title: Is heart-rate complexity a surrogate measure of cardiac output before, during, and after hemorrhage in a conscious sheep model of multiple hemorrhages and resuscitation?
abstract: BACKGROUND
  Despite its medical utility, continuous cardiac output (CO) monitoring remains a practical challenge on the battlefield and in the prehospital environment. Measuring a CO surrogate, perhaps heart-rate complexity (HRC), might be a viable solution when no direct monitoring of CO is available. Changes in HRC observed before and during hemorrhagic shock may be able to track the simultaneous changes in CO. The goal of this study was to test whether HRC is a surrogate measure of CO before, during, and after hemorrhage in a conscious sheep model of multiple hemorrhages and resuscitation.
  
  
  METHODS
  HRC was derived from 100-Hz electrocardiograms of 10 sheep records, 3 hours to 4 hours long, using the method of sample entropy. A real-time detection algorithm was used to detect the R-R interval sequences for HRC calculations. All records contained 100-Hz recordings of pulmonary arterial blood flow using Doppler transit time (criterion standard CO). Gold CO and estimated HRC values were analyzed using overlaid time-synchronized waveform plots as well as Bland-Altman, regression, and four-quadrant analysis.
  
  
  RESULTS
  Baseline CO varied from 3.0 L/min to 5.4 L/min, while posthemorrhage CO varied from 1.0 L/min to 1.8 L/min. Importantly, overlaid plots demonstrated an overall high similarity between CO and HRC waveforms before and during hemorrhage, but not during resuscitation. When the electrocardiogram quality was high, the correlation between CO and HRC within the first 45 minutes was greater than 0.75 (p < 0.0001; maximum r, 0.972). Scatter plots also depicted high linearity before and during hemorrhage. Four-quadrant analysis showed that instantaneous changes between consecutive beat-to-beat HRC measurements followed CO measurements (100% concordance rate), while 5-minute time points yielded a 76.19% concordance rate.
  
  
  CONCLUSIONS
  HRC has potential utility as a noninvasive tool for assessing the response of CO to life-threatening injuries such as hemorrhagic shock. However, further investigation and other animal models or human studies are needed.
authors.forename: Nehemiah T
authors.initials: NT
authors.lastname: Liu
authors.forename: George C
authors.initials: GC
authors.lastname: Kramer
authors.forename: Muzna N
authors.initials: MN
authors.lastname: Khan
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kinsky
authors.forename: José
authors.initials: J
authors.lastname: Salinas
mesh_terms: D000465:Algorithms; D000818:Animals; D002302:Cardiac Output / Q000502:physiology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006439:Hemodynamics; D017078:Laser-Doppler Flowmetry; D008887:Military Medicine; D011237:Predictive Value of Tests; D012151:Resuscitation; D012189:Retrospective Studies; D034561:Sheep, Domestic; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*; D014194:Traumatology / Q000379:methods*