1. Department of OUTCOMES RESEARCH

2. Perioperative Myocardial Injury
Daniel I. Sessler, M.D.
Michael Cudahy Professor and Chair
Department of OUTCOMES RESEARCH
Cleveland Clinic

3. Perioperative Mortality
Intraoperative mortality rare
Thirty-day mortality
1% in the United States
2% worldwide for inpatients ≥45 years old
1000 times more common than intraop mortality
“Myocardial Injury after Non-cardiac Surgery” = MINS

4. Surgery is a Major Cause of Death
Bartels, Anesthesiology 2013

5. Causes of Postoperative Death
(%)
Adjusted HR
(95% CI)
Attributable Fraction
Myocardial injury 18
4 (3-5) 24
Major bleeding 14
3 (2-4)
Sepsis 4
5 (4-7) 9
New AF 1
2 (1-3) 2
Stroke
0.3
5 (3-10)
VISION: Devereaux, JAMA 2017

6. Common, Silent, and Deadly
MI incidence 4% among inpatients >45 years
Mortality is 4% at 30 days
Myocardial Injury after Non-cardiac Surgery
“MINS”
18% of inpatients >45 yrs have troponin increase
93% without symptoms
It’s not just “troponitis”
8.5% have MI, cardiac arrest, or death

7. High-sensitivity Troponin T
Only 22% met Universal Definition of MI — but they still died
Population attributable risks: Age – 40%, MINS – 34%, and sepsis – 30%. Mortality increase by squares: 2, 3, 5, 8, 15.

8. MINS (Troponin T Increase)
Outcome
No MINS
(n = 13,822), %
MINS
(n = 1,194), % OR
(95% CI)
Nonfatal arrest
0.1
0.8
15 (6-37)
CHF
1.0
9.4
10 (8-13)
Stroke
0.4
1.9
5 (3-8)
Death
1.1
9.8
Composite
2.4
18.8
10 (8-12)
VISION: Devereaux JAMA 2012; Botto, Anesthesiology 2014

9. Post-Op Troponin & Long-term Death
Beattie, JACC 2017

10. Professional Society Guidance
Universal Definition of MI
“Routine monitoring of cardiac biomarkers in high-risk patients … after major surgery is therefore recommended.”
Canadian Cardiovascular Society
“Daily troponin measurements for 2-3 days in patients with moderate cardiovascular risk

11. Troponin Monitoring Who: inpatient surgery and: When
Age >45 years and ≥1 risk cardiovascular risk factor
Age >65 years
When
Preoperatively
25% elevated preoperatively, mostly chronically
First two days while hospitalized
94% of elevations detected within 2 days
Response thresholds
Preoperative-to-postoperative increase >5 ng/L and postoperative >20 ng/L
Postoperative >65 ng/L

12. Elevated Troponin? Cardiology consult
Occasional patients need catheterization ± angioplasty
Discussion of risk
Aspirin (22% secondary reduction) ± statins or ACEIs
Only one-third of MINS patients current treated
Heart rate and hypertension control
Lifestyle
Smoking cessation
Reasonable diet
Exercise

13. Risk Prediction Revised Cardiac Risk Index Exercise tolerance
Well validated
But assigns >50% patients to “intermediate risk”
Exercise tolerance
Neither patients nor physicians estimate well
Unclear if exercise tolerance is predictive
Stress echo
Expensive and virtually useless
CT angiography
Worsens clinical risk assessment

14. Brain Natiuretic Protein
Rodseth, J Am Coll Card, 2014
Enhances Revised Cardiac Risk Index
Correctly identifies 16% more high-risk patients
Correctly identifies 15% more low-risk patients
BNP
MI or Death Risk
<100 ng/mL 5%
>250
27%
NT pro-BNP
Risk of MI or Death
<300 ng/mL 5%
26%
>3000
40%
Optimal ng/mL threshold is BNP <92 or NT pro-BNP <300

15. Preoperative Troponin
Nagele, Am Heart J, 2013

16. Prevention: POISE-1 8,350 at-risk inpatients >45 years randomized
Metoprolol 100 mg extended-release for 30 days
Placebo
Primary outcome: death, MI, cardiac arrest
Fewer composite outcomes: 5.8% vs. 6.9%
More strokes: 4.1% vs. 2.2%
More death: 3.1% vs. 2.3%
Beta blockers prevent MI, but increase death
Devereaux, Lancet, 2008

17. Prevention: ENIGMA-2 Background Hypothesis
N2O increases plasma homocysteine
N2O impairs endothelial function
Hypothesis
N2O increases 30-day death or major CV events
MI required troponin elevation & clinical event
Randomized trial in 7,000 high-risk patients
70% nitrous oxide
70% nitrogen
Myles, Lancet, 2014

19. Prevention: POISE-2 Surgery Aspirin Clonidine
Inflammatory response activates platelets
Promotes tachycardia
Aspirin
Impairs platelet aggregation
Prevents non-operative primary & secondary MI
Clonidine
Moderates central sympathetic activation
Heart rate control
Less hypotension than beta blockers
Devereaux, NEJM (2 papers) 2014

20. POISE-2 Design Inpatients >45 years at cardiovascular risk
Blinded 2 X 2 factorial trial
Aspirin 100 mg/day vs. placebo for 7 or 30 days
Clonidine 75 µg/day vs. placebo for 72 hours
Primary outcome
Death or MI within 30 days
MI required troponin elevation and clinical events
Safety outcomes
Life-threatening bleeding (i.e., required reoperation)
Clinically important hypotension (syst < 90 mmHg & Rx)
Clinically important bradycardia (HR <55/min & Rx)

21. Aspirin, Death & MI
20% increase in major bleeding

22. POISE-2 Results, Clonidine
30-50% increase in hypotension & bradycardia %

23. No Safe Prophylaxis for MI
POISE-1: Beta blockers
Decrease myocardial infarctions by 30%
Cause devastating strokes and death
ENIGMA-2
Nitrous oxide has no effect on MI
POISE-2
Aspirin does not reduce MI; life-threatening bleeding
Clonidine doesn’t reduce MI; bradycardia & hypotension

24. Association Between MAP & Death
Mascha, Anesth 2015

25. Hypotension & Myocardial Injury

26. Hypotension and AKI
Salmasi, Anesthesiology 2017

27. Vasopressors do not Worsen AKI
1,080 Matched patients
Major spine surgery
With and without phenylephrine infusion
Farag, unpublished

28. Timing of Hypotension
Maheshwari, unpublished

29. Futier, et al. JAMA 2017 Randomized trial, n=292 high-risk patients
Norepinephrine to keep systolic pressure ±10%
Ephedrine for systolic pressure <80 mmHg
Primary outcome
Systemic inflammation and organ failure
56/147 versus 75/145 patients
Relative risk [95% CI: 0.56, 0.94], P=0.02
Considerations
Actual difference in systolic pressure only 6 mmHg
Most difference in kidney injury & mental status
Only 1 myocardial infarction

30. Hold ACEIs and ARBs
Roshanov, Anesthesiology Holding ACEIs and ARBs on the day of surgery reduced hypotension and the risk of a composite of death, MINS, or stroke by about 20%.

31. Tachycardia Hardly Matters
Ruetzler, unpublished
Abbott reports increased MINS & MI with heart rate >100 b/min; A&A 2017

32. High Risk on Surgical Wards
Heart attacks occur postoperatively
94% within two days
50% of deaths during initial hospitalization
Ward hypoxemia and hypotension
Common, profound, and prolonged
Cannot be reliably predicted

33. Blinded Saturation Over Time
Sun, A&A 2015

34. Hypoxemic Episode Duration
Nurses missed 90% of patients who had 1 continuous hour of saturation <90% 34

35. Continuous Ward Hypotension (n=265)
Nurses missed 70% of patients with MAP <65 mmHg for 15 minutes
Chang, unpublished

36. Postop Hypotension Matters Too
Sessler Anesthesiology, in press
Adjusted for baseline risk and hypotension in previous periods

37. Pain and MINS
Adjusted for baseline risk, type and duration of surgery, etc.
Turan, unpublished

38. ICU Hypotension & MINS Khanna, unpublished MINS/Mortality
<90 mmHg
≥90 mmHg
Hazard ratio (95% CI)
(Per 10 mmHg difference)
(versus 90 mmHg)
Khanna, unpublished

39. ICU Hypotension & AKI

40. Summary Myocardial injury after non-cardiac surgery Monitor troponin
Common, deadly, and mostly silent
Monitor troponin
Inpatients >45 years at risk, & all inpatients >65 years
Preoperatively and first two postoperative days while hospitalized
Risk stratification
RCRI, NT-Pro-BNP, and preoperative troponin all help
No known safe prophylaxis
Keep intraoperative MAP >65mmHg; prevent postoperative hypotension
Hold ACEIs and ARBs on the day of surgery

41. Department of OUTCOMES
RESEARCH