This is a lecture on Intravenous Induction Agents. It explores the different classes of induction agents, ranging from barbiturates to non-barbiturate agents. It also discusses the various indications and contraindications of such agents, the doses and different antidotes, and the expected adverse effects. This lecture was presented to undergraduate medical students at University Teaching Hospital (UTH), Lusaka, Zambia, department of Anaesthesia by Nghitukuhamba Tangi Elikana Kalipi (6th year medical student) at Cavendish University Zambia, School of Medicine. Moderated by Dr. Chanda

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.