Vet360, December 2016 - Page 25

TOXICOLOGY Checklist for the successful use of intravenous lipid emulsion therapy: • • • • • What is the lipophilicity (published Log-P value) of the toxicant? Is there an established, effective antidote available for the toxicant? Is the toxicosis severe enough to require nonstandard intervention? Is the present standard of care or antidote therapy cost prohibitive? Does the owner understand the experimental nature of the therapy, the possible side effects and consent to its off-label usage? followed by a constant rate infusion of 0.25ml/kg/min for 30 to 60 minutes. If no improvement is noted ILET is unlikely to work and must be discontinued. If some improvement is noted but some clinical signs persist intermittent boluses of 1.5ml/kg may be repeated at 4 – 6 hourly intervals for 24 hours and to a maximum of 8ml/kg/day. Alternatively, a constant rate infusion of 0.5ml/kg/hour for up to 24 hours is presumed to be reasonably safe. Reported side effects with the use of ILET in veterinary cases include post-infusion facial pruritus in a cat responsive to chlorpheniramine. Pancreatitis and hyperlipidaemia are the most common side effects reported to the American Animal Poison Control Center due to the use of lipid emulsions secondary to hyperlipidaemia. A single report of extravasation injury causing local pain and swelling has also been described. The side effects, of ILET secondary to microbial contamination when used as part of a parenteral nutrition protocol are well described, however patients requiring parenteral nutritional are more compromised than healthy animals presenting with acute toxicity Most commercial lipid emulsion preparations are stabile at room temperature for up to 2 years but once opened need to be used within 24 hours or discarded and replaced every 24 hours. Appropriate product storage and strict aseptic technique during the ILET is imperative to prevent contamination. Side effects described in human medicine can be grouped as directs effects including colloidal changes, pyrexia or anaphylaxis. These are rare with anaphylaxis reported in < 1% of humans and usually manifests within 20 minutes of administration. Fatty overload syndrome (FOS) is seen when an excess amount of lipid emulsion is administered. In humans FOS is seen at rates over 0.11g/kg/day. Clinical signs include fat embolism, hyperlipidaemia, hepatomegaly, icterus, splenomegaly, thrombocytopaenia, prolonged clotting times, haemolysis and neurological signs. These side effects are thought uncommon when using ILET in clinical toxicology due to the difference in administration technique. In toxicosis large boluses and infusions are given over short periods but the total daily dose is significantly less than that administered during parenteral nutrition. ILET should be avoided in patients that are critically ill patients or those suffering from severe pulmonary disease or sepsis as in humans it caused worsening of oxygenation and diffusion parameters on arterial blood gas measurement. In conclusion, ILET is a life-saving, non-specific treatment for a variety of lipophilic toxicities causing a rapid and dramatic improvement in clinical signs with decreased hospitalisation time. However, it does not replace conventional antidote therapy and supportive care. Commercial lipid emulsions are relatively inexpensive with a long shelf-life and easy to administer. Although the treatment is off-label and experimental, acceptance for its clinical use has grown, and continues to do so. Further research to elucidate on its safety and efficacy in clinical toxicology is needed. Appropriate case selection, understanding the mechanism of action of both ILET and toxicant, as well as sufficient resources in a hospital setting to allow for careful monitoring and exact administration technique is imperative for a successful outcome. List of toxicants whose side effects may potentially be reversed with the use of intravenous lipid emulsion therapy: Toxicant Log-P value Amlodipine* 1.90 Baclofen* 1.30 Carprofen* 4.13 Chlorpheniramine* 3.17 Chlorpromazine* 5.35 Clomipramine* 3.30 Cyclosporine* 3.00 Dexamethasone* 1.83 Diazepam* 2.82 Digoxin* 1.26 Diltiazem* 2.80 Ibuprofen ∆ 3.50 Itraconazole* 5.90 Ivermectin* 3.50 Ketoprofen* 3.12 Lidocaine* 2.26 Moxidectin* 4.10 Permethrin 6.10 Ŧ Promethazine* 2.85 Vinblastine* 3.69 * Fernandez et al., 2011 ∆ Bolfer et al., 2014 Ŧ Peacock et al., 2015 References available on Issue 06 | DECEMBER 2016 | 25