title: Prior Use of Calcium Channel Blockers Is Associated With Decreased Mortality in Critically Ill Patients With Sepsis: A Prospective Observational Study.
abstract: OBJECTIVE
  Experimental studies suggest that calcium channel blockers can improve sepsis outcome. The aim of this study was to determine the association between prior use of calcium channel blockers and the outcome of patients admitted to the ICU with sepsis.
  
  
  METHODS
  A prospective observational study.
  
  
  METHODS
  The ICUs of two tertiary care hospitals in the Netherlands.
  
  
  METHODS
  In total, 1,060 consecutive patients admitted with sepsis were analyzed, 18.6% of whom used calcium channel blockers.
  
  
  METHODS
  None.
  
  
  RESULTS
  Considering large baseline differences between calcium channel blocker users and nonusers, a propensity score matched cohort was constructed to account for differential likelihoods of receiving calcium channel blockers. Fifteen plasma biomarkers providing insight in key host responses implicated in sepsis pathogenesis were measured during the first 4 days after admission. Severity of illness over the first 24 hours, sites of infection and causative pathogens were similar in both groups. Prior use of calcium channel blockers was associated with improved 30-day survival in the propensity-matched cohort (20.2% vs 32.9% in non-calcium channel blockers users; p = 0.009) and in multivariate analysis (odds ratio, 0.48; 95% CI, 0.31-0.74; p = 0.0007). Prior calcium channel blocker use was not associated with changes in the plasma levels of host biomarkers indicative of activation of the cytokine network, the vascular endothelium and the coagulation system, with the exception of antithrombin levels, which were less decreased in calcium channel blocker users.
  
  
  CONCLUSIONS
  Prior calcium channel blocker use is associated with reduced mortality in patients following ICU admission with sepsis.
authors.affiliation: 1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 2The Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 3Department of Clinical Epidemiology, Bioinformatics, and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 4Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 5Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 6Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, the Netherlands. 7Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. 8Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Maryse A
authors.initials: MA
authors.lastname: Wiewel
authors.forename: Lonneke A
authors.initials: LA
authors.lastname: van Vught
authors.forename: Brendon P
authors.initials: BP
authors.lastname: Scicluna
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.forename: Jos F
authors.initials: JF
authors.lastname: Frencken
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Janneke
authors.initials: J
authors.lastname: Horn
authors.forename: Olaf L
authors.initials: OL
authors.lastname: Cremer
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Bonten
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D018806:APACHE; D000368:Aged; D000991:Antithrombins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D016638:Critical Illness; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D018805:Sepsis / Q000097:blood* / Q000401:mortality*
chemical_list: D000991:Antithrombins; D015415:Biomarkers; D002121:Calcium Channel Blockers; D015850:Interleukin-6; D016209:Interleukin-8; D011486:Protein C