Intravenous Induction Agents
- 1. Intravenous Induction Agents, and Muscle Relaxants Nghitukuhamba Tangi Elikana Kalipi 6th year medical student Cavendish University Zambia
- 2. Learning Objectives ► Introduction to Anaesthesia ► The ideal intravenous anaesthetic agent ► Intravenous anaesthetic agents ► Muscle relaxants
- 3. Introduction to anaesthesia ► The word ‘anaesthesia’ comes from the Greek language. ► It was coined by Oliver Wendell Holmes in a private letter to William Morton, dated November 21, 1846. ► It is divided into ‘an’ (absence) and ‘aesthesia’ (sensitiveness, perception) ► The principal aim of anaesthesia is the abolition of pain, during the whole period of surgical procedure; preoperative, perioperative and postoperative. ► Anaesthetic management is a control of vital functions of the body due to surgical intervention and to protect the patient from operative (surgical) stress. ► Another important feature of anaesthesia is the safety of the patient (golden rules of anaesthesia)
- 4. The Ideal Intravenous Anaesthetic Agent What makes an ideal agent? ► Rapid onset, and rapid recovery. ► Analgesic effects at sub-anaesthetic concentrations. ► Minimal cardiovascular and respiratory depression. ► No emetic effects. ► No excitatory or emergence phenomena. ► No interaction with neuromuscular blocking drugs/agents ► No release of histamine ► No hypersensitivity reactions ► Water soluble formulation ► Long shelf life ► No stimulation of porphyria
- 5. The ideal agent continued… ► no pain on injection ► no venous sequelae (thrombosis) ► no toxic effects on other organs
- 6. Classification of Intravenous Anaesthetic agents Classes Barbiturates 1. Thiopental Sodium 2. Methohexital Nob-barbiturates 1. Propofol 2. Ketamine 3. Etomidate Other (adjuvant) agents 4. Benzodiazepines (Midazolam). 5. Opioids (Fentanyl).
- 7. Barbiturates Thiopental Sodium ► Ultra short acting intravenous anaesthetic. ► Used for rapid intravenous induction of anaesthesia ► Has no analgesic effects. Physical properties ► Yellow powder with a sulphurous smell and a bitter taste ► Highly lipid soluble ► When combined with sodium carbonate it becomes water soluble ► Bacteriostatic in water with ph of 10.6 to 10.8 ► When injected, sodium bicarbonate is neutralized and the thiopental is converted to its lipid soluble non-ionized form (40% ionized at ph=7.4) ► Highly protein bound (75%)
- 8. Thiopental Sodium Physical properties continued… ► Dissolved in water to make a 2.5% solution (25mg/ml). ► Stable at room temp for about 2 weeks. ► Thiopental is a core medicine in the World Health Organization's ‘Essential Drugs List’, which is a list of minimum medical needs for a basic health care system.
- 9. Thiopental Sodium Pharmacokinetics; ► Dose 3-5 mg/kg. ► Onset 30-60 seconds (‘arm brain’ circulation time). ► Duration 5-10 minutes: due to redistribution of the drug into other tissues. ► Metabolized in the liver at 10 to 15% per hour. ► De-sulfuration produces pentobarbital, which undergoes oxidation. ► Less than 1% excreted unchanged in the urine. ► Half-life 10 hours
- 10. Thiopental Sodium Pharmacodynamics; Central Nervous System ► Decreases cerebral electrical & metabolic activity. ► Anticonvulsant. ► Reduces ICP. ► anti-analgesic : decreases pain threshold. ► Reduces intraocular pressure. Cardiovascular System ► Dose related depression of myocardial function. ► Increased coronary blood flow, heart rate & myocardial oxygen uptake. ► Reduced venous tone (preload). ► Decrease in BP. ► Little change in peripheral resistance.
- 11. Thiopental Sodium Pharmacodynamics continued… Respiratory ► Induction may be followed by apnea. ► Depressed brain response to hypercarbia and hypoxia. ► Functional residual capacity (FRC) reduced by 20%. Others ► Liver enzyme induction with prolonged use. ► Hypoalbuminemia increases unbound thiopental which increases its potency. ► Little or no effect on the kidneys or gravid uterus. ► Crosses the placenta.
- 12. Thiopental Sodium Administration; ► Dose is 3-6 mg/kg. ► Caution in hypovolaemia; may cause precipitous drop in BP. ► Caution in elderly. Contraindications & precautions: ► Acute intermittent porphyria or variegate porphyria. ► Previous hypersensitivity. ► Airway obstruction. ► Severe CVS disease. ► Severe hepatic disease.
- 13. Thiopental Sodium Side effects; ► Hypotension if given in hypovolemic, shocked patient. ► Respiratory depression. ► Tissue necrosis with tissue infiltration. ► Ischaemia with intra-arterial injection. ► Allergic reaction.
- 14. Non-barbiturates Propofol ► Intravenous anaesthetic and sedative avent, no analgesic effects. ► Phenol derivative. It works as an agonist on GABAa receptors. ► Emulsion consists of 1% propofol, soyabean oil, glycerol and purified egg phosphatide. ► Onset of 20-30 seconds, duration of 5-7 minutes. Half-life 6-7 hours.
- 15. Propofol Physical properties; ► Highly lipid soluble. ► White milky appearance. ► pH of 7. ► 20 ml ampoules at concentration of 10mg/ml. Administration: ► Dose 2-3 mg/kg. ► Elderly patients 1 mg/kg. ► Maintenance of anesthesia 6-12 mg/kg/hr (TIVA) or 4-6 ng/ml (TCI).
- 16. Propofol Pharmacodynamics; Central Nervous System ► Hypnotic/sedative. ► Decreases CBF and ICP. ► Anticonvulsant. ► Antiemetic. Cardiovascular System ► Decrease in BP due to drop in systemic vascular resistance and contractility. ► Hypotension more pronounced than with thiopental. ► Impairs the normal arterial baroreflex response to hypotension. ► Bradycardia.
- 17. Propofol Pharmacodynamics; Respitarory System ► Profound respiratory depression. ► Depression of upper airway reflexes. Miscellaneous ► No histamine release. ► Does not trigger malignant hyperthermia. ► Pain on injection site.
- 18. Propofol Indications; ► Induction and maintenance anaesthisia. ► Sedation with regional techniques. ► Sedation in ICU. Precautions; ► Egg and peanut allergy allergy. ► Shock and fixed cardiac output (severe AS or MS) cause profound drop in blood pressure. ► Propofol infusion syndrome. ► Young children. * Atropine for bradycardia induced by propofol.
- 19. Ketamine ► ‘Dissociative anesthesia’ (appears awake, but feels no pain). ► Associated with hallucinations and psychotic manifestations. ► Profound analgesic at subanaesthetic doses. ► Related to phencyclidine. ► NMDA antagonist, by blocking the effects of glutamate. ► 10 times more lipid soluble than thiopental sodium. ► pH = 3.5 - 5.5.
- 20. Ketamine Pharmacokinetics; ► Intravenous dose 1-2 mg/kg. Dissociated state in 15 seconds and unconsciousness within 45-60 seconds. Duration 10 – 15 minutes. ► Intravenous dose 5-10 mg/kg. Onset 5-10 minutes (peak plasma level approximately 15 minutes). ► Rapid absorption and distribution to the vessel rich tissues. ► Hepatic metabolism. ► <5% excreted unchanged in urine.
- 21. Ketamine Mechanism of action: ► NMDA receptor antagonist NMDA receptors may represent a subgroup of the sigma opiate receptors ► Opiate receptor theory Some affinity for opiate receptors, but cannot be reversed with naloxone. ► Miscellaneous receptor theory It reacts with muscarinic, cholinergic and serotonergic receptors
- 22. Ketamine Pharmacodynamics; Central Nervous System ► Increases CMRO2, CBF and ICP. ► Increase in muscle tone with movements. ► Unpleasant dreams, hallucinations or delirium (approximately 20%). Respiratory System ► Preserves laryngeal airway reflexes. ► Potent bronchodilator. ► CO2 response curve is shifted to the left (similar to opiates). ► FRC, minute ventilation, tidal volume, hypoxic pulmonary vasoconstriction unchanged. ► Increased secretions (example salivation).
- 23. Ketamine Pharmacodynamics continued… Cardiovascular System ► Central sympathomimetic; Increased BP, HR, CO, pulmonary arterial pressure, coronary blood flow and myocardial oxygen uptake. ► May cause direct myocardial depression. Others ► Minimal anorexia, nausea & vomiting. ► Placental transfer does occur, but minimal neonatal depression. ► Increase in skeletal muscle tone. ► Sympathetic stimulation leads to raised blood glucose and plasma cortisol levels.
- 24. Ketamine Indications; ► Induction of anesthesia. ► Sole anesthetic for diagnostic and surgical procedures. ► To supplement regional anesthetic. ► Severe asthma. ► Patients with cardiovascular collapse requiring emergency surgery. Cautions; ► Allergy to ketamine. ► History of psychosis. ► Increased ICP and IOP. ► Hypertensive disease.
- 25. Etomidate Physical properties; ► Imidazole derivative. ► Clear, colourless liquid. ► Concentration 2 mg/ml in 10 ml ampoule. ► Induction dose: 2-3 mg/kg. ► Has no analgesic effects Adverse features; ► Painful at injection site. ► Minimal cardiorespiratory changes during induction. ► High incidence of nausea and vomiting. ► ‘Seizure-like’ movements on induction. ► Adrenocortical suppression. ► May provoke porphyria.
- 26. Etomidate Beneficial features; ► Cardiovascular stabilty. ► No histamine release. ► Short acting and rapid metabolism. ► No accumulation with repeat doses.
- 27. Summary ► There is variety of intravenous induction Agents. ► Pros and cons for each individual agent. ► Important to know properties of each agents, and its mechanism of action. ► Choose carefully depending on patient’s individual characteristics.