Anesthesiological Strategies in Elective Craniotomy

Study Overview
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Brief Summary
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This protocol, NeuroMorfeo, aims to assess equivalence between volatile and intravenous anesthetics for neurosurgical procedures.

Detailed Description
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NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for a elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state evaluated with the ASA (I-III) and Glasgow Coma Scale (GCS) equal to 15, will be randomly assigned to one of three anesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanesthesia will be evaluated by comparing the intervals required to reach, after anesthesia discontinuation, a modified Aldrete score ≥ 9 (primary end-point). Two statistical comparisons have been planned: 1) sevoflurane + fentanyl vs. propofol + remifentanil; 2) sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anesthesia; intraoperative adverse events (i.e. hypotension, hypertension, requirement of osmotic agents or/and hyperventilation for controlling brain swelling); evaluation of surgical field; postoperative adverse events (as seizures, cough, shivering, agitation, postoperative hematoma and postoperative pain); patient's satisfaction and an analysis of costs. 411 patients will be recruited in 14 different Italian centers during an 18-month period. The recruitment started December 20th, 2007 and up to 11th March 2009.

Official Title
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Anesthesiological Strategies in Elective Craniotomy: Randomized, Equivalence, Open Trial

Conditions
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Anesthesia, Craniotomy, Neurosurgery

Intervention / Treatment
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* Drug: Sevoflurane + Fentanyl
* Drug: Sevoflurane + Remifentanyl
* Drug: Propofol + Remifentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patient scheduled for elective intracranial surgery under general anesthesia for a supratentorial mass lesion in the next 24 hours; Physical state, evaluated with the ASA (American Society of Anesthesiologists ) classification I (normal healthy patient), II (patient with mild systemic disease), or III (patient with severe systemic disease); Age 18-75 years; Normal preoperative level of consciousness, i.e. Glasgow Coma Scale (GCS) = 15; No signs of intracranial hypertension. Exclusion criteria: Severe cardiovascular pathology, as uncontrolled arterial hypertension, documented reduced coronary reserve. Renal or liver disease precluding the use of either anesthetic technique. Pregnancy . Known allergies to any anesthetic agent. Reduced preoperative level of consciousness, i.e. Glasgow Coma Scale (GCS) < 15. Body weight greater than 120 kg. History of drug abuse or psychiatric conditions. Documented disturbance of the hypothalamic region.Refusal to sign consent form. Participation in other clinical trials. Delayed awakening, because, due to the location or size of the lesion, postoperative sedation and mechanical ventilation are planned.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IF<br>Sevoflurane (Inhalation)+Fentanyl | Drug: Sevoflurane + Fentanyl<br>* Sevoflurane is maintained in a MAC range (0.75% to 1.25%) and fentanyl (2-3 microg/kg/hr or 0.7 microg/kg boluses). Just before incision of the scalp, fentanyl (1-2microg/kg/hr) can be supplemented, if necessary<br>|
| Experimental: IR<br>Sevoflurane (Inhalation)+Remifentanyl | Drug: Sevoflurane + Remifentanyl<br>* Sevoflurane is maintained in a MAC range (0.75% to 1.25%) and remifentanil (0.5-0.25 microg/kg/min reduced to 0.05-0.1 microg/kg/min after dural opening). Just before incision of the scalp, remifentanil can be supplemented, if necessary<br>|
| Experimental: ER<br>Propofol (Endovenous)+ Remifentanyl | Drug: Propofol + Remifentanyl<br>* Propofol is maintained with continuous infusion at 10 mg/kg/h for the first 10 minutes, then reduced to 8 mg/kg/h for the following 10 minutes and reduced to 6mg/kg/h thereafter and remifentanil 0.5-0.25 microg/kg/min reduced to 0.05-0.1 microg/kg/min after dural opening. Just before incision of the scalp, remifentanil could be supplemented, if necessary<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-anesthesia awaking time, assessed as the interval (min:sec)required to reach an ALDRETE score ≥ 9 |  | From estubation to aldrete score ≥ 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurovegetative stress |  | From induction of anesthesia to 24 hours after surgery | 
| Intraoperative and post-operative adverse events assessment |  | From induction of anesthesia to 24 hours after surgery | 
| Brain relaxation evaluated by a blinded neurosurgeon |  | From induction of anesthesia to 24 hours after surgery | 
| Patient's satisfaction |  | From induction of anesthesia to 24 hours after surgery | 
| Costs of the three strategies |  | From induction of anesthesia to end of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthesia, Craniotomy, Neurosurgery