1. Local Anesthetic Systemic Toxicity Update Dr MUHAMMAD AMIM ANWAR LNH

2. Local Anaesthetic Systemic Toxicity
J Clin Diagn Res. 2015 Feb;9(2):UD03-4. doi: /JCDR/2015/ Epub 2015 Feb 1.
Local Anaesthetic Systemic Toxicity in a Patient under General Anaesthesia (GA): A Diagnostic Challenge.
Prakash R1, Gautam S1, Kumar S1, Singh R1
A 25-year-old male patient undergoing laparotomy for acute duodenal perforation under general anaesthesia developed seizures after epidural administration of 0.5% bupivacaine. All other possible causes of seizures were ruled out. Seizures were controlled with antiepileptic drugs and patient recovered fully after withholding LA administration.

3. Local Anaesthetic Systemic Toxicity
A healthy 18-yr-old male (weight 60 kg, height 167 cm), with a history of febrile convulsions in childhood, developed a grand mal convulsion 10 min after the second of two injections of ropivacaine 150 mg, both given incrementally 15 min apart (total 300 mg), for combined axillary/interscalene brachial plexus block. Treatment was with oxygen, lung ventilation, and i.v. midazolam, and the patient made a complete recovery. Arterial plasma ropivacaine concentration 2 min after the onset of convulsions was only 2.13 mg litre(-1), suggesting that this patient was particularly susceptible tolocal anaesthetic toxicity.

4. Local Anaesthetic Systemic Toxicity

5. Local Anaesthetic Systemic Toxicity

6. Local Anaesthetic Systemic Toxicity

7. Pharmacology
Local Anaesthetics are the agents that reversibly blocks the sodium channels preventing the further depolarization and impulse propagation is disrupted.

8. Pharmacology
A local Anaesthetic consists of a lipophilic group attached to hydrophilic group by an ESTER or AMIDE CHAIN.
Esters: Cocaine, Procaine, Amethocaine, Benzocaine
Amides: Lignocaine, Prilocaine, Bupivacaine, Levobupivacaine

9. Pharmacology All the L A are weak bases with a pKa of 8-9
Their penetration increases at alkaline pH and decreases at acidic pH of infected or inflammed area.
Esters are metabolised by plasma pseudocholinestrase.
Amides are metabolised by liver microsomal enzymes P450

10. Maximum limit of safe dose
Esters : cocaine 3mg/kg, procaine 12mg/kg, chloroprocaine 12mg/kg, tetracaine 3mg/kg
Amides: prilocaine 8mg/kg, lignocaine 4-7mg/kg, bupivacaine 3mg/kg, ropivacaine 3mg/kg

11. Incidence and prevalence
Interest in local anesthetic toxicity has had several peaks, including one that coincided with the initial awareness of local anesthetic toxicities after the introduction of cocaine in 1884,
another that followed the linking of fatalities to the use of bupivacaine and etidocaine in the 1970s,
and another after the introduction of ropivacaine and levobupivacaine in the late 1980s

12. Incidence and prevalence
Injuries associated with regional anesthesia in the 1980s and 1990s: a closed claims analysis.
Lee LA1, Posner KL, Domino KB, Caplan RA, Cheney FW.
Half of the cases were block related
Of those half were due to cardiac arrest or unintentional intravascular administration
True incidence of LAST is difficult to measure
Reporting near misses is rare, reporting bias

13. Factors contributing to toxicity
Site
Method of injection
Drug, dose, concentration and adjuncts
Patient : body weight, comorbids

14. Drug Factors Vasoactivity Concentration Dose Route of administration
Rate of injection
Vascularity of the injection site
Presence of vasoconstrictors

15. Adverse Drug Reactions
1) Side effects 2) Overdose reactions 3) Local toxic effects (most common) 4) Allergic reactions

16. Detection of Toxicity
CNS
CVS
Sudden alteration in mental state or loss of consciousness with or without seizures
Cardiovascular collapse, conduction blocks, sinus bradycardia, asystole and ventricular arrythmias

17. Management STOP : Stop injecting the Local Anaesthetic
HELP : Call for help
O2 : Maintain Airway
Give 100% O2
Ensure adequate lung ventilation

18. Management MONITORS : Attach Monitors IV ACCESS
CONTROL SEIZURES: Benzodiazepine, Thiopentone or Propofol

19. Management IN CASE OF CIRCULATORY ARREST START CPR standard protocols
Manage Arrythmias ACLS protocols
Consider use of CPBypass if available

20. Management WITHOUT CIRCULATORY ARREST Treat : Hypotension Bradycardia
Tachyarrythmias

21. Management GIVE INTRAVENOUS LIPID EMULSION
Initial bolus dose 20% Lipid Emulsion 1.5ml/kg over 1 minute
Start an infusion of 20% Lipid Emulsion at 15ml/kg/hour (0.25 mL/kg/min for minutes)

22. Management
AFTER 5 MIN
Give a max of two repeat boluses in 5 min intervals:
if cardiovascular stability has not been
restored
an adequate circulation deteriorates

23. Management
Continue infusion at same rate but bouble the rate to 30ml/kg/hr if cardiovascular stability has not been restored an adequate circulation deteriorates

24. IMPORTANT
DO NOT EXCEED a MAXIMUM CUMULATIVE DOSE OF 12ml/kg

25. INTRALIPID LIPID SINK HYPOTHESIS :
Circulating lipid will absorb LA and shif the pharmacokinetics away from the tissue receptors.
METABOLIC HYPOTHESIS :
Lipids counteract LA inhibition of myocardial fatty acid metabolism thereby preserving ATP within heart.
Inotropic effect

26. Practical guidelines Preparation for LA Blocks Consent Explain
IV cannula
Emergency drugs and Equipment
Standard Monitors: ECG, Pulse oximeter, BP

27. Practical guidelines

28. Practical guidelines Frequent aspiration Test doses Minimum sedation
Use of ultrasound

29. Practical guidelines

30. Practical guidelines

31. Practical guidelines

32. SUMMARY L A Toxicity is a life threatening complication
Prompt detection and treatment is necessary for good patient outcome.
2012 ASRA Guidelines include : monitoring, emergency equipment, modified ACLS protocols
Familiarity with LIPID RESCUE

33. .
THANKS