Anesthesiological Strategies in Elective Craniotomy

Anesthesia Clinical Trial

— Neuromorfeo  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00741351
• Other study ID #: EudraCT number 2007-005279-32
• Secondary ID: AIFA FARM6FKJKK
• Status: Completed
• Phase: Phase 3
• First received: August 22, 2008
• Last updated: September 7, 2011
• Start date: December 2007
• Est. completion date: December 2009

Study information

• Verified date: September 2011
• Source: Azienda Ospedaliera San Gerardo di Monza
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 411
• Est. completion date: December 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anesthesia
• Craniotomy
• Neurosurgery

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Italy	Policlinico Consorziale di Bari	Bari
Italy	Ospedale Bellaria Bologna	Bologna
Italy	IRCCS Fondazione San Raffaele Milano	Milan
Italy	Istituto di Ricerche Farmacologiche Mario Negri - Dipartimento di Ricerca Cardiovascolare-	Milan
Italy	Azienda Ospedaliera San Gerardo	Monza
Italy	Ospedale Maggiore della Carità di Novara	Novara
Italy	Ospedale di Padova	Padua
Italy	Azienda Ospedaliera di Parma	Parma
Italy	Policlinico "A. Gemelli" Roma	Rome
Italy	Policlinico "Umberto I" Roma	Rome
Italy	Azienda Universitaria Senese	Siena
Italy	Ospedale San giovanni Battista Torino	Turin
Italy	Ospedale San Giovanni Bosco Torino	Turin
Italy	Ospedale di Circolo e Fondazione Macchi Varese	Varese
Italy	Azienda Ospedaliera Universitaria di Verona	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera San Gerardo di Monza

Country where clinical trial is conducted

Italy, 

References & Publications (25)

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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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000 Jul;85(1):109-17. Review. — View Citation

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

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. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Leslie K, Troedel S. Does anaesthesia care affect the outcome following craniotomy? J Clin Neurosci. 2002 May;9(3):231-6. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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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. — View Citation

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. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-anesthesia awaking time, assessed as the interval (min:sec)required to reach an ALDRETE score = 9		From estubation to aldrete score = 9	No
Secondary	Neurovegetative stress		From induction of anesthesia to 24 hours after surgery	No
Secondary	Intraoperative and post-operative adverse events assessment		From induction of anesthesia to 24 hours after surgery	Yes
Secondary	Brain relaxation evaluated by a blinded neurosurgeon		From induction of anesthesia to 24 hours after surgery	No
Secondary	Patient's satisfaction		From induction of anesthesia to 24 hours after surgery	No
Secondary	Costs of the three strategies		From induction of anesthesia to end of surgery	No