A multicentre, randomised, open-label, controlled trial evaluating equivalence of inhalational and intravenous anaesthesia during elective craniotomy

Eur J Anaesthesiol. 2012 Aug;29(8):371-9. doi: 10.1097/EJA.0b013e32835422db.

Abstract

Context: A clear preference for intravenous or inhalational anaesthesia has not been established for craniotomy in patients without signs of cerebral hypertension.

Objectives: 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.

Design: 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.

Setting: Fourteen Italian neuroanaesthesia centres participated in the study from December 2007 to March 2009.

Patients: 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.

Interventions: Patients were randomised to one of three anaesthesia maintenance protocols to determine if sevoflurane-remifentanil or sevoflurane-fentanyl were equivalent to propofol-remifentanil.

Main outcome measures: 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.

Conclusion: 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.

Trial registration: Eudract 2007-005279-32.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Airway Extubation
  • Analgesics, Opioid / administration & dosage
  • Analysis of Variance
  • Anesthesia, Inhalation* / adverse effects
  • Anesthesia, Intravenous* / adverse effects
  • Anesthetics, Inhalation / administration & dosage*
  • Anesthetics, Inhalation / adverse effects
  • Anesthetics, Intravenous / administration & dosage*
  • Anesthetics, Intravenous / adverse effects
  • Biomarkers / blood
  • Chi-Square Distribution
  • Craniotomy* / adverse effects
  • Elective Surgical Procedures
  • Female
  • Fentanyl / administration & dosage
  • Hemodynamics / drug effects
  • Humans
  • Italy
  • Linear Models
  • Male
  • Methyl Ethers / administration & dosage*
  • Methyl Ethers / adverse effects
  • Middle Aged
  • Piperidines / administration & dosage
  • Postoperative Pain / etiology
  • Postoperative Pain / prevention & control
  • Propofol / administration & dosage*
  • Propofol / adverse effects
  • Recovery of Function
  • Remifentanil
  • Sevoflurane
  • Shivering / drug effects
  • Time Factors
  • Treatment Outcome

Substances

  • Analgesics, Opioid
  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Biomarkers
  • Methyl Ethers
  • Piperidines
  • Sevoflurane
  • Remifentanil
  • Fentanyl
  • Propofol