title: Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage.
abstract: BACKGROUND
  Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (PbtO2) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH).
  
  
  METHODS
  We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and PbtO2 were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs).
  
  
  RESULTS
  One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (PbtO2 <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. PbtO2 <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion.
  
  
  CONCLUSIONS
  Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH.
authors.forename: Alois J
authors.initials: AJ
authors.lastname: Schiefecker
authors.forename: Bettina
authors.initials: B
authors.lastname: Pfausler
authors.forename: Ronny
authors.initials: R
authors.lastname: Beer
authors.forename: Florian
authors.initials: F
authors.lastname: Sohm
authors.forename: Jan
authors.initials: J
authors.lastname: Sabo
authors.forename: Viktoria
authors.initials: V
authors.lastname: Knauseder
authors.forename: Marlene
authors.initials: M
authors.lastname: Fischer
authors.forename: Anelia
authors.initials: A
authors.lastname: Dietmann
authors.forename: Werner O
authors.initials: WO
authors.lastname: Hackl
authors.forename: Claudius
authors.initials: C
authors.lastname: Thomé
authors.forename: Erich
authors.initials: E
authors.lastname: Schmutzhard
authors.forename: Raimund
authors.initials: R
authors.lastname: Helbok
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004008:Diclofenac / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007263:Infusions, Parenteral; D007427:Intracranial Pressure / Q000187:drug effects; D008991:Monitoring, Physiologic; D010100:Oxygen / Q000378:metabolism*; D011446:Prospective Studies; D012189:Retrospective Studies; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D010100:Oxygen