Is lipid emulsion therapy effective in calcium-channel-blocker and beta-blocker overdose?

intralipid-161x3002 out of 5 stars

Role of intravenous lipid emulsions in the management of calcium channel blocker and β-blocker overdose: 3 years experience of a university hospital. Sebe A et al.  Postgrad Med 2015 Feb;127:119-124.

Abstract

The authors of this study, from Cukurova University School of Medicine in Turkey, retrospectively reviewed patients admitted to their hospital who were treated with lipid rescue therapy (LRT) for refractory hypotension, heart block, or cardiac arrest following overdose from a calcium-channel-blocker (CCB) or a beta-blocker (BB).

They identified 15 patients(9 CCB, 6 BB.) There were two cardiac arrests; one of those patients died, the other survived with hypoxic encephalopathy. One additional patient survived with hypoxic encephalopathy. Twelve patients were reported discharged without sequelae.

The authors’ stated goal was to “assess the efficacy of lipid emulsion as antidotal therapy in severe CCB and BB intoxications.” Unfortunately, their study has so many flaws that they don’t even come close to an answer.For one thing, their chart review has almost no methods. In addition, some key data are missing, such as the time interval between initial administration of LRT and reversal of hypotension and hypoperfusion.

One other observation:the paper states that the CCB patients were treated with hyperinsulinemic euglycemia before LRT was started. However, their protocol was to give 1 g/kg dextrose followed by 0.5 U/kg/hour insulin. Most recommendations include an initial bolus dose of  0.5-1 U/kg. If this had been given, at least some of these patient might have responded and not needed LRT in the first place.

Like the authors, I am a believer in LRT for the patient in refractory shock from overdose of many cardiotoxic drugs. Unfortunately, I can not use the data in this paper to argue the point.

Related posts:

Excellent review of lipid rescue therapy

TPR Podcast #7: Interview with Guy Weinberg about lipid rescue therapy

Acute respiratory distress syndrome following intralipid emulsion therapy 

Complications associated with lipid emulsion therapy

Lipid rescue therapy can interfere with critical lab values

Case report: cocaine cardiotoxicity treated with intravenous lipid infusion

Lipid emulsion therapy for poisonings: a review

Lipid emulsion overdose

Tox on the web: 12 students hospitalized at Wesleyan College after “Molly” overdose

Four students arrested at Wesleyan College after “Molly” overdoses: Last weekend a dozen students and visitors at Wesleyan University in Middletown, Connecticut were hospitalized after apparently ingesting a drug or drugs labelled as “Molly.” Two victims were in critical condition and were medevacked to Hartford Hospital, the only Level 1 Trauma Center in the region. By mid-week, these two patients were still in hospital but reported to be improving. Four students have been arrested in connection with this incident.

As @forensictoxguy pointed out on his blog “The Dose Makes The Poison,” the reporting of this story on the media has been generally confusing. Some outlets described “Molly” as a pure potent form of MDMA (ecstasy), and reported that police attributed the extreme adverse effects to a “bad batch.” But as one official remarked, when it comes to “Molly” there is no such thing as a “good batch.” Users never no for sure what drug(s) their product contains; one report found that only 13% of “Molly” samples contained any MDMA at all. (And, of course, MDMA itself can be fatal.) Later statements from police indicated that the samples from Wesleyan contained several designer drugs.

Because of this uncertainty about what’s in the drug, using “Molly” has always been a form of pharmaceutical Russian Roulette. TPR has pointed this out before.

The Activated Charcoal Cleanse: Companies that make juice products intended for detox or cleanse programs are now offering a new type of product: drinks spiked with activated charcoal:

blackmagic_bottle_large

These would be great beverages to stock in the vending machine in emergency department waiting rooms. The drink pictured above is made with water, activated charcoal, lemon, Grade B maple syrup, and Himalayan sea salt. It is not clear how much activated charcoal one bottle contains. Of course, I’ve ordered some and will report back on a taste test when it arrives.

Podcast of the Week: ToxTalk has a great episode with Dr. Guy Weinberg (@lipidguy) discussing how the history of lipid rescue therapy progressed from clinical observation, to animal models, and then back to use in clinical medicine. There is also a little bit about possible mechanisms, a topic that will be continued in Part 2 that should be posted in the next several days. Highly recommended. To listen to Part 1, click here.

 

Excellent review of lipid rescue therapy

intralipid3.5 out of 5 stars

Intravenous Lipid Emulsion in the Emergency Department: A Systematic Review of Recent Literature. Cao D et al. J Emerg Med 2014 Dec 19 [Epub ahead of print]

Abstract

This excellent comprehensive review of lipid rescue therapy (LRT) is vitiated only by the unavoidable fact that available clinical evidence  is so inconclusive. As the authors point out, published literature consists mostly of case reports and small case series. The vast majority of these reported cases have good outcomes and reflect positive effects from ILE, but the evidence is marred by multiple confounding variables (such as concurrent treatment) that are impossible to correct for, and by publication bias. There have been no prospective randomized controlled trials.Intravenous lipid emulsion is now considered first-line therapy for local anesthetic systemic toxicity (LAST,) but generally reserved as a last-ditch effort for patients severely ill from other drugs who are not responding to more established interventions.

The authors conducted an extensive literature review to identify publications describing human overdose cases treated with LRT in which outcomes were reported. They found 94 articles and 40 abstracts, which are cited in a very complete bibliography current to 2014.

This entire review is well worth reading. I will touch on some points I found particularly interesting.

Table 1 lists the different drugs involved in overdose cases where LRT was used, along with whether the observed result was “positive effect” or “no apparent effect.” (For some reason they do not report possible negative effects, although one article cited in their reference list described 2 patients who developed asystole shortly after receiving LRT.) The list includes:

  • local anesthetics (primarily bupivacaine)
  • anti-depressants (including amitriptyline, citalopram, bupropion, and venlafaxine)
  • anti-psychotics (including quetiapine and olanzapine)
  • cardiovascular medications (primarily calcium-channel-blockers, beta-blockers and anti-arrhythmics)

There are cases cited of overdose with various other agents, including aconite, lamotrigine, baclofen, and chloroquine. Most of the drugs involved were lipophilic, but positive effects were observed also with water-soluble drugs, such as metoprolol, atenolol, labetalol, and amphetamine.

The authors note that at this time the recommendations for LRT dosing in overdose cases is empiric, based on the experience with treating LAST. They do not discuss a point we touched on in our recent podcast with Dr. Guy Weinberg. With LAST, a relatively large dose of toxic agent is rapidly taken up systemically, and quickly eliminated if the patient survives. With an oral overdose, systemic absorption can continue for hours or even days. Optimal LRT treatment in these cases might require a completely different dosing schedule. Unfortunately, that question has not been studied.

Related posts:

TPR Podcast #7: Interview with Guy Weinberg about lipid rescue therapy

Acute respiratory distress syndrome following intralipid emulsion therapy 

Complications associated with lipid emulsion therapy

Lipid rescue therapy can interfere with critical lab values

Case report: cocaine cardiotoxicity treated with intravenous lipid infusion

Lipid emulsion therapy for poisonings: a review

Lipid emulsion overdose

The Poison Review 2015-02-24 06:02:30

2.5 out of 5 stars

Evaluation of Residual Toxic Substances in the Stomach Using Upper Gastrointestinal Endoscopy for Management of Patients With Oral Drug Overdose on Admission. Miyauchi M et al. Medicine 2015 Jan;94:e463

Abstract

Despite many flaws, this paper has some interesting data that the authors use to come to exactly the wrong conclusion.

The authors studied patients presenting with oral non-liquid drug overdose. Using endoscopy they classified the contents of the stomach as: 1) tablet/food phase; 2) soluble/fluid phase; and 3) reticular/empty phase.(I’m not clear on the precise meaning of a “tablet/food phase,” but let that pass.) They then compare these findings to the time elapsed rom ingestion, which they claim they determined with precision without revealing exactly how this was accomplished.

They studied 167 patients. Their key finding was that only 12 of 73 patients (16%) with stomach contents in the tablet/food phase presented within 1 hour of ingestion; 3 of these patients actually presented more than 12 hours of the time of ingestion. The authors note that recent guidelines recommend that gastric lavage should not be performed routinely, but could be considered in a patient presenting less than one hour from an acute overdose. They argue that their results showing residual stomach contents more than 1 hour out for ingestion suggest that ” . . . the time that has elapsed since ingestion should not be a priority consideration when determining whether to perform gastric lavage.”  I agree that a sharp cutoff of 60 minutes has no scientific support.

The authors don’t seem to realize that this just confuses the matter. At least the one-hour rule had the advantage of simplicity, while also eliminating consideration of lavage in most patients. As I’ve argued before, lavage is an intervention without proven benefit but with known adverse effects. It also has not clear indications and involves significant opportunity costs. Although some very smart experienced toxicologists continue to use the modality, I believe that as a general proposition it should not longer be recommended.

After advocating for the elimination of the one-hour rule, the authors become unhelpfully vague:

The decision about when or whether to remove the stomach contents should be made based on the risk assessment of the particular intoxication and the benefits and potential risks of gastric lavage for each patient.

What they don’t mention is that no solid criteria exist with which to make this risk assessment, and it seems clear that none will be determined in the future. At best, the findings here support administration of activated charcoal if there are no contraindications, even if a number of hours has passed from the time of ingestion.
Related post:

Gastric Lavage? Fuggedaboutit!

 

Sundays with SMACC: Sonowars 2014

SonoWars from Social Media and Critical Care on Vimeo.

At the SMACC Gold conference last March in Australia, an epic Sonowars contest pitted the Northern Hemisphere against the Southern Hemisphere. Representing the North were Matt Dawson and Mike Mallin from the Ultrasound Podcast. Meeting the bell for the lands down under were James Rippey and Adrian Goudie from Ultrasound Village and The Sono Cave. The battle is both amusing and informative. The entire session lasts about 90 minutes. If time is limited, start watching at 56:00, where Dr. Rippey builds a heart out of clay to teach echocardiographic anatomy, and Dr. Mallin in turn rises to the challenge by creating a human heart (that is, a heart made of humans) to demonstrate acute right ventricular overload from a  massive pulmonary embolism.

A reminder: SMACC Chicago is coming June 23-26. The program is bigger and better than ever, and will include a new Sonowars battle, this time on the Northern Hemisphere’s home court. This conference will be huge, bringing together physicians, nurses, pharmacists, prehospital specialists and others active in both critical care and FOAMed (Free Open Access Medical Education.)

STUDENTS: Part 2 of the contest for free registration to SMACC Chicago is coming up in a few days. At exactly midnight (Chicago time CST) on February 24, 12 questions will be posted on the student page of the SMACC Chicago site. The top 3 fastest responses will win a student registration worth $350 US. Good luck to all.

Treating severe drug-induced hyperthermia with an ice-water bath

Ice Bath3 out of 5 stars

Ice water submersion for rapid cooling in severe drug-induced hyperthermia. Laskowski LK et al. Clin Toxicol 2015 Mar;53:181-184.

Abstract

There is still debate about the optimal method of cooling severely hyperthermic patients, such as those with core temperature > 104oF (40oC) who are exhibiting changes in mental status. Some common techniques include ice packs to the groin and axillae, cooling blankets, along with convection (evaporation) techniques such as cool sprays and fans. There is little debate, however, about the proposition that the faster these extremely hyperthermic patients are cooled the better the outcomes.

This fascinating paper present 2 spectacular cases of drug-induced severe hyperthermia treated by submerging the patient in an ice-water bath:

  1. A 27-year-old man was brought to the hospital with agitation after ingesting 4-fluoroamphetamine. (This was confirmed in the laboratory.) He rectal temperature was 106.5oF (41.4oC). He was immediately placed in an ice water bath, with core temperature measured every 5-60 seconds. After 22 minutes in the bath, he core temperature was 99.3oF (37.4oC). The patient received a total dose of 28 mg midazolam while submerged and did not exhibit shivering. On the second hospital day, he signed out against medical advice.
  2. A 32-year-old man was brought to hospital because of agitation and hallucinations after using cocaine. His rectal temperature was 112oF (44,4oC)!! He was paralyzed, intubated, and place in an ice-water bath. After 20 minutes in the bath, his core temperature was 102oF (38.8oC.) He was discharged after 10 days in hospital”in stable condition,” although no mention is made of his mental status.

These temperatures are impressive, especially in the second case. (I think 112oF is hot enough to sous vide a salmon.) In the discussion section, the authors describe their technique:

The steps to performing ice water submersion are straight-forward. Once hyperthermia is documented, the patient should be immediately undressed, wrapped in a sheet, and place in a water-impermeable bed (when available), while indirect patient care staff fill large plastic bags with ice to cover and surround the patient. Important nursing and patient care technician roles include establishment of IV access, administration of medication, and placement of cardiac leads, pulse oximetry and a rectal probe for continual core temperature monitoring. Benzodiazepines may be indicated to treat psychomotor agitation. Rapid sequence incubation and advanced cardiac life support measures, if indicated, can and should be performed with the patient in the ice bath. While a lack of evidence exists to guide a specific endpoint temperature, we recommend at endpoint core temperature of 39oC (102.2oF), at which point the patient should be moved to a new hospital bed and dried completely, to avoid an overshoot towards hypothermia.

In an editorial commentary piece, Dr. Edward Otten from the University of Cincinnati states that although defibrillation would be difficult to perform on a patient in an ice-water bath, significant cardiac arrhythmias are rare in hyperthermia. He also suggests that an esophageal thermometer might be a preferred method of measuring core temperature, since it does not come into contact with ice water.

This is a case series of only 2 patients, but very interesting and worth reading.