LipidRescue™ Resuscitation

MM, a 29 year old woman was brought to A&E resus by ambulance after having taken an overdose of amitriptyline combined with between ½ and a full bottle of wine. Obtaining a complete history of events from family was quite difficult and ambulance notes were fairly minimal. Initial thoughts were that she may have ingested 14 fifty mg tablets (700 mg or 7.7 mg/Kg), however this was later re-estimated at being up to 56 tablets equating to 2800 mg. With an estimated body weight of 90 Kg, this equals roughly 30 mg/kg, which is well into the toxic, and potentially lethal arrange.
The initial history suggested that the time of consumption was roughly 1 hour prior to admission, and 90 min prior to involvement of critical care. Initial GCS values recorded by paramedics were E3, V3, M6 = 12. At the time of our assessment it had dropped to E1, V1, M4 = 6/15. The patient was tachycardic at 125, BP maintained at approximately 120/70, with good saturations on oxygen. 12-lead ECG showed a QRS duration of 108 ms, and QTc of 486. She was tolerating an NP airway and taking regular but small volume respirations at a rate of 10 per min. ABG showed a pH of 7.30, PCO2 5.8, lac 2.6, HCO3 of 20.9 and BE -4.8. Pupils were 4 to 5 mm and responding poorly. Reflexes were brisk with several beats of ankle clonus and skin was warm, flushed and dry. All signs were pointing to a significant TCA overdose. The A&E and medical staff had begun fluid resuscitation with normal saline 1000 ml and gelofusine 500ml. No bicarbonate had yet been given.
Given the author’s previous experience with lipid rescue it was felt reasonable to attempt to improve her GCS and maintain her cardiac stability with a 1.5 ml/Kg bolus, followed by a .25mg/kg/min infusion. While the author made preparations to administer intralipid, a second anaesthetist was present throughout who was dedicated to airway management in the event that intubation became necessary. RSI drugs were drawn and an ODP was also present throughout.
Within a few moments of the 100 ml bolus of intralipid the patient’s heart rate dropped from 120 bpm to 95 bpm, and a few minutes later their appeared to be a slight increase in spontaneous movements of the patient’s limbs. Her formal GCS however remained unchanged. After 30 min of infusion the patient was essentially unchanged clinically. The ABG had deteriorated slightly to a pH of 7.27 and PCO2 of 6.4. Interestingly her QRS duration had decreased from 108 to 94 ms, while her QTc had increased from 486 to 508 ms. It was at this point that the estimate of actual ingestion was learned to be potentially as high as 30 mg/Kg.
Given this rather more significant ingestion it was decided to repeat both the bolus and infusion while final preparations were made to intubate the patient and take her to ITU for overnight care. Intubation with propofol and rocuronium proceeded uneventfully. A single bolus of 50 mmol of bicarbonate was administered and the patient was ventilated to an ETCO2 of 3.7 to 4.1 during transfer to ITU.
A repeat ECG 90 min after the previous one showed an unchanged QRS duration but a reduction in QTc to 476 ms. ABG had improved to pH 7.44, PCO2 4.4, HCO3 22.4, but lactate was steady at 2.4
The patient remained stable on the ITU for the next few hours, being sedated with propofol and fentanyl and ventilated to a normal pCO2 and pH. At roughly 7 hours post Intralipid ( 8 ½ to 9 hrs post ingestion) there was a return of tachycardia reaching a peak of 140 bpm and a deterioration in BE from -1.8 on ITU admission to -3.0 and then -5.1. Urine output deteriorated at this point to 15 ml/hr and a 500 ml colloid bolus was administered. This bolus improved urine output and maintained it for the remainder of the day, but interestingly, the tachycardia did not fully settle back to baseline for another 4 hours (14 hours post ingestion). At 11 hours post ingestion sedation was switched off and the patient was extubated about 30-45 min later.
Over the course of the day that patient remained drowsy, slightly agitated when awake and also had occasional jerky spontaneous movements. At 15 hrs post ingestion an infusion of bicarbonate 1.26% at 50ml per hour was commenced for 4 hours, although it is not exactly clear in the notes why this was performed and what the clinical response to it was.
At 22 hours post ingestion (when the author returned to duty) the patient was reviewed and found to be as described above. She had little recollection of the events the previous evening. She was unclear as to the number of tablets taken, but suggested 18 to 20 which equates to 1000 mg or only 9 mg/kg.
Discussion points:
Unlike previous experiences of the author and others; in this case of suspected isolated TCA OD (with minimal EtOH) the administration of 20% Intralipid appeared to have little effect on the patient’s GCS and as such we were unable to avert an intubation. Why this case differs from the others is difficult to say. Perhaps the 1.5 ml/Kg initial bolus was insufficient given the amount of TCA taken (potentially up to 30mg/Kg). Intuitively, if the mechanism of action of Intralipid is in fact as a ‘lipid sink’ then it is not unreasonable to consider the idea that doses need to be tailored not only to weight, but also quantity of drug ingested.
Although we were unable to improve the patient’s GCS, it is notable that despite what may have been a quite significant overdose, the patient remained remarkably haemodynamically stable with an immediate correction of tachycardia and no fall of BP even on induction with propofol.
Whether the QTc normalised as a result of the second bolus of intra-lipid or the more standard interventions such as fluid resuscitation, maintenance of normocapnia and correction of acidosis is difficult to say. The QRS duration did however respond fairly quickly to the first dose Intralipid, when the acidosis was still deteriorating.
The return of acidosis and tachycardia at 7 hours post Intralipid as described is curious. Could this be as a result of metabolism of the lipid sink and return of active TCA to the plasma or can it be described more simply by changes in general ITU management such as sedation being too light whilst intubated, sub-optimal ventilation and inadequate fluid resuscitation; or perhaps a combination of the two.
It has been noted that there seems to be a plethora of positive outcome cases on the lipid registry. Here is an example of a case where no significant response in GCS was obtained, and there was only a hint that the intralipid may have aided in the maintenance of haemodynamic stability.

just a few remarks from our clinical experience at a toxicologic ICU (vienna,austria)
the course of TCA ingestion is markedly characterized by enteral reabsorption of a significant dose of the hepatal excreted drug. in our opinion, repeated administration of activated charcoal is crucial in preventing reoccurence of disease. the above described clinical course (again tachycardia after hours of admission) in my opinion fits perfectly in this concept.
lipid rescue remains, despite all efforts including this excellent website, an aera of experimental therapy. we used physostigmin in TCA-overdose for more than 15 years, dealing well with all the problems described here and in other cases on LIPIDRESCUE.org. being an experimental therapy itself and in discussion for years, and its use being discouraged especially in angloamerican literature, we still consider it a very useful, fast acting and safe method to treat tachycardia, long-QT, hypotension and all the symptoms of central anticholinergic syndrom, avoiding a lot of intubations and CVAs for catecholamines, and avoiding the still unclear risk of high-dose-bolus of fat iv.
two years ago, we adopted a protocol for use of lipid rescue in life-threatening intoxication of a various number of drugs (including catastrophic TCA overdose) and used it once in verapamil-intoxication since. especially in cases of mixed intoxications with drugs as paracetamol, having at hands a standard antidot to prevent severe liver damage, the pharmacodynamic/-kinetic fate of this antidote remains totally unclear under conditions of lipid rescue. we think it may be unwise to use the latter (look also some other cases posted on this website).

the whole bunch of TCAintoxications we faced(and some of them with doses quite above the ones described above) never met our inclusion criteria for lipid rescue, being treated with repeated activated charcoal, physostigmin and standard ICU care.