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02intravenousinductionagents-160226094535 (1) (1).pdf
- 1. Intravenous Induction Agents Chairperson-Dr.H VAirani Moderator-Dr.Hema Presenter-Dr.Dharmaraj
- 2. What are IVinduction drugs • These are drugs that, when given intravenously in an appropriate dose, cause a rapid loss of consciousness. • One arm-brain circulation time • They are used: •To induce anaesthesia prior to other drugs being given to maintain anaesthesia. •As the sole drug for short procedures. •To maintain anaesthesia for longer procedures by intravenous infusion. •To provide sedation
- 3. Ideal IV inductiondrug Physical properties •Water soluble & stable in solution • Stable on exposure to light • Long shelf life • No pain on intravenous injection •Non-irritant when injected subcutaneously • Low incidence of thrombophlebitis • Cheap
- 4. Pharmacokinetic properties • Rapidonset in one arm-brain circulation time • Rapid redistribution to vessel rich tissue •Rapid clearance and metabolism •No active metabolites Pharmacodynamics properties • High therapeutic ratio •Minimal cardiovascular and respiratory effects •No histamine release/hypersensitivity reactions • No emetic effects • No involuntary movements •No emergence nightmares •No hang over effect •No adrenocortical suppression • Safe to use in porphyria
- 5.
- 6. e.g. •Thiopental • Thiamylal • Pentobarbital •Secobarbital • Methohexital Mechanisms of Action • Depress the reticular activating • Suppress transmission of excitatory neurotransmitters (acetylcholine) • Enhance transmission of inhibitory neurotransmitters (GABA) BARBITURATES
- 7. Structure • Barbiturates arebarbituric acid derivatives • Pale yellow colored powder • Kept in environment of nitrogen • The sodium salts of the barbiturates are water soluble • pH of 2.5% thiopental 10 .5 • Self life : 2 wk 2.5% thiopental solution BARBITURATES
- 8. Pharmacokinetics • Highly proteinbound (80%) • The duration of action of is determined by redistribution, not metabolism or elimination • Maximal brain uptake within 30 s • Subsequent redistribution to the peripheral lowers plasma and brain concentration to 10% of peak levels within 20–30 min • This pharmacokinetic profile correlates with clinical experience—patients typically lose consciousness within 30 s and awaken within 20 min. BARBITURATES
- 9. • BIOTRANSFORMATION • Hepaticoxidation to inactive water-soluble metabolites. • EXCRETION • Renal excretion • Important for less protein-bound and less lipid-soluble agents such as phenobarbital, • Water-soluble end products of hepatic biotransformation. BARBITURATES
- 10.
- 11. Effects on OrganSystems CARDIOVASCULAR • Fall in blood pressure • Elevation in heart rate RESPIRATORY • Ventilatory response to hypercapnia and hypoxia ---Decreases • Tidal volume --- decreased • Respiratory rate --- decreased • Bronchospasm in asthmatic patients or laryngospasm in lightly anesthetized patients • Barbiturates do not completely depress noxious airway reflexes • Release of histamine BARBITURATES
- 12. •Cerebral • Cerebral bloodflow --- Decrease • Intracranial pressure---Decrease • Cerebral perfusion pressure--- Increased • (CPP equals cerebral artery pressure minus cerebral venous pressure or intracranial pressure.) • Cerebral oxygen consumption --- Decrease • This effect of barbiturates may protect the brain from transient episodes of focal ischemia (eg, cerebral embolism) but probably not from global ischemia (eg, cardiac arrest). • To have an antianalgesic effect by lowering the pain threshold • Do not produce muscle relaxation. BARBITURATES
- 13. • RENAL • Reducerenal blood flow and glomerular filtration rate in proportion to the fall in blood pressure. • HEPATIC • Hepatic blood flow is decreased. • Induction of hepatic enzymes increases the rate of metabolism of some drugs • The induction of aminolevulinic acid synthetase stimulates the formation of porphyrin (an intermediary in heme synthesis), which may precipitate acute intermittent porphyria or variegate porphyria in susceptible individuals. • IMMUNOLOGICAL • Sulfur-containing thiobarbiturates evoke mast cell histamine release in vitro, whereas oxybarbiturates do not. BARBITURATES
- 14. Specific complication : Intra-arterialInjection • Immediate, intense vasoconstriction and excruciating pain that radiates along the distribution of the artery. • Severe Vasoconstriction may obscure distal arterial pulses. • Gangrene and permanent nerve damage may occur. BARBITURATES
- 15. Mechanism of Damage •Due to be the precipitation of thiopental crystals inflammatory response and arteritis microembolization that follows, eventually results in occlusion of the distal circulation. Treatment • Immediate attempts to dilute the drug --- injection of saline • Prevention of arterial spasm & sustain adequate blood flow— • lidocaine, papaverine, or phenoxybenzamine • stellate ganglion block or brachial plexus block BARBITURATES
- 16. •Structure • Propofol (2,6-diisopropylphenol) •Propofol is not water soluble • 1% solution (10 mg/mL) --- an oil-in-water emulsion Containing • soybean oil • glycerol • egg lecithin •Mechanisms of Action • Facilitation of inhibitory neurotransmission mediated by GABA. Propofol
- 17. Pharmacokinetics • DISTRIBUTION • Highlipid solubility • onset of action that is almost as rapid as that of thiopental (one-arm-to-brain circulation time). • Awakening from a single bolus dose is also rapid due to a very short initial distribution half-life (2–8 min). • Recovery --- rapid • Hangover --- less • This makes it a good agent for outpatient anesthesia. • BIOTRANSFORMATION • Hepatic and extra hepatic metabolism • EXCRETION • Primarily excreted in the urine • chronic renal failure does not affect clearance of the parent drug. Propofol
- 18. Effects on organ CARDIOVASCULAR •Blood pressure ---decrease due to a • Fall in systemic vascular resistance • Hypotension is more pronounced than with thiopental. • HR: No change /Bradycardia RESPIRATORY • Profound respiratory depressant following an induction dose---apnea • Inhibits hypoxic ventilatory drive and depresses the normal response to hypercarbia. • Depression of upper airway reflexes • Helpful during intubation or laryngeal mask placement in the absence of paralysis. • Lower incidence of wheezing • Safe in asthmatic patients. Propofol
- 19. CEREBRAL • Cerebral bloodflow---- decreases • Intracranial pressure---- decreases. • Antiemetic effects • preferred drug for outpatient anesthesia. • Anticonvulsant properties (ie burst suppression) • used to terminate status epilepticus. • Safely administered to epileptic patients. • Intraocular pressure----Decreases Propofol
- 20. Use : • Inductionof Anesthesia 1.5 to 2.5 mg/kg • Intravenous Sedation 25 to 100 µg/kg per minute IV • Maintenance of Anesthesia 100 to 300 µg/kg per minute IV • Nonhypnotic Therapeutic Applications • Antiemetic Effects • Mech –unknown • 10 to 15 mg IV • Anticonvulsant Activity • Attenuation of Bronchoconstriction Propofol
- 21. Specific complication • LacticAcidosis or propofol infusion syndrome • Prolonged high-dose infusions of propofol (>75 µg/kg per minute) for longer than 24 hours. • Mechanism – • Unclear • Cytopathic hypoxia of the electron transport chain and impaired oxidation of long-chain fatty acids • C/F • Unexpected tachycardia • Diagnosis • Arterial blood gases and serum lactate concentrations • Treatment • Metabolic acidosis in its early stages is reversible with discontinuation of propofol administration. Propofol
- 22. • Pain onInjection • Most common • Reduced by • 1% lidocaine • Potent short-acting opioid eg Fentanyl • Bacterial Growth • Supports the growth of Escherichia coli and Pseudomonas aeruginosa. • Recommendation: • An aseptic technique be used in handling propofol, as reflected by disinfecting the ampule neck surface or vial rubber stopper with 70% isopropyl alcohol. • The contents of the ampule containing propofol should be withdrawn into a sterile syringe immediately after opening and administered promptly. • The contents of an opened ampule must be discarded if they are not used within 6 hours. In the ICU, the tubing and any unused portion of propofol must be discarded after 12 hours. Propofol
- 23. Mechanisms of Action •N-methyl-D-aspartate receptor antagonist. • Produce dissociative Anaesthesia Structure : • structural analogue of phencyclidine KETAMINE
- 24. Pharmacokinetics • ABSORPTION • Intravenouslyor intramuscularly • Peak plasma levels are usually achieved within 10–15 min after intramuscular injection. • DISTRIBUTION • Ketamine is more lipid soluble and less protein bound than thiopental • Half-life is 10–15 min • Awakening is due to redistribution to peripheral compartments. • BIOTRANSFORMATION • Liver to several metabolites (eg, norketamine) • EXCRETION • End products of biotransformation are excreted renally KETAMINE
- 25. Uses • Induction ofAnesthesia • Intravenous ketamine, 1 to 2 mg/kg • Intramuscular administration of 4 to 8 mg/kg. • Analgesia • Subanesthetic doses of ketamine, 0.2 to 0.5 mg/kg IV. • Neuraxial Analgesia • Limited value. KETAMINE
- 26. Effects on organsystem Central Nervous System • cerebral blood flow --- Increase • CMRO2---Increase • Intracranial Pressure--- Increase Cardiovascular System • Sympathetic nervous system stimulation • Systemic and pulmonary arterial blood pressure---- increased • Heart rate ---- increased • Cardiac output---- increased • Myocardial oxygen requirements ---- increased KETAMINE
- 27. • But inCritically ill patients • Unexpected decreases in systemic blood pressure and cardiac output, which may reflect a depletion of endogenous catecholamine stores and exhaustion of sympathetic nervous system compensatory mechanisms. • Unmasking of ketamine's direct myocardial depressant effects. Ventilation and Airway • Depression of ventilation: not significant • Upper airway skeletal muscle tone :maintained, • Upper airway reflexes : intact • Salivary and tracheobronchial mucous gland: Increased secretions are increased • Use antisialagogue before ketamine • Bronchodilatory effects • Drug of choice for induction patients with asthma KETAMINE
- 28. Specific Complications Emergence Delirium(Psychedelic Effects) • In postoperative period visual, auditory, proprioceptive, and confusional illusions, which may progress to delirium. • Dreams and hallucinations can occur up to 24 hours after the administration of ketamine. • Mechanisms • Emergence delirium probably occurs secondary to ketamine- induced depression of the inferior colliculus and medial geniculate nucleus, thus leading to the misinterpretation of auditory and visual stimuli. KETAMINE
- 29. • The lossof skin and musculoskeletal sensations results in a decreased ability to perceive gravity producing a sensation of bodily detachment or floating in space • FACTORS ASSOCIATED WITH AN INCREASED INCIDENCE • Age greater than 15 years • Female gender • Dose greater than 2 mg/kg IV • History of frequent dreaming • PREVENTION OF KETAMINE-INDUCED EMERGENCE DELIRIUM • Midazolam (administer IV about 5 minutes before induction of anesthesia with ketamine) • Prospective discussion with patient about side effects of ketamine KETAMINE
- 30. • Structure • Carboxylatedimidazole-containing compound • Commercial Preparation • Etomidate is prepared as a fat emulsion, and pain on injection and venous irritation is unlikely. • Mechanism of Action • GABA receptors ETOMIDATE
- 31. Uses • Etomidate (0.2to 0.4 mg/kg IV) • As an alternative to propofol or barbiturates for the induction of anesthesia, especially in the presence of an unstable cardiovascular system. ETOMIDATE
- 32. Effects on organsystem •Central Nervous System • Potent direct cerebral vasoconstrictor that decreases cerebral blood flow and CMRO2 • Activate seizure foci • Caution in patients with focal epilepsy • Facilitate the localization of seizure foci in patients undergoing the cortical resection of epileptogenic tissue. •Cardiovascular System • Cardiovascular stability (minimal changes in heart rate, stroke volume, cardiac output) • Preferred for Induction of anesthesia in patients with little or no cardiac reserve. ETOMIDATE
- 33. • Ventilation • Depressanteffects on ventilation • Pain on Injection • Pain on injection and venous irritation has been virtually eliminated with use of etomidate preparations utilizing a lipid emulsion vehicle rather than propylene glycol • Myoclonus (spontaneous movements) • Caution in the use of this drug for the induction of anesthesia in patients with a history of seizure activity. • Adrenocortical Suppression • lasts 4 to 8 hours after an intravenous induction dose of etomidate. • Be considered desirable from the standpoint of “stress-free” anesthesia. ETOMIDATE
- 34. • E.g. • Midazolam •Diazepam MECHANISM OF ACTION • Facilitating the actions of γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the CNS • Benzodiazepines do not activate GABAA receptors but rather enhance the affinity of the receptors for GABA. Benzodiazepine
- 35. Benzodiazepine Uses and Dosesof Commonly Used Benzodiazepines
- 36. Effects on OrganSystems CARDIOVASCULAR •Minimal cardiovascular depressant effects even at induction doses. •Arterial blood pressure •Cardiac output decline slightly •Peripheral vascular resistance •Heart rate ---- slight rise •Midazolam tends to reduce blood pressure and peripheral vascular resistance more than diazepam. Benzodiazepine
- 37. RESPIRATORY •Depress the ventilatoryresponse to CO2 •Apnea may be less common after benzodiazepine induction than after barbiturate induction. •Ventilation must be monitored in all patients receiving intravenous benzodiazepines, and resuscitation equipment must be immediately available. Benzodiazepine
- 38. CEREBRAL • Cerebral oxygenconsumption, cerebral blood flow, and intracranial pressure----Reduce • Anti seizures properties • Antegrade amnesia------premedication • Mild muscle-relaxant property --- mediated at the spinal cord level, not at the neuromuscular junction. • Slower loss of consciousness and a longer recover Benzodiazepine
- 39. • E.g. • Morphine •Fentanyl • Sufentanyl • Meperidine Mechanisms of Action • Opioids bind to specific receptors located throughout the central nervous system and other tissues. • Four major types of opioid receptor • µ • Κ • σ • δ • Opiate–receptor activation inhibits the presynaptic release and postsynaptic response to excitatory neurotransmitters (eg, acetylcholine, substance P) from nociceptive neurons. OPIOIDS
- 40. Uses and Dosesof Common Opioids OPIOIDS
- 41. Effects on OrganSystems CARDIOVASCULAR •Do not seriously impair cardiovascular function. •Cardiac contractility--- do not depress (except meperidine) •Heart rate • Increase ----Meperidine • Decrease ---High doses of morphine, fentanyl, sufentanil. •Blood pressure --- Decreased • As a result of bradycardia, venodilation, and decreased sympathetic reflexes • Meperidine and morphine --- can lead to profound drops in systemic vascular resistance and arterial blood pressure due to histamine release • The effects of histamine release can be minimized in susceptible patients by slow opioid infusion, adequate intravascular volume, or pretreatment with H1 and H2 histamine antagonists. OPIOIDS
- 42. Respiratory • Respiratory rate–decrease • Apneic threshold( the highest PaCO2 at which a patient remains apneic) --- elevated • Hypoxic drive -- decreased. • Histamine-induced bronchospasm --- Morphine and meperidine • Chest wall rigidity ( fentanyl, sufentanil, and alfentanil) • Enough to prevent adequate ventilation. • Centrally mediated muscle contraction • After large drug boluses • Effectively treated with neuromuscular blocking agents. • Blunt airway reflex OPIOIDS
- 43. CEREBRAL • Effects oncerebral perfusion and intracranial pressure ---variable • Cerebral oxygen consumption, cerebral blood flow, and intracranial pressure--- slight reduction. • Stimulation of the medullary chemoreceptor trigger zone is ----high incidence of nausea and vomiting. • Physical dependence • Use of opioids in epidural and subdural spaces has revolutionized pain management. • Management of perioperative shivering ---Intravenous meperidine OPIOIDS
- 44. • GASTROINTESTINAL • slowgastric emptying time by reducing peristalsis. • Biliary colic may result from opioid-induced contraction of the sphincter of Oddi. • ENDOCRINE • Stress response to surgical stimulation ---decresed • Ischemic heart disease patients may benefit from attenuation of the stress response . OPIOIDS
- 45.