8/8 (HUP): CCB toxicity

Thanks to Dr. Francis DeRoos for walking us through a case of a young woman who presented with shock, and was ultimately found to have overdosed on calcium-channel blockers.

First, we talked about the importance of (1) the physical exam and (2) the EKG in diagnosing and risk stratifying patients with toxic ingestions. Assessing the skin, pupils, and sweat/lack thereof can give you valuable clues. See the toxidromes post from a few months ago for more info.

Here’s a cute chart that illustrates that:

Screen Shot 2017-08-08 at 3.24.24 PM
Common toxidromes (source: http://www.sketchymedicine.com)

We also talked about various causes of drug-induced bradycardia:

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Lithium tends to cause bradycardia most commonly in patients with underlying cardiac disease. Amiodarone has particularly been known to cause bradycardia in concert with certain of the new HCV medications (sofosbuvir or daclatasvir), including slow VT!

CCB toxicity can cause a variety of ECG changes, including sinus bradycardia and varying degrees of AV blockade. Remember to look at the rhythm strip carefully to make sure you’re not missing complete heart block!

Treatment options for CCB toxicity

  1. Calcium: may improve inotropy and blood pressure. You can give either calcium gluconate (short acting, can give peripherally but lower Ca content) or calcium chloride (3x the Ca content of Ca gluconate, must give centrally given risk of tissue damage w/ extravasation).
  2. Pacing: unlikely to be of much benefit even in hemodynamically significant bradycardia, given that the CCB is still bathing cardiomyoctes with its negative chronotropic effect.
  3. Vasopressors: something (like norepinephrine) with inotropic and vasoconstrictive effects is best, but there’s no trial proving the superiority of one vs another. Large doses may be needed.
  4. High-dose insulin/euglycemic therapy: CCBs block the calcium-dependent release of insulin from pancreatic beta cells, while at the same time increasing glycogenolysis. Insulin is also postulated to have a positive inotropic effect, especially in these patients in whom CCBs are exerting a negative inotropic effect. Massive doses of insulin (to the tune of 0.5-1U/kg/hour) may be needed given (along with dextrose) to maintain euglycemia.
  5. Lipid formulations: intravenous lipid rescue (initially used for bupivicaine toxicity) can be used as a ‘lipid sink’ to bind up unbound CCB. This is not without risks, as it can cause lipemic serum and higher rates of pancreatitis!
  6. ECMO/CPB: with refractory shock, there is also a role for putting patients on ECMO while using adjunctive therapies (above) to support them

Lastly, the paper of the day– which suggests that earlier Lasix administration in patients with decompensated heart failure may have a mortality benefit! See their central illustration, which suggests that there is a critical period (<60 min) where early diuretic administration might be particularly beneficial:

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  1. Matsue, Y. et al. 2017. Time-to-Furosemide Treatment and Mortality in Patients Hospitalized With Acute Heart Failure. Journal of the American College of Cardiology. 69, 25 (2017), 3042–3051.
  2. Kerns, W. 2007. Management of β-Adrenergic Blocker and Calcium Channel Antagonist Toxicity. Emergency Medicine Clinics of North America. 25, 2 (2007), 309–331.
  3. Life in the fast lane. Calcium Channel Blocker Toxicity.



Thanks to Fenton McCarthy, cardiac surgery fellow, for an incredible talk on extracorporeal membrane oxygenation (ECMO) and to everyone in the audience for creating a robust discussion.

We highlighted big differences between ECMO and cardiopulmonary bypass:
1) Cardiopulmonary bypass is a modality used almost exclusively for short periods of time in the OR
2) While similar, bypass circuits have a blood reservoir whereas ECMO circuits don’t

There are two main flavors of ECMO:

  1. Veno-arterial (VA) ECMO (see below): used if you have a cardiac problem (cardiac arrest, myocarditis, MI, cardiomyopathy, post-cardiac surgery) to provide circulatory support
    Screen Shot 2017-07-19 at 1.48.04 PM.png
    VA ECMO: blood drains from a vein, gets oxygenated, and pumped back into an artery. It flows retrograde from the femoral artery up the aorta. Poorly oxygenated blood being pumped by the failing heart can mix with well-oxygenated retrograde blood from the ECMO catheter, creating differential regional hypoxemia, also known as “North South syndrome”

    2. Veno-venous (VV) ECMO (see below): used primarily for respiratory failure (refractory hypoxemia, ARDS, etc). Complications are much less common with VV ECMO than VA ECMO.

    Screen Shot 2017-07-19 at 1.56.39 PM.png
    VV ECMO: blood is drained from the SVC or IVC and returned to the venous system.

    With VV ECMO, catheters can either go into the internal jugular vein or femoral vein. There’s also a catheter called an Avalon catheter (google it!) which is a single ‘catheter within a catheter’ that only requires placement of a cannula in the right IJ, and even permits ambulation!

We talked about some contraindications to ECMO (malignancy, unrecoverable neurological injury, age >75 among others, prolonged (>60 min) cardiac arrest, etc), and some tips for medicine residents if your patient is being considered for ECMO:

  • Have one point person who knows the patient well be the one to talk to the ECMO fellow
  • Get the unit charge RN involved early
  • Get extra stuff (laundry carts, trash can, etc) out of the room to create space to work

The question always comes up: should I pre-emptively put in IJ or femoral central lines to make ECMO cannulation easier if things are headed that way?

The answer (as with so many things)is a little nuanced: if all they have is an IJ line, it’s advisable to put one in the other side because they will still need separate central access, and having to do so after they’ve been placed on ECMO comes with the theoretical risk of air embolism.

If groin ECMO access is being considered, you could put in bilateral femoral lines, but it really depends on the experience of the operator: to be helpful, the groin lines really need to be within 1-2cm of the groin crease.

How’s the evidence?

Lastly, we touched on the CESAR trial, which is really the only major/recent randomized trial that looked at whether ECMO has any benefit. The short answer: possibly yes, but it may not be a fair comparison because the ECMO group may have gotten better overall medical care than the ‘conventional therapy’ group


  1. Peek et al. CESAR: conventional ventilatory support vs ECMO for severe adult respiratory failure. PMC1766357
  2. Brodie D et al. ECMO for ARDS in adults. PMID 22316467
  3. Ventetuolo et al. Extracorporeal life support in critically ill adults. PMC4214087

A quick aside on hypothermia (the topic of our question-of-the-day)

Hypothermic patients can have sinus bradycardia, PVCs/PACs, atrial fibrillation and J-waves (also known as Osborne waves, see below). The height of the Osborne wave corresponds with the degree of hypothermia.

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It is true that ‘you’re not dead until you’re warm and dead’. As the following NEJM table shows, hypothermia with hemodynamic instability is an indication to consider ECMO or cardiopulmonary bypass in order to speed rewarming:

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Brown et al. Accidental hypothermia. NEJM. PMID 23150960.

7/6 (HUP): common toxidromes

We went through an interesting case of a middle aged man found unconscious on the street, who was found to have a large anion and osmolar gap, and was ultimately found to have ethylene glycol toxicity. Along the way, we reviewed several important points:

  1. The importance of getting EKGs on anyone suspected of a toxic ingestion, as it can give you tons of valuable information and can help you diagnostically and therapeutically. You can and should trend EKGs to look for dynamic changes in QRS, QT and ST intervals!
    1. For example: terminal R wave in aVR –> very suggestive of TCA toxicityScreen Shot 2017-07-10 at 11.25.51 AM.pngScreen Shot 2017-07-10 at 11.37.26 AM.png
      Normal aVR
    2. QRS width in TCA poisoning is correlated with badness: QRS >100 is predictive of seizures, and >160 predictive of ventricular arrhythmias. You can and should trend QRS duration on serial EKGs to watch it shrink as you administer sodium bicarbonate!
  2. Toxic alcohols can create an anion and osmolar gap (EXCEPT isopropyl alcohol)

Screen Shot 2017-07-10 at 11.24.33 AM

Remember that sOsm and the anion gap can vary depending on when they’re drawn after the ingestion!

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Lastly, a note about the UDS

1. The ‘level 1’ drug screen (aka DA9) tests for many common drugs: amphetamines, benzos, cocaine, opiates, PCP, THC, methadone, barbiturates, and alcohol. Within those classes, certain drugs may not be tested for (for ex: fentanyl isn’t routinely tested for under opiates). Toxic alcohols are a send out.

2. If you’re looking for a specific drug, ask for a level 2 screen, which tests the sample against a library of 400-500 drugs. You have to have a specific drug(s) in mind- this isn’t just an automatic screen against every compound that wasn’t tested in the level 1!



  1. Yates, C. and Manini, A. 2012. Utility of the Electrocardiogram in Drug Overdose and Poisoning: Theoretical Considerations and Clinical Implications. Current Cardiology Reviews. 8, 2 (2012), 137–151.
  2. Kraut JAXing SX. Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis. Am J Kidney Dis 2011;58:480-484
  3. Burns, E. Tricyclic overdose (Sodium-channel blocker toxicity). Life in the Fast Lane. https://lifeinthefastlane.com/ecg-library/basics/tca-overdose/. Accessed July 2017.

6/27 PPMC Report: Cardiac Tamponade

Today we covered cardiac tamponade, its presentation, and an evidence-based approach to making the diagnosis!
PEARLS for tamponade:
1. A pulsus is your best friend! In the study by Curtiss et al (see below) a pulsus paradoxus >12 mmHg had an LR of 5.9 (95% CI 2.4-14) and for a cutpoint of greater than 10mmHg was 3.3 (95% CI, 1.8-6.3). When pulsus was 10mmHg or less, cardiac tamponade was unlikely (LR 0.03; 95% CI, 0.01-0.24). That is just wonderful when used in the right clinical context. Additionally, over multiple studies a pulsus had a pooled sensitivity of 82% (2). Not too bad!
2. We reviewed how to do a pulsus with some helpful tips from Dr. Gluckman and Dr. Foschnot. When performing a pulsus go HIGH when inflating the BP cuff. Then decrease by increments of 5mmHg. Stay at a given pressure as the patient breathes in and out listening for Korotkoff sounds that vary with respiration. Then do the same 5mmHg lower and continue this — pausing at a BP and allowing multiple respirations — until the Korotkoff sounds are present with every beat.
1. Curtiss EI, Reddy PS, Uretsky BF, Ceccheti AA. Pulsus Paradoxus: definition and relation to the severity of cardiac tamponade. Am Heart J. 1988;115:391-398.
2. Roy CL, Minor MA, Brookhart MA, Choudhry NK. 2007. Does this Patient with a Pericardial Effusion have Cardiac Tamponade? JAMA. 2007; 297(16):1810-1818.