title: Elevated serum creatine phosphokinase is associated with mortality  and inotropic requirement in critically injured adults.
abstract: BACKGROUND
  Hemeproteins such as free myoglobin can undergo autoxidation and catalyse lipid peroxidation, increasing oxidative stress. Creatine phosphokinase (CPK) elevation is a marker for free myoglobin after myocyte damage. Since oxidative injury is a key mechanism of injury-related organ dysfunction, we hypothesised that serum CPK levels correlate with mortality and need for inotropic medication and duration of inotropic support, i.e. shock, among critically injured patients.
  
  
  METHODS
  We conducted a retrospective review of 17,847 patients admitted to a single Trauma Intensive Care Unit over 9 years. 2583 patients with serum CPK levels were included in the analysis. Patient data were collected continuously into an electronic ICU repository. Univariate analysis was accomplished using Spearman correlation and the Mann–Whitney U test. Propensity score adjustment models accounting for potential confounders were used to assess the independent effect of CPK level on mortality, need for inotropic support, and duration of inotropic support.
  
  
  RESULTS
  Median CPK was significantly higher in patients who died (916 [IQR 332, 2472] vs. 711 [253, 1971], p = 0.004) and in those who required inotropic medications (950 [353, 2525] vs. 469 [188, 1220], p < 0.001). After adjusting for propensity score and potential confounders the odds of mortality increased by 1.10 (95% CI 1.02–1.19, p = 0.020) and the odds of inotropic medication use increased by 1.30 (95% CI 1.22–1.38, p < 0.001) per natural log unit increase in CPK. There was a significant association between CPK level and duration of inotropic support (Spearman's rho .237, p < 0.001) that remained significant in a propensity score-adjusted model.
  
  
  CONCLUSIONS
  In critically injured patients, elevated serum CPK level is independently associated with mortality, need for inotropic medication, and duration of inotropic support. This study is the first to evaluate the relationship of CPK level and mortality in addition to surrogate measures of shock in a population of critically injured patients. If these associations are verified prospectively, there may be a role for treatment with hemeprotein reductants, such as paracetamol, to mitigate the effects of shock and end-organ dysfunction.
authors.forename: Kendell J
authors.initials: KJ
authors.lastname: Sowards
authors.forename: Kaushik
authors.initials: K
authors.lastname: Mukherjee
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Norris
authors.forename: Ayumi
authors.initials: A
authors.lastname: Shintani
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: Addison K
authors.initials: AK
authors.lastname: May
mesh_terms: D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood*; D016638:Critical Illness / Q000401:mortality* / Q000628:therapy; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000201:enzymology* / Q000401:mortality* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D002316:Cardiotonic Agents; D003402:Creatine Kinase