POTD: Digoxin toxicity

Many of our patients are on digoxin, a potentially scary drug. Today we’re going to discuss what digoxin toxicity looks like, how to approach acute v. chronic toxicity, and digiFab/digiBind.

How does digoxin work?

1. Inhibits cardiac Na/K antiporter → increased intracellular Na, decreased intracellular K

   1. Decreased intracellular K →  HYPERKALEMIA in dig overdose

2. Increased intracellular Na → increased intracellular Ca

3. Increased Ca →  INOTROPY

4. Increased inotropy → reflex INCREASED VAGAL TONE

   1. In afib, this decreases conduction rate through AV node → slowed ventricular rate

Some pharmacology

• Oral bioavailability = 40-90% 

• Onset of action 2-6 hours after ingestion 

• CANNOT be removed via hemodialysis

• Renally excreted

• Things that INCREASE digoxin levels:

  • Amiodarone, carvedilol, ranolazine, ticagrelor

  • Verapamil, tacrolimus, cyclosporine 

  • Macrolides (Azithromycin)

  • Azoles

• Things that DECREASE digoxin levels:

  • Carbamazepine, fosphytoin, phenobarbital

  • Rifampin

Digoxin toxicity: Acute or Chronic

ACUTE - usually starts with GI sxs, and then later neuro sxs

CHRONIC - insidious onset neuro sxs

• Precipitating factors:

  • Any AKI causes accumulation since digoxin is renally excreted

  • Drug interactions that INCREASE digoxin levels (above)

  • Tissue sensitivity to digoxin increased by: Hypo-K, hypo-Mg, hyper-Ca, MI, hypoxemia

Symptoms:

• Arrhythmias:

  • Sinus bradycardia, high degree AV block

  • SVTs with AV block are CLASSIC

    • Afib with slow ventricular rate

    • Afib with junctional rhythm

    • Focal atrial tach with AV block

  • Junctional tachycardia

  • Ventricular arrhythmias usually in CHRONIC toxicity

    • Bidirectional v-tach strongly suggests digoxin

• GI sxs: nausea, vomiting, abd pain, diarrhea

• Neuro sxs: delirium, fatigue, visual changes (change in color perception, blurry vision, photophobia, blindness)

  • Rarely seizures

Some EKGs attached.

“Salvador dali mustache” = scooped ST segment with ST depression, flat/inverted T wave +/- prominent U wave, short QT

Checking digoxin levels:

• PO digoxin requires 6+ hours to distribute into tissues 

• ONLY POST-DISTRIBUTION levels actually reflect severity of intoxication

  • Used to calculate antiserum dose

• ACUTE intox: check baseline digoxin then repeat another in 6 hours

• CHRONIC intox: one digoxin level is fine assuming it was >6 hours after last dose

How much is too much?

• Normal/therapeutic is 0.5-2 ng/ml

• Scary levels:

  • ACUTE: > 10 ng/ml

  • CHRONIC: >4 ng/ml

• However - serum digoxin doesn’t actually correlate that much with tissue levels or cynical toxicity 

• After getting antidote, levels don’t mean anything

The antidote: digoxin specific antibody fragments (DSFab)

• Indications:

  • Significant arrhythmias or HD instability

  • K > 5-5.5 if it’s caused by digoxin

• Softer indications:

  • Acute ingestion > 10 mg

  • Moderate-severe GI sxs

  • Serum digoxin > 10-12 

  • Renal failure

  • AMS

• Should consult toxicologist or poison control if not sure 

  • Poison control: 1-800-222-1222

• Digibind or digifab available (2 diff brands)

  • Comes in vials of 40 mg antibody fragments, which neutralize 0.5 mg of digoxin

• Dosage:

  • Chronic poisoning: (dig level x wt in kg) / 100, can start lower initially

  • Acute ingestion of known dose: (mg digoxin ingested) x 1.6

  • Acute toxicity unknown levels: 5 vials (HD stable) or 10 vials (unstable)

  • Chronic toxicity unknown levels: 3-6 vials and reeval

  • Or you can use MDCalc

The most important thing about digoxin toxicity is to recognize it!! Hopefully this helps!

POTD: Cordis placement

Here is another addition to our video series. Today we go through how to place a cordis. For those who are unfamiliar with it, this is basically a fat central line that is primarily used for rapid infusion of fluids or blood. It only has a single lumen.

The trialysis lumen is actually larger than the cordis lumen, but the cordis is way faster and easier to place since there are less steps and less separate parts, so this makes to place for crashing patients who just need large bore access and not multiple ports. (Of note - oftentimes 2 large bore peripheral IVs in the AC is FINE for resuscitation. But you might need a crash cordis if it's taking too long to place the peripherals.)

To compare:

Standard triple lumen central line = 7 french

Trialysis catheter = 13 french 

Cordis = 6 french or 9 french

We have 2 size cordis kits, 6 french and 9 french. The 6 french is actually the size you use for TVP. Clinically it makes more sense to place a 9 french if you need large bore access, but just know that we have both sizes in resus. 

Of note, the 9 fr kit has the cooler blue syringe that allows you to place the wire through the syringe, reducing another step in the procedure. 9 fr kit also has the wire holder, which makes threading the wire easier. 

So in summary, if you have a patient bleeding out on to the floor, please reach for the 9 fr cordis kit since it is A) larger, and B) has better things inside of it, imo. 

Here is the video:

https://youtu.be/Ls5TdDg9eK0

Enjoy!

POTD: MTP & more!

You get a notification: GIB. Hypotensive. 

Patient arrives and they’re vomiting blood with a soft BP.

Do you send for emergent blood? Do you initiate MTP? Do you crack the fridge? What does “crack the fridge” mean? :O 

A chart comparing MTP, emergency blood transfusion, and “cracking the fridge” are attached, for a general overview.

Type O blood for all 3. 

• O positive for men b/c they don’t have Rh factor so it doesn’t matter for them 

• O negative for women just in case they are Rh negative

Emergent blood

• Patient can’t wait for cross-matched blood but they’re not SOO unstable that you need to crack the fridge. Could wait 10-15 minutes.

• Print “emergency blood transfusion request” form from Taylor health (shown below)

• Can do 1 or 2 units at a time. If you’re NOT running both bags at the SAME time, please order just 1 unit at a time. 

“Crack the fridge”

• Cracking the fridge does NOT automatically initiate MTP but because it often goes with it, PLEASE clarify with your team whether you are initiating MTP or not when you crack the fridge.

• Fridge contents: 4 u PRBC, 4 FFP, 1 platelets = 1st round of MTP

• The code is your attending’s 4 digit callback number, or the nurses have a number.

• To replace the fridge contents, just call the blood bank to restock.

• Pictured below: the blood fridge. Code entered via touchscreen.

  • Contents of the fridge also shown

Massive Transfusion Protocol, or MTP

• Patient needs ALL THE BLOOD. 

• Often used hand in hand with the fridge blood because they need it all and they need it fast

MTP: The process.

• Same taylor health form as emergency blood, shown above

• “The box” - 4 PRBC, 4 FFP, 1 platelets in the first round

  • Ror round two and onwards, same as round 1 but with cryoprecipitate if requested for very very bleedy patients

• Usually you crack the fridge, start using the 2 units in the fridge and call up to blood bank and they will continue to prepare more units

• When MTP is activated, resources are diverted to preparing blood for the ED. 

  • Primarily ties up the techs to prepare MTP. So places like the OR can’t get blood b/c all the blood bank techs are pulled to prepare more products for the MTP, until the MTP is done.

  • Use wisely but obviously use it when you need to

• MUST send someone from ED up to blood bank to get it, since the products are supposed to be in a cooler

  • This is the rate limiting step in getting the first box from blood bank, but this is why you crack the fridge first, to initiate MTP while waiting on blood bank

MTP: why do it?

• Patients with severe hemorrhage might actually get refractory hemorrhage due to:

  • Dilution of clotting factors (plts, fibrinogen)

  • Hypothermia from transfusion of cold products

  • Hypocalcemia induced coagulopathy

  • Acidosis

• MTP allows for balanced transfusion including clotting factors

• When should you do MTP?

  • NO set criteria for it. Based on clinical judgement.

  • Hemoglobin level has LITTLE benefit in determining need for MTP

  • Hypotension also is usually a late manifestation of hemorrhage so don’t always go solely off BP

Coagulation labs?

• You can’t actually trend these reliably b/c blood products are given so rapidly

• Thus, blood products are administered empirically in a 1:1:1 ratio of PRBC:FFP: Plt

What about cryoprecipitate?

• Fibrinogen may become depleted in massive transfusion due to dilution and there might not be enough fibrinogen in FFP

• In the US, cryoprecipitate is commonly used for fibrinogen supplementation.

• 10 u cryoprecipitate should increase fibrinogen by ~75 mg/dL

• Target fibrinogen > 150-200 mg/dL

• Diff hospitals have diff protocols for fibrinogen supplementation. Ours is described above.