Propofol ppt nandini

 Propofol is famously called as “Milk of
Amnesia”.
 Most common intravenous agent used for
induction and maintenance of
Anaesthesia.
 Preferred drug in Day care surgeries.
 Also used for sedation in intubated and
mechanically ventilated patients in ICU.
 The best choice in TIVA.

 Diprivan(1%)- 10% soyabean oil, 2.25%
glycerol, 1.2% egg phosphatide ,
0.005%disodium edenate.
 Ampofol(low lipid emulsion)- 5%soyabean
oil, 0.6% egg lecithin
 Diprifusor TCI devices
 Propofol lipura
 Fospropofol(Lusedra/Aquavan)

 Milky white coloured , sterile , non pyrogenic
oil in water emulsion
 Highly lipid soluble
 Slightly water soluble
 Molecular weight -178.271 D
 Octanol water partition coefficient-6761:1 at
pH- 6 to8.5
 Isotonic, pH-7-8.5
 2,6- diisopropylphenol(C12H18O)
 Weak acid, unionized, Pka-11
 Protein binding-95-98%

 Main Site of action - GABAa-BZD: Chloride
receptor complex in CNS - Binding of
propofol to GABAa receptor causes
prolongation of action of GABA and
increased duration of opening of chloride
channel resulting in hyperpolarization of
postsynaptic cell membrane and functional
inhibition of post synaptic neurons.
 Acts on hippocampus and prefrontal
cortex .
 Principal action responsible for sedation
and hypnosis.

 Widespread inhibition of NMDA(N-methyl-D-
aspartate) receptor through sodium channel
gating.
 Acts on GABA a and glycine receptors on
dorsal horn of spinal cord and inhibits the
excitatory action.
 Increases Dopamine concentration in nucleus
accumbens which is responsible for sense of
well being, drug abuse potential and pleasure
seeking behaviour.
 Decreases serotonin levels in area postrema –
anti emetic effect.

 Absorption- Intravenous
 Volume of distribution-3.5-4-5 L/kg
 Distribution- explained by three compartment linear model
 Rapidly equilibrates between plasma and brain accounting
for rapid onset of anaesthesia(one brain arm circulation
time)
 Onset-<40 seconds, peak effect -90-100 seconds, initial
redistribution half life-2-8minutes.
 Phase 1/very rapid distribution(half life- 1-8min)- rapidly
distributed to highly perfused organs like heart , lungs,
kidneys and liver.
 Phase 2/slow distribution(half life-30 -60 min)- rapidly
distributed from highly perfused tissues to muscle and fat.
 Phase 3/terminal elimination(half life-4 to24 hrs)-slowly
released from deep compartment with limited perfusion (fat)
to plasma and is metabolized.

 Elimination half time- 0.5 hrs -1.5 hrs
 Context sensitive half time- <40 min-8 hrs
 Short effect-site equilibration time
 Clearance rate-30-60ml/kg/min
 Metabolism- propofol is extensively metabolized by liver .It
undergoes conjugation by UDP-glucoronosyl transferase to form
inactive, water soluble sulfate and glucoronic acid metabolites which
are excreted by the kidneys.
 Propofol may also undergo ring hydroxylation by cytochrome-P450 to
form 4- hydroxypropofol which is then glucoronidated or sulfated.
 Extra-hepatic metabolism- Lungs-30% uptake(propofol converted to
2,6-diisopropyl-1,4-quinol) and kidneys -30%uptake.
 Less than 1%propofol is excreted unchanged in urine and only 2%in
faeces.
 No dosage adjustments are needed for patients with renal or hepatic
failure
 Geriatrics
age-related decrease in volume of distribution
Decresed rate of plasma clearance
cardiorespiratory effects including hypotension, apnea, airway
obstruction, and/or oxygen desaturation

 Blood levels of propofol during surgery
required for unconsciousness- 2-5 ug/ml.
 Patient becomes awake at plasma level less
than 1.5 ug/ml.
 ED90 for anaesthesia is 3.2ug/ml when
used with 67% of nitrous oxide.
 Larger doses required in children- higher
clearance rate(25%) and larger central
compartment volume(50%).

 CNS- decrease in cerebral metabolic oxygen
consumption, cerebral blood flow, ICP and cerebral
perfusion pressure.
 Cerebral autoregulation and reactivity to increased
PaCO2 is maintained.
 CVS- decreases SVR by 30%, decreases SBP by 25-40%
along with decrease in COP.
 Propofol blocks/resets baroreceptors, so there is little
(no) compensatory tachycardia due to decrease in
mean BP.
 A central cholinergic response may be responsible for
bradycardia.
 If ventilation is assisted or controlled(CPAP), there is
increase in the incidence and degree of depression on
COP.

 RS- dose dependent respiratory depression(first
reduction in tidal volume associated with tachypnoea
followed by apnoea).
 Apnoeaoccure in 25-30% of patients depending on the
dose and use of concomitant drugs like opoids, BZP .
 Decreased sensitvity of respiratory centre to increase
in CO2 and hypoxia via carotid body chemoreceptors.
 Laryngeal and cough reflexes are depressed.
 Propofol has a bronchodilator effect through direct
action on muscaranic action and attenuating vagal
response.
 Attenuates the magnitude of hypoxic pulmonary
vasoconstriction.

 Liver- blood flow is decreased. Prolonged infusions
have been associated with hepatocellular injury
accompanied by lactic acidosis, bradydysarrythmias
and rhabdomolysis.
 Kidney- vasoconstriction of splanchnic and renal
blood vessels which causes decrease in RBF and GFR.
 Prolonged infusions results in green urine due to
phenols in urine and due to increased uric acid
crystals in urine.
 Eyes- decrease in IOP by 30-40%, helps in blunting
increase in IOP due to succinylcholine or laryngoscopy.
 Pregnant uterus- crosses placenta (equilibrium
between mother and foetus is 2-3 min) and causes
neonatal depression.

 induction and maintenance of anesthesia
 Monitored anaesthesia care(MAC) sedation
 Combined sedation and regional
anaesthesia
 Short surgical procedure, ICU
sedation ,conscious sedation.

 Anti-emetic- 10-20 mg IV ,can be
repeated every 5-10 min or start infusion
of 10 ug/kg/min.
 Anti-pruritic- 10 mg IV is effective in the
treatment of pruritis associated with
neuraxial opoids and cholelithiasis.
 Attenuation of bronchospasm- Hence,
useful in asthamatics.
 Antioxidant- beneficial in acute lung
injury.

 Healthy Adults Less Than 55 Years of Age: 40 mg
every 10 seconds until induction onset (2-2.5
mg/kg).
 Elderly, Debilitated, or ASA III/IV Patients: 20 mg
every 10 seconds until induction onset (1-1.5
mg/kg).
 Cardiac Anesthesia: 20 mg every 10 seconds until
induction onset (0.5-1.5 mg/kg).
 Neurosurgical Patients: 20 mg every 10 seconds
until induction onset (1-2 mg/kg).
 Pediatric Patients - healthy, from 3-16 years of
age: 2.5-3.5 mg/kg administered over 20-30
seconds.

 Healthy Adults Less Than 55 Years of Age: 100-
200 μg/kg/min (6-12 mg/kg/h).
 Elderly, Debilitated, ASA III/IV Patients: 50-100
μg/kg/min (3-6 mg/kg/h).
 Pediatric Patients - healthy, from 2 months to 16
years of age: 125-300 μg/kg/min (7.5-18
mg/kg/h)
 Cardiac Anesthesia, Most Patients Require:
Primary propofol injectable emulsion with
secondary opioid: 100-150 μg/kg/min. Low-dose
propofol injectable emulsion with primary opioid:
50-100 μg/kg/min.
 Neurosurgical Patients: 100-200 μg/kg/min (6-
12 mg/kg/h).

 Initiation of MAC sedation- Healthy adults <55
yrs of age: most patients require an infusion of
100-150 ug/kg/min(6-9mg/kg/hr) for 3-5min or
a slow injection of 0.5 mg/kg over 3-5 min
followed immediately by a maintenance infusion.
 Elderly , debiliated, neurosurgical or ASA- III/IV
patients- require doses similar to healthy adults
but rapid boluses are to be avoided.
 Maintenance of MAC sedation- Healthy adults
<55 yrs of age: 25-75 ug/kg/min(1.5-4.5
mg/kg/hr)or incremental doses of 10 mg or 20
mg.
 Elderly , debiliated, neurosurgical or ASA- III/IV
patients- require 80% of the usual adult dose, but
rapid boluses are to be avoided.

 2 % aqueous solution of propofol is used in
ICU for initiation and maintenance of
sedation in intubated and mechanically
ventilated patients
 Initiation: 5 ug/kg/min(0.3 mg/kg/hr) for
at least 5 min with subsequent increments
of 5-10 ug/kg/min(0.3-0.6 mg/kg/hr)
over 5-10 min.
 Maintenance: 5-50 ug/kg/min(0.3-3
mg/kg/hr) or higher my be required.

 Airway
 Copious secretions
 Laryngospasm
 Respiratory
 Apnea, respiratory depression
 Hiccough
 Bronchospasm
 Cardiovascular
 Hypotension
 Dysrhythmias, bradycardia or tachycardia

 Central Nervous System
 Headache
 Dizziness, euphoria, confusion
 Clonic/myoclonic movements
 Seizures, disinhibition
 Other
 Pain or burning at the injection site is common
especially when the IV is in a small peripheral
vein
 Green urine

 Transient local pain: larger veins; prior
injection of IV lidocaine (1 ml of a 1% solution),
not exceeding 20 mg lidocaine/200mg
propofol.
 Post operative unconsciousness.
 rare reports of pulmonary edema.
 unexplained postoperative pancreatitis
 Pediatric patients
 no vagolytic activity
 Reports of bradycardia, asystole, and rarely, cardiac
arrest have been associated with propofol
 particularly when fentanyl is given
 anticholinergic agents

•Propofol is known to have
effects like amorous
behaviour , intense dreaming
and hallucinations.
•The famous legendary
singer Michael Jackson died
due to acute propofol and
benzodiazepine intoxication.

 It has been described in pediatric and adult patients
receiving prolonged infusions of propofol at
>75ug/kg/min(>5 mg/kg/hr) for>24-48 hrs.
 It is a rare but lethal complication .
 Basic pathology-mitochondrial toxicity(impaired oxidation
of long chain fatty acids affecting electron transport chain),
impaired tissue oxygenation and carbohydrate deficiency.
 Presentation- acute refractory bradycardia leaading to
asystole in presence of one or more of the following:
metabolic acidosis(base deficit>10 mmol/l),
hyperlipedemia, rhabdomyolysis, enlarged or fatty liver,
cardiomyopathy with acute cardiac failure and hyperkalemia.
 Treatment- prompt recognition of symptoms and
discontinuation of propofol infusion. ECMO(extra corporeal
membrane oxygenation) has been described in treatment of
some patients.

 Absolute contraindications:
1. Known hypersensitvity to propofol or any of its
components.
2. Allergies to egg, egg products, soyabeans or soy
products.
3. Disorders of fat metabolism.
 Relative contraindications:
1. Untreated hypertensive, hypovolemia and compromised
left ventricular function.
2. Paediatric patients <3 yrs.
3. Pregnant or lactating mother.
4. Known case of epilepsy.
5. Patients undergoing neurosurgery such as pallidotomy
as it temporary abolishes tremors in patients of
parkinsonism.

 dose requirements reduced:
 Premedication with narcotics (e.g., morphine,
meperidine, and fentanyl, etc.)
 In pediatric patients, administration of fentanyl
concomitantly with propofol may result in
serious bradycardia
 combinations of opioids and sedatives (e.g.,
benzodiazepines, barbiturates, chloral hydrate,
droperidol, etc.)
 more pronounced decreases in systolic,
diastolic, and mean arterial pressures and
cardiac output

 reduced in the presence nitrous oxide
 inhalational agents (e.g., isoflurane, enflurane, and
halothane) has not been extensively evaluated
 does not cause a clinically significant change in
onset, intensity or duration of action of the
commonly used neuromuscular blocking agents
(e.g., succinylcholine and nondepolarizing muscle
relaxants).
 Coadministration of 10 microg kg(-1)midazolam
decreases the dose and time required to achieve
hypnosis with propofol induction without delaying
emergence from anesthesia.
 Additional administration of flumazenil further
shortens the time to emerge from midazolam-
propofol anesthesia

 CONCLUSIONS:
 The plasma levels of fentanyl affect the concentrations of
propofol required for patients to regain consciousness.
 The BIS values for wakefulness are unaltered at the
different combinations of propofol and fentanyl
concentrations. Thus, the BIS appears to be a useful and
consistent indicator for level of consciousness during
emergence from propofol/fentanyl intravenous
anesthesia

 Pharmacology and physiology in
Anaesthetic practice- fourth edition-
Stoelting.
 Miller’s Anaesthesia- seventh edition.
 Lee’s synopsis of Anaesthesia.
 Journal of Clinical Anesthesia
Volume 13 • Number 4 • June 2001
Copyright © 2001 Elsevier

Propofol ppt nandini

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Propofol ppt nandini