| Study Summary: |
|
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.
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.
|