1. By PROF. Dr. Yieldez Bassiouni
General Anesthesia By
PROF. Dr. Yieldez Bassiouni

2. What is meant by general Anesthesia?
التخدير العامRusso Japanese war over Korea and Manchuria, china
What is meant by general Anesthesia?

3. is a controlled reversible state of:
General anesthesia
is a controlled reversible state of:
1. Loss of sensation
(analgesia)
2. Loss of consciousness
3. Skeletal muscle
relaxation(in some not needed for all surgery)

4. Not therapeutic or diagnostic
Aim of Anesthesia
Facilitates surgery
Not therapeutic or diagnostic
غير علاجية أو تشخيصية
غير العلاجية أو التشخيصية

5. Stages of General Anesthesia
Stage 1: Analgesia فقدان الألم
Loss of sensation but patient is still alert and speaking
Stage 2: Excitement إثارة
CNS excitation+  BP (irregular) +  respiratory rate
Stage 3: Surgical Anesthesia التخدير الجراحي
Regular respiration + relaxed skeletal muscles + eye movement stops and pupil is fixed
Stage 4: Coma→→→ death
Stage of Analgesia:
Analgesia without amnesia, impaired judgement, vertigo/ataxia, increased respiration, blood pressure, heart rate
Stage of Excitement:
Delirious, excited, amnestic. Irregular respirations, struggling, retching and vomiting
Stage of Surgical Anesthesia
Recurrence of regular respiration --> cessation, Loss of corneal, swallowing, eyelid reflexes Skeletal muscle relaxation Decreased blood pressure
Stage of Medullary Depression
Begins at cessation of spontaneous respiration --> severe depression of vasomotor and respiratory centers-->without support = Death

6. Mechanism of action
Anesthetic agents may enhance action of inhibitory neurotrasmitters such as GABA and glycine as well as blocking excitatory NTM actions such as glutamic acid
It is suggested that incorporation of the anesthetic drug into cell membrane phospholipids alters cell membrane fluidity
اندماج

7. Pre-anesthetic medications
These are drugs used to facilitate smooth induction of anesthesia and help to lower the dose and side effects of anesthetic drugs
Reduce postoperative pain
Provide amnesia, decrease anxiety
Decrease secretions(give antichlinergic due to vagal stimulation --- bradycardia ----- increase secretions)
مقدمة إستهلالية

8. Pre-anesthetic medications
Sedative hypnotics: BZs or barbiturates
Antihistaminics: H1 (anti-allergic) and H2 blockers (to reduce gastric acidity)
Anti-emetics: metoclopramide
Opioid analgesics: morphine or pethidine
5. Anti-cholinergics: scopolamine
Muscle relaxant , drugs to potentiate anesthesia action  adjuvants given
anesthesia
H1 blockers (anti-allergic) and H2 blockers (to reduce gastric acidity).

9. Classification of general anesthetic agents:
2) IV anesthetic
drugs
Inhaled volatile
agents
متطاير

10. IV anesthetic drugs

11. The term intravenous anesthetic agents means inducing anesthesia by drugs
administered intravenously.
Unbound, lipid soluble, unionized molecules cross the blood brain barrier the quickest.
Advantages of IV anesthesia include:
rapid and smooth induction of anesthesia
little equipment requirement (syringes, needles, catheters)
easy administration of drugs

12. PROPERTIES OF THE IDEAL INTRA- VENOUS ANAESTHETIC AGENT
o quick and smooth induction and recovery
o high therapeutic index
o no toxic metabolites & no emetic effects
o No involuntary movements
No emergence nightmares, No hang over effect
o potent, so small volume is required for anesthetic induction/maintenance
o compatible with other dugs ( muscle relaxants)
o no cardiopulmonary depression , no pain on injection
O No histamine release/hypersensitivity reactions
independent of liver and kidneys for metabolism and excretion
Ideal characteristics of IV anesthetics are
o high therapeutic index
o no toxic metabolites
o non-cummulative
o potent, so small volume is required for anesthetic induction/maintenance
o long shelf life and resistance to microbial contamination
o compatible with other dugs
o quick and smooth induction and recovery
o reversible with specific antagonist
o non-allergenic
o no cardiopulmonary depression
o independent of liver and kidneys for metabolism and excretion
o no effect on cerebral blood flow
o no endocrinologic effect
o no pain on injection
o inexpensive

13. intravenous Anesthetics
1- Ultra- short acting barbituates
-thiopental (Pentothal)
-methohexital (Brevital)
2- Benzodiazepines (adjuvant )
-diazepam (Valium)
-lorazepam (Ativan)
-midazolam (Versed)
3- Etomidate (Amidate)
4- Propofol (Diprivan)
sufentanil (Sufenta)

14. intravenous Anesthetics
5- Opioids
-fentanyl (Duragesic, Sublimaze)
-fentanyl- droperidol (neuroleptanalgesia)
-Morphine only with high doses, so not used
6- Dissociative anesthetics
-ketamine (Ketalar)

15. Sodium thiopental (pentothal)
An IV dose of 3-5 mg/kg results in loss of consciousness ( secs after administration). This is called the “arm brain” circulation time
It has a short duration of action min due to its redistribution away from the brain towards muscle and fat tissue
If its concentration is low enough in the brain, consciousness returns
It does not provide adequate skeletal muscle relaxation alone used in OB / GYN
( used in…. )

16. Sodium thiopental (pentothal)
Disadvantages:
1- hypotension
2- respiratory depression: dose-dependent respiratory depression
3- tissue necrosis : following i.v. infusion
4- it does not provide analgesia
5- no skeletal muscle relaxation
6- laryngeal spasm
7- bronchospasm: unusual but may be precipitated in asthmatics pts

17. Propofol (Diprivan® ) Disadvantages:
*High lipophilicity; rapid and smooth onset and rapid recovery
*Minimal nausea and vomiting
* Amnestic and anti-emetic effects
Disadvantages:
Not water soluble-- painful (50%)
Dose – related Respiratory depressant
vasodilation may produce a decline in blood pressure. Can be minimized by decreasing dose. 4. safe alternative for patients predisposed to malignant hyperthermia 5. high lipophilicity provides rapid and smooth onset, dose titratability, and rapid recovery from anesthesia
Propofol: salivation, arrhythmias, rash, apnea

18. Myocardial depression
Propofol & CVS
Myocardial depression
Propofol causes the most marked fall in blood pressure of all the induction
drugs. This is mainly due to systemic
vasodilatation.
May be slight increase in heart rate.
The fall in blood pressure is dose-
dependent and is most marked in the elderly and in shocked patients.
This
can be minimized by slow injection – avoiding inadvertent overdose.

19. Ketamine (Ketalar) * Structurally similar to phencyclidine
* Dissociative anesthesia; the patient is unconscious but appears awake and doesn’t feel pain night mares + hallucination
* Ketamine causes stimulation of the CVS. (increase HR, BP, CO)
* Good analgesic
Ketamine acts by noncompetitive antagonism at the N-methyl-D aspartate (NMDA) receptor in the brain and spinal cord.
Characteristic of sympathetic nervous system stimulation-- increase HR, BP, CO
Maintains laryngeal reflexes and skeletal muscle tone
Emergenceخروج can produce hallucinations and unpleasant dreams (15%)

20. Ketamine: advantages 1-Ketamine is a potent bronchodilator
can be used as in asthmatic patients
2- Potent analgesic in sub-anesthetic doses
3- can be administered i.v., i.m., orally, nasally, rectally, and epidurally. 
4- Suitable for shocked patients??
- increase HR, BP, CO
Maintains laryngeal reflexes and skeletal muscle tone
Emergence can produce hallucinations and unpleasant dreams (15%)

21. Ketamine: indications
Ketamine is primarily used for the induction and maintenance of general anesthesia, usually in combination with a sedative
1-Pediatric anesthesia (as the sole anesthetic for minor procedures or as an induction agent followed by muscle relaxant and endotracheal intubation)
2- Asthmatics or patients with chronic obstructive airway disease
3- To supplement spinal / epidural anesthesia / analgesia utilizing low doses
Ketamine is primarily used for the induction and maintenance of general anesthesia, usually in combination with a sedative
As part of a cream, gel, or liquid for topical application for nerve pain—the most common mixture is 10% ketoprofen, 5% Lidocaine, and 10% ketamine. Other ingredients found useful by pain specialists and their patients as well as the compounding pharmacists who make the topical mixtures include amitriptyline, cyclobenzaprine, clonidine, tramadol, and mepivicaine and other longer-acting local anaesthetics.

22. Ketamine: Disadvantages
1- The onset of action is slower than other induction drugs
2- ketamine increases cerebral blood flow, and intracranial pressure. Emergence can produce hallucination and unpleasant dreams (15 % esp. females & large dose of ketamine) usually be avoided by concomitant application of a sedative such as a BZ.
3- Generalized increase in the muscle tone and purposeful movements
4- It produces central sympathetic stimulation, which increases: arterial blood pressure, heart rate, and cardiac output
its psychotropic properties must be taken into account. Patients have reported vivid hallucinations, "going into other worlds" or "seeing God" while anesthetized, and these unwanted psychological side-effects have reduced the use of ketamine in human medicine. They can, however, usually be avoided by concomitant application of a sedative such as a benzodiazepine.[18]Characteristic of sympathetic nervous system stimulation-- increase HR, BP, CO
Maintains laryngeal reflexes and skeletal muscle tone
Emergence can produce hallucinations and unpleasant dreams (15%)

23. Thiopental Ketamine Propofol IV barbiturate Rapid induction
Short duration
Potent anesthetic but not analgesic
Slower onset & recovery
dissociative anesthesia
Good analgesia
Bronchodilator
Rapid induction, rapid pleasant recovery
No emesis
amnestic effect
No analgesia
Little Sk.m. relaxation
 BP & bradycardia
Laryngospasm, apnea, cough, bronchospasm
 sympathetic outflow
 cerebral blood
flow; postoperative
Hallucination, night mares
No analgesic action
Pain at injection site
Dose-related respiratory depression,
bradycardia, and hypotension
Associated with a bronchodilator effect due to  sympathetic outflow.

24. Benzodiazepines
They are used as adjuvant IV anesthetic agents for the following :
1 – amnesia
2 – minimal cardiac & respiratory
depressant effect
3 – anticonvulsant activity
4 – low incidence of tolerance and
dependence
5- availability of antagonist ‘ flumazenil’

25. Etomidate
is a short acting iv anaesthetic agent used for the induction of general anesthesia 
for sedation for short procedures such as reduction of dislocated joints, tracheal intubation
Rapid onset of action, usually within one minute. Duration of action 3-5 min.
Etomidate causes the least cardiovascular depression of the IV anaesthetics
Etomidate suppresses corticosteroid synthesis in the adrenal cortex by reversibly inhibiting 11-beta-hydroxylase, an enzyme important in adrenal steroid production; it leads to primary adrenal suppression.[

26. Etomidate: Disadvantages
Adrenal suppression: It supresses cortico- steroid synthesis in the adrenal cortex (Reduced cortisol plasma levels) 
Do not use etomidate for critically ill patients ( increased mortality).
Post operative vomiting is more common than with other induction agents.
Pain on injection is common and there is a high rate of thrombophlebitis
Etomidate has no analgesic activity
Etomidate suppresses corticosteroid synthesis in the adrenal cortex by reversibly inhibiting 11-beta-hydroxylase, an enzyme important in adrenal steroid production; it leads to primary adrenal suppression.[

27. Inhalational Anesthetics

28. Inhalational Anesthetics
Inhalational anesthesia refers to delivery of gases or vapors via the respiratory system to produce anesthesia
1- Gases like :Nitrous Oxide (N2O) prohibitedcyclopropane flammable and xenonexpensive by flowmeters
2-Volatile liquids are vaporized in a carrier gas (vaporizers). e.g. halothane, isoflurane, desflurane and sevoflurane
These are stored in gas cylinders and administered using flowmeters, rather than vaporisers. Cyclopropane is explosiveand is no longer used for safety reasons, although otherwise it was found to be an excellent anaesthetic. Xenon is odourless and rapid in onset, but is expensive and requires specialised equipment to administer and monitor.

29. Brain blood Pathway O2-Brain Anesthetic machine
O2 is bubbled in volatile Anesth. agnet
Mixture vapor
Anesthetic machine
Lungs
Diffuse across alveolar capillary membrane
blood
Brain

30. Ideal Characteristics
1. pleasant to inhale, permitting a smooth induction and recovery
2. potent to allow the concomitant administration of high oxygen
3. Rapid induction and recovery (low solubility)
4. easily and cheaply prepared in a pure form
5. No CV or respiratory effects, non-toxic to organ systems
6. safe for exposure to operating room staff
7. not flammable, not metabolized. And nvironmentally safe
8. being liquid at room temperature, but evaporating easily for administration by inhalation
being liquid at room temperature, but evaporating easily for administration by inhalation

31. Rate of induction and recovery Blood/Gas partition coefficient
Depends on
Blood/Gas partition coefficient
is the ratio of anesthetic concentration in blood compared to gas phase.
Solubility in blood:
More soluble = slower induction (slow onset) e.g. Halothane slower recovery
Less soluble = faster induction faster recovery
e.g. Nitrous oxide
Blood Gas Coefficient: solubility in blood
Arabic
English
Spanish
معامل الق
الدم 
 الغاز / معامل حاجز
MAC: minimum alveolar concentration (low MAC means high potency)

32. If drug is slow induction
Means good solubility in blood

33. Minimum Alveolar Concentration (MAC)
Anesthetic potency is measured in MAC. It allows us to compare the potency of the various inhalational agents
MAC is defined as the concentration of anesthetic that is required to produce immobility in 50% of patients exposed to a noxious stimulus (surgical incision)
The steady state minimum alveolar concentration (percent) of an inhalational agent that is required for immobility of 50% of the subjects exposed to a noxious stimulus (e.g., surgical incision)

34. MAC Value Halothane = 0.75% Isoflurane = 1.16% Euflurane = 1.68%
Sevoflurane = 2%
N2O = 105% fastest onset & recovery because not soluble
# Halothane is the most potent
# N2O alone is unable to produce adequate anesthesia ( require high conc. ) weak  low potency

35. Nitrous Oxide Physical property:
*Colorless, odorless, and nonflammable, laughing gas
Pharmacology
Good analgesic
Low solubility (fast on/off)
Minimal effects on heart rate and BP
Weak anesthetic- MAC = 105% (Low potency)
 it must be used as an adjunct anaesthetic, along with other agents
Safe, efficacious agentالمساعد
Simple linear compound
Low blood solubility (quick recovery)
* Not metabolized
* Only anesthetic agent that is inorganic
Minimal Myocardial effects

36. Halothane Halogenated hydrocarbon
# Most potent inhalational anesthetic
(MAC=0.75%)
# has a pleasant, non-irritant smell
# bronchodilator
# drug of choice in children
# Slow induction & slow recovery
# Hepatotoxicity
# Myocardial depressant
# Sensitizes myocardium to effects of exogenous
catecholamines ( ventricular arrhythmias)
Halothane is widely available, and has a number of advantages. It is non-flammable, has a pleasant, non-irritant smell, and induces unconsciousness more quickly than ether. Its disadvan tages are that it depresses the cardiovascular and respiratory systems, resulting in hypotension and hypoxia.
Most potent inhalational anesthetic
MAC of 0.75%
Efficacious in depressing consciousness
Very soluble in blood and adipose
Prolonged emergence
Sensitizes myocardium to effects of exogenous catecholamines-- ventricular arrhythmias

37. ISOfluranE Advantages Disadvantages Little risk of hepatic or renal
Rapid induction and recovery
Little risk of hepatic or renal
toxicity
Cardiovascular stability
Muscle relaxation
Few side effects
Disadvantages
Pungent odor  لاذع cough, breath
holding

38. Therapeutic advantages
Halothane
1956
Isoflurane
1984
Nitrous oxide
1799
Potency
High
weak
Induction& recovery
Slow
Rapid
Very rapid
Arrhythmia
1.  risk
2. sensitivity to catecholamines
No risk
Hepatotoxicity
 risk
( not in children)
Therapeutic advantages
-drug of choice in children
- Good for asthmatic bronchodilataion
1. Good muscle relaxation.
2. Rapid recovery
3. No sensitization to catecholamines
1. Rapid onset & recovery
2. Good analgesia
Halothane depresses the myocardium
Potent agents reduce myocardial O2 consumption
Halothane sensitizes myocardium to catechol-amines, predisposing to ventricular arrhythmias
Halothane Hepatitis” --

39. Sevoflurane Advantages
1. Well tolerated (non-irritant, sweet odor), even at high concentrations, making this the agent of choice for inhalational induction
2. Rapid induction and recovery
3. Does not sensitize the myocardium to
catecholamines as much as halothane
4. Bronchodilator
sevoflurane is pleasant to inhale and is rapid in onset and offset
بقدر ما

40. Sevoflurane Disadvantages
1. Less potent than similar halogenated agents
2. Risk of renal toxicity ( about 5% is metabolized and serum fluoride level is elevated)
free fluoride and renal toxicity with sevo

41. Thank You