Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT00507195 |
| Other study ID # |
pinocchio |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
July 23, 2007 |
| Last updated |
July 24, 2007 |
| Start date |
May 2007 |
Study information
| Verified date |
May 2007 |
| Source |
University of Roma La Sapienza |
| Contact |
Federico Bilotta, MD, PhD |
| Phone |
39 339 33 708 22 |
| Email |
bilotta[@]tiscali.it |
| Is FDA regulated |
No |
| Health authority |
Italy: Ethics Committee |
| Study type |
Observational
|
Clinical Trial Summary
The study proposes to analyze the difference in the rapidity of the recovery of post
operative cognition immediately after extubation and 20, 40 and 60 minutes post extubation
and neuropsychological complications (delirium) after 48 hours following general anesthesia
using a prospective, randomized approach. Patients undergoing any type of surgery with the
exception of cranial, cardiac or thoracic surgery can be enrolled in the study.
Description:
The rationale for this study comparing different types of anesthetic maintenance is based on
the amount of systemic metabolic breakdown and the low repartion rates within the various
tissues and the very rapid elimination of desflurane in respect to the other common
inhalation and intravenous anesthetics as possible factors in the rate of recovery of
cognitive function and the appearance of post operative delirium. After general anesthesia
with desflurane there is less residual hypnotic agent for elimination in the circulation and
tissue with respect to the amount given than with propofol or sevoflurance (1-3).
Perioperative cerebral injury correlated with surgical intervention and anesthesia can
result in a decline in cognitive function (4) defining the entity of post operative
cognitive dysfunction (POCD).
In this study it is possible to distinguish:
- Early POCD: attributable to anesthesia
- Long-Term POCD: could be attributable to of cognition associated with advanced age
rather than to procedural effects (surgery, anesthesia, or confinement to a hospital
bed)
The prevalence of POCD is higher in patients with advanced age (>70) and in cases where
general anesthesia is used for highly invasive surgery (orthopedic, abdominal and thoracic
surgery) (5-7). A consensus does not exist regarding tests for evaluation of POCD. In this
protocol we propose to use three scales concurrently that are commonly used for evaluation
of cognitive function.
Regarding neuropsychological complications, the scope of this study is to evaluate the
prevalence of post operative delirium with onset during the 48 hours following the end of
the surgical intervention.
Delirium fundamentally consists of three basic neuropsychological disorders:
- Visual or auditory hallucination
- Spatial-temporal disorientation
- Inappropriate language
Post operative delirium entails:
- An increase in morbidity and mortality
- An increase risk of neurological damage
- Significant discomfort for the patient, families and staff (6)
Some conditions predispose patients to the onset of post operative delirium: advanced age
(>70 years old), alcohol abuse, abnormalities in the pre-operative cognitive state, and
electrolyte or chemical imbalance (Na, K, glucose, etc.)
Protocol
After the induction of anesthesia, carried out using routine clinical practice determined by
the anesthesiologist the patient will be assigned to either the control group or the
comparison group (the assignment will have been made prior to induction). The control group
will receive either propofol or sevoflurance (with or without N2O at the discretion of the
anesthesiologist based on clinical needs). The comparison group will be given desflurane
(end tidal 5.0 - 6.0%) for maintenance of anesthesia (with or without N2O at the discretion
of the anesthesiologist based on clinical needs). According to a randomized sequence
patients will be assigned in a consecutive manor to the maintenance with the control
technique or with desflurane.
The objective of the study is to observe if there are differences in the point of recovery
of cognition, evaluated with the appropriate test in the immediate post operative period and
the onset of post operative delirium (visual or auditory hallucination, spatial or temporal
disorientation, or inappropriate language) within 48 hours following surgery.
Normal care should be used in the administration of benzodiazapam premedication to patients
at high risk for developing post operative delirium, but their use doe not represent
criteria for exclusion from the study. In addition hypotension should be avoided
(maintenance of a mean blood pressure of greater than 70 mmHg) as also intraoperative hyper
ventilation (avoid hypocapnia).
Every collaborator would initially enroll 10 patients (5 control group receiving propofol or
sevoflurance and 5 comparison group receiving desflurane) in order to become confident with
the method of the protocol and with the evaluation methods used for measuring cognitive
function.
Every collaborator and those relevant to the core study will be cited in the list of
coauthors. The databases consisting of the protocol data will be at the disposal of the
collaborators for further scientific work.
Statistical Analysis
The diagnostic characteristics of the patients registered will be described according to
categorical variables across a table of frequency. Continuous variables will be subjected to
summary statistics such as average, standard deviation, median, minimum and maximum. The
differences between the groups will be subjected to verification of the significance through
non-parametric (Chi Square and Fisher Exact Test for the non-continuous variables and the
Mann-Whitney or the Kruskall-Wallis for associations between the continuous variables. The
incidence of cardiovascular or respiratory complications, nausea and/or vomiting, shivering,
neurological complications and delirium will be tabulated through table of frequency.
Criteria for Enrollment
The study includes patients of any age and ASA physical status undergoing elective surgery.
All patients must have a Glascow Coma Score (GCS) equal to 15 before the intervention and
they must have undergone the following:
- Informed consent about anesthesia
- Preoperative evaluation including determination of ASA physical status and GCS
Laboratory testing
- Preoperative evaluation
- Routine laboratory tests
- Treatment and testing appropriate to the patient's condition
- ECG
- Chest x-ray
After the induction of anesthesia which can be done according to the normal routine of the
individual anesthesiologist, the patient will then be assigned according to a randomized
sequence to one of the two groups:
1a) Anesthesia with propofol (total intravenous anesthesia - TVA)
1b) Anesthesia with sevoflurane (with or without N2O) 2) Anesthesia with desflurane (with or
without N2O)
The anesthesiologist can use other agents (oppiods, _________, antihypertensives etc.)
according to the clinical need in the judgment of the anesthesiologist. The type and
quantity of drugs used in the Perioperative period must be reported on the anesthesia
record.
Intra operative monitoring
- ECG
- Blood pressure (invasive or non-invasive)
- SpO2
- EtCO2
- Et halogenated agent
- Urine output
Tests Before anesthetizing the patient they will be given three cognitive tests: SOMCT, RLAS
and MMSE. The same tests will be followed (repeated at emergence, after 20, 40, and 60
minutes after extubation. This will permit the evaluation of the level of recovery of
cognition compared to the value obtained before anesthesia with that obtained in the three
successive administrations of the tests after wake-up.
The Short Orientation Memory Concentration Test (SOMCT) investigates the patient's capacity
to know the current year or month or only one of the two and to repeat in numerical order
the inverse sequence of the months of the year. These variables permit the assignment of a
numerical score from 0 to 28 based upon the patient's cognitive function. Higher scores
indicate better cognitive function (12).
The Rancho Los Amigos Scale (RLAS) is a scale utilized to quantify the behavioral and
cognitive state after acute cerebral injury. Each state corresponds to one of eight levels
(I - VIII). Higher scores indicate a good state of behavior and cognition.
The Mini Mental State Examination (MMSE) is a test that is usually administered to adults or
the elderly who one suspects might have a memory or character disturbance (13). This test
requires the use of a pencil, a watch and some sheets of paper. The maximum attainable score
is 30. A compiled score of between 24 - 30 could indicate a psychological decline in
cognitive function of little importance. On the other hand scores below 24 can denote
cognitive disturbance much more severe as the score decreases.
The Wake-up The start of the study period coincides with the suspension of the hypnotics
(propofol/sevoflurane or desflurane). At this moment the timing of extubation begins which
is at the discretion of the anesthesiologists who would evaluate the patient as usual for
extubation criteria (respiratory dynamics, ability to maintain SpO2 >95%, Et CO2 between 30
- 40 mmHg, muscle strength, the presence of laryngeal reflexes, and swallowing, etc.) At
that point the anesthesiologist will bring the flow of fresh gas to a value greater than
that of the minute ventilation and change the circuit to an open system. The time between
the suspension of anesthesia and extubation will be recorded on the patient's anesthetic
record.
In order to evaluate memory quickly at termination of the anesthetic (after extubation) it
would be necessary to inform the patient of the correct time and day in the immediate wake
up period.
The patient is evaluated according to the Aldrete score (11) 5 minutes after the extubation
ane every 5 minutes after until an Aldrete score of 9-10 is obtrained. The patient that
reaches a score of 9-10 (capacity to move their extremities spontaneously and under command,
to breath and cough, have a mean blood pressure between 20% of the preoperative level, to
arouse themselves and the capacity to maintain an SpO2 greater than 90%) can begin to
undergo cognitive testing.
At the same time interval of evaluation of the recovery of cognition, the patient will be
evaluated (and treated?) for pain through use of an analogue visual scale (VAS 0 = no pain,
10 = maximum pain imaginable). The patient will then be asked for the information furnished
at awakening.
During the same period the blood pressure, heart rate, ECG, SpO2 will be measured to
evaluate cardiovascular, respiratory function, and the patient evaluated for
nausea/vomiting, shivering and any neurological abnormalities. Episodes of hypotension (mean
blood pressure less than 50 mmHg for a period greater than 5 minutes), hypertension (meant
blood pressure greater than 100 mmHg for a period greater than 5 minutes) will be recorded
and treated if necessary.
At 24 and 48 hours the presence of delirium will be evaluated, and in particular the
appearance of alteration of spatial or temporal orientation, auditory or visual
hallucinations or any inappropriate language, will be noted.
Information compiled for Patient Records
General Data This section has the aim to identify the researcher and to classify the
patient. Information will be obtained regarding the patients age, sex, height and weight and
the name of the medical center and the date of the intervention.
Preoperative data Needed therapy and medical condition including cardiac, respiratory,
neurologic and metabolic problems prior to surgery will be recorded.
Intra-operative data This data records factors related to the intervention including
anesthetic techniques utilized, fluid administered, duration of anesthesia and surgery, type
of surgery and the patient's position. It is of great importance to report episodes of
hypertension (systolic blood pressure <90 mmHg ) or hypertension (diastolic pressure >100
mmHg) that is protracted (duration longer than 5 minutes).
Post operative data This is data that relates to the wake up of the patients based on the
three groups studied. The evaluation at wake-up and the results from the Aldrete score, the
SOMCT, RLAS, and the MMSE according to the order specified in the discription of the
protocol. It is important to indicated episodes of protracted hypo or hypertension and
episodes of hypoxia (SpO2 < 95%) as well as the intensity of pain using the VAS (and
treatment?).
