Esmolol in Septic Shock
Atrial fibrillation: it’s a common arrhythmia we see in the ICU because it is one that is often a harbinger for imminent decompensation in our most critically ill patients. In our patient population, it has a reported incidence as high as 78% and new-onset of this arrhythmia is associated with a significant mortality (jumping from 22% to 44%; check out our afib episode for more information).
The high incidence and increased mortality in the ICU makes sense - the complete physiologic mess that happens in a lot of the disease states we see are the perfect prime for the heart and therefore the electrical chaos that ensues is an expected part of multi-organ dysfunction for our patients.
When it comes to treating this rhythm - as we know from our afib podcast - we don’t have any data on whether rate or rhythm control is best. It’s truly the wild wild west.
Most of what we know about afib does not apply to our acutely sick, critically ill, new-onset afib patients.
Atrial fibrillation in the critically ill is NOT the same as atrial fibrillation in the outpatient setting - it is ultimately reversible, and has a completely different etiology.
For our normotensive patients the best answer is rate control specifically with Diltiazem. But where this gets dicey is in our patients who are already hypotensive - meaning the rhythm is not causing worsening shock, but they were already in shock in the first place. One review found that 46% of people were hypotensive and 40% of people were on vasopressors/inotropes prior to the development of new onset afib in the ICU (3); it makes sense that this is a common conundrum that critical care providers face.
Ultimately, our goals are to reduce the work of the heart as well as counteract the sympathetic drive priming the heart without making an already hypotensive patient more hypotensive. We tend to shy away from beta blockers and calcium channel blockers for this reason - we are concerned about their effect on cardiac output. One other option would be to try Digoxin, which reduces heart rate by increasing vagal tone. But there have been studies that tell us that this drug may not work in our critically ill patients as well (2). It can also take a long time to work and is contraindicated in renal failure, which a lot of our patients have. So when we are reluctant to do rate control due to borderline or already low blood pressure, we jump to our favorite type of rhythm control - Amiodarone!
Amiodarone is a class III anti-arrhythmic that works by blocking potassium rectifier currents that are responsible for repolarization of the heart during the cardiac action potential, leading to a prolonged effective refractory period in cardiac myosites. (4) Simply put - it makes the heart less excitable.
Why can amiodarone be bad?
Bradycardia - usually related to the infusion rate
Dermatologic toxicity - it can cause SJS or TEN
Hepatotoxicity - must trend LFTs; although the US boxed warning is specifically for oral, not IV
Neurologic Toxicity - ranging from cognitive impairment to ataxia
Pulmonary Toxicity - this can be difficult to diagnose; specifically, hypersensitivity pneumonia or interstitial/alveolar pneumonitis. This US boxed warning is specifically for tablets, not necessarily IV
Hypothyroidism - due to thyroiditis
Torsades De Pointes / Vfib - ironically enough, amiodarone can actually potentiate more lethal arrhythmias
All of these can be scary things. But what other options do we have? The physiologic storm causing this arrhythmia are not always immediately fixable, therefore rhythm control can be fleeting or require you to continue it over a long period of time leading to a large accumulation of the drug (and higher risk of toxicity). It’s like if you went to put out a fire, but someone is right next to you lighting up another one as soon as you finish.
You have a patient with atrial fibrillation due to an angry heart - a hyperadrenergic state caused by hypotension and excess endogenous catecholamines
Amiodarone makes the heart less excitable; but doesn’t do anything about the rush of catecholamines causing the afib in the first place
What if you could block some of the excess catecholamines? Luckily, can look back at a drug that works on the heart by blocking catecholamines, specifically epinephrine and norephinephrine… beta blockers.
Does amio work?
Sure, amiodarone has its risks, but it can work in our septic shock patients, right? A review by Kanja et al. in Crit Care Med 2008 helped to answer this question (5). Four randomized control trials were included; specifically, only studies were selected on critically ill patients (as defined as being in the ICU) and over 16 years of age. Any studies on cardiac surgery patients were excluded; the primary outcome was to measure rhythm conversion to normal sinus rhythm within 1 to 24 hours (not mortality).
Amiodarone: 50-70% at 12h, 50% at 24h
Esmolol: 68% at 2h, 85% at 12h
Diltiazem: 33% at 2h, 62% at 12h
In this study, amiodarone did not have a better conversion rate than the BB/CCB.
But my patient is hypotensive!
It is true that beta blockers can have negative chronotropy and inotropy that may lead to inappropriately low cardiac output. But in a disease state such as septic shock, where the heart rate itself is not simply a marker of a sympathetic reaction but instead much more pathologic, could addressing the overstimulation of catecholamines with a drug that blocks catecholamines actually fix whats going on?
(7) “Concomitant use of beta-1 adrenoreceptor blocker and norepinephrine in patients with septic shock” - ten septic patients were given Esmolol drip; heart rate decreased from 142 +/- 11/min to 112 +/-9/min with insignificant reduction in cardiac index, no significant changes to Norepnieprhine infusion (0.13 +/- 0.17 to 0.17 +/- 0.19) or arterial lactate. Using well titratable beta blocker (Esmolol, in this study) seems to be safe and cardio-protective in septic shock patients with high cardiac output
(9) “Effect of Esmolol on hemodynamics and clinical outcomes in patients with septic shock” - a prospective RCT on patients with septic shock; Esmolol drip was titrated to decrease heart rate by 20%. The decrease in heart rate with the Esmolol drip was markedly more but there were no differences in MAP, lactic between the two groups. It is efficient and safe to use Esmolol for heart rate control in patients with septic shock after resuscitation
(10) “Microvascular Effects of Heart rate Control with Esmolol in patients with septic shock: a pilot study” - 25 septic shock patients with a heart rate greater than or equal to 95 bpm requiring Levophed received Esmolol to maintain a heart rate of less than 95 bpm; this pilot study demonstrated that heart rate control by a titrated Esmolol infusion in septic shock patients was associated with maintenance of stroke volume, preserved microvascular blood flow, and a reduction in Levophed requirements
Of note, many of this studies were vey small. Like many things in medicine further research is needed to better navigate the approach to treating atrial fibrillation in these very sick patients. BALGJEGLEGLKEALGKE
RESOURCES
1 https://www.ncbi.nlm.nih.gov/pubmed/29064934
2. http://journal.chestnet.org/article/S0012-3692(18)30545-2/fulltext
3 https://www.ncbi.nlm.nih.gov/pubmed/22226423
4 https://www.ncbi.nlm.nih.gov/books/NBK482154/
5: https://www.ncbi.nlm.nih.gov/pubmed/18434899
6 https://link.springer.com/article/10.1007/s40261-019-00762-z
7 https://link.springer.com/article/10.1007%2Fs00508-012-0209-y
8 https://jamanetwork.com/journals/jamasurgery/article-abstract/1719682
9 https://www.ncbi.nlm.nih.gov/pubmed/28524025?dopt=Abstract
10 https://insights.ovid.com/crossref?an=00003246-201309000-00011