Local anaesthetic

Question 1

Discuss risk assessment of LA toxicity

Answer 1

Most cases of LA toxicity are iatrogenic from inadvertent intracascular administration

Clinical manifestation correspond to the concentration achieved in the systemic ciruclation

Onset is rapid

Methaemoglobinaemia is not dose related but is more likley to complicate administration of benzocaine, lignocaine or prilocaine

Children: Paediatric fatalities are reported following ingestion of lignocaine containing local and topcial agents but doses up to 6mg/kg ingested are safe. Children are more likley to develop methaemoglininaemia after LA administration

Question 2

Discuss maximum doses of LA

Answer 2

Lignocaine 3mg/kg or 7mg/kg with adrenaline
Bupivicaine 1-2.5mg/kg
Prilocaine 5-7mg/kg
Ropivicaine 2.5-3mg/kg

Question 3

Discuss the toxic mechanisms of LA

Answer 3

Bind reversibily to sodium channes and act on peripheral nerves to inhibit sodium flux necessary to intiaite and propogate APs. Local anaethetic agents esepcially benzocaine, lignocaine and prilocaine may also cause methaemoglobinaemia

Question 4

Discuss toxicokinetics of LAs

Answer 4

Amide LA can be administered Topciall, sub cut, IV for regional block, epidural and intrathecal.
Systemic toxic effect correspond to peak concentation acheived in the systemic circulation and this is affect by muliple factors - total dose, rate of administration, route and location of administration, presence of torniquets and local blood flow

Toxcitity is rare after oral ingestion due to significant 1st pass metabolism

The amides have a small VD and a eliminated by hepatic metabolism, with elimination half life of around 2 hours for most agents

Question 5

Discuss clinical features of LA toxicity

Answer 5

Earliset symptoms of LA toxcitiy are neurological
-Tinnitus, dizziness, anxiety, confusion and perioral numbness

More severe toxicity is characterised by

• • CNS effects – seizure and commoa
• -CVS - bradycardia, hypotension, atrial and ventricular dysrhythmias, CVS collapse and asystole
• -Resp - respiratory depression and apnoea

In general neuro symptoms are the earliest sign of toxicity unless a massive OD has been taken in which case CVS collapse can be presenting compaint

Bupivicaine is particularly cardiotoxic due to prolonged binding of myocardial tissue

Methaemoglobinaemia is not dose rleated- it manifest intiially as blue discolouration of the mucous membrans but may progress to CNS and CVS manifestation of cellular hypoxia, culminating in death as concentration rise above 70%

Question 6

Discuss IX of LA toxicity

Answer 6

EUC, ABGs, methaemoglobin concentration

serial ECG for Nas channel blockade signs (prolonged PR and QRS, large terminal Rwave in AVR)

Question 7

Discuss management of LA intoxiciation

Answer 7

Resus
-Ventricular arrythmias should be treated with repeated boluses of bicarb 100mEq (1-2mEq/kg in children) repeated every 1-2 minutes until ECG resolution

-Seizures are terated with benzo

D- not indicated
e- not indicated
A- Sodi bic, intralipid, methylene blue if methaemoglobiaemia suspected
D- Children with ingested do not need observation unless >6mg/kg. Once resus high-dependency or ICU

Question 8

Discuss indication for Methylene blue

Answer 8

Indication indclude symptomatic drug induced methaemoglobinaemia (signs of hypoxaemia with chet pain, dyspnoea or confusion) (nitrates, local anaethetics)
Consider in patient with Met HB of> 20%

Has also been used in anaphylactic and toxic shock states where hypotension persists despite vasopressors

Question 9

Discuss contraindications for Methylene blue

Answer 9

G6pD defeincy as unable to reduce mehtylene blue to leucomehtylene blue. Haemolysis may also occur

Renal impairment – dose adjustment

Methaemoglobinaemia reducatse defiency

Nitrite induce methaemoglobinaemia followint the treatment of cyanide poisoingin

Hypersensitivity

Question 10

Discuss the mechanisms of action of methylene blue

Answer 10

Dramatically increase the natural rate of reduction of methb to hb. It is reduced to leukomethylene blue by methaemoglobin reductase which in turn reduces met HB to HB

Inhibts nitric oxide synthase and guanylate cyclase and scavengers endothelial nitiric oxide it appear to have both vasconstrictive and positive inotorpic effect

Once reduced to leukomethylene blue is largely excreted in the urine

Question 11

Discuss the administration and therapeutic end point of using methylene blue

Answer 11

Administer 1-2mg/kg IV slowly over 5 minutes followed by a normal saline flush to minimise venous irritation
Met Hb levels should be measured hourly until a consistent fall is documented – usually respond to a single dose howevere 1-2mg/kg can be repeated after 30-60 minutes if the initial response is inadequate

In rare instances of dapsone poisoning where persistant formation of metHB occurs repeated doses of methylene blue may be needed

Single dose of 1-2mg/kg has been suggested as an adjunct to shocked patients

End point is resolution of symptoms of hypoxaemia, reduced metHB % stabilistation of HD parameters

Patients with pre-exisiting condition that can intefere with oxygenation such as anaemia or coronary artery disease may need to be treated at levels of Met HB of 10%

Pulse ox is unreliable as both metHB and methylene blue can interfere with it

Question 12

Discuss adverse reaction to methylene blue

Answer 12

Local pain and irritation at the site of injection is common, extravasation can lead to tissue necrosis

Common non spefific symptoms include headahce, dizziness, restlessness, nausea, vomiting, chest discomfort and SOB
Blue staining of mucous membranes
Can cause a paradoxically methaemoglobinaemia when given in hgih doses secondary to direct oxidative effect on HB
ACute haemolytic anaemia may occur in G6PD

Question 13

Discuss differentials if metHB is not falling with methylene blue

Answer 13

• Massive ongoing exposure to oxidising agents
• sulfahaemoglobinaemia
• G6PD - defiency
• Methaemoglobin reductase defiency
• Abnormal HB
• Excessive methylene blue administration

Question 14

Discuss Toxicological indictionas for intralipid

Answer 14

Local anaethetic induced cardiotoxcitiy, resistant to resus protocols
Consider in refractory cardiac instability or arrest in the context of acute poisoning with highly lipid soluble agents, including propanalol, TCA and verapamil

Contra-indications inldude hypersensitivity to egg, soya or peanut protein

Question 15

Discuss mechanisms of action of intralipid

Answer 15

1) introduction of an intravascular lipid phase that extracts agent from tissue binding sites
2) increased myocardial ATP synthesis due to reversal of inhibition of fatty acid delivery to mitochondira
3) restoration of myocyte function by activation of calcium and potassium channesl and an increase in intracellular calcium

Question 16

Discuss administration of intralipid and therapeutic end points

Answer 16

Give 1-1.5ml/kg IVLE 20% as IV bolus over 1 minute
Repeat bolus once or twice at 3-5 minute intervals

Then if required
Infuse IVLE 0.25ml/kg/minutes until HD stable
Increase 0.5ml/kg//min if hypotension persists
increaseing the dose above 8ml/kg is unlikley to be beneficial

End point
Return of ROSC with stabilisation of haemodynamic parameters. Infusion can be restarted if hypotension returns

Question 17

Discuss contraindications to intralipid

Answer 17

Immediate allergy
Pulmonary hypertension, acute lung injury, haematuria, hypertriglyceridaemia and pancreatitis

Pregnancy - saftey not established but should not be witheld if life threatening condition

Paeds – nil reported cases but should be witheld