title: Multi-complexity measures of heart rate variability and the effect of vasopressor titration: a prospective cohort study of patients with septic shock.
abstract: BACKGROUND
  Septic shock is a common and often devastating syndrome marked by severe cardiovascular dysfunction commonly managed with vasopressors. Whether markers of heart rate complexity before vasopressor up-titration could be used to predict success of the up-titration is not known.
  
  
  METHODS
  We studied patients with septic shock requiring vasopressor, newly admitted to the intensive care unit. We measured the complexity of heart rate variability (using the ratio of fractal exponents from detrended fluctuation analysis) in the 5 min before all vasopressor up-titrations in the first 24 h of an intensive care unit (ICU) admission. A successful up-titration was defined as one that did not require further up-titration (or decrease in mean arterial pressure) for 60 min.
  
  
  RESULTS
  We studied 95 patients with septic shock, with a median APACHE II of 27 (IQR: 20-37). The median number of up-titrations, normalized to 24 h, was 12.2 (IQR: 8-17) with a maximum of 49. Of the up-titrations, the median proportion of successful interventions was 0.28 (IQR: 0.12-0.42). The median of mean arterial pressure (MAP) at the time of a vasopressor up-titration was 66 mmHg; the average infusion rate of norepinephrine at the time of an up-titration was 0.11 mcg/kg/min. The ratio of fractal exponents was not associated with successful up-titration on univariate or multivariate regression. On exploratory secondary analyses, however, the long-term fractal exponent was associated (p = 0.003) with success of up-titration. Independent of heart rate variability, MAP was associated (p < 0.001) with success of vasopressor up-titration, while neither Sequential Organ Failure Assessment (SOFA) nor Acute Physiology and Chronic Health Evaluation II (APACHE II) score was associated with vasopressor titration.
  
  
  CONCLUSIONS
  Only a third of vasopressor up-titrations were successful among patients with septic shock. MAP and the long-term fractal exponent were associated with success of up-titration. These two, complementary variables may be important to the development of rational vasopressor titration protocols.
authors.affiliation: Pulmonary and Critical Care, Intermountain Medical Center, Murray, UT, USA. samuel.brown@imail.org.|Pulmonary and Critical Care, University of Utah School of Medicine, Salt Lake City, UT, USA. samuel.brown@imail.org.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Brown
authors.affiliation: Pulmonary and Critical Care, Intermountain Medical Center, Murray, UT, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sorensen
authors.affiliation: Pulmonary and Critical Care, Intermountain Medical Center, Murray, UT, USA.|Pulmonary and Critical Care, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lanspa
authors.affiliation: Internal Medicine, University of Utah Medical Center and School of Medicine and George E. Wahlen VA Medical Center, Salt Lake City, UT, USA.|Molecular Medicine Program in the Eccles Institute of Human Genetics, Salt Lake City, UT, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Rondina
authors.affiliation: Pulmonary and Critical Care, Intermountain Medical Center, Murray, UT, USA.|Pulmonary and Critical Care, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Colin K
authors.initials: CK
authors.lastname: Grissom
authors.affiliation: Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA.
authors.forename: Sajid
authors.initials: S
authors.lastname: Shahul
authors.affiliation: School of Electrical Engineering & Computer Science, Oregon State University, Corvallis, OR, USA.
authors.forename: V J
authors.initials: VJ
authors.lastname: Mathews
mesh_terms: D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology*; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014662:Vasoconstrictor Agents
keywords: Heart Rate Variability; Physiological Variability; Sepsis; Shock