- Defintion : Reversible, controlled, loss of sensation
- Components:
- Analgesia
- Amnesia
- - Muscle relaxation
- Suppression of excessive autonomic responses (e.x: tachycardia, bronchospasm)
- Practical Conduct :
- Pre Anesthetic check up
- Just preoperative monitoring
- Induction
- Maintenance
- Recovery
- Post operative Care
Measures before surgery
- Control concurrent diseases (such as hypertension, DM, CAD) before entering OR.
- Patient have to be NPO before surgery, because patient will be given muscle relaxant that will
relax sphincters, and so stomach content will come out (there will be risk of aspiration).
Premedication
- Reasons for administration of premedications:
- Reduction of fear and anxiety ( catecholamine, risks)
- Reduction of saliva secretion (especially in cerebral palsy, infection)
- You can give atropine or glycopyrrolate
- Prevention of vagal reflexes (caused by surgical stimulation like squint operation
stretching of anal sphincter, or associated with medication such as beta-blockers)
- Give atropine
- As part of anesthetic technique e.g. use of narcotics (morphine)
- To produce amnesia
- Hyoscine ( Scopolamine) (rarely used)
- Benzodiazepines - it cause anterograde amnesia
- Diazepam-hyoscine –complete amnesia in 75% of patient
o For specific therapeutic effects
- Transdermal glyceryl nitrate patches for angina patients.
- Steroids
- Beta-blockers
Induction Agents
- Intravenous induction Agents
- Thiopentone Sodium
- Propofol (most common used)
- Etomodate
- Ketamine
- Benzodiazepines
-- medazolam (useful in cardiac surgery, because it is haemodynamically stable)
- Opioids
-- Fentanil
-- Sufentanil
-- Remifentanil
- Inhalational induction Agents
- Halothane
- Sevoflurane (most common used)
THIOPENTONE SODIUM
- Mechanism of Action:
- Enhance transmission of inhibitory neurotransmitters (GABA).
- Depress the reticular activating system (In brain stem, which control consciousness).
- Suppress transmission of excitatory neurotransmitters (acetylcholine).
- It was Introduce commercially as PENTOTHAL SODIUM in 1935
- It is 1st I.V anesthetic agent
- IV route only.
- pH of 2.5 % thiopentone Sod. is 10.5 (highly alkaline)
- > 2.5 % concentration causes: pain and thrombosis
- Slow infusion needed to reduce pain
- One arm brain circulation time – 30 sec.
- Effect loss by redistribution
- Short duration of action: 8-10 min
- Recovery: patient will wake drowsy
- Highly lipid soluble & higher protein bound
- Effect will be prolong in
- hypovolemic shock
- Liver disease (due to low serum albumin)
- Acidosis (due to increase non ionized fraction)
- Effect on Organs System
- Cardiovascular
-- Vasodilatation ( peripheral pooling of Blood)(BP drop up to 30% from base-line)
-- You need to give a good amount of fluid.
- Cerebral (thiopentone sodium is very good for neurosurgery, such as AVM, aneurysm)
-- Decrease in Cerebral Blood Flow (CBF)
-- Decrease in cerebral O2 consumption (up to 50%)
-- Brain protection (by constrict the cerebral vasculature)
- For controlling grand mal seizures (all types of epilepsy can be controlled by this drug)
- It have no Analgesic effect
- Contraindication
- Porphyries
- B. Asthma
PROPOFOL
- Mechanism of Action:
- Facilitation of inhibitory neurotransmission mediated by GABA
- Cause Pain during injection
- So add 2-3 ml of 1% Lignocaine in 18 ml propofol)
- only iv route
- V. high lipid soluble, effect is as fast as Thiopentone sod.
- 1\2 life 2-8 min.
- High clearance rate – 10 time that of thiopentone
- Recovery : v. rapid, due to Redistribution
- Recovery: without hangover, Smooth with clear mind.
- Good for day care surgery (induction of small surgery)
- Propofol Can use as TIVA (Total Intravenous Anaesthesia)
- Propofol is useful for neurosurgery (for brain mapping)
- Long term sedation in ICU – can cause
- Lipemia
- metabolic acidosis
- Excrete by kidney, however can be used safely in CRF (chronic renal failure)
- No preservative used, So high risk of infection, unless aseptic technique is used.
- Effect on Organ systems
- Cardiovascular System
-- Hypotension (BP drop 50% of base-line)
-- At least give 500 ml fluid before start propofol.
o Respiratory System
-- induce depression of upper airway reflex intubation without m.relaxant
o Cerebral
-- decreases cerebral blood flow
-- decreases the ICP
-- similar to thiopentone in cerebral protection
- Anti-pruritic
- Anti-emetic
- Potentiate nondepolarizing muscle relaxants
- Effect on various organs:
- Cardiovascular
-- Increase BP, HR, CO (central stimulation of sympathetic nervous system)
- Respiratory
-- Potent bronchodilator
-- Kitamine is the ideal inducing agent in Asthmatic patient.
- increase salivation (use Atropine or Glycopyrolate to decrease secretion)
- Cerebral
-- Increase cerebral O2 consumption, CBF, ICP not good for eye surgery and
neurosurgery.
- Profound analgesia
- Side effects: delirium, Hallucination.
Etomidate
- Short Acting Induction agent
- Produce Amnesia & Anesthesia
- No Analgesia
- Etomidate is the most emetogenic of the intravenous induction agents.
- Ideal induction agent for pts who are hemodynamically unstable (it don’t decrease BP)
- Useful for hypotension and shock situations.
Benzodiazepines
- Uses:
o For induction of anesthesia
o For sedation, amnesia, adjuncts to GA ,anticonvulsant, muscle relaxation, hypnotic
o Premedication
- Mechanism of action:
o Enhances the Inhibitory effect on various neurotransmitters (Specially GABA)
- It is not an analgesic
- Antidote: Flumazenil
- It crosses the placenta
- It cause Respiratory depression that is dose dependent.
- Examples
o Diazepam
o Lorazepam
o Midazolam
Diazepam
- Mainly for premedication
- long acting
- Metabolized in liver – active metabolites may prolong its clinical effect.
- Pain at I.V injection Site.
- ½ life 20 hr. ( for Lorazipam 15 hrs)
- It cause muscle relaxation
- It cause phlebitis
- It may cause late respiratory depression
Midazolam
- Short acting
- ½ life time 2-4 hr
- IV, IM, oral (after I.V push – peak level achieved in 30-90 min.)
- Water soluble
- End products are not active no late respiratory depression.
Lorazepam
- Long acting (Half life 10-12 hrs)
- prolong effect on respiratory suppression
Maintenance of general Anesthesia
- three component of maintenance anesthesia:
- Amnesia
- Analgesia
- Muscle relaxation
Drugs for Analgesia: Opioids (Narcotics)
- Examples:
- Long acting: Morphine, Meperidine (Pathidine), Methadone
- Short acting: Fentynil, Sufentynil, Alfentanil
- For postoperative pain you have to use long acting narcotics.
- Mode of action:
- Bind with specific opioid receptors in brain & Spinal Cord.
- Eliminated by liver
- Excreted in urine (in renal failure, there will be prolong effect)
- Effect on body:
- Analgesia
- Dose dependent Respiratory depression.
- Muscle rigidity
- N&V (nausea & Vomiting)
- Urine retention
- decrease in pupil size (miosis)
- Allergy
- The stress response to surgical stimulation is measured in the secretion of specific hormones,
including catecholamines, anti-diuretic hormone and cortisol.
- Opioids block the release of these hormones more completely than do volatile anesthetics.
- Narcotic antagonist (antidote): Naloxon
- Opioid receptors
- mu receptor (Morphine , Fentalyl), Causes:
-- Supraspinal Analgesia
-- Resp. depression
-- Muscle rigidity
-- Physical dependence
- Kappa receptor (Morphine) causes:
-- Sedation
-- Spinal analgesia
- Delta receptor, Causes
-- analgesia
- Sigma Receptor, Cause
-- Hallucinations
-- Respiratory stimulation
Morphine
- It is the most agent used for postoperative pain.
- Long acting (half life 2-4hr, duration of action: 3-4 hrs)
- Histamine release (So, don’t use morphine in asthmatic patient, it will trigger bronchospasm)
- Active metabolites:
-- morphine3 glucuronide
-- morphine 6 glucuronide
- Low fat soluble
Fentanyl & Sufentanil & Remifentanil
- They used for intraoperative anesthesia.
- high lipid soluble
- rapid onset & short duration of action
- end products are inactive no late respiratory depression.
- high incident of N&V
- Remifentanil is 200 time potent than morphine.
Pethidine (Meperidine)
- First synthetic opioid synthesized in 1932
- Indicated for the treatment of moderate to severe pain
- Can be used as Tablet, Syrup, IV ,IM
- It is used for chronic pain.
- It can be used for biliary spasm and renal colic (better than morphine).
Muscle Relaxent
- Muscle relaxation can be done by
- Inhalational agents
- Regional Nerve block
- Neuromuscular block (mostly used in GA)
- Muscle relaxants are commonly used during anesthesia to provide
- Relaxation for surgery
- To allow mechanical ventilation
- In intensive care
- No pain relief or Analgesia
- No unconsciousness or Amnesia
- Two types of muscle relaxant:
o Depolarizing Muscle Relaxants
-- Acetyl-choline receptor agonist
- Non-Depolarizing Muscle Relaxants
-- Competitive Antagonist
Succinylcholine (SUX)
- It is a depolarizing muscle relaxant
- Mechanism of action:
- Ach receptor agonist
- Act on Ach receptor – causes depolarization of end plate & adjacent muscle membrane.
- Succinylcholine is not metabolized by Acetylcholinestarase but by plasma cholinesterases or
Pseudocholinesterases (produce by liver, so in liver failure effect will be prolonged).
- Rapid onset of action (30-60 sec.) and short duration of action(< 10 min).
- Depolarizing block is ch\ by –
- Muscle fasciculation
o potentiation of block by anticholinesterases
- Indication
- Rapid sequence induction and intubation (rapid onset , Short duration, and no risk of
aspiration or regurgitation)
-- Useful in case of full stomach or difficult airways.
- Act on (cholinergic receptors) of SA node causing Bradycardia
- First muscle to relax with SUX is muscle around eye (loss of eyelash reflex) , then sphincters, the
last muscle is the diaphragm.
- Side effect
- Apnea & bradycardia
- Muscle pain
- Fasciculation
- Hyperkalemia (Increase
0.5mEq\L)
- Increase in Intra-gastric Pressure
- increase in Intra-ocular Pressure
- Malignant Hyperthermia
11 General Anesthesia
- A life threatening potassium elevation is possible in patients with
- burn injuries.
- massive trauma
o neurological disorders (upper & lower motor neuron lesion)
- C\I (contraindications):
- Prolong Paralysis (hemiplegia, paraplegia)
- Increase ICP
- Rhabdomyolysis
- Myopathies
- Hyperkalemia
Non depolarizing Muscle relaxants
- Function as competitive antagonists
- Examples:
- Short acting: mivacurim
- Intermediate acting: Rocuronium, Vecuronium, ,Atracurium, CisAtracurium.
- Long acting: Pancuronium, Tubocurarine
- They used for maintenance.
Rocuronium
- It is a non depolarizing muscle relaxan
- It is an aminosteroid
- More recent member
- Rapid onset (Rapid sequence induction and intubation could be done)
- Intermediate acting (20-30 min)
- Metabolized and excreted by liver
- good hemodynamic stability
- Sugammadex –(for reversal)
Vecuronium
- duration of action -30-40 min
- excreted primarily by bile, partially in urine
Pancuronium
- duration of action -30-40 min
- excreted mostly unchanged in urine
CisAtracurium
- No Histamine release
- purified form of atracurium
12 General Anesthesia
Atracurium
- It is a non-depolarizing neuromuscular blocking agent.
- intermediate-duration
- Metabolize itself in blood by Hofmann degradation and ester hydrolysis
- predictable onset and duration of action
- Atracurium is useful in Liver Failure & Renal failure patients.
- Histamine release: causing hypotension, reflex tachycardia, cutaneous flushing
- Not used in asthma
- Placental transfer is insignificant and the drug is widely used in obstetrics
General considerations in the use of muscle relaxants
- Respiration must be controlled via an endotracheal tube or other means.
- Always be certain that you will able to ventilate the patient by face mask before paralyzing
them.
- For rapid onset of action –suxamethonium (succinylcholine) should be used .
- Non-depolarising muscle relaxants take about 2-3 minutes to act and you should allow time for
relaxation to develop before attempting intubation.
- The supplemental dose should be about 25% of the initial dose.
- Never attempt to reverse the relaxation until at least 15-20 minutes after the last dose of
relaxant was given (except with Rocuronium, by using sugammadex)
- Nondepolarizing Muscle relaxants are not significantly metabolized (except mivacurium &
atracurium)
And so Need reversal agents (Cholinesterase inhibitors) that inhibit
acetylecholinesterase enzyme activity
Inhalational Anesthetics
- Act on reticular activating system
- They very useful for Induction in Pediatric patient.
- Indications for inhalational induction
- Adult patient with no I.V access
- Child with I.V access
- Neonate with I.V access
- Adult with difficult airway
- MAC (The alveolar concentration of an inhaled anesthetic that prevents movement in 50% in
response to surgical stimulus)
- MAC “minimal alveolar concentration” is a measure of potency
o Nitrous oxide MAC is 105% can’t used alone + need to give at least 30% oxygen
with it
- The Less MAC % the more potent anesthetics
- Blood/gas partial coefficient more time needed to be sleep / more delay in recovery
Halothane is the most potent, Desflurane is the most rapid action
ISOFURANE
- dilates coronary arteries ( but less potent than nitroglycerine or adenosine).
- Can cause (coronary steal syndrome) regional myocardial ischemia
- Better cardiac stability
DESFLURANE
- Low solubility of desflurane in blood and tissues causes a very rapid wash in and wash out of
anesthetic.
- very fast induction and recovery
- it is good for maintenance.
- It is not good for induction, it cause coughing.
SEVOFLURANE
- Excellent choice for rapid and smooth inhalational induction (because of non pungency and
rapid increases in alveolar anesthetic concentration).
- Rapid recovery
- Used for Pediatric induction
