Poison is in the dose...?

[MediMike]

***Details changed as always***

Recently had a gentleman in his 50s show up to one of our medium sized hospitals complaining of fatigue, mild dyspnea and dizziness x1 week. Only hx is paroxysmal AF, LVEF 45% and a recent hip fracture.  In ED had RVR 160s - 180s, hemodynamically stable, dyspneic.  COVID +.  Was given 10 of dilt followed by a gtt at 15mg/hr, then two 5mg doses of metoprolol.  He decompensated pretty quickly afterwards requiring intubation.  Also needed some push-dose epi while norepinephrine, phenyl and epinephrine drips were started.  POCUS showed an RV that was ok and a grossly abnormal LV, EF around 5%-10%.  No stress pattern. Lactate cranked to 9.5 > 18, shock liver, creatinine 1.3 > 2.1 in about 3 hours, trop 1.62 etc. etc.  You get the picture, sick dude.

Discussed high dose insulin therapy in the setting of inotrope and vasopressor refractory shock, doc I'm working with was arguing that it wasn't a "real overdose".  As there was a definite temporal relationship between the negative chrono-ino-tropes and his decompensation with echocardiographic evidence of cardiogenic shock I had a hard time agreeing with this.  Think I just wanted to debate it more than anything else...but what are ya'lls thoughts? I figured it was worth a shot as he was clearly getting worse and the risk:benefit seemed to be in his favor, and physiologically it makes sense.

IS there a difference between a therapeutically dosed medication having severe side effects resulting in cardiogenic shock and an "overdose"? Cause they seem like the same dang thing to me.

 

[LT_Oneal_PAC]

@MediMike

Ignoring hindsight about the doses being given, as I hate being Monday morning quarterback and I’m far from perfect…

I agree with both of you. I don’t think it’s true overdose, but we don’t know the exact mechanism by which high dose insulin works, as far as I can recall. There is all the theoretical talk of insulin resistance, but it could have other benefits. Insulin therapy is generally well tolerated and absolutely worth a try in this person, especially if we are that close to the CCB and BB being given.
 

while I don’t think it’s a “true overdose”, it could also be that in his shock state this is a relative toxic dose. Sort of like we treat those on beta blockers as having “relative tachycardia” if the heart rate is higher but not actually elevated above normal.
 

I would do it and see how he does over the next couple hours and you’ll know for sure.

agree with you’re last statement. In this situation, it’s the same thing.

[MediMike]

6 hours ago, LT_Oneal_PAC said:

@MediMike

Ignoring hindsight about the doses being given, as I hate being Monday morning quarterback and I’m far from perfect…

I agree with both of you. I don’t think it’s true overdose, but we don’t know the exact mechanism by which high dose insulin works, as far as I can recall. There is all the theoretical talk of insulin resistance, but it could have other benefits. Insulin therapy is generally well tolerated and absolutely worth a try in this person, especially if we are that close to the CCB and BB being given.
 

while I don’t think it’s a “true overdose”, it could also be that in his shock state this is a relative toxic dose. Sort of like we treat those on beta blockers as having “relative tachycardia” if the heart rate is higher but not actually elevated above normal.
 

I would do it and see how he does over the next couple hours and you’ll know for sure.

agree with you’re last statement. In this situation, it’s the same thing.

This idea of there being a "true overdose$ is what bugs me. If grandma takes a 5mg oxy and loses her respiratory drive it would be considered an OD, should be the same if we (not me) slam someone with beta blockers and CCBs and they develop acute HF...

The high dose insulin therapy increases FFA utilization by the heart, totally agree that the side effects are totally manageable, lots of fluid though and this guy was fairly hypoxic and proned as it was. I'll let ya know what happened when I pull his chart later 

[LT_Oneal_PAC]

19 minutes ago, MediMike said:

This idea of there being a "true overdose$ is what bugs me. If grandma takes a 5mg oxy and loses her respiratory drive it would be considered an OD, should be the same if we (not me) slam someone with beta blockers and CCBs and they develop acute HF...

The high dose insulin therapy increases FFA utilization by the heart, totally agree that the side effects are totally manageable, lots of fluid though and this guy was fairly hypoxic and proned as it was. I'll let ya know what happened when I pull his chart later 

I suppose I’m arguing semantics As I like to think of things as “relative”, but agree completely with you that when it comes down to it: overdose

[polarbebe]

13 hours ago, MediMike said:

***Details changed as always***

Recently had a gentleman in his 50s show up to one of our medium sized hospitals complaining of fatigue, mild dyspnea and dizziness x1 week. Only hx is paroxysmal AF, LVEF 45% and a recent hip fracture.  In ED had RVR 160s - 180s, hemodynamically stable, dyspneic.  COVID +.  Was given 10 of dilt followed by a gtt at 15mg/hr, then two 5mg doses of metoprolol.  He decompensated pretty quickly afterwards requiring intubation.  Also needed some push-dose epi while norepinephrine, phenyl and epinephrine drips were started.  POCUS showed an RV that was ok and a grossly abnormal LV, EF around 5%-10%.  No stress pattern. Lactate cranked to 9.5 > 18, shock liver, creatinine 1.3 > 2.1 in about 3 hours, trop 1.62 etc. etc.  You get the picture, sick dude.

Discussed high dose insulin therapy in the setting of inotrope and vasopressor refractory shock, doc I'm working with was arguing that it wasn't a "real overdose".  As there was a definite temporal relationship between the negative chrono-ino-tropes and his decompensation with echocardiographic evidence of cardiogenic shock I had a hard time agreeing with this.  Think I just wanted to debate it more than anything else...but what are ya'lls thoughts? I figured it was worth a shot as he was clearly getting worse and the risk:benefit seemed to be in his favor, and physiologically it makes sense.

IS there a difference between a therapeutically dosed medication having severe side effects resulting in cardiogenic shock and an "overdose"? Cause they seem like the same dang thing to me.

 

This is an unusual case and in my experience, cardiogenic shock secondary to rate control agents generally are accompanied by profound bradycardia.  You didn't mention the HR after the dilt/BB.  Was his rate controlled (HR 70s to 120s) after your meds then he decompensated?  If so, it is possible that his "LVEF 45%" was indeed PMH.  When was this official echo done?  Unless this official echo was read immediately before the decompensation; he could have presented with an EF of 15-20% and the negative inotropy from the rate control agents pushed it to 5-10% and the HR was the only way he was compensating (CO = HR x SV) to maintain a "normal" compensated hemodynamics.

Generally with cardiogenic shock with BB, will use dopamine peripherally (for HR 20s to 30s) then first trial glucagon gtt then insulin gtt with a D10 gtt after talking to tox.

The trop returned 1.62 after 3 hours.  Do you have high sensitivity troponin?  We are still using the regular troponin I.  If HS-troponin that doesn't seem too bad, if you use a regular troponin then that seems pretty bad after only 3 hours (since it peaks at 24 hours) - obviously highly concerning for ACS.

To answer your question, in my humble opinion given the known information on hand I can't question the management; I would have probably done exactly the same thing.  This is an unfortunate outcome and an adverse effect.  The dosing seems appropriate given the data you had and this is tough to Monday morning quarterback.

Unfortunately, I don't trust my POCUS skills to quantify the EF (or evaluate any valves) but only to give a general qualititative assessment of RV/LV function (good, ok or bad).  I know there are some ultrasound machines that have AI builtin that can give you an estimated EF from just two views.  Do you guys have this or were you a tech/worked in cardiology and can estimate EF?  I need to learn.

Thank you for sharing this case.

[MediMike]

7 hours ago, polarbebe said:

This is an unusual case and in my experience, cardiogenic shock secondary to rate control agents generally are accompanied by profound bradycardia.  You didn't mention the HR after the dilt/BB.  Was his rate controlled (HR 70s to 120s) after your meds then he decompensated?  If so, it is possible that his "LVEF 45%" was indeed PMH.  When was this official echo done?  Unless this official echo was read immediately before the decompensation; he could have presented with an EF of 15-20% and the negative inotropy from the rate control agents pushed it to 5-10% and the HR was the only way he was compensating (CO = HR x SV) to maintain a "normal" compensated hemodynamics.

Generally with cardiogenic shock with BB, will use dopamine peripherally (for HR 20s to 30s) then first trial glucagon gtt then insulin gtt with a D10 gtt after talking to tox.

The trop returned 1.62 after 3 hours.  Do you have high sensitivity troponin?  We are still using the regular troponin I.  If HS-troponin that doesn't seem too bad, if you use a regular troponin then that seems pretty bad after only 3 hours (since it peaks at 24 hours) - obviously highly concerning for ACS.

To answer your question, in my humble opinion given the known information on hand I can't question the management; I would have probably done exactly the same thing.  This is an unfortunate outcome and an adverse effect.  The dosing seems appropriate given the data you had and this is tough to Monday morning quarterback.

Unfortunately, I don't trust my POCUS skills to quantify the EF (or evaluate any valves) but only to give a general qualititative assessment of RV/LV function (good, ok or bad).  I know there are some ultrasound machines that have AI builtin that can give you an estimated EF from just two views.  Do you guys have this or were you a tech/worked in cardiology and can estimate EF?  I need to learn.

Thank you for sharing this case.

Thanks for the thoughts! I completely agree with you regarding unclear timing of the drop in EF, there's a high likelihood he walked in with a tachy induced CMP. It was the *cough* emergency department who administered the rate control meds rather than my team. (I actually check an EF prior to giving dilt or metop in just about everybody) I worked in a CCU for the first couple years with decent echo training so feel fairly comfortable guesstimating an EF.

The trop was the 'ol fashioned one. Agree with concerns for ACS, suspected T2 NSTEMI with all he had going on but certainly could have been a primary driver.

HR dropped from 160-180 to 30-40s before we got some chronotropes going.

Off to admit an undifferentiated neuro case... anyone else absolutely hate neuro?