Desflurane or Propofol Anesthesia in Elderly Obese Patients Undergoing Total Knee Replacement
|First Received Date ICMJE||December 14, 2010|
|Last Updated Date||July 18, 2011|
|Start Date ICMJE||December 2010|
|Estimated Primary Completion Date||December 2012 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||postoperative delirium and cognitive function [ Time Frame: 48 hours ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01270620 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Desflurane or Propofol Anesthesia in Elderly Obese Patients Undergoing Total Knee Replacement|
|Official Title ICMJE||Desflurane or Propofol Anesthesia in Elderly Obese Patients Undergoing Total Knee Replacement: A Pilot Assessment of Short-term and Long-term Differences in Outcome|
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.
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.
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.
All groups will receive pre-medication consisting in midazolam and fentanyl i.v. at the discretion of the regional anesthesia team in the preoperative area before the femoral block. A femoral block will be performed, on the side to be operated. Postoperatively, a continuous infusion of 0,2% ropivacaine will be started in the recovery room at the rate of 6 ml/h and adjusted to a maximum of 10 ml/h for the next 48 hours. In addition, postoperatively all patients will be provided with a patient controlled analgesia programmed to administer IV hydromorphone with a standardized dosing and lock out period.
The patient will be transferred to the OR room, and will receive standard monitoring consisting of oximetry, non-invasive blood measurement, end-tidal CO2. A monitoring strip will be applied to the forehead of all patients to allow monitoring of adequacy of anesthesia using the patient state index. After breathing 100% oxygen for 3 minutes patients in all groups will be induced with propofol (1 mg/kg), followed by fentanyl (1-2 micrograms/kg) and rocuronium (0.4 mg/kg) doses based on lean body weight. After tracheal intubation, lungs will be ventilated using a Apollo (Drager, Lubeck, Germany) with a respiratory rate of 10-12 bpm, an I:E ratio of 1:2, positive end-respiratory pressure of 5 cm H2O and an FiO2 of 0.4. Tidal volume will be adjusted to an end tidal CO2 of 35-40 mmHg. Blood pressure, heart rate, and patient state index values will be recorded at 1-min intervals during the induction and emergence periods. The end-tidal concentrations of desflurane and oxygen saturation, as well as PSI values, will be recorded at 5-min intervals during the maintenance period. A Foley catheter will be placed in all cases, and all patients will receive intravenous prophylactic antibiotics after anesthesia induction. Anesthesia will be maintained in group D with Desflurane and in group P with Propofol, administered by continuous infusion and titrated according to patient state index (30-50). If, at a patient state index value between 30-50 the patient shows signs of inadequate anesthesia such as an increase in systolic arterial blood pressure>20% from baseline or a heart rate greater than 90 in the absence of hypovolemia, sweating, flushing or movement and swallowing fentanyl, 50-100 mcg, may be administered. Persistent hypertension without signs of inadequate anesthesia will be treated with hydralazine, 1 mg IV, every 3 min until return to baseline value. If the increase in blood pressure is correlated to PSI more than 50, desflurane or propofol will be increased by 10% of the previous dose every 3 minutes until return to PSI at least to 50. In both groups patients with a heart rate less than 50 bpm not correlated with blood pressure variation will receive glycopyrrolate 0,2 mg every 3 minutes until heart rate is back to at least 50 bpm. In all patients, from anesthetic induction to end of surgery, a decrease in systolic blood pressure of more than 30% less than baseline values, not correlated with patient state index less than 30, will be treated with ephedrine 5 mg or phenylephrine 100 micrograms every 3 min until return to baseline value. If the decrease in blood pressure is correlated to PSI less than 30, desflurane or propofol wil be decreased by 10% of the previous dose every 3 minutes until return to PSI at least of 30. Desflurane and propofol will be stopped at completion of skin closure. Intraoperatively, patients will also receive 4 mg of ondansetron to decrease postoperative nausea.
The doses and mean infusion rates of all IV drugs and duration of anesthesia and surgery will be recorded. We will determine for each patient the percentage of time during which the patient state index values, blood pressure and heart rate values are outside the defined target range (patient state index 30-50, systolic blood pressure 70-120% of baseline value, heart rate 50-90 bpm). Ephedrine and phenylephrine consumption and the amount of intravascular fluid administration and all the intraoperative drug dose adjustments will be recorded. The esophageal temperature of the patients will be monitored and maintained at 36 C using a force-air warming blanket and warmed i.v. fluids. The degree of neuromuscular blockade will be monitored with accelerography using train of four stimulation at the adductor muscle at the hand. At the end of surgery patients will receive neostigmine 0.04mg/kg and glycopyrrolate 0.01mg/kg if needed to reverse neuromuscular blockade to a train of four ratio of 0.9. Times to spontaneous breathing, to eyes opening, following commands and to tracheal extubation will be recorded. Postoperative nausea and vomiting, visual analogue scale for pain scores and analgesic drug consumption will be measured in the post-anesthesia care unit and 6-8, 24 and 48 hrs postoperatively.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: propofol or desflurane
comparison of the incidence in delirium and post-operative cognitive dysfunction from propofol and desflurane in patients under general anesthesia
Other Name: suprane
|Study Arm (s)||Experimental: Propofol or desflurane
Patients will receive propofol or desflurane as general anesthetic
Intervention: Drug: propofol or desflurane
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||100|
|Estimated Completion Date||December 2014|
|Estimated Primary Completion Date||December 2012 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||65 Years and older|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01270620|
|Other Study ID Numbers ICMJE||SU-12062010-7277, IRB: 4593, SPO: 48391|
|Has Data Monitoring Committee||No|
|Responsible Party||Hendrikus Lemmens, Stanford University School of Medicine|
|Study Sponsor ICMJE||Stanford University|
|Collaborators ICMJE||Baxter Healthcare Corporation|
|Information Provided By||Stanford University|
|Verification Date||July 2011|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP