Anaesthetic drugs and Analgesia Flashcards
General Anaesthesia
A reversible loss of consciousness with absence of recall of noxious stimuli
Pain
An unpleasant sensory and emotional experience resulting from a noicioceptive stimulus, or expressed in terms of damage
Mechanisms of Anaesthesia
Affects various sites including the reticular activating system, cerebral cortex, hippocampus, limbic system and spinal cord
Synaptic transmission is decreased.
Efficacy correlates with oil/gas partition coefficient and protein binding affinity
Intravenous anesthetics
Increase GABA and glycine transmission
Used for IV induction of anaesthesia
Eg Propofol
Volatile anaesthetics
Inhalational agents used for maintenance
Potency correlates with lipid solubility as does onset/offset time
Isoflurane (sevoflurane can be used for gas induction)
Triad of anaesthesia
Hypnosis – Sleep component
Analgesia – pain relief
Paralysis – allow intubation and surgical access – if neuromuscular blocker is used risk of apnoea
Stages of anaesthesia (Guedel)
Stage 1 – Induction, from awake to analgesia with amnesia
Stage 2 – Excitement with delirious and irregular breathing and muscular activity with risk of aspiration
Stage 3 – Surgical, skeletal muscles relax and breathing is regular. eye movements slow and stop
Stage 4 – Overdose, severe brain stem or medullary depression with risk of death
Risks of anaesthesia (4,1,7)
Common – pain, sore throat, nausea, vomiting
Uncommon – Dental damage
Rare – Allergic reaction, aspiration, resp complications, VTE, pressure effects, awareness, death
Specific – eg central lines risk pneumothorax
Local Anaesthesia
Selective loss of sensation of a selective circumscribed region of skin/body by a controlled reversible procedure
Regional Anaesthesia
Local anaesthesia by produced by ‘up-stream’ administration of drugs
Mechanism of LA action
blockade of Na+ ion channels
Minimal blocking concentration (Cm) – influenced by temp, Ca2+, pH, nerve penetration and tissue binding
Succession of nervous blockade
Sympathetic –> pain –> temp –> touch –> motor
Structure of LA
Lipophillic aromatic head, intermediate ester or amide linkage and basic, hydrophilic head (amines)
Short duration/low potency LAs
Procaine or Chloroprocaine
Amino-esters. hydrolysed by pseudocholinesterases
LAs are all weak bases, in equilibrium between charged quarternary and uncharged tertiary amines
Intermediate duration and potency LAs
Lignocaine, prilocaine, cocaine
amino-amides
Long duration and high potency LAs
Bupivacaine, Ropivacaine & Tetracaine
Relationship of charge and function
The uncharged tertiary, lipophilic form can cross the epineurium and enter the nerve axon but the quarternary, charged form can exits the ion channels
Lipid solubility and protein binding determines potency and duration
What determines the potency of LAs?
Lipid solubility
What determines the duration of LAs?
Protein binding
What determines the rate of onset of LAs?
pH of the solution and pKa of the drug – lower pKa means more is in lipid soluble form so faster absorption and more rapid onset
Higher pKa means more effective blockade once within nerve
Factors changing the pharmacokinetics of LAs
Site of injection
Use of vasoconstrictors
Carbonation – decrease in pH
Alkalinisation – increases pH
Metabolism of LAs
Amides – Liver – conjugated and excreted in urine (2-3hr)
Easters – plasma and liver esterases (half life short)
Some metabolites are a risk of hypersensitivity
LA Toxicity
Common – accidental IV injection or CNS toxicity
Allergy – rare, metabolites
LA Overdose
Lignocaine >10ug/ml, Bupivacaine >3-5ug/ml
CNS stimulation then depression – sedation –> seizures due to selective inhibition of inhibitory fibres
early signs are circumoral and tongue numbness
LA CVS toxicity
at 2-3x CNS dose –> at first peripheral arteriolar vasodilatation –> dose related decrease in cardiac contracility and conduction
Particularly Bupivacaine
Treatment of toxicity
Supportive –> CNS –> oxygen, anticonvulsants
CVS –> Bretylium, phenytoin, Mg2+, Propofol, give lipid TPN to increase volume of dilution
CVS/CNS ratio
the ratio of drug needed to induce convulsions compared to cause CVS collapse –> Lignocaine is 7 while Bupivacaine is 2.7 (more cardiotoxic)
Safe dose of LA
Depends on injection site but generally Lignocaine 3mg/kg or 7mg/kg with Adr (Bupivacaine 2mg/kg)
1% lignocaine contains?
10mg per ml
So for a 70kg man max dose is 70x3=210mg=21ml of 1% or 10.5ml of 2%
With Adr this increases to 70x7=490ml=48ml of 1% or 24ml of 2%
Benefits of central blocks (spinals or Epidurals)
Avoid the risks of GA (difficult intubation, malignant hyperthermia, etc), good post-op analgesia, avoids sedation/N&V, reduced blood loss and reduced stress response
Epidurals
A needle with a catheter is inserted into the epidural space and the catheter left in place to provide anaesthetia to the epidural space - numbing just the area supplied and lasts longer (can be topped up) than spinals
Malignant Hyperpyrexia
triggered by volatile agents or suxamethonium resulting in the loss of normal Ca metabolism in muscle. An autosomal dominant condition with a defect in the ryanodine receptor. This leads to hypoxia, hypercapnia, hyperthermia and acidosis. Cell death then leads to release of K+, myoglobin and CK.
Spinals
25/27G blunt Needle introduced into the CSF and LA (may be mixed with dextrose to weight it down) is injected. this will anaesthise the whole body below the site of injection and some above as well.
Side effects of central blocks (spinals or Epidurals)
hypotension if sympathetic block (this can lead to N&V), post-dural puncture headache (worse with bigger needles and in the young), high blocks can effect the limbs and breathing,
Contraindications of central blocks
hypovolaemia, sepsis, LA allergy, advanced CVS disease, INR>1.5, care should be taken if there is previous major spinal surgery or CNS disease
Treatment of Malignant hyperthermia (MH)
100% oxygen, removal of trigger, active cooling and 1mg/kg (up to 10mg/kg) IV dantrolene. mortality is reduced from 80% to 5%.
Dantrolene
A skeletal muscle relaxant which prevents Ca release from the sacroplasmic reticulum.
Investigations for MH
a muscle biopsy should be taken and exposed to caffeine and halothane (contracture test). patients identified from this test should wear a medic alert bracelet.
Scoline apnoea (Suxamethonium apnoea)
4% of the population posess genetic variants in plasma cholinesterase enzymes meaning they process suxamethonium slower and this lead to immobilised awareness or hypoxiaemia if ventilation is not properly maintained. treatment is to maintain anaesthesia & ventilation until the paralysis has worn off. Mivacurium can produce a similar syndrome.
Cutaneous Porphryia
Cause photosensitivity/photodermatitis, blisters, necrosis of the skin and gums, itching, swelling and hair growth on the forehead. After exposure to sunlight urine can be red, brown or purple. Diagnosis is by PBG (porphobilinogen) in the urine.
Porphyria in anaesthesia
Can be triggered by anaesthetics like ketamin or etomidate. Many other drugs can also trigger attacks.
Corticospinal tracts
Upper motor neurons which decussate (80% forming the lateral tract but 20% don’t remaining the anterior tract) at the medulla and travel from the cortex anterior to the central gyrus and synapse with LMNs in the anterior horn
Epidurals are indicated in?
C-sections, Hernia Repair, Lower limb surgery, Total knee or hip replacement, Urological surgery, Vascular Surgery, Gynae or pelvic surgery, Pain relief for labour, Post-op after trunk/abdominal/orthopaedic surgery.
Nerves effected by epidurals
C fibres first, then progresses based on size. Clinically cold sensation is lost first and then pain then motor function. LA will also block Autonomic function (dangerous if T1 or above).
Spinal technique
As for epidural. Non-cutting dural-fibre splitting needle (24G sprotte or 26G Whitacre) - once in SAS check by presence of CSF then inject LA/opiod over 10-15seconds.
