Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT01214057 |
| Other study ID # |
HSC-MS-10-0014 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 2010 |
| Est. completion date |
October 2012 |
Study information
| Verified date |
October 2021 |
| Source |
The University of Texas Health Science Center, Houston |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to compare total intravenous anesthesia to inhaled anesthesia in
endoscopic sinus surgery for chronic sinusitis. The investigators will compare bleeding
during surgery, duration of surgery, blood flow to the nose and other parameters. The
investigators hypothesize that total intravenous anesthesia decreases bleeding and improves
the view during surgery.
Description:
Endoscopic sinus surgery (ESS) has revolutionized the surgical treatment of chronic sinus
disease, permitting outpatient sinus surgery with minimal morbidity. Previously performed
using local anesthesia, the majority of patients and surgeons now prefer general anesthesia
for comfort, stress containment and relative ease of accomplishing the surgical objectives1.
A critical factor in ESS is the amount of blood in the surgical field. Even for experienced
endoscopists, significant bleeding may compromise the safety and completeness of the intended
procedure. In addition, increased bleeding requires frequent suctioning therefore decreasing
the overall efficiency of the operation and prolonging operative time.
Techniques commonly used to minimize bleeding include but are not limited to topical
decongestion, local injection of vasoconstrictors, maintaining normothermia, head elevation,
and controlled hypotension. However, controlled hypotension is potentially a source of
excessive vasodilatation and risk factor for ischemic events. In fact, a considerable amount
of data has shown that the blood pressure and intraoperative bleeding are not necessarily
related, and hypotension on its own does not necessarily improve the surgical field2, 3.
In order to maintain a good peripheral perfusion the choice of anesthetics and other drugs is
an important consideration. It is known that both propofol and inhalation agents have a
vasodilatory effect in a concentration-dependent manner. However, the extent of reflex
tachycardia is quite variable. Compared with the apparent reflex tachycardia with isoflurane,
sevoflurane usually does not alter the heart rate. In contrast, propofol inhibits the
baroreflex and can even result in bradycardia. In this way, propofol suppresses the cardiac
output more than sevoflurane4. The lower intraoperative heart rate might help reduce the
amount of intraoperative blood loss.
Few studies have attempted to demonstrate a benefit of a total intravenous anesthesia (TIVA)
as the sole technique to optimize and reduce respectively blood pressure levels and
bleeding5-9. Besides its potential effects on decreasing peripheral perfusion, other possible
benefit of TIVA is the quality of the awakening and the reduced risk of post operative nausea
and vomiting (PONV).
Some of the studies on this subject are retrospective in nature with all the biases
associated with this type of study. Others, although prospective, measure outcomes based on
subjective parameters such as a grading system of the surgeon's appreciation of the
difficulty to visualize the operative field due to bleeding, without a correlation with
physiologic parameters. Furthermore, not blinding the surgeon to the type of anesthesia may
bias the appreciation of the amount of blood loss.
A more objective physiologic measure would be to quantify the blood flow to the mucosa of the
sinonasal cavity.
Hypothesis:
Compared to sevoflurane/remifentanyl anesthesia, total intravenous anesthesia with
propofol/remifentanyl is associated with lower blood to the sinonasal mucosa, less blood loss
and improved surgical field visualization in patients undergoing endoscopic sinus surgery for
chronic rhinosinusitis.
Null hypothesis:
Propofol/remifentanyl anesthesia has comparable results to sevoflurane/remifentanyl in terms
of blood flow to the sinonasal mucosa, blood loss and surgical field visualization in
patients undergoing endoscopic sinus surgery for chronic rhinosinusitis.
Specific Aims Specific Aim 1: Assess nasal blood flow to the sinonasal mucosa using the
Rhinolux We will use the Rhinolux system to determine if there are differences in the nasal
blood flow between patients with TIVA compared to inhaled anesthesia. The amount of blood
flow to the sinonasal mucosa will be measured following induction of general anesthesia with
sevoflurane/remifentanyl and compared to the amount of blood flow following induction of
general anesthesia with Propofol/remifentanyl. The rhinolux system will be used to measure
mucosal blood flow in a continuous fashion until the blood pressure goal is reached. The
blood pressure goal will be mean arterial pressure (MAP) of 70, between 60 and 80 mm Hg. A
graph with the measurements will be obtained, the time of induction and MAP at goal will be
recorded.
The Rhinolux (Rhios GmbH, Germany) is a new non-invasive device that is designed to measure
changes in the swelling of the nasal mucosa by a tissue light absorption technique similar to
that used in pulse oximetry. The principle is that a light emitter and a detector are placed
on two external surface locations opposite each other on the skin, recording the extinction
of light that passes the tissue between them as a function of time. The Rhinolux
transilluminates the nose at the lower level of the nasal bones, and the light extinction, ∆E
measured in optical densities (OD) is proportional to the amount blood in the
transilluminated tissue10-12.
Specific Aim 2: Measure the amount of blood loss. Blood loss will be measured by counting the
volume in the collection canisters and subtracting the volume of irrigation used
intraoperatively. The Neptune Waste Management System (NWMS) will be used for this purpose.
The NWMS is a closed suction system that digitally counts the amount of fluid suctioned13.
Serum hemoglobin (Hb) will be measured preoperatively in the holding area. Subsequently a 5
mL/kg bolus of normal saline 0.9% or Lactate Ringer will be given within 30 minutes before
the start of surgery. Serum Hb will be measured again in the post anesthesia care unit
(PACU). Fluid management will be strictly monitored. Maintenance IV fluids will be
administered at a rate of 1 ml / kg per hour, including all infusions. Fluid replacement will
be performed in a 1 to1 relation with crystalloids (either normal saline 0.9% or Lactate
Ringer Solution) for blood loss of less than 5 mL / kg. Colloids will be used for blood loss
greater than 5 mL / kg at a volume equal to the blood loss in excess. All fluids given will
be recorded in a separate sheet.
Specific Aim 3: Assign a surgical grade score to the operative field. The surgical grade
score will be based on the Boezaart surgical risk assessment score, which is a validated and
widely accepted score. This is an inexpensive, reliable, and sensitive tool to rapidly
evaluate intraoperative bleeding in ESS. The surgical grade score of the operative field will
be compared between the groups.
Specific Aim 4: Assess platelet function during anesthesia. To be able to exclude a different
explanation for differences in blood loss during surgery, the platelet function will be
assessed.
Thromboelastogram- Platelet Mapping. Thromboelastography-Platelet Mapping will be performed
on each patient and the results will be compared between the groups. The test will be
performed at two different points in time: before induction and in the PACU. This will serve
the purpose of determining the baseline platelet function, the effect of the anesthetic
combination used and possible changes after surgery has been performed, for each patient.
Thromboelastography is a measure of platelet function15. These test measures blood
viscoelastic properties during clot formation. The maximum amplitude in the
thromboelastographic trace is dependent on platelet function. Four values that represent clot
formation are determined by this test: the R value (or reaction time), the K value, the angle
and the MA (maximum amplitude). The R value represents the speed of clot formation (time
until the first evidence of a clot is detected). The K value is the time from the end or R
until the clot reaches 20 mm and this represents the speed of clot formation. The angle is
the tangent of the curve made as the K is reached and offers similar information to K. The MA
is a reflection of clot strength. A mathematical formula determined by the manufacturer can
be used to determine a Coagulation Index (CI) (or overall assessment of coagulability) which
takes into account the relative contribution of each of these 4 values into 1 equation.
In vivo, platelet aggregation tests have indicated in some studies a significant inhibition
of platelet function in sevoflurane-anesthetized patients, and after propofol anesthesia,
however no change in bleeding time occurred16.
Secondary aim:
Specific Aim 5: Comparison of operative time and quality of recovery. Surgical operating time
(SOT) is the time from the moment of injection of local anesthetic in the nasal cavity to the
end of application of the local hemostatic agents.
SOT will be documented for each patient and will later be compared between the groups. It is
theorized that a decreased blood loss will translate into a shorter operative time.
The quality of recovery will be based on alertness and ventilatory support/oxygenation at
arrival in the post anesthesia recovery unit (time from extubation) and 30 minutes after
arrival in the PACU, pain control (amount of opioid and non opioid analgesic) at discharge
(dismission home after second phase PACU or 23 hours day surgery), abnormal blood pressure or
heart rate values to necessitate intervention after PACU transfer, incidence of nausea and
vomiting, delay in discharge (if patient in day surgery dismission).
After receiving institutional review board approval and written informed consent, 30 adult
patients (ASA I and II) with chronic sinusitis involving a minimum of two paranasal sinuses
undergoing ESS will be randomly assigned to receive either sevoflurane/remifentanil (SR)
(n=15) or propofol/remifentanil (PR) (n=15) anesthesia. The decision to use 15 patients in
each arm is discussed under the statistical analysis section. Patients will undergo the
planned endoscopic sinus surgery at Memorial Hermann Hospital-Medical Center and the
Ambulatory Care Center at the Memorial Hermann Medical Plaza.
The Lund-MacKay (LM) CT score of the paranasal sinuses will also be obtained. This is a
scoring system based on CT scan that categorizes the amount of disease in the sinonasal
cavity17 (Table 1). Patients with a total LM score of more than 12 will be defined as high-LM
score patients and with a total LM score of 12 or less will be defined as low-LM score
patients. In addition at the time of surgery, the surgeon will evaluate and score the amount
of edema and redness of the nasal mucosa endoscopically before operation based on the
Kupferberg objective endoscopic staging system into stages 0, no evidence of disease; I,
edematous mucosa/allergic mucin; II, polypoid mucosa/allergic mucin; and III, polyps and
fungal debris18.
A blocked randomization method will be used, to balance patients with regards to the variable
of LM score (low or high), It will be important to balance the patients in this aspect since
this is a variable that can bias the results.
None of the patients will be pre-medicated. Patients with disease or medication related to
coagulation or the cardiovascular system disorders will be excluded. Patients will be blinded
to the type of anesthesia administered.
Anesthetic protocol Patients will be premedicated in holding area with dexamethasone and
midazolam. The patients will be monitored by American Society of Anesthesia (ASA) standards
with ECG, non-invasive blood pressure, pulse oximetry and temperature probe. The blood
pressure will be recorded every 2 min for the first 10 minutes then every 5 minutes.
Anesthesia will be induced with lidocaine 0.5 mg kg, propofol infusion at 250 mcg/kg/min (to
reduce visual bias of propofol infusion) and total volume infused will be adjusted for an
induction dose of 2-3 mg/kg before bolus of muscle relaxant, rocuronium 0.5 mg kg in both SR
and PR groups. Remifentanil infusion will be started at a rate of 0.4 mcg/kg/min 1-2 minutes
before the propofol infusion and a 100 ml 0.9% normal saline bag will be used to blind
surgeons in the sevoflurane group. Sevoflurane 1-3% will be administered in group SR, and the
infusion of propofol will be stopped. After intubation remifentanil infusion will be changed
to 0.2 mcg/kg/min in both groups and propofol will be maintained at 100-150 mcg/kg/min in the
TIVA group.
The target mean arterial blood pressure (MAP) will be maintained at 70-80 mm Hg by adjusting
the sevoflurane or propofol concentration within their range (between 1-3 vol% for
sevoflurane or 100-150 mg ml for propofol) according to the anaesthesiologist's judgement and
by surgeon request. If this failed, the remifentanil rate will be adjusted by 0.05 mg kg min.
End-tidal CO2 will be continuously monitored (Capnomac Ultima, Datex, Helsinki, Finland) and
adjusted to target concentration (Et 32-34 mm Hg) by controlling minute ventilation started
from 8 ml kg tidal volume and 10 cycle min respiration rate.
Intravenous fluid administration will be minimized. At induction 5 ml/kg will be used as
bolus and a maintenance background infusion of 1 ml/kg/hr will be used in both groups. In
order to limit the amount of fluids remifentanil wil be diluted at a concentration of 4 mg in
100 ml.
Postoperative analgesia/PONV. One microgram of fentanyl/kg and/or 0.05 mg of morphine would
be given if the patient's numeric rating scale (NRS) of pain is more than 6 before leaving
the OR. In the PACU Morphine 1-2 mg IV bolus every 5-10 minutes will be provided as well as
ondansetron 4 mg IV bolus. Alternative medications and or supplements will be provided and
noted if necessary.
Surgery Protocol
Patients will be positioned in the reverse Trendelenburg and four squeezed cottonoids soaked
with a mixed solution of epinephrine and lidocaine (1:100000 epinephrine:lidocaine 2% at 1:1)
will be applied topically to each nasal cavity. The surgical procedures will be performed by
3 surgeons with subspecialty training in endoscopic sinus surgery using a similar stepwise
technique. The surgeon will not be informed of the type of anesthesia administered. The IV
line and solutions will be foiled to prevent the surgeon from seeing the color of the
anesthetic agent used.
Statistical analysis
The amount of blood loss and the intraoperative mean remifentanyl infusion rate will be
described as the median (1st/3rd quartiles), and will be analyzed using a Mann-Whitney rank
sum test. The parameters except for blood loss and the remifentanyl infusion rate will be
reported as the mean and standard deviation (SD), and will be analyzed using Student's
t-test. The categorical data will be compared using a Chi-square test.
A P-value of .05 will be considered significant. The correlation of the parametric data will
be described using the Pearson's correlation coefficients, and the correlation of the
non-parametric data will be described using the Spearman's coefficients.
Power analysis: We reviewed studies that compared total intravenous anesthesia to combined
anesthesia (inhaled and intravenous) published in the english language through a pubmed
search. There were a total of 6 papers available for analysis. The studies found measured
different parameters including quantitative and qualitative information. For the purpose of
the power analysis we decided to use only the studies measuring blood loss in an objective
and quantitive way. The study from Sivaci, et al, had the appropriate information for a power
analysis. Thirty two patients were randomly allocated into two different groups. In their
study, the average estimated blood loss in the propofol group was 128.1 +/- 37.3 ml compared
with an average estimated blood loss of 296.9 +/- 97.8 ml in the sevoflurane group (p<0.01).
Their standard deviation was 37.3 and 97.8 respectively. The sample size calculation estimate
for an alpha of .05 and a power of 0.8, was of 4 patients in each group. This result is due
to the large difference in blood loss between the two groups. However, due to the results
from other studies with smaller differences, we decided to use a sample size comparable to
what has been used in the literature. Therefore a sample size of 15 was considered
appropriate for each arm. We consider that this sample size will have enough patients to
detect even a smaller difference than the previously mentioned.
This will be the first study evaluating Rhinolux and regarding this aspect there are no
sample size calculations that could be performed.
Estimated sample size for two-sample comparison of means:
Test Ho: m1 = m2, where m1 is the mean in population 1 and m2 is the mean in population 2
Assumptions:
alpha = 0.0500 (two-sided) power = 0.8000 m1 = 128.1 m2 = 296.9 sd1 = 37.3 sd2 = 97.8 n2/n1 =
1.00 Estimated required sample sizes: n1 =4, n2 = 4
