Anesthesiological Strategies in Elective Craniotomy - Full Text View

Purpose

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

Condition	Intervention	Phase
Anesthesia Craniotomy Neurosurgery	Drug: Sevoflurane + Fentanyl Drug: Sevoflurane + Remifentanyl Drug: Propofol + Remifentanyl	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Anesthesiological Strategies in Elective Craniotomy: Randomized, Equivalence, Open Trial

Resource links provided by NLM:

Drug Information available for: Fentanyl Fentanyl citrate Propofol Sevoflurane Remifentanil hydrochloride

U.S. FDA Resources

Further study details as provided by Azienda Ospedaliera San Gerardo di Monza:

Primary Outcome Measures:

Post-anesthesia awaking time, assessed as the interval (min:sec)required to reach an ALDRETE score ≥ 9 [ Time Frame: From estubation to aldrete score ≥ 9 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Neurovegetative stress [ Time Frame: From induction of anesthesia to 24 hours after surgery ] [ Designated as safety issue: No ]
Intraoperative and post-operative adverse events assessment [ Time Frame: From induction of anesthesia to 24 hours after surgery ] [ Designated as safety issue: Yes ]
Brain relaxation evaluated by a blinded neurosurgeon [ Time Frame: From induction of anesthesia to 24 hours after surgery ] [ Designated as safety issue: No ]
Patient's satisfaction [ Time Frame: From induction of anesthesia to 24 hours after surgery ] [ Designated as safety issue: No ]
Costs of the three strategies [ Time Frame: From induction of anesthesia to end of surgery ] [ Designated as safety issue: No ]

Enrollment:	411
Study Start Date:	December 2007
Study Completion Date:	December 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: IF Sevoflurane (Inhalation)+Fentanyl	Drug: Sevoflurane + Fentanyl 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
Experimental: IR Sevoflurane (Inhalation)+Remifentanyl	Drug: Sevoflurane + Remifentanyl 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
Experimental: ER Propofol (Endovenous)+ Remifentanyl	Drug: Propofol + Remifentanyl 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

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00741351

Locations

Italy
Policlinico Consorziale di Bari
Bari, Italy
Ospedale Bellaria Bologna
Bologna, Italy, 40100
Istituto di Ricerche Farmacologiche Mario Negri - Dipartimento di Ricerca Cardiovascolare-
Milan, Italy, 20100
IRCCS Fondazione San Raffaele Milano
Milan, Italy, 20100
Azienda Ospedaliera San Gerardo
Monza, Italy, 20052
Ospedale Maggiore della Carità di Novara
Novara, Italy, 28100
Ospedale di Padova
Padua, Italy, 35128
Azienda Ospedaliera di Parma
Parma, Italy, 43100
Policlinico "A. Gemelli" Roma
Rome, Italy
Policlinico "Umberto I" Roma
Rome, Italy
Azienda Universitaria Senese
Siena, Italy, 53100
Ospedale San giovanni Battista Torino
Turin, Italy
Ospedale San Giovanni Bosco Torino
Turin, Italy, 10057
Ospedale di Circolo e Fondazione Macchi Varese
Varese, Italy, 21100
Azienda Ospedaliera Universitaria di Verona
Verona, Italy, 37121

Sponsors and Collaborators

Azienda Ospedaliera San Gerardo di Monza

Investigators

Principal Investigator:	Giuseppe Citerio, MD	Azienda Ospedaliera San Gerardo Monza
Study Chair:	Antonio Pesenti, MD	Università delgi Studi Milano Bicocca
Study Chair:	Maria Grazia Franzosi, PhD	Istituto Di Ricerche Farmacologiche Mario Negri
Study Chair:	Roberto Latini, MD	Istituto Di Ricerche Farmacologiche Mario Negri

More Information

Publications:

Hans P, Bonhomme V. Why we still use intravenous drugs as the basic regimen for neurosurgical anaesthesia. Curr Opin Anaesthesiol. 2006 Oct;19(5):498-503. Review.

Todd MM, Warner DS, Sokoll MD, Maktabi MA, Hindman BJ, Scamman FL, Kirschner J. A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy. Propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide. Anesthesiology. 1993 Jun;78(6):1005-20.

Engelhard K, Werner C. Inhalational or intravenous anesthetics for craniotomies? Pro inhalational. Curr Opin Anaesthesiol. 2006 Oct;19(5):504-8. Review.

Magni G, Baisi F, La Rosa I, Imperiale C, Fabbrini V, Pennacchiotti ML, Rosa G. No difference in emergence time and early cognitive function between sevoflurane-fentanyl and propofol-remifentanil in patients undergoing craniotomy for supratentorial intracranial surgery. J Neurosurg Anesthesiol. 2005 Jul;17(3):134-8.

Talke P, Caldwell JE, Brown R, Dodson B, Howley J, Richardson CA. A comparison of three anesthetic techniques in patients undergoing craniotomy for supratentorial intracranial surgery. Anesth Analg. 2002 Aug;95(2):430-5, table of contents.

Gomberg-Maitland M, Frison L, Halperin JL. Active-control clinical trials to establish equivalence or noninferiority: methodological and statistical concepts linked to quality. Am Heart J. 2003 Sep;146(3):398-403.

Aldrete JA. The post-anesthesia recovery score revisited. J Clin Anesth. 1995 Feb;7(1):89-91. No abstract available.

Balakrishnan G, Raudzens P, Samra SK, Song K, Boening JA, Bosek V, Jamerson BD, Warner DS. A comparison of remifentanil and fentanyl in patients undergoing surgery for intracranial mass lesions. Anesth Analg. 2000 Jul;91(1):163-9.

Del Gaudio A, Ciritella P, Perrotta F, Puopolo M, Lauta E, Mastronardi P, De Vivo P. Remifentanil vs fentanyl with a target controlled propofol infusion in patients undergoing craniotomy for supratentorial lesions. Minerva Anestesiol. 2006 May;72(5):309-19. English, Italian.

Klingstedt C, Giesecke K, Hamberger B, Järnberg PO. High- and low-dose fentanyl anaesthesia: circulatory and plasma catecholamine responses during cholecystectomy. Br J Anaesth. 1987 Feb;59(2):184-8.

Nishiyama T, Yamashita K, Yokoyama T. Stress hormone changes in general anesthesia of long duration: isoflurane-nitrous oxide vs sevoflurane-nitrous oxide anesthesia. J Clin Anesth. 2005 Dec;17(8):586-91.

Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000 Jul;85(1):109-17. Review. No abstract available.

Bent JM, Paterson JL, Mashiter K, Hall GM. Effects of high-dose fentanyl anaesthesia on the established metabolic and endocrine response to surgery. Anaesthesia. 1984 Jan;39(1):19-23.

Heesen M, Deinsberger W, Dietrich GV, Detsch O, Boldt J, Hempelmann G. Increase of interleukin-6 plasma levels after elective craniotomy: influence of interleukin-10 and catecholamines. Acta Neurochir (Wien). 1996;138(1):77-80.

Ledowski T, Bein B, Hanss R, Paris A, Fudickar W, Scholz J, Tonner PH. Neuroendocrine stress response and heart rate variability: a comparison of total intravenous versus balanced anesthesia. Anesth Analg. 2005 Dec;101(6):1700-5.

Guzzetti S, Borroni E, Garbelli PE, Ceriani E, Della Bella P, Montano N, Cogliati C, Somers VK, Malliani A, Porta A. Symbolic dynamics of heart rate variability: a probe to investigate cardiac autonomic modulation. Circulation. 2005 Jul 26;112(4):465-70. Epub 2005 Jul 18. Erratum in: Circulation. 2005 Aug 30;112(9):e122. Mallani, Alberto [corrected to Malliani, Alberto].

Olsen KS, Pedersen CB, Madsen JB, Ravn LI, Schifter S. Vasoactive modulators during and after craniotomy: relation to postoperative hypertension. J Neurosurg Anesthesiol. 2002 Jul;14(3):171-9.

Leslie K, Troedel S. Does anaesthesia care affect the outcome following craniotomy? J Clin Neurosci. 2002 May;9(3):231-6. Review. No abstract available.

Hall GM, Young C, Holdcroft A, Alaghband-Zadeh J. Substrate mobilisation during surgery. A comparison between halothane and fentanyl anaesthesia. Anaesthesia. 1978 Nov-Dec;33(10):924-30.

Fung D, Cohen M, Stewart S, Davies A. Can the Iowa Satisfaction with Anesthesia Scale be used to measure patient satisfaction with cataract care under topical local anesthesia and monitored sedation at a community hospital? Anesth Analg. 2005 Jun;100(6):1637-43.

Citerio G, Stocchetti N, Cormio M, Beretta L. Neuro-Link, a computer-assisted database for head injury in intensive care. Acta Neurochir (Wien). 2000;142(7):769-76.

Piper I, Citerio G, Chambers I, Contant C, Enblad P, Fiddes H, Howells T, Kiening K, Nilsson P, Yau YH; BrainIT Group. The BrainIT group: concept and core dataset definition. Acta Neurochir (Wien). 2003 Aug;145(8):615-28; discussion 628-9.

Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ; CONSORT Group. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA. 2006 Mar 8;295(10):1152-60. Erratum in: JAMA. 2006 Oct 18;296(15):1842.

Le Henanff A, Giraudeau B, Baron G, Ravaud P. Quality of reporting of noninferiority and equivalence randomized trials. JAMA. 2006 Mar 8;295(10):1147-51.

Kaul S, Diamond GA. Good enough: a primer on the analysis and interpretation of noninferiority trials. Ann Intern Med. 2006 Jul 4;145(1):62-9.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Citerio G, Franzosi MG, Latini R, Masson S, Barlera S, Guzzetti S, Pesenti A. Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial--the NeuroMorfeo trial. Trials. 2009 Apr 6;10:19.

Responsible Party:	Dott. Giuseppe Citerio, MD, Azienda Ospedaliera San Gerardo di Monza
ClinicalTrials.gov Identifier:	NCT00741351 History of Changes
Other Study ID Numbers:	EudraCT number 2007-005279-32, AIFA FARM6FKJKK
Study First Received:	August 22, 2008
Last Updated:	September 7, 2011
Health Authority:	Italy: The Italian Medicines Agency

Keywords provided by Azienda Ospedaliera San Gerardo di Monza:

Anesthesia
Craniotomy
Neurosurgery

Additional relevant MeSH terms:

Fentanyl
Propofol
Remifentanil
Sevoflurane
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs

Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Analgesics, Opioid
Hypnotics and Sedatives
Platelet Aggregation Inhibitors
Hematologic Agents
Anesthetics, Inhalation

ClinicalTrials.gov processed this record on May 22, 2013

Anesthesiological Strategies in Elective Craniotomy (Neuromorfeo)