1. Basic principles of anaesthesia
Małgorzata Cyran

2. General anaesthesia
The main objective of general anaesthesia is to allow the performance of surgical procedures.
General anaesthesia consists of several components which can be obtained with the use of various substances.

3. These components are:
loss of consciousness and amnesia (intravenous and inhaled/volatile anaesthetics),
analgesia (opioids),
disabling or reduction of the physiological somatic, visceral-somatic and autonomic responses to noxious stimuli,
muscle flaccidity (muscle relaxants)

4. Components of general anaesthesia are:
• unconsciousness (hypnosis)
• pain relief/ loss of response to pain (analgesia)
• skeletal muscle relaxation (relaxatio)
• loss of motor reflexes (areflexia)

5. The stages of general anaesthesia
Induction
Maintenance phase
Emergence from anaesthesia

6. Inhaled anaesthetics
They are introduced through the lungs and distributed to the various tissues of the body by blood

7. The ideal volatile anaesthetic:
provides fast and pleasant induction (falling asleep) and emergence from anaesthesia (waking up),
good controllability - the ability to quickly change the depth of anaesthesia,
sufficiently strong analgesic effect, inhibition of reflexes and skeletal muscle paralysis,
a wide margin of safety,
lack of toxicity at clinical doses,
low cost

8. Inhaled anaesthetics do not meet all the requirements so an ideal anaesthetic doesn’t exist!
time of induction of anaesthesia is extremely long and is accompanied by a period of arousal,
for obtaining a sufficient depth of anaesthesia it is often necessary to use concentrations that lead to unwanted side effects, especially cardiovascular,
most of the inhaled anaesthetics are combined with other intravenous drugs as a component in combined anaesthesia

9. Inhaled anaesthetics
at a room temperature they remain in a volatile (nitrous oxide) or liquid state (isoflurane, desflurane, sevoflurane),
those remaining in a liquid state must first be converted into steam to be implemented through the lungs,
this is done with special evaporators, by which you can supply the anaesthetic in a specific concentration,
Nitrous oxide does not require evaporator (can be given from a gas cylinder or a central supply)

10. Volatile anaesthetics are always introduced as a mixture containing other gases: air, O2, N2O or O2. The total pressure of this mixture of gases is the total sum of the partial pressures of all the gases present in the mixture.
The level of the partial pressure of the inhaled anaesthetic determines the speed of reaching a state of equilibrium between the concentration of an anaesthetic in the breathing air and the concentration in blood.

11. The absorption of anaesthetic in the lungs depends on:
The solubility of the anaesthetic in the blood,
Cardiac output,
The difference between the partial pressures of alveolar air and blood in the pulmonary veins

12. Distribution of the anaesthetic
The amount of anaesthetic that is taken up by various tissues from the blood depends on:
the solubility of an anaesthetic in the tissue,
the blood supply,
the difference between the partial pressures of an volatile anaesthetic.

13. Rate of anaesthetics’ elimination:
1. nitrous oxide
2. desflurane
3. sevoflurane
4. isoflurane
The longer time of anaesthesia using a highly soluble anaesthetic, the slower the elimination through the lungs and the waking up period.

14. MAC
Minimum alveolar concentration (MAC 50) is a concentration of an inhaled anaesthetic in the lungs that is needed to prevent motor response in 50% of subjects in response to a surgical (pain) stimulus.
The lower the value of the MAC is, the greater the potency of an anaesthetic.
The administration of 70% nitrous oxide can reduce MAC by half.

15. Factors affecting the MAC
age (age reduces the need for an anaesthetic),
lower body temperature, hypothermia - reduces MAC,
pregnancy - reduces MAC,
opioids- reduce MAC
sedative and hypnotic agents - reduce MAC
chronic alcohol abuse - increases MAC
fever - increases MAC

16. Isoflurane molecular weight 184.5 Da boiling temperature of 48.5 C
vapor pressure at 20C at 238 mm Hg
partition coefficient blood / gas 1.4
MAC value 1.28 in 100% O2, 0.56% N2O 70

17. Isoflurane heart rate under isoflurane is variable,
mean arterial pressure is decreased,
myocardial contractility - negative inotropic effect,
cardiac output remains unchanged or
reduces the consumption of oxygen by the myocardium
enhances the effects of muscle relaxants

18. Isoflurane
reduces blood flow to the kidneys, decreases glomerular filtration rate and urine output
no negative effect on the liver,
has an irritating smell: apnea and coughing,
can trigger malignant hyperthermia

19. Desflurane Molecular weight 168 Da
the smell of acrid, irritating the airways
boiling temperature of 22.8 C
vapor pressure at 20 ° C is 664 mm Hg
partition coefficient blood / gas 0.42
value of the MAC50 6-9% vol. 100% O % in 70% N2O

20. Desflurane
the smallest partition coefficient blood / gas from all the volatile anaesthetics
increased heart rate
decreases the vascular resistance of the peripheral circulation and causes vasodilatation,
in a healthy person has a weak negative inotropic effect
decreases blood pressure
expanding effect on the coronary arteries
irritates the respiratory system during induction of anaesthesia (cough, laryngospasm, increased secretion) is NOT suitable for the introduction of inhaled anaesthesia in children nor in adults

21. Desflurane intensifies the effects of muscle relaxants
> 1 MAC increases cerebral blood flow
no toxic effect on the liver
requires a special evaporator
can trigger malignant hyperthermia
high usefulness in the low-flow or minimal-flow anaesthesia

22. Sevoflurane colourless, flammable liquid with a mild ether odour,
the molecular weight of Da
boiling point at 58.5 C
partition coefficient blood / gas 0.69
MAC value 2.05% by volume in 100% O2, 0.66% by volume to 70% N2O

23. Sevoflurane pretty good controllability 3-5% metabolised in the liver
reacts with the absorber lime and forms a compound A - nephrotoxic substance
cause weak or no changes in the heart rate
peripheral vasodilation, reduced vascular resistance
hypotension
negative inotropic effect

24. Sevoflurane
Sevoflurane is suitable for inhaled induction of anaesthesia in children (and adults)
enhances the effect of muscle relaxants
can cause malignant hyperthermia
reduces the oxygen consumption by the brain

25. Nitrous oxide (N2O) physical state at room temperature - gas
partition coefficient blood / gas 0.47
The value of the MAC 104
is a weak anaesthetic, is used as an additive to other anaesthetics
the maximum concentration of nitrous oxide should not exceed 70% !!!

26. Nitrous oxide negative inotropic effect
the impact on a healthy person is very weak and clinically insignificant
does not cause muscle relaxation
can lead to megaloblastic anaemia
diffuses in body cavities filled with air: air-filled loops of bowel eg. the obstruction, pneumothorax, emphysema, middle ear, air-filled tube cuff,

27. Nitrous oxide
the only volatile anaesthetic with an analgesic effect!!!
diffusion hypoxia while emerging from anaesthesia

28. Halothane colourless liquid with a very pleasant smell
sensitive to light
coefficient blood / gas 2.5
does not irritate the respiratory tract
a long waking-up period
20% of halothane is metabolised by the liver
inhibits the secretion in the airways

29. Halothane
reduces airway resistance in patients with spastic states of the bronchi by the inhibition of contraction and by promoting the relaxation of bronchi muscles,
has a strong depressing effect on myocardial contractility
decreases blood pressure, can cause bradycardia
can cause ectopic arrhythmias: even ventricular fibrillation
increased cerebral blood flow and increased intracranial pressure
decreases gastrointestinal motility
post- halothane liver failure

30. Intravenous Anaesthetics

31. Propofol fast and short acting anaesthetic without analgesic effect,
use: an introduction to anaesthesia, TIVA, sedation for diagnostic procedures, sedation for patients requiring intensive supervision (ICU)
insoluble in water, emulsion of soybean oil; white colour
dose of mg / kg
painful during the injection

32. Propofol sedation by binding to the B subunit of the GABA A receptor
decrease in blood pressure
a decreased cardiac output
causes transient apnea
bounds to plasma proteins in 98%

33. Thiopental belongs to barbiturates
a temporary decrease of blood pressure
increased heart rate
negative inotropic effect on the heart muscle
can cause abnormal heart rhythm
suppresses the respiratory centre - apnea

34. Thiopental dose of 2-5 mg / kg up to 500mg contraindicated in:
acute intermittent porphyria and mixed porphyria
severe asthma
allergy to barbiturates
heart failure, acute myocardial infarction
pericarditis, cardiac tamponade
hypovolemia, shock

35. Etomidate dose: 0.15-0.3 mg / kg
anaesthetic without the analgesic component,
myoclonus and can cause dyskinesia (after injection no change in EEG)
among intravenous anaesthetics it has the weakest impact on the cardiovascular system
recommended in patients at risk, in elderly patients

36. Ketamine
It can be used as individual anaesthetic in small surgical procedures
causes dissociate anaesthesia (hypnosis, unconsciousness, hallucinations, catalepsy
may cause involuntary movements
it may cause strange dreams and visual hallucinations associated with anxiety
causes stimulation of the cardiovascular system (tachycardia, increased blood pressure), increases intracranial pressure,
Do not use in patients with ischaemic heart disease

37. Ketamine
indications: daily surgical wound treatment/ extensive burn care, in non-cooperating children, patients with shock
it can be administered intramuscularly
dose: 1-2 mg / kg

38. Benzodiazepines
main effects: calming, anxiolytic, hypnotic, an anticonvulsant
They do not provide surgical anaesthesia
associated with opioids can lead to severe and prolonged respiratory depression,
short-acting: midazolam
average long-acting: flunitrazepam
long-acting: diazepam

39. Benzodiazepines Indications: premedication, sedation,
induction for the patients “at risk”,
supplements the action of opioids and ketamine,
anticonvulsant

40. Benzodiazepines Contraindications: myasthenia gravis
hypersensitivity to benzodiazepines
acute intoxication with alcohol and hypnotics
severe respiratory failure
Flumazenil - specific antidote for the benzodiazepines!

41. Opioids

42. Opioids Opioid receptors:
μ - analgesia (pain relief), respiratory depression, inhibition of intestinal peristalsis
κ - dysphoria, miosis and sedation, hallucinations.
δ - analgesia, dysphoria and hallucinations.

43. Opioids Effects: analgesia somnolence euphoria respiratory depression
muscle stiffness
miosis
nausea and vomiting
suppression of the cough reflex

44. Opioids
Analgesic potency of the opioid depends on the dose, the concentration of the opioid receptor, pain intensity, and many individual factors and circumstances.
Opioids themselves, even at very high doses do not induce unconsciousness in a reliable manner, so they must be associated with an intravenous anaesthetic or sedative-hypnotic substances.
Opioids do not cause amnesia.

45. Opioids
Respiratory depression caused by opioids is dose-dependent and reinforced by the lack of stimulation and sleep, or concomitant administration of intravenous anaesthetics and sedatives.
Clinical signs of respiratory depression: decreased respiratory rate and minute ventilation, apnea
Opioids can increase muscle tension, even their stiffness (muscles of the chest, abdomen and larynx)
All opioids in clinical doses cause constriction of the pupils.
nausea and vomiting, itching of the skin - a typical side effect

46. Opioids cause hypotension
bradycardia (it can be prevented or reversed by the administration of atropine)
constipation (decrease the motility of the gastrointestinal tract)
they increase the pressure in the bile ducts (spastic contraction of the sphincter of Oddi)

47. Fentanyl synthetic opioid μ-receptor agonist
50-100x stronger than morphine
endotracheal intubation dose of 1-5 ug / kg
combined anaesthesia ug / kg approximately every 30 minutes or a continuous infusion of 2-10 ug / kg / h

48. Alfentanyl tetrazole derivative of fentanyl short-term effect
a short treatment (15 min) or an analgesic component of TIVA

49. Sulfentanyl 7-10x times stronger than fentanyl
endotracheal intubation dose of ug / kg
administered as a supplement to combined anaesthesia and in TIVA

50. Remifentanyl the shortest half life of all the opioids (3-4 min)
not cumulative, its effect disappears quickly
TIVA
the start of the infusion of 0.1 to 0.25 to 0.5 ug / kg / min
easy controllability due to the rapid determination of the balance between blood and tissues,
16-30x more potent than alfentanil (comparable to fentanyl)

51. Naloxone pure opioid antagonist
administered to overcome the respiratory depression and limited awareness as a result of a residual activity of the opioids
mg, depression subsides after 1-2 min
it is advised to administer it in divided doses

52. Skeletal muscle relaxants
cause reversible flaccid paralysis of skeletal muscles
paralysis occurs as a result of the inhibition of the transfer of potentials in a neuromuscular junction
Depolarising and non-depolarising
They are used to facilitate endotracheal intubation and to improve operating conditions
the duration of the paralysis depends on the substance used

53. Depolarising block
caused by succinylcholine, it binds to presynaptic and postsynaptic receptors
motor end-plate is permanently depolarised and there is a flaccid paralysis of the muscles
succinylcholine increases muscle fasciculations (due to presynaptic effects)
precurarisation - providing a small dose of non-depolarising muscle relaxant before succinylcholine

54. Suxamethonium
after the administration - max. effect after sec; duration of aprox. 5 min
slightly releases histamine
can cause cardiac arrhythmias: sinus bradycardia, nodal rhythm, ventricular arrhythmias
endotracheal intubation dose of 1 mg / kg
the shortest-acting muscle relaxant
should not be used in children
indicated in suspected difficult intubation

55. Suxamethonium Contraindications: atypical cholinesterase
acquired deficiency of pseudocholinesterase
severe hyperkalemia
multi-organ trauma, prolonged immobilization
burns
malignant hyperthermia
myotonia, muscular dystrophies

56. Suxamethonium Side effects: bradycardia hypotonia increased salivation
increased secretion in the airways
increased tension of the gastrointestinal tract
Symptoms tend to occur mainly after multiple injections. For this reason, you should not repeat injection of succinylcholine!

57. Non-depolarising block
non-depolarising agents compete with acetylcholine for the subunit ⍺ of the choline receptor,
they do not have agonist activity,
long-acting: pancuronium;
average duration of acting: vecuronium, rocuronium, atracurium, cis- atracurium,
short-acting: mivacurium
nondepolarizing agents can release histamine from the mast cells
the impact on the cardiovascular system: tachycardia, arrhythmias, hypotension

58. Atracurium endotracheal intubation dose: 0.3-0.6 mg / kg
distribution route of elimination: Hofmann elimination, independent of the liver and kidney metabolism
releases histamine
acting time of min

59. Cis-atracurium endotracheal dose: 0.15-0.2 mg / kg
Five times stronger than atracurium
releases far less histamine than atracurium
Hofmann elimination
does not accumulate
acting time: about 45 minutes

60. Mivacurium
the shortest-acting non-depolarising skeletal muscle relaxant
endotracheal intubation dose: 0,2-0,25 mg / kg
not suitable for rapid intubation
releases histamine
acting time: min
liver failure extends the acting time

61. Rocuronium it has the fastest onset time
endotracheal intubation dose: mg / kg
satisfactory conditions for intubation after s
liver failure extends the acting time
it can be used for rapid intubation
acting time: 45 min

62. Vecuronium endotracheal intubation dose 0,08-0,1 mg / kg
it does not release histamine
distribution mainly in the liver
acting time: min

63. Pancuronium endotracheal intubation dose of 0.08-0.12 mg / kg
duration of action of more than 45 min
only long-term surgeries, procedures, after which the extubation is not planned/needed
side effects: tachycardia, increased salivation, prolonged exposure

64. Neostigmine an acetylcholinesterase inhibitor
inhibits the activity of acetylcholinesterase by increasing the amount of acetylcholine in the synaptic cleft
dose should not exceed 0.07 mg / kg
severe side effects: bradycardia, bronchospasm, stimulation of the gastrointestinal motility and increased salivary secretion and contraction of the bladder, miosis
to weaken the adverse effects of the muscarinic acetylcholinesterase inhibitors an anticholinergic agent (eg. atropine) should be given at the same time

65. Sugammadex eliminates the effect of rocuronium and vecuronium,
The minimum dose of 2mg / kg
immediate elimination of the effect 16 mg / kg

66. Bibliography: Anestezjologia. Larsen Tom. 1 R. Larsen wyd
Bibliography: Anestezjologia. Larsen Tom.1 R. Larsen wyd. III polskie, red. A. Kübler rok wydania: 2013

67. Thank you