INTRALIPIDS anaesthesia presentation....

intralipids for rescue in LAST

1. INTRALIPIDS MODERATOR : Dr Bhanu Gupta PRESENTER : Dr Kavya

2. DESCRIPTION Intralipid® 20% (A 20% Intravenous Fat Emulsion) is a sterile, non-pyrogenic fat emulsion prepared for intravenous administration as a source of calories and essential fatty acids. It is made up of 20% Soybean Oil, 1.2% Egg Yolk Phospholipids, 2.25% Glycerin, and Water for Injection. In addition, sodium hydroxide has been added to adjust the pH so that the final product pH is 8. pH range is 6 to 8.9. Intralipid 20% has an osmolality of approximately 350 mOsmol /kg water (which represents 260 mOsmoL /L of emulsion) and contains emulsified fat particles of approximately 0.5micron size.

3. The total caloric value, including fat, phospholipid and glycerin, is 2.0 kcal per mL of Intralipid 20%. The phospholipids present contribute 47 milligrams or approximately 1.5 mmol of phosphorus per 100 mL of the emulsion Intralipid 20% is supplied as a sterile emulsion in the following fill sizes: 100 mL, 250 mL and 500 ml Intralipid 20% should not be stored above 25°C (77°F). Do not freeze Intralipid 20%. If accidentally frozen, discard the bag.

4. INDICATIONS Intralipid® 20% is indicated as a source of calories and essential fatty acids for patients requiring parenteral nutrition for extended periods of time (usually for more than 5 days) and as a source of essential fatty acids for prevention of EFAD. As a rescue in local anaesthetic system toxicity As an antidote in lipophilic drug overdose such as * CCBS * TCA * Betablockers *Bupropion CONTRAINDICATIONS Intralipid 20% is contraindicated in patients with: • Disturbances of normal fat metabolism such as pathologic hyperlipemia, lipoid nephrosis or acute pancreatitis if accompanied by hyperlipidemia . • Known hypersensitivity to egg, soybean, peanut protein, or to any of the active ingredients or excipients in Intralipid 20%.

5. Local anesthetic systemic toxicity (LAST) It is a life-threatening adverse event. Occurs after the administration of local anesthetic drugs through various routes. Incidence 0.03%, or (1 episodes/3,000 peripheral nerve blocks) Adverse reaction proportional to plasma concentration of local anaesthetic Dose of drug administered Rate of absorption Site of injection Vasoactivity of drug Use of vasoconstrictor Biotransformation and elimination

6. Distribution of toxicity type •Isolated cerebral toxicity in 50 % of cases, • Combined cerebral and cardiac in 36 % of cases, • 14 % of cases exhibited cardiac toxicity alone. Time of toxicity presentation •26 % within 1 min •48 % within 5 min of injection •22% after 30 min or more

7. Mechanism Increasing plasma concentrations of LA initially affects cortical inhibitory pathways Inhibiting these pathways leads to Excitatory clinical features of sensory and visual changes, Muscular activation, Seizure activity. As the plasma concentrations of LA rises further, excitatory pathways are affected, Producing a depressive phase of neurological toxicity, Loss of consciousness, coma, and respiratory arrest. Central nervous system (CNS) toxicity

8. Most LA drugs readily cross BBB Effects of these drugs on the CNS are dose dependent They vary depending on the individual drug and unbound plasma concentration. Example lidocaine toxicity signs at various plasma levels

9. Cardiovascular toxicity Block of sodium , calcium and potassium channels Bupivacaine is cardiotoxic , strong attraction to myocardial sodium channel , slow dissociation from the sodium channels due to its lipophilic properties. It typically follows a two-stage pathway. • In the early stages, sympathetic nervous system activation during the CNS excitatory phase indirectly leads to hypertension and tachycardia. • A direct myocardial depressant effect occurs at higher concentrations. • Normal conduction is disrupted by direct sodium channel blockade,

10. CVS toxicity • Resting membrane potential become more negative, • Action potential propagation is impaired, at SA node & at the bundle of His. • Leading to prolonged PR, QRS, and ST intervals. • Re-entrant tachyarrhythmias and bradyarrhythmias occurs • Further potassium channel blockade worsens the condition by, prolonging the QT interval.

11. Pediatric dose 1.5ml/kg (300mg/kg) lipid emulsion 20% over 1 to 3 min Follow immediately with 0.25ml/kg/min for 30-60min . Doses can be increased to 0.5ml/kg/min based on response. Administer undiluted over 1-3 mins. A max of 10-12ml/kg can be administered over 24hrs. THERAPEUTIC ENDPOINT : Intravenous lipid emulsion therapy should be discontinued once hemodynamic stability in achieved.

12. PRACTICALITIES Can be administered via a peripheral vein or as central venous perfusion. If not administered immediately, use within 24 hours due to propensity to foster bacterial growth In general other drugs should not be co-administered with Intralipid due to incompatibility by its emulsive properties Administration may interfere laboratory measurements (Hb, amylase, lipase, Cr, ALT, bilirubin, Mg) Monitoring of serum amylase/lipase should occur for 2 days after Intralipid therapy to detect pancreatitis

13. LIPID THERAPY SIDE EFFECTS Allergic reaction , headache , somnolence , dizziness , dyspnea , diaphoresis , nausea and vomiting , hyperthermia , and hypercoagulability. Thrombocytopenia , jaundice , refeeding syndrome, leucopenia , hepatomegaly , splenomegaly, Fat overloading syndrome Pulmonary hypertension with long term therapy Yeast infection

14. CONSIDERATIONS Premature and low-birth weight infants (poor lipid clearance resulting in pulmonary accumulation and death) Severe hepatic dysfunction; poor lipid clearance Severely malnourished patients at risk of re-feeding syndrome Drug interactions Warfarin; Intralipid contains vitamin K1, counteracting the effect of vitamin K epoxide reductase inhibition by warfarin and reducing its efficacy

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