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9/28/2018
1
ACEP 2018
Cruising the LiteratureCardiology 2018Corey M. Slovis, M.D.
Vanderbilt University Medical CenterMetro Nashville Fire DepartmentNashville International Airport
Nashville, TN
CPREpinephrine
Heads Up CPRPCI S/P Arrest
TORArrest S/P Sex
EpinephrineNew Engl J Med 2018;379:711-21
• Large double blind placebo controlled trial
• 8,014 pts, UK EMS, adults ≥ 16 yo
• 4,015 pts, 1 mg epi Q 3-5 min
• 3,999 placebo receiving patients
What is the role of epinephrine in cardiac arrest?
The study evaluated 30 day outcomes and functional neurologic outcomes at
discharge and at 3 months
New Engl J Med 2018;379:711-21
Times and Dose
6.6 min Call to EMS arrival (median)
21.4 min Call to epinephrine or placebo
4.9 ± 2.5 mg Epinephrine dose (mean)
New Engl J Med 2018;379:711-21
9/28/2018
2
0%
10%
20%
30%
40%
50%
60%
Hu
nd
red
s
30.7
ROSC and EMS Transport
ROSC EMS Transport
11.7
Placebo Epi Placebo Epi
New Engl J Med 2018;379:711-21
36.3
50.8
0%
1%
2%
3%
4%
5%
2.4%
30 Day Survival
Placebo
3.2%
Epinephrine
New Engl J Med 2018;379:711-21
OR = 1.39p = 0.02
NNT = 112
New Engl J Med 2018;379:711-21
30 Day Neurologic Outcomes
0.0
0.5
1.0
1.5
2.0
2.51.9%
Rankin 0 - 3
Placebo
2.2%
Epinephrine
New Engl J Med 2018;379:711-21
OR = 1.18CI = 0.86-1.61
0.00.10.20.30.40.50.60.70.80.91.01.11.21.31.41.51.6
1.35%
Favorable Neurologic OutcomeRankin 0 - 2
Placebo
1.29%
Epinephrine
New Engl J Med 2018;379:711-21
0%
10%
20%
30%
40%
50%
60%
17.8%
Severe Neurologic Disability (30 d)Rankin 4, 5
Placebo
31.0%
Epinephrine
New Engl J Med 2018;379:711-21
9/28/2018
3
Adjusted AnalysisParamedic Witnessed
Favors Placebo Favors Epinephrine
New Engl J Med 2018;379:711-21
Adjusted AnalysisVF/pVT vs Non Shockable
Favors Placebo Favors Epinephrine
New Engl J Med 2018;379:711-21
Adjusted AnalysisMedical vs Traumatic
Favors EpinephrineFavors Placebo
New Engl J Med 2018;379:711-21
Epinephrine in Cardiac ArrestTake Homes
The role of epinephrine in cardiac arrestwill continue to be debated
Epinephrine increases survival butdoes not increase the rate of
neurologically intact survival
Epinephrine increases the number of neurologically devastated survivors
Positive Result Conclusion
Epinephrine in OOHCA arrest improves ROSC and likelihood
for hospital discharge
Neutral Result Conclusion
Epinephrine does not improve neurologically intact survival
in OOHCA
9/28/2018
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Negative Result Conclusion
Epinephrine in OOHCA just increases the likelihood of being neurologically
devastated without significantly increasing the number of neurologically
intact survivors
Heads Up CPR
Resuscitation 2018;128:51-5
• Heads up CPR ICP and CPP
• Porcine study of 20 pigs
• Confirms ICP and CPP
• However no improvement in cerebral oxygenation and/or metabolism
• Heads-up CPR is not yet of proven benefit in pigs or humans
PCI S/P Cardiac Arrest
JACC 2018;72:471-2
• 110,636 Medicare database AF pts
• 9,147 developed new AF in ED
• 25% new AFib diagnosed in ED
• Average age 77, 63% female
How often do ED physicians prescribe anticoagulants for stroke prophylaxis in newly
diagnosed Atrial Fibrillation?
Results
• High stroke risk and low/int bleed risk not correlation with increase likelihood of Rx
• Almost 2/3 of Rxs: Warfarin
JACC 2018;72:471-2
Less than 1 in 5 prescribed anticoagulation
9/28/2018
5
Resuscitation 2018;123:15-21
• 599 OHCA registry pts
• UPMC and Mercy Hospitals
• Early vs Later vs no Cath/PCI
• STEMI and no AMI pts
How valuable is PCI s/p cardiac arrest?
0%
10%
20%
30%
40%
50%
60%
70%56.2%
Survival to Discharge
Early Cath Lab47.2%
31%
CCU Only52.8%
p = 0.0001
Resuscitation 2018;123:15-21
0%
10%
20%
30%
40%
50%
60%
70%
65.6%
Survival to DischargeEarly PCI vs CCU
Early Cath Lab
31%
CCU Only
p = 0.0001
Resuscitation 2018;123:15-21
Am Heart J 2018;202:144-7
• Witnessed EMS arrests or within 3 min of EMS
• Pathway activated immediately
• 86 pts EMS screened 38 accepted
• Arrest until PCI start: 63 min
• No survivors among 17 non-VF pts
How valuable is immediate PCI during cardiac arrest?
PCI and Survival
• 70% of VF pts had a culprit lesion
• 92% of survivors had VF
• 1/3 of non STEMI VF arrests had acute lesion
• Mechanical CPR but no ECMO = 0% survival
• Low 30% 30 d survival (3 x of Sweden)
Am Heart J 2018;202:144-7
Early Coronary AngiographyTake Homes
• Early CCL essential to find intervenable lesions
• If PCI indicated: survival doubles with good neuro
• Non ST elevation AMI: intervenable lesions about 30% of time
• They, too, greatly benefit
• Be aggressive for high ROI
9/28/2018
6
TOR
EMS requests termination of CPR in progress for a 47 yo man found down.
You are NOT the EMS Medical Director. They have given 2 doses of epinephrine, ventilated the patient and performed high
quality CPR. They are enroute to you. The rhythm is slow PEA.
Should you stop CPR on arrival?
What are the TOR criteria?
Resuscitation 2018;130:21-27
• 227 CPR patients, 39.2% TOR +
• Excludes pregnancy, suspected drug OD
• Overall 8% TOR/non-TOR pts admitted
• Overall survivor to discharge: 1.3%
• All with good neuro outcomes
Do the TOR criteria apply to patients transported to the ED?
TOR Criteria and Survival
• Non shockable rhythms
• Arrest not-witnessed by EMS
• NO ROSC prior to transporting
Resuscitation 2018;130:21-27
0.0% survival in TOR + patients
Resuscitation 2018;130:21-27
TOR TOR and ED PhysiciansTake Homes
• No response to epi in an unwitnessed non VF/VT arrest portends non survival
• Stop sooner, not later
• Use low ETCO2 (< 10 mm Hg)
• And no US viewed wall motion
• Terminate more before EMS transport
9/28/2018
7
Circulation 2018;137:1638-40
Only 47% received CPR in these witnessed arrests
Maybe put on defib pads and hook up AED during the warm up
STEMI?
ECG STEMI Changes
JAMA Int Med 2018;178:133-4
JAMA Int Med 2018;178:133-4
JAMA Int Med 2018;178:133-4
9/28/2018
8
but…
STEMI = check K if RF(or really big T waves)
Time = Muscle
HyperK = ECG
ECG Changes Serum Level
Loss of P Wave 6.5 - 7.5
Widened QRS usually > 8
Tall Peaked T 5.5 -6.5
What are the 5 ECG Changes Seen in Hyperkalemia
• Tall Peaked T-Waves
• Prolonged P-R Interval
• Loss of P Wave
• Widening of QRS
• Sine Wave
9/28/2018
9
Symptomatic Bradycardia5 Rule Outs
• Abnormal VS: Hypoxia, Hypothermia
• Ischemia/Infarction
• Elevated ICP
• Beta Blocker-Calcium Blocker (and other) ODs
• Hyperkalemia
BRASH Syndrome
Bradycardia
Renal Failure
AV Blocker
Shock
Hyperkalemia
West J Emerg Med 2017;18:963-71
What ECG changes predict patient decompensation in HyperKalemia?
• 188 patients serum K ≥ 6.5 meq/L ( x = 7.1)
• Observational study, Brown University
• ECGs within 60 min of serum (mean = 18 min)
• Hemolyzed samples excluded
• Peaked Ts, P-R , QRS , Bradycardia, Junctional
Adverse Events
• 28 pts, average K = 7.5 meq/L
• Symptomatic Bradycardia in 22 pts
• VT: 2 pts
• Cardiac Arrest: 2 pts
• Death: 4 ptsall prior to calcium administration
West J Emerg Med 2017;18:963-71
9/28/2018
10
ECG Abnormalities and Adverse Events
West J Emerg Med 2017;18:963-71
ECG Predictors of Adverse Events
• QRS prolongation most common predictor- Seen in 79% of pts with adverse events- Average QRS 152 msec
• Bradycardia second most common predictor- Seen in 60% of pts with adverse event
• 86% of patients had > 1 ECG abnormality
West J Emerg Med 2017;18:963-71
No patient with only peaked Ts or prolonged P-R duration had an
adverse event
West J Emerg Med 2017;18:963-71
ECG Changes and HyperKalemiaTake Homes
• Widened QRS and Bradycardia in Hyperkalemia portends disaster
• Tall peaked T waves do NOT
• Do not use calcium for those patients who merely have peaked T waves and/or a prolongation of the P-R interval
Chest Pain andScoring Systems
JACC 2018;71:606-16
How does HEART, EDACS, simplified EDACS compare in predicting 60 day MACE
• 118,822 pts, Kaiser Group, retrospective study
• Electronic keyword text string search
• All patients chart evaluated using all 3 scores
• Used a Troponin I level < detectable
9/28/2018
11
JACC 2018;71:606-16JACC 2018;71:606-16
60 Day MACE Plus RevascTrop I < 0.02
JACC 2018;71:606-16
NPV % of R/O Pts
HEART 99.08 51.8%
EDACS 98.88 60.6%
Simplified 98.88 48.1%EDACS
60 day MACE for an undetectable troponin I (< 0.002) and a low risk
score is 99.5% for all 3 tests
JACC 2018;71:606-16
JACC 2018;71:606-16
Take Homes
• Undetectable troponin x 2 plus a low risk HEART or EDACS provides more than a 99% negative predictive value for a major adverse event
• These patients may not really benefit for subsequent stress testing
• Beware positive troponins, even just barely detectable ones
9/28/2018
12
Acad Emerg Med 2018;epub June
How does the HEART pathway perform in a randomized trial-over a 1 year study?
• 282 patients, single center trial
• ACC/AHA std care vs HEART pathway
• 1 year MACE and downstream testing
• Used 0 and 3 hour troponins
• HEART 0-3 pts: DC’d, follow up with PCP
HEAR Performance1 Year Results
• 66/141 patients had negative 0-3 hour troponin and a HEAR score of 0-3
• None of these discharged patients had a major adverse cardiac event (MACE) by 1 year
• NPV % 100%; Sensitivity for MACE: 100%
• But only 8% reduction in 1 year for cardiac testing
Acad Emerg Med 2018;epub June
0%
10%
20%
30%
40%
50%
60%
70%
80%63.1%
Objective Testing at 1 Year
Heart Pathway
71.6%
Usual Care
p = ns
Acad Emerg Med 2018;epub June
HEART Score and PathwayTake Homes
• First 1 year study of HEAR
• No longer HEART
• A subjective “objective” test
• Beware positive Trop
Am J Emerg Med 2017;35:704-9
Is “Low Risk” by HEART and other scoring systems really low risk?
• 434 pts from 7 EDs
• Average age 57 (49-64)
• Used HEART, TIMI, GRACE, EDACS
• Compared HEART ≤ 3 vs ≤ 2
HEART ≤ 3 has a miss rate of 3.6%
HEART ≤ 2 had a miss rate of 0
Am J Emerg Med 2017;35:704-9
9/28/2018
13
Acad Emerg Med 2018;25:434-43
Can a single initial high sensitivity Troponin allow early ED discharge when combined with a risk score?
• 2,258 low risk CP patients
• Pooled data from 4 Australian/NZ studies
• Used hs Troponin T and hs Troponin I
• EDACS: ED Assessment of Chest Pain Score
• 30 day MACE results
Results
• Evaluated ranges of Troponins + EDACS
• Boot strapping to find ≥ 98.5% sensitivity
• Threshold Trop I ≤ 7 ng/L; Trop T ≤ 8 ng/L
• EDACS Threshold score ≤ 15
• Allowed 30% of patients to be D/C’d
Acad Emerg Med 2018;25:434-43
Study found low levels of detectable hs Troponin plus low EDACS score almost as good as detecting no hs Troponin at all
(below level of detection)
Acad Emerg Med 2018;25:434-43
Detectable Troponin – implicit risk – be careful
This study says you will miss 1.5% of ACS – it’s the same as most studies before high sensitivity
Troponin were available
Acad Emerg Med 2018;25:434-43
JAMA 2017;318:1913-24
• Meta-analysis of 22,457 pts, 19 studies
• Abbott ARCHITECT-STAT HS Troponin
• Attempted to maximize patients at lowest risk
• Used < 5 ng; 5-99th percentile; > 99th
• 99th percentile HS Troponin I = 14-20 ng
What high-sensitivity Troponin I should be cut-off to R/O ACS?
A HS Troponin I of < 5 ng is seen in ½ of R/O ACS pts and yields a
NPV of 99.5 of AMI or Death at 30 d and a NPV of 99.9 for Death at 30 d
JAMA 2017;318:1913-24
9/28/2018
14
JACC 2018;72:620-32
• 0/1 hr Troponin I or T studied
• 4,368 serial Trop T pts; 3,500 serial Trop I pts
• Did not also use HEART pathway
• Used ESC 0-1 hr R/O pathway
Troponin Rule OutsJACC 2018;72:620-32
Troponin T: Trop I:
0 hr < 5 ng/L 0 hr < 2 ng/L
or or
0 hr < 12 ng/L 0 hr < 5 ng/L
and and1 hr < 3 ng/L 1 hr < 2ng/L
JACC 2018;72:620-32
NPV of 0/1 Hr R/OTroponin T and I
JACC 2018;72:620-32
hsT hsI
JAMA Cardiol 2018;3:112-113
• 1,690 R/O ACS pt; 15 US EDs HS Trop T
• Used 0, 3, 6-9, 12-24 hr levels
• Healthy volunteers 99th % = 19 ng/L
• Found 0 and 3 hr accuracy plateaued
Can a 0-3 hr HS Troponin T R/O 30 day ACS > 99% of patients?
A single HS Troponin T < 6 ng/L has a NPV of 99.4 and both a 0 and 3 hr of < 19 ng/L has a
NPV of 99.3 for 30 d ACI
JAMA Cardiol 2018;3:112-113
9/28/2018
15
The 0 and 1 hour rule out protocols yield at NPV for ACS of 99.8 for HS
Troponin T and 99.7 for HS Troponin I and allows early discharge for
1/2 - 2/3 of patients
JAMA Cardiol 2018;3:112-113
Circ 2018;138:in press
• 536 pts, Parkland Hospital, HS and Trop T
• Uses delta changes
• Above 52 ng/L = AMI, < 6 ng/L ≥ 3 hrs = R/O
• < 3 ng at 1 hr = R/O
• < 7 ng from baseline at 3 hrs = R/O
Can a multi-step 0, 1 and 3 hour protocol deal with the “indeterminate” patients when using
high-sensitivity Troponin (hsTrop)
Protocol providing 100%Sensitivity for AMI and 100%
Negative predictive values for R/O
Circ 2018;138:in press
Circ 2018;138:in press
Circ 2018;138:in press Circ 2018;138:in press
9/28/2018
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Circ 2018;138:in press
Circ 2018;138:in press
Take Homes onHigh Sensitivity Troponins
• Undetectable at 0-1 or 0-3 rules out AMI
• Delta testing excludes evolving AMI
• Early AMI presenters need values over time
• Using the 99th percentile may not be optimal
• Beware detectable Troponin
At the current time there is no universally accepted high sensitivity
Troponin protocol and objective scoring system that is “proven” to be optimal
All important decisions are made onincomplete information….
Yet we are responsible for everydecision we make.
Sheldon Kopp 1972JACC 2018;71:606-16
9/28/2018
17
How Important is Stress Testing??
Does CCTA add anything to a chest pain work up once AMI has been ruled out?
The SCOT-HEART trial
New Engl J Med 2018;379:924-33
• 4,146 Scottish CP pts, 3-7 year f/u
• Randomized to CCTA or routine case
• NOT ED pts, all CP pts
• Compared mortality, AMI, ReVasc rates
Treatments
• More preventative Rx if CCTA
• More anti-angonal Rx if CCTA
• More early angiography and ReVasc, too
• At 5 years no diff in ReVasc rates
New Engl J Med 2018;379:924-33
0%
1%
2%
3%
4%
5%
Hu
nd
red
s
0.2%0.4%
Cardiac Death or AMICCTA vs No CCTA
Death
2.1%
3.5%
CCTA CCTANo No
2.3%
3.9%
Combined
CCTA No
Non Fatal AMI
p = 0.004
New Engl J Med 2018;379:924-33
CCTA for CP PtsTake Homes
• Not an ED CP study
• Knowing coronary anatomy helps post ED Rx
• Allows more aggressive care
• My thoughts are R/O AMI is not enough
• Are coronaries: WNL, some CASHD, obstructed?
JAMA Int Med 2018;178:212-19
• 1,000 pts (40-74 yo) from ROMICAT-II
• No hx CAD, no CRF
• 118 pts no testing vs 882 CCTA or stress test
• Evaluated 28 day MACE
• Also ACS dx %; Angiography/PCI %
Is stress testing necessary if ECG is non ischemic and 2 Troponins are negative?
9/28/2018
18
0
2
4
6
8
10
12
14
0%
9%
Stress Testing vs No TestingACS Angiography 30 d PCI
ACS Dx
0%
10%
No NoTest Stress
2%
5%
30 d PCIAngiography
All p < 0.001
JAMA Int Med 2018;178:212-19
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
2.22%
28 Day MACE
No Testing
1%
CCTA or Stess
P = NS
JAMA Int Med 2018;178:212-19
Stress TestingTake Homes
It is getting harder and harder to justify routine stress testing
May miss 1-2% 30 d ACS just using ECG and Troponin without scoring system
Adding low HEART Score is key
JAMA Int Med 2017;177:1175-82
• 926,633 pts retrospective observational study
• Database study of ED CP pts. 18-64 yo
• Followed pts for 1 year
• Evaluated rates of PCI, CABG and AMI
• Compared weekday to weekend pts
Does stress testing decrease PCI or AMI?
Patients not randomized, those who underwent stress testing were older,
M > F and had more risk factors
JAMA Int Med 2017;177:1175-82
JAMA Int Med 2017;177:1175-82
Stress testing of patients with non ischemic ECG and negative biomarkers
results in longer ED/hospital stays, more angiography, more PCI but
no decrease in AMI over 1 year
9/28/2018
19
Acad Emerg Med 2018;25:293-300
Does shared decision making lead to decreased testing without increased risk to
patients and/or physicians?
• 834 CP patients evaluated 45 days s/p ED
• Multicenter trial, 5 EDs across USA
• All eligible for Stress or MD CT
• All kept health care diaries
• Compared usual care to shared decision making
Chest Pain Choice (CPC) Tool
• Provides 45 d personalized ACS risk
• Compares Obs admit to 3 d follow up
• Clearly explains management options
• Explain Stress or CCTA vs 3 d follow up
Acad Emerg Med 2018;25:293-300
Key FindingsAcad Emerg Med 2018;25:293-300
Shared decision making patients had 25.8% less advanced testing than
routine care over 45 days –without any worsening of outcomes
or increased number of adverse conditions
So what should you do:
- Do a very careful history
- Use HEART but diaphoresis &/or radiationto R arm or shoulder, Abn ECG = high risk
- Beware a single Troponin
- Be more careful in HS = 3
- Always involve the patient and family
Type 1 vs Type 2 MI?• It’s not STEMI vs NSTEMI
• Supply vs demand mismatch
• Mismatch due to non CASHD secondary process
• 2 x incidence vs AMI due to STEMI/NSTEMI
• Poorer survival (5 yr = 40% vs 60-65%)
JAMA 2018 online Jun 11
Male vs Femalein AMI Dx and Rx
9/28/2018
20
Circulation 2018;137:781-90
How different is AMI in males vs females less than age 55?
• 2,009 women, 976 men with AMI
• Young defined as 18-55
• About 90% of M and F pts has chest sx:- pain, pressure, tightness, discomfort
• Women had more additional symptoms
• 50% more F than M had no CP
Physicians much more likely to attribute AMI symptoms to another
disease in women than men
53.4% F vs 36.7% M, p < 0.001
Circulation 2018;137:781-90
Women and AMI
We need to be careful
“Atypical symptoms” may be typical in women
Be aware of our unconscious biases
Are women really treated differently for ACS if they are troponin positive?
• 7,272 pts from Vancouver, 2008-2013
• All pts troponin positive with ischemic CP
• 2,933 females: 4,339 males
• Evaluated % PCI, meds, mortality
• All had cTnI > 99th percentile
Acad Emerg Med 2018;25:413-24
Symptoms & Diagnosis in EDTroponin Positive Females
Acad Emerg Med 2018;25:413-24
• More respiratory symptoms(22.4% vs 14.8% F:M)
• Less classic chest pain symptoms(77.6% vs 85.2%)
• AMI less frequently diagnosed in ED(35.4% vs 52.5%)
• Less likely to be using evidence based meds:(ACE-I / ARB 0.32; BB 0.52, Statin 0.31)
Risk FactorsTroponin Positive Females
• Older 65 (70.8% vs 49.3%)
• More HT HT (39.8% vs 28.5%)
• More RF CRF (27.6% vs 18.7%)
Acad Emerg Med 2018;25:413-24
9/28/2018
21
05
101520253035404550556065
64.3
Troponin PositivePCI and MACE
PCI MACE
48.4
Female Male Female Male
OR = 0.52(0.39 – 0.70)
HR = 1.24*(0.94 – 1.65)*p – NS onceadjusted for difference
18.822.7
Acad Emerg Med 2018;25:413-24
How We Treat Women vs Men with ACS
Take Homes
• We as ED MDs are less aggressive with women and they do worse
• Even if Troponin positive, we are less aggressive with emergent PCI and/or cardiac meds
Lancet 2018;391:1693-1705
Does liberal oxygen therapy increase morbidity or mortality?
• 16,307 patients, 25 randomized trials
• Sepsis, CVA, Trauma, AMI, s/p CPR, Critically ill
• COPD, ECMO, Hyperbarics or Psych excluded
• Evaluated mortality in hospital, 30 d and/or longest
• Hospital stay, hospital acquired pneumonia, LOS
Lancet 2018;391:1693-1705
Study compares FiO2 given liberally at rates from 30% - 80% with a few at 100% FiO2 vs a majority of patients treated with no supplemental O2, or low flow (2-4 L/min) nasal prongs or titrated to O2 sat < 96%
Median FiO2 52% vs 21% for a median duration of 8 hours
Unrestricted oxygenation will increase mortality by about 21% at 30 days in
comparable patients with similar baseline O2 saturations
There were no differences in in-hospital complication
Lancet 2018;391:1693-1705
Oxygenation of Critically Ill PatientsTake Homes
94 – 96% Not higher
9/28/2018
22
PNAS 2018;115:8569-74
• Higher mortality seen when women with STEMI treated by male ED physician
• Female=Male when treated by female ED physicians
• Male physicians do better if more females in ED practice or they have treated more females in past
• Be careful of unconscious gender bias
Patient vs Doctor Gender
M Doc
F Pt
M Doc
M Pt
F Doc
F Pt
• 550 pts, Mecklenburg, NC EMS
• Mean E2B 80.8 min, SD 19.7 min
Prehosp Emerg Care 2018;in press Mar
Each 1 min increase in E2B above mean time increased mortality by 3%
or 30% for 10 minute delay
Pulmonary Embolus
Is Lytic Therapy indicated or justified in acute PE?
Thorax 2018;73:464-71
• 22 RCTs: 16 full, 1 low dose vs heparin
• 4 studies compared low vs full dose
• 1 study used catheter directed lytics
• Evaluated mortality, major bleeding, 1 CH
Results
• No lytic protocol significantly better than heparin
• No significant trend toward lower mortality though
• Full dose lytics risk of major bleeding
• Low dose lytics best for lowest mortality & safety
Thorax 2018;73:464-71
9/28/2018
23
Lytics in PETake Homes
• Use in arrest and peri arrest50 mg IV over 1 minute
• Full dose lytics only for massive PE(refractory hypoxia, hypotension)
• Half dose lytics appear as good as full
Critical Care Med 2018;46:1617-25
Can ½ dose TPA be used to treat PE?
• Retrospective cohort trial, 420 hospital database
• 699 pts treated with ½ dose TPA
• 3,069 full dose TPA
• Evaluated mortality, major bleeding, Escalation
• Propensity matching of 548 pts 1:1
0
2
4
6
8
10
12
14
16
18
20
0.5%BLS
Mortality and Cerebral Hemorrhage
Mortality ICH
13%
1/2 Full 1/2 Full
p = ns
p = ns
15.1%
0.4%
Critical Care Med 2018;46:1617-25
0%
10%
20%
30%
40%
50%
60%53.8%
Escalation in Therapy
½ Dose
41.4%
Full Dose
p=0.01
Critical Care Med 2018;46:1617-25
Half Dose Lytic PE TherapyTake Homes
• Not a ringing endorsement
• But not a controlled study
• 25.9% vs 7.3% required 2nd thrombolysis
• 14.2% vs 3.8% had mechanical fragmentation
• Role of ½ dose lytics remains very unclear
Acad Emerg Med 2018;25:995-1003
Can low risk PE patients be safely discharged from the ED?
• 114 randomized PE patients
• 51 ED D/C’d vs 63 admitted
• D/C pts placed on rivaroxaban 15 mg BID
• 90 day follow-up
• No high-risk PE patients
9/28/2018
24
Requiring Admission for PE
• Hemodynamically unstable
• Active or high-risk for bleeding
• Sys BP > 180; DBP > 110
• Hypoxic
• Already anti-coagulated
• Pregnant, Liver DSX, C-Cl < 30
Acad Emerg Med 2018;25:995-1003
Results
Acad Emerg Med 2018;25:995-1003
• No VTE reoccurrences in either group
• No VTE deaths in either group
• No differences in bleeding rates(1 minor in each group)
0
5
10
15
20
25
30
35
40
4.8
Hospital Stay in Hours
NOAC
33
Admit
p < 0.0001
Acad Emerg Med 2018;25:995-1003
± 16.8
± 48
Initial Visit Costs
• $1,496 ED with NOAC on DC
• $4,234 Admit Std of Care Rx
Acad Emerg Med 2018;25:995-1003
Sending Home PEsTake Homes
• First large study
• Safe in low-risk patients
• Cheaper, faster
• Avoids in-hospital days
• A “new” treatment consideration
Chest 2018;154:249-56
Can PE be an outpatient disease?The LOPE Study
• Prospective study, 200 pts, 5 EDs
• Intermountain Health, Salt Lake UT
• PESI < 86, TT Echo, Leg US
• 90 d mortality, Recurrent VTE, Major bleed
• Measured patient satisfaction; 100% follow-up
9/28/2018
25
Methods
• Low risk PESI < 86, no hypotension or hypoxia
• Admit to Obs for 12-24 hr (x=13 hrs)
• TTE to R/O RV strain
• Leg US to R/O Proximal DVT
• Discharge on NOAC
Chest 2018;154:249-56
Results
• No recurrent VTE, no mortality
• 1 major bleed on OP NOAC
• 91% stated they preferred OP care
Chest 2018;154:249-56
Out Patient Management of PETake Homes
• Safe
• But only in very select pts
• Low risk PESI, WNL Echo, No DVT
• Troponin and BNP testing not helpful
• Can be followed as OP
Acad Emerg Med 2018;25:828-35
Do subsegmental PEs (SSPE) require therapy?
• Systemic review and meta-analysis
• 15,563 patients from 14 studies
• 4.6% of PEs are SSPEs
Acad Emerg Med 2018;25:828-35
Do subsegmental PEs (SSPE) require therapy?
• 90 d VTE%:- 5.3% if treated vs 3.9% if not
• 90 d Bleed rate:- 8.1% if treated
• Death: 2.1% treated vs 3% not
“These data suggest clinical equipoise for decision to anticoagulate
patients with SSPE”
“However…lack of a controlled clinical trial”
Acad Emerg Med 2018;25:828-35
9/28/2018
26
JAMA 2018;319:559-66
Should we rely on using PERC in low risk for PE patients?
• 1,916 pts from 14 French EDs
• Used R/O PE pts with PE probability < 15%
• Each ED did 6 mos PERC vs no-PERC
• D-dimer for all non-PERC low risk pts
• 3 month follow-up
Results
• 1 VTE over 3 mos in PERC neg pt
• 0 VTEs in control group
• This PERC “miss” was VS–and CTA equivocal
• PERC stayed 43 minutes less
• Similar mortality: 0.3 vs 0.2 (1 pt)
JAMA 2018;319:559-66
0%
5%
10%
15%
20%
25%
13%
PERC vs D-Dimer For All
PERC
23%
No PERC
JAMA 2018;319:559-66
ED CTPA
PERC Take Homes
• Use it
• Especially when you want to D/C
• Study clearly supports its use
• But only in very low risk pts!
Atrial Fibrillation
West J Med 2018;19:417-22
Can PO Diltiazem be substituted for an IV Infusion to control Atrial Fibrillation with RVR?
• 111 adult pts with AF and RVR > 110 bpm
• Single center observational study from VCU
• Used 4 hour HR to measure efficacy
• PO dose: 30 mg (53%), 60 mg (41%)
• IV dose: 10 mg/hr median (2.5-20 hour range)
9/28/2018
27
Mean initial loading doses were 0.22 mg/kg oral and
0.24 mg/kg IV
West J Med 2018;19:417-22
0%
10%
20%
30%
40%
50%
60%
70%
80%
73.2%
HR Less Than 110 at 4 Hours
131 Initial HR
West J Med 2018;19:417-22
55.3%
145 Initial HR
P=0.049
PO IV
70 pts41 pts
PO Diltiazem vs IV Continuous InfusionTake Homes
• Small not well controlled study
• Variable loading dose, low IV infusion
• IV group had higher initial HR (140 vs 131)
• However- Consider PO Diltiazem in patients vs
continuous infusion in selected cases
Median infusion was 10 mg/hr
Loading dose was 16.8 mg
in 70 kg pt infusion rate was only 5.8 mg/hr
Too Little IV Diltiazem
Acad Emerg Med 2018;25:641-9
Can a simple to follow protocol allow more discharges in AFib/AFlut patients?
• 1,108 patients
• Retrospective before-after trial
• Academic community hospital
• Evaluated percent of pts admitted in 1 year
• Also 3 and 30 day returns
Study Assumptions and Hypothesis
• 20 yr AFib admits 60% in US
• No defined AHA/ACC discharge pathway
• Great care variations US vs Canada
• Future stroke is greatest risk
• AFib/AFlut rarely acutely life-threatening
Acad Emerg Med 2018;25:641-9
9/28/2018
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Acad Emerg Med 2018;25:641-9
• Arranged follow up within 3d
• Seen then in cardiology clinic
• Anticoagulation held until then
• Discharged on BB or Calcium Blocker
• Metoprolol 50 BID
• Diltiazem 120-180 ext release
Acad Emerg Med 2018;25:641-9
Current Common AFib PathwayMost EDs
• H/P, CXR, ECG, basic labs, thyroid
• IV rate control meds
• Cardiology consult
• Echo
• Admit
St. Joseph Murphy AlgorithmExclusions and Admit
• Underlying Acute Illness(sepsis, PE, etc.)
• Acute Coronary Syndrome
• Acute Heart Failure
• Syncope
• Hemodynamic instability
Acad Emerg Med 2018;25:641-9
Acad Emerg Med 2018;25:641-9
• Synchronized cardioversion not focus
• Rate-control IV meds discouraged
• Not specifically stated by patientsalmost all < 48 hr onset of AFib/AFlut
• About ½ “low morbidity”
• ¼ HF Hx, ¼ CAD, 1/8 DM0
10
20
30
40
50
60
70
80 63.6%
BLS
Hospital Admit Rates
All Patients Low Acuity
80%
Pre Post Pre Post
Acad Emerg Med 2018;25:641-9
16.1%P < 0.001
31.3%P < 0.001
67.4%
43.7%
9/28/2018
29
NOTE
• Pharmacological conversions not attempted
• IV rate control discouraged
• 50 mg PO Metoprolol
• 120-180 mg PO Diltiazem ER
• D/C cardioversion not increased
Acad Emerg Med 2018;25:641-9
Additional Findings
• Cardioversion rates pre : post:- 21.2% vs 17.2%
• 3 day ED return for any reason:- 1.19 vs 1.0%
• 30 day ED returns- 3.8% vs 3.0%
• 90% followed up in AFib clinic
• 10% went outside system
Acad Emerg Med 2018;25:641-9
Simplified AFib Discharge PathwaysTake Homes
• Single center trial
• Very simple, very impressive
• < 48 hr not specifically cited
• stroke risk ?
• This protocol will have users
Acad Emerg Med 2018;in press August
• 450 pts, double-blind, placebo controlled
• 3 groups of pts from 3 Tunisian hospitals
• High dose vs Low dose vs Placebo
• MgSO4 9 grams vs 4.5 grams vs Placebo
• Given over 30 minutes
Is Magnesium effective for rate control in “Rapid” Atrial Fibrillation?
Measured effectiveness as HR < 90or rate lowering by > 20%
Acad Emerg Med 2018;in press August
0%
10%
20%
30%
40%
50%
60%
70% 59.5%64.2%
EffectivenessHR < 90 or HR > 20%
9 Grams 4.5 Grams
43.6%
--
Acad Emerg Med 2018;in press August
High Dose Mg Low Dose Mg Placebo
9/28/2018
30
This paper is not what it seems
Acad Emerg Med 2018;in press August
• Essentially all patients got other rate control agents
• 45-50% received Digoxin
• 30% received Diltiazem
• 20% received Beta Blockade
Magnesium for Rate Control in AFTake Homes
• Adjunct? – maybe; Primary – NO
• 2.5 grams or 4.5 grams?
• 9 grams = lots of flushing (10-15%)
• Was very safe, < 1% hypotension
• Read this paper carefully
Annal Emerg Med 2018;71:96-108
How effective and safe is Ibutilide for ED conversion of Atrial Fibrillation and Atrial Flutter?
• 361 pts, 21 community EDs, 2009-2015
• Recent onset AFib/Flutter
• 61 yo median age (53-71 IQR); QTc > 480: 30%
• Evaluated conversion rate and complications
Ibutilide
• Class III antiarrhythmic, K channel blockade
• Slowed repolarization with QTc
• Usual dose: 1 mg x 2, 10 minute interval
• VTACH and/or Torsade's up to 5% each
• Almost always within 45 min – 1 hr
Annal Emerg Med 2018;71:96-108
ECG monitoring s/p Ibutilide is 4 hours
Annal Emerg Med 2018;71:96-108
Highest Risk for Ibutilide(% in this study)
• Heart Failure patients (5%)
• Prolonged QTc (29.4% > 480 mg)
• Hypokalemia (3.1% < 3.5 meq)
• Hypomagnesemia (0.9% < 1.6 meq/L)
Annal Emerg Med 2018;71:96-108
9/28/2018
31
Methods
• 69% received rate reducing meds
• Most received Diltiazem
• Half also received 1-2 grams MgSO4
• 2/3 pre-Ibutilide Cardiology consult
Annal Emerg Med 2018;71:96-108
Results
• 44% conversion to NSR at 90 min
• 54.8% to NSR at 4 hrs
• 75% for Atrial Flutter
• 91.8% electrical cardioversion s/p Ibutilide
• 0.6% VTach incidence – both s/p 2nd dose
Annal Emerg Med 2018;71:96-108
IbutilideTake Homes
• Great pre cardioversion
• Not impressive alone
• Similar to procainamide
• Requires 4 hrs of monitoring
• Can be used if hypoK/hypomag **But give 2 grams MgSO4 pre-drug!
Acad Emerg Med 2018;25:1065-75
• EM, Card, EP, IM, APP, RN, Pharm D
• Provides Flow Chart
• Includes med and/or DC Cardioversion if possible
• Recommends use of Ibutilide or Flecainide
• D/C on NOAC if no contraindication
Clear onset < 48 hrsor
Adequately anticoagulated ≥ 4 weeksAcad Emerg Med 2018;25:1065-75
Cardioversion Recommendations
200 J A-P pad placement
Acad Emerg Med 2018;25:1065-75
Electrical Conversion
9/28/2018
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Acad Emerg Med 2018;25:1065-75
Pharmacological Conversion• Pretreat with 2 grams MgSO4 over 30 min
• 1 gram Ibutilide over 10 min
• May repeat 10 min after 1st dose
• Monitor for Torsades x 4 hrs
• Do not use if:QTC > 450 msec; Hypo K; EF < 30%
Summary
Epi survival but bad Neuro too
Summary
PCI all VF/VT survivors
Not witnessed, no shock, no ROSC
HyperK: R/O if CRF STEMI
HEART works – beware scores > 2
Beware detectable HS Troponin
Summary
Stress tests: do less
Use shared decision making
Low risk PE can go home
Develop an AFib pathway
VanderbiltEM.com
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