Reduced Heart Rate Variability: An Indicator of Cardiac

Uncoupling and Diminished Physiologic Reserve in 1,425Trauma 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

BackgroundBackground

Cardiac uncoupling a predictor of mortalityCardiac uncoupling a predictor of mortality

– Cardiac uncoupling: Cardiac uncoupling: » the heart acting autonomously from central

regulation

– Reduction in heart rate variability(HRV) Reduction in heart rate variability(HRV) measured in the first 24 hrs of ICU staymeasured in the first 24 hrs of ICU stay

Physiologic reserve:Physiologic reserve:– Age, gender, pre-existiAge, gender, pre-existi

ng dxng dx

Physiologic exhaustioPhysiologic exhaustion:n:– Acidosis, coagulopathy,Acidosis, coagulopathy,

hypothermia hypothermia

Hypothesis:Hypothesis:– Deteriorating physiologic reserve triggers Deteriorating physiologic reserve triggers

cardiac uncoupling and foreshadows the onset cardiac uncoupling and foreshadows the onset of physiologic exhaustion.of physiologic exhaustion.

Methods -1Methods -1

Settings:Settings:– Vanderbilt University Medical Center(VUMC) Vanderbilt University Medical Center(VUMC)

level one trauma center. level one trauma center. – 3,500 trauma cases admitted annually3,500 trauma cases admitted annually– 31-bed dedicated trauma unit. 14 of 31 are ICU 31-bed dedicated trauma unit. 14 of 31 are ICU

beds. 700-800 admissions/yearbeds. 700-800 admissions/year

Method -2Method -2

Data source:Data source:– SIMON: data are prospectively captured during SIMON: data are prospectively captured during

the course of clinical care.the course of clinical care.– TRACS: more than 300 parameters are TRACS: more than 300 parameters are

captured via retrospectively.captured via retrospectively.– VUMC diagnostic laboratoryVUMC diagnostic laboratory

Inclusion criteria -1Inclusion criteria -1

Inclusion criteria -2Inclusion criteria -2

From DEC 15, 2000~ MAY 15, 2004From DEC 15, 2000~ MAY 15, 2004 Initial admission. Knock out in-hospital Initial admission. Knock out in-hospital

transfers or re-admissions.transfers or re-admissions.

Measurements -1Measurements -1

Demographics and outcome,Demographics and outcome,– Age, gender, ethnicity from TRACSAge, gender, ethnicity from TRACS

Physiologic reservePhysiologic reserve– Patient age and ISS, obtained form TRACSPatient age and ISS, obtained form TRACS

Measurements of physiologic reserveMeasurements of physiologic reserve– Acidosis, coagulopathy and hemorrhage severitAcidosis, coagulopathy and hemorrhage severit

yy Cardiac uncouplingCardiac uncoupling

Measurement -2Measurement -2 Acidosis: Acidosis:

– Initial lactate value(LACi)Initial lactate value(LACi)– Highest lactate value in 1Highest lactate value in 1stst 24 hrs after admissio 24 hrs after admissio

nn– Time to lactate normalization(LACt)Time to lactate normalization(LACt)

»△△ time: 1time: 1stst abnormal data till 1 abnormal data till 1stst normal data achiev normal data achieveded

» >72 hrs category for without a recorder normal data>72 hrs category for without a recorder normal data

– Deterioration in lactate over 1Deterioration in lactate over 1stst 24 hrs(LAC 24 hrs(LAC 24△24△ ))»△△ Data : admission data till highest abnormal data Data : admission data till highest abnormal data

{Normal lactate value: <2.5 mEq/L}

Measurement –3Measurement –3

Coagulopathy:Coagulopathy:– INRINR

Hemorrhage severityHemorrhage severity– Transfusion requirement (uPRBC)Transfusion requirement (uPRBC)

Measurement -4Measurement -4

Cardiac uncouplingCardiac uncoupling– Percentage of time in 1Percentage of time in 1stst 24 hrs that short-term 24 hrs that short-term

heart rate variability(HRV) falls within criticallheart rate variability(HRV) falls within critically low range.y low range.

{heart rate data is split into 5-min intervals}{heart rate data is split into 5-min intervals}

{critically low range: 0.3~0.6 bpm}{critically low range: 0.3~0.6 bpm}

Analysis Analysis

XX2 2 testtest Univariate logistic regressionUnivariate logistic regression

– Access the independence relationship between cardiac Access the independence relationship between cardiac uncoupling and each physiologic reserve.uncoupling and each physiologic reserve.

Multivariate logistic regressionMultivariate logistic regression– Characterize simultaneous contribution of multiple phyCharacterize simultaneous contribution of multiple phy

siologic reserve to risk of cardiac uncoupling.siologic reserve to risk of cardiac uncoupling.

Results -1Results -1

Results -2Results -2

Results -3Results -3

Results -4Results -4

57%

Results -5Results -5

Results -6Results -6

Results -7Results -7

Results -8Results -8

Discussions -1Discussions -1 Overview:Overview:

– Cardiac uncoupling fit nicely within the framework of Cardiac uncoupling fit nicely within the framework of physiologic reserve/exhaustion paradigm.physiologic reserve/exhaustion paradigm.

Strengths:Strengths:– Pts population is homogenousPts population is homogenous

– Data set is robust and uniqueData set is robust and unique

– Provide data on a new physiologic tool: cardiac Provide data on a new physiologic tool: cardiac uncoupling.uncoupling.

– possibility utilization of this noninvasive parameter for possibility utilization of this noninvasive parameter for prediction and evaluation in clinical practice.prediction and evaluation in clinical practice.

Discussions -2Discussions -2

Limitations:Limitations:– Current system does not contain reliable data on genetiCurrent system does not contain reliable data on geneti

cs, pre-existing disease, or preinjury medications.cs, pre-existing disease, or preinjury medications.

– Preinjury medication can affect in 2 ways:Preinjury medication can affect in 2 ways:» Certain medications have significant positive or negative effect Certain medications have significant positive or negative effect

on HRVon HRV

» Presence of preinjury anticoagulant/anti-platelet confusing prePresence of preinjury anticoagulant/anti-platelet confusing preexisting coagulopathy from consumptive coagulopathy. existing coagulopathy from consumptive coagulopathy.

– Relationship between hypothermia and cardiac uncouplRelationship between hypothermia and cardiac uncoupling is unknown.ing is unknown.

ConclusionsConclusions

Reduced heart rate variability is a new biomReduced heart rate variability is a new biomaker reflecting the loss of command and conaker reflecting the loss of command and control of the heart(cardiac uncoupling)trol of the heart(cardiac uncoupling)

Risk of cardiac uncoupling increase as physRisk of cardiac uncoupling increase as physiologic reserve deteriorating and physiologiiologic reserve deteriorating and physiologic exhaustion approaches.c exhaustion approaches.

Cardiac uncoupling provides a noninvasive, Cardiac uncoupling provides a noninvasive, overall measure of a pt’s clinical trajectory overall measure of a pt’s clinical trajectory over the 1over the 1stst 24 hrs. 24 hrs.