Intravenous lipid emulsion treatment for propranolol toxicity: Another piece in the lipid sink jigsaw fits

To the Editor:

We read with interest the case report by Jovic-Stosic et al. describing their treatment of a patient presenting with a severe propranolol and ethanol overdose with intravenous lipid emulsion (ILE).¹ They described the successful use of 20% Intralipid in a patient that responded inadequately to conventional resuscitative measures. It is commendable that the authors were able to determine the levels of propranolol, ethanol, diazepam and its active metabolite temazepam, before and after treatment with 20% Intralipid. The authors highlight two episodes in the resuscitation whereby the patient's haemodynamic parameters improved significantly in response to two separate 500ml aliquots of 20% Intralipid. In our opinion, this clearly supports the utility of ILE in reducing the toxicity of propranolol, whilst increasing the body of evidence in support of ILE in the treatment of lipophilic drug overdoses.²

The lipid sink theory is one of several proposed mechanisms to explain the beneficial effect of ILE. Following administration of ILE, an intravascular lipid compartment is created that has the capacity to sequester lipophilic drugs present at potentially lethal concentrations, thereby reducing their toxicity. The extent to which a drug is lipid soluble can be described by its log P value; propranolol is highly lipid soluble with a log P of 3. Therefore, we consider ILE to be entirely appropriate for the treatment of propranolol toxicity and are not at all surprised that the patient responded favourably to the administration of 20% Intralipid. We are puzzled by the authors’ statement that whereas propranolol levels decreased to half their admission level after 3.5 h but did not change significantly in the following 8 h that this did ‘not fit with the lipid sink theory’. On the contrary, we suggest that this finding can readily be explained and is entirely compatible with the lipid sink theory. Had the authors been able to measure just the concentration of free drug in the plasma, we strongly suspect that there would have been a consistent decrease in this value over time. Usual laboratory drug assays will measure the total plasma concentration of drugs and will be unable to differentiate between the free unbound active component and the significant proportion (i.e. up to 80% in some studies) of drug that is sequestered by ILE and rendered virtually inactive.³ Not only is the ability of ILE to achieve a ‘plateau level’ supported by several experimental studies, but it is also notable that in the first description of ILE binding with the lipophilic drug amitriptyline, plasma concentrations actually increased by 14% following administration of Intralipid.⁴ This implies the ILE sink mechanism could be responsible for assisting the extraction of lipophilic drugs from surrounding tissue and their retention within the intravascular compartment. Finally, we agree with Jovic-Stosic et al. that early administration of Intralipid to patients presenting with severe propranolol toxicity, in parallel with immediate and recognised interventions, may reduce the lethal toxic effects that this drug can produce when taken in overdose.⁵

Declaration of interest

Dr D. R. Uncles and Dr J. Willers are co-founding members of www.lipidregistry.org