Intravenous Versus Inhalational Anesthesia in Parkinson's Disease

• Sponsor: Columbia University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00615472
• Collaborator: (none)
• Enrollment: 58
• Location: 1
• Arms: 2
• Duration (Months): 90
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Parkinson's disease is a common progressive degenerative disease affecting 3% of all patients over the age of 65. Given their age and frailty, these patients frequently require surgical procedures with general anesthesia. However, after surgery, patients with Parkinson's disease have longer hospital stays and a greater chance of not returning to independent living compared to age-matched controls (Berman MF, unpublished data). In part, this is due to a higher rate of post-operative delirium, which had an incidence of 60% in this population in one study. There is anecdotal evidence from neurologists specializing in movement disorder suggesting that there is also significant deterioration in parkinsonian motor symptoms and cognition lasting for months or years following surgery and anesthesia. The basis for this deterioration is unknown. We hypothesize that these problems are caused by particular medications used during inhaled anesthesia for surgical procedures.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: Isoflurane; Drug: Remifentanil; Drug: Propofol	N/A

Detailed Description

We will compare the groups in terms of postoperative delirium, and cognitive and motor function changes. Patients randomized to an inhaled anesthetic will receive a standard anesthetic mix: an inhaled anesthetic with intravenous agents for rapid induction of anesthesia, narcotics for postoperative pain relief, and muscle relaxation. Patients randomized to IV anesthesia will receive a continuous infusion of propofol and remifentanil (ultrashort acting narcotic) instead of the inhalation anesthetics during the maintenance phase of the anesthetic. Other components of the anesthetic will be the same as in the "inhaled anesthetic" group.

We hypothesize that:

1. Patients with Parkinson's disease will have less postoperative delirium and less prolonged cognitive and motor changes after total intravenous anesthesia than following inhaled anesthesia.

2. Apolipoprotein E4 (Apo E4) allele will be associated with postoperative cognitive dysfunction in Parkinsonian patients

To test our hypotheses we will:

1. Randomize patients with Parkinson's disease having surgery for implantation of current generator for subthalamic stimulator to receive either a total intravenous anesthetic or an inhaled anesthetic.

2. Compare these two groups of patients for incidence of postoperative delirium and the degree of postoperative cognitive and motor dysfunction.

3. Test for an association between the (Apo E4) allele and postoperative cognitive change. A buccal sampling or cheek cell sampling method will be employed to obtain DNA for genotyping of the Apo E allele.

During the procedure, maintenance of anesthesia will differ for the two groups:

Group 1 Inhaled anesthesia: Patients will be maintained on oxygen and isoflurane 0 to 4%, titrated as needed to maintain a standard blood pressure (standard practice).

Group 2 Intravenous anesthesia: Patients will be ventilated with 50% oxygen in air. Patients will receive continuous propofol infusion 0.05 mg/kgmin to 0.15 mg/kgmin titrated as needed; and remifentanil (ultrashort acting narcotic) 0.1 ug/kgmin to 0.5 ug/kgmin. These will be titrated as needed to maintain a standard blood pressure. Both infusions will be turned off at the end of the procedure.

Testing of Motor and Cognitive Status. Patients who participate in the study will be given a mental status examination, tests of Parkinsonian motor symptoms, and tests of cognitive function in the preoperative period before implantation of the subthalamic electrodes and implantation of current generators. Subsets of these tests will be performed several times postoperatively (1 month and 4 months)

Implantation of Electrode (Stage I sedation anesthesia) Full testing will be done in the preoperative period. Patients are generally kept in the hospital overnight and discharged the following day. Mental status will be rechecked by the MMSE in the recovery room postoperatively .

Patients will be contacted by telephone to have their mental status assessed by telephone using using two well known examinations (Telephone Interview for Cognitive Status (TICS) and Centers for Disease Control and Prevention Health-Related Quality-of-Life 14Item Measure (CDC HRQOL14)) and a series of questions investigating how well patients are able to perform activities of daily living (ADLs) and instrumental activities of daily living (IADLs). These tests will be given at two time points, once before the surgery and then one month after surgery. We will look for changes in quality of life that may correlate with neuropsychometric test performance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Intravenous General Anesthesia Versus Inhalational General Anesthesia in Parkinson's Disease
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Inhaled Anesthesia - isoflurane	Drug: Isoflurane; Group 1 Inhaled anesthesia Patients will be maintained on 50% oxygen in air and isoflurane 0 to 4%, titrated as needed to maintain a standard blood pressure (standard practice). If needed, muscle relaxation will be provided by additional boluses or an infusion of mivacurium (4-10 ug/kg/min).; Other Names: Forane
Experimental: Group 2 Intravenous Anesthesia - propofol, remifentanil	Drug: Remifentanil; Group 2 Intravenous anesthesia Patients will be ventilated with 50% oxygen in air. Patients will receive continuous propofol infusion 0.05 mg/kg-min to 0.15 mg/kg-min titrated as needed; and remifentanil (ultra-short acting narcotic) 0.1 ug/kg-min to 0.5 ug/kg-min. These will be titrated as needed to maintain a standard blood pressure. Both infusions will be turned off at the end of the procedure. If needed, muscle relaxation will be provided by additional boluses or an infusion of mivacurium (4-10 ug/kg/min).; Other Names: Ultiva ; Drug: Propofol; Group 2 Intravenous anesthesia Patients will be ventilated with 50% oxygen in air. Patients will receive continuous propofol infusion 0.05 mg/kg-min to 0.15 mg/kg-min titrated as needed; and remifentanil (ultra-short acting narcotic) 0.1 ug/kg-min to 0.5 ug/kg-min. These will be titrated as needed to maintain a standard blood pressure. Both infusions will be turned off at the end of the procedure. If needed, muscle relaxation will be provided by additional boluses or an infusion of mivacurium (4-10 ug/kg/min).; Other Names: Diprivan

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Improved Postoperative Delirium and Cognitive and Motor Changes [Four months]

   A battery/Questionnaire of neuropsych examinations is given to the subjects to measure improvement based on change of scores and standard deviation. The battery consists of questions regarding delirium, cognitive and motor changes and yields a combination assessment of all 3 elements.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnosis of Parkinson's Disease with bilateral deep brain stimulation surgery indicated as treatment

Exclusion Criteria:

• Not fluent in English

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia Unviversity, Deparment of Anesthesiology	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University

Investigators

• Principal Investigator: Eric J Heyer, M.D., Ph.D., Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ali HH, Savarese JJ, Embree PB, Basta SJ, Stout RG, Bottros LH, Weakly JN. Clinical pharmacology of mivacurium chloride (BW B1090U) infusion: comparison with vecuronium and atracurium. Br J Anaesth. 1988 Nov;61(5):541-6.
• Brandt R, Spencer M, Folstein M: The Telephone Interview for Cognitive Status. Neuropsychiatry, Neuropsychology, and Behavioral Neurology 1:111-117, 1988.
• Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993 Aug 13;261(5123):921-3.
• Culley DJ, Yukhananov RY, Baxter MB, Crosby G: Longerterm cognitive performance after general anesthesia in aged rats. J Neurosurg Anesthesiol 12:395 (abstract 325), 2000.
• Friedman G, Froom P, Sazbon L, Grinblatt I, Shochina M, Tsenter J, Babaey S, Yehuda B, Groswasser Z. Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology. 1999 Jan 15;52(2):244-8.
• Golden WE, Lavender RC, Metzer WS. Acute postoperative confusion and hallucinations in Parkinson disease. Ann Intern Med. 1989 Aug 1;111(3):218-22.
• Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. Erratum in: Lancet 1998 Jun 6;351(9117):1742.
• Newman MF, Croughwell ND, Blumenthal JA, Lowry E, White WD, Spillane W, Davis RD Jr, Glower DD, Smith LR, Mahanna EP, et al. Predictors of cognitive decline after cardiac operation. Ann Thorac Surg. 1995 May;59(5):1326-30.
• Patten D, Foxon GR, Martin KF, Halliwell RF. An electrophysiological study of the effects of propofol on native neuronal ligand-gated ion channels. Clin Exp Pharmacol Physiol. 2001 May-Jun;28(5-6):451-8.
• Pepper PV, Goldstein MK. Postoperative complications in Parkinson's disease. J Am Geriatr Soc. 1999 Aug;47(8):967-72.
• Ruberg M, Ploska A, Javoy-Agid F, Agid Y. Muscarinic binding and choline acetyltransferase activity in Parkinsonian subjects with reference to dementia. Brain Res. 1982 Jan 28;232(1):129-39.
• Spreen O, Strauss E: A compendium of Neuropsychological tests. New York, Oxford University Press, 1998, ed second.
• van Laar T, Jansen EN, Essink AW, Neef C, Oosterloo S, Roos RA. A double-blind study of the efficacy of apomorphine and its assessment in 'off'-periods in Parkinson's disease. Clin Neurol Neurosurg. 1993 Sep;95(3):231-5.
• Violet JM, Downie DL, Nakisa RC, Lieb WR, Franks NP. Differential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics. Anesthesiology. 1997 Apr;86(4):866-74.
• Williams-Russo P, Sharrock NE, Mattis S, Szatrowski TP, Charlson ME. Cognitive effects after epidural vs general anesthesia in older adults. A randomized trial. JAMA. 1995 Jul 5;274(1):44-50.

• Responsible Party: Eric J. Heyer, MD, PhD, Professor of Clinical Anesthesiology, Columbia University
• ClinicalTrials.gov Identifier: NCT00615472
• Other Study ID Numbers: AAAA4885
• First Posted: Feb 14, 2008
• Last Update Posted: Jul 13, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Eric J. Heyer, MD, PhD, Professor of Clinical Anesthesiology, Columbia University: Parkinson's Disease; Deep brain stimulation (DBS); Subthalamic Nucleus; Total Intravenous Anesthesia; Inhalational Anesthesia
• Additional relevant MeSH terms: Parkinson Disease; Remifentanil; Propofol; Isoflurane

Study Results

Participant Flow

Recruitment Details	We enrolled only a few patients. Our neurocognitive battery was too hard for patients to get through. Therefore, the study was stopped.

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia
Arm/Group Description	Inhaled Anesthesia - isoflurane	Intravenous Anesthesia - propofol, remifentanil
Period Title: Overall Study
STARTED	30	28
COMPLETED	30	28
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia	Total
Arm/Group Description	Inhaled Anesthesia - isoflurane Isoflurane: Group 1 Inhaled anesthesia Patients will be maintained on 50% oxygen in air and isoflurane 0 to 4%, titrated as needed to maintain a standard blood pressure (standard practice). If needed, muscle relaxation will be provided by additional boluses or an infusion of mivacurium (4-10 ug/kg/min).	Intravenous Anesthesia - propofol, remifentanil Remifentanil: Group 2 Intravenous anesthesia Patients will be ventilated with 50% oxygen in air. Patients will receive continuous propofol infusion 0.05 mg/kg-min to 0.15 mg/kg-min titrated as needed; and remifentanil (ultra-short acting narcotic) 0.1 ug/kg-min to 0.5 ug/kg-min. Propofol: Group 2 Intravenous anesthesia Patients will be ventilated with 50% oxygen in air. Patients will receive continuous propofol infusion 0.05 mg/kg-min to 0.15 mg/kg-min titrated as needed	Total of all reporting groups
Overall Participants	30	28	58
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	30 100%	28 100%	58 100%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	67	69	68
Sex: Female, Male (Count of Participants)
Female	13 43.3%	12 42.9%	25 43.1%
Male	17 56.7%	16 57.1%	33 56.9%
Region of Enrollment (participants) [Number]
United States	30 100%	28 100%	58 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Improved Postoperative Delirium and Cognitive and Motor Changes
Description	A battery/Questionnaire of neuropsych examinations is given to the subjects to measure improvement based on change of scores and standard deviation. The battery consists of questions regarding delirium, cognitive and motor changes and yields a combination assessment of all 3 elements.
Time Frame	Four months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Inhaled Anesthesia - isoflurane Isoflurane: Group 1 Inhaled anesthesia Patients will be maintained on 50% oxygen in air and isoflurane 0 to 4%, titrated as needed to maintain a standard blood pressure (standard practice). If needed, muscle relaxation will be provided by additional boluses or an infusion of mivacurium (4-10 ug/kg/min).	Intravenous Anesthesia - propofol, remifentanil Remifentanil: Group 2 Intravenous anesthesia Patients will be ventilated with 50% oxygen in air. Patients will receive continuous propofol infusion 0.05 mg/kg-min to 0.15 mg/kg-min titrated as needed; and remifentanil (ultra-short acting narcotic) 0.1 ug/kg-min to 0.5 ug/kg-min. Propofol: Group 2 Intravenous anesthesia Patients will be ventilated with 50% oxygen in air. Patients will receive continuous propofol infusion 0.05 mg/kg-min to 0.15 mg/kg-min titrated as needed; and remifentanil (ultra-short acting narcotic) 0.1 ug/kg-min to 0.5 ug/kg-min.
Measure Participants	30	28
Number [participants]	6 20%	5 17.9%

Adverse Events

Time Frame	4 months
Arm/Group Title	Group 1		Group 2
Arm/Group Description	Inhaled Anesthesia - isoflurane Isoflurane: Group 1 Inhaled anesthesia Patients will be maintained on 50% oxygen in air and isoflurane 0 to 4%, titrated as needed to maintain a standard blood pressure (standard practice). If needed, muscle relaxation will be provided by additional boluses or an infusion of mivacurium (4-10 ug/kg/min).		Intravenous Anesthesia - propofol, remifentanil Remifentanil: Group 2 Intravenous anesthesia Patients will be ventilated with 50% oxygen in air. Patients will receive continuous propofol infusion 0.05 mg/kg-min to 0.15 mg/kg-min titrated as needed; and remifentanil (ultra-short acting narcotic) 0.1 ug/kg-min to 0.5 ug/kg-min. Propofol: Group 2 Intravenous anesthesia Patients will be ventilated with 50% oxygen in air. Patients will receive continuous propofol infusion 0.05 mg/kg-min to 0.15 mg/kg-min titrated as needed; and remifentanil (ultra-short acting narcotic) 0.1 ug/kg-min to 0.5 ug/kg-min.
All Cause Mortality
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/28 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.