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

Obesity Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01270620
• Other study ID #: SU-12062010-7277
• Secondary ID: IRB: 4593SPO: 48
• Status: Completed
• Phase: Phase 4
• First received: December 14, 2010
• Last updated: October 1, 2015
• Start date: December 2010
• Est. completion date: July 2015

Study information

• Verified date: October 2015
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Obesity

Intervention

Drug:
• propofol
comparison of the incidence in delirium and post-operative cognitive dysfunction from propofol and desflurane in patients under general anesthesia
• Desflurane
comparison of the incidence in delirium and post-operative cognitive dysfunction from propofol and desflurane in patients under general anesthesia

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Pedro Paulo Tanaka	Baxter Healthcare Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of Delirium	The primary end point was the incidence of postoperative delirium as measured by the Confusion Assessment Method (CAM).	48 hours	No
Primary	Recall of Digit Span	• 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	Change > 20% from baseline to 6-8 hours after surgery	No
Primary	Recall of Digit Span	• 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	Change > 20% from baseline to 48 hours after surgery	No
Primary	Digit Symbol Substitution Test	• 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	Change > 20% from baseline to 6-8 hours after surgery	No
Primary	Digit Symbol Substitution Test	• 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	Change > 20% from baseline to 48 hours after surgery	No
Primary	Trail Making Part A	• 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	Change > 20% from baseline to 6-8 hours after surgery	No
Primary	Trail Making Part A	• 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	Change > 20% from baseline to 48 hours after surgery	No
Primary	Trail Making Part B	• 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	Change > 20% from baseline to 6-8 hours after surgery	No
Primary	Trail Making Part B	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	Change > 20% from baseline to 48 hours after surgery	No
Secondary	- Time to Spontaneous Breathing After Desflurane/Propofol Discontinuation		first day	No
Secondary	- Time to Eye Opening After Desflurane/Propofol Discontinuation		first day	No
Secondary	- Time to Tracheal Extubation After Desflurane/Propofol Discontinuation		first day	No
Secondary	- Time to Following Command After Desflurane/Propofol Discontinuation		first day	No
Secondary	Nausea and Vomiting		48 hours	No
Secondary	Recovery Room Time		first day	No
Secondary	B-type Natriuretic Peptide		Change from Baseline to day one	No
Secondary	N-terminal proBNP		Change from baseline to day one	No
Secondary	Troponin I	Patients who had troponin level > 0.2 ng/mL	2 days	No
Secondary	BNP		Change form baseline to post-operative day 2	No
Secondary	ProBNP		Change from baseline to post-operative day 2	No
Secondary	Duration of Surgery		Time from Incision to closure of surgery	No
Secondary	Duration of Anesthesia		Time from induction to extubation	No
Secondary	Amount of Intraoperative Fentanyl		From the anesthesia induction until extubation	No