title: Effects of indomethacin test on intracranial pressure and cerebral hemodynamics in patients with refractory intracranial hypertension:  a feasibility study.
abstract: BACKGROUND
  Intracranial hypertension is the final pathway of many neurocritical entities, such as spontaneous intracerebral hemorrhage (sICH) and severe traumatic brain injury (sTBI).
  
  
  OBJECTIVE
  This study aimed to (1) determine alterations in intracranial pressure (ICP) and cerebral hemodynamics after an indomethacin (INDO) infusion test and the related association with survival in patients with refractory intracranial hypertension (RICH) secondary to sICH or sTBI and (2) assess the safety profile after INDO.
  
  
  METHODS
  INDO was administered in a loading dose (0.8 mg/kg/15 min), followed by a 2-hour continuous infusion (0.5 mg/kg/h) in RICH patients with ICP greater than 20 mm Hg who did not respond to first-line therapies. Changes in ICP, cerebral perfusion pressure (CPP), and cerebrovascular variables (assessed by transcranial Doppler and jugular bulb saturation) were observed. Clinical outcome was assessed at 1 and 6 months according to the Glasgow Outcome Scale and correlated with INDO infusion test response. Analysis of INDO safety profile was conducted.
  
  
  RESULTS
  Thirteen sICH and 10 sTBI patients were studied. The median GCS score at admission was 6. Within 30 minutes of INDO infusion, ICP decreased (42.0 ± 13.5 vs 27.70 ± 12.7 mm Hg; Δ%: -48.4%; P < .001), and both CPP (57.7 ± 4.8 vs 71.9 ± 7.0 mm Hg; Δ%: +26.0%; P < .001) and middle cerebral artery velocity (35.2 ± 5.6 vs 42.0 ± 5.1 cm·s(-1); Δ%: +26.1%; P < .001) increased. The CPP response to a 2-hour INDO infusion test was correlated (R2 = 0.72, P < .001) with survival. No adverse events were observed after INDO.
  
  
  CONCLUSIONS
  Our findings support the effectiveness and feasibility of an INDO test in decreasing ICP and improving cerebral hemodynamics in surviving RICH patients. Future studies to evaluate different doses, lengths of infusion, and longer term effects are needed.
authors.affiliation: Neurocritical Care Unit, Sanatorio Pasteur, Catamarca, Argentina. dagodoytorres@yahoo.com.ar
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Godoy
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Rabinstein
authors.forename: Alberto
authors.initials: A
authors.lastname: Biestro
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ainslie
authors.forename: Mario
authors.initials: M
authors.lastname: Di Napoli
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002908:Chronic Disease; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use*; D019586:Intracranial Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D007427:Intracranial Pressure / Q000187:drug effects*; D008297:Male; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D007213:Indomethacin