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