Local Anesthetic Systemic Toxicity Update Dr MUHAMMAD AMIM ANWAR LNH

1. LocalAnestheticSystemicToxicity UpdateDr MUHAMMAD AMIM ANWARLNH

2. Local Anaesthetic Systemic Toxicity • J ClinDiagn Res. 2015 Feb;9(2):UD03-4. doi: 10.7860/JCDR/2015/11104.5540. 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

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 30-60 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