INTRAVENOUS ANESTHESIA presentation.pptx

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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 GABA A 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)

8. T 1/2 = 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

9. 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

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

11. 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.

12. 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

13. 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

14. 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

15. 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

16. For Sedation : 30-60 μ g/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

17. 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

18. 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

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

20. 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

21. 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

22. 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.

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

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

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

31. Barbiturates