Atrial Fibrillation (AF) & Flutter complicating critical illness (2024)

CONTENTS

• Introduction
• Diagnosis of AF
• Investigation of the cause of AF
• Management – Overall approach
  • Emergent cardioversion
    • Is immediate cardioversion indicated?
    • How to perform DC cardioversion
  • (1) Universal AF stabilization package
  • (2) Rate vs. rhythm control decision
    • Rhythm control in critical illness
    • Rate control
  • (3) Anticoagulation
• Atrial flutter
• Pharmacopeia for AF in the ICU:
  • Amiodarone
  • Beta-blockers ➡️
  • Digoxin
  • Diltiazem ➡️
  • Ibutilide
  • Magnesium
• Podcast
• Pitfalls

introduction

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what this chapter is about

• AF is the most common arrhythmia encountered in the ICU. (29627355) The two most common scenarios are:
  • (1) A patient with chronic AF develops critical illness.
  • (2) A patient who was previously in sinus rhythm develops new-onset AF (NOAF) while in the ICU, secondary to the physiologic stress of critical illness (e.g., secondary to sepsis or pulmonary embolism).
• These situations are different from AF in other contexts, for example:
  • ICU patients are often hemodynamically tenuous, so they may respond poorly to the usual AF therapies (e.g., diltiazem).
  • DC cardioversion alone has a low success rate among critically ill patients (patients will usually revert back into AF).
  • The optimal heart rate for critically ill patients is unknown, but some patients may benefit from a mild compensatory tachycardia. Immediately pushing the heart rate down to a “normal” range (e.g., <100) can be dangerous.

atrial fibrillation classifications

• Lone AF: Patient <60 years old without predisposing factors for AF (e.g., no cardiopulmonary disease).
• New onset AF (NOAF): First episode of AF (discussed further below: ⚡️).
• Recurrent AF: Two or more paroxysmal or persistent episodes of AF.
• Paroxysmal AF: AF lasting <7 days (due either to self-termination or an intervention).
• Persistent AF: AF sustained for >7 days.
• Long-standing persistent AF: AF sustained for >1 year.
• Nonvalvular AF: AF in the absence of rheumatic mitral stenosis, prosthetic heart valve, or mitral valve repair. (Sadhu 2023; Griffin 2022)

diagnosis of AF

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general

• AF may be suspected on the basis of an irregularly irregular heart rate (either on clinical examination or telemetry).
• AF diagnosis should always be confirmed with a full 12-lead ECG.

diagnostic criteria for AF on ECG

• [1] There should be no regularity.
  • At very high rates, the heart rate may appear to be regular (“pseudo-regularization”).
  • When in doubt, calipers may help determine whether there is any regularity.
• [2] No P waves are seen; instead these may be replaced by fibrillation waves.
  • Fibrillation waves may be best seen in the inferior and right-sided precordial leads.
  • In some patients, fibrillation waves may be small and difficult to distinguish from artifact.
  • If it is unclear whether there are P waves or fibrillation waves, consider obtaining a Lewis Lead ECG. Also consider comparison to P wave morphology in prior ECGs (if the patient previously had large, well-defined P-waves and now they're gone, then this supports an AF diagnosis).
• (One exception to these criteria is that if AF is combined with heart block, then the ventricular response may be regular.)

heart rate among patients in AF

• For most patients who aren't on medications that suppress the AV node, AF will have a heart rate of ~120-180.
• If the heart rate is >>200, consider the possibility of an accessory tract (AF plus Wolff Parkinson White).
• If the heart rate is <100, conduction disease is likely.
  • Be careful when cardioverting patients with a heart rate <100, as there may be an increased risk of bradycardia.

evaluating the etiology of new-onset AF

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common causes of new-onset AF

• Electrolyte abnormalities:
  • Hypokalemia.
  • Hypomagnesemia.
• Toxicology / medications:
  • Beta-agonists (norepinephrine, epinephrine, dobutamine).
  • Theophylline.
  • Alcohol (holiday heart syndrome).
  • Substance use (especially cocaine, amphetamine, methamphetamine).
• Adrenergic states:
  • Alcohol withdrawal.
  • Pain, agitation.
  • Primary neurologic disorders (e.g., intracranial hemorrhage, ischemic stroke).
• Respiratory failure:
  • Pulmonary embolism.
  • Hypoxemia, hypercapnia (e.g., pneumonia, COPD).
• Primary cardiac disease:
  • Myocardial ischemia.
  • Pericarditis.
• Sepsis.
• Postoperative state (especially cardiothoracic surgery).
• Hypovolemia or fluid overload.
• Thyrotoxicosis.
• Swan-Ganz catheterization.

evaluation

• Basic evaluation:
  • ECG.
  • Electrolytes, including magnesium.
  • Review of medication list.
  • Review of the presence of any indwelling cardiac devices.
  • Echocardiogram.
• Additional tests as clinically warranted. For example:
  • If thoughtful review of ECG and history suggests ischemia, then obtain troponin.
  • If there is other evidence suggesting PE, CT angiography may be indicated.
  • TSH should be considered if there is no obvious cause of AF, or if other clinical features suggest thyrotoxicosis.

overall approach to AF

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Emergent cardioversion is only rarely required for patients with AF in the ICU. This is described in the following two sections, but it's generally inadvisable.

Three key components of management are:

• (1) Universal AF stabilization package (general supportive care). 📖
• (2) Rate versus rhythm control. 📖
• (3) Anticoagulation management. 📖

Of these, general supportive care is usually the most important. Uncontrolled AF in the ICU is often due to an underlying problem (e.g., sepsis, hemorrhage) – and fixing that problem is often the most important intervention.

is cardioversion indicated?

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how much is AF actually contributing to the patient's instability?

• The key question is: What is driving the instability? Is the atrial fibrillation causing the patient to be unstable? Or is atrial fibrillation merely triggered by underlying instability?
• Some key pieces of information can help:
  • (1) Heart rate: As a general rule, heart rates <150 are less likely to cause hemodynamic instability. The faster the heart rate is, the more likely it is causing trouble.
  • (2) Structural heart abnormalities (especially pulmonary hypertension, mitral stenosis, or diastolic heart failure) may render patients dependent on atrial kick. Such patients may tolerate AF poorly.
  • (3) Overall clinical context.
• Trying to sort this out is important:
  • DC cardioversion will stabilize the patient only if the AF is causing the instability.
  • ⚠️ If fast heart rate is due to an underlying process, then overly aggressive attempts to reduce the heart rate to a “normal” range may make matters worse (because a mild degree of tachycardia may actually have a compensatory, beneficial effect).

consider immediate DC cardioversion

• DC cardioversion is indicated if new-onset AF clearly caused the patient to be severely unstable. This is unusual – for most critically ill patients, the AF isn't the primary driver of instability.
• ⚠️ Stand-alone cardioversion will usually fail as a strategy for AF management in critical illness. (12576943) Even if cardioversion is successful, patients will usually revert to AF subsequently.
  • If possible, pretreatment or post-treatment with amiodarone +/- magnesium may enhance the likelihood of achieving and maintaining sinus rhythm.

AF with an accessory pathway (Wolff Parkinson White)

• An accessory pathway is an aberrant electrical connection between the atria and the ventricles that shouldn't exist.
• Normally, when in AF the heart rate is limited by the refractory period of the AV node. Although the AV node may allow for a fast heart rate (e.g. ~120-180), these heart rates are usually tolerated reasonably well.
• When AF occurs in the context of an accessory pathway, both the AV node and the accessory pathway can transmit beats to the ventricles. Since the accessory pathway often has a shorter refractory period than the AV node, it may drive the ventricle very rapidly (e.g. >200). This is dangerous because the extremely fast and uncoordinated contractions of the ventricle can promote ventricular tachycardia or cardiovascular collapse.
• AF with an accessory pathway produces a fairly distinctive pattern of ECG findings:
  • Irregularly irregular heart rate that may be extremely fast (e.g. >200).
  • Wide-complex beats can result from transmission over the accessory pathway.
  • Morphology varies between different beats (some beats are fusion complexes if the AV node and the accessory pathway fire at a similar time).
• AF with an accessory tract shouldn't be treated with medications that impair the AV node (eg. beta-blockers, calcium channel blockers, or amiodarone). Blockade of the AV node may merely cause a greater dominance of the accessory pathway, exacerbating matters (to a certain extent, the AV node and the accessory pathway are competing for control of the ventricle). Antiarrhythmics which may be used are procainamide or ibutilide.
• This is a unique situation where DC cardioversion is usually the treatment of choice (based on its efficacy and speed). If a patient with AF and an accessory pathway is displaying instability, proceeding directly to DC cardioversion is indicated.

how to perform electrical cardioversion for atrial fibrillation or flutter in critical illness

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[1] pre & post-treatment with antiarrhythmic

• Among critically ill patients, DC cardioversion alone usually fails to achieve sustained sinus rhythm. For example, DC cardioversion will often transiently elicit normal sinus rhythm, with a subsequent reversion into atrial fibrillation.
• Pre- and post-treatment with amiodarone may promote successful and sustained cardioversion. Amiodarone may subsequently be continued until the patient has recovered from their critical illness (e.g., for 1-2 weeks).
• Intravenous magnesium should also be considered.

[2] sedation

For intubated patients, numerous sedation strategies are available (so this won't be discussed further). For non-intubated patients, either midazolam or MidaKet are attractive (especially for unstable patients who may have difficulty tolerating propofol).

midazolam protocol for cardioversion

• Note: There are numerous potential sedation strategies for cardioversion. The use of midazolam monotherapy has been well validated to be safe and effective, even when performed by cardiologists. (32842955, 26734338, 25176628, 24157233, 17461869, 17312434)
• [0] Optimal candidates:
  • (a) No chronic use of benzodiazepines or alcohol.
  • (b) No history of seizures.
• [1] Load with midazolam 3-5 mg IV bolus (depending on age, weight).
• [2] Give 2 mg IV midazolam q2min PRN to target adequate sedation:
  • Eyes closed.
  • No response to gentle verbal/tactile stimuli.
  • Sluggish response to loud verbal commands or stronger tactile stimuli.
• [3] Perform cardioversion.
• [4] Reversal with 0.5-1 mg flumazenil IV if adverse effects result from sedation (e.g., mild hypoxemia, excessive somnolence, laryngospasm).

MidaKet sedation

• This may be useful for patients who are resistant to midazolam.
• Further discussion of MidaKet is here: 📖

[3] details of cardioversion procedure itself

pad positioning

• The recent EPIC trial found that anterior/lateral pad placement was more effective than anterior/posterior pad placement. (34814700)
• Hyperinflation may impair conduction of electricity to the heart. Hyperinflation may be countered by performing cardioversion at end-expiration. If cardioversion is failing due to marked hyperventilation, it may be reasonable to briefly disconnect the patient from the ventilator to promote chest deflation (if oxygenation allows).

electricity & synchronization

• Be sure to synchronize shock delivery.
• Use the maximal energy available (e.g., 200-360 J). The rationale for this is as follows:
  • (1) There is no evidence that a single high-energy shock is more dangerous than a low-energy shock. On the contrary, a high-energy shock might theoretically be less likely to knock the heart into ventricular tachycardia if shock isn't correctly synchronized.
  • (2) Initial use of the highest energy reduces the likelihood that repeat cardioversion will be needed. This is especially important among non-intubated patients, in whom sedation may wear off over time.

universal AF stabilization package

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The most important intervention for critically ill patients with AF is usually treating the causes of AF. There is a risk of getting overly focused on antiarrhythmics and cardioversion, but the most important interventions are often as follows:

hemodynamic optimization

• (1) Discontinue beta-adrenergic vasopressors as able.
  • Especially epinephrine and dobutamine may increase heart rate and should be weaned if possible.
• (2) For hypotension, add vasoconstrictors that don't stimulate beta receptors.
  • Phenylephrine is a good choice if needed to support blood pressure, without driving tachycardia. Phenylephrine infusions are often avoided due to fear that they will reduce the cardiac output, but they generally don't reduce the cardiac output. Phenylephrine usually increases preload by causing venoconstriction, thereby balancing out the effects of increasing the afterload. (discussed here)
  • Vasopressin is another option.
• (3) Optimize volume status.
  • AF may be caused by volume overload, which causes atrial dilation. If volume overload is present, diuresis may be beneficial.
  • If frank hypovolemia is present, then volume administration may be beneficial. However, note that hypovolemia is relatively uncommon among patients who are admitted to ICU.

treatment of pain/anxiety/withdrawal

• Untreated distress can drive sympathetic tone and aggravate AF.
• Pain and anxiety should always be treated adequately. However, uncontrolled AF may serve as a reminder to make especially sure that these issues are being attended to. 📖
• For uncontrolled anxiety, dexmedetomidine may be considered as an anxiolytic that will reduce sympathetic tone and decrease heart rate.

treatment of electrolyte abnormalities

• Hypokalemia and hypomagnesemia may promote AF, so if present these should be treated aggressively.
• If magnesium hasn't been checked recently, it is reasonable to empirically give 2-4 grams of magnesium sulfate provided that the patient's renal function is normal. (30025177) The magnesium level should be checked, but administration of magnesium doesn't need to wait until the level returns.
  • For patients with substantial hypomagnesemia, a magnesium infusion may help rapidly replete total body stores of magnesium and settle down the AF (see the magnesium infusion protocol here).

respiratory support

• Hypoxemia or respiratory distress may be drivers of AF.
• Respiratory failure should be aggressively treated (e.g., CPAP for heart failure, BiPAP for COPD, HFNC for pneumonia).

evaluation and treatment of other causes of hemodynamic instability

• Avoid anchoring excessively on AF as the cause of the patient's hemodynamic instability.
• For ongoing instability, evaluate broadly and treat appropriately. For example, uncontrolled AF could be a manifestation of sepsis, PE, thyrotoxicosis, or any cause of shock.
  • ⚠️ If AF is being driven by another underlying process, focusing solely on suppressing the heart rate with medications will fail – and may actually make the patient worse.

rate control versus rhythm control

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overview of evidentiary basis for rate control vs. rhythm control

• No RCTs have been performed comparing rate control vs. rhythm control in a general ICU population. However, several RCTs have been performed in other contexts (e.g., emergency department patients, patients status post cardiac surgery).
• Available studies show no differences in hard endpoints (e.g., mortality or stroke). However, this doesn't exclude the possibility that some subgroups of patients might benefit more from one strategy.
• Overall, both strategies are generally reasonable and the choice may depend on patient specifics.

factors favoring a rate-control strategy

• Longer duration of AF:
  • Chronic AF is perhaps the strongest indicator for a rate-control strategy. AF leads to electrical remodeling, which leaves the atria less able to convert to sinus rhythm. The longer patients are in AF, the harder it is to convert to sinus rhythm.
  • Onset of AF >48 hours previously, in a patient who isn't anti-coagulated: In this situation, conversion to sinus rhythm could theoretically increase the risk of stroke due to dislodging a clot from the atrial appendage. Exclusion of an atrial appendage thrombus may be achieved using transesophageal echocardiography or cardiac CT scanning.
• Reduced likelihood of success with a rhythm-control strategy:
  • Ongoing severe physiological stress (e.g., multiple vasopressors).
  • Uncontrolled thyrotoxicosis (e.g., active thyroid storm).
  • Severe left atrial dilation.

factors favoring a rhythm-control strategy

• Inability to tolerate AF hemodynamically: AF can cause hemodynamic instability, especially in patients who benefit from atrial kick:
  • Pulmonary hypertension.
  • Valvular heart disease (especially mitral stenosis).
  • Diastolic dysfunction.
  • Heart failure with reduced ejection fraction. (AF is one cause of reduced ejection fraction. Maintenance of sinus rhythm will sometimes improve the ejection fraction.)(38033089)
• NOAF (new-onset AF): Patients often develop new AF in the context of critical illness. If this occurs while being monitored in the hospital, it may warrant an attempt at rhythm control (explored further in the next section).
• Atrial flutter: This is often a transitional state, as the atria is deciding whether to settle down into sinus rhythm or atrial fibrillation. Atrial flutter is often difficult to treat using rate control, since the rate tends to be stubbornly stuck at around 150. (More on atrial flutter below.)
• Failure of rate control strategy (e.g., inability to achieve rate control). (36912134)

argument for attempting rhythm control in critically ill patients with new-onset AF (NOAF)

what is NOAF?

• New-onset AF (NOAF) refers here to AF that began during hospitalization for critical illness, in a patient who previously did not have chronic or paroxysmal AF. A common example is in patients with septic shock, wherein the prevalence of NOAF is ~10%. (32983720)
• The natural history of NOAF is usually to revert to sinus rhythm on its own, as the underlying critical illness resolves.
• NOAF correlates with worse outcomes, including mortality. However, it remains murky whether the NOAF causes worse outcomes, whether the NOAF merely is a marker of sicker patients, or both. (31089761)

several arguments can be made for attempting rhythm control in these patients:

• (#1) Most patients with NOAF will eventually revert back into sinus rhythm on their own. However, the risk of stroke may relate to the duration of time that the patient spends in AF (e.g., >48 hours in NOAF may increase stroke risks). If we can convert patients out of NOAF rapidly, this ought to reduce the risk of stroke.
• (#2) Not all patients with NOAF will spontaneously revert back into sinus rhythm (for example, one series found that 44% of patients were discharged in AF). (32983720) The longer AF is allowed to continue, the less likely it is to revert to sinus rhythm. Ongoing atrial fibrillation causes electrical remodeling of the atria, which perpetuates the atrial fibrillation (hence the clinical adage, “AF begets AF”). Prompt cardioversion out of NOAF could theoretically increase the likelihood that the patient could successfully revert to sinus rhythm and stay in sinus rhythm on a long-term basis.
• (#3) AF may impair cardiac function in a subset of patients, due to impaired atrial kick. Cardioversion out of NOAF might therefore improve cardiac function in some patients, allowing them to compensate better for their acute critical illness.
• (#4) Attempts at rhythm control for NOAF will typically involve magnesium and amiodarone (more on this below). Even when these strategies fail to achieve cardioversion, they will generally achieve rate control – so they may remain clinically beneficial.

related supporting evidence:

• Evidence from postoperative AF provides some support for pursuing a rhythm control strategy in other critically ill patients. For example, a multicenter RCT found that for AF following cardiac surgery, a rhythm control strategy increased the likelihood of being free from atrial fibrillation two months later (94% vs. 98%; p =0.02). (27043047)
• A recent multicenter RCT among outpatients found that a rhythm-control strategy among patients with onset of AF within <1 year led to a lower risk of adverse cardiovascular outcomes. (32865375) Likewise, the J-RHYTHM trial, a multicenter study involving patients with AF onset within <48 hours, found that rhythm control was associated with an improvement in composite outcomes. (19060419)

rhythm control strategy for critically ill patients

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For patients who are not crashing, rhythm control may take a stepwise approach:

(#1) magnesium infusion

• Magnesium is generally a good place to start.
• Among critically ill patients, magnesium seems to have similar efficacy when compared to other antiarrhythmics. In one RCT, a continuous magnesium infusion was actually superior to amiodarone. (7587256)
• Magnesium has an excellent safety profile, with one meta-analysis detecting no reported adverse events due to magnesium within any study. (32209631) The combination of reasonable efficacy plus a largely unparalleled safety record makes magnesium an evidence-based front-line agent for critically ill patients. (29627355)
• Even when magnesium alone doesn't cause cardioversion, it still offers the patient potential benefits. Magnesium augments the efficacy of other antiarrhythmic agents or DC cardioversion. (23731344, 21815963, 32861384) If rhythm control fails, magnesium also has some efficacy at reducing the heart rate. (15795711)
  • Even if the magnesium has failed to work alone, continuing the magnesium infusion may still remain beneficial (in combination with either amiodarone or ibutilide). For example, the combination of aggressive magnesium loading plus adequate doses of amiodarone achieved a cardioversion rate of 90% in one series of critically ill patients. (18320707)
• Dosing:
  • If GFR >30 ml/min, a magnesium infusion is preferable.
  • If GFR <30 ml/min, intermittent boluses may be used to target a level of ~3-4 mg/dL.
  • More on magnesium dosing below. 📖

(#2) amiodarone or ibutilide

amiodarone

• Amiodarone is usually the preferred antiarrhythmic for ICU patients due to its ability to both cardiovert patients and subsequently prevent recurrent AF.
• Amiodarone may be utilized if a magnesium infusion is ineffective. Depending on the urgency, amiodarone may be started shortly after magnesium, or after waiting several hours.
• Amiodarone is reasonably effective if dosed appropriately (more on the dose below 📖).
• If amiodarone fails to work immediately, continue the infusion. Some patients may have delayed cardioversion (e.g., within the first 24 hours after starting the amiodarone infusion).

ibutilide

• Ibutilide may be used to achieve rapid chemical cardioversion (e.g., within 1-2 hours). This is a desirable option if urgent cardioversion is a priority.
• Aggressive magnesium loading prior to ibutilide improves the safety and efficacy of ibutilide.
• Contraindications to ibutilide and dosing are discussed further in the section below on ibutilide. 📖

(#3) DC cardioversion might be considered among intubated patients

• Most patients with NOAF will cardiovert in response to steps #1-2 above (especially if ~24 hours are allowed for the magnesium and amiodarone infusions to take effect).
• Failure of magnesium and amiodarone to work suggests that the patient's heart doesn't want to go into a sinus rhythm (e.g., perhaps due to significant chronic atrial dilation, underlying structural heart disease, or profound systemic inflammation). In this situation, it's difficult to know whether to accept atrial fibrillation or continue efforts towards conversion to normal sinus rhythm.
  • For intubated patients, an attempt at cardioversion may be reasonable (since the risks of sedation are minimal).

follow-up care after cardioversion to sinus rhythm

• If the patient is successfully cardioverted, consider ongoing amiodarone therapy until their critical illness is significantly improved. If amiodarone is stopped while the patient is still critically ill, patients are likely to revert into AF. One multicenter study found that amiodarone had an 87% success rate at achieving cardioversion, but 42% of patients reverted back to AF during their ICU stay. (22226423)
• For patients who were cardioverted with ibutilide, amiodarone may be started ~6-12 hours afterwards.
• More on amiodarone dosing below.📖

rate control

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#1/3: set a safe heart rate goal

Cardiac Output = (Heart Rate)x(Stroke Volume)

• The target heart rate for outpatients is often regarded to be <110 (based on the RACE II trial). (20231232) However, nobody knows what the ideal heart rate is for critically ill patients. Some patients may benefit from a mild degree of compensatory tachycardia.
  • As shown above, cardiac output is equal to heart rate multiplied by stroke volume. At very fast heart rates (>>150), diastolic filling will become impaired, so the stroke volume will fall. However, at heart rates below ~150, the diastolic filling may often be OK, so the dominant driver of cardiac output may be the heart rate. Thus, for example, causing a drop in the heart rate from 130 to 90 may often cause a drop in the cardiac output.
• Trying to “normalize” the heart rate (e.g., targeting a rate below 100) may increase the risk of iatrogenic harm in patients with tenuous hemodynamics.
• For many critically ill patients, a heart rate goal below ~130 might be reasonable. The target may vary depending on patient specifics and clinical response. The optimal target may also vary over time – for example, initially a target of <130 may be reasonable, but as the patient recovers a lower target may become appropriate.

#2/3: select an agent for rate control

general approach to selecting an agent

• Four agents are generally used for rate control:
  • Digoxin 📖
  • Amiodarone 📖
  • Beta-blockers 📖
  • Diltiazem 📖
• The primary consideration when selecting an agent is often how stable the patient is (figure below).
  • For the most unstable patients (especially patients with severe systolic heart failure and longstanding AF), digoxin may be a consideration.
  • Amiodarone is generally a solid choice for ICU patients with the potential for hemodynamic instability (as is true for most ICU patients).
  • For patients with more robust hemodynamics and lower risk of hypotension, either a beta-blocker or diltiazem may be chosen (more on this below).

beta-blocker (usually metoprolol) vs. diltiazem?

• One of the longstanding controversies in AF management has always been selecting between metoprolol and diltiazem. There is no good data regarding this, specifically:
  • (1) There is no RCT-level evidence regarding the comparison of these agents for rate control in the ICU.
  • (2) There is no RCT-level evidence comparing metoprolol versus a diltiazem infusion (all available RCTs involve only a bolus of diltiazem, which is likely safer than starting a continuous infusion).
• Beta-blockers are preferred among patients with systolic heart failure (HFrEF).
• Many critically ill patients develop AF due to increased sympathetic tone. (24685669) This implies a greater utility of beta-blockers among ICU patients, since they address the underlying physiological problem. Some additional data support the utility of beta-blockers for AF among ICU patients:
  • One before/after study following a diltiazem shortage found that transitioning from diltiazem to metoprolol led to improved success and reduced rates of hypotension among ICU patients. A retrospective study among critically ill patients likewise found a lower rate of failure when using metoprolol, when compared to diltiazem. (28328711)
  • Beta-blockers are recommended as first-line agents for rate control following cardiac surgery (a situation with some parallels to AF among other critically ill patients). (31700500)
• More important than the drug selection might be proper dose titration. Specifically, continuous diltiazem infusions can cause problems if they are up-titrated and subsequently allowed to accumulate over time. Alternatively, intermittent dosing of metoprolol naturally encourages nurses to think about each dose and hold doses in patients who are beginning to become hypotensive.

#3/3: if the patient continues to have a fast rate:

Most importantly: re-evaluate to make sure there isn't an underlying problem (e.g. sepsis, hypovolemia). Ensure that the patient has been provided the full AF stabilization package. 📖

options include

• (1) Addition of magnesium.
• (2) Addition of digoxin may be considered in combination with a beta-blocker or diltiazem. (2A recommendation, 2023 AHA/ACC guidelines)
• (3) Transition to amiodarone is often useful (amiodarone is more hemodynamically stable and less likely to cause synergistic hypotension in combination with other agents).
  • ⚠️ Avoid combining beta-blockers and calcium-channel blockers (overlapping these agents may increase the risk of hypotension).
• (4) Failure of a rate-control strategy is an indication to consider attempting a rhythm-control strategy.

anticoagulation?

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scope of the problem

• Critically ill patients often have systemic inflammation, and may increase their risk for thromboembolic stroke compared to outpatients.
• Critically ill patients have numerous risk factors for bleeding (e.g., renal dysfunction, use of antiplatelet medications, invasive procedures).
• Risk scores for bleeding and thrombosis haven't been validated in the ICU (e.g., CHA2DS2-VASc, HAS-BLED). This makes it difficult to balance the risks versus benefits of anticoagulation accurately.

available evidence on new-onset AF

• There is no high-quality evidence to support anticoagulation for patients with new-onset AF secondary to critical illness.
• Retrospective studies suggest that anticoagulation for atrial fibrillation secondary to critical illness increases the bleeding risk, without reducing the incidence of stroke. (30089566) This finding appears robust, even if propensity matching is used in attempts to remove confounding variables. (27487456)
• A survey of intensivists in the UK found that most (64%) don't routinely anticoagulate patients with new-onset atrial fibrillation. (28929012)

current practice?

• New-Onset AF (NOAF)
  • For most patients with new-onset AF due to critical illness, the risks of anticoagulation seem to generally outweigh potential benefits. (32968991, 29627355) However, this remains largely unknown. For some patients at high stroke risk and low bleeding risk, anticoagulation might be beneficial.
  • The Canadian 2020 guidelines state that “In some cases, such as sepsis, the acute administration of intravenous anticoagulation increases the risk of bleeding, but does not appear to reduce the risk of ischemic events.” (33191198)
  • If the AF persists for weeks, then it becomes increasingly likely that the patient may develop ongoing AF. In this situation, anticoagulation may become beneficial.
• Chronic AF
  • For patients who appear to have chronic AF, anticoagulation may be considered similarly to that of outpatients (e.g., based on CHA2DS2-VASc scores).
  • Among patients with long-standing AF who have been previously on anticoagulation, this will often be continued (unless it is necessary to hold it for a procedure or bleeding).

atrial flutter

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basics

• Flutter is usually a short-lived transitional state, which either degenerates into atrial fibrillation or converts to sinus rhythm. As a transitional state, atrial flutter often resembles new-onset atrial fibrillation (NOAF).
• The management of atrial flutter is similar to that of AF, but a rhythm control strategy is more effective for the following reasons:
  • (1) Rate control in atrial flutter is often difficult (the heart rate tends to get “stuck” at ~150 b/m).
  • (2) Atrial flutter is often a transient state that is relatively easy to cardiovert into normal sinus rhythm.

acute management of atrial flutter

• Rhythm control may be considered, but this is particularly difficult and often fails. (31504425)
• Electrical cardioversion is highly effective (but it does require procedural sedation).
• Ibutilide ⚡️ is generally effective. (31504425)
• Amiodarone ⚡️ is less effective at acute cardioversion, but it does help control the ventricular rate. (31504425)
• Anticoagulation management is modeled off the treatment of atrial fibrillation (although the thromboembolic risk may be lower than with atrial fibrillation). (31504425)

chronic management of atrial flutter

• Catheter ablation is effective.
• Medication therapy:
  • 1st line: Rate control with beta-blocker, diltiazem, or verapamil.
  • 2nd line: Rhythm control with amiodarone. (31504425)

amiodarone

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amiodarone's role in rate control

• Amiodarone is often useful for patients with potential hemodynamic instability.
• There is a theoretical risk of causing stroke among patients who aren't anticoagulated and might cardiovert into sinus rhythm. However:
  • (1) For critically ill patients who are hemodynamically tenuous, this theoretical risk is often be superseded by the need to achieve hemodynamic stability.
  • (2) The risk of stroke relates more to the duration of atrial fibrillation than the act of cardioversion. Since most critically ill patients will eventually transition to sinus rhythm spontaneously, leaving patients in atrial fibrillation longer may actually increase stroke risk.

amiodarone dosing for rate control

• Load with 150 mg bolus, then infuse at 1 mg/minute.
• Achieving rate control may require reloading with 150 mg amiodarone 2-3 times (for a total of ~150-450 mg given in the form of boluses).
  • ⚠️ Don't conclude that amiodarone has failed to work without re-bolusing adequately.

amiodarone dosing for rhythm control

• The loading dose is either 300 mg or 5-7 mg/kg. (38033089) In practice 300 mg is often utilized, with additional boluses as needed up to a total of ~450-600 mg administered in boluses.
• This is followed by an infusion at ~1 mg/min (AHA/ACC guidelines recommend a maintenance dose of 1,200-3,000 mg via continuous infusion over 24 hours).
• 💡 Chemical cardioversion with amiodarone requires substantial doses.

amiodarone maintenance therapy

• Conversion to oral:
  • Infusion may be converted to oral administration after >24 hours.
  • Start at 400 mg PO BID, until the patient has received a total of 10 grams cumulative dose (IV plus PO). Subsequently, the dose may be decreased to 200 mg daily.
• Eventually transition to another agent:
  • Chronic use of amiodarone causes a host of side effects.
  • After patients recover from their critical illness, they will often be transitioned to a safer long-term regimen (e.g., a beta-blocker).

digoxin

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overview: role of digoxin for AF in the ICU

• Digoxin may have a role in rate control for selected patients (as described below).
• (Digoxin may actually tend to reduce the likelihood of conversion into sinus rhythm, so it doesn't have any role in a rhythm-control strategy.)

optimal candidates for digoxin have:

• (1) Chronic AF
  • Digoxin tends to perpetuate AF, rather than favoring cardioversion back to normal sinus rhythm.
  • Digoxin may be less effective in rate control of paroxysmal AF, so it shouldn't be used as a sole therapy for paroxysmal AF. (Griffin 2022)
• (2) Heart failure with reduced ejection fraction:
  • Digoxin is the only agent which reduces heart rate while simultaneously functioning as a positive inotrope.
  • Digoxin may be uniquely beneficial for patients with heart failure whose hemodynamics are very tenuous, who may have difficulty tolerating a negative inotrope.
• (3) Mild or moderate tachycardia for which immediate control isn't necessary:
  • Digoxin takes several hours to work and it's not tremendously potent.
  • Digoxin is less effective in hyperadrenergic states, since it functions primarily as a vagotonic agent.
• (4) Adequate renal function:
  • The presence of preserved renal function makes dosing of digoxin easier and a bit safer.
  • This isn't an absolute requirement, because careful dosing and monitoring within the ICU allow digoxin to be given safely even in the presence of renal dysfunction.

IV digoxin loading (digitalization)

• Digoxin takes a little while to work, but if given intravenously it may take effect within several hours. When initiated in the ICU, digoxin will nearly always be started with intravenous loading doses.
• Total IV loading dose: (package insert, 23616674)
  • Normal renal function: 8-12 mcg/kg ideal body weight (usually ~600-1,000 mcg).
  • Renal insufficiency: 6-10 mcg/kg ideal body weight.
  • Err on the lower end in patients with renal dysfunction, hypothyroidism, and/or reduced muscle mass.
• Typically, 50% of the total loading dose is given initially, followed by 25% given twice, every six hours. The first IV dose (typically ~400-600 mcg) takes effect within roughly 1-4 hours. Monitor for effect. If an adequate heart rate is achieved, then subsequent doses may be omitted. If bradycardia occurs, further administration should be held.

maintenance doses

• Typical maintenance dose:
  • Patients <70 years old with normal renal function: 250 mcg daily.
  • Patients over 70 years old –or- with renal dysfunction: 125 mcg daily.
  • Patients who are both >70 YO –and- have renal dysfunction: 62.5 mcg daily.
• The table below provides typical maintenance doses, based on the patient's renal function and body weight. (Package insert)
• Digoxin has a long half-life (~36-48 hours, or longer in renal insufficiency). Therefore, steady state may not be reached until about a week after a dose adjustment.

monitoring digoxin levels

• Drug level must be checked several hours after the last digoxin dose, to allow for distribution (e.g., >8 hours after an oral dose). Ideally this should be a trough level.
• The safest approach to digoxin dosing in the ICU among tenuous or dynamic patients is to closely monitor the digoxin level:
  • Check a trough digoxin level daily with AM labs.
  • Adjust the daily dose as needed, depending on the trough level.
  • As the patient stabilizes, digoxin levels may be spaced out.
• A therapeutic level is ~0.5-2 ng/mL
  • 0.5-1.2 ng/mL might be the optimal concentration for outpatients. (38033089)
  • 1-2 ng/mL levels may improve contractility, so these aren't unreasonable levels for closely monitored ICU patients.

if digoxin fails

• Digoxin is not an extremely powerful agent, so it may fail to achieve optimal heart rate control.
• If digoxin does fail, it may be combined with a beta-blocker or diltiazem.
  • The presence of digoxin may reduce the required dose of beta-blocker or diltiazem, thereby improving hemodynamic stability. (31700500) In particular, the combination of digoxin plus a beta-blocker may work well for some patients with systolic heart failure.

ibutilide

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basics

• Ibutilide is a useful antiarrhythmic agent for pharmacological cardioversion of AF in the ICU. (21209348, 10763074) Available studies suggest that ibutilide has a high success rate (~80%). (34916053)
• The main drawback of ibutilide is that it carries a risk of torsade de pointes (which requires monitoring for telemetry for at least four hours after administration). However, aggressive loading with magnesium prior to ibutilide administration mitigates this risk.
  • The need to monitor patients for several hours makes ibutilide challenging to use in the emergency department or medicine ward. This isn't an issue in the ICU, since patients are being monitored on telemetry regardless. (28969929)
• Ibutilide may be superior to procainamide among critically ill patients, because it has greater efficacy and no negative hemodynamic effects. (9581743, 9416896, 15773423)

comparison of ibutilide vs. amiodarone

• Advantages of ibutilide:
  • Ibutilide is more effective for urgent cardioversion of atrial fibrillation (e.g., within 1-2 hours). If there is a desire to rapidly stop AF, ibutilide may be preferable.
  • One very small RCT found that amiodarone and ibutilide were equally effective. The advantage of ibutilide was a reduced rate of hypotension, whereas the advantage of amiodarone was a reduced rate of recurrent AF. (12682468)
• Advantages of amiodarone:
  • Amiodarone has fewer contraindications than ibutilide (these are listed below).
  • Amiodarone can be seamlessly used as a single agent to achieve both cardioversion and maintenance of sinus rhythm. Alternatively, if ibutilide is utilized for cardioversion, the addition of amiodarone might be considered 4-6 hours afterwards to maintain sinus rhythm.

contraindications/cautions

• QT prolongation.
• Hypokalemia.
• Hypomagnesemia.
• Ejection fraction <40%. (38033089)
• Severe LV hypertrophy. (32860505)
• Theoretical interaction with amiodarone:
  • Theoretically, since ibutilide and amiodarone can both prolong the QT interval the combination of these drugs could promote torsade de pointes. However, although amiodarone prolongs the QTc interval, amiodarone doesn't actually tend to promote torsade de pointes significantly.
  • Evidence review reveals several studies have demonstrated that amiodarone and ibutilide can be given together safely and effectively. (28584642, 16029392, 12122531, 11208685, 17284902, 16176535)
  • The approach to rhythm control outlined above involves choosing either amiodarone or ibutilide. However, moderate doses of these drugs can likely be combined in a safe and effective fashion (especially in the context of ICU-level monitoring and aggressive magnesium supplementation). This decision should be individualized based on the risks vs. benefits (incorporating patient specifics, such as the actual QTc value).

dose & monitoring

• Preload with aggressive IV magnesium sulfate:
  • The main side effect of ibutilide is prolongation of QTc, which causes torsade de pointes. Coadministration with a magnesium infusion will dramatically reduce the risk of Torsades. (20723644)
  • Administration of magnesium has been shown to substantially improve the efficacy of ibutilide (14652979, 32861384) If ibutilide is being utilized following initiation of a magnesium infusion, ibutilide's efficacy may be maximized by delaying ibutilide administration until the magnesium level has risen over ~3.8 mg/dL. (32861384)
• The standard ibutilide dose is 1 mg infused over 10 minutes (or 0.01 mg/kg for patients <60 kg).
  • If AF persists for >10-20 minutes following the end of the infusion, the dose can be repeated once.
  • Most patients convert to sinus rhythm within 30-90 minutes. (38033089)
• ⚠️ If cardioversion occurs while ibutilide is being infused, the infusion should be stopped.
• Patients should be monitored for ~4 hours subsequently (although arrhythmias will generally occur within the first 1-2 hours after administration).

pharmaco*kinetics

• Half-life is 2-12 hours.
• Ibutilide is metabolized in the liver via oxidation to yield mostly inactive metabolites. (Dose adjustment isn't required for renal or hepatic dysfunction, because maintenance doses are not utilized.)

magnesium for AF

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overview

• Magnesium may promote both rhythm control and rate control.
• Magnesium is especially useful in patients with underlying hypomagnesemia.
• Achieving a slightly supra-normal magnesium level may be beneficial, especially for rhythm control.

dosing

• (1) Magnesium infusion:
  • Contraindicated among patients with renal failure (GFR <30 ml/min or oliguria).
  • Indications:
    • Cardioversion (rhythm control).
    • Patients with substantial hypomagnesemia (e.g., alcoholism).
    • (For patients with relatively normal magnesium levels who are undergoing rate control, a magnesium infusion often isn't worth the effort.)
  • The protocol below may be utilized. Most of the administered magnesium will be excreted, so a continuous infusion may be required to effectively replete intracellular magnesium levels. (18320707)
• (2) PRN magnesium boluses:
  • Magnesium boluses may be useful for patients who don't qualify for a magnesium infusion (in the absence of hypermagnesemia).
  • Intermittent boluses may be utilized, targeting a level of ~3-4 mg/dL.

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• Always look for other causes of instability among patients with AF and shock or difficulty controlling the ventricular rate. In some patients, this may be a “sinus tach equivalent” which is due to an underlying problem (e.g., sepsis, PE). In such patients, successful management depends on treating the underlying problem. Merely trying to squash the heart rate can be dangerous among these patients, as it may suppress a compensatory tachycardia.
• ACLS guidelines typically recommend immediate cardioversion for unstable patients with AF. However, among critically ill patients this has a low success rate.

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