1. Inhalational Agents
4th year MBChB tutorial

3. Synonyms Inhalational Agents Anaesthetic gases Anaesthetic Agents
Volatiles

4. History of Anaesthesia

5. How it all began...
October 1846 – Dr William Morton first demonstrated the use of Ether to induce anaesthesia
First use of ether in South Africa – 1847 in Grahamstown!

6. Ether dome Surgeon: John Collins Warren Comment: “Gentleman,
October 16th 1846 
First successful public demonstration of anaesthesia
Massachusetts General Hospital, Boston
 Anaesthetist: William Thomas Green Morton
Agent: Diethyl Ether
Patient: Gilbert Abbott
Operation: Excision of tumour under jaw
Surgeon: John Collins Warren
Comment: “Gentleman,
this is no humbug!”

7. Older volatiles Ether Chloroform
John Snow designed the first inhaler (forerunner to the modern vaporisers)
Administered chloroform to Queen Victoria for delivery of her last 2 children, lead to the birth of obstetric anaesthesia!
What else is John Snow famous for?
Chloroform
The first fatality from anaesthesia was a 15-year- old girl called Hannah Greener, who died on January 28, 1848 during surgery to remove an ingrown toenail!!!
Respiratory or Cardiac side-effects from overdose

8. Schimmelbusch Mask narcosis mask for dripping liquid ether
now obsolete, it was a mask constructed of wire, and covered with cloth.

9. Modern volatiles and vapourisers

10. Modern Volatiles
1930– introduction of cyclopropane and trichloroethylene
Halothane - The first modern non-flammable hydrocarbon was introduced in 1960
By the 1980s, the anaesthetic vaporiser had evolved considerably with several modifications and safety features

11. Vapourisers Colour coded vapourisers and bottles
Colour and key-filler system
Anaesthetic back-bar interlocks so you can’t switch on more than one vapouriser at a time

12. Vapouriser cassettes

13. Pharmacology of Volatiles

14. Uptake and Distribution
The speed at which you “go to sleep” depends on the anaesthetic agent’s partial pressure in the BRAIN
Delivery to the lungs
Uptake of agent from the lungs
Uptake of the agent into the tissues

15. 1) Delivery to the Lungs Inspired concentration Alveolar Ventilation
The higher the concentration of the agent, the faster the induction
Alveolar Ventilation
Induction is increased by increased ventilation
Induction in decreased by reduced ventilation eg
respiratory depression
obstructed airway

16. 2) Uptake of anaesthetic agent from the lungs
Solubility for the agent in the blood (blood/gas solubility co-efficient)
The more soluble the agent – the slower the induction!
The less soluble the agent – the more rapid the induction!
Why does this occur? Very difficult concept to grasp
If the circulation constantly carries the agent away, the alveolar concentration does not have a chance to build up and as a result the concentration in the brain rises slowly too
Cardiac output
If CO increased, increased agent uptake from alveoli, therefore slow inuction And vice versa

17. Alveolar to mixed venous partial pressure difference
Initially during induction, the tissues take up a large amount of the AA - anaesthetic agent (due to the concentration gradient)
The blood returning to the lungs i.e. the mixed venous blood therefore has a low concentration of the AA
Uptake of the AA from the alveoli to the blood in lungs is high ( also due to the concentration gradient)
Shunting
Blood that bypasses the alveoli will not come into contact with AA
Intrapulmonary or intracardiac shunts

18. 3) Uptake by the Tissues Tissue solubility Tissue bloodflow
Concentration gradient between blood and tissues
Greatest uptake – vessel-rich organs (heart, brain, lungs, kidneys, liver)
receive the largest portion of the CO
once equilibrium is achieved ...
Second phase – uptake by the muscle group
equilibrium is achieved within 1-3 hours
Last phase – uptake by the poorly vascularised tissues (fat, bone)
equilibrium takes many hours

19. Stages of Anaesthesia 1 Analgesia: From induction to LOC 2
Description 1
Analgesia: From induction to LOC 2
Excitement: LOC to automatic breathing; characterised by excitement, breath-holding, vomiting, coughing, swallowing, hiccoughing 3
Surgical anaesthesia
Light
Until eyeballs become fixed
Medium
Increasing intercostal paralysis
Deep
Diaphragmatic respiration 4
Overdose: From diaphragmatic paralysis to apnoea and death. All reflex activity is lost and pupils are widely dilated. Medullary paralysis

20. Recovery from Anaesthesia
The same factors that affect “going to sleep” affect “waking up” in reverse order!
Recovery is slow from soluble agents eg halothane
Recovery is fast from poorly soluble agents eg Desflurane and Sevoflurane

21. Metabolism of Volatile Agents
At the end of an anaesthetic, the major route of removal of the AA is via the lungs (via alveolar ventilation)
A small percentage of the AA will be metabolised in the liver
“Rules of 2’s”
Halothane 20%
Enflurane 2%
Isoflurane 0.2%
Sevoflurane 3-4%
Desflurane 0.02%
Harmful metabolites
Halothane Hepatitis
Fluorides from Methoxyflurane and Enflurane
Compound A from Sevoflurane
Carbon monoxide from Desflurane

22. Potency of Volatiles MAC (%)
Minimum Alveolar Concentration required to prevent 50% of young adults from moving in response to a standard surgical stimulus (skin incision) at sea level.
MAC is ↓ed by:
MAC is ↑ed by:
Sedatives
N2O
Analgesics
Elderly
Hypotension
Hypothermia
Myxoedema
Less effect:
Hypoxia, anaemia, pregnancy
Alcoholism
Children
Hyperthermia
Thyrotoxicosis

23. Specific Inhalational Agents

24. What is this?

25. Nitrous Oxide MAC: 105% Also known as Laughing gas
Entonox (50% O2 & 50% N2O)
Potent ANALGESIC, but poor anaesthetic
Reduces MAC
When used as a carrier gas, induction is pleasant and rapid (paediatrics)
Adverse Effects:
Negatively inotropic
Augments respiratory depression of other anaesthetic drugs
Diffuses into air-filled cavities of body (more soluble than N2) – increase volume and pressure
Bowel, middle ear, eye, lungs (tension pneumothorax)
PONV
Teratogenic – controversial
Bone Marrow Suppression

26. N2O in history
Davy and N2O
“prescription for scolding wives”

27. Diffusion Hypoxia N2O is much more soluble than NITROGEN (in air)
Diffusion Hypoxia can occur when you finish an anaesthetic where you used N2O in high concentration
70% N2O and 30% O2
The N2O enters the alveoli, from the blood, FASTER than NITROGEN enters the blood, from the alveoli (if you were giving the patient AIR only).
This reduces the partial pressure of O2 in the alveoli
Diffusion Hypoxia is not usually detectable in young fit patients
Safe Practice – give O2 (e.g. 40%) when switching off an anaesthetic with N2O

28. Halothane MAC: 0.75 % Halogenated hydrocarbon
Colourless liquid decomposed by light, stored in amber bottles
Non-irritant
Pleasant smell
Suitable for gas induction

29. Pharmacodynamics of Halothane
Respiratory
Dose-dependent respiratory depression
bronchodilator
Skeletal Muscle
Muscle relaxation
Trigger for MH (malignant hyperthermia)
Uterus
↓es uterine tone
Liver
↑ed liver enzymes post-op
Halothane Hepatitis
CNS
Potent hypnotic, no analgesia
↑ed CBF and ICP (minimised by hyperventilation)
CVS
Myocardial depression and vasodilatation
↓ed BP
Arrhythmias

30. Enflurane MAC: 1.68 % Halogenated Ether
Colourless liquid, more pungent than halothane, not suitable for gas induction
No longer available at GSH
Expensive
Adverse effects

31. Pharmacodynamics of Enflurane
Respiratory
Irritant to airways
Breath-holding
Laryngospasm
Skeletal Muscle
Greater relaxation than halothane
Enhances effects of muscle relaxants
Triggers MH
Liver
Less effect on liver enzymes
CNS
Epileptiform changes on EEG in epileptics
↑ed CBF and ICP
CVS
Bigger BP drop than Halothane
Tachycardia

32. Isoflurane
MAC: 1.14 %
Halogenated ether
Colouless
More expensive

33. Pharmacodynamics of Isoflurane
Respiratory
Irritant to airways
Not suitable for gas induction
Bronchodilator
Skeletal Muscle
Relaxant
Potentiates NDMR
Triggers MH
Uterus
Relaxes uterus
Liver
Low potential for toxicity
CNS
Least effect on ICP
Least effect on CBF
↓ed CMRO2 consumption
↓ed CSF production
Ideal for neurosurgery
CVS
Vasodilator
Coronary Steal phenomenon
Drops the BP
Tachycardia
More CVS stable than H

34. Sevoflurane MAC: ±2% Halogenated methyl isopropyl ether
Very pleasant and sweet-smelling
Best for gas induction
Expensive

35. Pharmacodynamics of Sevoflurane
CNS
Slight ↑ed CBF and ICP
↓ed CMRO2 consumption
Also good for neuro
CVS
Mild depression of cardiac contractility
Slight drop in BP, but less than with I or D
No increase in HR, so CO not as well maintained as with others
Respiratory
Dose-dependent depression
bronchodilator
Skeletal Muscle
Adequate muscle relaxation for intubation in children
Liver
No increased liver enzymes
Renal
Nephrotoxic endproducts
Fluoride
Compound A

36. Desflurane MAC: ±6 % Fluorinated methyl ether
Boiling point is very close to room temperature so it needs a special vapouriser
Very expensive
Limited availability at GSH
Most rapid induction and emergence of all the volatiles due to it’s low blood-gas solubility co-efficient
Not suitable for gas induction as very irritant and pungent
Similar effects on CNS, CVS, Respiratory and Skeletal Muscle
Triggers MH
Carbon monoxide production

37. Malignant Hyperthermia
Rare 1:15000
Pharmacogenetic disorder
Triggers: 2 drug classes
All volatiles
Suxamethonium
Acute hypermetabolic state within muscle tissue with induction of GA
Defect: Abnormal Ca receptor in muscle
Clinical signs
Tachycardia (& other CVS signs)
Hypercapnia (3 x ↑ )
Tachypnoea (if not paralysed)
High temperature (late!)
Skeletal muscle rigidity (early)
Arterial blood gas: Metabolic & Respiratory acidosis
↑ed K+, Ca++, creatine kinase
Myoglobinuria
Acute Renal Failure
Treatment: DANTROLENE iv and supportive in ICU