title: A multicentre, randomised, open-label, controlled trial evaluating equivalence of inhalational and intravenous anaesthesia during elective craniotomy.
abstract: BACKGROUND
  A clear preference for intravenous or inhalational anaesthesia has not been established for craniotomy in patients without signs of cerebral hypertension.
  
  
  OBJECTIVE
  The NeuroMorfeo trial was designed to test equivalence of inhalational and intravenous anaesthesia maintenance techniques in the postoperative recovery of patients undergoing elective supratentorial surgery.
  
  
  METHODS
  This trial is a multicentre, randomised, open-label, equivalence design. A balanced stratified randomisation scheme was maintained using a centralised randomisation service. Equivalence was tested using the two one-sided tests procedure.
  
  
  METHODS
  Fourteen Italian neuroanaesthesia centres participated in the study from December 2007 to March 2009.
  
  
  METHODS
  Adults, 18 to 75 years old, scheduled for elective supratentorial intracranial surgery under general anaesthesia were eligible for enrolment if they had a normal preoperative level of consciousness and no clinical signs of intracranial hypertension.
  
  
  METHODS
  Patients were randomised to one of three anaesthesia maintenance protocols to determine if sevoflurane-remifentanil or sevoflurane-fentanyl were equivalent to propofol-remifentanil.
  
  
  METHODS
  The primary outcome was the time to achieve an Aldrete postanaesthesia score of at least 9 after tracheal extubation. Secondary endpoints included haemodynamic parameters, quality of the surgical field, perioperative neuroendocrine stress responses and routine postoperative assessments.
  
  
  RESULTS
  Four hundred and eleven patients [51% men, mean age 54.8 (SD 13.3) years] were enrolled. Primary outcome data were available for 380. Median (interquartiles) times to reach an Aldrete score of at least 9 were 3.48 (2.02 to 7.56), 3.25 (1.21 to 6.45) and 3.32  min (1.40 to 8.33) for sevoflurane-fentanyl, sevoflurane-remifentanil and propofol-remifentanil anaesthesia respectively, which confirmed equivalence using the two one-sided tests approach. Between-treatment differences in haemodynamic variables were small and not clinically relevant. Urinary catecholamine and cortisol responses had significantly lower activation with propofol-remifentanil. Postoperative pain and analgesic requirements were significantly higher in the remifentanil groups.
  
  
  CONCLUSIONS
  Equivalence was shown for inhalational and intravenous maintenance anaesthesia in times to reach an Aldrete score of at least 9 after tracheal extubation. Haemodynamic variables, the quality of surgical field and postoperative assessments were also similar. Perioperative endocrine stress responses were significantly blunted with propofol-remifentanil and higher analgesic requirements were recorded in the remifentanil groups.
  
  
  BACKGROUND
  Eudract 2007-005279-32.
authors.affiliation: Neuroanesthesia and Neurointensive Care Unit, Anestesia e Rianimazione, San Gerardo Hospital, via Pergolesi 33, Monza 20900, Milano, Italy. g.citerio@hsgerardo.org
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Citerio
authors.forename: Antonio
authors.initials: A
authors.lastname: Pesenti
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.forename: Simona
authors.initials: S
authors.lastname: Barlera
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.forename: Maria G
authors.initials: MG
authors.lastname: Franzosi
mesh_terms: D000328:Adult; D000368:Aged; D060666:Airway Extubation; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000704:Analysis of Variance; D000769:Anesthesia, Inhalation / Q000009:adverse effects; D000771:Anesthesia, Intravenous / Q000009:adverse effects; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000009:adverse effects; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003399:Craniotomy / Q000009:adverse effects; D017558:Elective Surgical Procedures; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007558:Italy; D016014:Linear Models; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010149:Postoperative Pain / Q000209:etiology / Q000517:prevention & control; D010880:Piperidines / Q000008:administration & dosage; D015742:Propofol / Q000008:administration & dosage* / Q000009:adverse effects; D020127:Recovery of Function; D000077208:Remifentanil; D000077149:Sevoflurane; D012768:Shivering / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D015415:Biomarkers; D008738:Methyl Ethers; D010880:Piperidines; D000077149:Sevoflurane; D000077208:Remifentanil; D005283:Fentanyl; D015742:Propofol