Local Anesthetic Systemic Toxicity Update Dr MUHAMMAD AMIM ANWAR LNH

Local Anaesthetic Systemic Toxicity J Clin Diagn 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.

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.

Local Anaesthetic Systemic Toxicity

Local Anaesthetic Systemic Toxicity

Local Anaesthetic Systemic Toxicity

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

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

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

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

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

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

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

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

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

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

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

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

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

Management WITHOUT CIRCULATORY ARREST Treat : Hypotension Bradycardia Tachyarrythmias

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)

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

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

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

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

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

Practical guidelines

Practical guidelines Frequent aspiration Test doses Minimum sedation Use of ultrasound

Practical guidelines

Practical guidelines

Practical guidelines

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

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