Post on 01-Apr-2015
Blood Pressure Control is an Independent Predictor of Short-term
Mortality in Cardiac Surgery Patients:
Solomon Aronson, M.D.FACC,FCCP,FAHA,FASE
Professor and Executive Vice ChairmanDept of Anesthesiology
Duke University Health System
Analysis from the Three Randomized ECLIPSE Trials
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Disclosures
► Abbott (Research Support)
► Baxter (Speaker)
► Medwave (Director)
► Regado Biosciences (Consultant)
► The Medicines Company (Consultant)
3
Acknowledgements
Cornelius Dyke, MD Dean Kereiakes, MD
Jerrold H. Levy, MD Philip Lumb, MD
Albert Cheung, MD Howard Corwin, MD
Kevin Stierer, MD Mark Newman, MD
4
Background
► Maintaining optimal BP control during cardiac surgery is a significant and common challenge1-5
► No studies to-date have shown an association between targeted peri-operative blood pressure control and mortality
► This relationship was examined as part of the ECLIPSE safety program
1 Aronson, S. Circulation 115,733-42,2007 2 Cheung, A. J Card Surg, 2006, S8 3 Aronson, S. Anesth Analg 2002; 94:1079-844 Estafanous, F. Am J Cardiol, 1980, p685; 5 Landymore, R. Can J Surg, 1980
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Objective
► To examine the relationship of targeted peri-operative BP control to mortality
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Setting
► ECLIPSE, a phase III safety program required for FDA registration of Clevidipine 1512 randomized cardiac surgery pts Comparators: Nitroglycerin (NTG), Sodium nitroprusside
(SNP), Nicardipine (NIC)
► BP measurements were captured over 24 hours Frequency: Q5 min (pre-/intra-op), Q15 min (post-op) up
to 4h and Q60 min after 4h
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Treatment
► Clevidipine Initiated 2 mg/hr Titrated doubling increments Q 90s to 16 mg/hr 40 mg/hr maximum
► Comparators (NTG, SNP, NIC) admin per institutional practice
► Treatment duration up to discharge from the ICU
► Concomitant anti-hypertensives discouraged
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Inclusion Criteria
Pre-randomization
► ≥ 18 years of age
► Written informed consent
► Planned CABG, OPCAB, MIDCAB surgery and/or valve repair/replacement surgery
Post-randomization
► Require treatment for peri-operative HTN
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Exclusion Criteria
► Women of child bearing potential
► CVA ≤ 3 months of randomization
► Intolerance to calcium channel blockers
► Hypersensitivity to NTG, SNP or NIC
► Allergy to the lipid vehicle
► Permanent ventricular pacing
► Any disease/condition that would put the patient at risk
► Participation in another trial within 30 days
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Statistical Analysis
► Data pooled for 1512 patients
► A multiple logistic regression analysis was performed to determine the association of BP control with 30-day mortality
► BP control was expressed as the cumulative area under the curve (AUC) outside specified SBP ranges
► AUC was analyzed as a continuous variable
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AUC Analysis
Time (hours)
SBP
Lower
Upper
0 6 12 2418
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Baseline Characteristics
PatientsN=1512
Age, median (range) 65 (19-89)
Male 73%
Caucasian 83%
History of HTN 86%
CHF 19%
COPD 14%
Recent MI (< 6 mos) 18%
Prior CABG 4%
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Procedural characteristics
PatientsN=1512
Treatment Clevidipine NTG SNP NIC
49.7%18.4%18.7%12.8%
Surgery duration, median hrs 3.28
Procedure CABG Valve replacement/repair CABG & Valve replacement/repair Other
77.0%13.1%9.7%0.2%
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Logistic Regression Model Selection
►Candidate variables included: Demographics Baseline characteristics Medical history Treatment group AUC Procedural characteristics
p<0.05 required for inclusion in final output
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Logistic Regression Results: Predictors of Mortality
P-Value Odds Ratio
95% CI [Lower Limit, Upper Limit]
Surgery Duration (hour) <0.0001 1.517 [1.240, 1.856]
Age (year) 0.0003 1.070 [1.031, 1.110]
Pre-op Creatinine ≥ 1.2 mg/dL 0.0031 2.670 [1.392, 5.122]
AUC (1mmHg*min) 0.0069 1.003 [1.001, 1.004]
Additional surgical procedures 0.0089 2.409 [1.246, 4.655]
Pre-op Hgb (g/dL) 0.0135 0.824 [0.707, 0.961]
Pre-op SBP >160 or DBP > 105 0.0228 2.386 [1.147, 4.963]
History of COPD 0.0228 2.326 [1.125, 4.812]
History of recent MI (<6 months prior) 0.0312 2.197 [1.073, 4.497]
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I mmHg x 60 min
2 mmHg x 60 min
3 mmHg x 60 min
4 mmHg x 60 min
5 mmHg x 60 min
30-Day Mortality by Magnitude of AUC
Odds Ratio
95% CI [Lower Limit, Upper Limit]
1.20 [1.06, 1.27]
1.43 [1.13, 1.61]
1.71 [1.20, 2.05]
2.05 [1.27, 2.61]
2.46 [1.35, 3.31]
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Conclusions
► Excursions outside a targeted BP range are correlated with 30-day mortality
► This relationship is direct and proportionate to the magnitude of excursions outside the BP range
► These data suggest that great attention should be given to precise peri-operative BP control
► Future analysis of this finding is warranted