Amiodarone for…well…everything

Journal Club Podcast #40: January 2018

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A little discussion about the evidence for amiodarone in atrial fibrillation, stable V-tach, and shock-refractory VF/VT in cardiac arrest...

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Articles:

Article 1: Ortiz M, Martín A, Arribas F, et al; PROCAMIO Study Investigators. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. Eur Heart J. 2017 May 1;38(17):1329-1335. Answer Key.

Article 2: Chevalier P, Durand-Dubief A, Burri H, Cucherat M, Kirkorian G, Touboul P. Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis. J Am Coll Cardiol. 2003 Jan 15;41(2):255-62. Answer Key.

Article 3: Kudenchuk PJ, Brown SP, Daya M, et al; Resuscitation Outcomes Consortium Investigators. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2016 May 5;374(18):1711-22. Answer Key.

Article 4: Kudenchuk PJ, Leroux BG, Daya M, et al; Resuscitation Outcomes Consortium Investigators. Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo). Circulation. 2017 Nov 28;136(22):2119-2131. Answer Key.

Vignette:

Working in TCC can be draining, and on one particularly busy afternoon, you begin to suspect your own sanity. After back-to-back cardiac arrest patients, you wonder if perhaps you should have done something less stressful with your life, like maybe become a lobster boat captain or an ice road trucker.

Your first code is a middle-aged female who suffered cardiac arrest while watching Alabama beat Clemson during the Sugar Bowl (yeah...that's right!!!). She was initially noted to be in ventricular fibrillation (VF), and remained so after three rounds of defibrillation. As she arrives in the trauma room, you immediately continue CPR and set up to shock her again. Your attending orders amiodarone, and even though you remember hearing that this may not be very effective, you realize it's not the time to argue. The patient ends up with ROSC and goes to the cath lab when her ECG reveals an anterior STEMI.

Your second patient is an elderly male who was initially found to be in PEA by EMS, but then later developed fine VF after three rounds of epinephrine en route. You shock him three times in the trauma room without effect, and once again your attending calls for amiodarone. After twenty more minutes of CPR, the patient reverts to asystole and the code is soon called.

You end up giving amiodarone twice more in your shift, once to a patient with new-onset a-fib who ends up getting admitted after not converting to a sinus rhythm, and later to a patient with stable, wide-complex tachycardia (which you're pretty sure was ventricular tachycardia [VT]), and you start to wonder if your attending owns stock in the company that makes it. You search online after your shift and find an excellent rundown on the limits of amiodarone on RebelEM, which prompts you to perform your own literature search.

PICO Question:

Population: Adults patients with either new-onset atrial fibrillation, hemodynamically stable ventricular tachycardia (VT), or cardiac arrest due to ventricular fibrillation (VF) or VT

Intervention: IV Amiodarone

Comparison: Placebo or any alternative antiarrhythmic

Outcome: Conversion to normal sinus rhythm, need for hospital admission, survival, functional neurologic outcome, hypotension.

Search Strategy:

Three articles were chosen from the RebelEM blog (Ortiz 2017, Chevalier 2003, Kudenchuk 2016). A fourth article was chosen by reviewing the “similar articles” list for the Kudenchuk article (Kudenchuk 2017).

Bottom Line:

Amiodarone, which was first approved by the FDA in 1985, became a mainstay of arrhythmia management after being added to the ACLS guidelines in 2000. At that time, amiodarone was recommended ahead of lidocaine for management of hemodynamically stable wide-complex tachycardia but was only included as a consideration for refractory VF and pulseless VT. In the 2010 update, amiodarone was recommended as a “first line anti arrhythmic agent” in refractory VF/pulseless VT, based on limited evidence for improved rates of ROSC and hospital admission. In addition, amiodarone been recommended for use in recent-onset AF for over twenty years (Hou 1995). Given the rise in prominence of procainamide use in AF (see Ottawa Aggressive Protocol by Stiell et al), and an increased focus on longer term outcomes in cardiac arrest, we decided to review evidence for a variety of amiodarone indications frequently seen in the ED.

Stable Ventricular Tachycardia

PROCAMIO, a small, multicenter randomized controlled trial conducted at several hospitals in Spain enrolled 74 patients with hemodynamically stable, wide-complex tachycardia and randomized them to receive either IV amiodarone or IV procainamide over twenty minutes. Major cardiac events (clinical signs of hypoperfusion, dyspnea, hypotension, or acceleration of heart rate) occurred less frequently among patients receiving procainamide (OR 0.1; 95% CI 0.03 to 0.6). These patients also had a much higher rate of cardioversion (OR 3.3; 95% CI 1.2 to 9.3). Unfortunately, this was a very small study in which only a fifth of the number of planned patients was actually enrolled. Despite this limitation, it seems reasonable to use procainamide as a first line agent for hemodynamically stable wide-complex tachycardia rather than amiodarone.

Recent Onset Atrial Fibrillation

Procainamide has been used successfully in the management of recent-onset AF, with a previously documented conversion rate of around 60%, occurring at a median of 3 hours following drug infusion (Stiell 2010). In one systematic review and meta-analysis comparing IV amiodarone to placebo and class Ic antiarrhythmics (Chevalier 2003), amiodarone did not have a significantly higher rate of cardioversion compared to placebo at 1 to 2 hours, but did have a higher rate at 6 to 8 and 24 hours. Compared to class Ic antiarrhythmics, amiodarone was less effective at 1 to 2 and 6 to 8 hours, but had similar efficacy at 24 hours. Cardioversion with amiodarone by 6 to 8 hours occurred in 48-62% patients (depending on the individual study), which is fairly comparable to previously reported rates for procainamide. Given the lack of studies comparing procainamide to amiodarone head-to-head, it seems reasonable to consider either drug, though concerns regarding hypotension with amiodarone may sway many to use procainamide instead.

Refractory VF or Pulseless VT

A recent multicenter, randomized controlled trial conducted at 55 EMS services in North America sought to compare the effectiveness of amiodarone, lidocaine, and placebo in patients with out of hospital cardiac arrest (OHCA) due to refractory VF/pulseless VT. After excluding patients whose initial rhythm was not VF or VT, 3026 patients were enrolled and evenly split between groups. The authors found no significant difference in survival to hospital discharge between patients receiving amiodarone and placebo (ARR 3.2%; 95% CI -0.4% to 7.0%) and no difference between those receiving lidocaine and placebo (ARR 2.6%; 95% CI -1.0% to 6.3%). Unfortunately, despite the large number of patients enrolled, the outcome was fairly rare, which resulted in relatively wide 95% CIs. As a result, a potentially clinically meaningful survival improvement (3.2% for amiodarone and 2.6% for lidocaine) could not be shown to be statistically significant.

In a follow-up study, the authors of the previous study also looked at those patients initially enrolled but excluded because VF/pulseless VT was not their initial rhythm (i.e. those patients with an initially non-shockable rhythm). Again, they did not observe any statistically significant difference in survival to discharge between the three groups (1.9% for the placebo group, 3.1% for the lidocaine group, and 4.1% for the amiodarone group). Also, despite not finding a statistically significant difference, the study was not sufficiently powered to detect a potentially clinically significant improvement in mortality of 2% with amiodarone. Given this limitation for the last two studies, and the lack of any downside in this subset of patients, it seems reasonable to continue amiodarone use for patients with refractory VF/pulseless VT for both OHCA and in-hospital arrest.

NG Lavage for GI Bleeds

Journal Club Podcast #39: October 2017

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A discussion of the controversial practice of shoving a tube down someone's nose and sucking out stomach contents...

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Articles:

Article 1: Pateron D, Vicaut E, Debuc E, et al; HDUPE Collaborative Study Group. Erythromycin infusion or gastric lavage for upper gastrointestinal bleeding: a multicenter randomized controlled trial. Ann Emerg Med. 2011 Jun;57(6):582-9. Answer Key.

Article 2: Aljebreen AM, Fallone CA, Barkun AN. Nasogastric aspirate predicts high-risk endoscopic lesions in patients with acute upper-GI bleeding. Gastrointest Endosc. 2004 Feb;59(2):172-8. Answer Key.

Article 3: Palamidessi N, Sinert R, Falzon L, Zehtabchi S. Nasogastric aspiration and lavage in emergency department patients with hematochezia or melena without hematemesis. Acad Emerg Med. 2010 Feb;17(2):126-32. Answer Key.

Article 4: Huang ES, Karsan S, Kanwal F, Singh I, Makhani M, Spiegel BM. Impact of nasogastric lavage on outcomes in acute GI bleeding. Gastrointest Endosc. 2011 Nov;74(5):971-80. Answer Key.

Vignette:

It is a typical Saturday afternoon in TCC when you are roomed a patient with a history of COPD and GERD who appears short of breath. When they bring him back from triage in a wheelchair, you watch him shakily stand and transition to the stretcher, appearing dizzy when he does so. As you go in to greet the patient, you ask the nurse to get him started on the monitor. You can hear wheezing on your exam.

HR 116 RR 24 BP 88/54 Sat 100% Temp 36.3

During the review of systems, your patients embarrassedly admits to having several large bowel movements over the past two days that appeared dark and have progressively gotten more tarry throughout the day. He has had smaller episodes in the past, but nothing so large or frequent. He denies any vomiting, and specifically has had no hematemesis. DRE reveals black, heme positive stool.

His respiratory rate improves a little with a nebulizer, but he still appears short of breath. His labs are significant for a hemoglobin of 6.8, so you initiate your resuscitation. The patient’s vital signs improve slightly but do not normalize. When you hear back from your GI consult, he asks you to admit the patient for serial CBCs overnight after performing a nasogastric lavage.

However, you remember reading an editorial about NG lavage in evaluating GI bleeds in patients without hematemesis that was not entirely flattering. On top of that, you are concerned about worsening your patient’s already existing respiratory distress (or risk aspiration) if it is unnecessary. You decide to perform a quick search to see if there are any articles that might help you weight the pros and cons...

PICO Question:

Population: Adult patients with potential upper GI bleeding

Intervention: NG tube lavage

Comparison: No NG tube placement

Outcome: Mortality, transfusion requirement, need for surgery, gastric visualization at endoscopy, triage of patients

Search Strategy:

No formal search strategy was used. Two emergency medicine residents used multiple sources to identify articles that evaluated the use of NG lavage in potential upper GI bleeding with regards to any outcome.

Bottom Line

Considered to be one of the more painful procedures performed in the ED, nasogastric tube (NG) insertion is also associated with complication rates of 0.3% to 0.8% (Pillai 2005). NG tubes are often placed in patients with a known or suspected upper GI bleed, with potential goals of determining if the source is upper or lower, improving endoscopic visualization of the gastric fundus by lavage, and potentially triaging patients to urgent vs. non urgent endoscopy (particularly off hours). Unfortunately, very little evidence exists to support routine NG tube placement or lavage in these patients. We therefore sought to broadly evaluate the potential benefits of NG tube placement in patients with suspected or known upper GI bleeds.

One of the earlier studies performed sought to evaluate the predictive ability of NG lavage (NGL) in predicting the presence of a high risk lesion (spurting, oozing of blood, or a visible non-bleeding vessel) at endoscopy (Aljebreen 2005). A total of 520 patients with known upper GI bleeding were enrolled from the Canadian Registry of patients with Upper Gastrointestinal Bleeding undergoing Endoscopy (RUGBE). When considering a bloody NGL as a positive test (and coffee-ground, clear, or “other” aspirate as negative), the positive likelihood ratio (LR) was 2.00 and the negative LR was 0.68. When bloody or coffee-ground NGL was considered positive, the positive LR decreased to 1.20 and the negative LR decreased to 0.63. Overall, these likelihood ratios are quite poor, and would do very little to alter the probability of the disease, no matter the results.

Another study, conducted in Paris, France, compared NGL and erythromycin in terms of ability to clear the stomach and improve gastric visualization during endoscopy (Pateron 2011). In this randomized, controlled trial, 253 patients were randomized to either NGL until clear, a dose of IV erythromycin, or both NGL and erythromycin. The mean visualization score at the time of endoscopy was similar between all 3 groups, with no difference in duration of endoscopy, need for hemostasis, ability to identify the source of bleeding, or need for a second endoscopy.

A third study, undertaken in the West Los Angeles VA system, attempted to compare outcomes between patients with GI bleed who underwent NGL and those who did not (Huang 2011). This retrospective study included 632 patients, of whom 378 patients underwent NGL. The authors used propensity score matching to try and achieve prognostic balance between the two groups by balancing for several known confounding factors. Following propensity matching, two groups with 193 patients in each were compared. There was no significant difference in mortality (OR 0.84, 95% CI 0.37 to 1.92), mean length of stay (difference 0.80 days, 95% CI -1.4 to 3.0), need for emergency surgery (OR 1.51, 95% CI 0.42 to 5.43), or mean blood transfusion requirement (difference -0.18 units, 95% CI -0.98 to 0.62). Of note, significantly more patients in the NGL group underwent endoscopy (OR 1.71, 95% CI 1.12 to 2.62) and were more likely to undergo earlier endoscopy, suggesting that significant imbalance remained between the groups in spite of propensity matching. This finding significantly limits the internal validity of the study.

Finally, a systematic review was identified from 2010 that attempted to determine the accuracy of NGL in differentiating upper from lower GI bleeds in patients with hematochezia or melena without hematemesis (Palamidessi 2010). The authors identified 3 articles; unfortunately, one of these (Aljebreen 2005) did not actually address the question being asked, as it only included patients with upper GI bleeds. For the remaining two article, positive LRs were 4.74 and 4.44, while negative LRs were 0.2 and 0.65. As before, these likelihood ratios (with the exception of the negative LR of 0.2) suggest that the results of the test would do little to change the probability of an upper (or lower) GI hemorrhage.

In all, there is very little evidence to support the routine use of NG lavage in patients presenting to the ED with suspected upper GI hemorrhage. The only potential benefit not explored was the triage of patients to emergent, urgent, or non-urgent endoscopy, which would likely only be helpful during off hours. Given the poor ability of lavage to identify patients with high risk lesions, and given the significant discomfort associated with the procedure, this seems like a fairly soft reason to place an NG tube. Additional factors associated with poor outcomes in upper GI hemorrhage, such as older age, presence of upper GI malignancy, and variceal disease (Roberts 2012), in addition to signs of clinical instability may provide better triage of these patients, and should be considered prior to NG tube placement.