Critical Care Roundup

Journal Club Podcast #42: April 2018

Critical Care.jpg

A brief recap of four articles selected for review by the critical care folks...

Click Tabs Below to Expand

Articles:

Article 1: Jakob SM, Ruokonen E, Grounds RM, et al; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60. Answer Key.

Article 2: Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017 Jun;151(6):1229-1238. Answer Key.

Article 3: Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013 May;13(5):426-35. Answer Key.

Article 4: Glajchen M, Lawson R, Homel P, Desandre P, Todd KH. A rapid two-stage screening protocol for palliative care in the emergency department: a quality improvement initiative. J Pain Symptom Manage. 2011 Nov;42(5):657-62. Answer Key.

Search Strategy:

Four articles relevant to the critical care medicine in the emergency department were selected by the critical care medicine section. No formal literature search was performed.

Bottom Line:

PGY-1

These two blinded, randomized controlled trials comparing dexmedetomidine with midazolam and propofol demonstrated noninferiority of dexmedetomidine with regards to the proportion of time spent at the desired level of sedation, with a decreased in duration of mechanical ventilation compared to midazolam, but no difference compared to propofol. Imbalances in dosing, resulting in lower levels of sedation among patients receiving dexmedetomidine compared to the standard drugs, and lack of objective criteria for weaning of mechanical ventilation and extubation suggest that there may be issues with both internal and external validity. Additionally, patient-centered outcomes and cost were not assessed in this study, nor was the incidence or degree of delirium.

PGY-2

This single-center, before and after study demonstrated a rather large reduction in morality among patients with severe sepsis and septic shock treated with IV vitamin C, hydrocortisone, and thiamine. The results of this study are quite profound, and hence should be confirmed with additional prospective, randomized controlled trials. If this intervention is truly this beneficial, and truly reduces mortality to less than 10% in this patient population, routine use of this therapy should be initiated immediately.

PGY-3

In this meta-analysis evaluating the diagnostic capability of serum procalcitonin in the differentiation of sepsis from non-infectious SIRS, the reported pooled sensitivity and specificity correspond to positive and negative likelihood ratios of 3.7 and 0.29, which will only result in small changes in disease probability. Therefore, caution will need to be exercised when interpreting test results. Interval likelihood ratios may provide more clinically useful information, but were not provided. If procalcitonin is to become a relevant aspect of sepsis care, additional research will need to identify a particular clinical role with an improvement in patient-oriented outcomes.

PGY-4

This study suggests that an ED protocol to screen elderly patients with functional decline who would benefit from palliative care or hospice is feasible, but highly cost-ineffective. Additional means of implementing this protocol in a way that does not involve hiring additional, full-time staff should be sought and studied.

Prevalence of PE in Syncope Patients

Journal Club Podcast #41: March 2018

syncope.jpg

A look at the PESIT trial, which suggests a very high rate of PE in syncope patients, followed by a look at the rest of the evidence...

Click Tabs Below to Expand

Articles:

Article 1: Prandoni P, Lensing AW, Prins MH, et al; PESIT Investigators. Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope. N Engl J Med. 2016 Oct 20;375(16):1524-1531. Answer Key.

Article 2: Costantino G, Ruwald MH, Quinn J, et al. Prevalence of Pulmonary Embolism in Patients With Syncope. JAMA Intern Med. 2018 Jan 29. Answer Key.

Article 3: Frizell A, Fogel N, Steenblik J, Carlson M, Bledsoe J, Madsen T. Prevalence of pulmonary embolism in patients presenting to the emergency department with syncope. Am J Emerg Med. 2018 Feb;36(2):253-256. Answer Key.

Article 4: Oqab Z, Ganshorn H, Sheldon R. Prevalence of pulmonary embolism in patients presenting with syncope. A systematic review and meta-analysis. Am J Emerg Med. 2017 Sep 14. pii: S0735-6757(17)30740-4. Answer Key.

Vignette:

You’re working a TCC shift with Dr. Cohn, sitting right beside you. He’s drinking a Diet Coke, having not offered you one. You decide to go see your next patient, a 78 year old female, complaining of “feeling woozy”. She endorses syncope, shortness of breath, and leg pain. She is saturating 89% on room air, tachycardic to 104, and BP 117/76. She has many other reasons other than a pulmonary embolism to be feeling this way, but the syncope has you thinking. You remember reading an article that was all the rage a few months ago regarding syncope as a presenting complaint for PE. It was fake news, you said. So vague. But here you are. You’ve got a minute, and Dr. Cohn by your side. You search the literature and gently fall into the rabbit hole…

PICO Question:

Population: Adult patients presenting to the ED with syncope and those patients who were admitted to the hospital for syncope.

Intervention: Routine testing for pulmonary embolism (PE)

Comparison: Standard of care with PE workup based on clinical gestalt

Outcome: Prevalence of PE among these patients, mortality, development of CTEPH, adverse reaction to IV contrast, cancer rates.

Search Strategy:

PubMED was searched using the terms "pulmonary embolism" AND prevalance AND syncope (https://tinyurl.com/y7x4gs2u). This resulted in 93 citations, from which 4 relevant articles were chosen.

Bottom Line:

In 2016, the PESIT study from Italy, published in the New England Journal of Medicine, demonstrated an extremely high prevalence of pulmonary embolism (PE) among patients admitted to the hospital for syncope (Prandoni et al). The 17.3% prevalence observed in this study was shocking, and several editorials attempted to rationalize these findings (EPMonthly, R.E.B.E.L.EM, NUEMBlog). As a result, several studies have been published in the interim attempting to either replicate or refute these findings. We looked not only at the PESIT study, but two of these additional studies and a meta-analysis of data in an attempt to place these results in a broader context.

Two retrospective studies were identified, one involving patients from five separate longitudinal administrative databases from Canada, Denmark, Italy, and the United States (Costantino 2018), the other involving patients prospectively enrolled in a syncope database at the University of Utah Hospital (Frizell 2018). Both studies failed to demonstrate such a high prevalence of PE. In the former study, the rate of PE diagnosis among all ED patients ranged from 0.06% to 0.55% in the different databases, while the rate among hospitalized patients ranged from 0.15% to 2.10%. In the latter study, the prevalence of PE among all ED patients with syncope was 0.6%, while the rate among admitted patients was 2.3% (including 2 patients presumably diagnosed with PE within 30 days after hospital discharge, both of whom had a negative CT scan for PE while in the ED).

The meta-analysis we reviewed (Oqab 2017) included 9 studies involving 6608 ED patients and 3 studies involving 975 admitted patients, and demonstrated a similarly low prevalence of PE. The prevalence among all ED patients was 0.8%, and the prevalence among patients hospitalized for syncope was 1.0%. Interestingly, this study specifically excluded the PESIT trial from its meta-analysis. Inclusion of the PESIT study would likely increase the pooled prevalence, though likely not by a significant amount.

The PESIT study itself is the only prospective study of its kind in which all patients being admitted to the hospital for syncope were evaluated for PE. They used an algorithm in which a simplified Well's score for PE was calculated and a d-dimer was drawn in all patients. Those with a low-risk Well’s score and a negative D-dimer underwent no further testing, while anyone with a high-risk Well’s score or a positive D-dimer underwent either CT pulmonary angiography (CTPA) or ventilation-perfusion testing (V/Q). Interestingly, the enrolled population seems to be a very high-risk cohort. Nearly 11% of patients had cancer, 7% had recent prolonged immobility, and 5% had recent trauma or surgery. Of those patients diagnosed with PE, 45% were tachypneic, a third were tachycardic, a third were hypotensive, and 40% had clinical signs of DVT.

The authors note that 24 patients diagnosed with PE had no clinical manifestations of the diagnosis, including tachypnea, tachycardia, hypotension, or clinical signs or symptoms of DVT. Excluding patients with signs concerning for thromboembolic disease, the rate of PE among remaining patients was only around 5%. If you further excluded patients at high risk of PE (i.e. those with cancer, recent immobilization, or recent surgery) this number would likely be even lower. Previous calculations have estimated the test threshold for PE as low as 1.8% (Kline 2004), or as high as 5.5%. Based on this study, even excluding patients with obvious signs of PE or DVT, the prevalence of disease is still likely above the test threshold.

However, all of the other evidence suggests that the actual prevalence of PE among patients in the ED, or even being admitted to the hospital, is much lower, and is very likely to be below this threshold. For now, PE should certainly be considered in the differential for any patient presenting with syncope, but routine testing is not likely to benefit patients. Rather, patients with clinical signs or symptoms concern for PE, or significant risk factors, should undergo risk stratification via the PERC rule, modified Well’s score, or Geneva score, with additional testing based on pre-test probability.

Amiodarone for…well…everything

Journal Club Podcast #40: January 2018

arrhythmia.jpg

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

Click Tabs Below to Expand

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.