Post Your Cases > ? Rebound toxicity

A 39 year-old female was brought to ED with alleged history of ingestion of 12 grams of sustained-release verapamil 4 hours ago, she was treated with orogastric lavage, charcoal and intravenous calcium. As she was deteriorating, she was intubated and mechanically ventilated. She was started on vasopressors, but her blood pressures were persistently low. We gave 100mL of Intralipid 20% over 30 min followed by an infusion at 0.5 mL/kg/h for 8 hours. Her Bp rosed to 120/90 mmHg. noradrenaline infusion was tapered and stopped. Unfortunately, 50 minutes after administration of the last Intralipid her BP dropped and went to bradycardia. She was resuscitated as per AHA guidelines and improved with adrenaline infusion. This case raises suspicion of rebound toxicity. Kindly throw light on this issue.
November 14, 2012 | Unregistered CommenterSenthilkumaran
Hi Senthil,
I think it indicates the patient was continuing to absorb the verapamil. This raises a difficult therapeutic dilemma since you can't give ILE forever, yet some patients will decline when lipid infusion is discontinued. Some options include titering down to the very lowest infusion dose that sustains a viable BP; or you can take a lipid vacation and restart as the BP begins to sag; or you can consider plasmapharesis: remove blood, replace with colloid and/or blood and this will allow you to continue giving 'fresh' lipid while not driving up the TG concentration too much. good luck. I hope the pateint did well.
December 4, 2012 | Registered Commenter[Guy Weinberg]
Hi Senthil
I am also interested in this case: You omit to mention the patient's weight, but assuming a body weight of, say, 70Kg, based on the figures (and assuming the units you have used are correct) in your account, I calculate the patient received a total of 380ml Intralipid over an 8 hour+ period (i.e. 5.4 ml/Kg)

We have little information on prolonged infusion rates of lipid emulsions in the context of lipid soluble drug overdoses, however the rate you have stated approximates to that used when intralipid is employed as a component of TPN therapy, which appears to be clinically acceptable at this rate for this application. There is a consensus that a cumulative dose of 10-12 ml/Kg may reasonably be used to treat acute drug toxicity, however the time frame/interval before repeat dosing might be considered is not known.

Orally administered sustained release preparations in overdose present a number of different challenges to those of parenterally administered drugs (when manifestations of acute toxicity are likely to occur much more quickly) and the concept of maintaining plasma concentrations of lipid emulsions for a much longer period of time poses many questions, one of which reflects exactly the question you have asked. This question has the potential to generate some interesting and important research to provide the answer.
February 24, 2013 | Unregistered CommenterDavid Uncles