol or intravenous aminophylline. She is getting tired and her oxygen
saturation is falling. Can you do anything to help?
• ketamine for the treatment of asthma
• Ketamine is an effective bronchodilator and can be used for the patient
who is not responding to conventional bronchodilators such as salbutamol
and aminophylline.
• The doses of ketamine required are very low and problems with
hallucinations rare. A loading dose of 0.2 mg/kg iv is given initially
followed by an infusion of 0.5mg/kg/hr for 3 hours. This may be continued
if necessary. Close monitoring of the patient is required and an anaesthetist
should be available if necessary.
15. • Propofol is slightly soluble
in water , oil-in-water
emulsion
• pH of 6 to 8.5
• In addition to the active
component, the formulation
also contains soybean oil
(100 mg/mL), glycerol (22.5
mg/mL), egg lecithin (12
mg/mL); and disodium
edetate (0.005%)
Propofol(2,6 di-isopropylphenol)
18. Pharmacokinetics of propofol
Absorption Following an IV bolus
Distribution there is rapid equilibration between the plasma and the
highly perfused tissue of the brain as described earlier.
Plasma levels decline rapidly as a result of
redistribution,
Metabolism followed by a more prolonged period of hepatic
metabolism and renal clearance. The initial
redistribution half-life is between 2 and 4 minutes
Excretion Excretion Urinary excretion of conjugated metabolites
Clearance 20-30ml/kg/min Elimination half life 14-23
hours
19. System Effect positive Effect negative
CVS /-/ • This is mainly due to systemic
vasodilatation
Blood pressure heart rate or
slighty
RR /-/ • Act on the respiratory centre to
cause respiratory depression.
This effect is the most profound
with propofol and a period of
apnoea is usually seen. (25-35%)
• Propofol also markedly reduces
airway and pharyngeal reflexes,
making it the ideal drug to use
with the laryngeal mask
CNS • Anticonvulsant in normal
doses.
• Most minimum vomitin g and
naussea
CMRO, CBF, ICP reduced
Effect of Organ system
20. • Propofol infusion syndrome (PRIS) is defined as acute bradycardia
progressing to asystole combined with lipemic plasma, fatty liver
enlargement, metabolic acidosis with negative base excess >10 mmol . l -1,
rhabdomyolysis or myoglobinuria associated with propofol infusion
Etiology & Risk factors
• airway infection,
• severe head injury,
• high-dose long-term propofol sedation
for more than 48 h at more than 5 mg.
kg-1. h-1, increased catecholamine and
glucocorticoid serum levels
• low energy supply
• poor oxygen delivery,
• sepsis
• lipemia,
• likely due to a failure of hepatic lipid
regulation, possibly related to poor
oxygenation or low glucose plasma
levels
Bradycardia has to be combined with
• lipemic plasma,
• fatty liver enlargement,
• metabolic acidosis with negative
base excess >10 mmol . l-1,
• rhabdomyolysis or myoglobinuria
Symptoms and signs are lactacidosis,
arrhythmia, hypotension, renal, cardiac and
circulatory failure, oliguria, rhabdomyolysis,
elevated serum creatine kinase, serum urea
and serum potassium, lipemic plasma, liver
enlargement, ketonuria, increased liver
enzymes and green or red coloured urine.
Propofol infusion syndrom(PRIS)
21. Death was more likely if the patients were younger than 19 yearsof age, males or
received a vasopressor. Other identified risk factors for death were cardiac
manifestations, metabolic acidosis, renal failure, hypotension, rhabdomyolysis or
dyslipidemia
Pathophysiology
• PRIS are cytolysis of skeletal and cardiac
muscle cells
• Muscle biopsies and fat metabolism
analyses of patients with PRIS resemble
these found in mitochondrial cytopathias
and acquired acyl-carnitine metabolism
deficiencies by inhibition of beta
oxidation.
• PRIS may be aggravated by concomitant
diseases like cardiomyopathy.
• Low carbohydrate supply is a risk factor
for PRIS, because energy demand is
satisfied by lipolysis if carbohydrate
supply is low. Children are more prone to
the development of PRIS due to ow
glycogen storage and high dependence on
fat metabolism.43 Fat overload associated
with propofol infusion may also contribute
to increased plasma fatty acids
Therapy
• Propofol infusion must be stopped
immediately.
• Hemodynamic stabilization has to
be achieved by routine intensive
care procedures. Unfortunately,
bradycardia is often resistant to
catecholamines and external
pacing.
• Carbohydrate substitution is
recommended at 6-8 mg.kg.min
• Hemodialysis or hemofiltration is
recommended for elimination of
propofol and its potentially toxic
metabolites
22. • Sodium thiopentone (also known
as thiopental or pentothal) is
prepared by dissolving a
yellowish powder in sterile water
to provide a 2.5% solution (ie
25mg/ml).
• In this concentration 20mls of
solution will contain 500mg.
• Ph=10,8 alkaline
• Thiopentone can be used as the
sole anaesthetic agent for very
brief procedures.
Thiopentone (thiopentanyl sodium)
23. Acting Rapidly ,smooth barbiturates
Onset (arm-brain time ) 15—30 sec
Duration 5-10 min
Induction dose 3-7mg/kg
Pain injection 0/+ (Pain would suggest extravascular or intraarterial
injection)
Recovery time Rapidly
low incidence of nausea and vomiting.
• Following induction anaesthesia is usually maintained by breathing an anaesthetic
vapour such as halothane.
• Titrate the dose against effect; the loss of the eyelash reflex is a good guide to loss of
consciousness.
24. System Effect positive Effect negative
CNS • Thiopentone can also be used in
Intensive Care patients with head
injuries to control surges in
intracranial pressure.
• it posesses potent anticonvulsant
activity it may be given to treat
epileptic seizures
• CMRO, CBF
GIS and US • It does not have any direct toxic
effects on the liver or kidney, but
patients with liver or kidney
disease may require a lower dose
range than 3 to 7 mg/kg.
/-/
CVS • it increases heart rate, coronary
blood flow, and the oxygen demand
of the heart.
• Thiopentone directly depresses the
contractile force of the heart
• can cause hypotension in patients
who are hypovolaemic (eg
following haemorrhage).
• also causes a decrease in venous
tone, causing pooling of blood in
the peripheral veins;
Analgesic and muscle relaxant Thiopentone has no analgesic
properties, in fact in low doses it tends
to heighten sensitivity to pain. It has
poor muscle relaxant properties.
/-/
Effect of Organ system
25. • 1. Acute intermittent porphyria
• 2. Barbiturate allergy
• 3. Patients with a low circulating blood volume, such as after
haemorrhage, are prone to severe hypotension with thiopentone.
• 4. Patients with cardiac disease (particularly those with stenotic
heart valve lesions) are at risk from the cardiovascular depressant
effects of thiopentone. The drug must be carefully titrated against
effect.
• 5. Patients with partial airway obstruction should not be given an
intravenous anaesthetic agent in case total airway obstruction
develops.
• 6. In severe asthma it is thought that thiopentone may occasionally
cause bronchospasm.
Contraindications:
27. • Midazolam is a water
soluble benzodiazepine. It
comes as a clear solution.
1mg/ml
5mg/ml
• Actions: unconsiousness,
sedation , anxiolytic,
anticonvulant , amnesia
Benzodiazepines(Midazolam)
28. Acting
Sedation dose 0.05-0.1mg.kg(IV). Short duration
Oral dose (children) 0.5mg.kg Premedication 30min
preoperative
Induction dose 0.3mg.kg(0.2-0.4mg.kg
IV)
Onset time 30-90sec
Duration time 10-30min
Pain injection /-/
It undergoes hepatic metabolism (+glucorinide or oxidation)and renal elimination. In
the elderly, the lower hepatic blood flow and metabolic activity result in a significantly
prolonged half life.
Liver clearance rate : midazolam >lorazepam >diazepam
29. System Effect positive Effect negative
CvS /-/ Mild depressant*
RS /-/ Mild depressant *
CNS Anticonvulsant
,antiepileptic
CMRO2 and CBF
*-dose dependant (monitoring is important duration sedation)
When used as a sole induction drug, midazolam causes apnoea in up to 70% of
patients
The effects of midazolam can be reversed with flumazenil, a competitive
benzodiazepine antagonist. This should be given by intravenous injection in 100mcg
increments and should act with in 2 minutes. Flumazenil must be used cautiously, as it
can cause agitation and seizures
Effect of Organ system
30. • Diazepam is exclusively lipid
soluble, water insoluble due to its
carbon-containing ring structure.
• This property makes it a rapidly
absorbed by the oral route but also
means that it must be formulated
as a lipid emulsion (diazemuls)
for intravenous use
5mg/1ml
Diazepam
31. Diazepam
Induction dose 0.3-0.6mg.kg
Dose in children 0.2-0.3mg.kg
Onset time 45-60sec
Duration time 15-30min
Pain on injectin +++
Diazepam causes cardiorespiratory compromise, particularly when co-administered
with opioids.
32.
33. • Etomidate is an imidazole ester.
• It is usually presented as a lipid
emulsion or as a clear solution
containing propylene glycol at a
concentration of 2mg.ml
2mg/ml
Etomidate
34. Induction dose 0.2-0.3 mg.kg
Sedation dose 0.03-0.05mg.kg
Onset time 15-45sec
Duration time 3-12min
Pain on injectin +++
Recovery rapid (accompanied by nausea and
vomiting)
It is rapidly metabolized by hepatic and plasma esterases to yield inactive
metabolites. Excretion is predominantly urinary and the elimination half life varies
from 1 – 5 hours.
35. System Effect positive Effect negative
CVS • widely used to induce
anaesthesia in the shocked,
elderly or cardiovascularly
compromised patient
• Hemodynamic suitable
• Least cardiovascular
depression of the IV
anaesthetic drugs, with only a
small reduction in the cardiac
output and blood pressure.
• Deppressant trombocytes ,
prolonged bleeding time
RS /-/ • causes transient apnoea,
though less so than other
drugs, and can cause
cough or hiccups
Post operative nausea and vomiting is common after etomidate administration
MOST MINIMUM DEPRESSANT !!!!!
Effect of Organ system
36. • Etomidate inhibits 11-β-hydroxylase, an enzyme important in adrenal
steroid production.
• A single induction dose blocks the normal stress-induced increase in
adrenal cortisol production for 4-8 hours, and up to 24 hours in elderly and
debilitated patients.
• Continuous infusion of etomidate for sedation in critically ill patients has
been shown to increase mortality.
• Although no increase in mortality has been identified following a single
dose during induction of anesthesia, the use of etomidate has declined in
recent years due to a perceived potential morbidity
Etomidate
