Anasthesia 3

Drugs in General Anaesthesia (GA)

Induction agents:

• Depressants that act on GABA receptors.

• Increase chloride conductance.

• Lead to membrane hyperpolarization.

Intravenous GA Induction Agents

BARBITURATES:

• Good antiepileptic action (except methohexital).

• Mnemonic: Barbie
• 2 barbi
• methayil kidathi shock adipich seizure varuthunna barbi
• Thiyil idunna babri with gralicy smell. Touch neck head and sathym parayippikkum
1. Thiopentone Sodium
• Highly lipid soluble.
• Very short acting due to Redistribution.
2. Methohexital

Thiopentone Sodium:

• NEUROPROTECTIVE

• General properties:
• Yellow powder.
• pH 10.5 (most alkaline).
• With garlic/onion smell.

• Onset:
• 15 seconds (arm brain circulation time).

• Metabolism:
• Highly lipophilic.
• Termination of action by redistribution (brain => fat).
• Patient will have cycles of waking up and going to sleep
• Patient will have a hangover effect → do not remember anything

• Dose:
• 3-5 mg/kg.

• Use:
• AOC (Agent of choice):
• Neurosurgery (max. decrease in ICP).
• Hyperthyroidism
• Truth serum

• Complication:
• Accidental intraarterial administration:
• Pain.
• Pallor.
• Edema.
• Gangrene.
• Management:
• Retain cannula
• to prevent vasospasm
• Saline/heparin flush.
• Stellate ganglion block (2.5%)
• ⛔ lower cervical sympathetic ganglion
• ⛔ Sympathetic NS → Vasodilatation

Methohexital:

• Dose:
• 1-1.5 mg/kg (more potent than thiopentone).

• Disadvantage:
• Proconvulsant (avoided in neurosurgery).

• Indication:
• Electroconvulsive therapy.

NON BARBITURATES:

• Drugs summary
1. Propofol
• Painful.
• DOC for day care Surgery.
• Avoided in patients with egg allergy.
2. Ketamine
• Keettum ellam (↑ IOP, BP, PR), Nammada (NMDA ⛔) Kids (NMDA, Kids) Dissociative () and depressed (invivo depression) ayi → Cycle (Phencyclidine) vangathond

• Kunjungalde Sx use → like TOF, asthma (COPD), Pediatric Sx, burns, sick, depression

• Not kunjugalde Sx → like heart, htn, eye Sx → dont use

• ↑ IOP, HR, BP, Renal blood flow, RR, Liver Blood flow

• But Approved in Rx of chronic depression

ㅤ	Property
K	• Agent of choice in kids
E	• Emergence Reaction • (post operative delirium and hallucinations) • Cause Epilepsy → So avoid
T	• Thalamo-Cortical junction (site of action) • Dissociative Anesthesia
A	• Analgesic
M	• Meals (can be given in full stomach)
I	• ↑ BP/IOP/ICP • (Agent of choice in shock)
N	• NMDA Blocker
E	• Excellent bronchodilator

3. Etomidate
• AOC for CVS surgery.
• Most cardiostable
• Causes Adrenal Suppression.

Propofol:

• Form:
• White.
• Egg lecithin (used within 6 hours).
• Oily preparation (soya bean oil).
• Mixed with lignocaine to decrease pain.

• Properties:
• Antiemetic.
• Antipruritic.

• Dose:
• 1 - 2.5 mg/kg.

• Onset:
• 15 seconds.

• Duration:
• 8-10 minutes (without hangover).

• Agent of choice:
• day care/ liver/ kidney/ neuroSx/porphyria
• Total IV anesthesia
• Used in Malignant hyperthermia where Inhalational agents avoided
• Day care/ambulatory surgery.
• Monitored anesthesia care.
• Ambulatory Sx
• Office-based anesthesia.
• Ophthalmic surgery (max ↓↓ in IOP).
• LMA insertion.
• Resolution of laryngospasm (↓↓ reflexes).
• Endoscopy.
• Colonoscopy.

• Side effects:
• Propofol infusion syndrome (on prolonged infusion - 1 to 2 days):
• Green colour urine.
• Severe metabolic acidosis.
• Asystole.
• Addictive due to pleasant hallucinations.

Etomidate:

Side effects:

• Mnemonic: ETOMI date
• Emetic.
• Epileptogenic.
• Oily (Propylene Glycol)
• Tortures the hand → Painful
• Myoclonus.
• ⛔ adrenocortical synthesis.
• Date → Most Cardiostable
• AOC for
• Cardiac Sx
• Aneurysm Sx
• DC cardioversion

Dose:

• 0.2-0.3 mg/kg.

Ketamine:

• Form:
• Phencyclidine derivative.

• Properties:
• Dissociative anesthesia.
• NMDA receptor antagonist
• ↓↓ catecholamine release
• Depressant
• In vivo → prolonged use → d/t chronic release of catecholamines → depletion of catecholamines → depressant action

• Dose:
• IV 1 - 2 mg/kg.
• IM 4 - 6 mg/kg.

• Duration:
• Intrathecally used with local anesthesia to increase duration.
• But should be preservative free

• Agent of choice:
• Shock (↑↑ HR, ↑↑ BP).
• Asthma/COPD
• good bronchodilator
• Tetralogy of Fallot.
• Paediatric surgery.
• Low resource settings
• burns, sick, depressed
• Very good analgesic → Mx of chronic pain
• Opioid tolerance
• Approved in Rx of chronic depression

• Contraindications (C/I):
• HTN and cardiac conditions.
• Ocular surgery (increase IOP).

• Side effects:
• ↑ oral secretions
• Rx: Atropine/Glycopyrrolate
• Unpleasant hallucinations/ emergence reaction
• Reduces with midazolam

Inhalational Induction Agents

• Characteristics:
• Maintain depth of anesthesia.
• Induce sleep (paediatric).
• Depressants.
• Enter and exit circulation via lungs.

Classification:

• Meyer Overton Rule:
• Potency is proportional to lipid solubility.

Minimum Alveolar Concentration (MAC):

• Minimum amount of drug required to in alveoli produce immobility to painful stimulus in 50% of subjects

• MAC ∝ 1 / Potency

Order of Potency

• Least MAC → most potent

• MAC Is potent

• Methoxyflurane > Halothane > Isoflurane > Sevoflurane > Desflurane > N2O

MAC	Drug	Potency
Maximum	N₂O (104%)	Least
Minimum	Methoxyflurane	Most

• Pottan () BJ () cheyymbo → Me HIS Don’t Know
• Order of Potency () and B/G ratio ()

MAC vs Age

• Infant > Neonate > Adult

FACTORS AFFECTING UPTAKE:

Machine to Alveoli:

• Concentration effect:
• Higher inspired concentration leads to quicker induction.

• Second gas effect (Augmented in flow effect):
• In presence of N2O,
• concentration of IA increases.
• Reason:
• Rapid diffusion of N2O from alveoli to pulmonary circulation.

• Both effects seen simultaneously at start of surgery.

Diffusion hypoxia / Fink effect

• At End of surgery

• Rapid diffusion of N2O from pulmonary circulation to alveoli→ dilution of O2 in alveoli→ Hypoxia

• Management:
• O2 supplementation.

Alveoli To Pulmonary Circulation:

Blood gas partition coefficient (B/G ratio):

• Concentration of agent in blood / concentration of agent in alveoli

• Measure of Blood Solubility

• BPGC ∝ 1 / speed of onset

Increased B/G ratio :

• Increased concentration in blood.

• Increased solubility in blood.

• Delayed induction.

Systemic Effects Of Inhalational Agents:

Effects of N₂O

• Proven teratogen

• Disrupts Vit B₁₂ metabolism
• Megaloblastic anemia
• Subacute combined degeneration of spinal cord

• Contraindicated in
• Pneumothorax / Pneumomediastinum
• Middle ear surgery
• Pregnancy
• Retinal surgery

• Mnemonic: No (NO) PEEPing (Pregnancy, Pnumo, Ear, Eye, Pneumo)

Muscle Relaxants

• Aids in intubation/surgical relaxation.

• NEUROMUSCULAR BLOCKERS:
• May be 
• depolarizing or 
• non-depolarizing skeletal muscle relaxants.

Depolarizing Muscle Relaxants (DMR):

• Acts by stimulating NM receptors.

• Example is Succinylcholine (SCh).

Order of Anaphylaxis in Immediate Post Op period:

Succinylcholine (2 molecules of ACh)

• NOTE (similar to statins)
• Shortest acting MR [< 5 min]
• C/I in nerve and muscle injuries
• [Can cause severe hyperkalemia]
• malignant hyperthermia
• Fasciculations: Responsible for post operative muscle pain

• Dosage
• 1 – 2 mg/kg

• Duration
• < 10 min

• Onset of action
• 30 sec

• AOC
• Difficult intubation
• Rapid sequence intubation

Mechanism of Action

• Non-competitive blockade:
• ACh receptor
• Succinyl choline (2 molecules of ACh) → bind with 2 alpha units in post synaptic membrane → Receptor wide open → Rapid influx of sodium + efflux through voltage and time gated Na channel → Fasciculations
• After 30 sec → time gate closes while voltage gate is open → Sodium ions remains inside → non competitive blockade

• Metabolised by pseudocholinesterase (produced by liver)

Systemic Effects

• Bradyarrhythmia
• Rx: Atropine / Glycopyrrolate
• Atropine premedication is must for patients receiving Succinylcholine

• Muscle fasciculations
• Post-op myalgia

• ↑ ICP, ↑ IOP, ↑ Intragastric pressure (but paradoxically ↓ aspiration risk)

• Anaphylaxis

Contraindications

• Family h/o malignant hyperthermia & muscular dystrophies

• Pre-existing hyperkalemia

• Burns

• Acute liver failure

• Sepsis

• Hemiplegia / Paraplegia

Reasons for Prolonged Duration

1. ↓ PCE concentration
• Maximum 20 mins
• Causes
• Acute liver failure
• Neonates, pregnancy
• Drugs: Pyridostigmine

2. ↓ PCE activity
• Atypical pseudocholinesterase
• Dibucaine number (↑ affinity to normal pseudocholinesterase)
• Qualitative analysis of enzyme activity

Type	Dibucaine No.	Duration
Normal	80:20	<10 min
Heterozygous	50:50	45 min – 1 hr
Homozygous	20:80	6–8 hr

• Rx: Continue mechanical ventilation + Fresh frozen plasma

3. Phase II block
• Succinylcholine >5 mg/kg → receptor damage
• Causes prolonged duration of action
• Rx: Continue Mechanical ventilation
• Resembles NDMR block → Fade present → but Do not give Neostigmine

Butyrylcholinesterase/Pseudocholinesterase

• Metabolise Succinylcholine and Mivacurium

Train of four

Purpose:

• Assess relaxation recovery.

Method:

• Train of Four (TOF).
• Stimulate by 4 supramaximal currents.
• TOF ratio > 0.9
• Ratio of 4th stimulus to 1st stimulus
• safe extubation (Fully recovered from muscle relaxant)

Response:

• DMR
• constant diminution.

• NDMR or Phase II of DMR
• gradual fade.

---

Phase 2 block

• Succinylcholine >5 mg/kg → receptor damage

• Causes prolonged duration of action

• Rx: Continue Mechanical ventilation

• Resembles NDMR block → Fade present → but Do not give Neostigmine

Muscle Relaxants: NDMR

• Act by blocking NM receptors competitively.

• Example is d-Tubocurarine (Curare).

• Does not cause post operative muscle pain.

• Reversal Agents:
• Used to reverse action of NDMR after surgery.
• Neostigmine: Can cause cholinergic adverse effects.
• Suggamadex: No cholinergic side effects.

• Types:
• Steroidal compounds (green box).
• Curonium 
• No histamine released
• Curonium - steroid
• Benzylisoquinoline compounds (pink box).
• Curium 
• Release histamine
• Cis-atracurium releases less histamine than atracurium,
• so preferred
• Mivacurium [Shortest acting]

Reversal Of Block

• Sugammadex (New reversal agent):
• Cyclodextrin molecule
• Bind covalently
• Can be given at any time
• Used for reversal of Vecuronium/Rocuronium (in day care surgery)
• Side effects:
• Anaphylaxis
• Contraceptive failure

• Neostigmine:
• Administered on spontaneous breathing
• etCO2: Curare cleft
• Indirect reversal agent → Acetylcholinesterase Inhibitor
• Dose:
• 0.05 - 0.07 mg/kg
• Muscarinic Side effect:
• Bradycardia.
• Increased oral secretions.
• S/E avoided with co administration of
• Atropine/Glycopyrrolate.

Signs of adequate reversal:

• Regular respiration and adequate tidal volume.

• Spontaneous eye opening.

• Spontaneous limb movement.

• Able to protrude tongue, cough (no cyanosis).

• Able to lift head >5 sec (most reliable bedside test).

• Able to hold tongue depressor between central incisors.

• Train of four ratio > 0.9:
• Guaranteed recovery.

Paediatric Surgeries

• Preoperative Preparation:
• To decrease anxiety:
• Benzodiazepine syrup (midazolam).
• Ketamine IM 4-6 mg/kg (children >6 months age).
• Dissociative
• Parental accompaniment in OT.

• Fasting guidelines:
• 2 hours: Clear liquids.
• 4 hours: Breast milk.
• 6 hours: Solids , Non human milk
• 8 hours: Heavy fatty meal.

• Note:
• EMLA Cream = Eutectic mixture
• Lignocaine (2.5%) + Prilocaine (2.5%)
• Used for superficial procedures (IV cannulation).

Intraoperative Considerations:

• Induction of anaesthesia:
• Inhalational
• AOC: Sevoflurane (Sweet smelling) > Halothane (Inhalational agents)

• Muscle relaxant:
• AOC: Vecuronium/Atracurium.
• Avoid Succinylcholine in < 1 year → due to undiagnosed myopathies.
• Laryngoscope: Miller's blade.
• ET: Microcuffed > Uncuffed

• Prevention of hypothermia:
• OT temperature: 27-28°C.
• Warm fluids and heating devices.
• Hypothermia can lead to a decrease in brain activity
• EEG → slowing of the frequency and amplitude.

• Analgesic :
• Fentanyl 1-2 mcg/kg (Short acting agent)

Post-Operative Analgesia:

• Caudal anaesthesia:



• Type of epidural anasthesia

• Insertion at S4-S5 vertebral junction
• directed towards S2 segment.

• No risk of spinal cord injury.

• USG guidance can be used

• Administered only in postoperative phase in children > adults

• Increase risk of infection (due to bowel and bladder immaturity).

• Note:
• Duramater may extend upto S2
• Spinal cord → Upper end of L3

Day Care Anaesthesia / Surgery