Tuesday, May 2, 2017

GENERAL ANAESTHETIC

General anaesthetics are drugs that produce reversible loss of all sensation and consciousness. The main features of general anaesthesia are:
(i)     Loss of all sensation
(ii)   Sleep (unconsciousness)
(iii) Muscle relaxation and
(iv) Abolition of reflexes
THEORIES OF ANAESTHESIA
The mechanism of action of the general anaesthetics is not precisely known. A wide variety of drugs or chemicals produce general anaesthesia. Therefore, general anaesthesia is probably not exerted through specific receptors but by a more generalized membrane action. The different theories of anaesthesia are:
1. Lipid/water partition theory
If an anaesthetic agent is more lipid soluble then it will produce more intense anaesthesia. It has been found that minimal alveolar concentration (MAC) (i.e the lowest amount of anaesthetic in pulmonary alveoli needed to produce immobility) decreases with inhalational anaesthetics having higher o/w partition coefficient.
But this is not the perfect mechanism of action.
2. Surface tension theory
General anaesthetics reduce surface tension at cell membrane and thus affect its permeability, electrical and/or enzymatic properties. However, this is not generally accepted.
3. Inhibition of energy production/utilization
Higher concentrations of general anaesthetics in the brain directly inhibit metabolic processes and oxygen consumption in neurons. But it is an effect rather than the cause.
4. Clathrates formation theory
Water is normally partially structured, i.e. has crystal like molecular arrangement. General anaesthetics are believed to fill up the spaces between the microcrystals (clathrates) and make water more structured; thus they plug the pores and impede ionic fluxes. However, there is no evidence of clathrate formation at body-temperature.
5. Membrane expansion theory
The anaesthetics occupy space in the membrane and expand it disproportionately (about 10 times their molecular volumes). This causes increased surface pressure in the membrane, thereby closing ion channels. This has been prompted by the fact that application of external pressure reverses anaesthesia.
6. Membrane fluidization / perturbation theory
Anaesthetic, by dissolving in the membrane lipids, increases the degree of disorder in their structure, favoring a gel-liquid transition (fluidization). Normally, fluidization occurs at high temperatures; anaesthetic may make it possible to occur at lower temperature. This affects the state of membrane bound proteins that regulate ionic fluxes.

STAGES OF ANAESTHESIA
When a general anaesthetic is administered first the higher functions of brain are lost then progressively lower segments of the brain are involved. In case of spinal cord lower segments are affected somewhat earlier than the higher segments.
The vital centers located in the medulla are paralyzed the last as the depth of anaesthesia increases.
When ether is administered as inhalation the following four stages are seen. The IIIrd stage is again divided into 4 planes.


1. Stage of Analgesia
Starts from beginning of anaesthetic inhalation and lasts upto the loss of consciousness.
Pain is progressively abolished.
Patient remains conscious, can hear, and feels a dream like state.
Reflexes remain normal.
·         Though some minor and even major operations can be carried out during this state, it is rather difficult to maintain - Use is limited to operations taking short time.
II. Stage of Delirium
From loss of consciousness to the beginning of regular respiration.
Apparent excitement is seen, patient may shout, struggle and hold his breath; muscle tone increases, jaws are tightly closed, breathing is jerky; vomiting, involuntary micturation or defecation may occur.
Heart rate and blood pressure may rise.
Pupils dilate due to sympathetic stimulation.
No stimulus should be applied or operative procedure carried out during this stage.
This phase is cut short by rapid induction, premedication, etc.
III. Surgical anaesthesia
Extends from onset of regular respiration to cessation of spontaneous breathing. This has been divided into 4 planes that may be distinguished as:
Plane 1                        Roving eye balls. T
This plane ends when eyes become fixed.
Plane 2                        Loss of corneal and laryngeal reflexes.
Plane 3                        Pupil starts dilating and light reflex is lost.
Plane 4                        Intercostal paralysis, shallow abdominal respiration, dilated pupil.
Most surgical operations are done in Plane 2 and Plane 3.  Plane 4 is never attempted.
IV. Medullary paralysis
Cessation of breathing to failure of circulation and death. Pupil is widely dilated, muscles are totally flabby, pulse is thready or imperceptible and blood pressure is very low.

PROPERTIES OF AN IDEAL ANAESTHESIA
A. For the patients:
It should be pleasant, non-irritating, should not cause nausea or vomiting.
Induction and recovery should be fast with no after effects.
B. For the surgeon
It should provide adequate analgesia, immobility and muscle relaxation.
It should not be inflammable and nonexplosive (so that hot cautery may be used).
C. For the anaesthetist
Its administration should be easy, controllable and versatile.
Margin of safety should be wide - no fall in blood pressure.
Heart, liver and other organs should not be affected.
It should be potent so that low concentrations are needed and oxygenation of the patient does not suffer.
Rapid adjustments in depth of anaesthesia should be possible.
It should be cheap, stable and easily stored.
It should not react wit rubber tubing or sodalime glass.
Dose:-
Most inhalational anaesthetics have a steep concentration - response curve. Increasing the concentration only by 1/3 over MAC makes almost all individuals immobile (at MAC only 50% of the patients are immobilized), and 2-4 MAC is often lethal.


Complications of general anaesthesia:
A. During anaesthesia
(i)     Respiratory depression.
(ii)   Salivation, respiratory secretions - less now as non-irritant anaesthetics, are mostly used.
(iii) Cardiac arrhythmias.
(iv) Fall of blood pressure.
(v)   Aspiration of gastric contents.
(vi) Laryngospasm and asphyxia.
(vii)Delirium, convulsions.
(viii)Fire and explosion.
B. After anaesthesia
(i)     Nausea and vomiting.
(ii)   Persisting sedation: impairs psychomotor function.
(iii) Pneumonia
(iv) Organ toxicities: liver and kidney damage.
CLASSIFICATION OF GENERAL ANAESTHETICS
1. Inhalation anaeshetics:
            (a) Gases:                     Nitrous oxide (N2O)
                                                Cyclopropane
            (b) Volatile liquids       Ether
                                                Chloroform
                                                Halothane
                                                Enflurane
                                                Trichloroethylene
                                                Isoflurane
2. Intravenous anaesthetics:
(i) Inducing agents:      Thiopentane sodium
                                    Methohexitone sodium
(ii) Slower acting drugs:
                                    (a) Benzodiazepines e.g.                      Diazepam
                                                                                    Lorazepam
                                                                                    Midazolam
                                    (b) Dissociative anaesthesia e.g.          Ketamine
                                    (c) Neutoleptic analgesia i.e. Fentanyl + droperidol.

GASEOUS  ANAESTHETICS
Nitrous oxide (N2O)
It is also called laughing gas. It is an inorganic gas, colorless and sweet in taste.
It is heavier than air. It is insoluble in blood and it does not combine with haemoglobin. It is carried in blood in the form of physical solution.
It does not decompose in the body. So the oxygen of nitrous oxide is not available for tissue respiration. It is excreted unchanged through the lungs. A small quantity may be eliminated through skin.
Advantages:
1.      Induction and recovery are quick.
2.      No irritation to mucous membranes.
3.      It can produce analgesia which can be used for minor surgery or tooth extraction.
4.      It is non-toxic to liver and kidney.
Disadvantages:
1.      It is not a potent anaesthetic.
2.      Muscle relaxation is not adequate.
3.      Special apparatus is required for its use.
4.      It produces euphoria and excitation during induction.
Cyclopropane
It is the simplest cyclic hydrocarbon. it is colorless gas with a sweet odour and taste.  
It is heavier than air.
It is rapidly absorbed and completely eliminated through lung.
A small amount is metabolized in the body and eliminated as CO2 and water.
Advantages:
1.      Induction is quick and pleasant and recovery is smooth and rapid.
2.      Useful for major surgery like thoracic and abdominal surgery.
3.      Less-irritant to mucous membranes. So coughing and respiratory secretions are less.
4.      Does not affect blood pressure and cardiac rate.
5.      It does not produce any visceral damage.
Disadvantages:
1.      Explosive when combined with oxygen.
2.      It causes increased capillary bleeding.
3.      Produces cardiac arrhythmia and reflux bradycardia.
4.      Nausea and vomiting are produced during bradycardia.
5.      It requires complicated instruments for use.

VOLATILE LIQUIDS
Ether (C2H5 - O - C2H5) [Diethyl ether]
It is a colorless and volatile liquid with a pungent odour. It is highly inflammable and explosive. It is quickly absorbed and eliminated through lungs.
Advantages;
1.      It produces satisfactory muscle relaxation.
2.      It does not produce liver or kidney damage.
3.      It can be given by open drop (through congestion of eye, soreness of trachea and ether burns on face can occur) without the need for any equipment, and is relatively safe in inexperienced hands.
4.      It is cheap hence still popular in developing countries.
Disadvantages:
1.      It is highly soluble in blood - induction is prolonged.
2.      Unpleasant with struggling, breath holding, salivation and marked respiratory secretions (atropine must be given as premedication to prevent the patient from drowning in his own secretions).
3.      Recovery is slow.
4.      Produces nausea and vomiting during  recovery.
5.      Inflammable and explosive.

Chloroform:
It is a clear liquid with a sweet odour.
Advantages:
1.      Non-inflammable and non-explosive.
2.      Induction is rapid and pleasant.
3.      It is less irritant to mucous membranes.
4.      Does not produce capillary bleeding.
Disadvantages:
1.      It decomposes into phosgene, a poisonous gas and this can be prevented by the addition of 1% alcohol.
2.      Produces cardiac arrhythmias due to sensitization of myocardium to adrenaline.
3.      Fall in blood pressure and decrease in cardiac output are produced.
4.      It is toxic liver.
5.      Produces nausea and vomiting during recovery.


Halothane:
It is volatile liquid wit sweet odour, non-irritant and non-inflammable.
Advantages:
1.      Non-inflammable and non-explosive.
2.      It has intermediate solubility in blood - induction is reasonably quick and pleasant.
3.      It is a potent anaesthetic.
4.      Non-irritant to mucous membranes.
5.      It produces relaxation of bronchial smooth muscles and hence is helpful in asthmatic patients.
Disadvantages:
1.      Halothane causes direct  depression of myocardial contractility by reducing inter-cellular Ca++ concentration. Cardiac output is reduced with falling of blood pressure. Myocardium  is sensitized to adrenaline and may produce cardiac arrhythmia.
2.      Muscle relaxation is not adequate and analgesia is poor. (This poor analgesia and muscle relaxation and neuromuscular blockers.)
3.      It is toxic to liver.
4.      It is expensive.
Trichloroethylene
It is clear, colorless liquid with a characteristic odour.
Advantages:
1.      Induction is rapid.
2.      It does not irritate mucous membranes.
3.      It is useful for short operations and in dentistry.
Disadvantages:
1.      Muscle relaxation is not adequate.
2.      Produces cardiac arrhythmias due to sensitization of myocardium to adrenaline.
3.      Produces nausea and vomiting during recovery.
4.      It is not useful for long operations.

INTRAVENOUS ANAESTHETICS
INDUCING AGENTS
These are drugs which on intra-venous injection produce loss of consciousness in one arm-brain circulation time (approximately 11 seconds); are generally used for induction because of rapidity of onset of action. Anaesthesia is then usually maintained by an inhalation agent. They also serve to reduce the amount of maintenance anaesthetic. Supplemented with analgesics and muscle relaxants, they can also be used as the sole anaesthetic.

1. Ultrashort acting barbiturates:
E.g. Thiopentone sodium, methohexitone sodium.
These ultra short-acting barbiturates produce hypnosis, deep sleep and unconsciousness in that order. These drugs have short duration of action due to high lipid solubility rapid destruction in the liver.
Advantages:
1.      Injection produces unconsciousness in 15 to 20 secs. Its undissociated form has high lipid solubility -enters brain almost instantaneously. Other less vascular tissues (like muscles, fats, etc.); gradually takes up the drug - blood concentration falls and drug comes out from the brain. Consciousness is regained in 10 to 20 mins.
2.      Respiration is quiet and salivation is absent.
3.      Less post-anaesthetic complications.
Disadvantages:
1.      Extravenous injection or inadvertent intra-arterial injection produces intense pain - necrosis and gangrene may occur. Poor analgesic. Painful procedures should not be carried out under its influence unless an opioid or N2O has been given, otherwise the patient may struggle, shout and show reflex changes in blood pressure and respiration.
2.      It is weak muscle relaxant.
3.      Respiratory depression with large doses is severe.

2. SLOWER ACTING DRUGS
1. Benzodiazepines
e.g. Diazepam, Lorazepam, Midazolam
Advantages:
(i)     Benzodiazepine in large dose injected i.v. produce sedation, amnesia and then unconsciousness in 5-10 minutes.
(ii)   Does not markedly depress respiration, cardiac contractility or blood pressure.
Disadvantages:
(i)     Benzodiazepines decrease muscle tone by central action but require neuromuscular blocking drugs for muscle relaxation of surgical grade.
(ii)   Relatively large dose is required.
2. Ketamine
It is a non-barbiturate general anaesthetic. It produces “dissociative anaesthesia” characterized by superficial sleep and complete analgesia. [Light sleep and feeling of dissociation from ones own body and the surroundings].
Advantages:
(i)     It is useful only for short procedures like dressing of burns and bronchoscopy.
(ii)   It does not affect respiration.
Disadvantages:
(i)     Delirium and hallucinations are produced during induction and recovery.
(ii)   Blood pressure and heart rate are increased.
(iii) Muscle relaxation is poor.
(iv) It produces laryngospasm and salivation.
3. Fentanyl-Droperidol combination
Fentanyl is a short acting (30 to 50 minutes), potent opioid analgesic related to pethidine, while droperidol is a rapidly acting potent neuroleptic related to haloperidol. When a combination of these i injected i.v a state of “neurolept analgesia” is produced, i.e., intense analgesia without unconsciousness.
This state lasts for 30-40 mins.
Patients remain drowsy but conscious and his cooperation can be commanded.
Neurolept analgesia is quite suitable for endoscopies, angiographies, burn dressing, etc. and has been used for a variety of minor surgical procedures in severely ill or otherwise poor risk patients.

PREANAESTHETIC MEDICATION
The term ‘preanaesthetic medication’ refers to the use of drugs prior to the administration of anaesthetics, so as to make anaesthesia safe and agreeable to the patient. Pre-medication aims at providing the following effects:
1.      Sedation  : To reduce anxiety of the patient before surgery. This can be achieved by sedative, hypnotics and tranquilizers. Usually morphine and its derivatives and barbiturates are given.
2.      Analgesia: achieved by morphine and pethidine. They reduce pain-sensation and also reduce the amount of general anaesthesia required.

3.      Inhibition of parasympathetic activity: so as to decrease bronchial and salivary secretion induced by drugs like ether.

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