Desflurane or Propofol Anesthesia in Elderly Obese Patients Undergoing Total Knee Replacement

This study has been completed.
Sponsor:
Collaborator:
Baxter Healthcare Corporation
Information provided by (Responsible Party):
Pedro Paulo Tanaka, Stanford University
ClinicalTrials.gov Identifier:
NCT01270620
First received: December 14, 2010
Last updated: October 1, 2015
Last verified: October 2015
  Purpose
You are invited to participate in a research study assessing your mental status in the first days after your surgery and how you will be doing in the 2 years following the surgery. The investigators hope to learn more about the incidence of postoperative confusion and a possible relation with 2 anesthesia techniques that are routinely used. The first one is an anesthesia technique that uses the inhaled anesthetic gas desflurane and the second one is an anesthesia technique that uses the anesthetic propofol administered by infusion in a vein. The investigators are also looking to see if there is a relationship between anesthesia technique and cardiovascular outcomes. You were selected as a possible participant in this study because at your age this phenomenon appears to have a greater incidence.

Condition Intervention Phase
Obesity
Arthritis
Drug: propofol
Drug: Desflurane
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Desflurane or Propofol Anesthesia in Elderly Obese Patients Undergoing Total Knee Replacement: A Pilot Assessment of Short-term and Long-term Differences in Outcome

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Assessment of Delirium [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    The primary end point was the incidence of postoperative delirium as measured by the Confusion Assessment Method (CAM).

  • Recall of Digit Span [ Time Frame: Change > 20% from baseline to 6-8 hours after surgery ] [ Designated as safety issue: No ]
    • The Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised is a test that requires subjects to repeat a series of digits that have been verbally presented to them both forward and, in a later independent test, reverse order. It measures attention and working memory

  • Recall of Digit Span [ Time Frame: Change > 20% from baseline to 48 hours after surgery ] [ Designated as safety issue: No ]
    • The Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised is a test that requires subjects to repeat a series of digits that have been verbally presented to them both forward and, in a later independent test, reverse order. It measures attention and working memory

  • Digit Symbol Substitution Test [ Time Frame: Change > 20% from baseline to 6-8 hours after surgery ] [ Designated as safety issue: No ]
    • The Digit Symbol Substitution Test (DSST) measures attention, working memory, sustained visual attention and psychomotor speed. Subjects are given a table that pairs digits and symbols, and asked to decipher a code using the table, completing as many as possible in 90 seconds. The DSST has been found to be more sensitive than other tests to changes in high-levels of cognition

  • Digit Symbol Substitution Test [ Time Frame: Change > 20% from baseline to 48 hours after surgery ] [ Designated as safety issue: No ]
    • The Digit Symbol Substitution Test (DSST) measures attention, working memory, sustained visual attention and psychomotor speed. Subjects are given a table that pairs digits and symbols, and asked to decipher a code using the table, completing as many as possible in 90 seconds. The DSST has been found to be more sensitive than other tests to changes in high-levels of cognition

  • Trail Making Part A [ Time Frame: Change > 20% from baseline to 6-8 hours after surgery ] [ Designated as safety issue: No ]
    • Trail Making Test is an executive measure of sequencing and cognitive flexibility. Trail A requires the subject to rapidly sequence a straightforward series. The scoring for this test is the time in seconds required for completion of the test

  • Trail Making Part A [ Time Frame: Change > 20% from baseline to 48 hours after surgery ] [ Designated as safety issue: No ]
    • Trail Making Test is an executive measure of sequencing and cognitive flexibility. Trail A requires the subject to rapidly sequence a straightforward series. The scoring for this test is the time in seconds required for completion of the test

  • Trail Making Part B [ Time Frame: Change > 20% from baseline to 6-8 hours after surgery ] [ Designated as safety issue: No ]
    • Trail Making Test is an executive measure of sequencing and cognitive flexibility. Trail B is a more difficult cognitive flexibility task requiring the subject to follow a sequential pattern while shifting cognitive sets and reflects executive functioning, although other cognitive abilities, such as psychomotor speed and visual scanning, are necessary for successful completion of the task. The scoring for this test is the time in seconds required for completion of the test

  • Trail Making Part B [ Time Frame: Change > 20% from baseline to 48 hours after surgery ] [ Designated as safety issue: No ]
    Trail Making Test is an executive measure of sequencing and cognitive flexibility. Trail B is a more difficult cognitive flexibility task requiring the subject to follow a sequential pattern while shifting cognitive sets and reflects executive functioning, although other cognitive abilities, such as psychomotor speed and visual scanning, are necessary for successful completion of the task. The scoring for this test is the time in seconds required for completion of the test


Secondary Outcome Measures:
  • - Time to Spontaneous Breathing After Desflurane/Propofol Discontinuation [ Time Frame: first day ] [ Designated as safety issue: No ]
  • - Time to Eye Opening After Desflurane/Propofol Discontinuation [ Time Frame: first day ] [ Designated as safety issue: No ]
  • - Time to Tracheal Extubation After Desflurane/Propofol Discontinuation [ Time Frame: first day ] [ Designated as safety issue: No ]
  • - Time to Following Command After Desflurane/Propofol Discontinuation [ Time Frame: first day ] [ Designated as safety issue: No ]
  • Nausea and Vomiting [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Recovery Room Time [ Time Frame: first day ] [ Designated as safety issue: No ]
  • B-type Natriuretic Peptide [ Time Frame: Change from Baseline to day one ] [ Designated as safety issue: No ]
  • N-terminal proBNP [ Time Frame: Change from baseline to day one ] [ Designated as safety issue: No ]
  • Troponin I [ Time Frame: 2 days ] [ Designated as safety issue: No ]
    Patients who had troponin level > 0.2 ng/mL

  • BNP [ Time Frame: Change form baseline to post-operative day 2 ] [ Designated as safety issue: No ]
  • ProBNP [ Time Frame: Change from baseline to post-operative day 2 ] [ Designated as safety issue: No ]
  • Duration of Surgery [ Time Frame: Time from Incision to closure of surgery ] [ Designated as safety issue: No ]
  • Duration of Anesthesia [ Time Frame: Time from induction to extubation ] [ Designated as safety issue: No ]
  • Amount of Intraoperative Fentanyl [ Time Frame: From the anesthesia induction until extubation ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: December 2010
Study Completion Date: July 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Propofol
Patients will receive propofol as general anesthetics.
Drug: propofol
comparison of the incidence in delirium and post-operative cognitive dysfunction from propofol and desflurane in patients under general anesthesia
Active Comparator: Desflurane
Patients will receive desflurane as general anesthetics.
Drug: Desflurane
comparison of the incidence in delirium and post-operative cognitive dysfunction from propofol and desflurane in patients under general anesthesia
Other Name: Suprane

  Hide Detailed Description

Detailed Description:

Trial Objectives:

This will be a randomized, prospective, single-center, assessor blinded pilot study comparing two different anesthesia techniques in 100 elderly obese patients undergoing primary total knee arthroplasty.

Endpoints:

  • The incidence of postoperative delirium as measured by the Confusion Assessment Score. Confusion assessment score will be administered at baseline, one hour after arrival in the post anesthesia care unit and 6-8, 24 and 48 hrs postoperatively.
  • Cognitive function as measured by Test for Attentional Performance, Digit-Symbol-Substitution Test, Recal of Digit Span , Well-being Test BF-S, Spielberger State-Trait Anxiety Inventory and the Trail Making Test A and B. Cognitive function tests will be administered at baseline, 6-8 and 48 hrs post operatively. Postoperative Cognitive Dysfunction is defined as a 20% decline of the baseline values.

Intraoperative

  • Sensory block (femoral)
  • Blood pressure
  • Heart rate
  • Patient state index values
  • Degree of neuromuscular blockade
  • Esophageal temperature
  • End tidal concentration of CO2
  • End tidal concentration of desflurane
  • Amount of vasopressors (ephedrine or phenylephrine)
  • Amount of intravascular fluid administration
  • Dose and mean infusion rates of all IV drugs (propofol)
  • Duration of anesthesia
  • Duration of surgery
  • Time to spontaneous breathing after desflurane/propofol discontinuation
  • Time to eye opening after desflurane/propofol discontinuation
  • Time to tracheal extubation after desflurane/propofol discontinuation
  • Time to following command after desflurane/propofol discontinuation

Post operative

  • Nausea and vomiting: one hour after arrival in the post anesthesia care unit and 6-8, 24 and 48 hrs postoperatively
  • Pain visual analogue score measured one hour after arrival in the post anesthesia care unit and 6-8, 24 and 48 hrs postoperatively
  • Recovery room time
  • Amount of local anesthetics (ropivacaine)
  • Amount of opioids (Patient controlled analgesia hydromorphone)

Cardiovascular

  • B-type natriuretic peptide measured preoperatively and on postoperative days 1 and 2
  • N-terminal proB-type natriuretic peptide measured preoperatively and on postoperative days 1 and 2
  • Troponin I measured preoperatively and on postoperative days 1 and 2
  • Patients will be followed by a blinded investigator for a 2 year period to record the development of cardiac complications defined by a broad composite that included cardiac death and nonfatal myocardial infarction. Cardiac composite including: all-cause mortality, acute myocardial infarction, unstable angina, congestive heart failure, new atrial or ventricular dysrhythmia requiring treatment, and cerebrovascular insult.

Protocol This will be a randomized, prospective, single-center, assessor blinded study comparing two different anesthesia techniques in 100 elderly obese patients undergoing primary total knee arthroplasty. We expect to enroll all patients in a 2 year period.

The study will be performed according to the Declaration of Helsinki principles, and written informed consent will be obtained from each patient. Preoperatively baseline values will be obtained for the cardiovascular, mental status, respiratory and pain outcome measures.

Mental status: During their preoperative visit patients will be given the neuropsychological tests in the following order: 1. Confusion Assessment Method . The confusion assessment method is a screening instrument for delirium consisting of four clinical criteria: (1) acute onset and fluctuating course, (2) inattention, (3) disorganized thinking, and (4) altered level of consciousness. For a person to be considered delirious, both the first and the second criteria and either the third or the fourth criteria have to be present. The confusion assessment method has a high inter-observer reliability (0.8 -1.0), a sensitivity of 94-100%, and a specificity of 90-95%. 2. Modified Mini-Mental State Examination. This extended measure of general cognition was developed to overcome shortcomings of the traditional Mini-Mental State Examination score, specifically its ceiling effects and narrow range of possible scores. The Modified Mini-Mental State Examination will be administered at the preoperative visit to assess the baseline cognitive function of the patient. 3. Computerized Test for Attentional Performance , Digit-Symbol-Substitution Test, Recall of Digit Span, Well-being Test BF-S, Spielberger State-Trait Anxiety Inventory and the Trail Making Test A and B.

Patients will be visited for the first 2 days after surgery or until discharge, whichever came first, and the confusion assessment method will be administered one hour after arrival in the post anesthesia care unit and 6-8, 24 and 48 hrs postoperatively to determine whether the patient is experiencing delirium. Each patient will be interviewed by the same trained research assistant before surgery and during the postoperative visits. We will define the occurrence of delirium as the patient meeting the confusion assessment method criteria for delirium on any of the postoperative assessments. If a patient is positive for delirium, a second member of the research team will be consulted to verify the diagnosis. Cognitive function tests will be administered, 6-8 and 48 hrs post operatively. Postoperative Cognitive Dysfunction is defined as a 20% decline of the baseline values.

Cardiovascular: Preoperative testing will include 12-lead ECG. Blood samples for Natriuretic peptide levels and N-terminal proB-type natriuretic peptide and Troponin I will be obtained at the time of the admission and on postoperative day 1 and day 2. Plasma NT-proB-type natriuretic peptide will be determined using the Elecsys proB-type natriuretic peptide sandwich immunoassay on an Elecsys 2010 (Roche Diagnostics, Basel, Switzerland). Two cut offs for NT-proB-type natriuretic peptide will be selected before the analyses, 300 pg/ml and 600 pg/ml, with a value of less than 300 pg/ml shown to be optimal for ruling out heart failure as a predictor. B-type natriuretic peptide will be determined using immunoradiometric assay kit. Values of B-type natriuretic peptide (pg/mL) 31.0 ± 2.4 are considered normal for patients over 65 years old.

After discharge from the hospital patients will be followed blindly for a 2 year period to record the development of cardiac complications defined by a broad composite that included cardiac death and nonfatal myocardial infarction. Cardiac composite including: all-cause mortality, acute myocardial infarction, unstable angina, congestive heart failure, new atrial or ventricular dysrhythmia requiring treatment, and cerebrovascular insult. Information will be collected at 1, 3, 6, 12, 18 and 24 months after surgery.

Outcome measures and postoperative complications including nausea and vomiting will be recorded by an assessor blinded to the treatment allocation.

Patients will be randomly allocated to one of two treatment groups on the day of surgery using a computer generated assignment. Group D will receive desflurane and group P will receive propofol.

  Eligibility

Ages Eligible for Study:   65 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 65 years old
  • Body mass index > 30 kg/m2
  • Undergoing primary total knee arthroplasty surgery
  • American society of anesthesiology classification II-III

Exclusion Criteria:

  • Patient refusal to participate in the study
  • Patient refusal or failure of regional block
  • Patients with preexisting neuro-cognitive disorders
  • Known intolerance to any of the drugs to be used according to the study protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01270620

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Pedro Paulo Tanaka
Baxter Healthcare Corporation
Investigators
Principal Investigator: Hendrikus Lemmens Stanford University
Study Director: Pedro Paulo Tanaka Stanford University
  More Information

Responsible Party: Pedro Paulo Tanaka, Clinical Associate Professor, Stanford University
ClinicalTrials.gov Identifier: NCT01270620     History of Changes
Other Study ID Numbers: SU-12062010-7277  IRB: 4593  SPO: 48391 
Study First Received: December 14, 2010
Results First Received: July 18, 2015
Last Updated: October 1, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Stanford University:
elderly obese

Additional relevant MeSH terms:
Anesthetics
Propofol
Desflurane
Isoflurane
Central Nervous System Depressants
Physiological Effects of Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics, Inhalation

ClinicalTrials.gov processed this record on July 21, 2016