Treating digoxin toxicity: is less more?

Digifab3 out of 5 stars

Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Chan BSH, Buckley NA. Clin Toxicol 2014 Aug 4 [Epub ahead of print]

Abstract

This long detailed paper seems to be a manifesto masquerading as a review article. It is quite informative and well worth reading. But I’d keep in mind that the authors appear to have a (not so) hidden agenda: to decrease the dose of digoxin-specific antibody fragments administered in most cases of acute and chronic digoxin toxicity.

The authors state their objective up front:

To review the pharmacology, efficacy, effectiveness, indications, safety and dosage of digoxin-Fab. On the basis of the reviewed data. to propose a regimen of administering digoxin-fab to patients with digoxin poisoning based on pharmacokinetic principles.

Although they identified 140 relevant citations, they are not clear on exactly how these were selected. (Their reference list contains only 69 papers.) They note that there have been no randomized clinical trials on digoxin toxicity.

The authors say this about indications for using digoxin-specific antibody fragments:

There is general agreement that digoxin-Fab is indicated in patients with life-threatening tachy-bradyarrhythmias, hyperkalaemia (> 6 mmol/L) or haemodynamic instability with concentrations (e.g. digoxin > 2 μg/L or > 2.6 nmol/L) that support digoxin may be a contributing cause.

They point out that in acute toxicity, dose calculations based on serum digoxin levels taken before distribution is complete (approximately 6 hours) may overestimate the amount of digoxin-Fab required. They argue that 2 vials of digoxin would likely neutralize all free digoxin in the central compartment in cases of acute overdose, with clinical benefit evident within 60 minutes. The dose could be repeated if there were no clinical response.

Chronic toxicity usually involves a much lower total body load than in cases of acute ingestion, and lower doses of digoxin-Fab are generally recommended. Therefore:

. . . we recommend giving 1 vial (40 mg) at a time and observe for clinical response. If none is observed after 60 min, a second ampoule of digoxin-Fab may be administered, to neutralize digoxin re-distributing from the peripheral compartment.

The authors may very well be correct that much lower doses of digoxin-Fab than those generally used may suffice. However, I think there are a number of weaknesses in their argument and would be reluctant to adopt their suggestions at this time. With regard to acute toxicity, it would be hard to titrate the need for additional doses of digoxin-Fab, since clinical effect will not be evident for 30 minutes to an hour. When treating actual or potentially life-threatening toxicity, it seems to me risky to delay getting a reliably sufficient dose of antidote on board as soon as possible. Although the authors’ suggestions are based on pharmacokinetic modeling, there are not enough clinical data available to indicate whether their 2-vials-and-observe” protocol would be safe and effective.

I’m even more doubtful about their recommendation for treating chronic poisoning  If the indication is life-threatening toxicity, giving a single vial and then observing for an hour seems foolish. The one advantage to this is to save on the cost of digoxin-Fab. (The current price of a vial of Digibind is $728 USD.) since with chronic toxicity relatively few vials of digoxin-Fab are required in most cases, this protocol would not produce significant savings.

Of course, in treating stable patients without signs of immediate life-threatening manifestations of digoxin poisoning, the incremental start-low-and-titrate-to-response method may work just fine. Unfortunately, this paper in my opinion does not distinguishing adequately between truly life-threatening cases and those that are less dire. It is, however, dense with good information and definitely worth a look. II found it  extremely helpful to think through the authors’ recommendations and see if they made sense.

 

 

 

 

 

It has recently been suggested that the therapeutic blood level of digoxin be reduced from 0.8-2.0 μg/L to 0.5-0.8 μg/L in patients with congestive heart failure. (Contrary to the authors’ implication, I do not believe that this suggestion has been universally accepted.)

 

Hydrogen peroxide ingestion: can bedside ultrasound help?

http://www.youtube.com/watch?v=ed6mpRKmx14

3 out of 5 stars

Young Woman With Epigastric Pain and Vomiting. Manning EP et al. Ann Emerg Med 2014 Sep;64:330.

Full Text

This brief case is part of the Annals of Emergency Medicines‘s series “Image of the Month.” A 23-year-old woman develops epigastric pain and vomiting after investing a cleaning agent. Abdominal exam was unremarkable. a CT of the abdomen demonstrated gas in the portal veins.

The cleaning agent was hydrogen peroxide, which causes injury by two mechanisms: 1) corrosive tissue injury, and 2) gas formation. A previous case report indicated that even dilute 3% hydrogen peroxide can cause gas emboli to the portal system. Images that accompany this case reveal erosions in the esophagus and stomach, as well as gas embolization to the portal veins. The patient was treated with hyperbaric oxygen with resolution of her abdominal pain.

It would have been interesting to see a bedside ultrasound in this case. Gas in the portal veins should show up as unusual hyperechoic densities in the liver. This may be an indication for referral to a hyperbaric oxygen center.

The video clip above is not from this case, but nicely illustrates ultrasound findings associated with gas in the portal system. Additional images can be seen here. My recent column in Emergency Medicine News discussed other possible uses for bedside ultrasound imaging in toxicology cases.

Blowguns, poison darts, and tajem poison

This interesting short film illustrates the meticulous care that goes into making a poison dart blowgun. The poison mentioned in the video — tajem — is made from latex obtained from the bark of a specific tree. I was not able to find out details about how it acts, but it appears to be cardiotoxic and produce fatal arrhythmias. One source mentions that there are several natural antidotes. Hunting with tajem-tipped poison darts is practiced by the Penan people in Borneo.

Body packers: can CT determine the number of drug packets?

Body packer

Body packer

2.5 out of 5 stars

Sensitivity and specificity of CT scanning for determining the number of internally concealed packages in ‘body-packers.’ Asha SE et al. Emerg Med J 2014 Feb 19. doi: 10.1136/emermed-2013-203389. [Epub ahead of print]

Abstract

Although the abdominal CT scan has been shown to be relatively accurate for determining the presence or absence of drug packets in suspected body packers, there is no good data as whether or not the test is accurate in determining the number of such packets.

The abstract of this paper suggests that the authors — from Sydney’s St. George Hospital — retrospectively reviewed hospital records of 50 confirmed body packers to study whether or not abdominal CT was reliable for counting the number of packets in the GI tract of these patients. However, buried in the results section is an admission that because of missing data only 24 cases were available for analysis. Thus, the study is merely half as large as they suggest up front, and their (in my opinion) ill-advised statistical analysis is much less convincing.

In any case, they found that the accuracy for determining the number of ingested packets was poor — a conclusion that should be obvious even without the study by looking at come of their CT images of intestines chock-a-block with drug packets. They found that CT was accurate if the person had ingested less than 15 packets, but this conclusion is based — according to my count — on results from a scant 6 patients.

The authors end up recommending that with a stable, asymptomatic suspected body packer who admits to ingesting drug packets, clinicians could omit the initial CT scan on admission. Instead, they suggest the patient could be given laxatives and observed until there were several clear bowel movements. At that point, a CT could be obtained to confirm that all packets had passed. Despite the weakness of the data, this seems like a reasonable approach to me.
Related posts:

MRI for body packers?

Low-dose abdominal CT is superior to plain film for imaging suspected body packers

Cannabis body packers

Treatment protocol for symptomatic body packers (mules)

Cocaine mules: what to do with body packers

 

 

 

 

 

 

CPC: salicylate toxicity

aspirin3.5 out of 5 stars

A 21-Month-Old Boy with Lethargy, Respiratory Distress, and Abdominal Distention. Klig JE et al. N Engl J Med 2014 Aug 21;371:767-773.

Reference

This case discussion — part of the New England Journal‘s Case Records of the Massachusetts General Hospital series — makes a number of important points about managing salicylate toxicity. It is not a complete review; since the patient did not need mechanical ventilation, the tricky subject of intubating a salicylate-toxic patient is not covered.

Some of the key points:

  • Hyperthermia in these patients is an indicator of severe toxicity.
  • The salicylate level is not a reliable indicator of severity.
  • Alkalinizing the serum in these cases (to a pH of 7.50-7.55) is even more important than alkalinizing the urine.
  • Maintaining a normal serum potassium level is critical to achieving the goal of enhanced elimination.
  • A decreasing serum salicylate level is not reassuring if the patient is deteriorating clinically.
  • Hemodialysis not only enhances elimination of salicylate but also helps correct electrolyte and acid-base abnormalities.

This paper is worth seeking out and reading.

 

Related posts:

Discussion of salicylate toxicity misses several key points

Pearl: falsely normalized anion gap in salicylate overdose

Excellent guidelines for managing salicylate overdose

Salicylate toxicity can present with a normal-anion-gap metabolic acidosis

Salicylate toxicity: the great masquerader

 

 

 

Tox Tunes #86: Let’s Go Get Stoned (Big Mama Thornton)

http://www.youtube.com/watch?v=spkcAjt-TKU

Big Mama Thornton (1926-1984) was a powerful rhythm and blues singer who recorded and/or wrote a number of songs that were big hits for other artists. “Let’s Go Get Stoned” — written by Nickolas Ashford, Valerie Simpson, and Josephine Armstead — went to the top of th eR&B charts when Ray Charles released his version in 1966. Thornton recorded Leiber and Stoller’s song “Hound Dog” in 1952. It was popular, but not the monster hit Elvis Presley had with the song in 1956.

Thornton recorded her own song “Ball and Chain” in the early 1960s. Her career got a boost after the then little-known Janis Joplin stunned the audience at the 1967 Monterrey Pop Festival with an electrifying performance of the song. Unfortunately, as so often happened in those days, Thornton did not have rights to the song and thus earned no royalties when it was included on Joplin’s second album Cheap Thrills, released in 1968.

Here’s Joplin’s transcendent Monterrey Pop performance:

http://www.youtube.com/watch?v=Bld_-7gzJ-o

And here’s Big Mama’s original version of the song:

http://www.youtube.com/watch?v=n-rNX1DKuMI