3. Local Anaesthetics lecture:

LA drugsBasic structure is made up of 3 components:Lipophilic groupHydrophilic groupIntermediate chain to connect the two which can be either an amine or an ester

Amides: EstersLignocaine ProcaineBupivacaine ChloroprocaineL-bupivacaine TetracaineRopivacaine Cocaine

Amides are metabolized by the liver whereas esters are hydrolysed by pseudo-cholinesterase.

Chemical and physical characteristics:1. Lipid solubility

The higher the solubility, the more potent the drug2. pKa (the pH where 50% of the drug is non-ionized)

The higher, the slower the onset of action3. Protein binding

The higher the binding, the longer the duration of action4. Isomerism

L-isomers are more potent than, but less cardio toxic the R-isomers5. Nerve anatomy

Large diameter nerves are more difficult to blockNon-myelinated nerves are easier to block than myelinatedNerves with high impulse traffic block easier than low activity nerves

Aδ (myelinated) and C(non-myelinated) fibers are pain fibers. Pain and temp are also transmitted via these tracts (lateral spinothalamic and post. Columns)

Note: Bupivacaine is a long acting and potent drug. Lignocaine is shorter acting and the onset is rapidBupivacaine is more potent than lignocaine as it is more lipid soluble and has a higher

pKa and protein binding value

Conversion:1% = 1g/100ml = 1000mg/100ml

= 10mg/ml(Multiply by 10)

S/E of local anaesthetics?

A) Immediate complications: Toxic reactions Hypotension Resp. distress Pain on injection

B) Intermediary complications: Motor paralysis Urinary retention

C) Late complications: Neurological damage:

o Nerve traumao Anterior spinal artery syndromeo Arachnoiditiso Pressure on the cord

Pneumothorax Headache

Clinical signs and symptoms of toxicity:

CNS CVSInitial phase Initial phaseCircumoral parasthesias HTTinnitus Tachycardia during the CNS excitation phaseConfusion

Excitatory phase Intermediary phaseConvulsions Myocardial depression

↓ Cardiac outputHypotension

Depressive phase Terminal phaseL.O.C. Peripheral vasodilationComa Severe hypotensionResp. arrest Sinus bradycardia

Conduction defectsVentricular dysrythmias

Maximum doses:

Lignocaine w/ adrenaline 7mg/kg w/out adrenaline 3-4mg/kg

Bupivacaine, L-bupivacaine, Ropivacaine w/ or w/out adrenaline 2mg/kg (max 150mg)

Therefore in 60 kg man:Lignocaine w/ adrenaline = 420mg w/out adrenaline = 180-240mgBupivacaine, etc w/ or w/out adrenaline = 120mg

Mx of toxicity:

1. General Anticipate toxicity Have resuscitation equipment available before anaesthesia is administered Maintain respiration-give O2 and ventilate the patient CVS should be supported. Rx hypotension with α and β-agonists. (ephedrine

10mg boluses, phenylephrine 50-100μg boluses, adrenaline 5-10µg boluses)2. Specific

Convulsions: IV thiopentone 100-200mg or diazepam 5-20mg Ventricular fibrillation: Intralipid, K+ channel openers, Bretilium tosylate

o K+ channel openers improve AV conduction, but cause myocardial depression

o Intralipid is main solute for TPN and propofol. Extremely effective antidote to bupivacaine induced CNS collapse.

Advantages and disadvantages of regional:Advantages:

patient remains conscious maintain his own airway aspiration of gastric contents unlikely smooth recovery requiring less skilled nursing care as compared to general

anesthesia

Disadvantages: patient may prefer to be asleep practice and skill is required for the best results some blocks require up to 30 minutes or more to be fully effective analgesia may not always be totally effective-patient may require additional

analgesics, IV sedation, or a light general anesthetic

4. Essentials of airway mx

Mx of laryngospasm after extubation? (5)The best mx is the avoidance thereof. If it does happen:

Give suxamethonium LM or try and intubate again (RSI) Bag and ventilate. The positive pressure should help open the airways to allow

oxygen in.

Formula for oxygen flux? (4)

How to manage a failed intubation? (5) Ventilate the patient Try laryngoscoping and intubating the patient again. (you have 3 attempts.

Ventilate between them) Between each attempt, try and improve the situation. (change the position, etc) If cant intubate after 3 tries, place LMA. If cant intubate and ventilate →Cricothyroidotomy Consider:

o Airway patencyo Risk of aspirationo Need for intubationo Need for GAo Nature of m. relaxant used

5. IV induction agents

a) Barbiturates Sodium thiopentone

ADME:Absorption: IVDistribution: all well-perfused organs

It has a high lipid solubility and therefore the blood-brain [] reaches equilibrium within 1 min (short acting) redistributes to other tissues (muscle and fat) causes short duration of action

Metabolism: Liver (10-15%/hr) 85% plasma protein binding to albumin. Binding decreased in pts with acidosis or hypoalbuminaemia. NB as the unbound fraction of thiopentone is the active part, therefore if less bound, more active… So one must decrease the dose.

Excretion: small percentage excreted unchanged in the kidneys.

Pharmacodynamics: CNS

o Sedation, hypnosis, anticonvulsant effectso Protection in focal but not global ischaemiao Beneficial for neurological compromised as:

↓ICP CMRO2 (cerebral oxygen consumption) ↓

Respo Depression is dependant on:

Dose Rate of administration Admin of other CNS ↓

o Sensitivity to CO2 is ↓o Depression is self-limiting

Larynx and bronchio May sensitize to reflex activityo May more readily cause laryngospasm and bronchospasm in

susceptible pts CVS

o ↓CO due to peripheral vasodilation and depression of myocardial contractility

o HYPOTENSION May be life-threatening in pt with fixed cardiac output as they

cant compensate by ↑stroke volume e.g. Constrictive pericarditis, tight mitral or aortic valves, complete heart block, etc.

S/E: Extravenous injection

o Ulceration and damage to surrounding tissueo Rx: inject 1% lignocaine to dilute and anaesthetize area

Intra-arterial injectiono Early

White hand, intense burning pain Skin discolouration Delayed induction

o Late Oedema Blisters and ulceration Gangrene → loss of limb

C/I: Absolute

o Porphyria variegateo Airway obstructiono Fixed COo Shocko Adrenal insufficiency

Relativeo Status asthmaticuso Hypovolaemiao Severe anaemiao Severe liver disease dystrophica myotonia

b) Non-barbiturates

PropofolPhysio-chemistry:

Highly soluble 1% propofol dissolved in Intralipid(soybean oil, glycerol and egg phosphate) Easily colonized with bact Milky white 20ml ampoule, with 10mg/ml

ADME: Absorption: IV

Distribution: large volume of distribution Half life 2-8 min Elimination half-life 1-3 hours Protein binding=98%

Metabolism: liver and probably the lungs Conjugated to inactive glucuronides and sulphates

Excretion: kidneys, faeces and lungsRenal disease does not influence kinetics

Pharmacodynamics: CNS

o Hypnotic. Lower doses can cause induction but onset is delayedo Subhypnotic doses→sedation and amnesiao ↓ICP by 30% (not as much as thiopentone)o CMRO2 ↓ 36%o Cerebral perfusion ↓10%o ↓intra ocular pressure 30-40%

Respo Apnoea (good for putting in LMA)o ↓resp rate for at least 2 mino ↓minute volume for at least 4min

CVSo 25-40% ↓ in SBP during induction (X use in Hypovolaemia)

Other non-hypnotic uses of propofol:AntiemesisAntipruriticSedation

EtomidateThe 4-5 B’sBrandBeweging

Associated with grand mal epilepsy High incidence of myoclonic movements

Braking Nausea and vomiting in 30-40%

Bynier Inhibits the synthesis of adrenal gland hormones

Baie stabiel Minimal ↓ of CVS Less than 10% change in Mean arterial pressure 10% increase in heart rate (minimal)

Benzodiazepines

2 commonly used: Diazepam 5mg/ml in 2ml ampoulePoorly soluble in H2O, dissolved in 40% propylene glycolIM painful and poorly absorbed

Midazolam 1or 5mg/ml in ampouleWater solubleLow incidence of pain after IM/IVClosed ring structure with phys pH of 7.4 may enhance

lipid solubilityMost lipid soluble as well as most potent benzo available

ADME:Absortion: IM/IVDistribution:Metabolism: Liver (microsomal or glucuronides conjugation)

Diazepam: 2 active metabolites (desmethyldiazepam, oxazepam)Therefore prolonged effects and half-life of 96hours

Midazolam: rapid oxidation of ring, no active metabolites. Short actionElimination: significant differences

Termination due to redistribution from GABA receptor to less fat rich tissue.

Uses: Anxiolysis Sedation Induction and maintenance of anaesthesia Decrease MAC of halothane by 30%

Anterograde amnesia Increase threshold for convulsions of LA

S/E: Interindividual variation with midozalam biggest prob Thrombophlebitis Prolonged effects if combined with opiate Synergism with induction agents, opioids, sedatives in comb with benzo’s to

give severe resp depression and drop in arterial BP

Ketamine:

ADME:A: IM/IV/PO/PRD: very fat solubleM: liver (microsomal)E:kidney

Pharmacodynamics: CNS

o 1-2mg/kgo Induces cataleptic stateo Onset of action 30sec-1min and in signified by nystagmuso Protective reflexes (corneal, cough, swallowing)retained to an extento ↑lacrimation, salivation, skeletal m. tone

Respo Good bronchodilatoro Unwanted S/E: hypersalivation (give anticholinergic)

CVSo CVS stimulation(releases Nor-adrenaline and inhibits uptake of

catecholamines)o Can block this with barbiturates or benzoo The ↑NA causes HT, tachycardia and ↑CO

7. Muscle relaxants

Contra-indications for the use of scoline? (5)

Absolute:Spinal cord injuriesBurns patients from 24hrs→20-60days

Relative:Severe traumaSevere intra-abdominal sepsisProlonged immobilsation (as more extra-junctional receptors have formed)Disuse atrophyCNS injury/infection from 10 days→60days after insult

S/E of scoline: Scoline apnoea Massive release of potassium Myalgia Malignant hyperpyrexia Masseter muscle spasm (in children) Hypersensitivity

Signs of inadequate muscle relaxation?

Difference cisatracurium and atracurium:

Atracurium CisatracuriumIsomer number 10 1breakdown Hoffmann elimination and

ester hydrolysisOnly Hoffmann elimination

Duration of action Shorter than Longer thanRenal failure Drug of choice Not drug of choice

Breakdown of atracurium: Hoffmann elimination

o Spontaneous breakdown at N body temp and pHo Breakdown product is called laudanosineo Excreted by the kidneys

Ester hydrolysis

According to the notes, the ED95 is: Dose required to decrease the amplitude of a single twitch (with a nerve

stimulator) with 95% Indicates the potency of a muscle relaxant

8. Opioids

10. Fluids

Calcium:

Potassium:

18. Obstetrics

Aorta caval compression syndrome:

Dx: pt in supine position has a 30-56% ↓ in COImproves with left lateral tilt and when the baby is out of the uterus

When will present? Last trimesterWhat will present with?

o Palenesso Hypotensiono Sweatingo Reflex bradycardia

Rx:o Left lateral tilt (tilted 15 degrees to the left)o Get the baby outo Do not do CPR unless in left lateral tilt position

Pre-eclampsia

Triad: HT Proteinuria Generalized oedema

Very illHypovolaemiaHypersensitive to exogenous and endogenous vasopressorsMay develop cerebral haemorrhage and pulm. OedemaMay have received magnesium sulphate therapy. (be careful. Non-depolarisers will lengthen magnesium sulphate action)

Rx:1. Fluids2. Left lateral tilt3. Pulse rate. If slow give ephedrine or adrenaline, not phenylephrine4. Oxygen

19. PaedsFluid management for 23kg toddler undergoing inguinal hernia repair? Show calculations. (4)

Maintenance: 1ml/kg/hr= 23mls per hourDeficits: depends on how many hours NPOReplacement: replace fluids lost per ml.

Then in 1st hour: maintenance + 50% deficits + replacementIn 2nd hour: maintenance + 25% deficits + replacementIn 3rd hour: maintenance + 25% deficits + replacement

Or use 50th percentile weight (kg) = (age x 2) + 9 (???)

Difference between adult and paediatric airway?

Faster resp rate Lower lung compliance Greater chest wall compliance (chest wall collapse with inspiration & low

RV) Hypoxic and hypercapnic ventilator drives not fully developed→ depressed

ventilation Large head and tongue Narrow nasal passages Anterior and cephalic larynx Long epiglottis Narrowest part of airway at cricoids (if under 5 years) Short trachea and neck

Prominent adenoids and tonsils Weak intercostals and diaphragmatic muscles High resistance to airflow (paucity of small airways and alveoli) Horizontal ribs

Blood volume of neonate (premature / fullterm); infant ; adult (F & M)?

Adult F:Adult M:

27. CPR

The dose of adrenaline depends on the condition:Hypotension: 10-20μg/as per response (wait to see what happens)Anaphylaxis: 5-10µg/kg IVCardiac arrest: 10-20μg/kg IVCan give adrenaline every 4min(the halflife of adrenaline)

Dose of joules for “defibrillation”Adults:Monophasic manual defibrillator= 360JBiphasic manual defibrillator= 150-200J

Children:4J/kg in both debfibrillator types (for first and subsequent shocks)

Why we ventilate with 100% oxygen: The FRC of the lung includes the ERV and RV. This is +/- 35ml/kgLets now say that a person has 2500ml left in his lungs. This translates to 500ml of oxygen as room air has only 20% oxygen.The baseline oxygen consumption is 3.5ml/kg/min or 1 MET. (more in babies, can be up to 7-8MET)So if this person is about 70kg, that would make his oxygen consumption per min 240ml. Therefore if he had to go into cardiac arrest at the end of expiration, he would only have about 2 min of oxygen to spare before things became critical.If we were to give him 100% oxygen, this would give him 10min (5x 2min).

Contributing causes that we must treat: (the H’s and T’s)