86: Updated intravenous lipid emulsion in drug toxicity guidelines

In this episode I’ll discuss updated toxicology guidelines when using intravenous lipid emulsion (ILE) for drug toxicity. 
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Back in episode 30 I discussed the use of ILE for drug toxicity.  In April 2016 the American College of Medical Toxicology published guidance for using ILE.   The most significant change to the ILE recommendations is a 10-fold reduction in the maintenance infusion of ILE after the first few minutes of treatment for enteral drug toxicities.   Here are the new guidelines:

1) A 20 % lipid emulsion (e.g., Intralipid) should be administered as a 1.5 mL/kg bolus. The bolus should be administered over 2–3 minutes. A repeat bolus can be considered if there is a failed response to the first bolus. 

2) The bolus may be followed immediately by an infusion of 20 % lipid emulsion at a rate of 0.25 mL/kg/min. After 3 minutes of this infusion rate, response to the bolus and initial infusion should be assessed. If there has been a significant response, the infusion rate may be adjusted to 0.025 mL/kg/min (i.e., 1/10 the initial rate). This recommendation is based on concerns for adverse effects from extremely high cumulative rates of lipid infusion, and a desire to be able to monitor the impact of initial therapy in a dynamic enteral overdose situation. Blood pressure, heart rate, and other available hemodynamic parameters should be recorded at least every 15 minutes during the infusion. 

3) If there is an initial response to the bolus followed by the re-emergence of instability during the lowest-dose infusion, the infusion rate could be increased back to 0.25 mL/kg/min or, in severe cases, the bolus could be repeated. There is no known maximal dose, but other authors have suggested a maximum dose of 10 mL/kg.

There are several good reasons for reducing the maintenance infusion rate:

1.  There is a case report of ILE clogging CRRT filters, possibly contributing to a patient’s death.
2.  Acute respiratory distress syndrome and ventilation/perfusion mismatch have also been reported in patients who have received traditional ILE dosing for drug toxicity
3.   A physiologically based pharmacokinetic-pharmacodynamic model suggests that the reduced maintenance infusion rate is sufficient to produce a plasma triglyceride concentration that will provide the scavenging and cardiotonic benefits of ILE.
4. This model is supported by two case reports where a lower ILE maintenance infusion rate was used successfully: case one & case two.

Unfortunately the ACMT guidelines suffer from the same lack of practicality when it comes to actually administering  ILE in a real-world toxicology scenario.   

The main problem is the disconnect between the recommended administration rate and the maximum administration rate possible on an IV infusion pump.  I’ve yet to see a “smart” pump that is able to deliver a medication faster than 999 mL/hr (16.67 mL/min).   But in any patient over 66 kg, the necessary infusion rate to deliver 0.25 mL/kg/min exceeds 999 mL/hr.  

This leaves the clinician with the choice of hanging an ILE infusion in multiple IV sites.  Unfortunately the logistics (establishing/tying up a 2nd line, getting an extra ILE bag, etc…) make this impractical.   

I would like future guidelines to take into account the limitations of available “smart” pump technology.  

The same total ILE dose that 0.25 mL/kg/min over 3 minutes provides can be infused as follows using conventional “smart” pumps: 

~ 70 kg patient = 20% IV lipid emulsion at 999 mL/hr for 3 minutes

~ 90 kg patient = 20% IV lipid emulsion at 999 mL/hr for 4 minutes

~ 110 kg patient = 20% IV lipid emulsion at 999 mL/hr for 5 minutes 

After the high-dose infusion is complete, the rate can be dropped to 0.025 mL/kg/min as the guidelines recommend  for the remainder of treatment. Note:  There is a typo in the original copy of the ACMT guidelines where they report the maintenance infusion rate as 0.025 mg/kg/min instead of 0.025 mL/kg/min.  Thanks to @druginfogeek on twitter for pointing this out! 

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