cardiac arrest

Does cardiac standstill on bedside echo equal 100% mortality?

You’re in the midst of catching up on notes during a hectic overnight shift when out of the corner of your eye you see a stretcher zoom into the trauma bay – with an EMT leaning over the side performing chest compressions. As the team gathers, the paramedics give report. The patient is a middle-aged male, no known past medical history, who was acting normally about half an hour ago when he suddenly collapsed in front of his family. They started CPR within a couple minutes of the patient collapsing, and called EMS. The paramedics continued CPR, placed a supraglottic airway, and placed the patient on the monitor. He has had a slow, organized rhythm without pulse throughout the arrest. He has received several doses of epinephrine without response. The patient has been pulseless for a little over half an hour by the time he arrives. The ED crew takes over CPR, IV access is obtained, and the patient switched over to the ER monitors, which show a slow, wide-complex, relatively disorganized rhythm. The patient shows no signs of life. Your attending physician calls for the ultrasound, and calls out to the team that if the bedside echo shows cardiac standstill, you will consider terminating further resuscitative efforts.

Clinical Question:

Does cardiac standstill on bedside echo universally predict mortality in OHCA?

Literature Review:

A systematic review of studies investigating the diagnostic accuracy of bedside echo in OHCA was published by a Canadian group in Annals in 2012 [1]. This was a well-done study, with a broad search strategy, rigid but logical inclusion & exclusion criteria, and quality assessment with a modified version of the QUADAS instrument.
Eight studies were included in the final analysis, with a total of 568 patients. Of the 378 patients with cardiac standstill on bedside echo, only 9 (2.4%, 95% CI 1.3% – 4.5%) achieved ROSC. The authors pooled results of the included studies to devise a 2x2 table and determine test characteristics of bedside echo. This revealed a sensitivity of 91.6% (95% CI 84.6% - 96.1%) and specificity of 80.0% (95% CI 76.1% - 83.6%). The positive likelihood ratio is 4.26 (95% CI 2.63 - 6.92) and the negative likelihood ratio is 0.18 (95% CI 0.10 - 0.31). Heterogeneity was minimal (0.0%) for the negative likelihood ratio, but was significant (82.1%) for the positive likelihood ratio. The authors conclude, “While there is insufficient evidence to support using echo in isolation to decide whether or not to continue with cardiopulmonary resuscitations, the presence or absence of VWM in the context of the pretest survival likelihood can provide emergency personnel with further information to assist making that difficult decision whether to stop cardiopulmonary resuscitation with more confidence.”

It is important to note that the outcome of interest in this systematic review was survival to admission, which is not necessarily a good predictor of neurologically-intact long-term survival past discharge, which is the ultimate patient-centered outcome of OHCA. Further limitations included variable inclusion/exclusion of traumatic arrest patients in the included studies, and variability in application of bedside ultrasound. Namely, there were significant differences in training level of examiners, degree of external review of OCHA studies, and definition of “cardiac standstill” between the included studies.
This paper was the focus of a “Systematic Review Snapshot,” authored by our very own Dr. Brian Cohn and published in Annals in 2013 [2].

I attempted a PubMed search using the same search strategy as the authors in the original systematic review (available in the online supplementary material), but I did not discover any further studies on this topic that have been published since that paper in 2012.

Take-home Points:

- Cardiac standstill does not universally lead to failure of resuscitation of OHCA.
- The best-available current evidence does not support the use of bedside echo alone to predict outcomes in OHCA patients.
- Other factors influencing likelihood of neurologically-intact survival (down time, underlying rhythm, patient age/comorbidities, etiology of arrest, etc.) should be taken into account when interpreting bedside echo results.
- More research is needed to determine true prognostic factors associated with survival from OHCA.

Submitted by C. Sam Smith, MD. @CSamSmithMD
Faculty review by Brian Cohn +EMJClub 

References:
[1] Acad Emerg Med. 2012 Oct;19(10):1119-26.
[2] Ann Emerg Med. 2013 Aug;62(2):180-1.

Cardiac arrest, add antibiotics to the kitchen sink?

Clinical scenario:
You get a page out for a 55 yo M in cardiac arrest, EMS reports PEA on their arrival, patient has received 3 rounds of epi prior to arrival, patient achieves return of spontaneous circulation (ROSC) after 5 minutes of ACLS while in the ED. When family arrives they report the patient had been feeling unwell for several days and had a significant cough.  No obvious infiltrate was seen on initial chest xray.  The patient's BP is stable on an epi infusion. You admit the patient to the ICU. Your attending requests drawing blood cultures and starting the patient on broad spectrum antibiotics, and cites data stating antibiotics improves mortality in out of hospital cardiac arrest. You perform a brief literature review. 

Literature Review:
Out of hospital cardiac arrest (OHCA) has a very high mortality rate, where approximately only 23% make it to the hospital alive, and 7.6% survive to hospital discharge. (1) The most common etiology of out of hospital cardiac arrest is presumed to be myocardial in origin. However, several retrospective studies indicate that sepsis and bacteremia may also be a significant contributing factor to OHCA. A study by Coba et al in published in 2014 performed a prospective study to identify the incidence of bacteremia in OHCA patients. They enrolled 173 patients, where all patients had two sets of blood cultures drawn, 77 patients met exclusion criteria (trauma, pregnant, pediatric, single positive culture of skin flora). The overall incidence of bacteremia was 37% (65 patients). The most common bacterial species cultured were streptococcus and staphylococcus and Ecoli and klebsiella for gram positive and gram negative bacteria respectively. Bacteremic OHCA patient had significantly higher lactates, lower pH, and more frequent use of vasopressors. Notably the ED survival was significantly lower in the bacteremic patients (25%) compared to nonbacteremic patients (40%). However, 28 day mortality difference was insignificant in bacteremic vs nonbacteremic patients (93.8 vs 92.6%). The figure below by Coba et al lays out the proposed inter-relationships between bacteremia and sudden cardiac arrest. (1)
Proposed association between bacteremic infection and sudden cardiac arrest. From Coba et al.



Although there is very little data examining pre-existing bacteremia in OHCA, there has been a significant amount of research studying infection following ROSC in OHCA. The most commonly cited sources of post ROSC infection are lung possibly from aspiration during arrest, or gut likely from translocation of flora secondary to low flow state during arrest.  Davis et al performed a retrospective analysis on 138 patients admitted to the ICU following OHCA, and showed that 97.8% had at least one positive mark of infection within 72 hours (positive blood culture, consolidation on cxr, CRP greater than 100 or wbc greater than 11 or less than 4 x10^9 ). In this study approximately 38.4% of patients received antibiotics during the first 7 days of their ICU stay. The authors showed that mortality was significantly lower among those receiving antibiotics versus those not receiving antibiotics (56.6% versus 75.3%). However, highest mortality was within the first three days, and for patients who survived to day 3, there was no difference in mortality between those who received antibiotics already and those who had not. (2)

Take home points:
OHCA is typically presumed to be a primary myocardial event, however there is some data to suggest that sepsis is potentially a significantly under reported cause. Furthermore, there is also data to suggest that following ROSC, infection is quite common, and antibiotics may reduce early mortality. However, caution must be taken, as of yet there are no RTC's comparing prophylactic antibiotics versus placebo in OHCA.

Expert Commentary:

Dr. Holthaus one of our own critical care and sepsis guru's was nice enough to provide some of his own thoughts on this topic, and cardiac arrest in general. 

Things we'd like to see examined in future cardiac arrest RCTs:
1) Antibiotics during arrest - push dose, timing, coverage.
2) Propofol - control for this or exclude as a variable since it has been shown to cause some mitochondrial dysfunction and may be thwarting potential resuscitation benefits.
3) Epi dosing - frequency, continue 1mg push dose vs lower dose vs maximum that is less likely to cause or further exacerbate either ischemic or post-inflammatory cardiomyopathy.
4) Vasopressin-Steroid-Epi- for ED arrest. Link to VSE study in JAMA . VSE (vasopresson-steroids-epi) better than Epi alone for in-hospital arrest Vasopressin (20u, q 3-5min, max 100u, w 1 mg epi pushes)-Methypred (40mg IV x1) w better ROSC (84% vs 66%) and better CPC1/2 survival (14% vs 5%).  Major caveat is time to ACLS was very low at 2 min for both which is way faster than many we see in the ED that are frequently >10 min downtime before EMS.  Hypothesis generating, re-hinting at potential beneficial role of vasopressin and steroids for shock (like sepsis). 
5) ED ECMO for cardiac arrest or refractory/severe shock
6) Remote ischemic conditioning immediately after ROSC- 5 min thigh BP tourniquet to >20mmHg above SBP then deflate, repeat 3-4 times, reportedly induces systemic circulation of a protein that blocks CNS/cardiac opening of the "mitochondrial permeability transition pore" which is the final common pathway for ischemic reperfusion injury).  On recent ED ECMO podcast (Shiner-Bellezo) Link to podcast Remote ischemic conditioning 

Personally since everything (ACLS) isn't getting much results, if I can remember to I will do Vasopressin-Methypred-Epi dosing, I am less excited about a lot of epi (ie 3 pushes tells me if they're trending toward making it or not), I've pushed zosyn and then hung vancomycin in a code (after learning about Coba study). I have generally avoided propofol in past because of known myocardial suppression, and now with concern for mitochondrial insult, I just use fentanyl/versed. In addition I  will try thigh remote ischemic reconditioning, and continue targeted temperature management to 33-36C while hoping for ED ECMO (which I think will be the biggest game changer)  

Submitted and Edited by Louis Jamtgaard PGY-3 @Lgaard
Faculty Review by Chris Holthaus

References

 1) Coba V et al. The incidence and significance of bacteremia in out of hospital cardiac arrest.
Resuscitation. 2014 Feb;85(2):196-202. d

2)Davies K et al. Early antibiotics improve survival following out-of hospital cardiac arrest.Resuscitation 2013 May; 84 (5) : 616-9.