We read with interest the case report by Jakkala-Saibaba and colleagues describing the successful treatment of cocaine overdose with lipid emulsion [1]. They report rapid reversal of severe cardiovascular instability following intravenous lipid emulsion administration. Their case is a welcome contribution to the body of published laboratory and clinical case studies [2], and raises some interesting points that we believe warrant further discussion.

In their case report, the authors initiated a correction of the profound acidosis using intravenous bicarbonate and invasive ventilation. In doing so, it is likely they indirectly increased the capacity for lipid emulsion to bind cocaine, as an increase from a pH < 6.80 to 7.21 renders it approximately 3 times more lipid soluble [3]. Previously, drug lipid solubilities expressed as their log P values, have been used to determine the ability of lipid emulsion to suppress the toxic effects of nitrates in vitro [4]. Log P values are determined when the drug is presented as the unionised species. However, when pH values outside the normal physiological range are considered, expression of lipid solubility by its log D value at a specified pH may be more appropriate as this takes into account both the ionised and unionised species [5]. Therefore, log D values may be a more precise measure of lipid solubility with which to guide clinical treatment using lipid emulsion. In this case, the log D(6.8) and log D(7.2) values would have been more appropriate, with values 0.3 and 0.9 respectively [3].

Secondly, the supply of street cocaine currently available in the UK may contain adulterants, such as the local anaesthetic benzocaine. This replicates the numbing effect of cocaine and gives the user a false assurance of quality [6]. Several case reports have been published describing cocaine-associated methaemoglobinaemia, not directly attributable to cocaine or its metabolites, but rather due to benzocaine [7]. The patient described by Jakkala-Saibaba et al. presented with a relatively low pulse oximetry reading (93%) in the presence of a high PaO₂ 38.2 kPa. The manifestation of hypoxia in the absence of hypoxaemia might suggest another form of haemoglobin was present, such as methaemoglobin. However, in this case the patient is known to have possessed a normal methaemoglobin concentration of 1.5% as determined by co-oximetry (personal communication from authors). Nevertheless, benzocaine is unionised throughout the pH range 6-8 and hence possesses identical log P and log D values, both with a value of 1.50 [3]. This implies that a patient’s acidaemia would not affect the lipid solubility of benzocaine. Thus, bearing in mind that benzocaine may complicate cocaine overdose, the lipid sink effect would be sustained (in contrast to cocaine) at these low pH values described (i.e. < 6.8). Therefore, it is important to note that lipid emulsion may reduce the amount of methaemoglobin formed through sequestering benzocaine and contribute further to the improvement in a patients’ clinical condition.

Finally, the authors should be commended on their implementation of well recognised and established interventions in the treatment of a lipophilic drug overdose. There is an increasing need to determine which lipophilic drug toxidromes are amenable to treatment with lipid emulsion; especially when one considers that many overdoses include combinations of lipid soluble and/or lipid insoluble drugs. Lipid emulsion is fast becoming a useful adjunct in the treatment of lipophilic drug toxicities and we endorse the authors’ statement regarding its use in the treatment of ‘cocaine overdose with life-threatening cardiovascular arrhythmias and collapse’. Recognising the requirement to treat acidaemia and awareness of other drugs that could potentially be present in a cocaine overdose will further improve the appropriateness of lipid emulsion for this clinical scenario. 

We would encourage clinicians who have deployed intravenous lipid emulsions for treatment of lipid soluble drug toxidromes to report their cases to the Lipid Registry (www.lipidregistry.org) and consider posting their experiences on the Lipid Rescue website (www.lipidrescue.org). 

TL Samuels

A Papadopoulou

JW Willers

 DR Uncles

Department of Anaesthesia and Intensive Care

Worthing Hospital

Worthing

Email: dr.tsamuels@gmail.com

DR Uncles and JW Willers are co-founders of the Lipid Registry website (www.lipidregistry.org). No other external funding or competing inteests declared.

References

1. Jakkala-Saibaba R, Morgan PG, Morton GL. Treatment of cocaine overdose with lipid emulsion. Anaesthesia 2011; 66: 1168–70.
2. Jamaty C, Bailey B, Larocque A, Notebaert E, Sanogo K, Chauny JM. Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies. Clinical Toxicology 2010; 48: 1-27.
3. Chemicalize. Physiochemical properties for Cocaine. www.chemicalize.org/structure/#!mol=CN1[C%40H]2CC[C%40%40H]1[C%40H]%28[C%40H]%28C2%29OC%28%3DO%29c3ccccc3%29C%28%3DO%29OC&source=fp (accessed 3 December 2011)
4. Samuels TL, Willers JW, Uncles DR, Monteiro R, Halloran C, Dai H. In vitro suppression of drug-induced methaemoglobin formation by Intralipid^® in whole human blood: observations relevant to the ‘lipid sink theory’. Anaesthesia 2011 doi: 10.1111/j.1365-2044.2011.06914.x
5. Uncles DR, Willers JW, Samuels TL, Papadopoulou A, Short S, Short G. Investigating the effect of ionisation on the behaviour of lipophilic drugs in an intravenous lipid emulsion in vitro. Anaesthesia 2011 doi:10.1111/j.1365-2044.2011.06962.x
6. Hunter L, Gordge L, Dargan PI, Wood DM. Methaemoglobinaemia associated with the use of cocaine and volatile nitrites as recreational drugs: a review. British Journal of Clinical Pharmacology 2011; 72: 18-26.
7. Chakladar A, Willers JW, Pereskokova E, Beaumont PO, Uncles DR. White powder, blue patient: methaemoglobinaemia associated with benzocaine-adulterated cocaine. Resuscitation 2010; 81: 138-9.