1. Reduced Heart Rate Variability: An Indicator of Cardiac Uncoupling and Diminished Physiologic Reserve in 1,425 Trauma Patients The Journal of TRAUMA Injury, Infection, and Critical Care. 60(6): 1165-1174, June 2006. John A. Morris Jr., MD, Patrick R. Norris, MS, Asli Ozdas, PhD, Lemuel R. Waitman, PhD, Frank E. Harrell Jr., PhD, Anna E. Williams, BA, Hanqing Cao, PhD, and Judith M. Jenkins, MS, RN

2. Background Cardiac uncoupling a predictor of mortality Cardiac uncoupling a predictor of mortality –Cardiac uncoupling: » »the heart acting autonomously from central regulation –Reduction in heart rate variability(HRV) measured in the first 24 hrs of ICU stay

3. Physiologic reserve: Physiologic reserve: –Age, gender, pre- existing dx Physiologic exhaustion: Physiologic exhaustion: –Acidosis, coagulopathy, hypothermia

4. Hypothesis: Hypothesis: –Deteriorating physiologic reserve triggers cardiac uncoupling and foreshadows the onset of physiologic exhaustion.

5. Methods -1 Settings: Settings: –Vanderbilt University Medical Center(VUMC) level one trauma center. –3,500 trauma cases admitted annually –31-bed dedicated trauma unit. 14 of 31 are ICU beds. 700-800 admissions/year

6. Method -2 Data source: Data source: –SIMON: data are prospectively captured during the course of clinical care. –TRACS: more than 300 parameters are captured via retrospectively. –VUMC diagnostic laboratory

7. Inclusion criteria -1

8. Inclusion criteria -2 From DEC 15, 2000~ MAY 15, 2004 From DEC 15, 2000~ MAY 15, 2004 Initial admission. Knock out in-hospital transfers or re-admissions. Initial admission. Knock out in-hospital transfers or re-admissions.

9. Measurements -1 Demographics and outcome, Demographics and outcome, –Age, gender, ethnicity from TRACS Physiologic reserve Physiologic reserve –Patient age and ISS, obtained form TRACS Measurements of physiologic reserve Measurements of physiologic reserve –Acidosis, coagulopathy and hemorrhage severity Cardiac uncoupling Cardiac uncoupling

10. Measurement -2 Acidosis: Acidosis: –Initial lactate value(LACi) –Highest lactate value in 1 st 24 hrs after admission –Time to lactate normalization(LACt) » △ time: 1 st abnormal data till 1 st normal data achieved »>72 hrs category for without a recorder normal data –Deterioration in lactate over 1 st 24 hrs(LAC △ 24 ) » △ Data : admission data till highest abnormal data {Normal lactate value: <2.5 mEq/L}

11. Measurement –3 Coagulopathy: Coagulopathy: –INR Hemorrhage severity Hemorrhage severity –Transfusion requirement (uPRBC)

12. Measurement -4 Cardiac uncoupling Cardiac uncoupling –Percentage of time in 1 st 24 hrs that short-term heart rate variability(HRV) falls within critically low range. {heart rate data is split into 5-min intervals} {critically low range: 0.3~0.6 bpm}

13. Analysis X 2 test X 2 test Univariate logistic regression Univariate logistic regression –Access the independence relationship between cardiac uncoupling and each physiologic reserve. Multivariate logistic regression Multivariate logistic regression –Characterize simultaneous contribution of multiple physiologic reserve to risk of cardiac uncoupling.

14. Results -1

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16. Results -3

17. Results -4 57%

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19. Results -6

20. Results -7

21. Results -8

22. Discussions -1 Overview: Overview: –Cardiac uncoupling fit nicely within the framework of physiologic reserve/exhaustion paradigm. Strengths: Strengths: –Pts population is homogenous –Data set is robust and unique –Provide data on a new physiologic tool: cardiac uncoupling. –possibility utilization of this noninvasive parameter for prediction and evaluation in clinical practice.

23. Discussions -2 Limitations: Limitations: –Current system does not contain reliable data on genetics, pre-existing disease, or preinjury medications. –Preinjury medication can affect in 2 ways: »Certain medications have significant positive or negative effect on HRV »Presence of preinjury anticoagulant/anti-platelet confusing preexisting coagulopathy from consumptive coagulopathy. –Relationship between hypothermia and cardiac uncoupling is unknown.

24. Conclusions Reduced heart rate variability is a new biomaker reflecting the loss of command and control of the heart(cardiac uncoupling) Reduced heart rate variability is a new biomaker reflecting the loss of command and control of the heart(cardiac uncoupling) Risk of cardiac uncoupling increase as physiologic reserve deteriorating and physiologic exhaustion approaches. Risk of cardiac uncoupling increase as physiologic reserve deteriorating and physiologic exhaustion approaches. Cardiac uncoupling provides a noninvasive, overall measure of a pt’s clinical trajectory over the 1 st 24 hrs. Cardiac uncoupling provides a noninvasive, overall measure of a pt’s clinical trajectory over the 1 st 24 hrs.