Anaesthetics – Principles and Pharmacology Flashcards
define anaesthesia?
without feeling or perception
types of drugs used in anaesthesia
o Inhalational anaesthetics o IV anaesthetics o Muscle relaxants o Local anaesthetics o Analgesics
techniques and equipment used in anaesthesia
o Tracheal intubation o Ventilation o Fluid therapy o Regional anaesthesia o Monitoring o Main areas of progress o Use of improved technology e.g. USS, fibre optics, CPUs, BIS, sensors etc
name the componenets of the triad of anaestheisa
analgesia
hypnosis
relaxation
what kind of drugs produce relaxation
muscle relaxations
local anaesthetics
GAs
what kind of drugs produce hyponosis
GAs
Opiates
what kind of drugs produce analgesia
local anaesthetics
opiates
(GAs)
with a patient under GA why is pain relief still needed?
Pain relief, can also be taken in this context to mean “removal of perception of unpleasant stimulus” since not all unpleasant stimuli patients need protected from are necessarily painful. E.g. handling of gut. If patient is unconscious and therefore unaware of pain, analgesia usually still required to suppress reflex autonomic responses to painful stimulus.
what kind of operations require relaxation of skeletal muscle?
body cavity access
permit artificial ventilation
advantages of balanced anaesthesia
Big advantage of balanced anaesthesia is that it allows a great degree of control over the individual components of the triad. And allows different drugs and techniques to be used to achieve each of the individual “targets” as it were while tailoring the technique to each patient and procedure. Helps keep doses of individual drugs down. Balanced anaesthesia allows you to titrate doses separately and therefore more accurately to requirements. This avoids over dosage and allows enormous flexibility. E.g. we can use much less general anaesthetic agent to provide hypnosis for abdominal surgery if we use a muscle relaxant to provide the muscle relaxation needed for access and immobility. Additionally, we could use less of each of these if we added in an epidural anaesthetic (regional local anaesthesia) to provide additional analgesia and muscle relaxation.
issues with balanced anaesthesia
polypharmacy - reactions + allergy
muscle relaxants and airway, awareness
how do GAs work?
All general anaesthetic agents work by suppressing neuronal activity in a dose dependant fashion. This is largely done by opening chloride channels which hyperpolarise the neurones or suppressing excitatory synaptic activity. They interfere with neuronal ion channels causing them to hyperpolarise and thus less likely to fire. Inhalational agents dissolve in membranes causing a direct physical effect. IV agents have allosteric binding through GABA receptors opening chloride channels.
describe loss of function with administration of GAs
Cerebral function is lost from the top down. The most complex processes are interrupted first – LOC early and hearing later. More primitive functions are lost later. Reflexes are relatively spared as they are primitive and involve a small number of synapses. Not surprisingly the most complex processes which rely on the greatest and most complex neuronal activity are the most susceptible to inhibition in this way and therefore cerebral function is lost “from the top down” with relative sparing of the simpler more primitive functions including reflexes (i.e. spinal reflexes) and other automatic functions.
name two IV GAs
thiopentone
propofol
advantages of IV GAs
• Rapid onset of unconsciousness o 1 arm-brain circulation time • Rapid recovery o Due to disappearance of drug from circulation o Redistribution vs metabolism
how do IV GAs work so quickly and wear off rapidly?
They are highly fat-soluble drugs and cross membranes extremely
quickly. They also leave the circulation very quickly indeed and if given as a once off “bolus” dose will
cause only temporary unconsciousness as they disappear very rapidly from the circulation and
consequently the brain. This rapid fall in blood concentration is due mainly to the drug leaving the
circulation and moving to other parts of the body (compartments). Metabolism of the drug (i.e. the
Figure 3 Ion Channels
process of the drug being destroyed and removed from the body) actually contributes very little to
the termination of action of an intravenous anaesthetic agent given as a bolus.
how do you measure inhalational anaesthetics
• Uptake and excretion via lungs
o Concentration gradient – lungs > blood > brain
o Cross alveolar BM easily
o Arterial concentration equates closely to alveolar partial pressure
• MAC = minimum alveolar concentration
o Measure of potency
o Low number = high potency
induction with inhalational agents
Inhalational anaesthetic agents are all halogenated hydrocarbons and are taken up and almost
exclusively excreted via the lungs. At induction the patient is given a relatively high concentration of
the agent to breath. The gas then moves down the concentration gradient in to the patients’ blood
and finally brain to achieve a high enough partial pressure there to produce unconsciousness.
what is MAC?
MAC is the concept of the concentration of the drug required in the alveoli which is required to produce anaesthesia with any particular agent. Therefore, a low MAC value means an agent is potent. E.g. Halothane (MAC = 0.8%) is more potent than Desflurane (MAC = 6%) because it takes a lesser concentration of the agent to produce the same effect
when is inhalational induction useful?
potentially obstructing airway
main role for inhalational anaesthetics
maintainence
physiology of GA: CVS
• Central o Depress CV centre § Reduce sympathetic outflow § Negative inotropic/chronotropic effect on heart § Reduced vasoconstrictor toon à vasodilation • Direct o Negatively inotropic o Vasodilation § Decreased peripheral resistance o Venodilation § Decreased venous return § Decrease CO
how do the CVS effects of GA occur?
All general anaesthetic agents IV or inhalational have adverse effects on the cardiovascular system and are almost universally depressant (Ketamine is the exception). Central effects arise due to the depressant effects of the agent on the CNS and, more specifically, the cardiovascular centres and nuclei in the brainstem. They reduce sympathetic nerve activity and have direct negative chronotropic and inotropic effects on the heart and cause venous and arterial vasodilatation. Effects also arise from the direct effects of anaesthetic agents on vascular smooth muscle and myocardium. They compound the effects of the reduced sympathetic activity. By causing vasodilatation general anaesthetic agents reduce the venous return to the heart and the cardiac output (CO) therefore falls. This is compounded by the negative inotropic effects of the general anaesthetic agent which worsen the fall in the CO. The arterial vasodilatation leads to a reduction in the systemic vascular resistance (SVR). As you can see from the equation Mean arterial pressure (MAP) = CO x SVR. Therefore, any reductions in CO and SVR are multiplicative. e.g. if both CO and SVR are reduced by 1/3 this results in the MAP being more than halved! (Because 2/3 x 2/3 = 4/9).
respiratory effects of GA
• All anaesthetic agents are respiratory depressants o Reduce hypoxic and hypercarbic drive o Decreased tidal volume and increased rate • Paralyse cilia • Decrease FRC o Lower lung volumes o VQ mismatch o May be prolonged effect
how do the respiratory effects of GAs come about
In addition to being CVS depressants – all GA agents (again largely excepting Ketamine) are respiratory depressants. The respiratory depression due to anaesthetic agents is characterised by reduced tidal volumes (often greatly so) and a high respiratory rate. Contrast with opiate respiratory depression which largely preserves tidal volume and is characterised by a low respiratory rate. They produce the respiratory depression by reducing hypoxic and hypercarbic drive via the depression of the brainstem respiratory centres. Perhaps the most important effect of general anaesthetic agents however is their effect on lung volumes. These are often greatly reduced and this fall in lung volumes interferes with ventilation perfusion matching in the lungs. This effect persists into the postoperative period and is the main reason anaesthetists are so keen patients are given postoperative oxygen. Because this effect can persist for several days patients therefore often need postoperative oxygen for several days.
what kind of muscle do relaxants work on?
skeletal
indications for muscle relaxants
o Ventilation and intubation
o When immobility is essential
§ Microscopic surgery, neurosurgery
o Body cavity surgery (access
problems with muscle relaxants
o Awareness
o Incomplete reversal à
§ Airway obstruction, ventilatory insufficiency in immediate post op period
o Apnoea = dependence on airway and ventilatory support
why the need for intra operative analgesia?
o Prevention of arousal
o Opiates contribute to hypnotic effects of GA
o Suppression of reflex responses to painful stimuli
§ Tachycardia, hypertension
why regional anaesthesia
Intense/complete analgesia
o No direct hypnotic effects
examples of local anaesthetics
lignocaine, bupivacaine and ropivacaine
how do local anaesthetics work?
Work by blocking Na+ channels and preventing axonal action potential from propagating.
Pharmacologically filthy with effects on every tissue so toxic if delivered wrongly (intravenously!!).
Much progress in ability to deliver analgesia with regional techniques, either alone or in conjunction
with GA. Biggest benefit is avoidance of reliance on opioid analgesics.
limiting factors for use of local anaesthetics
o High plasma levels
o IV injection
o Absorption > rate of metabolism = high plasma levels
o Therefore vasoconstrictors – reduce blood flow, reduce absorption
what does LA toxicitiy depend on
o Dose used
o Rate of absorption (site dependant)
o Patient weight
o Drug (bupivacaine > lignocaine > prilocaine
signs and symptoms of local anaesthetic toxicity
- Circumoral and lingual numbness and tingling
- Light-headedness
- Tinnitus, visual disturbances
- Muscular twitching
- Drowsiness
- Cardiovascular depression
- Convulsions
- Coma
- Cardiorespiratory arrest
differential blockade in LA
One useful property of LA block of peripheral nerves is differential block. This is due to differential
penetration into different nerve types. Myelinated, thick fibres are relatively spared. Pain fibres are
blocked easily (luckily). Due to the different physical attributes of different nerve fibre types (thickness
and myelination) some are easier for LA to block than others. Luckily for us motor fibres are relatively
to block and pain fibres relatively easy. This means we can provide analgesia without paralysis. Very
useful – e.g. patient with abdominal surgery can get good analgesia from epidural analgesia but still
be able to use abdominal muscles to cough.
• Retain awareness/consciousness
• Lack of global effects of GA
• Derangement of CVS physiology proportional to size of anaesthetised area
• Relative sparing of respiratory function
types of regional and llocal anesthesia
• Local anaesthesia • Field blocks – hernia repair • Plexus blocks • Limb blocks e.g. femoral N and sciatic N Figure 6 Neuraxial Block CVS • Central neural (neuraxial) block o Epidural o Spinal
physiology of neuraxial block: resp
• Inspiratory function (relatively) spared
o Unless high block
• Expiratory function relatively impaired
o Cough dependent on abdo muscle function
• Decrease FRC – airway closure c.f. GA
• Increased V/Q mismatch
Respiratory effects are produced by the motor block produced by LA block of mixed spinal nerves.
Higher and more extensive blocks interfere with respiratory function more. Abdo muscles are
primarily expiratory function while inspiratory muscle (intercostals and accessory muscles) are served
by higher nerve roots. Therefore, inspiration will tend to be relatively spared compared with
expiration in spinal and epidural anaesthesia.
