title: Endogenous glycosides in critically ill patients.
abstract: OBJECTIVE
  To determine the incidence of critically ill patients displaying endogenous digitalis-like-immunoreactive substances (DLIS) and to examine the relationship of these hormones to routine laboratory variables, the underlying disease, myocardial function, hemodynamic status, severity of illness, systemic inflammation, and mortality rate.
  
  
  METHODS
  Sera of 401 consecutive critically ill patients, not treated with cardiac glycosides, were analyzed for DLIS (digitoxin and digoxin, TDx; Abbott Diagnostics, North Chicago, IL) and endogenous ouabain. Normal values of endogenous ouabain were determined in 62 healthy volunteers. We measured pro- and anti-inflammatory mediators (L-selectin, tumor necrosis factor-alpha, interleukin-1beta, interleukin-2, interleukin-6, interleukin-10), C-reactive protein, and serum amyloid A protein as well as patients' Acute Physiology and Chronic Health Evaluation II and Goris scores. In a subgroup of patients with a pulmonary artery catheter (n = 95), we determined cardiac output, pulmonary artery occlusion pressure, systemic and pulmonary vascular resistance, left ventricular stroke volume, and right and left stroke work.
  
  
  METHODS
  Two surgical intensive care units of an university hospital.
  
  
  METHODS
  Sera of 401 consecutive critically ill patients.
  
  
  METHODS
  Blood sampling.
  
  
  RESULTS
  Of the 401 patients tested, 343 had nonmeasurable DLIS concentrations (DLIS-negative), and 58 (14.5%) had positive digoxin (n = 18) or digitoxin (n = 34) concentrations (DLIS-positive) or were positive in both tests (n = 6). Mean endogenous ouabain concentrations were nine-fold increased in DLIS-positive (3.59 +/- 1.43 nmol/L) and three-fold increased in DLIS-negative (1.34 +/-.81 nmol/L) patients compared with controls (0.38 +/- 0.31 nmol/L). DLIS and ouabain concentrations closely correlated with the Acute Physiology and Chronic Health Evaluation II and Goris score and were associated with increased concentrations of transaminases, bilirubin, aldosterone, cortisol, serum creatinine, fractional sodium excretion, proinflammatory mediators, C-reactive protein, and serum amyloid A (p <or=.009). The hospital mortality rates of DLIS-positive and DLIS-negative patients were 12% and 3.2%, respectively, and for patients with ouabain concentrations above and below 2 nmol/L 38.6% and 0.6%, respectively. In DLIS-positive patients with pulmonary artery catheter (n = 23), cardiac output, stroke volume, and left ventricular stroke work were decreased, and pulmonary artery occlusion pressure and central venous pressure were increased (p <or=.009).
  
  
  CONCLUSIONS
  Different types of endogenous glycosides including endogenous ouabain are elevated in a significant proportion of critically ill patients. The occurrence of these substances is associated with increased morbidity and hospital mortality rates, possibly due to systemic inflammatory processes. DLIS but not endogenous ouabain concentrations were found to be related to left ventricular function.
authors.affiliation: Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Münster, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Berendes
authors.forename: Paul
authors.initials: P
authors.lastname: Cullen
authors.forename: H
authors.initials: H
authors.lastname: Van Aken
authors.forename: Walter
authors.initials: W
authors.lastname: Zidek
authors.forename: Michael
authors.initials: M
authors.lastname: Erren
authors.forename: Michael
authors.initials: M
authors.lastname: Hübschen
authors.forename: Thomas
authors.initials: T
authors.lastname: Weber
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirtz
authors.forename: Martin
authors.initials: M
authors.lastname: Tepel
authors.forename: Michael
authors.initials: M
authors.lastname: Walter
mesh_terms: D018806:APACHE; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002298:Cardenolides; D002302:Cardiac Output; D016022:Case-Control Studies; D002496:Central Venous Pressure; D016638:Critical Illness / Q000401:mortality; D004077:Digoxin / Q000097:blood*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D019041:L-Selectin / Q000097:blood; D007813:Laparotomy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure; D012503:Saponins / Q000097:blood*; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013318:Stroke Volume; D013896:Thoracic Diseases / Q000097:blood / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014947:Wounds and Injuries / Q000097:blood
chemical_list: D002298:Cardenolides; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012503:Saponins; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; C034504:digoxin-like factors; D019041:L-Selectin; D016753:Interleukin-10; D004077:Digoxin; D002097:C-Reactive Protein