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1. INTRAVENOUS
ANESTHESIA

2. Propofol
• 2,6 Di-Isopropyl Phenol
• Milky White
• pH 7
• Stable at room temperature
• To be diluted with 5% Dextrose

3. • 1% propofol
• 10% soybean oil (Medium )
• 1.2% purified egg phospholipid (Emulsifier )
• 2.25% of glycerol ( Tonicity-adjusting agent )
• Sodium hydroxide ( Change the pH )
• EDTA (Bacteriostatic agent )

4. Fospropofol
• Water-soluble prodrug of propofol
• Fospropofol Propofol
(Prodrug) (Active metabolite)
• 1.86 mg of fospropofol sodium is the molar equivalent of 1
mg propofol
• Not associated with pain on injection
• Mild to moderate perineal paresthesias and pruritis minutes
after a bolus injection of fospropofol ( due to Formaldehyde
byproduct )
• More potent , Slower onset , More Vd

5. Mechanism of action
• Sedative hypnotic
• GABAA Modulator
• increases binding affinity of GABA for the GABAA receptor
• coupled to a chloride channel,
• Activation of the receptor leads to hyperpolarization of the
nerve membrane.
• No direct action on spinal cord

6. Pharmacokinetics
• Intravenous administration for the induction of general
anesthesia and for moderate to deep sedation
• rapid onset of action
• Produce unconsciousness within 30 seconds
• Recovery from propofol is more rapid
• Minimal residual CNS effect
• Fast blood brain barrier achieved

7. • Hepatic clearance: 30-60 ml/kg/min
[If 50 kg patient= 1500-3000 ml/min]
• But, Hepatic blood flow : 800-1200 ml/min
• As propofol hepatic clearance > Hepatic blood flow,
 Extrahepatic elimination does occur.i.e Renal and Pulmonary
• Under hepatic clearance,
Propofol glucoronidation Inactive metabolites
(Water soluble excreted
in urine)

9. • T1/2 = 30 – 90 min
• Context sensitive half life : 40 minutes
Drug Interactions:
• Midazolam can reduce the required propofol dose by more
than 10%
• Hence , Many clinicians administer a small amount of
midazolam (eg, 30 mcg/kg) prior to induction with propofol

10. • Pharmacokinetics of propofol may be altered by various factors
(e.g., gender, weight, preexisting disease, age, and concomitant
medication )
 Reduced cardiac output ( in elderly) ; hence Low Vd
Decreased
elimination
 In a hemorrhagic shock , propofol concentrations increased 20
%.
 Women have a larger volume of distribution and higher
clearance rates
 Relatively larger central compartment volume (50%) and a more
rapid clearance (in children ) ; hence large dose requirement

11. Pharmacodynamics
Effects on CNS :
• Decreases cerebral blood flow
• Decreases intracranial pressure
• Provide a comparable degree of cerebral protection
• Reduces intraocular pressure
• Has anticonvulsant properties

12. • Effects on Cardiovascular system
• decrease in arterial blood pressure
• Decease in preload and cardiac contractility
• markedly impairs the normal arterial baroreflex response to
hypotension
• Rarely, Vagally mediated reflex bradycardia
• Heart rate unaffected
• Decrease in arterial blood pressure from propofol during the
infusion phase is much less than intravenous bolus dose.

13. Effects on Respiratory system
• Profound respiratory depressant
• Causes apnea following an induction dose
• Inhibits hypoxic ventilatory drive and depresses the normal
response to hypercarbia
• Depression of upper airway reflexes
• Decreases tidal volume
• Increases respiratory frequency
• Induces bronchodilation in patients with COPD
• Potentiates hypoxic pulmonary vasoconstriction

14. Other Effects
• does not trigger malignant hyperthermia
• does not enhance neuromuscular blockade
• Possesses significant antiemetic activity ( 10 mg in adults )
• Associated with the development of pancreatitis, which may
be related to hypertriglyceridemia
• Intralipid : excellent culture medium,
• Hence , More infection associated with propofol

15. Uses
• Induction :
 intravenous induction dose is 1 to 2.5 mg/kg.
 in elderly patients ;
 1 mg/kg (with premedication)
 1.75 mg/kg (without premedication)
 In children ;
 2-3 mg/kg

16. • Maintenance :
 After an induction dose, an infusion dose : 100 to 200
μg/kg/min
 If 50 kg patient ;
• 5 – 10 mg/min
• 300 - 600 mg/ hr
• 30 – 60 ml/ hr

17. • For Sedation :
 30-60 μg/kg/min
 Infusion should be individually titrated to the desired effect
 In 50 kg patient;
• 1.5 – 3 mg / min
• 90 – 180 mg / hr
• 9 – 18 ml / hr
 Recommended maximal dose of propofol infusion rate :
80 μg/kg/min

18. SIDE EFFECTS AND
CONTRAINDICATIONS
• Allergic reaction
• Abuse Potential
• During induction :
• pain on injection
• Myoclonus
• Apnea
• Hypotension
• rarely, thrombophlebitis of the vein
• Potential risks to fetal brain development
• Bacterial growth ; E.Coli & Pseudomonas aerogenosa

19. Propofol Infusion Syndrome
• Rare but lethal syndrome
• Associated with infusion of propofol at 4 mg/kg/h or more
for 48 hours or longer
• Acute refractory bradycardia leading to asystole
• Along with 1 or more of following:
• metabolic acidosis (base deficit >10 mmol/ L 1)
−
• rhabdomyolysis
• Hyperlipidemia
• enlarged or fatty liver

20. Ketamine
• structural analogue of phencyclidine
• one-tenth as potent, yet retains many of phencyclidine’s
psychotomimetic effects
• Highly lipid soluble

21. Mechanism of action
• inhibit N-methyl-D-aspartate (NMDA) channels and neuronal
hyperpolarization-activated cationic (HCN1 ) channels
• functionally “dissociates” sensory impulses from the limbic
cortex (which is involved with the awareness of sensation)
• patient to appear conscious (eg, eye opening, swallowing,
muscle contracture) but unable to process or respond to
sensory input
• additional actions on endogenous analgesic pathways

22. Pharmacokinetics
• administered orally, nasally, rectally, subcutaneously, and
epidurally, but in usual clinical practice it is given
intravenously or intramuscularly
• Peak plasma levels are usually achieved within 10 to 15 min
after intramuscular injection

23. • Ketamine increase in cerebral blood flow and cardiac output
• Hence, rapid brain uptake and subsequent redistribution
• Awakening is due to redistribution from brain to peripheral
compartments.
• Biotransformed in the liver to several metabolites, one of
which is norketamine
• End products of ketamine biotransformation are excreted
renally.

24. Pharmacodynamics
• Effects on CNS
• increases cerebral oxygen consumption
• increase in CMRO2
• Increases cerebral blood flow
• Increases intracranial pressure
• Dilates pupil moderately and causes nystagmus
• Lacrimation and Salivation common

25. • Emergence reactions:
• vivid dreaming
• extracorporeal experiences (sense of floating out of body)
• illusions (misinterpretation of a real, external sensory experience)
• Occurs in 1st hour then abates
• Benzodiazepine attenuates incidence & severity of Emergence
rxn
• Antidepressant effects : 0.5 mg/kg, given as a 40-minute infusion

26. • Effects on Cardiovascular system
• Increases arterial blood pressure, heart rate, and cardiac
output
• Increases in pulmonary artery pressure and myocardial
work
• Causes systemic release of catecholamines
• Inhibition of the vagal nerve
• Inhibition of norepinephrine reuptake at peripheral nerves
• Direct myocardial depressant ; use cautiously in patient with
depleted catecholamine stores

27. • Effects on Respiratory system:
• minimal response on the central respiratory drive
• Response to CO2 preserved
• Transient (1-3 minutes) decrease in minute ventilation after the
bolus administration
• Relaxes bronchial smooth muscle
• Increases oral secretions
• Can produce upper airway obstruction followed by laryngospasm

28. Uses
• Induction and Maintenance of Anesthesia
• Desirable in:
• Unstable cardiovascular patients suffering from hypovolemia
• hemorrhagic shock
• cardiovascular depression in sepsis
• reactive airway disease
• Trauma patients with extensive blood loss
• In children with difficult vein access

29. • Sedation and analgesia
• Dose : 0.3-0.6 mg/kg IV over 2-3 min
2-4 mg/kg IM
0.5 to 1 mg/kg via Epidural / Caudal (Safety
controversial)
• During burn dressing changes , debridement procedures
• Supplementation of regional anesthesia

30. Side Effects
• Increases HR, BP ,CO
• Stimulates oral secretion ( Antisialogue ; Glycopyrolate
helpful )
• Increases ICP and IOP
• Increases muscle tone
• Potentiation of Neuromuscular blockade

31. Contraindications
• Raised ICP
• Raised IOP and Penetrating eye injuries
• Psychiatric disorders
• As sole anesthetic agent in Hypertensives, IHD and CVA
patients

32. Barbiturates